bluuebunny/crossref_metadata_2025 huggingface dataset:
Using a Biopsychosocial Approach to Examine Differences in Post-Traumatic Stress Symptoms Among Arab and Jewish Israeli Mothers Following A Child’s Traumatic Medical Event
Authors: Hussien Sewar , Sadeh Yaara , Dekel Rachel , Shadmi Efrat , Brezner Amichai , Landa Janna , Silberg Tamar
Published: December 2020

Background: Parents of children following a traumatic medical event (TME) are known to be at high risk for developing severe post-traumatic stress symptoms (PTSS). Findings on the negative impact of TMEs on parents’ PTSS have been described in different cultures and societies worldwide. However, in some cases, a specific ethnic group may also be a minority within a given region or a country, contributing to increased risk for parental PTSS following a child’s TME.Objectives: The current study aimed to examine differences in PTSS between Israeli-Arab and Israeli-Jewish mothers, following a child’s TME. More specifically, we aimed to examine the risk and protective factors affecting mother’s PTSS from a biopsychosocial approach.Methods: Data were collected from medical files of children following TMEs, hospitalized in a pediatric rehabilitation department, during the period 2008–2018. The sample included 47 Israeli-Arab mothers and 47 Israeli-Jewish mothers. Mothers completed the psychosocial assessment tool (PAT), the post-traumatic diagnostic scale (PDS).Results: Arab mothers self-reported significantly higher levels of PTSS than their Jewish counterparts. Further, Arab mothers perceived having more social support than Jewish mothers did. Finally, our prediction model indicated that both Arab ethnicity and pre-trauma family problems predicted higher levels of PTSS among mothers of children following TMEs.Conclusions: Focusing on ethnic and cultural effects following a child’s TME may help improve our understanding of the mental health needs of mothers from different minority ethnic groups and aid in developing appropriate health services and targeted interventions for this population.
N-terminal Pro-brain Natriuretic Peptide plasma levels are Associated With a Short-Term Diagnosis of Cancer in Patients with Coronary Artery Disease
Authors: Tuñón José , Aceña Álvaro , Pello Ana , Ramos-Cillán Sergio , Martínez-Milla Juan , González-Lorenzo Óscar , Fuentes-Antras Jesús , Tarín Nieves , Cristóbal Carmen , Blanco-Colio Luis Miguel , Martín-Ventura José Luis , Huelmos Ana , Gutiérrez-Landaluce Carlos , López-Castillo Marta , Alonso Joaquín , López-Bescós Lorenzo , Alonso-Pulpón Luis , Egido Jesús , Mahíllo-Fernández Ignacio , Lorenzo Óscar
Published: December 2020

Background N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels are increased in patients with cancer. In this paper we test whether NT-proBNP may identify patients who are going to receive a future cancer diagnosis (CD) in the short term. Methods We studied 962 patients with stable coronary artery disease and free of cancer and heart failure at baseline. NT-proBNP, galectin-3, monocyte chemoattractant protein-1, high-sensitivity C-reactive protein, high-sensitivity cardiac troponin I (hsTnI), and calcidiol (vitamin D) plasma levels were assessed. The primary outcome was new CD. Results After 5.40 (2.81-6.94) years of follow-up, 59 patients received a CD. NT-proBNP [HR 1.036 CI (1.015-1.056) per increase in 100 pg/ml; p=0.001], previous atrial fibrillation [HR 3.140 CI (1.196-8.243); p=0.020], and absence of previous heart failure [HR 0.067 CI (0.006-0.802); p=0.033] were independent predictors of a receiving a CD in first three years of follow-up. None of the variables analyzed predicted a CD beyond this time. A previous history of heart failure was present in 3.3% of patients receiving a CD in the first three years of follow-up, in 0.0% of those receiving this diagnosis beyond three years, and in 12.3% of patients not developing cancer (p=0.036). Conclusions In patients with coronary artery disease, NT-proBNP is an independent predictor of CD in the first three years of follow-up but not later, suggesting that it could be detecting subclinical undiagnosed cancers. The existence of previous heart failure does not account for these differences. New studies in large populations are needed to confirm these findings.
The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: a Systematic Review and Meta-analysis
Authors: Gan Kai , Gao Yue , Liu KuangZheng , Xu Bin , Chen Ming
Published: December 2020

Objective: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in a variety of tumors and associated with patients’ prognosis, but its role in bladder cancer remains unclear. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in bladder cancer and its potentiality as an immunotherapy target.Methods: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and bladder cancer. UALCAN website was used to obtain TCGA (The cancer genome atlas) database.Results: Our study includes 14 articles, 1398 patients. HER2 expression was significantly higher in bladder cancer than in normal tissues. Our meta-analysis results did not reveal any effect of gender on the expression of HER2 levels in bladder cancer patients. However, HER2 expression in male patients was significantly higher than that in women according to TCGA databases. HER2 expression was also associated with carcinoma in situ, multifocal tumors, large tumor size, high tumor stage and grade, lymph node metastases, risk of recurrence and progression, low recurrence-free survival (RFS) rate. HER2 expression status had no effect on overall survival.Conclusions: Our meta-analysis showed that HER2 expression was related to pathological malignancy and poor prognosis in bladder cancer which indicated that it could be used as an effective biomarker and therapeutic target.
Assessment of the YKL-40 concentration in patients with tick-borne encephalitis
Authors: Czupryna Piotr , Kulczyńka-Przybik Agnieszka , Mroczko Barbara , Wondim Mulugeta , Grygorczuk Sambor , Borawski Karol , Pancewicz Sławomir , Moniuszko Anna
Published: December 2020

Background
Tick-Borne Encephalitis (TBE) is a viral infection of the Central Nervous System (CNS) caused by Tick-Borne Encephalitis Virus (TBEV). It might take several clinical courses such as: meningitis, meningoencephalitis or meningoencephalomyelitis. The aim this study was to compare the YKL-40 concentration in cerebrospinal fluid (CSF) of patients with different clinical presentations of TBE and patients with excluded meningitis (control group).
Methods
The concentration of YKL-40 in CSF was determined using Fujirebio tests (Ghent, Belgium) in 32 patients with TBE: group I—patients with meningoencephalitis (n = 16); group II—patients with meningitis (n = 16). The control group (CG) consisted of 17 patients in whom inflammatory process in central nervous system was excluded.
Results
The concentration of YKL-40 was significantly higher in encephalitis group than in CG after 7 days from the last dose of treatment. The concentration in patients with neuroinflammation had significantly different concentration of YKL-40 compared to patients with no neuroinflammation control groups. ROC curve analysis indicates that: CSF YKL-40 concentration at cut off 783.87 differentiated TBE patients from CG with 100% specificity and 70% sensitivity and CSF YKL-40 concentration at cut off 980.11 differentiated meningitis from meningoencephalitis with 87.5% specificity and 62.5% sensitivity.
Conclusions
YKL-40 takes part in TBE pathogenesis, its concentration is the highest at the early stage of Central Nervous System involvement and decreases in the convalescent period. As YKL-40 is significantly higher in meningitis than in meningoencephalitis, it might be used as biomarker in differentiation of these clinical forms of TBE.
Endometriosis of the lung: case report and literature review
Authors: Yao Jin , Zheng Hong , Nie Hui , Huang Jiajia , Tan Na , Li Chengfang , Dong Xiaoli , Zhang Wen , Wang Jinjing
Published: December 2020

Background:Lung endometriosis is an extremely rare gynecological disease. Literature reports suggest that most patients will show generic symptoms such as hemoptysis, pneumothorax, and hemopneumothorax, which can often result in misdiagnosis. There are case reports of 18 patients with lung endometriosis describing clinical manifestation, imaging changes, treatment and prognosis. To provide further information on this rare disease, we present a case of pulmonary endometriosis and a review of lung endometriosis.Case presentation:We report on a 19-year-old female who was admitted to hospital due to repeated menstrual hemoptysis for 3 months. Computed tomography during menstruation showed patchy high-density shadows sized approximately 0.5 cm × 0.5 cm × 0.5 cm in the right middle lobe of the lung. Following menstruation, hemoptysis and changes on CT imaging disappeared. Thoracoscopic right middle lobectomy, right lower lung repair, and closed thoracic drainage were performed. Postoperative histopathology confirmed lung endometriosis. There was no recurrence of symptoms after 6 months of follow-up. Conclusions: We review the literature on factors associated with lung endometriosis, diagnosis, and treatment options. We propose that the diagnosis for lung endometriosis should be made by comprehensively integrating patient reproductive history, clinical and imaging details as well as histopathology. Surgical resection appears to be an effective treatment for lung endometriosis.
The reciprocal loop of MALAT1 and HIF-1α facilitates gemcitabine resistance in pancreatic cancer by enhancing glycolysis
Authors: Zhang Zhengle , Han Han , Gong Qiong , Rong Yuping , Li Hanjun , Zhu Zhongchao , Mei Pei , Zhao Chuanbing , Tang Zhigang , Tao Jing
Published: December 2020

Background

Profound chemoresistance is a prominent and intractable problem in pancreatic cancer. Gemcitabine, a first-line chemotherapeutic drug for pancreatic cancer, has provided only minimal benefits for patients; however, the underlying mechanisms remain to be investigated. Enhanced aerobic glycolysis has been suggested to be correlated with the phenotype of drug resistance, while MALAT1 has been indicated to be associated with poor gemcitabine response. However, the implicated regulatory mechanisms still need to be further explored.
Methods

The mRNA level of MALAT1, HIF-1α, and glycolytic enzymes were analyzed by qRT-PCR. The protein level of HIF-1α and glycolytic enzymes were detected by western blot analysis. The glucose uptake and lactate level were measured by glucose uptake and lactate production assay, respectively. The cell apoptosis was evaluated by apoptosis analysis using Annexin V/propidium iodide (PI) staining. The sensitivity to gemcitabine was measured by MTT assay. The binding of HIF-1α to the promoter of MALAT1 was tested by ChIP assay. The xenograft model of pancreatic cancer was established to examine the combined effect of MALAT1 knockdown and gemcitabine chemotherapy in vivo.
Results

In this study, we showed that low concentrations of gemcitabine promoted the expression of key glycolytic enzymes, such as GLUT1, HK2, and LDHA, as well as glucose uptake and lactate production in pancreatic cancer cells, while inhibition of glycolysis suppressed gemcitabine chemoresistance. In addition, we found that MALAT1 expression was induced by gemcitabine and mediated enhanced glycolysis and chemoresistance. Silencing MALAT1 inhibited the level of gemcitabine-induced HIF-1α expression and reinforced gemcitabine-induced apoptosis in vitro and in vivo. Furthermore, HIF-1α could bind the promoter of MALAT1 transcriptionally and mediate the glycolysis induced by gemcitabine.
Conclusions

Our data suggest a critical role of glycolytic metabolism in acquired gemcitabine resistance through the positive feedback loop of MALAT1 and the HIF-1α signaling pathway. Our results will provide a basis for developing potential therapeutic targets to reverse gemcitabine resistance.
Purinergic Signaling Participates in a Transition Between Functional States of Reactive Microglia and Controls Astrocyte-Driven Neuroinflammation in the Model of Trimethyltin-Induced Neurodegeneration
Authors: Dragić Milorad , Mitrović Nataša , Adžić Marija , Nedeljković Nadežda , Grković Ivana
Published: December 2020

BackgroundThe present study aims to explore the involvement of purinergic signaling in the rodent model of hippocampal degeneration induced by trimethyltin (TMT), which results in behavioral and neurological dysfunction similar to Alzheimer’s disease. Our study has provided novel evidence that TMT induced extracellular depositions of amyloid β, which might be the cause of the well-defined progressive hippocampal neurodegeneration and gliosis. MethodsWe have applied enzyme histochemistry and immunohistochemistry to study spatial and temporal patterns of ectonucleotidase NTPDase1/CD39 and eN/CD73 expression, gene expression analysis and immunochemistry to analyze cellular localization of select purinoreceptors and pro-inflammatory cytokines previously associated with microglia and astrocytes activation. ResultsOur study demonstrated that all Iba1-ir microglial cells, irrespective of the cell shape and localization, upregulated NTPDase1/CD39, while the induction of eN/CD73 has been observed only at amoeboid microglia, localized within the hippocampal layers with pronounced cell death. Marked induction of P2Y12R and P2Y6R at amoeboid microglia might reflect the transition from rod to amoeboid microglia and the adaptation to the migratory and phagocytic properties of the latter. Based on the expression of the microglial polarization markers, the majority of microglia belonged to the M2-like functional state. A significant change in purinergic signaling components accompanied the response of reactive astrocytes, which occupied the areas with pronounced cell death. Reactive astrocytes, which markedly expressed adenosine A2A and P2Y1 receptors, showed massive induction of complement component C3, NF-kB and IL-1β, suggesting that astrocyte-derived inflammation might be responsible for prolonged and spreading neurodegeneration in TMT model.Conclusion﻿This study put glia-associated purinergic signaling in the center of molecular pathogenesis of AD-like disease. Our findings suggest that the ectonucleotidases and purinergic signaling play significant role in microgliosis, astrocyte-driven neuroinflammation and prolonged neurodegeneration in the TMT model.
Integration of Family Planning Services With HIV Treatment for Women of Reproductive Age Living With HIV Attending ART in Special Zone of Oromia Regional State, Ethiopia
Authors: Demissie Dereje Bayissa , Mmusi-Phetoe Rose
Published: December 2020

Background: In settings where HIV prevalence is high, management of sexual and reproductive health is critical to reducing HIV transmission and maternal mortality. Integration of family planning with HIV services is appropriate model for HIV therapy, HIV prevention and care with family planning services in a resource limiting area like Ethiopia. The aims of the study were to determine the status of integration of family planning services with HIV treatment for women of reproductive age in Oromia, Ethiopia Methods: A Health facility based cross-sectional study design was conducted with quantitative data collection approach was used to collect data from women living with HIV attending ART clinics in special zone of surrounding Finfinne, Oromia Region in five health centres. Simple random sampling computer-generated sample was used to select 654 respondents. The returned questionnaires were checked for completeness, cleaned manually, coded and entered into EPI INFO 7.1.6 version. These were then transferred to statistical Package for Social Sciences 23.0 for further analysis. Bivariate and multivariable logistic regressions analysis was used to identify factors associated with integration family planning with HIV services with the significant association at adjusted odds ratio (AOR) with 95% confidence interval (CI) to controlled effects of possible confounders from final model. Result: After discarded16 spoiled questionnaires, the completed response rate of this study was 97.6% (654/670). There were 654 respondents whose ages ranged between 18 and 49 years. The mean age of the respondents was 31.86 years with a SD of ±6.0 years. Most of the respondents in the sample were in the age group 26-35 (n=374, 57%), and only 96 (14.7%) were in the age group 18-25. This study determined the overall integration FP-HIV services were 55.8% among reproductive age women living with HIV in Oromia regional state of special zone health centres. Almost all respondents (n=635, 97.1%) preferred integrated sexual reproductive health and HIV services at the same facility, from the same providers, and 622 (95%) were very or mostly satisfied with the utilisation of integrated family planning/HIV services.Conclusion: The identified factors that affected the integration of family planning with HIV services were educational and occupational status, residence, discussion of family planning with healthcare providers, fertility desire and CD4 counts. Therefore, Ministry of health should engage women in the planning, implementation and evaluation of the integrated family planning/HIV services.
A Machine Learning Algorithm to Predict Hyperglycemic Cases Induced by PD-1/PD-L1 Inhibitors in the Real World
Authors: Yang Jincheng , Lin Weilong , Shi Liming , Deng Ming , Yang Wenjing
Published: December 2020

Background: Diabetes mellitus and cancer are amongst the leading causes of deaths worldwide; hyperglycemia plays a major contributory role in neoplastic transformation risk. From reported adverse events of PD-1 or PD-L1 (programmed death 1 or ligand 1) inhibitors in post-marketing monitoring, we aimed to construct an effective machine learning algorithm to predict the probability of hyperglycemic adverse reaction from PD-1/PD-L1 inhibitors treated patients efficiently and rapidly. Methods: Raw data was downloaded from US Food and Drug Administration Adverse Event Reporting System (FDA FAERS). Signal of relationship between drug and adverse reaction based on disproportionality analysis and Bayesian analysis. A multivariate pattern classification of Support Vector Machine (SVM) was used to construct classifier to separate adverse hyperglycemic reaction patients. A 10-fold-3-time cross validation for model setup within training data (80% data) output best parameter values in SVM within R software. The model was validated in each testing data (20% data) and two total drug data, with exactly predictor parameter variables: gamma and nu. Results: Total 95918 case files were downloaded from 7 relevant drugs (cemiplimab, avelumab, durvalumab, atezolizumab, pembrolizumab, ipilimumab, nivolumab). The number-type/number-optimization method was selected to optimize model. Both gamma and nu values correlated with case number showed high adjusted r2 in curve regressions (both r2 >0.95). Indexes of accuracy, F1 score, kappa and sensitivity were greatly improved from the prediction model in training data and two total drug data. Conclusions: The SVM prediction model established here can non-invasively and precisely predict occurrence of hyperglycemic adverse drug reaction (ADR) in PD-1/PD-L1 inhibitors treated patients. Such information is vital to overcome ADR and to improve outcomes by distinguish high hyperglycemia-risk patients, and this machine learning algorithm can eventually add value onto clinical decision making.
MiR-190 Promotes Malignant Transformation and Progression of Human Urothelial Cells through CDKN1B Inhibition
Authors: Huang Shirui , Hua Xiaohui , Kuang Mengjiao , Zhu Junlan , Mu Haiqi , Tian Zhongxian , Zheng Xiaoqun , Xie Qipeng
Published: December 2020

BackgroundAlthough miR-190 has been reported to be related to human diseases, especially in the development and progression of cancer, its expression in human bladder cancer (BC) and potential contribution to BC remain unexplored.MethodsqRT-PCR was used to verify the expression level of miR-190 and CDKN1B. Flow cytometry (FCM) assays were performed to detect cell cycle. Soft agar assay was used to measure anchorage-independent growth ability. Methylation-Specific PCR, Dual-luciferase reporter assay and Western blotting were used to elucidate the potential mechanisms involved.ResultsOur studies revealed that downregulation of the CDKN1B/p27 protein is an important event related to miR-190, promoting the malignant transformation of bladder epithelial cells. miR-190 binds directly to CDKN1B 3’-UTR and destabilizes CDKN1B mRNA. Moreover, miR-190 downregulates TET1 by binding to the TET1 CDS region, which mediates hypermethylation of the CDKN1B promoter, thereby resulting in the downregulation of CDKN1B mRNA. These two aspects led to miR-190 inhibition of p27 protein expression in human BC cells. However, the increased expression of miR-190 in BC and its upstream regulatory mechanism remain unclear. A more in-depth mechanistic study showed that c-Jun promotes the transcription of Talin2, the host gene of miR-190, thus upregulating the expression of miR-190 in human BC cells.ConclusionIn this study, we found that miR-190 plays an important role in the development of BC. Taken together, these findings indicate that miR-190 may promote the malignant transformation of human urothelial cells by downregulating CDKN1B, which strengthens our understanding of miR-190 in regulating BC cell transformation.
Oleandrin Induces Immunogenic Cell Death Via the PERK/elF2α/ATF4/CHOP Pathway in Breast Cancer
Authors: Li Xiaoxi , Zheng Jian , Chen Shi , Meng Fan-dong , Ning Jing , Sun Shu-lan
Published: December 2020

Background Chemotherapeutic agents have been linked to immunogenic cell death (ICD) induction that is capable of augmenting antitumor immune surveillance. The cardiac glycoside oleandrin, which inhibits Na+/K+-ATPase pump (NKP), has been shown to suppress breast cancer growth via inducing apoptosis. However, the implications of oleandrin in antitumor immune response and potential ICD induction remain unexplored till now, which is investigated in the present study.Methods Calreticulin (CRT) exposure was detected by immunofluorescence and flow cytometry, and high mobility group protein B1 (HMGB1) and Adenosine Triphosphate (ATP) secretion was quantified by ELISA and both the intracellular and extracellular expression of Heat shock protein 70/90 (HSP70/90) was detected by western blotting in breast cancer cells treated with oleandrin. Dendritic cells (DCs) were co-cultured with oleandrin-treated breast cancer cells before the expressions of activation markers and cytokines were examined by quantitative real time polymerase chain reaction (qRT-PCR), ELISA, and flow cytometry. Immune activation effects of oleandrin were determined in murine breast cancer model using BALB/C mice. The differential mRNA expression incurred by oleandrin was investigated by mRNA sequencing and subsequently confirmed by qRT-PCR and Western blotting. Results Oleandrin treatment induced CRT exposure on cell surface and the release of HMGB1, HSP70/90 and ATP. The maturation and activation of DCs were increased by co-culturing with oleandrin-treated cancer cells, which subsequently enhanced CD8+ T cell cytotoxicity. In animal models, oleandrin inhibited tumor growth and increased tumor infiltrating lymphocytes including DCs and T cells. Mechanistically, oleandrin induced endoplasmic reticulum (ER) stress associated caspase independent immunogenic cell death (ICD) mainly through PERK/elF2α/ATF4/CHOP pathway. Activation of IRE1 pathway but not ATF6, the other two canonical sensors of ER stress, was also observed. Conclusion Oleandrin triggered ER stress and induced ICD-mediated immune destruction of breast cancer cells. Oleandrin combined with immune checkpoint inhibitors might improve the efficacy of immunotherapy.
What Are the Survival Factors in Surgically Resected Synchronous Multiple Primary Lung Cancers: A Retrospective Study
Authors: Li Haichao , Wang Kai , Zhang Xingxing , Chen Rong , Zhao Jian
Published: December 2020

BackgroundWith the popularization of high-resolution computed tomography (HRCT), the detection rate of synchronous multiple primary lung cancer (SMPLC) is increasing. We retrospectively analyzed the surgical results of SMPLC patients in our hospital to determine the best treatment, surgical prognosis and survival analysis.MethodsA total of 78 SMPLC patients met the diagnostic criteria underwent complete resection and lymph node dissection or sampling without any preoperative induction therapy in the Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University. We analyzed the postoperative survival rate, and further studied the relationship between survival rates and sex, age, preoperative symptoms, tumor location, tumor number, tumor size, lymph node metastasis, TNM stage, surgical type, surgical frequency, histopathologic types, vascular infiltration, visceral pleural invasion and postoperative therapy.ResultsAmong 78 patients, the 1-,2-,3-,4- and 5-year disease free survival (DFS) rates were 93.42%, 86.84%, 77.78%, 62.96%, and 60.00%, respectively, while the 1-,2-,3-,4- and 5-year overall survival (OS) rates were 94.73%, 92.11%, 82.22%, 77.78%, and 65.00%, respectively. TNM stage of the largest tumor (II:HR=7.40,III:9.01,p=0.002) was an independent risk factor for DFS. Smoking history (HR=4.34,p=0.039) and TNM stage of the largest tumor (II:HR=9.38,III:9.42,p=0.003) were independent risk factors for overall survival.ConclusionsFirst, SMPLC is different from intrapulmonary metastasis and its clinical stage is also different from the 8th (2015) edition TNM classification for lung cancer. Second, when pulmonary function permits, surgery (complete resection and lymph node dissection) is a significantly beneficial treatment for patients with SMPLC. Third, TNM stage of the largest tumor (II:HR=7.40,III:9.01,p=0.002) was an independent risk factor for DFS. Smoking history (HR=4.34,p=0.039) and TNM stage of the largest tumor (II:HR=9.38,III:9.42,p=0.003) were independent risk factors for overall survival.
Pyrroloquinoline Quinone Regulates the Redox Status in Vitro and Vivo of Weaned Pigs via the Nrf2/HO-1 Pathway
Authors: Huang Caiyun , Fan Zijuan , Han Dandan , Johnston Lee J , Ma Xi , Wang Fenglai
Published: December 2020

BackgroundOxidative stress is a main cause of piglet gut damage and diarrhea. Pyrroloquinoline quinone (PQQ), is a novel redox cofactor with antioxidant properties. However, the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood. Therefore, the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line (IPEC-J2) challenged with H2O2.ResultsExperiment 1, 144 Duroc × Landrace × Yorkshire pigs (weaned at 28 d) were allocated to four groups: receiving a basal diet (control) and diets supplemented with 0.15, 0.30, and 0.45 % PQQ. On d 28, growth performance, diarrhea incidence and redox factors were measured. Experiment 2, IPEC-J2 were treated with or without PQQ in the presence or absence of H2O2 for indicated time points. Experiment 3, IPEC-J2 were transfected with or without Nrf2 siRNA, then treated according to Experiment 2. The cell viability, redox factors, protein of tight junctions and Nrf2 pathway were determined. In vivo, PQQ supplementation demonstrated dose-related improvements in average daily gain, and gain to feed ratio (Linear P < 0.05). During d 0-28, compared to controls, 0.45% PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum, and increased concentration of SOD in liver; 0.3% PQQ supplementation decreased ileal and liver MDA concentration; and 0.15% PQQ supplementation decreased ileal MDA concentration (P < 0.05). In vitro, compared to cells cultured with H2O2, pre-treatment with PQQ increased cell viability, tight junction proteins expression including ZO-1, ZO-2, occludin and claudin-1; and decrease ROS concentration and level of Caspase-3 (P < 0.05); as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2, HO-1. Notably, Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H2O2-induced intracellular changes. Conclusions﻿PQQ administration attenuated oxidative stress in weaned pigs which is associated with activation of Nrf2/HO-1 pathway.
A Novel Automatic Cough Frequency Monitoring System Combining a Triaxial Accelerometer and a Stretchable Strain Sensor
Authors: Otoshi Takehiro , Nagano Tatsuya , Izumi Shintaro , Hazama Daisuke , Katsurada Naoko , Yamamoto Masatsugu , Tachihara Motoko , Kobayashi Kazuyuki , Nishimura Yoshihiro
Published: December 2020

BackgroundObjective evaluations of cough frequency are considered important for assessing the clinical state of patients with respiratory diseases. While cough monitors with audio recordings are used in research settings, they are rarely used in clinical settings. Issues regarding privacy and background noise (especially the sounds of someone else’s cough) with audio recordings are barriers to the wide use of these monitors in clinical settings; to solve these problems, we developed a novel automatic cough frequency monitoring system combining a triaxial accelerator and a stretchable strain sensor.MethodsEleven healthy adult volunteers and 10 adult patients with cough were enrolled. The participants sat in a chair and wore two devices for 30 minutes for the cough measurements. An accelerator was attached to the epigastric region, and a stretchable strain sensor was worn around their neck. When the subjects coughed, these devices displayed specific waveforms. For the development of the algorithm, the participants’ measurement data from both devices were divided into consecutive small “units” lasting 5 seconds each. Whether each unit corresponded to a “cough unit” was determined by the observer who manually counted the cough records. Then, the data from all the participants were categorized into a training dataset and a test dataset. Using a variational autoencoder, a machine learning algorithm with deep learning, the components of the test dataset were automatically judged as being a “cough unit” or “non-cough unit”.ResultsThe sensitivity and specificity in detecting coughs among 21 participants were 92% and 96%, respectively. The triaxial accelerometer only yielded a sensitivity of 91% and specificity of 95%. Therefore, the diagnostic accuracy improved slightly when the accelerometer was combined with a stretchable strain sensor.Conclusions﻿According to the results of the current study, a cough frequency monitor with good performance can be created by combining an accelerometer and another biometric sensor. Our cough monitor is suitable for ambulatory settings because the devices are small and light. Our cough monitoring system, which does not require audio recordings, has the potential to be widely used in clinical settings without any concerns regarding privacy or background noise.
Up-regulation of nPKC Contributes to Proliferation of Pulmonary Artery Smooth Muscle Cells in Hypoxia-induced Pulmonary Hypertension
Authors: Shi Yiwei , Jiang Rui , Qin Xiaojiang , Gao Anqi , Hou Xiaomin , Chen Liangjing , Xu Xinrong , Chai Lina , Guo Yunting , Zhao Liangyuan , Wu Furong
Published: December 2020

Background It has been indicated that protein kinase C (PKC) plays a vital role in the pathogenesis of hypoxia-induced pulmonary hypertension (PH). The functions or the pathogenic roles of PKCs vary from different types, and their related downstream pathways may also be distinct. Therefore, the specific role of different types of PKC deserves to be elucidated. Discussions regarding conventional PKC (cPKC) have dominated research in recent years, however, the relationship between novel PKC (nPKC) and the development of PH remain unclear. In addition, it is less known whether nPKC has a direct effect on the proliferation of pulmonary artery smooth muscle cells (PASMCs). This study is designed to investigate the role of nPKC in mediating PASMCs proliferation in PH and the underlying mechanisms. Methods Mouse PASMCs was isolated using magnetic separation technology. The PASMCs were divided into 24 h group, 48 h group and 72 h group according to different hypoxia treatment time, then detected cell proliferation rate and nPKC expression level in each group. We treated PASMCs with agonists or inhibitors of PKCδ and PKCε and exposed them to hypoxia or normoxia for 72 h, then measured the proliferation of PASMCs. We also constructed a lentiviral vector containing siRNA fragments for inhibiting PKCδ and PKCε to transfected PASMCs, then examined their proliferation. Results PASMCs isolated successfully by magnetic separation method and were in good condition. Hypoxia promoted the proliferation of PASMCs, and the treatment for 72 h had the most significant effect. Hypoxia upregulated the expression of PKCδ and PKCε in mouse PASMCs, leading to PASMCs proliferation. Moreover, Our study demonstrated that hypoxia induced upregulation of PKCδ and PKCε expression resulting to the proliferation of PASMCs via up-regulating the phosphorylation of AKT and ERK. Conclusions Our study provides clear evidence that increased nPKC expression contributes to PASMCs proliferation and uncovers the correlation between AKT and ERK pathways and nPKC-mediated proliferation of PASMCs. These findings may provide novel targets for molecular therapy of pulmonary hypertension.
Evidence for a Potential Common Gene Network of Smith-Magenis and Potocki-Lupski Syndromes, DAND (DEAF1-Associated Neurodevelopmental Disorder) and ZEB1-Associated Neurodevelopment Disorder
Authors: Chen Li , Jensik Philip J , Yuan Xi , Liu Muyin , Saffen David , Elsea Sarah H
Published: December 2020

Background: Neuropsychiatric disorders are highly heterogeneous and often display overlapping phenotypes, suggesting possible defects in common genetic networks. We previously reported pathogenic variants in deformed epidermal autoregulatory factor-1 (DEAF1) that contribute to DEAF1-associated neurodevelopmental disorder (DAND) and predicted that DEAF1 regulates expression of retinoic acid induced 1 (RAI1), the causative gene of Smith-Magenis syndrome (SMS) and Potocki-Lupski Syndrome (PTLS), through a putative DEAF1 binding sequence (DBS) in RAI1 intron 2, suggesting a common genetic network of these disorders that needs further study. Methods: In this study, we tested the DEAF1 binding and transcriptional regulation of RAI1 using luciferase reporter gene assay, EMSA and ChIP. We explored the upstream regulator of DEAF1 using bioinformatics analysis, qPCR and ChIP, and generated a potential network involving these genes based on patients’ phenotype and bioinformatics analysis.Results: We demonstrated that DEAF1 binds to the RAI1 DBS and regulates RAI1 expression in vitro, and a pathogenic variant in the DEAF1 SAND domain was defective in binding the RAI1 DBS. We also obtained evidence that DEAF1 expression is regulated by the transcription factor ZEB1 via predicted binding sites in DEAF1 intron 1. Microdeletions and variants in ZEB1 have been implicated in brain developmental disorders, including intellectual disability (ID), autism, agenesis of corpus callosum (ACC) and corneal dystrophy. Patients harboring deletions or pathogenic variants of ZEB1, DEAF1 or RAI1 display partially overlapped symptoms, including ID, autistic features, speech impairment, developmental delay and dysmorphologies.Conclusions: Together, these results provide evidence for a common molecular network in ZEB1-associated neurodevelopment disorder, DAND, SMS and PTLS.
Validation of Perceived Physical Fatigability Using the Simplified-Chinese Version of the Pittsburgh Fatigability Scale
Authors: Hu Yixin , Zhang Hangming , Xu Weihao , Zhao Ming , Liu Juan , Wu Linna , Zou Lin , Zuo Jing , Liu Yunxia , Bair Woei-Nan , Qiao Yujia(Suanna) , Glynn Nancy W.
Published: December 2020

Background: The Pittsburgh Fatigability Scale (PFS) was developed to capture fatigue and demand in a single tool, filling a gap that no validated questionnaire existed to measure perceived fatigability. Since fatigability is a more sensitive measure of a person’s susceptibility to fatigue, we validated the simplified-Chinese version of the PFS among Chinese community-dwelling older adults.Methods: The PFS was translated into the simplified-Chinese by the translation, retro-translation method. Internal consistency of the Physical subscale of the PFS was evaluated by Cronbach’s alpha. Convergent validity and discriminant validity were evaluated against physical performance measures (i.e., Short Physical Performance Battery & Timed Up and Go Test) and daily living performance (i.e., Barthel Index & Instrumental activity of daily living).Results: The simplified-Chinese version of PFS Physical scores showed strong internal consistency (Cronbach’s alpha=0.81). Higher PFS Physical scores were associated with worse physical performance, and daily living performance (|correlation coefficient| range: 0.36-0.56, p<.001). Age- and sex-adjusted PFS Physical scores had moderate to good overall discrimination for correctly classifying people by their physical performance and daily living performance (AUCs range 0.70-0.87, p<.001)Conclusions: The PFS simplified-Chinese version is a valid instrument to assess perceived physical fatigability in Chinese-speaking older adults with good convergent validity. Thus, the PFS, with low cost and greater feasibility, is a desired tool to measure fatigability in large population studies.
Effects of Exogenous Nerve Growth Factor on The Expression of BMP-9 and VEGF in The Healing of Rabbit Mandible Fracture With Local Nerve Injury
Authors: Yang Sen , Cheng Jiao , Man Cheng , Jiang Lian , Long Guogeng , Zhao Wenjun , Zheng Dexin
Published: December 2020

Background: Mandibular fracture healing is a complex process involving nerves and growth factors. Nerve growth factor (NGF) not only facilitates the maintenance of sympathetic neurite growth but also stimulates other growth factors that can promote the essential osteogenesis and angiogenesis for fracture healing. Therefore, it is necessary to analyze the combined effects of NGF, bone morphogenic protein-9 (BMP-9), and vascular endothelial growth factor (VEGF) to accelerate the healing of mandible fractures.Methods: The models of mandible fracture with local nerve injury established in forty-eight rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group, and intact group. The recovery of nerve reflex was assessed by observing the number of rabbits with lower lip responses to acupuncture. The fracture healing was observed with visual and CBCT, and then callus tissues from the mandibular fracture area were collected for hematoxylin and eosin (HE) staining observation, and the expression of BMP-9 and VEGF in callus at different stages was detected by quantitative real-time PCR (qRT-PCR).Results: Needling reaction in the lower lip showed the number of animals with nerve reflex recovery was significantly higher in the NGF group than that in the GS and blank groups at the 2nd and 4th weeks after the operation. The combined results of macroscopic observation, CBCT examination, and histological analysis showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in the NGF group and the amount of callus formation and reconstruction was better than that in the GS group at the 2nd week after the operation. The qRT-PCR results indicated that the expression levels of BMP-9 and VEGF in the four groups reached the highest values at the 2nd week, while the expression levels of both in the NGF group were significantly higher than that in the GS group.Conclusion: The exogenous NGF could accelerate the healing of mandible fractures. This work will provide a new foundation and theoretical basis for clarifying the mechanism of fracture healing, thereby promoting fracture healing and reducing the disability rate of patients.
Wrapping the Stump of the Gastroduodenal Artery Using the Ligamentum Teres Hepatis During Laparoscopic Pancreaticoduodenectomy – A Center’s Preliminary Experience
Authors: Meng Lingwei , Cai He , Cai Yunqiang , Li Yongbin , Peng Bing
Published: December 2020

Background: The present study aims to assess the preliminary outcomes of the effectiveness of wrapping the ligamentum teres hepatis (LTH) around the gastroduodenal artery stump for the prevention of erosion hemorrhage after laparoscopic pancreaticoduodenectomy (LPD).Methods: We reviewed 247 patients who had undergone LPD between January 2016 and April 2019. The patients were divided into 2 groups according to whether LTH wrapped the stump of the gastroduodenal artery: group A (119 patients) who underwent the LTH wrapping procedure, and group B (128 patients) who did not undergo the procedure. The perioperative data from the two groups were reviewed to assess the effectiveness of the LTH procedure for the prevention of postpancreatectomy hemorrhage (PPH) and other complications.Results: No differences were observed in the clinical characteristics between the 2 groups. The data from 247 patients were acceptable for analysis: 119 patients underwent wrapping, and 128 patients did not. The incidence of clinically relevant pancreatic fistula (8.4% vs 3.9%), biliary fistula (2.5% vs 1.6%), intra-abdominal infection (10.1% vs 3.9%) and delayed gastric emptying (13.4% vs 16.4%) showed no significant difference between group A and group B. The 90-day mortality and 90-day reoperation rates (0.8% vs 0.8% and 5.0% vs 3.1%) were also similar between group A and group B. Furthermore, postpancreatectomy hemorrhage of Grade B and C occurred in 0 patients (0.0%) in the wrapping group, which was significantly less frequent than the occurrence in the nonwrapping group (7 patients; 5.5%, P=0.02).Conclusions: Wrapping the LTH around the gastroduodenal artery stump after LPD does not reduce the incidence of clinically relevant pancreatic fistula, biliary fistula or delayed gastric emptying. However, this procedure has a trend of reducing the rate of PPH of Grade B and C after LPD and is simple to perform.
Determinants of Developing Symptomatic Disease in Ethiopian COVID-19 Patients: A Case-Control Study
Authors: Leulseged Tigist Workneh , Alemahu Degu G. , Hassen Ishmael S. , Maru Endalkachew H. , Zewde Wuletaw C. , Chamesew Nigat W. , Yegele Kalkidan T. , Abebe Daniel S. , Abdi Firaol M. , Menyelshewa Etsegenet Y. , Gerbi Tegenu G. , Hagos Helen T.
Published: December 2020

Background: Studies show that having some symptoms seems to be associated with more severe disease and poor prognosis. Therefore, knowing who is more susceptible to symptomatic COVID-19 disease is important to provide targeted preventive and management practice. The aim of the study was to assess the determinants of having symptomatic disease among COVID-19 patients admitted to Millennium COVID-19 Care Center in Ethiopia.Methods: A case-control study was conducted from August to September 2020 among a randomly selected 765 COVID-19 patients (372 Asymptomatic and 393 Symptomatic patients). Chi-square test and independent t-test were used to detect the presence of a statistically significant difference in the characteristics of the cases (symptomatic) and controls (asymptomatic), where p-value of <0.05 considered as having a statistically significant difference. Multivariable binary logistic regression was used to assess a statistically significant association between the independent variables and developing symptomatic COVID-19 where Adjusted Odds ratio (AOR), 95% CIs for AOR, and P-values were used for testing significance and interpretation of results. Results: The result of the multivariable binary logistic regression shows that age group (AOR= 1.818, 95% CI= 1.210, 2.731, p-value=0.004 for 30-39 years; AOR= 1.611, 95% CI= 1.016, 2.554, p-value=0.043 for 40-49 years and AOR= 4.076, 95% CI= 2.582, 6.435, p-value=0.0001 for years and above), sex (AOR= 1.672, 95% CI= 1.216, 2.299, p-value=0.002) and history of diabetes mellitus (AOR= 2.406, 95% CI= 1.384, 4.181, p-value=0.002) were found to be significant factors that determine the development of symptomatic disease in COVID-19 patients.Conclusions: Developing a symptomatic COVID-19 disease was found to be determined by exposures of old age, male sex, and being diabetic. Therefore, patients with the above factors should be given enough attention in the prevention and management process, including inpatient management, to pick symptoms earlier and to manage accordingly so that these patients can have a favorable treatment outcome.
Prevalence and Risk Factors of Hemodynamic Instability Associated with Preload-Dependence During Continuous Renal Replacement Therapy in a Prospective Observational Cohort of Critically Ill Patients
Authors: CHAZOT Guillaume , BITKER Laurent , MEZIDI Mehdi , CHEBIB Nader , CHABERT Paul , CHAUVELOT Louis , FOLLIET Laure , DAVID Guillaume , PROVOOST Judith , YONIS Hodane , Richard Jean-christophe
Published: December 2020

BackgroundHemodynamic instability is a frequent complication of continuous renal replacement therapy (CRRT). Postural tests (i.e. passive leg raising in the supine position or Trendelenburg maneuver in the prone position) combined with measurement of cardiac output are highly reliable to identify preload-dependence and may provide new insights into the mechanisms involved in hemodynamic instability related to CRRT (HIRRT). We aimed to assess the prevalence and risk factors of HIRRT associated with preload-dependence in ICU patients.MethodsWe conducted a single-center prospective observational cohort study in ICU patients with acute kidney injury KDIGO 3, started on CRRT in the last 24 hours, and monitored with a PiCCO® device. The primary endpoint was the rate of HIRRT episodes associated with preload-dependence during the first 7 days after inclusion. HIRRT was defined as the occurrence of a mean arterial pressure below 65 mm Hg requiring therapeutic intervention. Preload-dependence was assessed by postural tests every 4 hours, and during each HIRRT episode. Data are expressed in median [1rst quartile-3rd quartile], unless stated otherwise.Results42 patients (62% male, age 69 [59–77] year, SAPS-2 65 [49–76]) were included 6 [1–16] hours after CRRT initiation and studied continuously for 121 [60–147] hours. A median of 5 [3–8] HIRRT episodes occurred per patient, for a pooled total of 243 episodes. 131 episodes (54% [CI95%: 48%-60%]) were associated with preload-dependence, 108 (44%, [CI95%: 38%-51%]) without preload-dependence, and 4 were unclassified. Multivariate analysis (using variables collected prior to HIRRT) identified the following variables as risk factors for the occurrence of HIRRT associated with preload-dependence: preload-dependence before HIRRT (odd ratio (OR) = 3.82, p < 0.001), delay since last HIRRT episode > 8 hours (OR = 0.56, p < 0.05), lactate (OR = 1.21 per 1-mmol.L− 1 increase, p < 0.05), cardiac index (OR = 0.47 per 1-L.min− 1.m− 2 increase, p < 0.001) and SOFA at ICU admission (OR = 0.91 per 1-point increase, p < 0.001). None of the CRRT settings was identified as risk factor for HIRRT.Conclusions:In this single center study, HIRRT associated with preload-dependence was slightly more frequent than HIRRT without preload-dependence in ICU patients undergoing CRRT. Testing for preload-dependence to adjust fluid removal by CRRT could help preventing HIRRT occurrence during CRRT.