bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Comprehensive Evaluation of Crohn's Disease Activity by Intestinal Computed Tomography Enterography Combined with Endoscopy and Biochemical Indicators
Authors: Liu yajun , tian feiyan , yi jun , gong lingqi , chen lulu , chen shuijiao , liu xiaowei
Published: September 2020

Background: The treatment goal for Crohn’s disease (CD) has turned towards mucosal healing and resolution of the transmural inflammation. The purpose of this study was to evaluate how well computed tomography enterography (CTE) correlated with other treatments, in particular, endoscopy and biochemical indicators, in newly diagnosed patients with CD.Methods: 123 patients with CD who received CTE in the Xiangya Hospital of Central South University, China, from April 2017 to April 2019 were included. Clinical case data and imaging results were retrospectively reviewed. The clinical activity of CD was determined by the Crohn’s disease activity index (CDAI) score and biochemical indicators. The relationships between CTE and endoscopy, CDAI score, and inflammatory markers were evaluated.Results: The diagnostic rate of CTE in the 123 CD patients was 68.3% (84/123). Logistic regression analysis showed that the specific CTE manifestations related to CD activity were intestinal wall stratification, comb sign, and abdominal abscesses (P < 0.05). Spearman’s rank correlation analysis showed that inflammatory markers correlated positively with different CTE imaging manifestations. The CTE findings were consistent with colonoscopy results in 136 intestinal segments (73.1%) in terms of lesion location but were not consistent in 50 intestinal segments (26.9%).Conclusion: intestinal CTE has a high degree of completion and is well tolerated, in contrast to endoscopy which is both invasive and unable to reflect the level of intestinal mucosal infiltration. In conclusion, intestinal CTE combined with endoscopy and biochemical indicators is both comprehensive and effective in evaluating the condition of CD patients.
Temporal Changes of Haematological and Radiological Findings of the COVID-19 Infection - A Review of Literature
Authors: Lim Albert Yick Hou , Leng Goh Jun , Mae Chua Chui Wei , Heng Bee Hoon , Abisheganaden John Arputhan , George Pradeep Paul
Published: September 2020

Background: COVID-19 is a systemic viral infection with many clinical manifestations especially affecting the hematopoietic system and haemostasis. Few studies have highlighted the prognostic value of blood findings such as lymphopenia, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, LDH, CRP, cardiac troponin, low-density lipoproteins and chest radiographic abnormality. A study of progressions of blood and radiological results may help to identify patients at high risk of severe outcomes. This systematic review aimed to assess the temporal progression of blood and radiology findings of patients with COVID-19. Methods: Comprehensive systematic literature search was conducted on Medline, Embase and Cochrane databases to identify articles published for peripheral blood investigation and radiological results of COVID-19 patients. Results: A total of 27 studies were included in this review. The common laboratory features reported include lymphopenia, elevated levels of C-reactive proteins and lactate dehydrogenase. For radiological signs, ground-glass opacifications, consolidations, and crazy paving patterns were frequently reported. There is a correlation between lymphocyte count, neutrophil count and biomarkers such as C-reactive proteins and lactate dehydrogenase; at a later phase of the disease (more than 7 days since onset of symptoms), lymphopenia worsens while neutrophil count, C-reactive protein levels and lactate dehydrogenase levels increase. Frequencies of ground-glass opacifications and ground-glass opacifications with consolidations decrease at a later phase of the disease while that of consolidation and crazy paving pattern rises as the disease progresses. More extensive lung involvement was also seen more frequently in the later phases. Conclusions: The correlation between temporal progression and the reported blood and radiological results may be helpful to monitor and evaluate disease progression and severity.
Innovative Trial Approaches in Immune-Mediated Inflammatory Diseases: Current Use and Future Potential
Authors: Grayling Michael J , Bigirumurame Theophile , Cherlin Svetlana , Ouma Luke , Zheng Haiyan , Wason James
Published: September 2020

Background: Despite progress that has been made in the treatment of many immune-mediated inflammatory diseases (IMIDs), there remains a need for improved treatments. Randomised controlled trials (RCTs) provide the highest form of evidence on the effectiveness of a potential new treatment regimen, but they are extremely expensive and time consuming to conduct. Consequently, much focus has been given in recent years to innovative design and analysis methods that could improve the efficiency of RCTs. In this article, we review the current use and future potential of these methods within the context of IMID trials.Methods: We provide a review of several innovative methods that would provide utility in IMID research. These include novel study designs (adaptive trials, Sequential Multi-Assignment Randomised Trials, basket, and umbrella trials) and data analysis methodologies (augmented analyses of composite responder endpoints, using high-dimensional biomarker information to stratify patients, and emulation of RCTs from routinely collected data). IMID trials are now well-placed to embrace innovative methods. For example, well-developed statistical frameworks for adaptive trial design are ready for implementation, whilst the growing availability of historical datasets makes the use of Bayesian methods particularly applicable.To assess whether and how these innovative methods have been used in practice, we conducted a review via PubMed of clinical trials pertaining to any of 51 IMIDs that were published between 2018-20 in five high impact factor clinical journals. Results: Amongst 97 articles included in the review, 19 (19.6%) used an innovative design method, but most of these were relatively straightforward examples of innovative approaches. Only two (2.1%) reported the use of evidence from routinely collected data, cohorts, or biobanks. Eight (9.2%) collected high-dimensional data. Conclusions: Application of innovative statistical methodology to IMID trials has the potential to greatly improve efficiency, to generalise and extrapolate trial results, and to further personalise treatment strategies. Currently, such methods are infrequently utilised in practice. New research is required to ensure that IMID trials can benefit from the most suitable methods.
The impact of climate change on the productivity of conservation agriculture
Authors: Su Yang , Gabrielle Benoît , Makowski David
Published: September 2020

Conservation agriculture (CA) is being promoted as a set of management practices that can sustain crop production while providing positive environmental externalities. However, its impact on crop productivity is still hotly debated, and how this productivity will be affected by climate change remains uncertain. Here we compared the productivity of CA vs. conventional tillage (CT) systems under current and future climate conditions using a probabilistic machine-learning approach at the global scale. We reveal large differences in the probability of yield gains with CA across crop types, climate zones, and geographical regions. We show that, for most crops, CA performed better in continental, arid and temperate regions than in tropical ones. Under future climate conditions, the relative productive performance of CA is expected to increase for maize in almost all cropping areas within the tropical band, thus improving the competitiveness of CA for this major crop.
New Prediction Model for Cardiac Arrest Time of Palliative Care Patients in the Intensive Care Unit: A Single Center Retrospective Cohort Study
Authors: Takaki Shunsuke
Published: September 2020

Background: The trend of population ageing is a significant health issue in Japan and palliative care and end of life care are becoming key components of medical care. In the terminal care setting, the ability to accurately predict the time of death is an important research objective because it may allow family members to share valuable moments with the patient before death. Previous studies have investigated the time to death following withdrawal of therapy and several predictors of the time of death have been defined. The aim of this study was to determine an algorithm for the prediction of cardiac arrest time in the palliative care setting. Method: We retrospectively collected data of patients in the Yokohama City University Hospital between 2010 and 2016. Vital signs were collected until cardiac arrest, with continuous blood pressure recordings of <80 mmHg. We hypothesized that a breakdown of the autonomic nervous system was close to the time of cardiac arrest. We used the shock index (SI) defined as heart rate divided by systolic blood pressure (SBP) as the ratio variable for determination of the terminal phase. Results: A total of 4330 patients were admitted to the ICU. Of these, 19 patients were included to this study. We developed an exponential decay model using the SI and SBP: predicted Shock Index = 0.995 +(6.931-0.995) e -0.035 x SBP AUC 0.650 (0.512 to 0.788). The disparity between the real heart rate and predicted hear rate was -10 bpm (sensitivity, 49.9%; specificity, 75.8%; likelihood ratio, 2.06). In the validation data set, sensitivity was 52.7 %, specificity was 79.8 %, PPV was 35.7 %, and NPV was 88.8 %. LR was 2.61. Predicted residual time to cardiac arrest was calculated as follows: 12.3 + (0.18 x age) + (male: -6.0, female: 0) + (heart rate x 0.65) + (0.28 x Systolic Blood Pressure) + (0.34 x Heart Rate) + (-0.25 x Respiratory Rate). Conclusions: The new prediction model estimates the breakdown of the autonomic nervous system within 120 minutes of cardiac arrest. These algorithms might improve palliative care for last timing in the terminal situation.
Mutant Glucocorticoid Receptor Binding Elements on the Interleukin-6 Promoter Regulate Dexamethasone Effects
Authors: Chang Wen-Teng , Hong Ming-Yuan , Chen Chien-Liang , Hwang Chi-Yuan , Tsai Cheng-Chieh , Chuang Chia-Chang
Published: September 2020

BackgroundGlucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines. ResultsFive putative GR binding sites and other transcriptional factor binding sites were identified on the interleukin (IL)-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, NF-κB, AP-1, and Sp1-2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The first and third GR binding sites (GR2 and GR3) were noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation. ConclusionsWe concluded that selective GR2 and GR3 modulators might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.
Adaptation and Validation of the Portuguese Peabody Developmental Motor Scales - 2 edition: A Study With Children Aged 12 to 48 Months
Authors: Rebelo Miguel , Serrano João , Duarte-Mendes Pedro , Paulo Rui , Marinho Daniel Almeida
Published: September 2020

Background: The purpose of this study was to examine the psychometric properties of Peabody Developmental Motor Scales II (PDMS-2 - Folio & Fewell, 2000) using a Portuguese sample.Methods: The validation of the Portuguese version of the PDMS-2 was applied according to the manual, for 392 children, from two institutions, from 12 to 48 months, with an analysis of the internal consistency (α Cronbach), of Temporal Stability (ICC) and Construct validity (confirmatory factor analysis).Results: The results of the confirmatory factorial analysis (χ2 = 55.614; df=4; p=.06; χ2/df =13.904; SRMR=.065; CFI=.99, TLI=.99, RMSEA=.068) of two factors (Gross Motor and Fine Motor) as the original version. Most of the subtests had good internal consistency (α = .85) and good test-retest stability (ICC = .98 to .99).Conclusions: These results indicate that the Portuguese version of the PDMS-2 is an accurate and valid instrument to evaluate the gross and fine motor skills of children aged 12 to 48 months, can be used as a reference instrument by health and education professionals, as an indicator and support for the assessment of motor skills, thus having a assessment instrument that allows to detect maladjustments, deficiencies or precociousness, so that the child can later receive the appropriate intervention
A Comparison of Random Forest and Decision Tree for Suicide Ideation Classification
Authors: Mohammadian-Khoshnoud Mayam , Omidi Tahereh , Faradmal Javad , Poorolajal Jalal
Published: September 2020

Background: Suicide resulted from complex interaction factors. Most classical statistical methods were not efficiently enough to cover this complexity. With the new branch of statistics as statistical/machine learning, complex relationships between risk factors and responses can be modeled. Methods: We aimed to identify the high-risk groups for suicide using different classification methods including logistic regression(LR), decision tree(DT), and random forest(RF). Also, the prediction accuracy of the models is compared. This study used data obtained from a cross-sectional study conducted in in the Hamadan University of Medical Sciences from 2015-2016 to investigate the prevalence of suicidal ideation and related risk factors among university students. The LR, DT, and RF models were used to evaluate the high-risk group for suicide. Finally, the applied all three models were compared using sensitivity(SE), specificity(SP), and the area under receiver operating characteristics (ROC) curves. Results: In the training sample, the area under the ROC curve of the DT was greater than the LR and RF. But in the validation sample, the RF model has the best performance and the DT has the worst performance among these methods.Discussion: In this study, the risk factors for suicide were different for men and women. According to the results of the DT, substance abuse, average, general health score, faculty of education, depression were the risk factors on suicidal ideation in both genders. But despair about the future, residence (parents' house/dormitory) were among the factors contributing to the suicidal ideation of men. On the other hand, parents’ education, interested in the discipline and anxiety influence factors on suicidal ideation in women. The results of RF indicated that depression, general health score, average, anxiety and substance abuse were important risk factors for suicidal ideation in both genders. Also, the faculty of education and age are risk factors for suicide in women. Conclusions: In the training sample, the DT had better performance but in the validation sample, the RF model provided better results. The LR was the best model for diagnosis of the patient and the DT and RF are considered the best models to diagnosis a healthy individual.
Relationship Between Surgical R0 Resectability and Findings of Peripancreatic Vascular Invasion on CT Imaging After Neoadjuvant S-1 and Concurrent Radiotherapy in Patients with Borderline Resectable Pancreatic Cancer
Authors: Yasuta Sho , Kobayashi Tatsushi , Aizawa Hidetoshi , Takahashi Shinichiro , Ikeda Masafumi , Konishi Masaru , Kojima Motohiro , Kuno Hirofumi , Uesaka Katsuhiko , Morinaga Soichiro , Miyamoto Atsushi , Toyama Hirochika , Takakura Norihisa , Sugimachi Keishi , Takayama Wataru
Published: September 2020

BackgroundBorderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis because the tumor is in contact with major vessels. This study evaluated the relationship between the margin-negative (R0) resection rate and findings indicating peripancreatic vascular invasion on multidetector computed tomography (MDCT) imaging after neoadjuvant chemoradiotherapy (NACRT) in patients with BRPC.MethodsTwenty-nine BRPC patients who underwent laparotomy after neoadjuvant S-1 with concurrent radiotherapy were studied retrospectively. Peripancreatic major vessel invasion was evaluated based on the length of tumor-vessel contact on MDCT. The R0 resection rates were compared between the progression of vascular invasion (PVI) group and the non-progression of vascular invasion (NVI) group. ResultsThere were 3 patients with partial responses (10%), 25 with stable disease (86%), and 1 with progressive disease (3%) according to the RECISTv1.1 criteria. Regarding vascular invasion, 9 patients (31%) were classified as having PVI, and 20 patients (69%) were classified as having NVI. Of the 29 patients, 27 (93%) received an R0 resection, and all the PVI patients received an R0 resection (9/9; R0 resection rate = 100%). The R0 resection rates did not differ significantly between the PVI and NVI groups (P = 1.000, 100% vs. 90%).ConclusionsPatients with BRPC after NACRT achieved high R0 resection rates regardless of the vascular invasion status. BRPC patients can undergo R0 resections unless progressive disease is observed after NACRT.Trial registrationUMIN-CTR, UMIN000009172. Registered 23 October 2012, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000010762
Expression Dominance and Homeolog Expression Bias Upon Chilling Stress in A Hybrid Weed Between the Invasive Sphagneticola Trilobata and the Native S. Calendulacea in South China and its Implications for Invasiveness
Authors: Wu Wei , Ni Guangyan , Wang Longyuan , Zhang Hui , Li yongquan , Chen Ping , Guo Wei
Published: September 2020

Background The role of hybridization or admixture in the biological invasion has been recognized in many invasive species. S ubgenome dominance was reported to occur instantly following the hybridization of divergent genomes, however, investigations on their consequences on physiological response were still scarce . For invasive species, thermotolerance was critical to their range expansions. In this study, a F1 weed between a chilling sensitive invasive S. trilobata and the tolerant native S. calendulacea were treated with consecutive chilling stress, Using physiological assay and RNA-sequencing, differential physiological response and transcriptome profile s were compared with a n emphasis on the patterns of the expression dominance and homeolog expression bias in the F1 hybrids. Results P hysiological assay including content of Malondialdehyde content, superoxide dismutase activity and et al. demonstrated these F1s resembled the chilling tolerant maternal parent S. calendulacea . For both parents and the F1, the numbers and categories of the enriched pathways or gene ontology terms showed extensive divergence, and an overall resemblance between F1s and S. calendulacea w as observed. For the homeologs with altered expression, expression level dominance was the most prominent pattern. With increased chilling stress, the increased magnitude of up-regulations and decreased magnitude of down-regulations of the Spc- homeologs in the F1s were jointly contributed to the ir resemblance to chilling tolerant parent S. calendulacea . Irrespective of the total homeolog expressive level, increased magnitude of homeolog expression bias toward the chilling tolerant parent S. calendulacea in the F1s also provided another line of evidence for their physiological resemblance. Conclusion The two Sphagneticola species showed significant differential response upon chilling stress. expression dominance and persistent S. calendulacea homeolog bias in the F1s were attributed to the overall resemblance to the tolerant native species S. calendulacea. Given their vigorous growth, it cations us that the F1 hybrid have great potential to expand northwards and become an awesome weed in the future.
The Landscape of Renal Replacement Therapy in Veterans Affairs Medical Center Intensive Care Units
Authors: Vangala Chandan , Shah Maulin , Dave Natasha N. , Attar Layth Al , Navaneethan Sankar D. , Ramanathan Venkat , Crowley Susan , Winkelmayer Wolfgang C.
Published: September 2020

Background Outpatient dialysis is standardized with several evidence-based measures of adequacy and quality that providers aim to meet while providing treatment. By contrast, in the intensive care unit (ICU) there are different types of continuous and prolonged renal replacement therapies with numerous and varied strategies for addressing patient care and a dearth of nationally accepted quality parameters. In order to eventually understand what quality measures are appropriate for ICU-related renal replacement therapy (RRT), we first aimed to capture the variety and prevalence of basic strategies and equipment utilized in the ICUs of Veteran Affairs (VA) medical facilities with inpatient hemodialysis capabilities.Methods Via email to the dialysis directors of all 87 VA facilities that provided inpatient hemodialysis during 2018, we requested participation in a survey regarding aspects of RRT in VA ICUs. Questions centered around mode of therapy, equipment, solutions, prescription authority, nursing, anticoagulation, antimicrobial dosing, and access.Results Seventy-six centers completed the questionnaire, achieving a response rate of 87.4%. Fifty-five centers or 72.4%, reported using some form of prolonged or continuous renal replacement therapy (CRRT) in addition to intermittent hemodialysis. Of these 55 centers, 42 reported being specifically CRRT-capable. Over half of the respondents had the capabilities to perform prolonged intermittent renal replacement therapy (PIRRT). Twelve centers (21.8%) were equipped to use slow low efficient dialysis (SLED) alone. Therapy was overwhelmingly prescribed by nephrologists (94.4% of centers).Conclusions Within the VA system, ICU-related RRT practice is quite varied. Variation in processes of care, prescription authority, RRT nursing care coordination, medication management, and safety practices present opportunities for developing cross cutting measures of quality of intensive care RRT that are agnostic of modality choice.
COVID-19 Induced Stress, Lifestyle Changes and Weight-gain in Youth during a 4-Month Lockdown: A Prospective Cohort Study
Authors: Liu Suixin , Dun Yaoshan , Jeffrey Ripley-Gonzalez , Zhou Nanjiang , You Baiyang , Li Qiuxia , Li Hui , Zhang Wenliang , Thomas Randal , Olson Thomas , Liu Jie , Dong Yuchen
Published: September 2020

The COVID-19 (coronavirus disease-19) has resulted in nationwide lockdowns, cessation of school and work, and social distancing. Reducing the negative impacts, such as weight-gain, has garnered global attention. In this dual-center prospective cohort study of 12,889 students, we assessed weight-gain in a youth during the 4-month COVID-19 lockdown, and examined the associations between weight-gain and COVID-19 induced stress, depression and self-reported physical activity, dietary habits and sedentary time. Participants gained an average of 2.6 kg (95% CI: 2.0 to 3.2 kg) for males and 2.1 kg (1.9 to 2.4 kg) for females. An increase in overweight and obese individuals as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in males and females respectively (P<0.001). Weight change was independently associated with severe COVID-19 induced stress, sedentary time, and depression score. Techniques to relieve COVID-19 induced stress, reduce sedentary time through increased physical activity, and improve dietary habits in youth may be warranted to help prevent and/or reverse weight-gain associated with the lockdown period of COVID-19.Registration: Registered with ChiCTR, registration no.: ChiCTR2000033514
Use and Impact of High Intensity Treatments in Patients with Traumatic Brain Injury Across Europe: A CENTER-TBI Analysis
Authors: Huijben Jilske , Dixit Abhishek , Stocchetti Nino , Maas Andrew , Lingsma Hester , Jagt Mathieu van der , Nelson David , Citerio Giuseppe , Wilson Lindsay , Menon David , Ercole Ari
Published: September 2020

Purpose: To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs).Methods: We studied high TIL treatments (metabolic suppression, hypothermia (<35oC), intensive hyperventilation (PaCO2 <4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended(GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP.Results: 313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.4). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE > 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR: 1.4, 95% CI [1.0 -2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome.Conclusion: Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies.Take home message: Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a stepwise escalation strategy from lower to higher intensity level therapy is often lacking. Further research is necessary to study the impact of high therapy intensity treatments.Trial registration: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered 08/06/2014, https://clinicaltrials.gov/ct2/show/NCT02210221?id=NCT02210221&draw=1&rank=1 and with Resource Identification Portal (RRID: SCR_015582).
Prediction of Mortality in a Patient With Acute Poisoning
Authors: Han Kap Su , Kim Su Jin , Lee Eui Jung , Shin Joong Ho , Lee Ji Sung , Lee Sung Woo
Published: September 2020

Objective: This study aimed to develop a scoring system for predicting the in-hospital mortality of acute poisoning patients at the emergency department (ED). Methods: This was a retrospective analysis of the Injury Surveillance Cohort generated by the Korea Center for Disease Control and Prevention (KCDC) from 2011–2018. We developed the new-Poisoning Mortality Scoring system (new-PMS) to generate a prediction model using the derivation group (2011–2017 KCDC cohort). Points were computed for each category of each variable. The sum of these points was the new-PMS. The validation group (2018 KCDC cohort) was subjected to external temporal validation. The performance of new-PMS in predicting mortality was evaluated using receiver operating characteristic (ROC) curves for both groups. For simple interpretation in clinical settings, risk groups were categorized as very low, low, intermediate, and high according to the new-PMS; we suggested the mortality curve according to new-PMS. Results: Of 57326 poisoning cases, 42568 were selected. Of these, 34352 (80.7%) and 8216 (19.3%) were enrolled in the derivation and validation groups, respectively. New-PMS was the sum of points for each category of 10 predictors. The range of new-PMS was -20 to 3420 points. The area under the ROC curve of new-PMS was 0.942 (95% CI: 0.934–0.949) and 0.946 (95% CI: 0.930–0.963) for the derivation and validation groups, respectively. The mean predicted mortality and the observed mortalities of the high-risk group (new-PMS ≥1048) were 9.7% (95% CI: 9.3 – 10.0) and 10.0% for the derivation group and 8.4% (95% CI: 7.7 – 9.1) and 7.4% for the validation groups, respectively. Conclusions: New-PMS showed good performance in predicting in-hospital mortality for both groups. As mortality sharply increased with the high risk-group of the new-PMS, early hemodynamic stabilization of acute poisoning patients at the ED may improve their clinical outcomes. New-PMS contributes to clinical decision-making for acute poisoning patients in clinical settings.
Identification of Key Genes in HCV-induced HCC at Early Stage on the Background of HCV-cirrhosis
Authors: Nie Jiao , Du Chao , Lu Lin , Gao Xiaozhong
Published: September 2020

Background: Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors worldwide. Hepatitis C virus (HCV)-induced cirrhosis (HCV-cirrhosis) is one of the leading causes of HCC occurrence. Due to the lack of effective biomarkers, most patients with HCV-induced HCC (HCV-HCC) are at advanced stages when they are first diagnosed. Our study aims to employ transcriptomic profiling dataset to identify potential biomarkers that can predict HCV-HCC at early stage on the background of HCV-cirrhosis. Methods: The dataset incorporating HCV-cirrhosis and HCV-HCC subjects at different stages from Gene Expression Omnibus was analyzed to identify gene signature-related to HCV-HCC on the background of HCV-cirrhosis. Multiple-genes based risk score-related prediction model was established to predict HCV-HCC samples at different stages, and receiver-operating characteristic (ROC) curve analysis was used to select the best cutoff value of risk scores for prediction and to evaluate the prediction model. Samples with risk scores higher than cutoff value were defined as high score group.Results: Highly clustered 20 genes were identified and were all gradually increased as HCV-HCC progressed from HCV-cirrhosis to very advanced HCC. Compared with HCV-cirrhosis, the prevalence of HCV-HCC at any of the stages in high score group was 100%. The risk score-related prediction model based on the 20 genes-biomarker got the accuracy of over 95.2 % with area under ROC (AUC) over 0.94. To implement the biomarker easily in real life and make it economical, we tried to limit the gene numbers. Interestingly, CDKN3 and FAM83D were significantly decreased in HCV-cirrhosis tissues as compared to normal tissues and then increased as HCV-HCC progressed. The results were attractive that the prediction model based on this 2 genes-biomarker indicated that prevalence of HCV-HCC in high score group was still 100% and got the predictive accuracy of over 95.2 % with AUC over 0.96, revealing even a better performance.Conclusion: Our study indicated a 2-genes-based biomarker that could identify HCV-HCC at earlier stages on the background of HCV-cirrhosis, which might be a promising biomarker for early diagnosis of HCV-HCC and potential novel treatment target.
Neuroanatomical Alterations in Patients With Tinnitus Before and After Sound Therapy: A Combined VBM and SCN Study
Authors: Wei Xuan , Lv Han , Chen Qian , Wang Zhaodi , Liu Chunli , Zhao Pengfei , Gong Shusheng , Yang Zhenghan , Wang Zhenchang
Published: September 2020

Background: Many neuroanatomical alterations have been detected in patients with tinnitus in previous studies. However, little is known about morphological and structural covariance network (SCN) changes before and after long-term sound therapy. This study aimed to explore alterations in brain anatomical and SCN changes in patients with idiopathic tinnitus using voxel-based morphometry (VBM) analysis 24 weeks before and after sound therapy. Methods: Thirty-three tinnitus patients underwent magnetic resonance imaging scans at baseline and after 24 weeks of sound therapy. Twenty-six age- and sex-matched healthy control (HC) individuals also underwent two scans over a 24-week interval; 3.0T MRI and high-resolution 3D structural images were acquired with a 3D-BRAVO pulse sequence. Structural image data preprocessing was performed using the VBM8 toolbox. The Tinnitus Handicap Inventory (THI) score was acquired in the tinnitus group to assess the severity of tinnitus and tinnitus-related distress. Two-way mixed model analysis of variance (ANOVA) and post hoc analyses were performed to determine differences between the two groups (patients and HCs) and between the two scans (at baseline and at the 24th week). Two-sample t tests, paired-samples t tests, and Pearson’s correlation analysis were used in the post hoc analysis.Results: Interaction effects between the two groups and the two scans demonstrated significantly different gray matter (GM) volume in the right parahippocampus gyrus, right caudate, left superior temporal gyrus, left cuneus gyrus and right calcarine gyrus; we found significantly decreased GM volume in the above five brain regions among the tinnitus patients before sound therapy (baseline) compared to that in the HC group. The 24-week sound therapy group demonstrated significantly greater brain volume compared with the baseline group among these brain regions. We did not find significant differences in brain regions between the 24-week sound therapy and HC groups. The SCN results showed that the left superior temporal gyrus and left rolandic operculum were significantly different in nodal efficiency, nodal degree centrality and nodal betweenness centrality after FDR correction. Decreased THI scores and GM volume changes between the left thalamus and right thalamus were not correlated. Conclusions: This study characterized the effect of sound therapy on brain GM volume, especially in the left superior temporal lobe. Notably, sound therapy had a normalizing effect on tinnitus patients.
Intervening in the S1PR1/STAT3 Signaling Pathway Attenuates Valvular Damage Due to Rheumatic Heart Disease
Authors: Xian Shenglin , Chen Ang , Wu Yunjiao , Wen Hong , Lu Chuanghong , Wen Jianlin , Huang Feng , Zeng Zhiyu
Published: September 2020

Background: Rheumatic heart disease (RHD) affects many patients every year, but its pathogenesis is still unclear. Recent studies have found that the sphingosine 1-phosphate receptor 1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in valvular damage by promoting the differentiation of T helper 17 (Th17) cells during the development of valvular damage caused by RHD. In this work, we investigated whether altering the S1PR1/STAT3 signaling pathway attenuates valvular damage due to RHD. Methods: Inactivated Group A streptococci (GAS) was used to establish the RHD rat model. Recombinant adeno-associated virus (serotype 9) vectors carrying the S1PR1 overexpression sequence was used to overexpress the expression of S1PR1. STAT3-small interfering RNA (STAT3-siRNA) was used to inhibit the expression of STAT3. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the mRNA expression of S1PR1, STAT3, collagen type III α1 chain (Col3a1) and fibroblast-specific protein 1 (FSP1). Western blotting (WB) and immunohistochemistry were used to detect the protein expression of S1PR1, STAT3, phosphorylated (p-) STAT3, retinoic acid-related orphan receptor gamma T (RORγt). Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the levels of interleukin (IL)-6 and IL-17. Haematoxylin and eosin (H&E) staining and Sirius red staining were used to evaluate the degree of inflammation and fibrosis in valve tissues.Results: The expression of S1PR1 in valve tissues of RHD model rats was decreased. The levels of IL-6 and IL-17 in valves and serum of RHD model rats were increased as well as an increase of p-STAT3. The degree of valvular inflammation and fibrosis of RHD model rats was increased. Overexpression of S1PR1 and Inhibition of STAT3 overexpressed S1PR1 expression and decreased STAT3 expression respectively and reduced the total amount of p-STAT3, resulting in decreased expression of IL-6, IL-17 and RORγt and reduced the degree of valvular inflammatory and fibrosis. Conclusions: These results suggest that the S1PR1/STAT3 signaling pathway is involved in regulating the Th17 cell-related cytokines during the vavular damage due to RHD, and altering the S1PR1/STAT3 signaling pathway could affect the expression of Th17 cell-related cytokines then attenuate the vavular damage due to RHD.
The Reasons Why Fractional Flow Reserve and Instance Wave-Free Ratio are Similar Using Wave Separation Analysis
Authors: Min Soohong , Kang Gwansuk , Paeng Dong-Guk , Choi Joon Hyouk
Published: September 2020

Background and Objectives: Fractional flow reserve(FFR) and instantaneous wave-free ratio(iFR) are the two most commonly used coronary indices of physiological stenosis severity based on pressure. To minimize the effect of wedge pressure (Pwedge), FFR is measured during hyperemia conditions, and iFR is calculated as the ratio of distal and aortic pressures (Pd/Pa) in the wave-free period. The goal of this study was to predict Pwedge using the backward wave (Pback) through wave separation analysis(WSA) and to reflect the effect of Pwedge on FFR and iFR to identify the relationship between the two indices.Methods: An in vitro circulation system was constructed to calculate Pwedge. The measurements were performed in cases with stenosis percentages of 48, 71, and 88% and with hydrostatic pressures of 10 and 30 mmHg. Then, the correlation between Pback by WSA and Pwedge was calculated. In vivo coronary flow and pressure were simultaneously measured for 11 vessels in all patients. The FFR and iFR values were reconstructed as the ratios of forward wave at distal and proximal sites during hyperemia and at rest, respectively.Results: Based on the in vitro results , the correlation between Pback and Pwedge was high(r=0.990, p<0.0001). In vivo results showed high correlations between FFR and reconstructed FFR(r=0.992, p<0.001) and between iFR and reconstructed iFR(r=0.930, p<0.001).Conclusions: Reconstructed FFR and iFR were in good agreement with conventional FFR and iFR. FFR and iFR can be expressed as the variation of trans-stenotic forward pressure, indicating that the two values are inferred from the same formula under different conditions.
Analysis of Traditional Risk Factors of Atherosclerosis and Novel Risk Markers of Inflammation in Coronary Ectasia Can We Solve The Enigma ??
Authors: Mariappan Selvaganesh , S Sivakumar G , R Saravanan R , S Satheeshkumar , R Veeramani S , S Balasubramanian , A.S Arul
Published: September 2020

Background: Coronary artery ectasia(CAE) is speculated as a variant of atherosclerosis. The pathogenesis of CAE remains an enigma. Here in our study, we aimed to elucidate the role of traditional risk factors of atherosclerosis and inflammation in coronary ectasia.Methods and Results: This comparative study was carried in a tertiary hospital in South India.Patients with coronary artery ectasia and obstructive coronary artery disease were included as cases and controls . Traditional risk factors of atherosclerosis and risk markers of inflammation (neutrophil-lymphocyte ratio(NLR), red cell distribution width (RDW), mean platelet volume (MPV) )were evaluated and comparative analysis was done. Coronary ectasia was observed in 5.6%(n=136)of the study population. Among those with ectasia,112(82.4%) patients were having significant obstructive CAD (mixed group), isolated ectasia observed in24 (17.6%)patients. Isolated ectasia had an inverse association with diabetes mellitus and male:female ratio of (7:1). DM was seen only in 25% of isolated ectasia groups compared to 42.9%, 47.4% among mixed and obstructive CAD groups respectively (p < 0.05). Traditional risk factors were not significantly different between the mixed group and obstructive CAD group. Inflammatory markers were significantly higher among the both ectasia group compared to obstructive CAD group NLR: 3.98±0.89, 3.58±0.56, 2.82±0.60 p <0.001. RDW:12.59±0.60, 12.29±0.85,12.02±0.70, p<0.005. MPV was elevated in all three groups but not much different among groups.Conclusion: Coronary ectasia commonly seen in association with obstructive CAD, the prevalence of traditional risk factors of atherosclerosis is similar between CAE+CAD, obstructive CAD group suggest atherosclerosis as the underlying pathophysiology. Elevated markers of inflammation suggest overlying inflammation on atherosclerosis to be the contributor of ectasia.
Ectopic ACTH Syndrome and Hypothyroidism Due to Right Renal Small Round Blue Cell Tumor: A Case Report
Authors: Mao Weipu , Xu Jiajia , Lu Haowen , Wang Yali , Zhang Lihua , Ming Chen
Published: September 2020

Background: Small round blue cell malignancies are rare and highly aggressive tumors that are commonly located in the soft tissues or axial bones of the bone or trunk and are particularly rare in the kidney. The common cause of ectopic ACTH syndrome is pulmonary neuroendocrine tumors, such as small cell carcinomas and carcinoid tumors. Here, we present an unusual case of ectopic ACTH syndrome and hypothyroidism caused by small round blue cell tumor of the right kidney.Case presentation: A 19-year-old girl presented with a history of right lumbar pain and discomfort for 2 months, aggravated for 2 days. Abdominal contrast-enhanced computed tomography and computed tomography angiography showed right suprarenal pole occupancy with subepithelial hemorrhage. Preoperative hormone levels including plasma total cortisol (PTC), adrenocorticotrophic hormone (ACTH) and thyroid hormone measurements were abnormal, indicating that the patient had Cushing syndrome and hypothyroidism. The patient underwent right radical nephrectomy. Histopathological analysis revealed a renal small round blue cell tumor (consistent with a primitive neuroectodermal tumor), with positive immunohistochemistry for CD99 and Ki67 (about 10%) and molecular pathology for EWSR1 gene fusions. PTC, ACTH and thyroid hormone returned to normal after surgery.Conclusions: We report a rare ectopic ACTH syndrome and hypothyroidism due to renal small round blue cell tumor. The clinical manifestation of renal small round blue cell tumor is non-specific and the diagnosis relies on pathological morphology, immunohistochemistry and fusion gene detection. At present, surgery combined with radiotherapy and chemotherapy is used in the treatment, but the prognosis is still not optimistic.
Abnormal Expression of MST1 and YAP1 in Fetal Heart Tissue in a Hyperglycemic Environment and Their Roles in Mediating Apoptosis
Authors: Su Dongmei , Li Yanhua , Guan Lina , Li Qian , Shi Cuige , Ma Xu , Song Yonghui
Published: September 2020

Background：Gestational diabetes mellitus is a risk factor for congenital heart defects. The article aimed to investigate the expression and roles of Mst1, Yap1, Last1/2 and Survivin in modulating HG-induced cardiomyocyte apoptosis and maternal diabetes-induced heart abnormality. Methods：The gene and protein expression were assessed by quantitative PCR, western blot, and immunohistochemical staining. The protein phosphorylation level were analyzed by western blot .Knockdown of gene expression were assessed by RNA interference. Hoechst 33342 staining assay were performed to explore H9C2 apoptosis. Diabetes mellitus was induced in rats using streptozotocin.Results：Our results revealed that increased MST1 protein levels in the heart tissues of the offspring of diabetic rats in vivo occurred concomitantly with HG-induced apoptosis in H9C2 cardiomyocytes in vitro. Knockdown and overexpression experiments showed that MST1 played a key role in mediating HG-induced apoptosis in cardiomyocytes. Downregulation of YAP1 was associated with HG-induced, MST1-mediated cardiomyocyte apoptosis. Further study showed that MST1 downregulated the protein level of YAP1 through mediation of YAP1 phosphorylation on Ser127 and Ser397; this process also required LATS1/2 participation. MST1 overexpression increased the phosphorylation levels of LATS1/2, which were also shown to be increased in the heart tissues of diabetic offspring. We also found that YAP1 mediated the expression of Survivin during HG-induced apoptosis, and the Survivin-inhibitor YM155 partially inhibited the role of YAP1 in suppressing apoptosis induced by HG in cardiomyocytes. Conclusion：These findings reveal a regulatory mechanism of MST1/YAP1/Survivin signaling in modulating cardiomyocyte apoptosis in vitro and maternal diabetes-induced congenital heart defects in vivo.
Designing an Evidence-Based Behavior Change Strategy to Promote Antibiotic Use in Primary Healthcare in Gezira State, Sudan
Authors: Lohiniva Anna-Leena , Elwali Einas S. , Abuobaida Duha , Abdulrahim Ashwag , Bukuluki Paul , Talaat Maha
Published: September 2020

Background: Abuse of antibiotics is a major contributing factor to the emergence of antibiotic resistance (ABR) globally. Misuse and overuse of antibiotics is common also in Sudan. Addressing antibiotic use is a key component of AMR response.Objectives: The project aimed to develop a theory driven behavior change strategy based on local understanding of drivers of antibiotic use at primary healthcare settings in Gezira State in Sudan. The strategy is needed to enhance the prescribers’ appropriate prescription of antibiotics and to reduce the patient’s demand towards unnecessary antibiotics.Methods: The strategy was designed based on the Theoretical Domains Framework (TDF) to identify behavioral barriers and the Behavior Change Wheel to select appropriate behavior change techniques (BCTs). The process included two major elements (1) a formative qualitative research study using focus group discussions and in-depth interviews targeting prescribers and patients. (2) a knowledge co-production workshop that utilized the results of the qualitative study and aimed to design a salient, legitimate and credible behavior change strategy identifying relevant behavior change techniques (BCTs) to overcome key barriers.Results: The main TDF domains that emerged from the discussions with prescribers were knowledge of antibiotics and AMR, skills to answer patient demand on antibiotics, prescription habits and work exhaustion, social influences, intention to change prescription practices and environmental factors. The main TDF domains that emerged through discussions with patients were antibiotic use habits, social influences, professional role belief in capabilities and intention to change. The workshop discussions resulted in the selection of five BTCs that included education, training, modeling, enablement and persuasion.Conclusion: This study, using the TDF and BCW taxonomy, explored the fact that antibiotic prescribing is influenced by many social and contextual factors. Knowledge co- production offered real benefits in addressing these complexities to come up with a set of context appropriate behavior change interventions.