bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overall reduced lymphocyte subsets worsening disease severity and prognosis in COVID-19 severe cases with diabetes mellitus in Chengdu, China
Authors: Liu Dafeng , Wang Yong , Lan Lijuan , Liu Yaling , Zhao Bennan , Bao Lei , Chen Hong , Yang Min , Li Qingfeng , Zeng Yilan 
Published: June 2020

Abstract
Background The outbreak of coronavirus disease 2019 (COVID-19) is widespread throughout China and the world. Methods Demographic, clinical data of 95 confirmed cases with COVID-19 on admission at the Public and Health Clinic Centre of Chengdu from January 16 to March 16, 2020, were retrospectively collected and analyzed. Of them 76, 19 cases were enrolled in non-DM group (without DM), DM group (with DM), respectively; according to the disease severity 57, 19, 8, 11 cases were further divided into non-severe non-DM subgroup (light and common type and without DM), severe non-DM subgroup (severe and critical illness type and without DM), non-severe DM subgroup (light and common type and with DM), severe DM subgroup (severe and critical illness type and with DM), respectively. The severe rate and the prognosis was compared between two groups. The data of peripheral lymphocyte and subsets, age, glucose metabolism parameters were compared between four subgroups, and its relationship to the disease severity, the viral negative conversion time, and the prognosis were analyzed.Results In this COVID-19 cohort the proportion of DM was 20%. Patients with DM had significantly higher severe rate and worse prognosis than those without DM, the difference was significant (severe rate ,cured, unhealed and death in DM and non-DM groups:61.11%vs.25.00%,26.32%,68.42%;5.26%vs.71.05%,26.32%,2.68%,х2=2.940, 3.394,P=0.003,0.001,respectively),simultaneously the proportion of DM in severe cases was higher than that in non-severe cases, the obvious difference was found (36.67% vs.12.31%,х2=2.744,P=0.006).Severe cases with DM tended to have the lowest lymphocytes count levels and percentage values, as well as the lowest T cells count levels and percentage values, helper T cells count levels and percentage values, suppressor T cells count levels, B cells count levels and percentage values compared with those severe cases without DM and non-severe cases with or without DM. The important influencing factors were that age, DM, lymphocyte percentage values and helper T cells percentage values for the disease severity, lymphocyte percentage values and B cell percentage values for the viral negative conversion time, and age, the disease severity and the viral negative conversion time for the prognosis.Conclusions The COVID-19 severe cases with DM had the lowest lymphocytes count level and percentage value, especially T and B lymphocytes count levels and percentage value. Overall decreased lymphocytes subsets and DM maybe worsen prognosis by worsening the disease severity and prolonging the viral negative conversion time. Combination immunomodulatory therapy based on comprehensive treatment might improve prognosis of the COVID-19 severe cases with DM.
Design of a GFP reporter for splicing analysis in mammalian cells
Authors: Menezes Arthur T. , Nagasse Helder Y. , Coltri Patricia Pereira 
Published: June 2020

Abstract
Objective: The great majority of eukaryotic genes are formed by exons and introns. Pre-RNA transcripts are extensively processed in the nucleus, with the addition of a cap group at the 5′ end, intron removal and exon ligation (splicing) followed by addition of a poly-A tail at 3′ end. Splicing is performed by specialized macromolecular machinery named spliceosome, composed of five small ribonucleoprotein particles (snRNPs) and several proteins. The activity of this complex is highly accurate due to coordinated activity of its components. Altered splicing has already been related to the development of several diseases as amyotrophic lateral sclerosis and different types of cancer. Detailed understanding of splicing regulation in eukaryotic cells can be achieved using splicing reporter systems. Results: We designed a new splicing reporter plasmid suitable for analysis in mammalian cells. Our reporter is based on splicing of the GFP sequence. The greatest advantages of this system are the ease of visualization of the splicing outcome, by using a fluorescence microscope to confirm GFP expression from the reporter. Also, quantification of splicing efficiency using real-time PCR is possible. The use of this system allows rapid and easy detection of the splicing results in cultured cells.
Usefulness of Tissue Doppler-derived Atrial Electromechanical Delay for Identifying Patients with Paroxysmal Atrial Fibrillation
Authors: Akamatsu Kanako , Ito Takahide , Miyamura Masatoshi , Kanzaki Yumiko , Sohmiya Koichi , Hoshiga Masaaki 
Published: June 2020

Abstract
Background: Tissue Doppler imaging (TDI)-derived atrial electromechanical delay (AEMD) has been reported to be useful for detecting paroxysmal atrial fibrillation (PAF). However, its usefulness remains unknown when analyzed along with patients seemingly at high-risk for AF as controls. From this standpoint, we investigated whether AEMD would be of use for identifying patients with PAF. Methods: We retrospectively analyzed TDI recordings to obtain AEMD in 63 PAF patients. Thirty-three patients with multiple cardiovascular risk factors (MRFs) but without history of AF and 50 healthy individuals served as disease and healthy controls, respectively. AEMD was defined as the time-interval between the electrocardiogram P-wave and the beginning of the spectral TDI-derived A’ for the septal (septal EMD) and lateral (lateral EMD) sides of the mitral annulus. Results: There was no significant difference in the left atrial volume index between PAF patients and disease controls (28 ± 9 mL/m 2 vs. 27 ± 5 mL/m 2 ). PAF patients had longer AEMD, particularly for the lateral EMD (75 ± 23 ms), compared with disease (62 ± 22 ms, P = 0.009) and healthy (54 ± 24 ms, P <0.001) controls. Multivariate logistic regression analysis revealed that the lateral EMD (OR 1.25, 95%CI 1.03 – 1.52, P = 0.023), along with the left atrial volume index (OR 2.25, 95%CI 1.44 – 3.51, P <0.001), was one of the significant independent associates of identifying PAF patients. Conclusions: This cross-sectional study indicates that even analyzed together with MRFs patients, AEMD remains useful for identifying patients at risk for AF. Our results need to be confirmed by a large-scale prospective study.
Risk Factors for Sub–therapeutic Serum Concentrations of Magnesium Sulfate in Severe Preeclampsia of Chinese Patients
Authors: Li Jingjing , Tang Lian , Tang Ruiheng , Peng Lan , Chai Liqiang , Zhu Liping , Yu Yanxia 
Published: June 2020

Abstract
Background: Magnesium sulfate (MgSO 4 ) is the standard drug for eclampsia prophylaxis and treatment. In China, the effective therapeutic serum magnesium level is 1.8–3.0 mmol/L. There is little information on how to achieve and maintain effective therapeutic concentrations. This study aimed to investigate risk factors for sub-therapeutic serum concentrations of MgSO 4 in patients with severe preeclampsia. Methods: Patients with severe preeclampsia who received MgSO 4 intravenous infusion were retrospectively reviewed. The maternal demographic characteristics, regimens for the administration of MgSO 4 , and lab test results of patients were collected. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were conducted for the risk factors influencing the serum magnesium concentration. Results: A total of 93 patients with severe preeclampsia were included in the study. 52 (55.91%) patients did not attain therapeutic serum magnesium levels. A multivariate logistic regression analysis identified creatinine clearance (Ccr), whether the loading dose was given, and measurement time of serum magnesium concentration (referring to the time interval from measurement of blood magnesium concentration to the beginning of maintenance dose administration) as independent risk factors for sub - therapeutic serum magnesium concentration (P < 0.05). ROC curve analysis indicated that the continuous variable Ccr had a significant predictive value for the serum magnesium concentration, which resulted in a cutoff point of 132.82 mL/min; while measurement time had limited predictive value, with cutoff point of 2.375 h. Conclusions: Ccr, whether the loading dose was given, and measurement time were independent risk factors for sub - therapeutic serum magnesium concentration. A loading dose of MgSO 4 everytime before the maintenance dose, as well as an infusion time of more than 2.375 hours for MgSO 4 maintenance dose are recommended for all the patients with severe PE. Routine evaluation of serum magnesium levels is a recommended practice for women with severe PE whose Ccr is ≥ 132.82 mL/min.
Bipolar Affective Disorders and Psychotic Disorders in War Torn Area Eastern of the Democratic Republic of Congo
Authors: Vivalya Mutume , Vagheni Martial Mumbere , Adelard Kalima Nzanzu , Rock Kasereka Masuka , Kitoko Manzekele Bin , Mugizi Wilson , Ashaba Scholastic 
Published: June 2020

Abstract
The authors have removed this preprint from Research Square.
Influence of Tumor Location on Short- and Long-Term Outcomes After Laparoscopic Surgery for Rectal Cancer: A Propensity Score Matched Cohort Study
Authors: Yang Hong , Yao Zhendan , Cui Ming , Xing Jiadi , Zhang Chenghai , Zhang Nan , Liu Maoxing , Xu Kai , Tan Fei , Su Xiangqian 
Published: June 2020

Abstract
Background: This study aimed to evaluate the short- and long-term outcomes after laparoscopic resection for low rectal cancer (LRC) compared with mid/high rectal cancer (M/HRC). Methods: Patients with rectal cancer undergoing laparoscopic resection with curative intent were retrospectively reviewed between 2009 and 2015. After matched 1:1 by using propensity score analysis, perioperative and oncological outcomes were compared between LRC and M/HRC groups. Multivariate analysis was performed to identify independent factors of overall survival (OS) and disease-free survival (DFS). Results: Of 373 patients who met the criteria for inclusion, 260 patients were matched for the analysis. Laparoscopic surgery for LRC required longer operative time (P＜0.001) and more blood loss volume (P＜0.001) compared with M/HRC, and the LRC group tended to have a higher incidence of postoperative complications (18.5% vs. 10.0%, P=0.051). There was no significant difference in local recurrence between the two groups (6.2% vs. 2.3%, P=0.216), whereas distant metastasis was more frequent in LRC patients compared with M/HRC (19.2% vs. 9.2%, P=0.021). The LRC group showed significantly inferior 5-year OS (78.1% vs. 88.8%, P=0.008) and DFS (76.2% vs. 89.0%, P=0.004) compared with the M/HRC group. Multivariate analysis indicated that tumor location was an independent predictor of OS (HR=2.095, 95% CI 1.142-3.843, P=0.017) and DFS (HR=2.320, 95% CI 1.251-4.303, P=0.008). Conclusion: Tumor location of the rectal cancer significantly affected the clinical and oncological outcomes after laparoscopic surgery, and it was an independent predictor of OS and DFS.
A Novel Chalcone derivative suppresses Melanoma cell growth through targeting Fyn/Stat3 pathway
Authors: Tang Ling , Long Jing , Li Keke , Zhang Xu , Chen Xiang , Peng Cong 
Published: June 2020

Abstract
Background: Fyn has been documented to have oncogenic features in multiple tumors, which might be a potential therapeutic target, however, few studies on the function role of Fyn and its specific inhibitors in melanoma. Methods: We investigated the impacts of Fyn and its inhibitor Lj-1-60 on melanoma through bioinformatics analysis, western blot, cell viability, cell cycle and apoptosis and xenograft tumor model as well as immunohistochemical staining. Pull-down and in vitro kinase assay were used to demonstrate Lj-1-60 targeting Fyn. Transcriptome sequencing and RT-PCR were adopted to confirm the potential mechanisms of Lj-1-60 in melanoma. Results: Our findings showed that Fyn was overexpressed in melanoma cells and knocked down of Fyn suppressed the proliferation of melanoma cells. To identify the potential inhibitors of Fyn, our in-house library including total of 111277 chemicals was conducted to vitro screening, among those compounds, 83 inhibitors were further detected to explore the effect on melanoma cells growth and discovered a novel chalcone derivative Lj-1-60 that exhibited low cellular toxicity and high anti-tumor efficacy. Lj-1-60 directly was associated with Fyn and inhibited the Fyn kinase activity with Stat3 as substrate. What’s more, Lj-1-60 suppressed the proliferation of melanoma in vitro and in vivo through inducing cell cycle arrest and apoptosis. Moreover, the activation of Stat3 had also been abrogated both in Lj-1-60 treated melanoma cells or Fyn knocked down cells. Conclusion: Our study revealed a novel Fyn inhibitor that could significantly suppress melanoma growth, which is a promising potential inhibitor for melanoma treatment.
Procalcitonin levels in children with bloodstream infections caused by different species: a cohort study
Authors: Bejarano José Iván Castillo , Ranero Agustín De Colsa , Rivera Oscar Tamez , Lozoya Andrés Guillen , Saldaña Napoleón González , Anaya Alfonso Huante , Benavente Ismael Herrera , Santos Abiel Mascareñas de los 
Published: June 2020

Abstract
Background: Timely diagnosis and accurate identification of the causative microorganism in sepsis is crucial in order to offer targeted treatment and increase survival rates. Previous studies have aimed to identify biomarkers that could potentially predict blood culture positivity in patients with bacteremia; however, most of the research has been performed in adult populations. The aims of this study were to analyze procalcitonin (PCT) levels in confirmed bloodstream infections by species in children and assess their utility in immunocompromised patients.Methods: Medical records of children younger than 18 years admitted from 2011 to 2018 were reviewed. Subjects who met the diagnostic criteria for sepsis, with PCT levels collected within a 72-hour period prior to obtaining a blood culture were included. Kruskal-Wallis test was used to compare differences among groups. Receiver-operating characteristic curves were used to evaluate PCT cut-offs. Results: A total of 120 patients were included. Mean age was 55 months. Mean PCT levels in immunosuppressed patients was 26.68 mcg/L, compared to 8.78 in the immunocompetent group. Subjects with bacteremia by Gram-negative bacilli (GNB) had the highest mean PCT levels (18.2 ± 34.2) (p < 0.001). Sensitivity and specificity were 78% and 53% for Gram-positive cocci (GPC), 60.9% and 33.3% for GNB, and 75% and 25% for yeasts, respectively. Subgroup analysis showed 87.5% sensitivity and 16.7% specificity of PCT for predicting documented GNB bacteremia in immunodeficient children. Conclusions: PCT may be considered as a surrogate biomarker in immunocompromised children, and a viable tool to differentiate etiology by species.
FSTL1 aggravates Cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy
Authors: Liu Ying , Xu Jiawei , Liu Tian , Wu Jinxiang , Zhao Jiping , Wang Junfei , Zou Minfang , Cao Lili , Liu Xiaofei , Pan Yun , Huang Siyuan , Dong Liang 
Published: June 2020

Abstract
Background
Cigarette smoke (CS) is a major risk factor for COPD. Follistatin-like protein 1(FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulaton, airway inflammation and remodeling.
Methods
Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1+/- mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA) ,an inhibitor of autophagy, were applied in CS exposed WT mice. The lung tissue and serum from patients and murine models were tested for FSTL1 and autophagy associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed by Electron Microscope Technology(EMT). LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined by ELISA. Airway remodeling and lung function were also assessed.
Results
Both FSTL1 and autophagy biomarkers increased in COPD patients and CS exposed WT mice. Autophagy activation was upregulated in CS exposed mice accompanied by airway remodeling and airway inflammation. FSTL1+/- mice showed a lower level of CS-induced autophagy compared with control mice. FSTL1+/- mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS exposed WT mice with 3-MA pretreatment have a similar manifestation with CS exposed FSTL1+/- mice.
Conclusions
FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke induced COPD.
Herb-Drug interactions between Aidi injection and doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma
Authors: Lu Yuan , Pan Jie , Zhang Shuai , Chunhua Liu , Sun Jia , Li Yueting , Chen Siying , Huang Jing , Cao Chuang , Wang Yonglin , Li Yongjun , Liu Ting 
Published: June 2020

Abstract
Background

Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC.
Methods

Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
Results

Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The plasma drug concentration-time curves (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI.
Conclusions

Increased levels of DOX were found in the plasma of HCC rats pretreated with ADI, which may lead to enhanced efficacy but also potential toxicity.
Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation
Authors: Gottwald Dorian , Putz Florian , Hohmann Nora , Büttner-Herold Maike , Hecht Markus , Fietkau Rainer , Distel Luitpold 
Published: June 2020

Abstract
Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.
Financial reimbursement - Irrelevant for GPs' readiness to implement brief intervention to reduce alcohol consumption? A cross-sectional vignette study
Authors: Fankhaenel Thomas , Schulz Katrin , Petersen Lars Eric , Klement Andreas , Frese Thomas 
Published: June 2020

Abstract
BACKGROUND: General Practitioners' (GPs) readiness to implement screening and brief intervention (SBI) to treat patients with excessive alcohol consumption is low. Several studies identified crucial barriers such as insufficient financial reimbursement. In contrast to the barriers-account, we assume that low implementation readiness of GPs should rather not be attributed to barriers but rather to crucial inherent characteristics of SBI. To test our assumption, we conducted a vignette study assessing the GPs' readiness to implement SBI in comparison to a pharmacological intervention also designed for the treatment of excessive drinkers in relation to standard or above-standard financial reimbursement. According to our hypothesis GPs should be less ready to implement SBI regardless of financial reimbursement.METHODS: A convenience sample of GPs was recruited to answer the questionnaire. To assess the GPs' implementation readiness a 4-item 6-point Likert scale was developed and pretested. RESULTS: One hundred forty GPs completed the questionnaire. GPs were more ready to implement the pharmacological intervention than SBI, F(1,132)=27.58, p>.001 (main effect). We found no effect for financial reimbursement, F(1,132)=3.60, ns, and no interaction effect, F(1,132)=2.20, ns.CONCLUSIONS: Further research should investigate more thoroughly the crucial characteristics of SBI to initiate a modification process finally leading to more effective primary care dependency prevention.