bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy Evaluation of Thymosin Alpha 1 in Non-severe Patients With COVID-19: A Retrospective Cohort Study Based on Propensity Score Matching
Authors: Huang ChenLu , Fei Ling , Xu Wei , Li WeiXia , Xie XuDong , Li Qiang , Chen Liang 
Published: April 2021

Objective: Thymosin alpha 1 (Thymosin-α1) is a potential treatment for patients with COVID-19. We aimed to determine the effect of Thymosin-α1 in non-severe patients with COVID-19.Methods: We retrospectively enrolled 1,388 non-severe patients with COVID-19. The primary and secondary clinical outcomes were evaluated with comparisons between patients treated with or without Thymosin-α1 therapy.Results: Among 1,388 enrolled patients, 232 patients (16.7%) received both Thymosin-α1 therapy and standard therapy (Thymosin-α1 group), and 1,156 patients (83.3%) received standard therapy (control group). After propensity score matching (1:1 ratio), baseline characteristics were well-balanced between the Thymosin-α1 group and control group. The proportion of patients that progressed to severe COVID-19 is 2.17% for the Thymosin-α1 group and 2.71% for the control group (p = 0.736). The COVID-19-related mortality is 0.54% for the Thymosin-α1 group and 0 for the control group (p = 0.317). Compared with the control group, the Thymosin-α1 group had significantly shorter SARS-CoV-2 RNA shedding duration (13 vs. 16 days, p = 0.025) and hospital stay (14 vs. 18 days, p &lt; 0.001). No statistically significant difference was found between the Thymosin-α1 group and control group in duration of symptoms (median, 4 vs. 3 days, p = 0.843) and antibiotic utilization rate (14.1% vs. 15.2%, p = 0.768).Conclusion: For non-severe patients with COVID-19, Thymosin-α1 can shorten viral RNA shedding duration and hospital stay but did not prevent COVID-19 progression and reduce COVID-19-related mortality rate.
Temporal and Spatial Dynamics of Inflammasome Activation After Ischemic Stroke
Authors: Lu Danli , Hu Mengyan , Zhang Bingjun , Lin Yinyao , Zhu Qiang , Men Xuejiao , Lu Zhengqi , Cai Wei 
Published: April 2021

Background: The inflammasome represents a highly pro-inflammatory mechanism. It has been identified that inflammasome was activated after ischemic stroke. However, the impact of inflammasomes on stroke outcomes remains contradictory. The participating molecules and the functioning arena of post-stroke inflammasome activation are still elusive.Methods: In the present study, blood samples from stroke patients were collected and analyzed with flow cytometry to evaluate the correlation of inflammasome activation and stroke outcomes. A stroke model was established using male C57/Bl6 mice with transient middle cerebral artery occlusion (tMCAO, 1 h). The dynamics of inflammasome components, cell type, and location of inflammasome activation and the therapeutic effects of inhibiting post-stroke inflammasome executors were evaluated.Results: We found that a high level of inflammasome activation might indicate detrimental stroke outcomes in patients and mice models. Post-stroke inflammasome activation, especially NLRP3, cleaved Caspase-1, cleaved Caspase-11, IL-1β, IL-18, and GSDMD, peaked at 3–5 days and declined at 7 days with the participation of multiple components in mice. Macrophage that infiltrated into the ischemic lesion was the main arena for post-stroke inflammasome activation among myeloid cells according to the data of mice. Among all the members of the Caspase family, Caspase-1 and −11 served as the main executing enzymes. Inhibiting Caspase-1/−11 signaling efficiently suppressed DAMPs-induced macrophage inflammasome activation and displayed neuroprotection to stroke models including infarct size (Control: 48.05 ± 14.98; Cas1.i: 19.34 ± 12.21; Cas11.i: 21.43 ± 14.67, P &lt; 0.001) and neurological deficit score (0 d-Control: 2.20 ± 0.63; 0 d-Cas1.i: 2.20 ± 0.63; 0 d-Cas11.i: 2.20 ± 0.63; 1 d-Control: 2.50 ± 0.53; 1 d-Cas1.i: 1.50 ± 0.71; 1 d-Cas11.i: 2.00 ± 0.67; 2 d-Control: 2.30 ± 0.48; 2 d-Cas1.i: 1.30 ± 0.48; 2 d-Cas11.i: 1.50 ± 0.53; 3 d-Control: 2.00 ± 0.67; 3 d-Cas1.i: 1.20 ± 0.42; 3 d-Cas11.i: 1.30 ± 0.48, P &lt; 0.001).Conclusions: Taken together, inflammasome activation played a detrimental role in stroke pathology. Targeting post-stroke inflammasome executing enzymes fitting in the dynamics of macrophages might obtain potential and efficient therapeutic effects.
High-Grade Inflammation Attenuates Chemosensitivity and Confers to Poor Survival of Surgical Stage III CRC Patients
Authors: Ying Hou-Qun , You Xia-Hong , Liao Yu-Cui , Sun Fan , Cheng Xue-Xin 
Published: April 2021

Background: Heterogeneous clinical and molecular characteristics are reported in colorectal cancer (CRC) with different tumor laterality. However, the outcome of left- and right-sided patients with stage I–III CRC and the role of chronic inflammation in survival differences between them remain unclear.Method: A prospective study including 1,181 surgical patients with stage I–III CRC was carried out to investigate the involvement of circulating fibrinogen-to-pre-albumin (Alb) ratio (FPR) and primary tumor sidedness in the clinical outcome of those patients. We further investigated the effect of FPR on adjuvant chemotherapy response and recurrence in stage III patients.Results: Our study showed that the right tumor location was significantly associated with poor recurrence-free survival (RFS) (p = 0.04, adjusted HR = 1.41, 95% CI = 1.02–1.94) and overall survival (OS) (p = 0.04, adjusted HR = 1.55, 95% CI = 1.01–2.38) only in the stage III disease. In these patients, T4 stage distribution (83.39 vs. 70.94%, p &lt; 0.01) within right-sided cases was significantly higher than left-sided patients. Moreover, preoperative FPR within right-sidedness (p &lt; 0.01), T4 stage (p &lt; 0.05), and large cancer bulk (≥5 cm) (p &lt; 0.05) subgroups was significantly elevated compared to their counterparts, and it was gradually rising following the increased cancer bulk (p trend &lt; 0.01). High-FPR distribution (52.30 vs. 27.00%, p &lt; 0.01) within right-sided patients with the stage III disease was significantly higher than that in the left-sided cases. RFS (plog−rank &lt; 0.01) and OS (plog−rank &lt; 0.01) of the high-FPR patients were extremely inferior to the low-FPR cases, and the significant associations were observed when they were adjusted by other confounders including primary tumor location (p &lt; 0.01, adjusted HR = 1.96, 95% CI = 1.42–2.70 for RFS; p &lt; 0.01, adjusted HR = 2.44, 95% CI = 1.59–3.75 for OS). Additionally, RFS of adjuvant chemotherapy-treated high-FPR patients was superior to the patients without chemotherapy (plog−rank = 0.01) but was inferior to the low-FPR patients undergoing the treatment, especially in the 5-FU- and XELOX-treated subgroup.Conclusion: These findings indicate that chronic high-grade inflammation weakens chemotherapy efficacy and contributes to the poor prognosis of stage III surgical CRC patients.
Pre-Immunotherapy Contrast-Enhanced CT Texture-Based Classification: A Useful Approach to Non-Small Cell Lung Cancer Immunotherapy Efficacy Prediction
Authors: Shen Leilei , Fu Hongchao , Tao Guangyu , Liu Xuemei , Yuan Zheng , Ye Xiaodan 
Published: April 2021

Objective: To investigate the utility of the pre-immunotherapy contrast-enhanced CT-based texture classification in predicting response to non-small cell lung cancer (NSCLC) immunotherapy treatment.Methods: Sixty-three patients with 72 lesions who received immunotherapy were enrolled in this study. We extracted textures including histogram, absolute gradient, run-length matrix, gray-level co-occurrence matrix, autoregressive model, and wavelet transform from pre-immunotherapy contrast-enhanced CT by using Mazda software. Three different methods, namely, Fisher coefficient, mutual information measure (MI), and minimization of classification error probability combined average correlation coefficients (POE + ACC), were performed to select 10 optimal texture feature sets, respectively. The patients were divided into non-progressive disease (non-PD) and progressive disease (PD) groups. t-test or Mann–Whitney U-test was performed to test the differences in each texture feature set between the above two groups. Each texture feature set was analyzed by principal component analysis (PCA), linear discriminant analysis (LDA), and non-linear discriminant analysis (NDA). The area under the curve (AUC) was used to quantify the predictive accuracy of the above three analysis models for each texture feature set, and the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were also calculated, respectively.Results: Among the three texture feature sets, the texture parameter differences of kurtosis (2.12 ± 3.92 vs. 0.78 ± 1.10, p = 0.047), “S(2,2)SumEntrp” (1.14 ± 0.31 vs. 1.24 ± 0.12, p = 0.036), and “S(1,0)SumEntrp” (1.18 ± 0.27 vs. 1.28 ± 0.11, p = 0.046) between the non-PD and PD group were statistically significant (all p &lt; 0.05). The classification result of texture feature set selected by POE + ACC and analyzed by NDA was identified as the best model (AUC = 0.812, 95% CI: 0.706–0.919) with a sensitivity, specificity, accuracy, PPV, and NPV of 88.2, 76.3, 81.9, 76.9, and 87.9%, respectively.Conclusion: Pre-immunotherapy contrast-enhanced CT-based texture provides a new method for clinical evaluation of the NSCLC immunotherapy efficacy prediction.
30-Day Mortality Following Palliative Radiotherapy
Authors: Vázquez Miriam , Altabas Manuel , Moreno Diana C. , Geng Abraham A. , Pérez-Hoyos Santiago , Giralt Jordi 
Published: April 2021

Purpose30-day mortality (30-DM) is a parameter with widespread use as an indicator of avoidance of harm used in medicine. Our objective is to determine the 30-DM followed by palliative radiation therapy (RT) in our department and to identify potential prognosis factors.Material/MethodsWe conducted a retrospective cohort study including patients treated with palliative RT in our center during 2018 and 2019. Data related to clinical and treatment characteristics were collected.ResultsWe treated 708 patients to whom 992 palliative irradiations were delivered. The most frequent primary tumor sites were lung (31%), breast (14.8%), and gastrointestinal (14.8%). Bone was the predominant location of the treatment (56%), and the use of single doses was the preferred treatment schedule (34.4%). The 30-DM was 17.5%. For those who died in the first month the median survival was 17 days. Factors with a significant impact on 30-DM were: male gender (p &lt; 0.0001); Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 2–3 (p = 0.0001); visceral metastases (p = 0.0353); lung, gastrointestinal or urinary tract primary tumors (p = 0.016); and single dose RT (p = &lt;0.0001). In the multivariate analysis, male gender, ECOG PS 2–3, gastrointestinal and lung cancer were found to be independent factors related to 30-DM.ConclusionOur 30-DM is similar to previous studies. We have found four clinical factors related to 30-DM of which ECOG was the most strongly associated. This data may help to identify terminally ill patients with poor prognosis in order to avoid unnecessary treatments.
A Multistate Trial of an Early Surveillance Program for Autism Within General Practices in Australia
Authors: Barbaro Josephine , Masi Anne , Gilbert Melissa , Nair Radhika , Abdullahi Ifrah , Descallar Joseph , Dissanayake Cheryl , Eastwood John , Hasan Iqbal , Jalaludin Bin , Karlov Lisa , Khan Feroza , Kohlhoff Jane , Liaw S. T. , Lingam Raghu , Mendoza Diaz Antonio , Ong Natalie , Tam Chun Wah Michael , Unwin Katy , Woolfenden Sue , Eapen Valsamma 
Published: April 2021

Background: The early detection of developmental conditions such as autism is vital to ensure children can access appropriate and timely evidence-based supports, services, and interventions. Children who have undetected developmental conditions early in life are more likely to develop later health, developmental, learning, and behavioral issues, which in turn can have a cumulative effect over the life course.Methods: The current protocol describes a multi-site, cluster randomized control trial comparing a developmental surveillance pathway for autism to usual care, using opportunistic visits to general practitioners (GPs). Units of randomization are GP clinics across two Australian states (New South Wales and Victoria), with thirty clinics within each state, each of which will aim to recruit approximately forty children aged between ~18- and 24-months, for a total of ~2,400 participants. Children will be randomized to two clusters; namely, an autism surveillance pathway (ASP) or surveillance as usual (SaU). The screening process for the ASP arm involves primary and secondary screenings for developmental concerns for autism, using both parent and GP reports and observations. Children in both arms who show signs of developmental concerns for autism will be offered a full developmental assessment by the research team at 24 months of age to determine the efficacy of developmental surveillance in successfully identifying children with autism.Trial Registration: The trial is registered with ANZCTR (ACTRN12619001200178) and reporting of the trial results will be according to recommendations in the CONSORT Statement.
Case Report: A Rare Presentation of NSAID-Induced Secondary Membranous Nephropathy in a Pediatric Patient
Authors: Shah Siddharth , Elder M. Asope , Hata Jessica 
Published: April 2021

Background: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, but it is responsible for &lt;5% of nephrotic syndrome cases in children. MN has primary and secondary forms. Secondary MN is caused by viral infections, autoimmune diseases like lupus, or drugs. Non-steroid anti-inflammatory drug (NSAID)-induced secondary MN is rarely described in the pediatric population. Thus, the clinical presentation and time to recovery are vastly unknown in the pediatric subgroup.Clinical Presentation: We report a case of a 15-year-old female who presented with acute onset of nephrotic range proteinuria, significant hypoalbuminemia, hyperlipidemia, and lower extremity edema related to the presence of nephrotic syndrome. She had a history of ibuprofen use periodically for 6 months before presentation because of menstrual cramps and intermittent lower abdominal pain. After the presentation, we performed a renal biopsy that reported stage 1–2 MN, likely secondary. The phospholipase A2 receptor (PLA2R) antibody on the blood test and PLA2R immune stain on the renal biopsy sample were negative. We performed a comprehensive evaluation of the viral and immune causes of secondary MN, which was non-revealing. She had stopped ibuprofen use subsequent to the initial presentation. She was prescribed ACE inhibitor therapy. After 6 months of ACE inhibitor treatment, the proteinuria had resolved.Conclusion: Proteinuria can last for several weeks when NSAID induces secondary MN and nephrotic syndrome. With the widespread use of NSAIDs prevalent in the pediatric community, further studies are needed to evaluate and study the role of NSAIDs in this condition.
Reverse Remodeling in Human Heart Failure after Cardiac Resynchronization Therapy Is Associated With Reduced RHO-Kinase Activation
Authors: Ocaranza Maria Paz , Jalil Jorge E. , Altamirano Rodrigo , León Ana de , Moya Jackeline , Lonis Alejandra , Gabrielli Luigi , Nab Paul Mac , Córdova Samuel , Paredes Alejandro , Vergara Ismael , Bittner Alex , Sabat Karime , Pastorini Karla 
Published: April 2021

Background: Reverse remodeling is a clinically relevant endpoint in heart failure with reduced ejection fraction (HFrEF). Rho-kinase (ROCK) signaling cascade activation correlates with cardiac remodeling and left ventricular (LV) systolic dysfunction in HFrEF patients. Cardiac resynchronization therapy (CRT) is effective in HFrEF, especially when there is a left bundle block, as this treatment may stimulate reverse remodeling, thereby improving quality of life and prolonging survival for patients with this severe condition. Here, we evaluate the hypothesis that ROCK activation is reduced after effective CRT in HFrEF.Methods: ROCK activation in circulating leukocytes was evaluated in 28 HFrHF patients, using Western blot (myosin light chain phosphatase subunit 1 phosphorylation, MYPT1p/t), before and three months after initiation of CRT. LV systolic function and remodeling were assessed by echocardiography.Results: Three months after CRT, LV ejection fraction increased an average of 14.5% (p &lt; 0.001) in 13 patients (responders), while no change was observed in 15 patients (non-responders). End-systolic diameter decreased 16% (p &lt; 0.001) in responders, with no change in non-responders. ROCK activation in PBMCs decreased 66% in responders (p &lt; 0.05) but increased 10% in non-responders (NS). LV end-diastolic diameter was also 5.2 mm larger in non-responders vs. responders (p = 0.058). LV ejection fraction, systolic diameter, and ROCK activation levels were similar in both groups at baseline.Conclusion: In HFrEF patients, 3 months of effective CRT induced reverse myocardial remodeling, and ROCK activation was significantly decreased in circulating leukocytes. Thus, decreased ROCK activation in circulating leukocytes may reflect reverse cardiac remodeling in patients with heart failure.
Toxicology and Pharmacokinetics Study of Intradiscal Injection of Simvastatin in Rabbits
Authors: Huang Xiaodong , He Wei , Wang Weiheng , Fan Quanchun , Ye Xiaojian , Wu Zenghui , Lin Chia-Ying 
Published: April 2021

To test the pharmacokinetics and toxicology of whole organs and tissues after intradiscal injection of simvastatin in rabbits. To provide the information needed to support human clinical trials. Twelve male and twelve female rabbits were randomly divided into four groups: control group (0 mg/ml), low dose group (0.1 mg/ml), medium dose group (1 mg/ml) and high dose group (10 mg/ml). Simvastatin at different concentrations of 10 μl was injected into L3/4, L4/5 and L5/6 intervertebral discs in each group. Poly (ethylene glycol) -poly (lactic-co-glycolic acid) -poly (ethylene glycol) (PEG-PLGA-PEG) polymer as the drug carrier. The pharmacokinetics of blood samples were measured by LC-MS/MS. Cerebrospinal fluid was obtained and the drug concentration was measured. Blood routine, blood biochemistry and urine of all animals were analyzed and evaluated. The heart, kidney, liver and spleen of each animal were observed and weighed. The intervertebral disc tissues were stained with hematoxylin and hematoxylin (H&amp;E), and then qualitatively analyzed by optical microscopy. 28 days after intradiscal injection of simvastatin, 28 days after simvastatin intradiscal injection, there was no significant difference between the weight, food residue, blood routine, blood biochemistry, urine routine results and the weight of each organ in the four groups (p &gt; 0.05). The serum concentration of simvastatin is lower than the lowest measurable concentration. The histological score of the intervertebral disc in the high-dose group was significantly higher than that in the other three groups at 28 days (p &lt; 0.05). Three doses of simvastatin were injected into male and female animals respectively, showing no toxic effects. Microscopic histological evaluation of the intervertebral disc showed that the high dose group (10 mg/ml) had damage to the intervertebral disc tissue.
Leflunomide Induces Dose-Dependent Lung Injury in Mice via Stimulating Vimentin and NLRP3 Inflammasome Production
Authors: El-Sherbiny Mohamed , Atef Hoda , Eladl Mohamed Ahmed , Mohamed Abdelaty Shawky , El-Shafey Mohamed , Ali Howaida S. , Zaitone Sawsan A. , Alomar Suliman Y. , Alqahtani Saeed Awad M. , Aloyouni Sheka Yagub , Attia Mohammed A. 
Published: April 2021

Recently, the therapeutic importance of the anti-rheumatic drug, leflunomide, has been increased after the involvement of leflunomide in treating other autoimmune diseases and its promising role in retarding human malignancies. Few studies have focused on the safety in human or animals without clear outlining of the pathologic features on target organs. One clinical study related leflunomide with significant pulmonary complications in predisposed individuals. The current study examined the dose-dependent lung injury produced by leflunomide in healthy mice. Albino mice were allocated into four different groups. Group (1): Vehicle control group, Group (2–4): mice received leflunomide (2.5, 5 or 10 mg/kg), respectively, for 8 weeks and then lungs were dissected from the mice for histopathological examination and fibrosis evaluation (Masson’s trichrome staining and α-smooth muscle actin immunohistochemistry). Enzyme linked immunosorbent assay was used to assess the vimentin and other inflammatory factors in the lung homogenate whereas Western blot analysis was employed to assess α-smooth muscle actin, vimentin and collagen 1. Results indicated that leflunomide induced dose-dependent pulmonary injury and the high dose and increased the vimentin, inflammatory markers (NLRP3 and interlukin-1β). Histologic examination showed distorted architecture, marked inflammatory cells infiltrate and increase collagen content. The findings were supported by Western blotting and the immunohistochemical study which showed greater pulmonary α-smooth muscle actin and vimentin content. In conclusion, the current results highlighted that leflunomide produced dose-dependent pulmonary toxicities that requires further investigation of the nature of injury.
The Efficacy and Safety of Pulmonary Vasodilators in Pediatric Pulmonary Hypertension (PH): A Systematic Review and Meta-analysis
Authors: Shu Tingting , Chen Huaqiao , Wang Lu , Wang Wuwan , Feng Panpan , Xiang Rui , Wen Li , Huang Wei 
Published: April 2021

Background: We performed a meta-analysis to evaluate the efficacy and safety of pulmonary vasodilators in pediatric pulmonary hypertension (PH) patients.Methods: We searched electronic databases including PubMed, EMBASE, and the Cochrane Library up to May 2020, and conducted a subgroup analysis for pulmonary vasodilators or underlying disease.Results: Fifteen studies with 719 pediatric PH patients were included in the meta-analysis. Adverse events did not differ (p = 0.11, I2 = 15%) between the pulmonary vasodilators group and the control group, neither in the subgroups. In total, compared with the control group treatment, pulmonary vasodilators significantly decreased the mortality (p = 0.002), mean pulmonary artery pressure (mPAP, p = 0.02), and mechanical ventilation duration (p = 0.03), also improved the oxygenation index (OI, p = 0.01). In the persistent pulmonary hypertension of the newborn (PPHN) subgroup, phosphodiesterase type 5 inhibitors (PDE5i) significantly reduced mortality (p = 0.03), OI (p = 0.007) and mechanical ventilation duration (p = 0.004). Administration of endothelin receptor antagonists (ERAs) improved OI (p = 0.04) and mechanical ventilation duration (p &lt; 0.00001) in PPHN. We also found that in the pediatric pulmonary arterial hypertension (PPAH) subgroup, mPAP was pronouncedly declined with ERAs (p = 0.006). Systolic pulmonary artery pressure (sPAP, p &lt; 0.0001) and pulmonary arterial/aortic pressure (PA/AO, p &lt; 0.00001) were significantly relieved with PDE5i, partial pressure of arterial oxygen (PaO2) was improved with prostacyclin in postoperative PH (POPH) subgroup (p = 0.001). Compared with the control group, pulmonary vasodilators could significantly decrease PA/AO pressure (p &lt; 0.00001) and OI (p &lt; 0.00001) in the short-term (duration &lt;7 days) follow-up subgroup, improve mPAP (p = 0.03) and PaO2 (p = 0.01) in the mid-term (7–30 days) follow-up subgroup, also decrease mortality, mPAP (p = 0.0001), PA/AO pressure (p = 0.0007), duration of mechanical ventilation (p = 0.004), and ICU stay (p &lt; 0.00001) in the long-term follow subgroup (&gt;30 days).Conclusion: Pulmonary vasodilators decrease the mortality in pediatric PH patients, improve the respiratory and hemodynamic parameters, reduce the mechanical ventilation duration.