bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Release of Peripheral Immune Inflammatory Cytokines Promote an Inflammatory Cascade in PCOS Patients via Altering the Follicular Microenvironment
Authors: Liu Yishan , Liu Hao , Li Zitao , Fan Hualin , Yan Xiumin , Liu Xiao , Xuan Jianyan , Feng Du , Wei Xiangcai 
Published: May 2021

BackgroundHormones and immune imbalance are critical factors in polycystic ovary syndrome (PCOS). The alternation of immune microenvironment of oocytes may play a significant role in infertility of PCOS patients.ObjectiveThis study explores the role of follicular fluid microenvironment change in inflammatory pathways activation of granulosa cells (GCs) in PCOS women infertility.MethodsWe enrolled 27 PCOS patients and 30 controls aged 22 to 38 years who underwent IVF and collected their luteinized granulosa cells (LGCs). Meanwhile, a granulosa-like tumor cell line (KGN) as a cell-model assisted this study. Key inflammatory markers in human ovarian GCs and follicular fluid were detected by RT-qPCR, Western blotting, or ELISA. The KGN cells were treated with follicle supernatant mixed with normal medium to simulate the microenvironment of GCs in PCOS patients, and the inflammation indicators were observed. The assembly of NLRP3 inflammasomes was detected by immunofluorescence techniques. Dihydroethidium assay and EdU proliferation assay were used to detect ROS and cell proliferation by flow cytometry.ResultsCompared with normal controls (n = 19), IL-1β (P = 0.0005) and IL-18 (P = 0.021) in the follicular fluid of PCOS patients (n = 20) were significantly increased. The NF-κB pathway was activated, and NLRP3 inflammasome was formatted in ovarian GCs of PCOS patients. We also found that inflammation of KGN cells was activated with LPS irritation or stimulated by follicular fluid from PCOS patients. Finally, we found that intracellular inflammation process damaged mitochondrial structure and function, which induced oxidative stress, affected cellular metabolism, and impaired cell proliferation.ConclusionInflammatory microenvironment alteration in the follicular fluid of PCOS patients leads to activated inflammatory pathway in GCs, serving as a crucial factor that causes adverse symptoms in patients. This study provides a novel mechanism in the inflammatory process of PCOS.
Case Report: Viral Pneumonia Could Prompt the Advancement of Immune-Mediated Liver Disease
Authors: Li Qian , Wang Jun , Zhou Xueshi , Lu Hongzhou , Lu Mengji , Huang Lihua 
Published: May 2021

Background: The impact of the influenza A (H1N1) and SARS-CoV-2 virus on the development of autoimmune hepatitis has not been described previously.Methods: In this case series, we evaluated the dynamic changes in liver function of three patients with autoimmune hepatitis who presented with viral infection (two with the H1N1 and one with the SARS-CoV-2 virus) during the recent COVID-19 outbreak.Result: Patient 1 was a 68-year-old woman with a history of hepatitis of unknown origin before being infected with the H1N1 virus. Autoimmune hepatitis with an exacerbation of liver injury was diagnosed during the infection. Patient 2 was a 48-year-old woman with pre-existing autoimmune hepatitis. Despite being on immunosuppressant therapy (using glucocorticoids), liver injury recurred with elevated total bilirubin and gamma-glutamyl transferase levels post H1N1 infection. Patient 3 was a 61-year-old woman with probable autoimmune hepatitis. Liver injury recurred with a flare in alanine transaminase/aspartate transaminase levels post SARS-CoV-2 infection, in spite of the patient being on liver protection therapy (using ursodeoxycholic acid).Conclusion: The case series raises the possibility that COVID-19 or influenza induced pneumonia triggers the progression of autoimmune hepatitis.
Mitomycin C Inhibits Esophageal Fibrosis by Regulating Cell Apoptosis and Autophagy via lncRNA-ATB and miR-200b
Authors: Zhang Yin , Wang Qinge , Xu Yuping , Sun Jing , Ding Yanbo , Wang Li , Chen Bingfang , Sun Kewen , Chen Jianping 
Published: May 2021

Benign esophageal strictures (BESs) frequently results from esophageal fibrosis. The transformation of fibroblasts into fibrocyte is an important cause of fibrosis. The treatment of fibrosis is challenging. Some previous studies have indicated the antifibrotic effect of mitomycin C (MMC). However, the mechanism of action of MMC and its optimal dose for treatment remains unclear. In the present study, the role of MMC in fighting fibrosis and its mechanism was investigated. Human esophageal fibroblast cells (HEFs)were treated without or with MMC, at 2, 5, 10 μg/ml, combining with mimic lncRNA-ATB, miR-200b inhibitor, rapamycin (RAPA), and 3-Methyladenine (3-MA). The cell viability, and cell apoptosis were evaluated. In addition, expression of apoptosis related proteins (caspase8 and caspase3), autophagy related proteins (LC3II and ATG5) and fibrosis related proteins (α-SMA collagen-1 and TGF-β) were also evaluated. Furthermore, autophagosome was observed by transmission electron microscope. Results showed that the expression of lncRNA-ATB was down-regulated and miR-200b was up-regulated after treated with MMC. And MMC induced cell apoptosis and inhibited cell autophagy. On the other hand, RAPA, mimic lncRNA-ATB and miR-200b inhibitor reduced fibrogenic effect of MMC on HEFs. Collectively, this study suggests that MMC inhibited esophageal fibrosis by regulating cell apoptosis and autophagy via downregulating lncRNA-ATB and upregulating miR-200b.
Circulating Neurofilament Light Predicts Cognitive Decline in Patients With Post-stroke Subjective Cognitive Impairment
Authors: Wang Jian-Hong , Huang Jie , Guo Fu-Qiang , Wang Fang , Yang Shu , Yu Neng-Wei , Zheng Bo , Wang Jian 
Published: May 2021

BackgroundSubjective cognitive impairment (SCI) is common after acute ischemic stroke and adversely affects the quality of life. SCI is associated with an increased risk of developing mild cognitive impairment and dementia. Identifying biomarkers which could predict long-term cognitive outcomes of post-stroke SCI is of importance for early intervention. This study aims to investigate the association between circulating neurofilament light (NfL) and long-term cognitive function in patients with post-stroke SCI.MethodsThis longitudinal study recruited 304 patients with post-stroke SCI, and serum NfL levels were determined at baseline. These patients were followed up for 12 months for the observation of cognitive change. Cognitive performances were assessed by a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) scale.ResultsThe patients were divided into a progression group (as determined by decreased TICS-40 scores) and a stable group (as determined by increased or unchanged TICS-40 scores). The progression group had significantly higher serum NfL levels than the stable group at baseline. Serum NfL levels were predictive for longitudinal cognitive decline during follow-up.ConclusionThese findings imply that circulating NfL could predict the long-term cognitive change of patients with post-stroke SCI.
Transitions of Care Coordination Intervention Identifies Barriers to Discharge in Hospitalized Stroke Patients
Authors: Zimmerman William Denney , Grenier Rachel E. , Palka Sydney V. , Monacci Kelsey J. , Lantzy Amanda K. , Leutbecker Jacqueline A. , Geng Xue , Denny Mary Carter 
Published: May 2021

Background: Prolonged hospital lengths of stay increase costs, delay rehabilitation, and expose acute ischemic stroke patients to hospital-acquired infections. We designed and implemented a nurse-driven transitions of care coordinator (TOCC) program to facilitate the transition of care from the acute care hospital setting to rehabilitation centers and home.Methods: This was a single-blinded, prospective, randomized pilot study of 40 participants to evaluate the feasibility of implementing a TOCC program led by a stroke nurse navigator in hospitalized acute ischemic stroke patients. The intervention consisted of a stroke nurse navigator completing eight specific tasks, including meeting with stroke patients and their families, facilitating communication between team members at multi-disciplinary rounds, assisting with referrals to rehabilitation facilities, providing stroke education, and arranging stroke clinic follow-up appointments, which were confirmed to be completed by independent study personnel. The primary outcome was to assess the feasibility of the program. The secondary outcomes included comparing hospital length of stay (LOS) and patient satisfaction between the TOCC and usual care groups. We also explored the association between patient-level variables and LOS.Results: The TOCC program was feasible with all pre-specified components completed in 84.2% (95% CI: 60.4–96.6%) and was not significantly different from the assumed completion rate of 75% (p = 0.438). There was no significant difference in median LOS between the two groups [TOCC 5.95 days (4.02, 9.57) vs. usual care 4.01 days (2.00, 10.45), false discovery rate (FDR)-adjusted p = 0.138]. There was a trend toward higher patient median satisfaction in the TOCC group [TOCC 35.00 (33.00, 35.00) vs. usual care 30 (26.00, 35.00), FDR-adjusted p = 0.1] as assessed by a questionnaire at 30 days after discharge. The TOCC study allowed us to identify patient variables (gender, insurance, stroke severity, and discharge disposition) that were significantly associated with longer hospital LOS.Conclusion: A TOCC program is feasible and can serve as a guide for future allocation of resources to facilitate transitions of care and avoid prolonged hospital stays.
An Audit and Comparison of pH, Measured Concentration, and Particulate Matter in Mannitol and Hypertonic Saline Solutions
Authors: Carr Christopher J. , Scoville Jonathan , Ruble James , Condie Chad , Davis Gary , Floyd Candace L. , Kelly Logan , Monson Ken , Reichert Ethan , Sarigul Buse , Hawryluk Gregory W. J. 
Published: May 2021

Background: The preferred hyperosmolar therapy remains controversial. Differences in physical properties such as pH and osmolality may be important considerations in hyperosmolar agent selection. We aimed to characterize important physical properties of commercially available hyperosmolar solutions.Methods: We measured pH and concentration in 37 commonly-used hyperosmolar solutions, including 20 and 25% mannitol and 3, 5, 14.6, and 23.4% hypertonic saline. pH was determined digitally and with litmus paper. Concentration was determined by freezing point and vapor pressure osmometry. Salinity/specific gravity was measured with portable refractometry. Particulate matter was analyzed with filtration and light microscopy and with dynamic light scattering nephelometry.Results: pH of all solutions was below physiological range (measured range 4.13–6.80); there was no correlation between pH and solution concentration (R2 = 0.005, p = 0.60). Mannitol (mean 5.65, sd 0.94) was less acidic than hypertonic saline (5.16, 0.60). 14/59 (24%) pH measurements and 85/111 concentration measurements were outside manufacturer standards. All 36/36 mannitol concentration measurements were outside standards vs. 48/72 (67%) hypertonic saline (p &lt; 0.0001). All solutions examined on light microscopy contained crystalline and/or non-crystalline particulate matter up to several hundred microns in diameter. From nephelometry, particulate matter was detected in 20/22 (91%) solutions.Conclusion: We present a novel characterization of mannitol and hypertonic saline. Further research should be undertaken, including research examining development of acidosis following hyperosmolar therapy, the relevance of our findings for dose-response, and the clinical relevance of particulate matter in solution.
Different Impact of Heart Rate Variability in the Deep Cerebral and Central Hemodynamics at Rest: An in silico Investigation
Authors: Scarsoglio Stefania , Ridolfi Luca 
Published: May 2021

Background: Heart rate variability (HRV), defined as the variability between consecutive heartbeats, is a surrogate measure of cardiac vagal tone. It is widely accepted that a decreased HRV is associated to several risk factors and cardiovascular diseases. However, a possible association between HRV and altered cerebral hemodynamics is still debated, suffering from HRV short-term measures and the paucity of high-resolution deep cerebral data. We propose a computational approach to evaluate the deep cerebral and central hemodynamics subject to physiological alterations of HRV in an ideal young healthy patient at rest.Methods: The cardiovascular-cerebral model is composed by electrical components able to reproduce the response of the different cardiovascular regions and their features. The model was validated over more than thirty studies and recently exploited to understand the hemodynamic mechanisms between cardiac arrythmia and cognitive deficit. Three configurations (baseline, increased HRV, and decreased HRV) are built based on the standard deviation (SDNN) of RR beats. For each configuration, 5,000 RR beats are simulated to investigate the occurrence of extreme values, alteration of the regular hemodynamics pattern, and variation of mean perfusion/pressure levels.Results: In the cerebral circulation, our results show that HRV has overall a stronger impact on pressure than flow rate mean values but similarly alters pressure and flow rate in terms of extreme events. By comparing reduced and increased HRV, this latter induces a higher probability of altered mean and extreme values, and is therefore more detrimental at distal cerebral level. On the contrary, at central level a decreased HRV induces a higher cardiac effort without improving the mechano-contractile performance, thus overall reducing the heart efficiency.Conclusions: Present results suggest that: (i) the increase of HRV per se does not seem to be sufficient to trigger a better cerebral hemodynamic response; (ii) by accounting for both central and cerebral circulations, the optimal HRV configuration is found at baseline. Given the relation inversely linking HRV and HR, the presence of this optimal condition can contribute to explain why the mean HR of the general population settles around the baseline value (70 bpm).
Tumor Control Probability Modeling for Radiation Therapy of Keratinocyte Carcinoma
Authors: Prior Phillip , Awan Musaddiq J. , Wilson J Frank , Li X. Allen 
Published: May 2021

SummarySkin cancer patients may be treated definitively using radiation therapy (RT) with electrons, kilovoltage, or megavoltage photons depending on tumor stage and invasiveness. This study modeled tumor control probability (TCP) based on the pooled clinical outcome data of RT for primary basal and cutaneous squamous cell carcinomas (BCC and cSCC, respectively). Four TCP models were developed and found to be potentially useful in developing optimal treatment schemes based on recommended ASTRO 2020 Skin Consensus Guidelines for primary, keratinocyte carcinomas (i.e. BCC and cSCC).BackgroundRadiotherapy (RT) with electrons or photon beams is an excellent primary treatment option for keratinocyte carcinoma (KC), particularly for non-surgical candidates. Our objective is to model tumor control probability (TCP) based on the pooled clinical data of primary basal and cutaneous squamous cell carcinomas (BCC and cSCC, respectively) in order to optimize treatment schemes.MethodsPublished reports citing crude estimates of tumor control for primary KCs of the head by tumor size (diameter: ≤2 cm and &gt;2 cm) were considered in our study. A TCP model based on a sigmoidal function of biological effective dose (BED) was proposed. Three-parameter TCP models were generated for BCCs ≤2 cm, BCCs &gt;2cm, cSCCs ≤2 cm, and cSCCs &gt;2 cm. Equivalent fractionation schemes were estimated based on the TCP model and appropriate parameters.ResultsTCP model parameters for both BCC and cSCC for tumor sizes ≤2 cm and &gt;2cm were obtained. For BCC, the model parameters were found to be TD50 = 56.62 ± 6.18 × 10-3 Gy, k = 0.14 ± 2.31 × 10−2 Gy−1 and L = 0.97 ± 4.99 × 10−3 and TD50 = 55.78 ± 0.19 Gy, k = 1.53 ± 0.20 Gy−1 and L = 0.94 ± 3.72 × 10−3 for tumor sizes of ≤2 cm and &gt;2 cm, respectively. For SCC the model parameters were found to be TD50 = 56.81 ± 19.40 × 104 Gy, k = 0.13 ± 7.92 × 104 Gy−1 and L = 0.96 ± 1.31 × 10-2 and TD50 = 58.44 ± 0.30 Gy, k = 2.30 ± 0.43 Gy−1 and L = 0.91± 1.22 × 10−2 for tumors ≤2cm and &gt;2 cm, respectively. The TCP model with the derived parameters predicts that radiation regimens with higher doses, such as increasing the number of fractions and/or dose per fraction, lead to higher TCP, especially for KCs &gt;2 cm in size.ConclusionFour TCP models for primary KCs were developed based on pooled clinical data that may be used to further test the recommended kV and MV x-ray and electron RT regimens from the 2020 ASTRO guidelines. Increasing both number of fractions and dose per fraction may have clinically significant effects on tumor control for tumors &gt;2 cm in size for both BCC and cSCC.
An Approach to Accelerate Healing and Shorten the Hospital Stay of Patients With Anastomotic Leakage After Esophagectomy: An Explorative Study of Systematic Endoscopic Intervention
Authors: Zhong LeQi , Zhong JiuDi , Tan ZiHui , Wei YiTong , Su XiaoDong , Wen ZheSheng , Rong TieHua , Hu Yi , Luo KongJia 
Published: May 2021

ObjectiveTo explore the comprehensive role of systemic endoscopic intervention in healing esophageal anastomotic leak.MethodsIn total, 3919 consecutive patients with esophageal cancer who underwent esophagectomy and immediate esophageal reconstruction were screened. In total, 203 patients (5.10%) diagnosed with anastomotic leakage were included. The participants were divided into three groups according to differences in diagnosis and treatment procedures. Ninety-four patients received conventional management, 87 patients received endoscopic diagnosis only, and the remaining 22 patients received systematic endoscopic intervention. The primary endpoint was overall healing of the leak after oncologic esophageal surgery. The secondary endpoints were the time from surgery to recovery and the occurrence of adverse events.Results173 (85.2%; 95% CI, 80.3-90.1%) of the 203 patients were successfully healed, with a mean healing time of 66.04 ± 3.59 days (median: 51 days; range: 13-368 days), and the overall healing rates differed significantly among the three groups according to the stratified log-rank test (P&lt;0.001). The median healing time of leakage was 37 days (95% CI: 33.32-40.68 days) in the endoscopic intervention group, 51 days (95% CI: 44.86-57.14 days) in the endoscopic diagnostic group, and 67 days (95% CI: 56.27-77.73 days) in the conventional group. The overall survival rate was 78.7% (95% CI: 70.3 to 87.2%) in the conventional management group, 89.7% (95% CI: 83.1 to 96.2%) in the endoscopic diagnostic group and 95.5% (95% CI: 86.0 to 100%) in the systematic endoscopic intervention group. Landmark analysis indicated that the speed of wound healing in the endoscopic intervention group was 2-4 times faster at any period than that in the conservative group. There were 20 (21.28%) deaths among the 94 patients in the conventional group, 9 (10.34%) deaths among the 87 patients in the endoscopic diagnostic group and 1 (4.55%) death among the 22 patients in the endoscopic intervention group; this difference was statistically significant (Fisher exact test, P &lt; 0.05).ConclusionTailored endoscopic treatment for postoperative esophageal anastomotic leakage based on endoscopic diagnosis is feasible and effective. Systematic endoscopic intervention shortened the treatment period and reduced mortality and should therefore be considered in the management of this disease.
Potential Impact of ALKBH5 and YTHDF1 on Tumor Immunity in Colon Adenocarcinoma
Authors: Yan Guanyu , An Yue , Xu Boyang , Wang Ningning , Sun Xuren , Sun Mingjun 
Published: May 2021

BackgroundALKBH5 and YTHDF1 are regarded as the eraser and reader, respectively, in N6-methyladenosine (m6A) modification. Recently, immune contexture has been drawing increasing attention in terms of the progression and treatment of cancers. This study aimed to determine the relationship between ALKBH5/YTHDF1 and immunological characteristics of colon adenocarcinoma (COAD).MethodsExpression of ALKBH5 and YTHDF1 was investigated across TCGA and GEO validated in our study. Patients with COAD were divided into two clusters using consensus clustering based on the expression of ALKBH5 and YTHDF1. We then compared their clinical characteristics and performed gene set enrichment analysis (GSEA) to identify the functional differences. Immune infiltration analyses were conducted using ESTIMATE, CIBERSORT, and ssGSEA. In addition, we evaluated the expression of the targets of immune checkpoint inhibitors (ICIs) and calculated the tumor mutation burden (TMB) of the tumor samples. Weighted gene co-expression network analysis (WGCNA) was used to identify the genes related to both ALKBH5/YTHDF1 expression and immunity. GSE39582 was utilized for external validation of immunological features between the two clusters.ResultsCluster 2 had high expression of ALKBH5 and lesser so of YTHDF1, whereas Cluster 1 had just the reverse. Cluster 1 had a higher N stage and pathological stage than Cluster 2. The latter had stronger immune infiltration, higher expression of targets of ICIs, more TMB, and a larger proportion of deficiency in mismatch repair-microsatellite instability-high (dMMR-MSI-H) status than Cluster 1. Moreover, WGCNA revealed 14 genes, including PD1 and LAG3, related to both the expression of ALKBH5/YTHDF1 and immune scores.ConclusionsALKBH5 and YTHDF1 influence immune contexture and can potentially transform cold tumors into hot tumors in patients with COAD.
Different Doses of Fingolimod in Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Wu Xin , Xue Tao , Wang Zilan , Chen Zhouqing , Zhang Xuwei , Zhang Wei , Wang Zhong 
Published: May 2021

Background: The efficacy and safety of fingolimod for relapsing-remitting multiple sclerosis (RRMS) had been well verified in several large randomized controlled trials (RCTs) during the past decade. However, there are fewer systematic comparisons of different doses of fingolimod and whether the dose of 0.5 mg/d is the optimal one still remains to be solved.Objective: The objective of this systematic review was to evaluate the efficacy and safety of the four existing doses of fingolimod in the treatment of RRMS, especially the dose of 0.5 mg/d.Methods: MEDLINE, EMBASE, Cochrane Library, and clinicaltrials.gov were searched for RCTs which were performed to evaluate different doses of fingolimod and the corresponding control (placebo or DMTs) up to October 2020. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) was analyzed and calculated with a random effect model.Results: We pooled 7184 patients from 11 RCTs. Fingolimod 0.5 mg/d was superior to control group in all eight efficacy outcomes including annualized relapse rate (ARR) (MD −0.22, 95%CI −0.29 to −0.14, p &lt; 0.00001) but surprisingly showed a higher risk of basal-cell carcinoma (RR 4.40, 95%CI 1.58 to 12.24, p = 0.004). Although 1.25 mg/d is more than twice the dose of 0.5 mg/d, the effect size was almost similar between them. Dose of 5 mg/d obtained an unsatisfactory efficacy while showing a greater risk of adverse events than other three doses (RR 1.17, 95%CI 1.05 to 1.30, p = 0.003). Additionally, fingolimod 0.25 mg/d not only showed a better performance in delaying the disease progress of magnetic resonance imaging (MRI), but also achieved a certain degree of patient treatment satisfaction.Conclusion: At present, 0.5 mg/d remains to be the optimal dose of fingolimod for RRMS patients but trials of a lower dose are still of great clinical significance and should be paid more attentions.