bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology, Treatment and Prognosis Analysis of Small Cell Breast Carcinoma: A Population-Based Study
Authors: Zhu Jiahao , Wu Gang , Zhao Yutian , Yang Bo , Chen Qingqing , Jiang Jianwei , Meng You , Ji Shengjun , Gu Ke 
Published: April 2022

BackgroundPrimary small cell breast carcinoma (SCBC) is an uncommon malignancy with highly invasive behavior. The aim of this study was to find out more about the incidence, clinicopathologic characteristics and identify potential prognostic factors of SCBC.MethodsData of patients with primary diagnosis of SCBC between 1975 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence after adjustment for age and percentage change per year in incidence were calculated. Disease-specific survival (DSS) and overall survival (OS) were analyzed among these SCBC patients identified from the SEER database. The whole cohorts were randomized into training and validation cohorts as ratio of 7: 3. Cox regression analysis was performed to determine predictors of survival with the training cohorts. Predictive models were constructed with training cohorts, and nomogram validation was performed using receiver operating characteristic curves, concordance indices and calibration curves in both training and validation cohorts.Results323 SCBC patients were enrolled finally during the research period. The overall incidence after adjustment for age between 1990 and 2018 was 0.14 per million per year, and the prevalence of the incidence has plateaued. Most of these tumors were poorly differentiated or undifferentiated. The most prevalent presenting stage was Stage II. Patients identified in this study were randomly divided into training (n = 226) and testing (n = 97) cohorts. Multivariate Cox proportional hazards model showed that chemotherapy, surgery and stage were important predictors of DSS and OS.ConclusionSCBC is considered an infrequent breast neoplasm with aggressive characteristics. Tumor stage is associated with poor prognosis. Combination of surgery and chemotherapy is the main treatment for SCBC.
Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes
Authors: Zhang Haiyue , Hu Yiling , Pan Dongli , Xv Yuehua , Shen Weifeng 
Published: April 2022

Background and Aims: Antithrombin (AT) is the most important physiological inhibitor in vivo, and coagulation factor II (FII) or prothrombin is a coagulation factor vital to life. The purpose of our research was to illustrate the connection between gene mutations and the corresponding deficiencies of AT and FII.Methods: Functional and molecular analyses were performed. The possible impact of the mutation was analyzed by online bioinformatics software. ClustalX-2.1-win and PyMol/Swiss-Pdb Viewer software were used for conservative analyses and to generate molecular graphic images, respectively.Results: The proband showed a lower limb venous thrombosis and acute pulmonary embolism infarction with reduced AT activity (50%). His mother, with subcutaneous ecchymosis, had reduced activities of AT and FII, of 44 and 5%, respectively. Molecular analysis showed that both the proband and his mother carried c.964A &gt; T (p.Lys322stop) heterozygotes in SERPINC1. The difference was that his mother carried homozygous c.494C &gt; T (p.Thr165Met) in F2, while the proband was wild type. Bioinformatics and model analysis indicated that mutations may destroy the function and structure of AT and FII protein.Conclusion: This study identified a novel mutation of SERPINC1 and a missense mutation of F2, which may be the molecular mechanism leading to AT and FII deficiency in this family. It will help genetic diagnosis and counseling for thrombotic families.
Evaluating the Causal Effects of TIMP-3 on Ischaemic Stroke and Intracerebral Haemorrhage: A Mendelian Randomization Study
Authors: Xiao Linxiao , Zou Xuelun , Liang Yan , Wang Yuxiang , Zeng Lang , Wu Jianhuang 
Published: April 2022

Aim: Since tissue inhibitors of matrix metalloproteinase 3 (TIMP-3) was reported to be a potential risk factor of atherosclerosis, aneurysm, hypertension, and post-ischaemic neuronal injury, it may also be a candidate risk factor of stress. Therefore, this study was designed to explore the causal role of TIMP-3 in the risk of ischaemic stroke (IS) and intracerebral haemorrhage (ICH), which are the two main causes of stress via this Mendelian Randomisation (MR) study.Methods: The summarised data of TIMP-3 level in circulation was acquired from the Cooperative Health Research in the Region of Augsburg public database and the outcome of IS and ICH was obtained from genome-wide association studies conducted by MEGASTROKE and the International Stroke Genetics Consortium, respectively. Five statistical methods including inverse-variance weighting, weighted-median analysis, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test, and MR-Robust Adjusted Profile Score were applied to evaluate the causal role of TIMP-3 in the occurrence of IS and ICH. Inverse-variance weighting was applied for assessing causality. Furthermore, heterogeneity and pleiotropic tests were utilised to confirm the reliability of this study.Results: We found that TIMP-3 could be a positively causal relationship with the incidence of IS (OR = 1.026, 95% CI: 1.007–1.046, p = 0.0067), especially for the occurrence of small vessel stroke (SVS; OR = 1.045, 95% CI: 1.016–1.076, p = 0.0024). However, the causal effects of TIMP-3 on another IS subtype cardioembolic stroke (CES; OR = 1.049, 95% CI: 1.006–1.094, p = 0.024), large artery stroke (LAS; OR = 1.0027, 95% CI: 0.9755–1.0306, p = 0.849) and ICH (OR = 0.9900, 95% CI: 0.9403–1.0423, p = 0.701), as well as ICH subtypes were not observed after Bonferroni corrections (p = 0.00714).Conclusion: Our results revealed that high levels of circulating TIMP-3 causally increased the risk of developing IS and SVS, but not CES, LAS, ICH, and all ICH subtypes. Further investigation is required to elucidate the underlying mechanism.
Early B Cell and Plasma Cell Kinetics Upon Treatment Initiation Portend Flares in Systemic Lupus Erythematosus: A Post-Hoc Analysis of Three Phase III Clinical Trials of Belimumab
Authors: Parodis Ioannis , Gomez Alvaro , Chow Jun Weng , Borg Alexander , Lindblom Julius , Gatto Mariele 
Published: April 2022

ObjectiveTo investigate changes in B cell subsets in relation to disease flares upon initiation of standard therapy (ST) plus belimumab or placebo in patients with systemic lupus erythematosus (SLE).Patients and MethodsUsing data from the BLISS-76, BLISS-SC and BLISS Northeast Asia trials, we investigated associations of relative to baseline rapid (through week 8) and early (through week 24) changes in peripheral B cell subsets, anti-dsDNA and complement levels with the occurrence of disease flares from week 24 through week 52 (Mann-Whitney U tests) or the entire study follow-up (Cox regression analysis), assessed using the SELENA-SLEDAI Flare Index.ResultsPatients on ST alone who flared displayed less prominent early decreases in CD19+CD20-CD138+ long-lived plasma cells (-16.1% versus -35.1%; P=0.012). In all arms combined, patients who developed severe flares showed less prominent early decreases in CD19+CD20-CD138+ long-lived plasma cells (-23.5% versus -39.4%; P=0.028) and CD19+CD27brightCD38bright SLE-associated plasma cells (-19.0% versus -27.8%; P=0.045). After adjustment for rapid changes, early increases in overall CD19+CD20+ B cells (HR: 1.81; 95% CI: 1.08–3.05; P=0.024) and early increases or no return after a rapid expansion in CD19+CD20+CD27+ memory B cells (HR: 1.58; 95% CI: 1.18–2.11; P=0.002) portended subsequent severe flares. Patients who developed flares of any severity showed no or less prominent rapid (0.0% versus -12.5%; P&lt;0.001) or early (-1.9% versus -21.7%; P&lt;0.001) decreases in anti-dsDNA levels, and patients who developed severe flares showed no or less prominent early decreases in anti-dsDNA levels (0.0% versus -13.3%; P=0.020). Changes in complement levels exhibited no ability to distinguish flaring from non-flaring patients.ConclusionsIncrease or lack of decrease in certain circulating B cell subsets or anti-dsDNA levels upon treatment initiation for active SLE heralded subsequent severe disease flares. A rapid expansion of memory B cells may signify sustained response to therapy when followed by a subsequent drop, while no return or delayed increases in memory B cells may portend flaring. Peripheral B cell and serological marker kinetics may help identify patients in whom therapeutic modifications could protect against flare development, and may hence prove a useful complement to traditional surveillance and early treatment evaluation in SLE.
AMG853, A Bispecific Prostaglandin D2 Receptor 1 and 2 Antagonist, Dampens Basophil Activation and Related Lupus-Like Nephritis Activity in Lyn-Deficient Mice
Authors: Pellefigues Christophe , Tchen John , Saji Chaimae , Lamri Yasmine , Charles Nicolas 
Published: April 2022

Systemic lupus erythematosus is a complex autoimmune disease during which patients develop autoantibodies raised against nuclear antigens. During the course of the disease, by accumulating in secondary lymphoid organs (SLOs), basophils support autoreactive plasma cells to amplify autoantibody production. We have recently shown that murine lupus-like disease could be controlled by 10 days of oral treatment with a combination of prostaglandin D2 (PGD2) receptor (PTGDR) antagonists through the inhibition of basophil activation and recruitment to SLOs. Importantly, inhibiting solely PTGDR-1 or PTGDR-2 was ineffective, and the development of lupus-like disease could only be dampened by using antagonists for both PTGDR-1 and PTGDR-2. Here, we aimed at establishing a proof of concept that a clinically relevant bispecific antagonist of PTGDR-1 and PTGDR-2 could be efficient to treat murine lupus-like nephritis. Diseased Lyn-deficient female mice received treatment with AMG853 (vidupiprant, a bispecific PTGDR-1/PTGDR-2 antagonist) for 10 days. This led to the dampening of basophil activation and recruitment in SLOs and was associated with a decrease in plasmablast expansion and immunoglobulin E (IgE) production. Ten days of treatment with AMG853 was consequently sufficient in reducing the dsDNA-specific IgG titers, circulating immune complex glomerular deposition, and renal inflammation, which are hallmarks of lupus-like disease. Thus, bispecific PTGDR-1 and PTGDR-2 antagonists, such as AMG853, are a promising class of drugs for the treatment or prevention of organ damage in systemic lupus erythematosus.
Effect of Factor H on Complement Alternative Pathway Activation in Human Serum Remains on Porcine Cells Lacking N-Glycolylneuraminic Acid
Authors: Lee Haneulnari , Park Eun Mi , Ko Nayoung , Choi Kimyung , Oh Keon Bong , Kang Hee Jung 
Published: April 2022

BackgroundTriple knockout (TKO) donor pigs lacking alpha-1,3-galactose (Gal),N-glycolylneuraminic acid (Neu5Gc), and Sd(a) expressions were developed to improve the clinical success of xenotransplantation. Neu5Gc, a sialic acid expressed on cell surfaces, recruits factor H to protect cells from attack by the complement system. Lack of Neu5Gc expression may cause unwanted complement activation, abrogating the potential benefit of gene-modified donor pigs. To investigate whether TKO porcine cells display increased susceptibility to complement activation in human serum, pathway-specific complement activation, apoptosis, and human platelet aggregation by porcine cells were compared betweenalpha-1,3-galactosyltransferasegene-knockout (GTKO) and TKO porcine cells.MethodsPrimary porcine peripheral blood mononuclear cells (pPBMCs) and endothelial cells (pECs) fromGTKO and TKO pigs were used. Cells were incubated in human serum diluted in gelatin veronal buffer (GVB++) or Mg++-EGTA GVB, and C3 deposition and apoptotic changes in these cells were measured by flow cytometry. C3 deposition levels were also measured after incubating these cells in 10% human serum supplemented with human factor H. Platelet aggregation in human platelet-rich plasma containingGTKO or TKO pECs was analyzed.ResultsThe C3 deposition level inGTKO pPBMCs or pECs in GVB++was significantly higher than that of TKO pPBMCs or pECs, respectively, but C3 deposition levels in Mg++-EGTA-GVB were comparable between them. The addition of factor H into the porcine cell suspension in 10% serum in Mg++-EGTA-GVB inhibited C3 deposition in a dose-dependent manner, and the extent of inhibition by factor H was similar betweenGTKO and TKO porcine cells. The percentage of late apoptotic cells in porcine cell suspension in GVB++increased with the addition of human serum, of which the net increase was significantly less in TKO pPBMCs than inGTKO pPBMCs. Finally, the lag time of platelet aggregation in recalcified human plasma was significantly prolonged in the presence of TKO pECs compared to that in the presence ofGTKO pECs.ConclusionTKO genetic modification protects porcine cells from serum-induced complement activation and apoptotic changes, and delays recalcification-induced human platelet aggregation. It does not hamper factor H recruitment on cell surfaces, allowing the suppression of alternative complement pathway activation.
Platelet-Depletion of Whole Blood Reveals That Platelets Potentiate the Release of IL-8 From Leukocytes Into Plasma in a Thrombin-Dependent Manner
Authors: Quach Huy Quang , Johnson Christina , Ekholt Karin , Islam Rakibul , Mollnes Tom Eirik , Nilsson Per H. 
Published: April 2022

ObjectiveIn a recent study, we found an elevated level of interleukin 8 (IL-8) in response to bacterial incubation in thrombin-sufficient human whole blood anticoagulated by the fibrin polymerization blocking peptide GPRP. Whether thrombin directly activated leukocytes or mediated the release via thrombin-dependent activation of platelets remains unresolved. Herein, we addressed the role of thrombin and platelets in IL-8 release.MethodsWe separated platelets from whole blood using a combination of 0.7% (w/v) citrate and GPRP for attenuating the hemostatic response during the separation of platelets. Cytokine responses were compared in whole blood and platelet-depleted blood upon Escherichia coli incubation. Cytokine responses were also profiled with and without reconstitution of either platelets or the supernatant from activated platelets.ResultsPlatelets were not activated during the separation process but responded to stimuli upon re-calcification. Plasma levels of IL-1β, IL-1Ra, IL-6, IL-8, IP-10, MIP-1α, and MIP-1β were significantly reduced in platelet-depleted blood compared to whole blood, but recovered in the presence of platelets, or with the supernatant of activated platelets. The leukocyte fraction and platelets were each found to contribute to the elevation of IL-8 at around 5 ng/ml; however, if combined, the release of IL-8 increased to 26 ng/ml. This process was dependent on thrombin since the levels of IL-8 remained at 5 ng/ml in whole blood if thrombin was blocked. Intracellular staining revealed that monocytes were the main source for IL-8 expression.ConclusionOur findings suggest that the release of IL-8 is mediated by the leukocytes, mainly monocytes, but potentiated via thrombin-dependent activation of platelets.
COVID-19 and Acute Kidney Injury: A Systematic Review
Authors: Sabaghian Tahereh , Kharazmi Amir Behnam , Ansari Ali , Omidi Fatemeh , Kazemi Seyyedeh Neda , Hajikhani Bahareh , Vaziri-Harami Roya , Tajbakhsh Ardeshir , Omidi Sajjad , Haddadi Sara , Shahidi Bonjar Amir Hashem , Nasiri Mohammad Javad , Mirsaeidi Mehdi 
Published: April 2022

IntroductionAcute kidney injury (AKI) has been associated with an increased mortality rate among hospitalized patients with Coronavirus disease 2019 (COVID-19). The current review aimed to evaluate the symptoms, complications, and treatments performed to manage AKI in patients with COVID-19.MethodsWe searched PubMed/Medline, Web of Science, and Embase for the relevant scientific literature published up to February 1, 2022. The following keywords were used: “COVID-19”, “SARS-CoV-2”, and “Acute kidney injury”.ResultsForty-four studies with a total number of 114 COVID-19 patients with AKI (Mean age: 53.6 years) were included in our systematic review. The most common comorbidities in patients with COVID-19 suffering from AKI were the history of diabetes, hypertension, and hyperlipidemia. Twelve out of the 44 included studies reported a history of chronic kidney disease (CKD) in this group of patients. Focal segmental glomerulosclerosis (FSGS) and acute tubular necrosis (ATN) were the most common pathological evidence. The average length of hospital stay was 19 days, and the average duration of need for mechanical ventilation was 3 days.ConclusionsThe current systematic review shows that AKI frequently complicates the course of COVID-19 hospitalizations and is associated with increased severity of illness, prolonged duration of hospitalization, and poor prognosis. Given the extent of the adverse impact of AKI, early detection of comorbidities and renal complications is essential to improve the outcomes of COVID-19 patients.
Comparison of Visual Outcomes Between Toric Intraocular Lenses and Clear Corneal Incisions to Correct Astigmatism in Image–Guided Cataract Surgery
Authors: Ding Ning , Song Xudong , Wang Xiaozhen , Wei Wenbin 
Published: April 2022

PurposeTo compare the astigmatism correction effects of toric intraocular lenses (IOL) and clear corneal incisions during image-guided cataract surgery.MethodsAll patients with regular corneal astigmatism of 0.75–1.5 D underwent cataract surgery and astigmatism correction using the Callisto eye image-guided system. One group had implantation of an AcrySof toric IOL. Another group had implantation of aspheric IOL with 3.0 mm single clear corneal incision (SCCI) on the steep axis. Uncorrected and best-corrected spectacle visual acuity, refraction, and toric IOL axis were evaluated at 1, 4, and 12 weeks postoperatively.ResultsSixty-eight eyes of 68 patients were included. The mean residual refractive cylinder was 0.34 ± 0.40 D in the toric group and 0.64 ± 0.57 D in the SCCI group. There were no significant differences in residual refractive cylinder, spherical equivalent, uncorrected distance visual acuity (UDVA), and best-corrected spectacle visual acuity (BCSVA) between groups. The percentage of the residual cylinder within ± 0.50 D was 75 and 56% for toric and SCCI cases, respectively (p &gt; 0.1). The mean surgical induced astigmatism vector was 0.61 ± 0.29 D in the SCCI group and 1.04 ± 0.38 D in the toric group. The mean magnitude of error was negative (−0.54 ± 0.48 D) and the correction index was &lt;1.0 (p &lt; 0.05) in SCCI group. At 3 months, all toric IOL alignment errors were within 5 degrees from the intended axis.ConclusionsBoth toric IOL and SCCI can correct low and medium astigmatism effectively with the help of a precise image-guided system.
Correlation Between Clinical Factors and Pregnancy Outcome Following Repeat Cerclage: A Retrospective Analysis of a Chinese Population
Authors: Cai Benshuo , Xia Yajun , Na Xinni 
Published: April 2022

BackgroundThe role of repeat cerclage (RC) among patients with prolapsed membranes remains controversial. We aimed to investigate the effectiveness of RC and assess the correlation between clinical factors and pregnancy outcome following RC.MethodsThe clinical data of patients who underwent RC for prolapsed membranes after prior cerclage were retrospectively investigated. The clinical characteristics of patients were compared between singleton and twin pregnancies. The clinical characteristics of singleton pregnancies were compared between the gestational age (GA) at delivery &lt;28 weeks' and ≥28 weeks' groups. Receiver operating characteristic (ROC) curve analysis was performed to determine predictive factors. Singleton patients were divided into two groups according to GA at RC as follows: GA &lt;22.3 weeks and GA ≥22.3 weeks. Pregnancy outcomes were compared between groups.ResultsThe mean GA at delivery of singleton pregnancies was significantly higher than that of twin pregnancies. The mean latency between RC and delivery of singleton pregnancies was significantly longer than their twin counterparts. There were significant differences in the pregnancy outcomes between the GA &lt;22.3 weeks group and GA ≥22.3 weeks group. Kaplan–Meier survival curves showed a lower incidence of neonatal death in the GA ≥22.3 weeks group compared with that in the GA &lt;22.3 weeks group.ConclusionsRC may be an effective method to prolong the duration of pregnancy among patients with singleton pregnancy. However, the selection of RC for patients with twin pregnancies remains controversial. GA at RC appears to be fair for predicting pregnancy outcomes following RC.
Comparing the Efficacy and Safety of Cell Transplantation for Spinal Cord Injury: A Systematic Review and Bayesian Network Meta-Analysis
Authors: Xu Xiongjie , Liang Zeyan , Lin Yike , Rao Jian , Lin Fabin , Yang Zhelun , Wang Rui , Chen Chunmei 
Published: April 2022

ObjectiveTo compare the safety and effectiveness of transplanted cells from different sources for spinal cord injury (SCI).DesignA systematic review and Bayesian network meta-analysis.Data SourcesMedline, Embase, and the Cochrane Central Register of Controlled Trials.Study SelectionWe included randomized controlled trials, case–control studies, and case series related to cell transplantation for SCI patients, that included at least 1 of the following outcome measures: American Spinal Cord Injury Association (ASIA) Impairment Scale (AIS grade), ASIA motor score, ASIA sensory score, the Functional Independence Measure score (FIM), International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), or adverse events. Follow-up data were analyzed at 6 and 12 months.ResultsForty-four eligible trials, involving 1,266 patients, investigated 6 treatments: olfactory ensheathing cells (OECs), neural stem cells/ neural progenitor cells (NSCs), mesenchymal stem cells (MSCs), Schwann cells, macrophages, and combinations of cells (MSCs plus Schwann cells). Macrophages improved the AIS grade at 12 months (mean 0.42, 95% credible interval: 0–0.91, low certainty) and FIM score at 12 months (42.83, 36.33–49.18, very low certainty). MSCs improved the AIS grade at 6 months (0.42, 0.15–0.73, moderate certainty), the motor score at 6 months (4.43, 0.91–7.78, moderate certainty), light touch at 6 (10.01, 5.81–13.88, moderate certainty) and 12 months (11.48, 6.31–16.64, moderate certainty), pinprick score at 6 (14.54, 9.76–19.46, moderate certainty) and 12 months (12.48, 7.09–18.12, moderate certainty), and the IANR-SCIFRS at 6 (3.96, 0.62–6.97, moderate certainty) and 12 months (5.54, 2.45–8.42, moderate certainty). OECs improved the FIM score at 6 months (9.35, 1.71–17.00, moderate certainty). No intervention improved the motor score significantly at 12 months. The certainty of other interventions was low or very low. Overall, the number of adverse events associated with transplanted cells was low.ConclusionsPatients with SCI who receive transplantation of macrophages, MSCs, NSCs, or OECs may have improved disease prognosis. MSCs are the primary recommendations. Further exploration of the mechanism of cell transplantation in the treatment of SCI, transplantation time window, transplantation methods, and monitoring of the number of transplanted cells and cell survival is needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD 42021282043.