bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine
Authors: Richardson Shakyra , Medhavi Fnu , Tanner Tayhlor , Lundy Stephanie , Omosun Yusuf , Igietseme Joseph U. , Carroll Darin , Eko Francis O. 
Published: June 2021

Efficacious vaccines are needed to control genital chlamydial diseases in humans and the veterinary industry. We previously reported a C. abortus (Cab) vaccine comprising recombinant Vibrio cholerae ghosts (rVCG) expressing the conserved and immunogenic N-terminal region of the Cab polymorphic membrane protein D (rVCG-Pmp18.1) protein that protected mice against intravaginal challenge. In this study, we investigated the immunomodulatory effect of the hematopoietic progenitor activator cytokine, Fms-like tyrosine kinase 3-ligand (FL) when co-administered with the rVCG-Pmp18.1 vaccine as a strategy to enhance the protective efficacy and the potential mechanism of immunomodulation. Groups of female C57BL/6J mice were immunized and boosted twice intranasally (IN) with rVCG-PmpD18.1 with and without FL or purified rPmp18.1 or rVCG-gD2 (antigen control) or PBS (medium) per mouse. The results revealed that co-administration of the vaccine with FL enhanced antigen-specific cellular and humoral immune responses and protected against live Cab genital infection. Comparative analysis of immune cell phenotypes infiltrating mucosal and systemic immune inductive tissue sites following immunization revealed that co-administration of rVCG-Pmp18.1 with FL significantly enhanced the number of macrophages, dendritic and NK cells, γδ and NK T cells in the spleen (systemic) and iliac lymph nodes (ILN) draining the genital tract (mucosal) tissues compared to rVCG-Pmp18.1 alone. Furthermore, FL enhanced monocyte infiltration in the ILN, while CD19+ B cells and CD4+ T cells were enhanced in the spleen. These results indicate that the immunomodulatory effect of FL is associated with its ability to mobilize innate immune cells and subsequent activation of robust antigen-specific immune effectors in mucosal and systemic lymphoid tissues.
FABP5, a Novel Immune-Related mRNA Prognostic Marker and a Target of Immunotherapy for Multiple Myeloma
Authors: Jia Haipeng , Zhang Xiaofen , Liu Xinxin , Qiao Ruifang , Liu Yan , Lv Sulong , Zhu Hongbo , Wang Jie , Kong Qiuhong , Zhang Hong , Zhang Zhirong 
Published: June 2021

Objective: Multiple myeloma is an incurable hematological malignancy. It is imperative to identify immune markers for early diagnosis and therapy. Here, this study analyzed immune-related mRNAs and assessed their prognostic value and therapeutic potential.Methods: Abnormally expressed immune-related mRNAs were screened between multiple myeloma and normal bone marrow specimens in the GSE47552 and GSE6477 datasets. Their biological functions were then explored. Survival analysis was presented for assessing prognosis-related mRNAs. CIBERSORT was utilized for identifying 22 immune cell compositions of each bone marrow specimen. Correlation between FABP5 mRNA and immune cells was then analyzed in multiple myeloma.Results: Thirty-one immune-related mRNAs were abnormally expressed in multiple myeloma, which were primarily enriched in B cells-related biological processes and pathways. Following validation, FABP5 mRNA was a key risk factor of multiple myeloma. Patients with its up-regulation usually experienced unfavorable outcomes. There were distinct differences in the infiltration levels of B cells naïve, B cells memory, plasma cells, T cells CD4 naïve, resting memory CD4 T cells, activated memory CD4 T cells, Tregs, resting NK cells, M0 macrophages, M1 macrophages, M2 macrophages, and neutrophils between multiple myeloma and normal samples. FABP5 mRNA had correlations to B cells memory, B cells naïve, dendritic cells activated, macrophages M0, macrophages M1, macrophages M2, neutrophils, activated NK cells, resting memory CD4 T cells, CD8 T cells and Tregs.Conclusion: Collectively, our data showed that FABP5 mRNA was related to immune microenvironment, which could be a target of immunotherapy and prognostic marker for multiple myeloma.
Approaches in the Treatment of Cesarean Scar Pregnancy and Risk Factors for Intraoperative Hemorrhage: A Retrospective Study
Authors: Lin Yaying , Xiong Chang , Dong Chunlin , Yu Jinjin 
Published: June 2021

Background: Cesarean scar pregnancy (CSP) involves a rare form of placental attachment that often leads to life-threatening conditions. The best treatment for CSP has been debated for decades. We aimed to evaluate the different treatments for CSP and analyzed the risk factors for intraoperative hemorrhage.Methods: CSP patients treated at the Affiliated Hospital of Jiangnan University were reviewed retrospectively from January 2014 to 2020. CSP was classified into three types based on the location and shape of gestational tissue, blood flow features, and thickness of the myometrium at the incision site. The clinical characteristics, types, approaches of treatment, and clinical outcomes of CSP were analyzed.Results: A total of 55 patients were included in this study, 29 (52.7%) of whom underwent transvaginal curettage after uterine artery embolization (UAE) and 22 (40%) of whom underwent transabdominal ultrasound-guided hysteroscopic curettage (USHC) in type I and II. Four patients (7.3%) classified as type III underwent laparoscopic cesarean scar resection (LCSR). Intraoperative blood loss, blood transfusion rate, and scar diverticulum were significantly higher in type II than in type I (P &lt; 0.05). Even though USHC showed no differences in intraoperative blood loss, length of stay, and scar diverticulum compared with curettage after UAE (P &gt; 0.05), superiority was found in surgical time and hospitalization cost (P &lt; 0.05). Furthermore, the type of CSP (OR = 10.53, 95% CI: 1.69–65.57; P = 0.012) and diameter of the gestational sac (OR = 25.76, 95% CI: 2.67–248.20; P = 0.005) were found to be risk factors for intraoperative hemorrhage.Conclusions: Transabdominal ultrasound-guided hysteroscopic curettage is an effective and relatively safe treatment option for patients with CSP. Type of CSP and diameter of the gestational sac were found to be associated with excessive intraoperative hemorrhage.
The Auxiliary Diagnostic Value of a Novel Wearable Electrocardiogram-Recording System for Arrhythmia Detection: Diagnostic Trial
Authors: Zhang Shaomin , Xian Hong , Chen Yi , Liao Yue , Zhang Nan , Guo Xinyu , Yang Ming , Wu Jinhui 
Published: June 2021

Background: AMAZFIT®, a novel wearable electrocardiogram (ECG)-recording system is used for the measurement, acquisition, and storage of single-lead cardiac waveforms for adults. The aim of the study was to evaluate the accuracy of AMAZFIT® for diagnosing arrhythmia in older patients.Methods: From May to December 2019, we recruited 291 elderly individuals with an average age of 78±10 years old, and 41.9% women. All cardiac waveforms were obtained from the AMAZFIT® which included limb and chest leads. Two trained technicians reviewed all ECG data to determine cardiac rhythm using standard diagnostic criteria. We evaluated the accuracy of AMAZFIT® for identifying arrhythmia by comparing the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios with those of a standard 12-lead ECG.Results: Of the 291 participants, 197 older adults had arrhythmias, including AF (n = 119), first-degree AVB (n = 28), PACs (n = 25), and PVCs (n = 28). Three of these participants had arrhythmias of AF and PVCs. Chest lead data from 100% and limb lead data from 4.7% of the participants were analyzed. An evaluation of AMAZFIT® for atrial fibrillation (AF) reported a sensitivity, specificity, PPV, NPV PLR, and negative likelihood ratio (NLR) of 93.28, 95.35, 93.28, 95.35, 20.06, and 0.07%, respectively. AMAZFIT® also demonstrated excellent sensitivity for premature atrial contractions (PACs) (84.00%) and premature ventricular contractions (PVCs) (89.29%). However, the device demonstrated a low sensitivity for first-degree atrioventricular block (32.14%).Conclusions: The AMAZFIT® showed significantly higher sensitivity and specificity for AF, PACs, and PVCs. This portable ECG-recording device based on an algorithm has a potential auxiliary diagnostic value for identifying arrhythmia compared with a standard 12-lead ECG device.
Behçet's Syndrome in a Chinese Pedigree of NLRP3-Associated Autoinflammatory Disease: A Coexistence or Novel Presentation?
Authors: Liu Jinjing , Yu Xin , Li Chaoran , Wang Yi , Yu Weihong , Shen Min , Zheng Wenjie 
Published: June 2021

Objectives:NLRP3-associated autoinflammatory disease (NLRP3-AID) and Behçet's syndrome (BS) both belong to autoinflammatory diseases and rarely co-occur. Here we reported a Chinese pedigree of NLRP3-AID presented with BS.Methods: We recorded a Chinese pedigree of NLRP3-AID presented with BS. Whole-exome sequencing was performed to find the hereditary susceptibility gene, and Sanger sequencing was performed on a consecutive cohort of 30 BS patients. We also reviewed the English literature on vasculitis associated with NLRP3-AID.Results: The proband was a 45-year-old Chinese Han woman. She and her 12-year-old daughter presented with recurrent fevers, cold-induced urticaria, oral, and genital ulcers, conjunctivitis, uveitis, optic atrophy, erythema nodosum, headache, and hearing loss. They were initially suspected of having BS, and both responded poorly to corticosteroids and immunosuppressants, while anti-TNF therapy was moderately effective. Pedigree analysis revealed another four relatives with similar symptoms, and a heterozygous NLRP3 gene mutation c.1316C&gt;T, p.Ala439Val was identified by whole-exome sequencing and Sanger sequencing. However, we did not discover NLRP3 gene mutation by Sanger sequencing in a confirmative cohort of 30 BS cases. A few case reports of vasculitis coexisting with NLRP3-AID, including a case of glomerulonephritis, and five cases of retinal vasculitis, were summarized through literature review.Conclusions: Our study is the first report of NLRP3-AID associated with BS. The coexistence of NLRP3-AID and BS reveals the extensive heterogeneity of the pathogenesis of systemic autoinflammatory diseases and calls for specific therapeutics.
Superb Microvascular Imaging Technology Can Improve the Diagnostic Efficiency of the BI-RADS System
Authors: Cai Siman , Wang Hongyan , Zhang Xiaoyan , Zhang Li , Zhu Qingli , Sun Qiang , Li Jianchu , Jiang Yuxin 
Published: June 2021

BackgroundTo explore whether superb microvascular imaging (SMI)SMI can improve the diagnostic efficiency by evaluating the vascular index (VI) and vascular architecture (VA) in breast lesions.MethodsThis is a retrospective study of data collected prospectively for research use. Taking 225 consecutive cases of breast lesions from November 2016 to December 2017 as a training set, the VI values and VA types of benign and malignant lesions were calculated based on the pathological results. Taking 238 consecutive cases of breast lesions from January 2018 to October 2018 as the verification set, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated to compare the diagnostic efficacy.ResultsThe training set included 225 breast lesions and the validation set 238 breast lesions. The VI value in the malignant group (10.3 ± 8.0) was significantly higher than that in the benign group (4.3 ± 5.0)(P&lt;0.001). A VI value of 4.05 was used as the diagnostic threshold for differentiating benign from malignant lesions, with a sensitivity of 80.5%, a specificity of 61.9%, an accuracy of 71.1%, a PPV of 62.9%, a NPV of 76.9%, and an area under the curve of 0.758 (0.696-0.819). There was a significant difference in the types of benign and malignant VA (P &lt; 0.001), and the PPV of the root hair-like and crab claw-like VAs were 93.9% and 100.0%, respectively. The diagnostic sensitivity, specificity, accuracy, PPV, NPV and area under the AUC curve were 58.0%, 98.2%, 97.0%, 70.3% and 0.781, respectively (95%CI: 0.719-0.844). SMI combined with conventional ultrasound improved the diagnostic specificity (70.0% vs. 90.0%), accuracy (87.4% vs. 96.6%), and PPV (82.5% vs. 93.2%) without decreasing the diagnostic sensitivity (99.3%), yielded higher diagnostic performance with the area under the ROC curve was 0.941 (95%CI: 0904-0.979) compared with conventional US alone (P &lt; 0.001).ConclusionA VI value 4.05 is a cut-off value with good diagnostic efficacy. The residual root-like and crab claw-like VAs are the characteristic VAs of malignant lesions. Conventional ultrasound combined with the VI and VA can improve the diagnostic specificity, accuracy and PPV without reducing the diagnostic sensitivity.
Prospective Observational Study of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma: Microbiota Profiling and Cytokine Expression
Authors: Badros Ashraf Z. , Meddeb Mariam , Weikel Dianna , Philip Sunita , Milliron Todd , Lapidus Rena , Hester Lisa , Goloubeva Olga , Meiller Timothy F. , Mongodin Emmanuel F. 
Published: June 2021

PurposeDefine incidence and risk factors of osteonecrosis of the jaw (ONJ) and explore oral microbial signatures and host immune response as reflected by cytokine changes in saliva and serum in multiple myeloma (MM) patients on bisphosphate (BP) therapy.Patients and MethodsA single center observational prospective study of MM patients (n = 110) on &gt;2 years of BP, none had ONJ at enrollment. Patients were followed every 3 months for 18 months with clinical/dental examination and serial measurements of inflammatory cytokines, bone turnover markers, and angiogenic growth factors. Oral microbiota was characterized by sequencing of 16S rRNA gene from saliva.ResultsOver the study period 14 patients (13%) developed BRONJ, at a median of 5.7 years (95% CI: 1.9–12.0) from MM diagnosis. Chronic periodontal disease was the main clinically observed risk factor. Oral microbial profiling revealed lower bacterial richness/diversity in BRONJ. Streptococcus intermedius, S. mutans, and S. perioris were abundant in controls; S. sonstellatus and S anginosus were prevalent in BRONJ. In the saliva, at baseline patients who developed BRONJ had higher levels of MIP-1β; TNF-α and IL-6 compared to those without BRONJ, cytokine profile consistent with M-1 macrophage activation. In the serum, patients with BRONJ have significantly lower levels of TGF beta and VEGF over the study period.ConclusionPeriodontal disease associated with low microbial diversity and predominance of invasive species with a proinflammatory cytokine profile leading to tissue damage and alteration of immunity seems to be the main culprit in pathogenesis of BRONJ.
The Non-Steroidal Mineralocorticoid Receptor Antagonist KBP-5074 Limits Albuminuria and has Improved Therapeutic Index Compared With Eplerenone in a Rat Model With Mineralocorticoid-Induced Renal Injury
Authors: Jaisser Frédéric , Tan Xiaojuan , Chi Shuangshuang , Liu Jinrong , Wang Ping , Bush Mark , Benn Vincent , Yang Y. Fred , Zhang Jay 
Published: June 2021

The therapeutic indices (TIs) and efficacy of the non-steroidal mineralocorticoid receptor antagonist (MRA) KBP-5074 and steroidal MRA eplerenone were evaluated in a uninephrectomized Sprague Dawley rat model of aldosterone-mediated renal disease. In two parallel studies, rats were placed on a high-salt diet and received aldosterone by osmotic mini-pump infusion over the course of 27 days. The urinary albumin-to-creatinine ratio (UACR) was evaluated after 7, 14, and 26 days of treatment. Serum K+ was evaluated after 14 and 27 days of treatment. Urinary Na+, urinary K+, and urinary Na+/K+ ratio were evaluated after 7, 14, and 26 days of treatment. The TI was calculated for each drug as the ratio of the concentration of drug producing 50% of maximum effect (EC50) for increasing serum K+ to the EC50 for lowering UACR. The TIs were 24.5 for KBP-5074 and 0.620 for eplerenone, resulting in a 39-fold improved TI for KBP-5074 compared with eplerenone. Aldosterone treatment increased UACR, decreased serum K+, and decreased urinary Na+ relative to sham-operated controls that did not receive aldosterone infusion in both studies, validating the aldosterone/salt renal injury model. KBP-5074 prevented the increase in UACR at 0.5, 1.5, and 5 mg/kg BID while eplerenone did so only at the two highest doses of 50 and 450 mg/kg BID. Both KBP-5074 and eplerenone blunted the reduction in serum K+ seen in the aldosterone treatment group, with significant increases in serum K+ at the high doses only (5 mg/kg and 450 mg/kg BID, respectively). Additionally, the urinary Na+ and Na+/K+ ratio significantly increased at the middle and high doses of KBP-5074, but only at the highest dose of eplerenone. These results showed increased TI and efficacy for KBP-5074 compared with eplerenone over a wider therapeutic window.
Clinical Analysis of Intravenous and Oral Sequential Treatment With Voriconazole for Candida Central Nervous System Infection in Six Premature Infants
Authors: Zhu Yingying , Gong Xiaohui , Li Zhiling , Wang Danni , Yan Chongbing 
Published: June 2021

Objective: The aim of the study was to observe the clinical efficacy and safety of intravenous and oral sequential treatment with voriconazole for Candida central nervous system (CNS) infection in premature infants.Methods: The study included retrospective analysis of the clinical data of six premature infants with Candida CNS infection admitted to the neonatology department in Shanghai Children’s Hospital between November 2016 and November 2019. By reviewing the characteristics of voriconazole based on the literature, it showed that infants without gastrointestinal dysfunction could be effectively treated by intravenous and oral sequential therapy with voriconazole (both 7 mg/kg/dose, every 12 h). Clinical manifestations, the time required for the cerebrospinal fluid (CSF), blood culture, nonspecific infection markers such as platelets and C-reactive protein (CRP) to turn normal, and drug-related side effects were observed and recorded in the process of treatment. All data were statistically analyzed by T test and Mann–Whitney U test.Results: A total of six premature infants were diagnosed with Candida CNS infection, two cases were diagnosed by a positive CSF culture and four cases were clinically diagnosed. Blood culture was positive for Candida in five cases. Among the 6 patients, 4 cases were Candida albicans and 2 cases were Candida parapsilosis. All the six cases were cured. After 3–5 days of treatment, symptoms such as lethargy, apnea, and feeding intolerance were improved and disappeared; a repeated blood culture turned negative in 3–7 days; CSF returned to normal in 15 ± 9 days on an average. Brain abscess, meningeal inflammation, and other infectious lesions were cleared on cranial magnetic resonance imaging (MRI) after treatment. The average total course of voriconazole was 61 ± 29 days, and the average oral treatment was 28 ± 15 days. No Candida recurrence was found during the treatment, and no drug-related side effects such as skin rash, liver and kidney function impairment, or visual abnormalities were found. The white blood cells, CSF glucose/plasma glucose ratio, and protein in CSF were significantly improved after the treatment (p &lt; 0.05). No statistically significant difference was identified in the liver and kidney function indexes (p &gt; 0.05).Conclusion: Voriconazole is a relatively safe and effective alternative treatment for Candida CNS infection in preterm infants. No severe drug-related side effects were detected.
Identification of Koumine as a Translocator Protein 18 kDa Positive Allosteric Modulator for the Treatment of Inflammatory and Neuropathic Pain
Authors: Xiong Bojun , Jin Guilin , Xu Ying , You Wenbing , Luo Yufei , Fang Menghan , Chen Bing , Huang Huihui , Yang Jian , Lin Xu , Yu Changxi 
Published: June 2021

Koumine is an alkaloid that displays notable activity against inflammatory and neuropathic pain, but its therapeutic target and molecular mechanism still need further study. Translocator protein 18 kDa (TSPO) is a vital therapeutic target for pain treatment, and recent research implies that there may be allostery in TSPO. Our previous competitive binding assay hint that koumine may function as a TSPO positive allosteric modulator (PAM). Here, for the first time, we report the pharmacological characterization of koumine as a TSPO PAM. The results imply that koumine might be a high-affinity ligand of TSPO and that it likely acts as a PAM since it could delay the dissociation of 3H-PK11195 from TSPO. Importantly, the allostery was retained in vivo, as koumine augmented Ro5-4864-mediated analgesic and anti-inflammatory effects in several acute and chronic inflammatory and neuropathic pain models. Moreover, the positive allosteric modulatory effect of koumine on TSPO was further demonstrated in cell proliferation assays in T98G human glioblastoma cells. In summary, we have identified and characterized koumine as a TSPO PAM for the treatment of inflammatory and neuropathic pain. Our data lay a solid foundation for the use of the clinical candidate koumine to treat inflammatory and neuropathic pain, further demonstrate the allostery in TSPO, and provide the first proof of principle that TSPO PAM may be a novel avenue for the discovery of analgesics.
Towards Measuring the Maxwell–Boltzmann Distribution of a Single Heated Particle
Authors: Su Xiaoya , Fischer Alexander , Cichos Frank 
Published: June 2021

The Maxwell–Boltzmann distribution is a hallmark of statistical physics in thermodynamic equilibrium linking the probability density of a particle’s kinetic energies to the temperature of the system that also determines its configurational fluctuations. This unique relation is lost for Hot Brownian Motion, e.g., when the Brownian particle is constantly heated to create an inhomogeneous temperature in the surrounding liquid. While the fluctuations of the particle in this case can be described with an effective temperature, it is not unique for all degrees of freedom and suggested to be different at different timescales. In this work, we report on our progress to measure the effective temperature of Hot Brownian Motion in the ballistic regime. We have constructed an optical setup to measure the displacement of a heated Brownian particle with a temporal resolution of 10 ns giving a corresponding spatial resolution of about 23 pm for a 0.92 μm PMMA particle in water. Using a gold-coated polystyrene (AuPS) particle of 2.15 μm diameter we determine the mean squared displacement of the particle over more than six orders of magnitude in time. Our data recovers the trends for the effective temperature at long timescales, yet shows also clear effects in the region of hydrodynamic long time tails.