bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum matrix metalloproteinase 7 and accelerated glomerular filtration rate decline in a general non-diabetic population
Authors: Enoksen Inger T , Svistounov Dmitri , Norvik Jon V , Stefansson Vidar T N , Solbu Marit D , Eriksen Bjørn O , Melsom Toralf 
Published: August 2021

Abstract

Background
Age-related reduction of glomerular filtration rate (GFR) is a major contributor to the global chronic kidney disease (CKD) epidemic. We investigated whether baseline serum levels of the pro-fibrotic matrix metalloproteinase 2 (MMP2), MMP7 and their inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP1), which mediates fibrosis development in aging animals, were associated with GFR decline in a general non-diabetic population.

Methods
In the Renal Iohexol Clearance Survey, we measured GFR using iohexol clearance in 1627 subjects aged 50–64 years without self-reported diabetes, kidney or cardiovascular disease. After a median of 5.6 years, 1324 had follow-up GFR measurements. Using linear mixed models and logistic regression analyses, we evaluated the association of MMP7, MMP2 and TIMP1 with the mean GFR decline rate, risk of accelerated GFR decline (defined as subjects with the 10% steepest GFR slopes: ≥1.8 mL/min/1.73 m2/year) and incident CKD [GFR &lt;60 mL/min/1.73 m2 and/or urinary albumin to creatinine ratio (ACR) ≥3.0 mg/mmol].

Results
Higher MMP7 levels (per standard deviation increase of MMP7) were associated with steeper GFR decline rates [−0.23 mL/min/1.73 m2/year (95% confidence interval −0.34 to −0.12)] and increased risk of accelerated GFR decline and incident CKD [odds ratios 1.58 (1.30–1.93) and 1.45 (1.05–2.01), respectively, in a model adjusted for age, sex, baseline GFR, ACR and cardiovascular risk factors]. MMP2 and TIMP1 showed no association with GFR decline or incident CKD.

Conclusions
The pro-fibrotic biomarker MMP7, but not MMP2 or TIMP1, is associated with increased risk of accelerated GFR decline and incident CKD in middle-aged persons from the general population.
Clinical features related to lymphatic metastasis in grade 3 endometroid endometrial cancer: a retrospective cross-sectional study
Authors: Wang Bo , Wang Qian , Shi Yue , Shao Wen-Yu , Liao Jiong-Bo , Luo Xue-Zhen , Chen Xiao-Jun , Wang Chao 
Published: August 2021

Abstract

Background
Endometrial cancer (EC) has been one of the most general cancers with respect to gynecological malignancies; however, there are debates on clinical strategies concerning treatments especially for patients with grade 3 (G3) endometroid endometrial cancer (EEC). Present study aimed to evaluate the lymphatic metastasis (LM) related factors and figure out the necessity of lymphadenectomy for G3 EEC patients.

Methods
From January 2009 to April 2019, 3751 EC patients were admitted to Obstetrics and Gynecology Hospital of Fudan University. Clinical characteristics include age, grade, stage, and clinical pathological features. A total of 1235 EEC patients were involved in the multivariable analysis. Three hundred and eighty-one patients were involved in the survival analysis and the data attributed to sufficient follow-up information. Kaplan-Meier curve and log-rank test were utilized to analyze the survival rate.

Results
Among the 1235 EEC patients, 181 (14.7%) were categorized as G3 and 1054 (85.3%) were grade 1 to grade 2 (G1-2). Multivariate analysis demonstrated that lymphovascular space invasion, adnexal involvement, and cervical stroma involvement were independent risk factors of LM in G3 cohort with odds ratio 3.4, 5.8, and 8.9; 95% confidence interval 1.1–10.6, 1.5–22.4, and 2.8–28.0, respectively. LM rates increased from 3.3% (3/92) to 75% (9/12) for G3 EEC cohort as related factor numbers increased from one to three. There were no differences between G3 and G1-2 EEC in overall survival and progression free survival. Additionally, no survival advantage was observed for G3 EEC patients at early stage with different plans of adjuvant treatment.

Conclusions
For G3 EEC patients without other pathological positive factor, the LM rate is lower than those with other pathological positive factor. Survival analysis showed no difference between G3 cohort and G1-2 cohort. Also, different adjuvant treatments had no impact on the overall survival for G3 EEC patients.
The mineralocorticoid receptor blocker spironolactone lowers plasma interferon-γ and interleukin-6 in patients with type 2 diabetes and treatment-resistant hypertension
Authors: Thangaraj Sai Sindhu , Oxlund Christina Stolzenburg , Fonseca Micaella Pereira Da , Svenningsen Per , Stubbe Jane , Palarasah Yaseelan , Ketelhuth Daniel F.J. , Jacobsen Ib. Abildgaard , Jensen Boye L. 
Published: August 2021

Background:
The mineralocorticoid receptor antagonist spironolactone lowers blood pressure in patients with resistant hypertension despite antihypertensive treatment with angiotensin-converting inhibitors (ACEi) and angiotensin-II receptor blockers (ARB). In preclinical studies, spironolactone suppresses pro-hypertensive interleukin 17A (IL-17A).

Objectives:
Plasma samples were analysed from a randomized, double-blind placebo-controlled trial with spironolactone given to patients with type 2 diabetes mellitus (T2DM) and resistant hypertension on three antihypertensive drugs. We tested the hypothesis that spironolactone-induced antihypertensive effects are associated with suppression of IL-17A and related cytokines.

Methods:
Interferon-γ (IFN-γ), IL-17A, tumor necrosis factor-α (TNF-α), IL-6, IL-1β and IL-10 were assessed in plasma with immunoassay in samples before and after 16 weeks of treatment with placebo or spironolactone (12.5-25–50 mg/day).

Results:
Spironolactone significantly reduced plasma IFN-γ and IL-6 while IL-17A, TNF-α, IL-1β and IL-10 were unchanged. IL-6 was more sensitive to higher doses of spironolactone. At baseline, serum aldosterone correlated positively with diastolic night blood pressure. Urine albumin/creatinine-ratios correlated positively with plasma IL-6 at baseline. There were no relations between aldosterone and cytokine concentrations at baseline; between cytokine concentration and blood pressure at baseline; and between cytokine concentration decrease and blood pressure decrease, except for IFN-γ, after treatment. The spironolactone-induced elevation in plasma potassium related inversely to blood pressure but not to changes in cytokines. In macrophages in vitro, spironolactone suppressed lipopolysaccharide (LPS)-induced TNF-α, IL-6, IL-1β and IL-10 levels.

Conclusion:
The antihypertensive action of spironolactone in resistant hypertensive patients is associated with suppressed IFN-γ and IL-6 and not IL-17A. Spironolactone exerts anti-inflammatory actions in vivo on macrophages and T-cells.
Effects of opioid rotation to buprenorphine/naloxone on pain, pain thresholds, pain tolerance, and quality of life in patients with chronic pain and opioid use disorder
Authors: Veldman Stijn , van Beek Maria , van Rijswijk Steffie , Ellerbroek Hannah , Timmerman Hans , van der Wal Selina , Steegers Monique , Schellekens Arnt 
Published: August 2021

Abstract
Long-term opioid use in patients with chronic noncancer pain (CNCP) can lead to opioid use disorder (OUD) and has been associated with hyperalgesia and reduced quality of life (QoL). Studies suggest antihyperalgesic properties of buprenorphine, and buprenorphine or naloxone (BuNa) has shown beneficial effects on QoL in patients with OUD without CNCP. This study investigated the added value of BuNa in patients with CNCP with OUD on self-reported pain, pain thresholds, pain tolerance, and QoL. In the current study, 43 outpatients with CNCP and OUD were included for inpatient conversion from full μ-receptor agonist opioids to BuNa. Self-reported pain, pain thresholds, pain tolerance, and QoL were determined at baseline and after 2 months of follow-up, using, respectively, a Visual Analogue Scale (VAS-pain and VAS-QoL), quantitative sensory testing, and EuroQol-5 dimensions. In total, 37 participants completed the protocol, and their data were analyzed. The mean VAS-pain score decreased from 51.3 to 37.2 (27.5%, F = 3.3; P = 0.044), whereas the pressure pain threshold and electric pain threshold or tolerance increased after substitution (F = 7.8; P = 0.005 and F = 44.5; P < 0.001, respectively), as well as QoL (EuroQol-5 dimensions questionnaire: F = 10.4; P = 0.003 and VAS-QoL: F = 4.4; P = 0.043). We found that conversion of full μ-receptor agonists to BuNa, in patients with CNCP with OUD, was accompanied with lower self-reported pain, higher pain thresholds, higher pain tolerance, and improved QoL. Despite several study limitations, these data suggest that BuNa might be of value in patients with CNCP with OUD. Future studies should investigate long-term effects of BuNa in randomized trials.
Implementation and Evaluation of Gradient Strip Antimicrobial Susceptibility Testing in US Public Health Laboratories to Respond to Resistant Gonorrhea
Authors: Raphael Brian H. , Pham Cau D. , Sharpe Samera , Mauk Kerry , Harvey Alesia , Khubbar Manjeet , Triplett Laura , Soge Olusegun O. , Denny Michael , Palavecino Elizabeth L. , Finney Rose , Olsen Aaron , Carlson Jonathan , St. Cyr Sancta B. , Schlanger Karen , Kersh Ellen N. ,   for the Strengthening the US Response to Resistant Gonorrhea Working Group
Published: August 2021

Background
Gradient strip antimicrobial susceptibility testing using Etest is conducted by local public health jurisdictions participating in the Strengthening the US Response to Resistant Gonorrhea (SURRG) program to inform public health responses to resistant gonorrhea. Proficiency testing results across the participating laboratories were analyzed and a comparison of Etest with the agar dilution method was conducted.

Methods
Laboratories participating in SURRG performed Etest for azithromycin (AZM), cefixime (CFX), and ceftriaxone (CRO). Concurrence between minimum inhibitory concentrations (MICs) obtained with Etest versus the agar dilution method using corresponding isolates was defined as ±1 double dilution. Specific levels of reduced susceptibility were termed “alerts” and included isolates with the following MICs: ≥2.0 μg/mL (AZM), ≥0.25 μg/mL (CFX), and ≥0.125 μg/mL (CRO). Categorical (alert/nonalert) agreement was calculated for MICs determined using Etest and agar dilution methods.

Results
Strengthening the US Response to Resistant Gonorrhea laboratories had high proficiency testing scores (≥98%) and low levels of interlaboratory variations in MICs. The overall concurrence of MICs (essential agreement) determined using agar dilution, and Etest was 96% (CRO), 96% (CFX), and 95% (AZM). Depending on the antibiotic tested, between 27% and 66% of isolates with alert MICs determined by Etest also had alert MICs using the reference agar dilution methodology; however, most of these alert MICs were detected at threshold levels.

Conclusions
This study demonstrates that MICs produced by SURRG laboratories using Etest have a high level of concurrence with agar dilution. Although confirmation of specific alert MICs varied, Etest facilities rapid detection and response to emerging resistant gonorrhea.
Bacterial Vaginosis and Its Association With Incident Trichomonas vaginalis Infections: A Systematic Review and Meta-Analysis
Authors: Seña Arlene C. , Goldstein Linda A. , Ramirez Gilbert , Parish Austin J. , McClelland R. Scott 
Published: August 2021

Background
Bacterial vaginosis (BV) has been associated with an increased risk for acquisition of human immunodeficiency virus and sexually transmitted infections. We evaluated the association between BV and incident Trichomonas vaginalis (TV) infection in women.

Methods
MEDLINE and ClinicalTrials.gov were searched for articles published between January 1, 1980, and May 7, 2021. Observational studies in women that evaluated the relationship between having/not having BV and the risk for acquiring TV were included.

Results
Fourteen studies were included in the systematic review; 12 studies were included in meta-analyses involving 18,424 participants. Most studies used Nugent scoring to diagnose BV. For TV diagnosis, 12 studies used wet mount microscopy or culture, and 2 used nucleic acid amplification tests. There was diversity in the measures of association used, so an overall effect size could not be calculated. The majority of studies reported odds ratios, which showed an increased risk of incident TV among women with BV versus without BV (adjusted odds ratio, 1.87; 95% confidence interval, 1.45–2.40; P = 0.007). However, there were heterogeneity and potential confounding factors (eg, age, sexual partners) reported among studies.

Conclusions
This systematic review and meta-analysis provide evidence for a nearly 2-fold higher risk for acquiring TV among women with BV compared with women without BV.
Evaluation of commercial anti-SARS-CoV-2 antibody assays and comparison of standardized titers in vaccinated healthcare workers
Authors: Saker Kahina , Escuret Vanessa , Pitiot Virginie , Massardier-Pilonchéry Amélie , Paul Stéphane , Mokdad Bouchra , Langlois-Jacques Carole , Rabilloud Muriel , Goncalves David , Fabien Nicole , Guibert Nicolas , Fassier Jean-Baptiste , Bal Antonin , Trouillet-Assant Sophie , Trabaud Mary-Anne 
Published: August 2021

AbstractWith the availability of vaccines, commercial assays detecting anti-SARS-CoV-2 antibodies (Ab) evolved towards quantitative assays directed to the spike glycoprotein or its receptor binding domain (RBD). The main objective of the present study was to compare the Ab titers obtained with quantitative commercial binding Ab assays, after 1 dose (convalescent individuals) or 2 doses (naïve individuals) of vaccine, in healthcare workers (HCW).Antibody titers were measured in 255 sera (from 150 HCW) with 5 quantitative immunoassays (Abbott RBD IgG II quant, bioMérieux RBD IgG, DiaSorin Trimeric spike IgG, Siemens Healthineers RBD IgG, Wantai RBD IgG). One qualitative total antibody anti RBD detection assay (Wantai) was used to detect previous infection before vaccination. The results are presented in binding Ab units (BAU)/mL after application, when possible, of a conversion factor provided by the manufacturers and established from a World Health Organization (WHO) internal standard.There was a 100% seroconversion with all assays evaluated after two doses of vaccine. With assays allowing BAU/ml correction, Ab titers were correlated (Pearson correlation coefficient, ρ, range: 0.85-0.94). The titer differences varied by a mean of 10.6% between Siemens and bioMérieux assays to 60.9% between Abbott and DiaSorin assays. These results underline the importance of BAU conversion for the comparison of Ab titer obtained with the different quantitative assays. However, significant differences persist, notably, between kits detecting Ab against the different antigens.A true standardization of the assays would be to include the International Standard in the calibration of each assays to express the results in IU/mL.
High-grade Ovarian Cancer Associated H/ACA snoRNAs Promote Cancer Cell Proliferation and Survival
Authors: Faucher-Giguère Laurence , Roy Audrey , Deschamps-Francoeur Gabrielle , Couture Sonia , Nottingham Ryan M. , Lambowitz Alan M. , Scott Michelle S. , Elela Sherif Abou 
Published: August 2021

AbstractSmall nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, the nature and extent of snoRNAs contribution to the biology of cancer cells remain largely unexplored. In this study, we examined the abundance patterns of snoRNA in high-grade serous ovarian carcinomas (HGSC) and serous borderline tumours (SBT) and identified a subset of snoRNA associated with increased invasiveness. This subgroup of snoRNA accurately discriminates between SBT and HGSC underlining their potential as biomarkers of tumour aggressiveness. Remarkably, knockdown of HGSC-associated H/ACA snoRNAs, but not their host genes, inhibits cell proliferation and induces apoptosis of model ovarian cancer cell lines. Wound healing and cell migration assays confirmed the requirement of these HGSC-associated snoRNA for cell invasion and increased tumour aggressiveness. Together our data indicate that H/ACA snoRNAs promote tumour aggressiveness through the induction of cell proliferation and resistance to apoptosis.
Dual signaling via interferon and DNA damage response elicits entrapment by giant PML nuclear bodies
Authors: Scherer Myriam , Read Clarissa , Neusser Gregor , Kranz Christine , Müller Regina , Full Florian , Wörz Sonja , Reichel Anna , Schilling Eva-Maria , Walther Paul , Stamminger Thomas 
Published: August 2021

ABSTRACTPML nuclear bodies (PML-NBs) are dynamic interchromosomal macromolecular complexes implicated in epigenetic regulation as well as antiviral defense. During herpesvirus infection, PML-NBs induce epigenetic silencing of viral genomes, however, this defense is antagonized by viral regulatory proteins such as IE1 of human cytomegalovirus (HCMV). Here, we show that PML-NBs undergo a drastic rearrangement into highly enlarged PML cages upon infection with IE1-deficient HCMV. Importantly, our results demonstrate that dual signaling by interferon and DNA damage response is required to elicit giant PML-NBs. DNA labeling revealed that invading HCMV genomes are entrapped inside PML-NBs and remain stably associated with PML cages in a transcriptionally repressed state. Intriguingly, by correlative light and transmission electron microscopy (EM), we observed that PML cages also entrap newly assembled viral capsids demonstrating a second defense layer in cells with incomplete first line response. Further characterization by 3D EM showed that hundreds of viral capsids are tightly packed into several layers of fibrous PML. Overall, our data indicate that giant PML-NBs arise via combined interferon and DNA damage signaling which triggers entrapment of both nucleic acids and proteinaceous components. This represents a multilayered defense strategy to act in a cytoprotective manner and to combat viral infections.
Structural dynamics determine voltage and pH gating in human voltage-gated proton channel
Authors: Han Shuo , Peng Sophia , Vance Joshua , Tran Kimberly , Do Nhu , Gates Decker , Bui Nauy , Gui Zhenhua , Wang Shizhen 
Published: August 2021

AbstractVoltage-gated ion channels are key players of electrical signaling in cells. As a unique subfamily, voltage-gated proton (Hv) channels are standalone voltage sensors without separate ion conductive pores. They are gated by both voltage and transmembrane proton gradient (i.e ΔpH), serving as acid extruders in most cells. Amongst their many functions, Hv channels are known to regulate the intracellular pH of human spermatozoa and compensate for the charge and pH imbalances caused by NADPH oxidases in phagocytes. Like the canonical voltage sensors, the Hv channel is a bundle of 4 helices (named S1 through S4), with the S4 segment carrying 3 positively charged Arg residues. Extensive structural and electrophysiological studies on voltage-gated ion channels generally agree on an outwards movement of the S4 segment upon activating voltage, but the real time conformational transitions are still unattainable. With purified human voltage-gated proton (hHv1) channel reconstituted in liposomes, we have examined its conformational dynamics at different voltage and pHs using the single molecule fluorescence resonance energy transfer (smFRET). Here we provided the first glimpse of real time conformational trajectories of the hHv1 voltage sensor and showed that both voltage and pH gradient shift the conformational dynamics of the S4 segment to control channel gating. Our results suggested the biological gating is determined by the conformational distributions of the hHv1 voltage sensor, rather than the conformational transitions between the presumptive ‘resting’ and ‘activated’ conformations. We further identified H140 as the key residue sensing extracellular pH and showed that both the intracellular and extracellular pH sensors act on the voltage sensing S4 segment to enrich the resting conformations. Taken together, we proposed a model that explains the mechanisms underlying voltage and pH gating in Hv channels, which may also serve as a general framework to understand the voltage sensing and gating in other voltage-gated ion channels.
Physical localization of 45S rDNA in Cymbopogon and the analysis of differential distribution of rDNA in homologous chromosomes of Cymbopogon winterianus
Authors: Thakur Shivangi , Kumar Upendra , Malik Rashmi , Bisht Darshana , Balyan Priyanka , Mir Reyazul Rouf , Kumar Sundip 
Published: August 2021

AbstractCymbopogon, commonly known as lemon grass, is one of the most important aromatic grasses having therapeutic and medicinal values. FISH signals on somatic chromosome spreads off Cymbopogon species indicated the localization of 45S rDNA on the terminal region of short arms of a chromosome pair. A considerable interspecific variation in the intensity of 45S rDNA hybridization signals was observed in the cultivars of Cymbopogon winterianus and Cymbopogon flexuosus. Furthermore, in all the varieties of Cymbopogon winterianus namely Bio-13, Manjari and Medini, a differential distribution of 45S rDNA was observed in a heterologous pair of chromosome 1. The development of Cymbopogon winterianus var. Manjari through gamma radiation may be responsible for breakage of fragile rDNA site from one of the chromosomes of this heterologous chromosome pair. While, in other two varieties of Cymbopogon winterianus (Bio-13 and Medini), this variability may be because of evolutionary speciation due to natural cross among two species of Cymbopogon which was fixed through clonal propagation. However, in both the situations these changes were fixed by vegetative method of propagation which is general mode of reproduction in the case of Cymbopogon winterianus.
Bacterial keratitis: similar bacterial and clinical outcomes in female versus male New Zealand White rabbits infected withSerratia marcescens
Authors: Romanowski Eric G. , Yadav Sanya , Stella Nicholas A. , Yates Kathleen A. , Romanowski John E. , Dhaliwal Deepinder K. , Shanks Robert M. Q. 
Published: August 2021

AbstractFemales and males respond differently to a number of systemic viral infections. Differences between females and males with respect to the severity of keratitis caused by Gram-negative bacteria such asSerratia marcescensare less well established. In this study we injected female and male New Zealand White rabbit corneas with a keratitis isolate ofS. marcescensand evaluated the eyes after 48 hours for a number of clinical and microbiological parameters. No statistical differences in bacterial burden and corneal scores were recorded between female and male rabbits although there was a non-significant trend toward a higher frequency of female rabbits demonstrating hypopyons. This data suggests that for experimental bacterial keratitis studies involving Gram-negative rods, a single sex or mixed group of rabbit is sufficient for evaluating pathology and bacterial burdens. This will reduce the number of animals used for subsequent studies.