bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial
Authors: Hogan Julien , Perez Aubriana , Sellier-Leclerc Anne-Laure , Vrillon Isabelle , Broux Francoise , Nobili Francois , Harambat Jerome , Bessenay Lucie , Audard V , Faudeux Camille , Morin Denis , Pietrement Christine , Tellier Stephanie , Djeddi Djamal , Eckart Philippe , Lahoche Annie , Roussey-Kesler G , Ulinski Tim , Boyer Olivia , Plaisier Emmanuelle , Cloarec Sylvie , Jolivot Anne , Guigonis Vincent , Guilmin-Crepon Sophie , Baudouin Veronique , Dossier Claire , Deschênes Georges 
Published: September 2020

IntroductionGuidelines for the treatment of steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS) are lacking. Given the substantial impact of SDNS/FRNS on quality of life, strategies aiming to provide long-term remission while minimising treatment side effects are needed. Several studies confirm that rituximab is effective in preventing early relapses in SDNS/FRNS; however, the long-term relapse rate remains high (~70% at 2 years). This trial will assess the association of intravenous immunoglobulins (IVIgs) to rituximab in patients with SDNS/FRNS and inform clinicians on whether IVIg’s immunomodulatory properties can alter the course of the disease and reduce the use of immunosuppressive drugs and their side effects.Methods and analysisWe conduct an open-label multicentre, randomised, parallel group in a 1:1 ratio, controlled, superiority trial to assess the safety and efficacy of a single infusion of rituximab followed by IVIg compared with rituximab alone in childhood-onset FRNS/SDNS. The primary outcome is the occurrence of first relapse within 24 months. Patients are allocated to receive either rituximab alone (375 mg/m²) or rituximab followed by IVIg, which includes an initial Ig dose of 2 g/kg, followed by 1.5 g/kg injections once a month for the following 5 months (maximum dose: 100 g).Ethics and disseminationThe study has been approved by the ethics committee (Comité de Protection des Personnes) of Ouest I and authorised by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé). Results of the primary study and the secondary aims will be disseminated through peer-reviewed publications.Trial registration numberNCT03560011.
Impact of home-based family planning counselling and referral on modern contraceptive use in Karachi, Pakistan: a retrospective, cross-sectional matched control study
Authors: Hackett Kristy , Henry Elizabeth , Hussain Imtiaz , Khan Mirbaz , Feroz Khalid , Kaur Navdep , Sato Ryoko , Soofi Sajid , Canning David , Shah Iqbal 
Published: September 2020

ObjectivesTo assess: (1) the impact of a reproductive health program on modern contraceptive use from baseline to program close; (2) the sustained impact from baseline to follow-up 36 months later; and (3) the exposure-adjusted impact at program close and follow-up.DesignRetrospective, cross-sectional matched control study.SettingKarachi, Pakistan.Participants2561 married women aged 16–49 years.InterventionsThe Willows Program, a community-based family planning counselling and referral program implemented from 2013 to 2015.Primary and secondary outcome measuresThe primary outcome was community-level modern contraceptive prevalence rate (mCPR), measured for January 2013 (baseline), June 2015 (program close) and at follow-up 36 months later. A secondary outcome was exposure-adjusted mCPR (among women reporting a family planning home visit) at program close and at follow-up.ResultsThere was no significant effect on community-level mCPR at program close (2.4 percentage point increase in intervention over comparison; 95% CI −2.2 to 7.0) or at follow-up (1.9 percentage point decrease; 95% CI −6.7 to 2.8). Only 18% of women in the intervention area reported receiving a family planning visit in the preceding 5 years. Among those reporting a visit, we observed a significant 10.3 percentage point increase (95% CI 4.6 to 15.9) from baseline to close, and a non-significant 2.0 percentage point increase (95% CI −3.8 to 7.8) from baseline to follow-up, relative to matched women in the comparison area. The cost per new modern method user was US$1089, while the cost per user-year during the intervention period was US$455.ConclusionsThe program had a positive short-term effect on women who received a family planning visit; however, this effect was not sustained. Program coverage was low and did not significantly increase community-level family planning use. Findings highlight the need to increase community coverage of high-quality counselling and contextually relevant interventions for family planning demand generation.
Comparing racing performance following arthroscopic surgery of metacarpophalangeal/metatarsophalangeal and carpal joints in Thoroughbred racehorses rehabilitated using conventional and underwater treadmill therapies
Authors: Potenza Korin N , Huggons Nick A , Jones Andrew R E , Rosanowski Sarah M , McIlwraith C Wayne 
Published: September 2020

BackgroundRehabilitation of horses using underwater treadmill therapy has been shown to improve joint range of motion, joint mobility, stride length and proprioceptive parameters with experimental studies. However, studies investigating the prognosis and return to function following rehabilitation are lacking.MethodsA retrospective study of Thoroughbred racehorses treated with arthroscopic surgery for osteochondral fragments of the metacarpophalangeal (MCP) or metatarsophalangeal (MTP) joints or carpal joints undergoing conventional rehabilitation or underwater treadmill assisted rehabilitation at the same facility were included. The objective of the current study was to investigate if underwater treadmill assisted rehabilitation following arthroscopy in the Thoroughbred racehorse was positively associated with returning to racing, time to return to racing and postoperative racing performance including Beyer Speed Figures.ResultsSurgery was performed on 165 horses on 174 surgical occasions; 70 (40.2 per cent) underwent underwater treadmill rehabilitation, with the remainder undergoing conventional rehabilitation. The time to return to racing was a median of 227 (IQR 185–281) days and 239 (IQR 205–303) days for underwater treadmill and conventional rehabilitation, respectively (P=0.16). Of the horses that raced presurgery, 83 per cent (58/70) of underwater treadmill rehabilitated horses and 61 per cent (63/104) of horses undergoing conventional rehabilitation returned to racing following surgery (P=0.02).ConclusionUnderwater treadmill rehabilitation is superior in returning a Thoroughbred racehorse to racing following arthroscopic surgery of the carpus and/or MCP/MTP joints.
Superconductivity and intra-unit-cell electronic nematic phase in the three-band model of cuprates
Authors: Zegrodnik Michal , Biborski Andrzej , Spałek Jozef 
Published: September 2020

Abstract
The intra-unit-cell nematic phase is studied within the three-band Emery model of the cuprates by using the diagrammatic expansion of the Gutzwiller wave function (DE-GWF). According to our analysis a spontaneous rotational (C4) symmetry breaking of the electronic wave function, leading to the nematic behavior, can appear due to electron correlations induced mainly by the onsite Coulomb repulsion, even in the absence of the corresponding intersite oxygen–oxygen repulsion term. The latter has been considered as the triggering factor of the nematic state formation in a number of previous studies. Also, we show that at the transition to the nematic phase, electron concentration transfer from d- to p-orbitals takes place, apart from the usually discussed px∕py polarization. The nematicity appears in a similar doping range as the paired phase, showing that both phases may have a common origin, even though they compete. As we show a coexistence region of both superconductivity and nematicity appears in a relatively wide doping range. The results are discussed in view of the experimental findings corresponding to the relation between nematicity and pseudogap behavior.

Graphical abstract
NT‐proBNP by Itself Predicts Death and Cardiovascular Events in High‐Risk Patients With Type 2 Diabetes Mellitus
Authors: Malachias Marcus V. B. , Jhund Pardeep S. , Claggett Brian L. , Wijkman Magnus O. , Bentley‐Lewis Rhonda , Chaturvedi Nishi , Desai Akshay S. , Haffner Steven M. , Parving Hans‐Henrik , Prescott Margaret F. , Solomon Scott D. , De Zeeuw Dick , McMurray John J. V. , Pfeffer Marc A. 
Published: September 2020

Background
NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) improves the discriminatory ability of risk‐prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT‐proBNP by itself for death and cardiovascular events in high‐risk patients with T2DM.

Methods and Results

Cox proportional hazards were used to create a base model formed by 20 variables. The discriminatory ability of the base model was compared with that of NT‐proBNP alone and with NT‐proBNP added, using C‐statistics. We studied 5509 patients (with complete data) of 8561 patients with T2DM and cardiovascular and/or chronic kidney disease who were enrolled in the ALTITUDE (Aliskiren in Type 2 Diabetes Using Cardiorenal Endpoints) trial. During a median 2.6‐year follow‐up period, 469 patients died and 768 had a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke, or heart failure hospitalization). NT‐proBNP alone was as discriminatory as the base model for predicting death (C‐statistic, 0.745 versus 0.744,
P
=0.95) and the cardiovascular composite outcome (C‐statistic, 0.723 versus 0.731,
P
=0.37). When NT‐proBNP was added, it increased the predictive ability of the base model for death (C‐statistic, 0.779 versus 0.744,
P
<0.001) and for cardiovascular composite outcome (C‐statistic, 0.763 versus 0.731,
P
<0.001).

Conclusions
In high‐risk patients with T2DM, NT‐proBNP by itself demonstrated discriminatory ability similar to a multivariable model in predicting both death and cardiovascular events and should be considered for risk stratification.

Registration

URL:
https://www.clini​caltr​ials.gov
; Unique identifier: NCT00549757.
Dose‐dependent association of proton pump inhibitors use with gastric intestinal metaplasia among Helicobacter pylori‐positive patients
Authors: Snir Yifat , Leibovitzh Haim , Leibovici‐Weissman Yaara , Vilkin Alex , Cohen Arnon D. , Shochat Tzippy , Niv Yaron , Dotan Iris , Feldhamer Ilan , Boltin Doron , Levi Zohar 
Published: September 2020

AbstractBackgroundGastric intestinal metaplasia is a pre‐cancerous condition associated with multiple factors.ObjectiveWe evaluated whether cumulative proton pump inhibitor dose is associated with the diagnosis of gastric intestinal metaplasia while controlling for multiple variables.MethodsWe retrospectively identified patients who underwent upper endoscopy with gastric biopsy between 2005 and 2014. Covariate data retrieved included age, sex, ethnicity, smoking status, Helicobacter pylori status (based on clarithromycin‐amoxicillin‐proton pump inhibitor issued), cumulative proton pump inhibitor issued within 10 years (quartiles [PPI‐Q1–4] of daily drug dose), anti‐parietal cell antibodies, body mass index and comorbidity index.ResultsOf the 14,147 included patients (median age 63.4 years; women 54.4%; Helicobacter pylori‐positive 29.0%), 1244 (8.8%) had gastric intestinal metaplasia. Increasing age, Helicobacter pylori infection, smoking, anti‐parietal cell antibodies and proton pump inhibitor use were all associated with the diagnosis of gastric intestinal metaplasia. Upper quartiles of cumulative proton pump inhibitor doses (PPI‐Q4 and PPI‐Q3 vs. PPI‐Q1) were associated with the diagnosis of gastric intestinal metaplasia: adjusted odds ratios 1.32 (95% confidence interval [CI] 1.111.57) and 1.27 (95% CI 1.07–1.52), respectively, for the whole cohort (Ptotal 0.007, Ptrend 0.013), 1.69 (95% CI 1.23–2.33) and 1.40 (95% CI 1.04–1.89), respectively, for Helicobacter pylori‐positive patients (Ptotal 0.004, Ptrend 0.005) and 1.21 (95% CI 0.98–1.49) and 1.20 (95% CI 0.96–1.49), respectively, for Helicobacter pylori‐negative patients (Ptotal 0.288, Ptrend 0.018). Upper quartiles of proton pump inhibitor dose were associated with a 5–10‐fold increased risk of low‐grade dysplasia.ConclusionsAmong Helicobacter pylori‐positive patients, proton pump inhibitor use appears to be associated with a dose‐dependent increased likelihood of gastric intestinal metaplasia.
Interferon-beta enhances sensitivity to gemcitabine in pancreatic cancer
Authors: Blaauboer Amber , Booy Stephanie , van Koetsveld Peter M. , Karels Bas , Dogan Fadime , van Zwienen Suzanne , van Eijck Casper H. J. , Hofland Leo J. 
Published: September 2020

Abstract
Background
Adjuvant gemcitabine for pancreatic cancer has limited efficacy in the clinical setting. Impaired drug metabolism is associated with treatment resistance. We aimed to evaluate the chemosensitising effect of interferon-beta (IFN-β).

Methods
BxPC-3, CFPAC-1, and Panc-1 cells were pre-treated with IFN-β followed by gemcitabine monotherapy. The effect on cell growth, colony formation, and cell cycle was determined. RT-qPCR was used to measure gene expression. BxPC-3 cells were used in a heterotopic subcutaneous mouse model.

Results
IFN-β increased sensitivity to gemcitabine (4-, 7.7-, and 1.7-fold EC50 decrease in BxPC-3, CFPAC-1, and Panc-1, respectively; all P < 0.001). Findings were confirmed when assessing colony formation. The percentage of cells in the S-phase was significantly increased after IFN-β treatment only in BxPC-3 and CFPAC-1 by 12 and 7%, respectively (p < 0.001 and p < 0.05, respectively). Thereby, IFN-β upregulated expression of the drug transporters SLC28A1 in BxPC-3 (252%) and SLC28A3 in BxPC-3 (127%) and CFPAC-1 (223%) (all p < 0.001). In vivo, combination therapy reduced tumor volume with 45% (P = 0.01). Both ex vivo and in vivo data demonstrate a significant reduction in the number of proliferating cells, whereas apoptosis was increased.

Conclusions
For the first time, we validated the chemosensitising effects of IFN-β when combined with gemcitabine in vitro, ex vivo, and in vivo. This was driven by cell cycle modulation and associated with an upregulation of genes involving intracellular uptake of gemcitabine. The use of IFN-β in combination with gemcitabine seems promising in patients with pancreatic cancer and needs to be further explored.
Long-term exposure to PM10 and NO2 in relation to lung function and imaging phenotypes in a COPD cohort
Authors: Kwon Sung Ok , Hong Seok Ho , Han Young-Ji , Bak So Hyeon , Kim Junghyun , Lee Mi Kyeong , London Stephanie J. , Kim Woo Jin , Kim Sun-Young 
Published: September 2020

Abstract
Background
Ambient air pollution can contribute to the development and exacerbation of COPD. However, the influence of air pollution on objective COPD phenotypes, especially from imaging, is not well studied. We investigated the influence of long-term exposure to air pollution on lung function and quantitative imaging measurements in a Korean cohort of participants with and without COPD diagnosis.

Methods
Study participants (N = 457 including 296 COPD cases) were obtained from the COPD in Dusty Areas (CODA) cohort. Annual average concentrations of particulate matter less than or equal to 10 μm in diameter (PM10) and nitrogen dioxide (NO2) were estimated at the participants’ residential addresses using a spatial air pollution prediction model. All the participants underwent volumetric computerized tomography (CT) and spirometry measurements and completed survey questionnaires. We examined the associations of PM10 and NO2 with FVC, FEV1, emphysema index, and wall area percent, using linear regression models adjusting for age, gender, education, smoking, height, weight, and COPD medication.

Results
The age of study participants averaged 71.7 years. An interquartile range difference in annual PM10 exposure of 4.4 μg/m3 was associated with 0.13 L lower FVC (95% confidence interval (CI), − 0.22- -0.05, p = 0.003). Emphysema index (mean = 6.36) was higher by 1.13 (95% CI, 0.25–2.02, p = 0.012) and wall area percent (mean = 68.8) was higher by 1.04 (95% CI, 0.27–1.80, p = 0.008). Associations with imaging phenotypes were not observed with NO2.

Conclusions
Long-term exposure to PM10 correlated with both lung function and COPD-relevant imaging phenotypes in a Korean cohort.
Epigenetic approach in obesity: DNA methylation in a prepubertal population which underwent a lifestyle modification
Authors: Gallardo-Escribano Cristina , Buonaiuto Verónica , Ruiz-Moreno M. Isabel , Vargas-Candela Antonio , Vilches-Perez Alberto , Benitez-Porres Javier , Romance-Garcia Angel Ramon , Ruiz-Moreno Alejandro , Gomez-Huelgas Ricardo , Bernal-Lopez M. Rosa 
Published: September 2020

Abstract
Background
Metabolically healthy obesity (MHO) is a considerably controversial concept as it is considered a transitory condition towards the development of different pathologies (type 2 diabetes, insulin resistance, or cardiovascular disease). MHO is closely related to lifestyle and environmental factors. Epigenetics has become an essential biological tool to analyze the link between obesity and metabolic status. The aim of this study was to determine whether MHO status is conditioned by the DNA methylation (DNAm) of several genes related to lipid metabolism (lipoprotein lipase, retinoid X receptor alpha, liver X receptor, stearoyl-CoA desaturase, sterol regulatory element binding factor 1), and inflammation (LEP) in peripheral blood mononuclear cells (PBMCs) from 131 prepubertal subjects with MHO phenotype after lifestyle modifications with personalized Mediterranean diet (MedDiet) combined with a physical activity (PA) program.

Results
The DNAm of all studied genes were significantly modified in the population after 12 months of lifestyle modifications (MedDiet and PA). In addition, associations were found between the DNAm studies and BMI, homeostatic model assessment of insulin resistance, monounsaturated fatty acid and polyunsaturated fatty acid, moderate-vigorous PA, fat mass, and adherence to MedDiet.

Conclusions
It was found that DNAm of genes related to lipid metabolism and inflammation are also present in childhood and that this methylation profile can be modified by interventions based on MedDiet and PA.
Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants
Authors: Wang Yu , Zhang Lin , Wu Yun , Zhu Rongping , Wang Yan , Cao Yan , Long Wei , Ji Chenbo , Wang Huaiyan , You Lianghui 
Published: September 2020

Abstract
Background
The therapeutic role of mesenchymal stem cells (MSCs) has been widely confirmed in several animal models of premature infant diseases. Micromolecule peptides have shown promise for the treatment of premature infant diseases. However, the potential role of peptides secreted from MSCs has not been studied. The purpose of this study is to help to broaden the knowledge of the hUC-MSC secretome at the peptide level through peptidomic profile analysis.

Methods
We used tandem mass tag (TMT) labeling technology followed by tandem mass spectrometry to compare the peptidomic profile of preterm and term umbilical cord MSC (hUC-MSC) conditioned medium (CM). Gene Ontology (GO) enrichment analysis and ingenuity pathway analysis (IPA) were conducted to explore the differentially expressed peptides by predicting the functions of their precursor proteins. To evaluate the effect of candidate peptides on human lung epithelial cells stimulated by hydrogen peroxide (H2O2), quantitative real-time PCR (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were, respectively, adopted to detect inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression levels at the mRNA and protein levels.

Results
A total of 131 peptides derived from 106 precursor proteins were differentially expressed in the preterm hUC-MSC CM compared with the term group, comprising 37 upregulated peptides and 94 downregulated peptides. Bioinformatics analysis showed that these differentially expressed peptides may be associated with developmental disorders, inflammatory response, and organismal injury. We also found that peptides 7118TGAKIKLVGT7127 derived from MUC19 and 508AAAAGPANVH517 derived from SIX5 reduced the expression levels of TNF-α, IL-1β, and IL-6 in H2O2-treated human lung epithelial cells.

Conclusions
In summary, this study provides further secretomics information on hUC-MSCs and provides a series of peptides that might have antiinflammatory effects on pulmonary epithelial cells and contribute to the prevention and treatment of respiratory diseases in premature infants.
Roles of stay-green (SGR) homologs during chlorophyll degradation in green plants
Authors: Jiao Baozhen , Meng Qingwei , Lv Wei 
Published: September 2020

AbstractChlorophyll (Chl) degradation is one of the most obvious signs of leaf senescence and fruit ripening. Stay-green (SGR) homologs that can remove magnesium from Chl a are the most important components in Chl degradation pathway in green plants. SGR homologs are not only universally involved in Chl breakdown during the senescence of green organs, but also play crucial roles in other organs during plant growth and development, such as fruit mature and nodule development. In this review, we focus on the diverse functions of SGR homologs in plant growth and development. A better understanding of SGR would be helpful for providing a theoretical basis for further illustrating the regulatory mechanism of SGR homologs.
Can 3D surgical planning and patient specific instrumentation reduce hip implant inventory? A prospective study
Authors: Di Laura Anna , Henckel Johann , Hothi Harry , Hart Alister 
Published: September 2020

Abstract
Background
Modern designs of joint replacements require a large inventory of components to be available during surgery. Pre-operative CT imaging aids 3D surgical planning and implant sizing, which should reduce the inventory size and enhance clinical outcome. We aimed to better understand the impact of the use of 3D surgical planning and Patient Specific Instrumentation (PSI) on hip implant inventory.

Methods
An initial feasibility study of 25 consecutive cases was undertaken to assess the discrepancy between the planned component sizes and those implanted to determine whether it was possible to reduce the inventory for future cases. Following this, we performed a pilot study to investigate the effect of an optimized inventory stock on the surgical outcome: we compared a group of 20 consecutive cases (experimental) with the 25 cases in the feasibility study (control). We assessed: (1) accuracy of the 3D planning system in predicting size (%); (2) inventory size changes (%); (3) intra and post-operative complications.

Results
The feasibility study showed variability within 1 size range, enabling us to safely optimize inventory stock for the pilot study. (1) 3D surgical planning correctly predicted sizes in 93% of the femoral and 89% of the acetabular cup components; (2) there was a 61% reduction in the implant inventory size; (3) we recorded good surgical outcomes with no difference between the 2 groups, and all patients had appropriately sized implants.

Conclusions
3D planning is accurate in up to 95% of the cases. CT-based planning can reduce inventory size in the hospital setting potentially leading to a reduction in costs.