bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addition of cystatin C predicts cardiovascular death better than creatinine in intensive care
Authors: Helmersson-Karlqvist Johanna , Lipcsey Miklos , Ärnlöv Johan , Bell Max , Ravn Bo , Dardashti Alain , Larsson Anders 
Published: April 2021

ObjectiveDecreased kidney function increases cardiovascular risk and predicts poor survival. Estimated glomerular filtration rate (eGFR) by creatinine may theoretically be less accurate in the critically ill. This observational study compares long-term cardiovascular mortality risk by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation; Caucasian, Asian, paediatric and adult cohort (CAPA) cystatin C equation and the CKD-EPI combined creatinine/cystatin C equation.MethodsThe nationwide study includes 22 488 intensive care patients in Uppsala, Karolinska and Lund University Hospitals, Sweden, between 2004 and 2015. Creatinine and cystatin C were analysed with accredited methods at admission. Reclassification and model discrimination with C-statistics was used to compare creatinine and cystatin C for cardiovascular mortality prediction.ResultsDuring 5 years of follow-up, 2960 (13 %) of the patients died of cardiovascular causes. Reduced eGFR was significantly associated with cardiovascular death by all eGFR equations in Cox regression models. In each creatinine-based GFR category, 17%, 19% and 31% reclassified to a lower GFR category by cystatin C. These patients had significantly higher cardiovascular mortality risk, adjusted HR (95% CI), 1.55 (1.38 to 1.74), 1.76 (1.53 to 2.03) and 1.44 (1.11 to 1.86), respectively, compared with patients not reclassified. Harrell’s C-statistic for cardiovascular death for cystatin C, alone or combined with creatinine, was 0.73, significantly higher than for creatinine (0.71), p<0.001.ConclusionsA single cystatin C at admission to the intensive care unit added significant predictive value to creatinine for long-term cardiovascular death risk assessment. Cystatin C, alone or in combination with creatinine, should be used for estimating GFR for long-term risk prediction in critically ill.
Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials
Authors: Wang Zi-Xian , Wu Hao-Xiang , Xie Li , Lin Wu-Hao , Liang Fei , Li Jin , Yang Zhi-Min , Xu Rui-Hua 
Published: April 2021

BackgroundProgression-free survival (PFS) exhibits suboptimal performance as the surrogate endpoint for overall survival (OS) in trials studying immune checkpoint inhibitors (ICIs). Here we propose a novel surrogate endpoint, modified PFS (mPFS), which omits the events of disease progression (but not deaths) within 3 months after randomization.MethodsPubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized trials studying ICIs in advanced solid tumors with available PFS and OS data up to May 2020. Individual patient-level data (IPD) for PFS and OS were reconstructed for eligible trials. A simulation-based algorithm was used to match the reconstructed, disconnected PFS and OS IPD, and 1000 independent simulated datasets of matched PFS-OS IPD were generated for each trial. mPFS durations and statuses were then measured for each of the matched PFS-OS IPD. Trial-level correlation between Cox HRs for PFS or mPFS and HRs for OS was assessed using Pearson correlation coefficient (rp) weighted by trial size; patient-level correlation between PFS or mPFS and OS was assessed using Spearman’s rank correlation coefficient (rs). Findings were further validated using the original IPD from two randomized ICI trials.ResultsFifty-seven ICI trials totaling 29,429 participants were included. PFS HR showed moderate correlation with OS HR (rp=0.60), and PFS was moderately correlated with OS at the patient level (median rs=0.66; range, 0.65–0.68 among the 1000 simulations). In contrast, mPFS HR achieved stronger correlation with OS HR (median rp=0.81; range, 0.77–0.84), and mPFS was more strongly correlated with OS at the patient level (median rs=0.79; range, 0.78–0.80). The superiority of mPFS over PFS remained consistent in subgroup analyses by cancer type, therapeutic regimen, and treatment setting. In both trials with the original IPD where experimental treatment significantly improved OS, mPFS successfully captured such clinical benefits whereas PFS did not.ConclusionsmPFS outperformed PFS as the surrogate endpoint for OS in ICI trials. mPFS is worthy of further investigation as a secondary endpoint in future ICI trials.
Risk of cardiac manifestations in adult mitochondrial disease caused by nuclear genetic defects
Authors: Lim Albert Zishen , Jones Daniel M , Bates Matthew G D , Schaefer Andrew M , O'Sullivan John , Feeney Catherine , Farrugia Maria E , Bourke John P , Turnbull Doug M , Gorman Gráinne S , McFarland Robert , Ng Yi Shiau 
Published: April 2021

ObjectiveRegular cardiac surveillance is advocated for patients with primary mitochondrial DNA disease. However, there is limited information to guide clinical practice in mitochondrial conditions caused by nuclear DNA defects. We sought to determine the frequency and spectrum of cardiac abnormalities identified in adult mitochondrial disease originated from the nuclear genome.MethodsAdult patients with a genetically confirmed mitochondrial disease were identified and followed up at the national clinical service for mitochondrial disease in Newcastle upon Tyne, UK (January 2009 to December 2018). Case notes, molecular genetics reports, laboratory data and cardiac investigations, including serial electrocardiograms and echocardiograms, were reviewed.ResultsIn this cohort-based observational study, we included 146 adult patients (92 women) (mean age 53.6±18.7 years, 95% CI 50.6 to 56.7) with a mean follow-up duration of 7.9±5.1 years (95% CI 7.0 to 8.8). Eleven different nuclear genotypes were identified:TWNK,POLG, RRM2B, OPA1, GFER,YARS2,TYMP,ETFDH,SDHA,TRIT1andAGK. Cardiac abnormalities were detected in 14 patients (9.6%). Seven of these patients (4.8%) had early-onset cardiac manifestations: hypertrophic cardiomyopathy required cardiac transplantation (AGK;n=2/2), left ventricular (LV) hypertrophy and bifascicular heart block (GFER;n=2/3) and mild LV dysfunction (GFER;n=1/3,YARS2;n=1/2, TWNK;n=1/41). The remaining seven patients had acquired heart disease most likely related to conventional cardiovascular risk factors and presented later in life (14.6±12.8 vs 55.1±8.9 years, p<0.0001).ConclusionsOur findings demonstrate that the risk of cardiac involvement is genotype specific, suggesting that routine cardiac screening is not indicated for most adult patients with nuclear gene-related mitochondrial disease.
Performance and emission characteristics of a micro-gasifier-based cook stove using solid biomass, Melia dubia and Casuarina
Authors: Omsakthivel U. , Lakshmanan T. , Sekar S. , Stalin B. 
Published: April 2021

Many large-scale improved cooking stove systems have been introduced in various developing countries to replace existing obsolete conventional biomass cooking stoves. Improved cooker stoves exhibit higher performance and lower emissions. In this work, two solid biomass fuels, Melia dubia and Casuarina, were investigated on a dry basis in a forced micro-gasifier stove. The effect of the M. dubia and Casuarina fuels on the thermal efficiency and emission reduction of the forced micro-gasifier stove was analysed using the water boiling test protocol version 4.2.3. The experimental results revealed that the thermal efficiency of the micro-gasifier stove for the fuels M. dubia and Casuarina are 42% and 40%, respectively. The fuel consumption of the micro-gasifier stove was estimated to be 86 g/L for M. dubia and 90 g/L for Casuarina. The carbon monoxide and particulate matter emissions of M. dubia were slightly lower than those of Casuarina. Emissions of carbon monoxide and particulate matter were detected for M. dubia at 22 ppm and 0.05 mg/m3, respectively, and for Casuarina at 25 ppm and 0.07 mg/m3, respectively. The efficiency and emission values for the selected fuels, M. dubia and Casuarina, have shown promising results for the selected micro-gasifier stove.
Ambulatory chest physiotherapy in mild-to-moderate acute bronchiolitis in children under two years of age — A randomized control trial
Authors: Pinto Frederico Ramos , Alexandrino Ana Silva , Correia-Costa Liane , Azevedo Inês 
Published: April 2021

Objective: The aim of this study was to compare the role of a chest physiotherapy (CP) intervention to no intervention on the respiratory status of children under two years of age, with mild-to-moderate bronchiolitis. Methods: Out of 80 eligible children observed in the Emergency Room, 45 children completed the study with 28 randomized to the intervention group and 17 to the control group. The intervention protocol, applied in an ambulatory setting, consisted of combined techniques of passive prolonged slow expiration, rhinopharyngeal clearance and provoked cough. The control group was assessed with no chest physiotherapy intervention. The efficacy of chest physiotherapy was assessed using the Kristjansson Respiratory Score at the admission and discharge of the visit to the Emergency Room and during clinical visits at day 7 and day 15. Results: There was a significant improvement in the Kristjansson Respiratory Score in the intervention group compared to the control group at day 15 [1.2 (1.5) versus 0.3 (0.5); [Formula: see text]-value[Formula: see text], in the control and intervention groups, respectively], with a mean difference (95% CI) of [Formula: see text] ([Formula: see text] to [Formula: see text]). Conclusion: Chest physiotherapy had a positive impact on the respiratory status of children with mild-to-moderate bronchiolitis. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04260919 .
Loss of TIMP4 (Tissue Inhibitor of Metalloproteinase 4) Promotes Atherosclerotic Plaque Deposition in the Abdominal Aorta Despite Suppressed Plasma Cholesterol Levels
Authors: Hu Mei , Jana Sayantan , Kilic Tolga , Wang Faqi , Shen Mengcheng , Winkelaar Gerrit , Oudit Gavin Y. , Rayner Katey , Zhang Da-wei , Kassiri Zamaneh 
Published: April 2021

Objective:
Atherosclerosis is accumulation of lipids and extracellular matrix in the arterial wall. TIMPs (tissue inhibitor of metalloproteinases) can impact plaque deposition by regulating ECM (extracellular matrix) turnover. TIMP4 also influences lipid metabolism and smooth muscle cell (SMC) proliferation. We investigated the role of TIMP4 in atherosclerosis.

Approach and Results:

Mice lacking low-density lipoprotein receptor (
Ldlr
−/−
) and
Timp4
(
Timp4
−/−
/
Ldlr
−/−
) were fed high-fat diet (HFD) or regular laboratory diet. After 3 or 6 months, HFD-fed male and female
Timp4
−/−
/
Ldlr
−/−
mice exhibited higher plaque density in the abdominal aorta (but not in aortic valves, arch, thoracic aorta) compared with
Ldlr
−/−
mice. Although plasma lipid and cholesterol levels were lower in
Timp4
−/−
/
Ldlr
−/−
-HFD, cholesterol content in the abdominal aorta was higher along with elevated inflammatory cytokines, MMP (matrix metalloproteinase) activities, CD68
+
/calponin
+
macrophage-like SMCs in
Timp4
−/−
/
Ldlr
−/−
-HFD compared with
Ldlr
−/−
-HFD mice. In vitro, oxidized LDL (low-density lipoprotein) markedly increased CD68 expression, reduced SMC markers, increased lipid uptake, and reduced cholesterol efflux protein ABCA1 (ATP-binding cassette transporter A1) in
Timp4
−/−
/
Ldlr
−/−
compared with
Ldlr
−/−
primary SMCs from abdominal, but not thoracic aorta. TIMP4 expression in the abdominal aorta (in vivo) and its corresponding SMCs (in vitro) was ≈2-fold higher than in the thoracic aorta and SMCs; TIMP4 levels decreased following HFD.
Timp4
-deficiency in bone marrow–derived macrophages did not alter their foam cell formation capacity.

Conclusions:
TIMP4 protects against plaque deposition in the abdominal aorta independent of plasma cholesterol levels. TIMP4 prevents proteolytic degradation of ABCA1 in SMCs, hindering cholesterol accumulation and transdifferentiation to macrophage-like foam cells, representing a novel negative regulator of atherosclerosis.
Can the World Be Redeemed? Geʾulah versus Pidyon: Toward a Mundane, Non-Eschatological Approach to Redemption
Authors: Cooper Julie E. 
Published: April 2021

Abstract
In this essay, I juxtapose two conceptions of redemption, as expressed by the Hebrew terms geʾulah and pidyon. I contend that today, the non-eschatological conception of redemption that animates the term pidyon is more politically salient than traditional cautions against geʾulah-inspired apocalypticism. Indeed, restoring the more mundane understanding of redemption suggested by pidyon – as release from inherited narratives and obligations – may help us break the stalemate that has descended upon Israeli politics.
Can vermicompost and biochar control Meloidogyne javanica on eggplant?
Authors: Ebrahimi Mohsen , Mousavi Amir , Souri Mohammad Kazem , Sahebani Navazolah 
Published: April 2021

Summary
The root-knot nematode, Meloidogyne javanica, is the most damaging species of plant-parasitic nematodes in eggplant cultivation in Iran. We studied the effect of pistachio and date palm biochars, vermicompost and a mixture of each of these biochars with vermicompost on M. javanica. To investigate the effect of these organic materials on survival, hatching and attraction of the second-stage juvenile (J2) towards the root, bioassays were performed in the laboratory using extracts of organic material. Vermicompost extract increased J2 mortality and decreased hatching and the number of J2 attracted to the eggplant roots. However, either type of biochar alone or mixed with vermicompost did not cause J2 mortality, nor did they inhibit hatching and attraction of J2 towards the root. To determine the effect of organic matter on J2 invasion and reproduction, pot experiments were performed in a completely randomised design with four replications in the glasshouse. Vermicompost reduced the number of J2 that penetrated the roots, number of egg masses and the final population of M. javanica eggs and J2. The suppressing effect of vermicompost might be attributed to the release of toxic compounds such as ammonium and improved soil nutrient and plant growth, leading to plants more tolerant to nematode damage. Pistachio and date biochars alone or combined with vermicompost had no adverse effect on the nematode reproduction compared to non-treated soil. Both types of biochar reduced the suppressing effect of vermicompost, most probably due to the absorbance of suppressive compounds in vermicompost by the high surface area of the biochar.
Singing to the Wind
Authors: Provenza Antonietta 
Published: April 2021

Abstract
This paper focuses on a passage of Himerius’ Oration 47 (Simon. fr. 251 Poltera = 535 PMG + p. 157 SLG), where Simonides is cited for a song that leads a ship with favourable winds, and on a passage in Plutarch’s Quaestiones Convivales (722b–c) quoting a Simonidean fragment (17 Poltera = 595 PMG) on the propagation of sounds through still air. I argue that they both can be linked with the Argonautic myth of Orpheus. In fact, the former might have some connections with the myth of Oreithyia and Boreas, parents of Zetes and Kalaïs, involved in the Argonautic expedition; moreover, it has some similarities with a fragment from Euripides’ Hypsipyle (752g Kannicht) representing Orpheus on the Argo. The latter fragment, in its turn, seems to refer to Orpheus’ encounter with the Sirens, and to presuppose common assumptions that were later examined and better developed by Aristotle and his school.
“Melodias Visuais, Poesias Musicais: Antiguidade Sonoras”
Authors: Cerqueira Fábio Vergara , Santos Amanda Basilio 
Published: April 2021

Abstract
This report deals with the activities carried out at the XX Jornada de História Antiga [XX Ancient History Conference], promoted by LECA (Laboratory of Studies on Ancient Ceramics) and held at UFPEL (Universidade Federal de Pelotas, Brasil); the conference was devoted to ancient Greek and Roman music, with a multidisciplinary approach. Here we present its aims, a description of the meeting, and some of the outcomes which resulted from the event.
Higher throughput drug screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia
Authors: Lee Dani Do Hyang , Cardinale Daniela , Nigro Ersilia , Butler Colin R. , Rutman Andrew , Fassad Mahmoud R. , Hirst Robert A. , Moulding Dale , Agrotis Alexander , Forsythe Elisabeth , Peckham Daniel , Robson Evie , Smith Claire M. , Somavarapu Satyanarayana , Beales Philip L. , Hart Stephen L. , Janes Sam M. , Mitchison Hannah M. , Ketteler Robin , Hynds Robert E. , O'Callaghan Christopher 
Published: April 2021

BackgroundDevelopment of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies followed by ciliated differentiation at the air–liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique's broader utility, including in pre-clinical PCD research, has been restricted by the limited number of basal cells that can be expanded from such biopsies.MethodsWe describe an immunofluorescence screening method, enabled by extensive expansion of basal cells from PCD patients and the directed differentiation of these cells into ciliated epithelium in miniaturised 96-well transwell format ALI cultures. As proof-of-principle, we performed a personalised investigation in a patient with a rare and severe form of PCD (reduced generation of motile cilia), in this case caused by a homozygous nonsense mutation in the MCIDAS gene.ResultsInitial analyses of ciliary ultrastructure, beat pattern and beat frequency in the 96-well transwell format ALI cultures indicate that a range of different PCD defects can be retained in these cultures. The screening system in our proof-of-principal investigation allowed drugs that induce translational readthrough to be evaluated alone or in combination with nonsense-mediated decay inhibitors. We observed restoration of basal body formation but not the generation of cilia in the patient's nasal epithelial cells in vitro.ConclusionOur study provides a platform for higher throughput analyses of airway epithelia that is applicable in a range of settings and suggests novel avenues for drug evaluation and development in PCD caused by nonsense mutations.
Dietary intake of vitamin A, lung function and incident asthma in childhood
Authors: Talaei Mohammad , Hughes David A. , Mahmoud Osama , Emmett Pauline M. , Granell Raquel , Guerra Stefano , Shaheen Seif O. 
Published: April 2021

BackgroundLongitudinal epidemiological data are scarce on the relationship between dietary intake of vitamin A and respiratory outcomes in childhood. We investigated whether a higher intake of preformed vitamin A or pro-vitamin β-carotene in mid-childhood is associated with higher lung function and with asthma risk in adolescence.MethodsIn the Avon Longitudinal Study of Parents and Children, dietary intakes of preformed vitamin A and β-carotene equivalents were estimated by food frequency questionnaire at 7 years of age. Post-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and forced expiratory flow at 25–75% of FVC (FEF25–75%) were measured at 15.5 years and transformed to z-scores. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years.ResultsIn multivariable adjusted models, a higher intake of preformed vitamin A was associated with higher lung function and a lower risk of incident asthma: comparing topversusbottom quartiles of intake, regression coefficients for FEV1and FEF25–75%were 0.21 (95% CI 0.05–0.38; ptrend=0.008) and 0.18 (95% CI 0.03–0.32; ptrend=0.02), respectively; odds ratios for FEV1/FVC below the lower limit of normal and incident asthma were 0.49 (95% CI 0.27–0.90; ptrend=0.04) and 0.68 (95% CI 0.47–0.99; ptrend=0.07), respectively. In contrast, there was no evidence for association with β-carotene. We also found some evidence for modification of the associations between preformed vitamin A intake and lung function byBCMO1,NCOR2andSCGB1A1gene polymorphisms.ConclusionA higher intake of preformed vitamin A, but not β-carotene, in mid-childhood is associated with higher subsequent lung function and lower risk of fixed airflow limitation and incident asthma.
Lung ultrasound assessment for pneumothorax following transbronchial lung cryobiopsy
Authors: Laursen Christian B. , Pietersen Pia I. , Jacobsen Niels , Falster Casper , Juul Amanda D. , Davidsen Jesper R. 
Published: April 2021

BackgroundIatrogenic pneumothorax is a common and clinically important transbronchial cryobiopsy (TBCB) complication. A study was conducted to assess the diagnostic accuracy and clinical impact of immediate post-procedure lung ultrasound for diagnosing iatrogenic pneumothorax in patients suspected of interstitial lung disease (ILD) undergoing TBCB.Study design and methodsIn patients undergoing TBCB due to suspected ILD, lung ultrasound of the anterior surface of the chest was performed immediately after the TBCB procedure prior to extubation. Presence of lung point was used as a definite sign of pneumothorax. Chest radiography was routinely performed 2 h after TBCB and was used as the reference standard.ResultsA total of 141 consecutive patients were included. Post-procedure lung ultrasound identified definite pneumothorax in five patients (3.6%, 95% confidence interval (CI) 1.5–8.3%). Chest radiography at 2 h identified 19 patients (13.5%, 95% CI 8.7–20.2%) with pneumothorax following TBCB. The diagnostic accuracy of lung ultrasound for diagnosing pneumothorax was as follows: sensitivity: 21.1% (95% CI 6.1–45.6%), specificity: 99.2% (95% CI 95.5–100.0%), positive predictive value (PPV): 80.0% (95% CI 28.4–99.5%) and negative predictive value (NPV): 89.0% (95% CI 82.5–93.7%). Post-procedure lung ultrasound had a clinical impact in five patients (3.6%, 95% CI 1.5–8.3), of which four had a pleural drain inserted prior to extubation and one underwent prolonged observation prior to extubation.InterpretationLung ultrasound performed immediately following TBCB has a clinical impact by identifying patients with pneumothorax in need of immediate treatment prior to extubation and by monitoring pneumothorax size in the operating room. Supplementary imaging prior to patient discharge is still needed however, as the majority of pneumothoraxes develop later in the post-procedure period.