bluuebunny/crossref_metadata_2025_split huggingface dataset:
6 Monate Zulassung von Kaftrio® in Deutschland – erste Erfahrungen aus dem „wahren Leben“ von Menschen mit CF
Authors: Thomassen J. C. , Meyer M. , Hagmeyer L. , Striegel A. K. , Metz F. , Körner R. , Rietschel E. , van Koningsbruggen-Rietschel S. 
Published: February 2022

Zusammenfassung
Hintergrund
Mit der Weiterentwicklung der „Cystic-fibrosis-transmembrane-conductance-regulator“(CFTR)-Modulatoren und der Zulassung von Kaftrio® (Elexacaftor, Tezacaftor, Ivacaftor) für einen Großteil der Menschen mit CF steht neben der etablierten symptomatischen Therapie nun eine weitere vielversprechende Therapieoption zur kausalen Behandlung der CF zur Verfügung.

Fragestellung
Ziel der hier vorliegenden Arbeit ist es, erste Effekte der Kaftrio®-Therapie auf den klinischen Phänotyp von Menschen mit CF 6 Monate nach der Zulassung zu untersuchen sowie die Ergebnisse in den Kontext neuer daraus resultierender Fragestellungen für die zukünftige Behandlung von CF-Patient*innen zu stellen.

Material und Methoden
Im Rahmen dieser Arbeit wurden anonymisiert klinische Daten (FEV1, Body-Mass-Index, HbA1c, Schweiß-Chlorid-Konzentration, Leberwerte) von 56 an der Uniklinik Köln betreuten Patient*innen retrospektiv ausgewertet, die die Voraussetzungen für eine Behandlung mit Kaftrio® erfüllt haben (Alter >12 Jahre, F508del homozygot oder heterozygot) und die mindestens >4 Wochen Kaftrio® eingenommen haben. Unterschiede zwischen den Gruppen wurden mithilfe des „Paired-t“-Tests berechnet. Ein p-Wert <0,05 wurde als statistisch signifikant gewertet.

Ergebnisse
In der untersuchten Kohorte konnte unter Kaftrio®-Therapie ein durchschnittlicher Anstieg der Einsekundenkapazität (FEV1-Werte in % des Sollwertes) um 11,3 % nachgewiesen werden. Ferner kam es unter Kaftrio® zu einem signifikanten Anstieg des Body-Mass Index (BMI) (+0,89 kg/m2), einer deutlichen Reduktion der Schweiß-Chlorid-Konzentration um durchschnittlich 58,8 mmol/l sowie zu einem Anstieg der Leberwerte.

Diskussion
Unsere retrospektive Datenerhebung bestätigt die aus den Zulassungsstudien beschriebenen positiven Effekte der Kaftrio®-Therapie auf den klinischen Phänotyp der Menschen mit CF. Mit der Besserung der Lungenfunktion, des Ernährungsstatus und der daraus resultierenden gesteigerten Lebenserwartung wird neben der Reevaluation bisheriger Behandlungsstandards der Fokus zukünftig auch auf dem Erhalt der Lebensqualität durch frühzeitige Diagnostik und effiziente Therapie möglicher Begleiterkrankungen liegen müssen.
Urinary albumin/creatinine ratio tertiles predict risk of diabetic retinopathy progression: a natural history study from the Adolescent Cardio-Renal Intervention Trial (AdDIT) observational cohort
Authors: Benitez-Aguirre Paul Z. , Marcovecchio M. Loredana , Chiesa Scott T. , Craig Maria E. , Wong Tien Y. , Davis Elizabeth A. , Cotterill Andrew , Couper Jenny J. , Cameron Fergus J. , Mahmud Farid H. , Neil H. Andrew W. , Jones Timothy W. , Hodgson Lauren A. B. , Dalton R. Neil , Marshall Sally M. , Deanfield John , Dunger David B. , Donaghue Kim C. ,   on behalf of the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)
Published: February 2022

Abstract
Aims/hypothesis
We hypothesised that adolescents with type 1 diabetes with a urinary albumin/creatinine ratio (ACR) in the upper tertile of the normal range (high ACR) are at greater risk of three-step diabetic retinopathy progression (3DR) independent of glycaemic control.

Methods
This was a prospective observational study in 710 normoalbuminuric adolescents with type 1 diabetes from the non-intervention cohorts of the Adolescent Cardio-Renal Intervention Trial (AdDIT). Participants were classified as ‘high ACR’ or ‘low ACR’ (lowest and middle ACR tertiles) using baseline standardised log10 ACR. The primary outcome, 3DR, was determined from centrally graded, standardised two-field retinal photographs. 3DR risk was determined using multivariable Cox regression for the effect of high ACR, with HbA1c, BP, LDL-cholesterol and BMI as covariates; diabetes duration was the time-dependent variable.

Results
At baseline mean ± SD age was 14.3 ± 1.6 years and mean ± SD diabetes duration was 7.2 ± 3.3 years. After a median of 3.2 years, 83/710 (12%) had developed 3DR. In multivariable analysis, high ACR (HR 2.1 [1.3, 3.3], p=0.001), higher mean IFCC HbA1c (HR 1.03 [1.01, 1.04], p=0.001) and higher baseline diastolic BP SD score (HR 1.43 [1.08, 1.89], p=0.01) were independently associated with 3DR risk.

Conclusions/interpretation
High ACR is associated with greater risk of 3DR in adolescents, providing a target for future intervention studies.

Trial registration
isrctn.org ISRCTN91419926.

Graphical abstract
Comparable results between crosslinked polyethylene and conventional ultra-high molecular weight polyethylene implanted in total knee arthroplasty: systematic review and meta-analysis of randomised clinical trials
Authors: Bistolfi Alessandro , Giustra Fortunato , Bosco Francesco , Faccenda Carlotta , Viotto Marianna , Sabatini Luigi , Berchialla Paola , Sciannameo Veronica , Graziano Eugenio , Massè Alessandro 
Published: February 2022

Abstract
Purpose
Total knee arthroplasty (TKA) has experienced exponential growth over the last decade, including increasingly younger patients with high functional demands. Highly crosslinked polyethylene (HXLPE) has been proven effective in reducing osteolysis and loosening revisions while improving long-term survival and performance in total hip arthroplasty; nevertheless, this superiority is not demonstrated in TKA. The aim of this systematic review and meta-analysis was to examine whether HXLPE improved overall survival and postoperative functional and radiological outcomes compared to conventional polyethylene (CPE) in TKA.

Methods
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a literature search of five databases (PubMed, Medline, Scopus, Science Direct and Embase) was made. A PICOS model was performed. The initial screening identified 2541 studies. Each eligible clinical article was analysed according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (LoE). Only randomised clinical trials (RCTs) of LoE 1 and 2 were included. The methodological quality of the articles was assessed using the Risk of Bias 2 (RoB 2) tool.

Results
Six clinical studies were included in the final study. This systematic review and meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO). A total of 2285 knees were included. Eight outcomes (total reoperations, reoperations for prosthesis loosening and infections, radiolucent lines, osteolysis, mechanical failure, postoperative KSS knee score and function score) were analysed. For none of them, a statistically significant difference was found about the superiority of HXLPE over CPE (p > 0.05).

Conclusions
There were no statistically significant differences between HXLPE and CPE for TKA concerning clinical, radiological, and functional outcomes; nevertheless, HXLPE did not show higher failure rates or complications and can be safely used for TKA.

Level of evidence
II.
Semi-quantitative magnetic resonance imaging scoring of the knee detects previous injuries in professional soccer players
Authors: Welsch Goetz Hannes , Behr Anna-Maria , Frosch Karl-Heinz , Tahir Enver , Pachowsky Milena , Henes Frank Oliver , Adam Gerhard , Maas Kai-Jonathan , Warncke Malte Lennart 
Published: February 2022

Abstract
Purpose
The medical examination (“medical”) is an important procedure in professional soccer since it has high economic relevance. In addition to clinical tests, magnetic resonance imaging (MRI) is used to assess joint health. In the present study, the reliability of semiquantitative knee MRI during the “medical” in professional soccer was tested, and its relationship with clinical data and days missed due to knee injury was observed.

Methods
In this cross-sectional study, between 2012 and 2019, 69 newly assigned players (age 18–35 years) from a professional soccer club underwent MRI (3.0 T) of both knee joints during their “medical”. Reported knee injuries and previously missed days due to injury were obtained from player anamnesis and the “transfermarkt.com” database. Based on the established “Whole-Organ Magnetic Resonance Imaging Score” (WORMS), two independent radiologists graded the MRI results. Further evaluation was based on the mean score of both knees.

Results
The mean WORMS for all subjects was 13.9 (median 10.5, range 0–61). Players with previous injuries had significantly higher scores than players without reported injuries (22.1 ± 17.7 vs. 8.9 ± 4.4, p < 0.002). Three outliers (previously undetected injuries) in the group of players without reported injuries were observed (6.7%). The WORMS was significantly correlated with a prior knee injury (r: 0.424, p < 0.0001) and days missed due to injury (r: 0.489, p < 0.001). Age was correlated with the WORMS (r: 0.386, p < 0.001). In a linear regression model, prior injury was the only significant predictor of a high WORMS (p = 0.001). The WORMS was a significant predictor of days missed due to injury (p < 0.0002) and prior injury (sensitivity: 78%, specificity: 91%, p = 0.006). The intraclass correlation coefficient was excellent (0.89).

Conclusion
Semiquantitative knee MRI for WORMS determination during the soccer “medical” is a robust and reliable method. Prior injury, even in players without documented trauma, was detected by the WORMS, and previously missed days due to injury were correlated with the semiquantitative MR knee score.

Level of evidence
Level III.
Development and implementation of crater and flank tool wear model for hard turning simulations
Authors: Cappellini Cristian , Abeni Andrea 
Published: February 2022

AbstractThis paper concerns the tool wear in hard turning of AISI 52100 hardened steel by means of PCBN tools. The purposes of this work are the development of a tool wear model and its implementation in a FEM-based procedure for predicting crater and flank wear progression during machining operations for studying the influence of tool wear on the process in terms of tool geometry modifications and stress variation on the tool. The developed tool wear model, able to update the geometry of the worn tool as a function of the wear rate, has been implemented in the utilized Deform 2D FEM software. This new analytical model differs from the already proposed methods of existing research, since it concerns both crater and flank wear evaluation. The validation of the model has been achieved by the comparison between experimental and simulated wear parameters. For doing this, an extended experimental campaign has been accomplished. The comparison results have shown good agreement. Once validated, the FEM strategy has been utilized for examining the influence of tool wear on the effective rake angle and the related tool stresses, individuating the excessive positive rake angle value as the final tool breakage mechanism.
Inhibition of neurite outgrowth and enhanced effects compared to baseline toxicity in SH-SY5Y cells
Authors: Lee Jungeun , Escher Beate I. , Scholz Stefan , Schlichting Rita 
Published: February 2022

AbstractEarly life exposure to environmental chemicals can cause developmental neurotoxicity (DNT). The impairment of key neurodevelopmental processes such as neurite outgrowth inhibition can be used as endpoints for screening of DNT effects. We quantified neurite-specific effects using the ratio of effect concentrations for cytotoxicity and neurite outgrowth inhibition (SRcytotoxicity). Baseline cytotoxicity, the minimal toxicity of any chemical, was used to quantify enhanced cytotoxicity (toxic ratio, TR) and neuronal-specific toxicity (SRbaseline) by comparing baseline cytotoxicity with the effects on cell viability and neurite outgrowth, respectively. The effects on cell viability and neurite length were measured based on image analysis in human neuroblastoma SH-SY5Y cells. Baseline cytotoxicity was predicted from hydrophobicity descriptors using a previously published model for SH-SY5Y cells. Enhanced cytotoxicity and neuronal-specific toxicity were more often observed for hydrophilic chemicals, which indicates that they are more likely to act through specific modes of action (MOA) on cell viability and neurite outgrowth. Hydrophobic chemicals showed a tendency to act through baseline toxicity without showing specific or enhanced toxicity, but were highly potent considering their low effect concentrations for both cytotoxicity and neurite outgrowth inhibition. The endpoint-specific controls (narciclasine, colchicine, cycloheximide, and rotenone), two carbamates (3-hydroxycarbofuran and carbaryl), and two redox cyclers (diquat and paraquat) showed distinct neurite-specific effects (SRcytotoxicity > 4). By comparing neurite-specific effects with enhanced cytotoxicity, one can explain whether the observed effects involve specific inhibition of neurite outgrowth, other specific MOAs, or merely baseline toxicity arising from hydrophobicity.
Evaluation and validation of methodologies for the extraction of per- and polyfluoroalkyl substances (PFASs) in serum of birds and mammals
Authors: Szabo Drew , Marchiandi Jaye , Green Mark P. , Mulder Raoul A. , Clarke Bradley O. 
Published: February 2022

AbstractAdvances in analytical techniques have allowed greater detection of environmental contaminants from small volumes of sample. Four methodologies were evaluated for the extraction of 53 per- and polyfluoroalkyl substances (PFASs) from eight classes in 200 µL of avian and mammal serum. Spiked serums at four concentrations (0, 0.5, 5.0 and 25 ng mL−1) were prepared by protein precipitation (PPT), enhanced matrix removal (EMR), weak anion exchange (WAX), and hydrophilic-lipophilic balance (HLB) solid-phase extraction cartridges. The extract from each methodology was analysed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC–MS/MS), and concentrations were compared with known concentrations in the spiked media. EMR performed the best overall, with 40 of 53 compounds effectively recovered at 5 ng mL−1. Furthermore, EMR was effective overall at concentrations ranging from 0.5 to 25 ng mL−1for 39 out of 53. Similarly, PPT was effective for 35 of 53 compounds at all spiked serum concentrations. There was a negative correlation between internal standard recovery for compounds with increasing octanol–water coefficients (Kow) for WAX (R =  − 0.65,p = 0.0043) and HLB (R =  − 0.62,p = 0.0077) extractions, indicating methanol may not be a suitable solvent for long-chain PFAS extraction from protein-rich tissues. EMR and PPT represent fast and effective methodologies for the extraction of PFASs from low volumes of serum which allows greater accuracy and precision that can be applied to future human and wildlife biomonitoring programmes.
FFF-based high-throughput sequence shortlisting to support the development of aptamer-based analytical strategies
Authors: Marassi Valentina , Mattarozzi Monica , Toma Lorenzo , Giordani Stefano , Ronda Luca , Roda Barbara , Zattoni Andrea , Reschiglian Pierluigi , Careri Maria 
Published: February 2022

AbstractAptamers are biomimetic receptors that are increasingly exploited for the development of optical and electrochemical aptasensors. They are selected in vitro by the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure, but although they are promising recognition elements, for their reliable applicability for analytical purposes, one cannot ignore sample components that cause matrix effects. This particularly applies when different SELEX-selected aptamers and related truncated sequences are available for a certain target, and the choice of the aptamer should be driven by the specific downstream application. In this context, the present work aimed at investigating the potentialities of asymmetrical flow field-flow fractionation (AF4) with UV detection for the development of a screening method of a large number of anti-lysozyme aptamers towards lysozyme, including randomized sequences and an interfering agent (serum albumin). The possibility to work in native conditions and selectively monitor the evolution of untagged aptamer signal as a result of aptamer-protein binding makes the devised method effective as a strategy for shortlisting the most promising aptamers both in terms of affinity and in terms of selectivity, to support subsequent development of aptamer-based analytical devices.
Graphical abstract
Proximate composition and amino acid profile of European eel skin: influence of body weight
Authors: Gómez-Limia Lucía , Carballo Javier , Rodríguez-González Mirian , Martínez Sidonia 
Published: February 2022

AbstractFish processing industries worldwide are discarding million kilograms of fish waste per year. The disposal of these wastes is an important handicap in fish processing industry. The thick eel skin is considered a waste product in the fish processing industry and in the home and is usually converted into low market-value products. The aims of this study were to evaluate the variations in the general chemical composition and amino acid content of eel skin in relation to body weight. The moisture content decreased and the lipid content increased with the weight of the eels. Eel skin had a high protein content, which did not vary significantly with eel weight. Glycine was the most abundant amino acid. The predominant essential amino acid was leucine. The smaller eels contained higher levels of threonine, valine, isoleucine, leucine, lysine, glutamic acid and tyrosine than the other groups. The larger eels contained higher levels of methionine, hydroxyproline, glycine, arginine, alanine and proline than the other groups. The protein indices showed that the skin from smaller eels was of higher nutritional quality.
Graphical abstract
Deformations of Half-Sided Modular Inclusions and Non-local Chiral Field Theories
Authors: Lechner Gandalf , Scotford Charley 
Published: February 2022

AbstractWe construct explicit examples of half-sided modular inclusions$$\mathcal {N}\subset \mathcal {M}$$N⊂Mof von Neumann algebras with trivial relative commutants. After stating a general criterion for triviality of the relative commutant in terms of an algebra localized at infinity, we consider a second quantization inclusion$$\mathcal {N}\subset \mathcal {M}$$N⊂Mwith large relative commutant and construct a one-parameter family$$\mathcal {N}_\kappa \subset \mathcal {M}_\kappa $$Nκ⊂Mκ,$$\kappa \ge 0$$κ≥0, of half-sided inclusions such that$$\mathcal {N}_0=\mathcal {N}$$N0=N,$$\mathcal {M}_0=\mathcal {M}$$M0=Mand$$\mathcal {N}_\kappa '\cap \mathcal {M}_\kappa =\mathbb {C}1$$Nκ′∩Mκ=C1for$$\kappa >0$$κ>0. The technique we use is an explicit deformation procedure (warped convolution), and we explain the relation of this result to the construction of chiral conformal quantum field theories on the real line and on the circle.
Cerebral venous sinus thrombosis after adenovirus-vectored COVID-19 vaccination: review of the neurological-neuroradiological procedure
Authors: Wittstock Matthias , Walter Uwe , Volmer Erik , Storch Alexander , Weber Marc-André , Großmann Annette 
Published: February 2022

AbstractCerebral venous and sinus thrombosis (CVST) after adenovirus-vectored COVID-19 ChAdOx1 nCov-19 (Oxford–AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) is a rare complication, occurring mainly in individuals under 60 years of age and more frequently in women. It manifests 4–24 days after vaccination. In most cases, antibodies against platelet factor-4/polyanion complexes play a pathogenic role, leading to thrombosis with thrombocytopenia syndrome (TTS) and sometimes a severe clinical or even fatal course. The leading symptom is headache, which usually increases in intensity over a few days. Seizures, visual disturbances, focal neurological symptoms, and signs of increased intracranial pressure are also possible. These symptoms may be combined with clinical signs of disseminated intravascular coagulation such as petechiae or gastrointestinal bleeding. If TTS-CVST is suspected, checking d-dimers, platelet count, and screening for heparin-induced thrombocytopenia (HIT-2) are diagnostically and therapeutically guiding. The imaging method of choice for diagnosis or exclusion of CVST is magnetic resonance imaging (MRI) combined with contrast-enhanced venous MR angiography (MRA). On T2*-weighted or susceptibility weighted MR sequences, the thrombus causes susceptibility artefacts (blooming), that allow for the detection even of isolated cortical vein thromboses. The diagnosis of TTS-CVST can usually be made reliably in synopsis with the clinical and laboratory findings. A close collaboration between neurologists and neuroradiologists is mandatory. TTS-CVST requires specific regimens of anticoagulation and immunomodulation therapy if thrombocytopenia and/or pathogenic antibodies to PF4/polyanion complexes are present. In this review article, the diagnostic and therapeutic steps in cases of suspected TTS associated CSVT are presented.
Post-void bladder ultrasound in suspected cauda equina syndrome—data from medicolegal cases and relevance to magnetic resonance imaging scanning
Authors: Todd Nicholas , Dangas Katerina , Lavy Chris 
Published: February 2022

Abstract

Objective
Post-void residual (PVR) scans of less than 200 ml are increasingly being used to rule out the likelihood of cauda equina syndrome (CES) and to delay emergency MRI scanning in suspected cases. This study was done to review a series of 50 MRI confirmed cases of CES and to test the hypothesis that a PVR of less than 200 ml was unlikely to be present.

Methods
Fifty consecutive medicolegal cases involving CES were audited. Records were reviewed to see if PVR scans were done. MRI scans were reviewed, clinical and radiological diagnosis reviewed, and treatment recorded.

Results
Out of 50 CES cases, 26 had had PVR scans. In 14/26 (54%) the PVR scan was ≤ 200 ml. In one case, the CES diagnosis was in question leaving 13/26 (50%) cases where there was a clear clinical and MRI diagnosis of CES despite the PVR being ≤ 200 ml. All 13 were classified as incomplete cauda equina syndrome (CESI) and all proceeded to emergency decompression.

Conclusions
This study is the first in the literature to demonstrate that there is a significant group of CES patients who require emergency decompression but have PVRs ≤ 200 ml.
The results demonstrate the existence of a significant group of CESI patients whose bladder function may be deteriorating, but they have not yet reached the point where the PVR is over 200 ml. Given the accepted understanding that CESI is best treated with emergency decompression, such patients are likely to have worse outcomes if MRI scanning and therefore surgery is delayed. We recommend the following:

PVR is recommended as an assessment tool in suspected CES.

A PVR of ≤ 200 reduces the likelihood of having CES but does not exclude it; clinical suspicion of CES should always lead to an MRI scan.

Further investigation of PVR as a prognostic tool is recommended.