bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individuelle computergestützte 3D-Planung zur Platzierung von Epithesenankern in Kombination mit einem implantierbaren transkutanen Knochenleitungshörgerät bei Patienten mit Ohrfehlbildungen
Authors: Seiwerth Ingmar , Plößl Sebastian , Herzog Michael , Schilde Sebastian , Radetzki Florian , Krämer Steffen , Rahne Torsten , Plontke Stefan K. 
Published: August 2022

Zusammenfassung
Hintergrund
Die simultane Versorgung mit der Bonebridge (MED-EL, Innsbruck, Österreich), einem teilimplantierbaren, aktiven transkutanen Knochenleitungshörgerät, sowie mit Ankern für Ohrepithesen kann eine Herausforderung darstellen, da beide Implantate Magnete enthalten und um ein begrenztes Areal im vorgesehenen Implantationsgebiet konkurrieren.

Material und Methoden
Die Bestimmung der optimalen Implantatposition für den Massenschwingers („floating mass transducer“, FMT) und die Epithesenanker erfolgte mittels einer Software zur 3‑dimensionalen (3D-)Planung („virtuelle Chirurgie“) anhand individueller 3D-Computermodelle der Schädel und der Implantate. Die Interaktion zwischen den magnetischen Epithesenankern und dem FMT wurde mittels statischer Magnetkräfte gemessen. In einer retrospektiven Datenanalyse wurden chirurgische und audiologische Ergebnisse evaluiert.

Ergebnisse
Zwischen den Jahren 2014 und 2021 wurde an 6 Ohren bei 5 Patienten (männlich: n = 3, weiblich: n = 2, Alter: 17–56 Jahre) die 3D-Planung einer simultanen Implantation der Bonebridge und von Ohrepithesenankern durchgeführt. Die individuelle präoperative Planung war hinsichtlich der optimalen Platzierung von Epithesenankern in Kombination mit der Bonebridge äußerst hilfreich. Audiologisch zeigte sich 3 Monate und > 11 Monate postoperativ ein klarer Nutzen. Es konnten keine Interaktionen zwischen den magnetischen Epithesenankern und dem FMT nachgewiesen werden. Bei 2 Patienten musste aufgrund einer Wundinfektion bzw. aufgrund von Wundheilungsstörungen eine Revisionsoperation erfolgen. Es wurden keine Langezeitkomplikationen (3–5 Jahre postoperativ) beobachtet.

Diskussion
Die präoperative 3D-Planung stellt einen deutlichen Nutzen bei der simultanen audiologischen und ästhetischen Rehabilitation mithilfe der Bonebridge und Ohrepithesenankern dar.
Transiente epileptische Amnesie – ein seltenes Phänomen bei Temporallappenepilepsien
Authors: Pukropski Jan , von Wrede Randi , Helmstaedter Christoph , Surges Rainer 
Published: August 2022

Zusammenfassung
Hintergrund
Die transiente epileptische Amnesie (TEA) ist ein seltenes Phänomen bei Temporallappenepilepsien, das häufig nicht erkannt oder als transiente globale Amnesie (TGA) fehldiagnostiziert wird. Als Ursache werden iktale und postiktale Störungen der Gedächtnisbildung postuliert, was auch durch das Ansprechen auf Antiepileptika gestützt wird. Angesichts der zunehmenden Zahl neu auftretender Epilepsien im höheren Lebensalter ist auch mit einer Zunahme der TEA zu rechnen.

Ziel der Arbeit
Analyse typischer Merkmale der TEA in einer monozentrischen Fallserie.

Material und Methoden
Mittels interner Datenbankanalyse wurden unter 7899 Patient*innen über einen Zeitraum von 8 Jahren 10 Patient*innen mit TEA identifiziert. Klinische Merkmale sowie Befunde der Zusatzdiagnostik wurden retrospektiv untersucht. Die Daten sind als Mittelwert ± SD angegeben.

Ergebnisse
Bei allen 10 Patient*innen wurde die Diagnose einer Temporallappenepilepsie gestellt. Das Lebensalter bei Erstmanifestation der TEA lag bei 59,1 ± 6,7 Jahren, die Diagnose wurde mit einer Latenz von 21,9 ± 26,3 Monaten gestellt. Eine TEA-Episode dauerte 56 ± 37 min an und trat pro Jahr 16 ± 9,9-mal auf; 6 von 10 Patient*innen berichteten über häufiges Auftreten direkt nach dem Erwachen. Bei 9 von 10 Patient*innen wurde über weitere Anfallstypen bzw. weitere semiologische Elemente während der TEA berichtet. Hinweise auf neuropsychologische Störungen temporaler Funktionen ergaben sich bei 8 von 10 Patient*innen, Hinweise auf eine depressive Störung bei 6 von 10 Patient*innen. Im Schlaf aktivierte epilepsietypische Aktivität wurde bei 4 Patient*innen temporal links sowie bei 2 Patient*innen temporal beidseits nachgewiesen. Bei 3 Patient*innen wurden mittels Kernspintomographie typische Auffälligkeiten im Bereich der temporomesialen Strukturen (bei 2 links, bei 1 rechts) nachgewiesen. Eine antiepileptische Therapie verbesserte die Anfallskontrolle bei 7 von 10 Patient*innen (Anfallsfreiheit bei 6 Patienten), bei 3 Patienten ist die therapeutische Wirkung unbekannt.

Diskussion
TEA sind selten, treten im höheren Erwachsenenalter auf und werden erst nach etwa 2 Jahren korrekt als epileptisches Phänomen diagnostiziert. Die gründliche Erfassung von Begleitsymptomen, die Umstände und das rezidivierende Auftreten sowie Hinweise auf eine Temporallappenepilepsie in den apparativen Zusatzuntersuchungen ermöglichen die Differenzierung zur TGA.
Potential of the zebrafish (Danio rerio) embryo test to discriminate between chemicals of similar molecular structure—a study with valproic acid and 14 of its analogues
Authors: Brotzmann Katharina , Escher Sylvia E. , Walker Paul , Braunbeck Thomas 
Published: August 2022

AbstractValproic acid is a frequently used antiepileptic drug and known pediatric hepatotoxic agent. In search of pharmaceuticals with increased effectiveness and reduced toxicity, analogue chemicals came into focus. So far, toxicity and teratogenicity data of drugs and metabolites have usually been collected from mammalian model systems such as mice and rats. However, in an attempt to reduce mammalian testing while maintaining the reliability of toxicity testing of new industrial chemicals and drugs, alternative test methods are being developed. To this end, the potential of the zebrafish (Danio rerio) embryo to discriminate between valproic acid and 14 analogues was investigated by exposing zebrafish embryos for 120 h post fertilization in the extended version of the fish embryo acute toxicity test (FET; OECD TG 236), and analyzing liver histology to evaluate the correlation of liver effects and the molecular structure of each compound. Although histological evaluation of zebrafish liver did not identify steatosis as the prominent adverse effect typical in human and mice, the structure–activity relationship (SAR) derived was comparable not only to human HepG2 cells, but also to available in vivo mouse and rat data. Thus, there is evidence that zebrafish embryos might serve as a tool to bridge the gap between subcellular, cell-based systems and vertebrate models.
Chromatographic separation of glycated peptide isomers derived from glucose and fructose
Authors: Schmutzler Sebastian , Hoffmann Ralf 
Published: August 2022

Abstract
Amino groups in proteins can react with aldehyde groups in aldoses or keto groups in ketoses, e.g., d-glucose and d-fructose, yielding Schiff bases that rearrange to more stable Amadori and Heyns products, respectively. Analytical strategies to identify and quantify each glycation product in the presence of the corresponding isomer are challenged by similar physicochemical properties, impeding chromatographic separations, and by identical masses including very similar fragmentation patterns in tandem mass spectrometry. Thus, we studied the separation of seven peptide families, each consisting of unmodified, glucated, and fructated 15mer to 22mer peptides using reversed-phase (RP) and hydrophilic interaction chromatography (HILIC). In RP-HPLC using acidic acetonitrile gradients, unglycated peptides eluted ~ 0.1 to 0.8 min after the corresponding glycated peptides with four of seven peptides being baseline separated. Isomeric glucated and fructated peptides typically coeluted, although two late-eluting peptides were partially separated. Neutral eluents (pH 7.2) improved the chromatographic resolution (Rs), especially in the presence of phosphate, providing good and often even baseline separations for six of the seven isomeric glycated peptide pairs with fructated peptides eluting earlier (Rs = 0.7 to 1.5). Some glucated and unmodified peptides coeluted, but they can be distinguished by mass spectrometry. HILIC separated glycated and unmodified peptides well, whereas glucated and fructated peptides typically coeluted. In conclusion, HILIC efficiently separated unmodified and the corresponding glycated peptides, while isomeric Amadori and Heyns peptides were best separated by RP-HPLC using phosphate buffered eluents.
Optimized scaling of translational factors in oncology: from xenografts to RECIST
Authors: Baaz Marcus , Cardilin Tim , Lignet Floriane , Jirstrand Mats 
Published: August 2022

Abstract
Purpose
Tumor growth inhibition (TGI) models are regularly used to quantify the PK–PD relationship between drug concentration and in vivo efficacy in oncology. These models are typically calibrated with data from xenograft mice and before being used for clinical predictions, translational methods have to be applied. Currently, such methods are commonly based on replacing model components or scaling of model parameters. However, difficulties remain in how to accurately account for inter-species differences. Therefore, more research must be done before xenograft data can fully be utilized to predict clinical response.

Method
To contribute to this research, we have calibrated TGI models to xenograft data for three drug combinations using the nonlinear mixed effects framework. The models were translated by replacing mice exposure with human exposure and used to make predictions of clinical response. Furthermore, in search of a better way of translating these models, we estimated an optimal way of scaling model parameters given the available clinical data.

Results
The predictions were compared with clinical data and we found that clinical efficacy was overestimated. The estimated optimal scaling factors were similar to a standard allometric scaling exponent of − 0.25.

Conclusions
We believe that given more data, our methodology could contribute to increasing the translational capabilities of TGI models. More specifically, an appropriate translational method could be developed for drugs with the same mechanism of action, which would allow for all preclinical data to be leveraged for new drugs of the same class. This would ensure that fewer clinically inefficacious drugs are tested in clinical trials.
Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update
Authors: Brannagan Thomas H. , Coelho Teresa , Wang Annabel K. , Polydefkis Michael J. , Dyck Peter J. , Berk John L. , Drachman Brian , Gorevic Peter , Whelan Carol , Conceição Isabel , Plante-Bordeneuve Violaine , Merlini Giampaolo , Obici Laura , Plana Josep Maria Campistol , Gamez Josep , Kristen Arnt V. , Mazzeo Anna , Gentile Luca , Narayana Arvind , Olugemo Kemi , Aquino Peter , Benson Merrill D. , Gertz Morie ,   for the NEURO-T. T. R. Open-Label Extension Investigators
Published: July 2022

Abstract
Background
Hereditary transthyretin amyloidosis (hATTR/ATTRv) results from the deposition of misfolded transthyretin (TTR) throughout the body, including peripheral nerves. Inotersen, an antisense oligonucleotide inhibitor of hepatic TTR production, demonstrated a favorable efficacy and safety profile in patients with the polyneuropathy associated with hATTR in the NEURO-TTR (NCT01737398) study. We report longer-term efficacy and safety data for inotersen, with a median treatment exposure of 3 years.

Methods
Patients who satisfactorily completed NEURO-TTR were enrolled in its open-label extension (OLE) study. Efficacy assessments included the modified Neuropathy Impairment Score + 7 (mNIS + 7), Norfolk Quality of Life–Diabetic Neuropathy (Norfolk QoL-DN) questionnaire total score, and the Short Form 36 (SF-36v2) Health Survey Physical Component Summary score. Safety and tolerability were also assessed. Efficacy is reported for patients living in Europe and North America (this cohort completed the study approximately 9 months before the remaining group of patients outside these regions); safety is reported for the full safety dataset, comprising patients living in Europe, North America, and Latin America/Australasia. This study is registered with ClinicalTrials.gov, identifier NCT02175004.

Results
In the Europe and North America cohort of the NEURO-TTR study, 113/141 patients (80.1%) completed the study, and 109 patients participated in the OLE study. A total of 70 patients continued to receive inotersen (inotersen–inotersen) and 39 switched from placebo to inotersen (placebo–inotersen). The placebo–inotersen group demonstrated sustained improvement in neurological disease progression as measured by mNIS + 7, compared with predicted worsening based on projection of the NEURO-TTR placebo data (estimated natural history). The inotersen–inotersen group demonstrated sustained benefit, as measured by mNIS + 7, Norfolk QoL-DN, and SF-36v2, compared with estimated natural history as well as compared with the placebo–inotersen group. With a maximum exposure of 6.2 years, inotersen was not associated with any additional safety concerns or increased toxicity in the OLE study. Platelet and renal monitoring were effective in reducing the risk of severe adverse events in the OLE study.

Conclusion
Inotersen treatment for > 3 years slowed progression of the polyneuropathy associated with hATTR, and no new safety signals were observed.
Efficacy of a loading dose of IV salbutamol in children with severe acute asthma admitted to a PICU: a randomized controlled trial
Authors: Boeschoten Shelley A. , Buysse Corinne M. P. , de Winter Brenda C. M. , van Rosmalen Joost , de Jongste Johan C. , de Jonge Rogier C. , Heisterkamp Sabien G. J. , van Woensel Job B. , Kneyber Martin C. J. , van Zwol Annelies , Boehmer Annemie L. M. , de Hoog Matthijs ,   on behalf of the Dutch collaborative PICU research network (SKIC)
Published: August 2022

AbstractThe optimal dose regimen for intravenous (IV) treatment in children with severe acute asthma (SAA) is still a matter of debate. We assessed the efficacy of adding a salbutamol loading dose to continuous infusion with salbutamol in children admitted to a pediatric intensive care unit (PICU) with SAA. This multicentre, placebo-controlled randomized trial in the PICUs of four tertiary care children’s hospitals included children (2–18 years) with SAA admitted between 2017 and 2019. Children were randomized to receive either a loading dose IV salbutamol (15 mcg/kg, max. 750 mcg) or normal saline while on continuous salbutamol infusion. The primary outcome was the asthma score (Qureshi) 1 h after the intervention. Analysis of covariance models was used to evaluate sensitivity to change in asthma scores. Serum concentrations of salbutamol were obtained. Fifty-eight children were included (29 in the intervention group). Median baseline asthma score was 12 (IQR 10–13) in the intervention group and 11 (9–12) in the control group (p = 0.032). The asthma score 1 h after the intervention did not differ significantly between the groups (p = 0.508, β-coefficient = 0.283). The median increase in salbutamol plasma levels 10 min after the intervention was 13 μg/L (IQR 5–24) in the intervention group and 4 μg/L (IQR 0–7) in the control group (p = 0.001). Side effects were comparable between both groups.Conclusion: We found no clinical benefit of adding a loading dose IV salbutamol to continuous infusion of salbutamol, in children admitted to the PICU with SAA. Clinically significant side effects from the loading dose were not encountered.

What is Known:• Pediatric asthma guidelines struggle with an evidence-based approach for the treatment of SAA beyond the initial steps of oxygen suppletion, repetitive administration of inhaled β2-agonists, and systemic steroids.• During an SAA episode, effective delivery of inhaled drugs is unpredictable due to severe airway obstruction.

What is New:• This study found no beneficial effect of an additional loading dose IV salbutamol in children admitted to the PICU.• This study found no clinically significant side effects from the loading dose.
Manufacturing of Integrated Cooling Channels by Directed Energy Deposition for Hot Stamping Tools with Ball Burnished Surfaces
Authors: Komodromos Anna , Kolpak Felix , Tekkaya A. Erman 
Published: August 2022

AbstractHot stamping tools require cooling channels, preferably with a high positioning flexibility. Conventionally, these are machined. This represents a disadvantage because of the limited accessibility for milling tools and the low flexibility. By means of the Directed Energy Deposition (DED) process, a flexible design of the cooling channels is possible. Different geometries of cooling channels can be manufactured by DED in order to control the heat balance in the hot stamping tool. In this context an agreement between the additive producibility and the surface fraction of the cooling channels, which contributes to the effective heat at the tool surface, is important. Experimental and numerical analyses demonstrate that a possible configuration in this field is the drop shaped cooling channel. To reduce the surface roughness after the DED process, the tool surfaces are ball burnished subsequently. The resulting roughness and the waviness of the tool surface are reduced but not leveled completely. Texturing of the surface can be applied to in fluence the material flow in the hot stamping process which is implemented by DED. The combination of the described methods allows for manufacturing hot stamping tools with near-surface cooling channels and a global or local adjustment of the surface properties of the tools.
Medizinethische Stellungnahme des Klinischen Ethikkomitees (KEKo) zum Urteil des Verfassungsgerichtshofs G 139/2019 vom 11. Dezember 2020 aus der Sichtweise einer öffentlich-rechtlichen Krankenanstalt
Authors: Brunner Jürgen ,   Klinisches Ethikkomitee (KEKo), Anegg Hildegard , Baubin Michael , Bellmann Romuald , Brunner Jürgen , Doppler Thomas , Ganner Michael , Hoffmann-Weltin Yvonne , Lintner Martin M. , Pfausler Bettina , Pölzl Gerhard , Quitterer Josef , Riccabona Ursula , Stühlinger Verena , Swoboda Ulrike , Weyrer Walpurga , Walzel Markus , Weiskopf Michael , Wildt Ludwig 
Published: August 2022

ZusammenfassungIn der Medizinethischen Stellungnahme des Klinischen Ethikkomitees (KEKo) Innsbruck zum Urteil des Verfassungsgerichtshofs G 139/2019 vom 11.12.2020 werden aus der Sichtweise einer öffentlich-rechtlichen Krankenanstalt die Auswirkungen zum assistierten Suizid auf Kliniken und Angehörige von Gesundheitsberufen diskutiert, und zwar aus juristischer, philosophischer, ethischer und seelsorgerlicher Sichtweise. Mögliche Lösungen für drohende Dilemmata für Kliniken und Angehörige von Gesundheitsberufen nach dem vorliegenden Entwurf des Sterbeverfügungsgesetzes werden aufgezeigt.
Production of artificial aggregates by granulation and carbonation of recycled concrete fines
Authors: Kursula Kalle , Perumal Priyadharshini , Ohenoja Katja , Illikainen Mirja 
Published: August 2022

AbstractThere is a growing need to find ways to reuse fine concrete waste from the construction industry. In this study, recycled concrete fines were granulated and used as lightweight aggregates. Ladle slag, a steel industry residue, was used as a co-binder in different ratios (0, 10, 20, and 30%). The materials were blended and granulated, and then the granules were cured in three conditions: ambient condition, humidity chamber, and carbonation chamber. The results showed that the ladle slag content of 30% cured in a humidity chamber produced the strongest granules, with a crushing strength of 127 N, which was 135% greater than a commercial lightweight aggregate. The granules generally had satisfactory density and water absorption with a higher ladle slag content. Carbonation increased the granule strength with a low ladle slag content and decreased the granules’ water absorption. The improved physical and mechanical properties of carbonated granules are attributed to the formation of calcium carbonate during the carbonation process. The granules produced in this study show good potential for use as lightweight aggregates in the construction industry.
Graphical abstract
Consensus Head Acceleration Measurement Practices (CHAMP): Origins, Methods, Transparency and Disclosure
Authors: Arbogast Kristy B. , Caccese Jaclyn B. , Buckley Thomas A. , McIntosh Andrew S. , Henderson Kyvory , Stemper Brian D. , Solomon Gary , Broglio Steven P. , Funk James R. , Crandall Jeff R. 
Published: August 2022

AbstractThe use of head kinematic measurement devices has recently proliferated owing to technology advances that make such measurement more feasible. In parallel, demand to understand the biomechanics of head impacts and injury in sports and the military has increased as the burden of such loading on the brain has received focused attention. As a result, the field has matured to the point of needing methodological guidelines to improve the rigor and consistency of research and reduce the risk of scientific bias. To this end, a diverse group of scientists undertook a comprehensive effort to define current best practices in head kinematic measurement, culminating in a series of manuscripts outlining consensus methodologies and companion summary statements. Summary statements were discussed, revised, and voted upon at the Consensus Head Acceleration Measurement Practices (CHAMP) Conference in March 2022. This manuscript summarizes the motivation and methods of the consensus process and introduces recommended reporting checklists to be used to increase transparency and rigor of future experimental design and publication of work in this field. The checklists provide an accessible means for researchers to apply the best practices summarized in the companion manuscripts when reporting studies utilizing head kinematic measurement in sport and military settings.
Attrition from Care Among Men Initiating ART in Male-Only Clinics Compared with Men in General Primary Healthcare Clinics in Khayelitsha, South Africa: A Matched Propensity Score Analysis
Authors: Cassidy Tali , Cornell Morna , Makeleni Bubele , Horsburgh C. Robert , Duran Laura Trivino , de Azevedo Virginia , Boulle Andrew , Fox Matthew P. 
Published: July 2022

AbstractMen have higher rates of attrition from antiretroviral therapy (ART) programs than women. In Khayelitsha, a high HIV prevalence area in South Africa, two public sector primary healthcare clinics offer services, including HIV testing and treatment, exclusively to men. We compared attrition from ART care among men initiating ART at these clinics with male attrition in six general primary healthcare clinics in Khayelitsha. We described baseline characteristics of patients initiating ART at the male and general clinics from 1 January 2014 to 31 March 2018. We used exposure propensity scores (generated based on baseline health and age) to match male clinic patients 1:1 to males at other clinics. The association between attrition (death or loss to follow-up, defined as no visits for nine months) and clinic type was estimated using Cox proportional hazards regression. Follow-up time began at ART initiation and ended at attrition, clinic transfer, or dataset closure. Before matching, patients from male clinics (n = 784) were younger than males from general clinics (n = 2726), median age: 31.2 vs 35.5 years. Those initiating at male clinics had higher median CD4 counts at ART initiation [Male Clinic 1: 329 (IQR 210–431), Male Clinic 2: 364 (IQR 260–536), general clinics 258 (IQR 145–398), cells/mm3]. In the matched analysis (1451 person-years, 1568 patients) patients initiating ART at male clinics had lower attrition (HR 0.71; 95% CI 0.60–0.85). In separate analyses for each of the two male clinics, only the more established male clinic showed a protective effect. Male-only clinics reached younger, healthier men, and had lower ART attrition than general services. These findings support clinic-specific adaptations to create more male-friendly environments.