bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing from a two-tiered to a one-tiered trauma team activation protocol: a before–after observational cohort study investigating the clinical impact of undertriage
Authors: Thorsen Kenneth , Narvestad Jon Kristian , Tjosevik Kjell Egil , Larsen Johannes Wiik , Søreide Kjetil 
Published: May 2021

AbstractBackgroundThe aim of this study was to compare the effect of the change in TTA protocol from a two-tier to one-tier, with focus on undertriage and mortality.Material and methodsA before–after observational cohort study based on data extracted from the Stavanger University Hospital Trauma registry in the transition period from two-tier to a one-tier TTA protocol over two consecutive 1-year periods (2017–2018). Comparative analysis was done between the two time-periods for descriptive characteristics and outcomes. The main outcomes of interest were undertriage and mortality.ResultsDuring the study period 1234 patients were included in the registry, of which 721 (58%) were in the two-tier and 513 (42%) in the one-tier group. About one in five patients (224/1234) were severely injured (ISS > 15).Median age was 39 in the two-tier period and 43 years in the one-tier period (p = 0.229). Median ISS was 5 for the two-tier period vs 9, in the one-tier period (p = 0.001). The undertriage of severely injured patients in the two-tier period was 18/122 (15%), compared to 31/102 (30%) of patients in the one-tier period (OR = 2.5; 95% CI 1.8–4.52). Overall mortality increased significantly between the two TTA protocols, from 2.5 to 4.7% (p = 0.033), OR 0.51 (0.28–0.96)ConclusionA protocol change from two-tiered TTA to one-tiered TTA increased the undertriage in our trauma system. A two-tiered TTA may be beneficial for better patient care.
Glycosylation is a key in SARS-CoV-2 infection
Authors: Reis Celso A. , Tauber Rudolf , Blanchard Véronique 
Published: May 2021

AbstractSARS-CoV-2 causes the respiratory syndrome COVID-19 and is responsible for the current pandemic. The S protein of SARS-CoV-2-mediating virus binding to target cells and subsequent viral uptake is extensively glycosylated. Here we focus on how glycosylation of both SARS-CoV-2 and target cells crucially impacts SARS-CoV-2 infection at different levels: (1) virus binding and entry to host cells, with glycosaminoglycans of host cells acting as a necessary co-factor for SARS-CoV-2 infection by interacting with the receptor-binding domain of the SARS-CoV-2 spike glycoprotein, (2) innate and adaptive immune response where glycosylation plays both a protective role and contributes to immune evasion by masking of viral polypeptide epitopes and may add to the cytokine cascade via non-fucosylated IgG, and (3) therapy and vaccination where a monoclonal antibody-neutralizing SARS-CoV-2 was shown to interact also with a distinct glycan epitope on the SARS-CoV-2 spike protein. These evidences highlight the importance of ensuring that glycans are considered when tackling this disease, particularly in the development of vaccines, therapeutic strategies and serological testing.
Analysis of machining-induced residual stresses of milled aluminum workpieces, their repeatability, and their resulting distortion
Authors: Weber Daniel , Kirsch Benjamin , Chighizola Christopher R. , D’Elia Christopher R. , Linke Barbara S. , Hill Michael R. , Aurich Jan C. 
Published: May 2021

AbstractMachining-induced residual stresses (MIRS) are a main driver for distortion of thin-walled monolithic aluminum workpieces. Before one can develop compensation techniques to minimize distortion, the effect of machining on the MIRS has to be fully understood. This means that not only an investigation of the effect of different process parameters on the MIRS is important. In addition, the repeatability of the MIRS resulting from the same machining condition has to be considered. In past research, statistical confidence of MIRS of machined samples was not focused on. In this paper, the repeatability of the MIRS for different machining modes, consisting of a variation in feed per tooth and cutting speed, is investigated. Multiple hole-drilling measurements within one sample and on different samples, machined with the same parameter set, were part of the investigations. Besides, the effect of two different clamping strategies on the MIRS was investigated. The results show that an overall repeatability for MIRS is given for stable machining (between 16 and 34% repeatability standard deviation of maximum normal MIRS), whereas instable machining, detected by vibrations in the force signal, has worse repeatability (54%) independent of the used clamping strategy. Further experiments, where a 1-mm-thick wafer was removed at the milled surface, show the connection between MIRS and their distortion. A numerical stress analysis reveals that the measured stress data is consistent with machining-induced distortion across and within different machining modes. It was found that more and/or deeper MIRS cause more distortion.
Selection of safe artemisinin derivatives using a machine learning-based cardiotoxicity platform and in vitro and in vivo validation
Authors: Kadioglu Onat , Klauck Sabine M. , Fleischer Edmond , Shan Letian , Efferth Thomas 
Published: May 2021

AbstractThe majority of drug candidates fails the approval phase due to unwanted toxicities and side effects. Establishment of an effective toxicity prediction platform is of utmost importance, to increase the efficiency of the drug discovery process. For this purpose, we developed a toxicity prediction platform with machine-learning strategies. Cardiotoxicity prediction was performed by establishing a model with five parameters (arrhythmia, cardiac failure, heart block, hypertension, myocardial infarction) and additional toxicity predictions such as hepatotoxicity, reproductive toxicity, mutagenicity, and tumorigenicity are performed by using Data Warrior and Pro-Tox-II software. As a case study, we selected artemisinin derivatives to evaluate the platform and to provide a list of safe artemisinin derivatives. Artemisinin from Artemisia annua was described first as an anti-malarial compound and later its anticancer properties were discovered. Here, random forest feature selection algorithm was used for the establishment of cardiotoxicity models. High AUC scores above 0.830 were achieved for all five cardiotoxicity indications. Using a chemical library of 374 artemisinin derivatives as a case study, 7 compounds (deoxydihydro-artemisinin, 3-hydroxy-deoxy-dihydroartemisinin, 3-desoxy-dihydroartemisinin, dihydroartemisinin-furano acetate-d3, deoxyartemisinin, artemisinin G, artemisinin B) passed the toxicity filtering process for hepatotoxicity, mutagenicity, tumorigenicity, and reproductive toxicity in addition to cardiotoxicity. Experimental validation with the cardiomyocyte cell line AC16 supported the findings from the in silico cardiotoxicity model predictions. Transcriptomic profiling of AC16 cells upon artemisinin B treatment revealed a similar gene expression profile as that of the control compound, dexrazoxane. In vivo experiments with a Zebrafish model further substantiated the in silico and in vitro data, as only slight cardiotoxicity in picomolar range was observed. In conclusion, our machine-learning approach combined with in vitro and in vivo experimentation represents a suitable method to predict cardiotoxicity of drug candidates.
Pharmacogenetic association of diabetes-associated genetic risk score with rapid progression of coronary artery calcification following treatment with HMG-CoA-reductase inhibitors —results of the Heinz Nixdorf Recall Study
Authors: Pechlivanis Sonali , Jung Dominik , Moebus Susanne , Lehmann Nils , Mahabadi Amir A. , Hoffmann Per , Erbel Raimund , Nöthen Markus M. , Bachmann Hagen S. 
Published: May 2021

AbstractHMG-CoA-Reductase inhibitors (HMGRIs) are currently the most widely used group of drugs in patients with coronary artery disease (CAD) and are given preemptively to patients with high levels of cholesterol, including those with diabetes mellitus (DM). However, intake of HMGRIs also increases the progression of coronary artery calcification (CAC) and the risk of developing DM. This study aimed to investigate whether HMGRI intake interacts with the diabetes-associated genetic risk score (GRS) to affect CAC progression using data from the population-based Heinz Nixdorf Recall (HNR) study. CAC was measured in 3157 participants using electron-beam computed tomography twice, at baseline (CACb) and 5 years later (CAC5y). CAC progression was classified as slow, expected, or rapid based on predicted values. Weighted DM GRS was constructed using 100 diabetes mellitus–associated single nucleotide polymorphisms (SNPs). We used log-linear regression to evaluate the interaction of HMGRI intake with diabetes-associated GRS and individual SNPs on CAC progression (rapid vs. expected/slow), adjusting for age, sex, and log(CACb + 1). The prevalence of rapid CAC progression in the HNR study was 19.6%. We did not observe any association of the weighted diabetes mellitus GRS with the rapid progression of CAC (relative risk (RR) [95% confidence interval (95% CI)]: 1.01 [0.94; 1.10]). Furthermore, no indication of an interaction between GRS and HMGRI intake was observed (1.08 [0.83; 1.41]). Our analyses showed no indication that the impact of HMGRIs on CAC progression is significantly more severe in patients with a high genetic risk of developing DM than in those with a low GRS.
Unilateral traumatic brain injury of the left and right hemisphere produces the left hindlimb response in rats
Authors: Bakalkin Georgy , Nosova Olga , Sarkisyan Daniil , Hallberg Mathias , Zhang Mengliang , Schouenborg Jens , Marklund Niklas , Watanabe Hiroyuki 
Published: May 2021

AbstractTraumatic brain injury and stroke result in hemiplegia, hemiparesis, and asymmetry in posture. The effects are mostly contralateral; however, ipsilesional deficits may also develop. We here examined whether ablation brain injury and controlled cortical impact (CCI), a rat model of clinical focal traumatic brain injury, both centered over the left or right sensorimotor cortex, induced hindlimb postural asymmetry (HL-PA) with contralesional or ipsilesional limb flexion. The contralesional hindlimb was flexed after left or right side ablation injury. In contrast, both the left and right CCI unexpectedly produced HL-PA with flexion on left side. The flexion persisted after complete spinal cord transection suggesting that CCI triggered neuroplastic processes in lumbar neural circuits enabling asymmetric muscle contraction. Left limb flexion was exhibited under pentobarbital anesthesia. However, under ketamine anesthesia, the body of the left and right CCI rats bent laterally in the coronal plane to the ipsilesional side suggesting that the left and right injury engaged mirror-symmetrical motor pathways. Thus, the effects of the left and right CCI on HL-PA were not mirror-symmetrical in contrast to those of the ablation brain injury, and to the left and right CCI produced body bending. Ipsilateral effects of the left CCI on HL-PA may be mediated by a lateralized motor pathway that is not affected by the left ablation injury. Alternatively, the left-side-specific neurohormonal mechanism that signals from injured brain to spinal cord may be activated by both the left and right CCI but not by ablation injury.
Investigating the Microchannel Architectures Inside the Subchondral Bone in Relation to Estimated Hip Reaction Forces on the Human Femoral Head
Authors: Taheri Shahed , Yoshida Takashi , Böker Kai O. , Foerster Robert H. , Jochim Lina , Flux Anna Lena , Grosskopf Birgit , Lehmann Wolfgang , Schilling Arndt Friedrich 
Published: May 2021

AbstractThe interplay between articular cartilage (AC) and subchondral bone (SB) plays a pivotal role in cartilage homeostasis and functionality. As direct connective pathways between the two are poorly understood, we examined the location-dependent characteristics of the 3D microchannel network within the SB that connects the basal cartilage layer to the bone marrow (i.e. cartilage-bone marrow microchannel connectors; CMMC). 43 measuring points were defined on five human cadaveric femoral heads with no signs of osteoarthritis (OA) (age ≤ 60), and cartilage-bone cylinders with diameters of 2.00 mm were extracted for high-resolution scanning (n = 215). The micro-CT data were categorized into three groups (load-bearing region: LBR, n = 60; non-load-bearing region: NLBR, n = 60; and the peripheral rim: PR, n = 95) based on a gait analysis estimation of the joint reaction force (young, healthy cohort with no signs of OA). At the AC-SB interface, the number of CMMC in the LBR was 1.8 times and 2.2 times higher compared to the NLBR, and the PR, respectively. On the other hand, the median Feret size of the CMMC were smallest in the LBR (55.2 µm) and increased in the NLBR (73.5 µm; p = 0.043) and the PR (89.1 µm; p = 0.043). AC thickness was positively associated with SB thickness (Pearson's r = 0.48; p < 1e-13), CMMC number. (r = 0.46; p < 1e-11), and circularity index (r = 0.61; p < 1e-38). In conclusion, our data suggest that regional differences in the microchannel architecture of SB might reflect regional differences in loading.
Outcomes of Tracheal Resections in Well‐Differentiated Thyroid Cancer—A case series and meta‐analysis
Authors: Warshavsky Anton , Rosen Roni , Nard‐Carmel Narin , Muhanna Nidal , Ungar Omer , Abergel Avraham , Fliss Dan M. , Horowitz Gilad 
Published: May 2021

AbstractBackgroundTracheal invasion in thyroid cancer is a well‐known form of advanced disease. There is an ongoing controversy over outcomes of tracheal shaving in this situation. The aim of this study was to compare the results of tracheal shaving to radical resections in patients with low‐volume tracheal involvement.MethodsAn institutional case series and a meta‐analysis was conducted. All studies that included patients diagnosed with well‐differentiated thyroid cancer (WDTC) and tracheal invasion were analyzed. Patients with low‐volume tracheal invasion (according to the Shin classification) were extracted from the various studies and subsequently included in this study. The outcomes of tracheal shaving and radical resection were consolidated and compared. All recurrences and mortality over 10 years of follow‐up were calculated using the Kaplan–Meier method.ResultsInstitutional case series included 22 patients diagnosed with WDTC and tracheal invasion that underwent resection. There was one case of recurrence (4.5%) during the follow‐up period and no mortality. The meta‐analysis yielded a total of 284 patients from six studies who met the inclusion criteria. The 10‐year overall survival was 82.4% for the shave group and 80.8% for the resection group. The combined Kaplan–Meier curves revealed no statistically significant difference between the two techniques (hazard ratio [HR] = 0.86, P = .768). The combined 10‐year local control rate of the shave group was 90.2%.ConclusionsThe outcomes of tracheal shaving in low‐volume invasion are similar to more aggressive forms of tracheal resections. Shave resection is oncologically safe in carefully selected WDTC patients demonstrating minimal tracheal invasion.
Time pressure predicts decisional regret in men with localized prostate cancer: data from a longitudinal multicenter study
Authors: Hilger Caren , Schostak Martin , Otto Isabella , Kendel Friederike 
Published: May 2021

Abstract
Purpose
A substantial proportion of men with localized prostate cancer (lPCa) later regret their treatment decision. We aimed to identify factors contributing to decisional regret.

Methods
We conducted a longitudinal study, in which men with lPCa were surveyed at four measurement points: T0 (baseline) = prior to treatment; T1 = 6; T2 = 12; T3 = 18 months after baseline. χ2-tests and independent t-tests were used to compare men undergoing different treatments [Active Surveillance (AS) vs. local treatment]. Logistic regression models were fitted to investigate the associations between predictors (time pressure, information provided by the urologist, impairment of erectile functioning, satisfaction with sexual life) and the criterion decisional regret.

Results
At baseline, the sample included N = 176 men (AS: n = 100; local treatment: n = 76). At T2 and T3, men after local therapies reported higher regret than men under AS. Decisional regret at T3 was predicted by time pressure at baseline (OR 2.28; CI 1.04–4.99; p < 0.05), erectile dysfunction at T2 and T3 (OR 3.40; CI 1.56–7.42; p < 0.01), and satisfaction with sexual life at T1–T3 (OR 0.44; CI 0.20–0.96; p < 0.05).

Conclusions
Time pressure, erectile dysfunction, and satisfaction with sexual life predict decisional regret in men with lPCa. Mitigating time pressure and realistic expectations concerning treatment side effects may help to prevent decisional regret in PCa survivors.

Trial registration number
DRKS00009510; date of registration: 2015/10/28.
Impact of air–sea coupling on the climate change signal over the Iberian Peninsula
Authors: de la Vara Alba , Cabos William , Sein Dmitry V. , Teichmann Claas , Jacob Daniela 
Published: May 2021

AbstractIn this work we use a regional atmosphere–ocean coupled model (RAOCM) and its stand-alone atmospheric component to gain insight into the impact of atmosphere–ocean coupling on the climate change signal over the Iberian Peninsula (IP). The IP climate is influenced by both the Atlantic Ocean and the Mediterranean sea. Complex interactions with the orography take place there and high-resolution models are required to realistically reproduce its current and future climate. We find that under the RCP8.5 scenario, the generalized 2-m air temperature (T2M) increase by the end of the twenty-first century (2070–2099) in the atmospheric-only simulation is tempered by the coupling. The impact of coupling is specially seen in summer, when the warming is stronger. Precipitation shows regionally-dependent changes in winter, whilst a drier climate is found in summer. The coupling generally reduces the magnitude of the changes. Differences in T2M and precipitation between the coupled and uncoupled simulations are caused by changes in the Atlantic large-scale circulation and in the Mediterranean Sea. Additionally, the differences in projected changes of T2M and precipitation with the RAOCM under the RCP8.5 and RCP4.5 scenarios are tackled. Results show that in winter and summer T2M increases less and precipitation changes are of a smaller magnitude with the RCP4.5. Whilst in summer changes present a similar regional distribution in both runs, in winter there are some differences in the NW of the IP due to differences in the North Atlantic circulation. The differences in the climate change signal from the RAOCM and the driving Global Coupled Model show that regionalization has an effect in terms of higher resolution over the land and ocean.
Disruptions of neurological services, its causes and mitigation strategies during COVID-19: a global review
Authors: García-Azorín David , Seeher Katrin M. , Newton Charles R. , Okubadejo Njideka U. , Pilotto Andrea , Saylor Deanna , Winkler Andrea Sylvia , Charfi Triki Chahnez , Leonardi Matilde 
Published: May 2021

Abstract
Background
The COVID-19 pandemic leads to disruptions of health services worldwide. To evaluate the particular impact on neurological services a rapid review was conducted.

Methods
Studies reporting the provision of neurological services during the pandemic and/or adopted mitigation strategies were included in this review. PubMed and World Health Organization’s (WHO) COVID-19 database were searched. Data extraction followed categories used by WHO COVID-19 pulse surveys and operational guidelines on maintaining essential health services during COVID-19.

Findings
The search yielded 1101 articles, of which 369 fulfilled eligibility criteria, describing data from 210,419 participants, being adults (81%), children (11.4%) or both (7.3%). Included articles reported data from 105 countries and territories covering all WHO regions and World Bank income levels (low income: 1.9%, lower middle: 24.7%, upper middle: 29.5% and high income; 44.8%). Cross-sectoral services for neurological disorders were most frequently disrupted (62.9%), followed by emergency/acute care (47.1%). The degree of disruption was at least moderate for 75% of studies. Travel restrictions due to lockdowns (81.7%) and regulatory closure of services (65.4%) were the most commonly reported causes of disruption. Authors most frequently described telemedicine (82.1%) and novel dispensing approaches for medicines (51.8%) as mitigation strategies. Evidence for the effectiveness of these measures is largely missing.

Interpretation
The COVID-19 pandemic affects all aspects of neurological care. Given the worldwide prevalence of neurological disorders and the potential long-term neurological consequences of COVID-19, service disruptions are devastating. Different strategies such as telemedicine might mitigate the negative effects of the pandemic, but their efficacy and acceptability remain to be seen.
Does the non-absorbable suture closure of the jejunal mesenteric defect reduce the incidence and severity of internal hernias after laparoscopic Roux-en-Y gastric bypass?
Authors: Schneider Romano , Schulenburg Michaela , Kraljević Marko , Klasen Jennifer M. , Peters Thomas , Wölnerhanssen Bettina , Peterli Ralph 
Published: May 2021

Abstract
Purpose
Internal hernias (IH) are frequent complications after laparoscopic Roux-en-Y gastric bypass (LRYGB). Closure of the jejunal mesenteric and the Petersen defect reduces IH incidence in prospective and retrospective trials. This study investigates whether closing the jejunal mesenteric space alone by non-absorbable suture and splitting the omentum can be beneficial to prevent IH after LRYGB.

Methods
Observational cohort study of 785 patients undergoing linear LRYGB including omental split at a single institution, with 493 patients without jejunal mesenteric defect closure and 292 patients with closure by non-absorbable suture, and a minimal follow-up of 2 years. Patients were assessed for appearance and severity of IH. Additionally, open mesenteric gaps without herniated bowel as well as early obstructions due to kinking of the entero-enterostomy (EE) were explored.

Results
Through primary mesenteric defect closure, the rate of manifest jejunal mesenteric and Petersen IH could be reduced from 6.5 to 3.8%, but without reaching statistical significance. The most common location for an IH was the jejunal mesenteric space, where defect closure during primary surgery reduced the rate of IH from 5.3 to 2.4%. Higher weight loss seemed to increase the risk of developing an IH.

Conclusion
The closure of the jejunal mesenteric defect by non-absorbable suture may reduce the rate of IH at the jejunal mesenteric space after LRYGB. However, the beneficial effect in our collective is smaller than expected, particularly in patients with good weight loss. The Petersen IH rate remained low by consequent T-shape split of the omentum without suturing of the defect.