bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-level expression of aryl-alcohol oxidase 2 from Pleurotus eryngii in Pichia pastoris for production of fragrances and bioactive precursors
Authors: Jankowski Nina , Koschorreck Katja , Urlacher Vlada B. 
Published: September 2020

Abstract
The fungal secretome comprises various oxidative enzymes participating in the degradation of lignocellulosic biomass as a central step in carbon recycling. Among the secreted enzymes, aryl-alcohol oxidases (AAOs) are of interest for biotechnological applications including production of bio-based precursors for plastics, bioactive compounds, and flavors and fragrances. Aryl-alcohol oxidase 2 (PeAAO2) from the fungus Pleurotus eryngii was heterologously expressed and secreted at one of the highest yields reported so far of 315 mg/l using the methylotrophic yeast Pichia pastoris (recently reclassified as Komagataella phaffii). The glycosylated PeAAO2 exhibited a high stability in a broad pH range between pH 3.0 and 9.0 and high thermal stability up to 55 °C. Substrate screening with 41 compounds revealed that PeAAO2 oxidized typical AAO substrates like p-anisyl alcohol, veratryl alcohol, and trans,trans-2,4-hexadienol with up to 8-fold higher activity than benzyl alcohol. Several compounds not yet reported as substrates for AAOs were oxidized by PeAAO2 as well. Among them, cumic alcohol and piperonyl alcohol were oxidized to cuminaldehyde and piperonal with high catalytic efficiencies of 84.1 and 600.2 mM−1 s−1, respectively. While the fragrance and flavor compound piperonal also serves as starting material for agrochemical and pharmaceutical building blocks, various positive health effects have been attributed to cuminaldehyde including anticancer, antidiabetic, and neuroprotective effects. PeAAO2 is thus a promising biocatalyst for biotechnological applications.

Key points
• Aryl-alcohol oxidase PeAAO2 from P. eryngii was produced in P. pastoris at 315 mg/l.
• Purified enzyme exhibited stability over a broad pH and temperature range.
• Oxidation products cuminaldehyde and piperonal are of biotechnological interest.
Graphical abstract
Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC
Authors: Kramer Vasko , Fernández René , Lehnert Wencke , Jiménez-Franco Luis David , Soza-Ried Cristian , Eppard Elisabeth , Ceballos Matias , Meckel Marian , Benešová Martina , Umbricht Christoph A. , Kluge Andreas , Schibli Roger , Zhernosekov Konstantin , Amaral Horacio , Müller Cristina 
Published: September 2020

Abstract
Introduction
PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties.

Methods
Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120–160 μg) [177Lu]Lu-PSMA-ALB-56 followed by whole-body SPECT/CT imaging over 7 days. Volumes of interest were defined on the SPECT/CT images for dosimetric evaluation for healthy tissue and tumor lesions. General safety and therapeutic efficacy were assessed by measuring blood biomarkers.

Results
[177Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177Lu]Lu-PSMA-ALB-56 in the blood with the highest uptake in tumor lesions at 48 h post injection. Compared with published data for other therapeutic PSMA radioligands (e.g. PSMA-617 and PSMA I&T), normalized absorbed doses of [177Lu]Lu-PSMA-ALB-56 were up to 2.3-fold higher in tumor lesions (6.64 ± 6.92 Gy/GBq) and similar in salivary glands (0.87 ± 0.43 Gy/GBq). Doses to the kidneys and red marrow (2.54 ± 0.94 Gy/GBq and 0.29 ± 0.07 Gy/GBq, respectively) were increased.

Conclusion
Our data demonstrated that the concept of albumin-binding PSMA-radioligands is feasible and leads to increased tumor doses. After further optimization of the ligand design, the therapeutic outcomes may be improved for patients with prostate cancer.
Response to neoadjuvant treatment among rectal cancer patients in a population-based cohort
Authors: Alwers Elizabeth , Jansen Lina , Kather Jakob , Amitay Efrat , Bläker Hendrik , Kloor Matthias , Tagscherer Katrin E. , Roth Wilfried , Herpel Esther , Chang-Claude Jenny , Brenner Hermann , Hoffmeister Michael 
Published: September 2020

AbstractBackgroundIn rectal cancer, prediction of tumor response and pathological complete response (pCR) to neoadjuvant treatment could contribute to refine selection of patients who might benefit from a delayed- or no-surgery approach. The aim of this study was to explore the association of clinical and molecular characteristics of rectal cancer with response to neoadjuvant treatment and to compare patient survival according to level of response.MethodsResected rectal cancer patients were selected from a population-based cohort study. Molecular tumor markers were determined from the surgical specimen. Tumor response and pCR were defined as downstaging in T or N stage and absence of tumor cells upon pathological examination, respectively. The associations of patient and tumor characteristics with tumor response and pCR were explored, and patient survival was determined by degree of response to neoadjuvant treatment.ResultsAmong 1536 patients with rectal cancer, 602 (39%) received neoadjuvant treatment. Fifty-five (9%) patients presented pCR, and 239 (49%) and 250 (53%) patients showed downstaging of the T and N stages, respectively. No statistically significant associations were observed between patient or tumor characteristics and tumor response or pCR. Patients who presented any type of response to neoadjuvant treatment had significantly better cancer-specific and overall survival compared with non-responders.ConclusionIn this study, patient characteristics were not associated with response to neoadjuvant treatment, and molecular characteristics determined after surgical resection of the tumor were not predictive of pCR or tumor downstaging. Future studies should include molecular biomarkers from biopsy samples before neoadjuvant treatment.
Non-statin lipid-lowering therapy over time in very-high-risk patients: effectiveness of fixed-dose statin/ezetimibe compared to separate pill combination on LDL-C
Authors: Katzmann Julius L. , Sorio-Vilela Francesc , Dornstauder Eugen , Fraas Uwe , Smieszek Timo , Zappacosta Sofia , Laufs Ulrich 
Published: September 2020

Abstract
Background
Many patients at very-high atherosclerotic cardiovascular disease risk do not reach guideline-recommended targets for LDL-C. There is a lack of data on real-world use of non-statin lipid-lowering therapies (LLT) and little is known on the effectiveness of fixed-dose combinations (FDC). We therefore studied prescription trends in oral non-statin LLT and their effects on LDL-C.

Methods
A retrospective analysis was conducted of electronic medical records of outpatients at very-high cardiovascular risk treated by general practitioners (GPs) and cardiologists, and prescribed LLT in Germany between 2013 and 2018.

Results
Data from 311,242 patients were analysed. Prescriptions for high-potency statins (atorvastatin and rosuvastatin) increased from 10.4% and 25.8% of patients treated by GPs and cardiologists, respectively, in 2013, to 34.7% and 58.3% in 2018. Prescription for non-statin LLT remained stable throughout the period and low especially for GPs. Ezetimibe was the most prescribed non-statin LLT in 2018 (GPs, 76.1%; cardiologists, 92.8%). Addition of ezetimibe in patients already prescribed a statin reduced LDL-C by an additional 23.8% (32.3 ± 38.4 mg/dL), with a greater reduction with FDC [reduction 28.4% (40.0 ± 39.1 mg/dL)] as compared to separate pills [19.4% (27.5 ± 33.8 mg/dL)]; p < 0.0001. However, only a small proportion of patients reached the recommended LDL-C level of < 70 mg/dL (31.5% with FDC and 21.0% with separate pills).

Conclusions
Prescription for high-potency statins increased over time. Non-statin LLT were infrequently prescribed by GPs. The reduction in LDL-C when statin and ezetimibe were prescribed in combination was considerably larger for FDC; however, a large proportion of patients still remained with uncontrolled LDL-C levels.

Graphic abstract
High risk of hip dislocation following polyethylene liner exchange in total hip arthroplasty—is cup revision necessary?
Authors: Dammerer D. , Schneider F. , Renkawitz T. , Putzer D. , Bogensperger M. , Biedermann R. 
Published: September 2020

Abstract
Purpose
Polyethylene (PE) wear remains a common reason for revision surgery following total hip arthroplasty (THA). An established treatment method is isolated liner exchange in a well-fixed acetabular cup and entails a known high risk of hip dislocation after revision surgery. The purpose of this retrospective study was to determine the rate of hip dislocation after liner exchange.

Methods
Patients were included if (1) the PE liner was removable, (2) the acetabular shell was stable with acceptable orientation, (3) no osteolysis around the acetabular cup was found and (4) no dislocation of the THA occurred before revision surgery. We reviewed medical histories and performed radiological measurements using Einzel-Bild-Röntgen-Analyse (EBRA) software. EBRA measurements and statistical investigations were performed by two independent investigators.

Results
A total of 82 patients were included in our study. Mean follow-up was six (range: 3.6–9.9) years. In 13 (15.8%) patients THA dislocations occurred at a mean postoperative period of 20.2 (range: 1–44) weeks after revising the PE liner. This is equivalent to an absolute risk increase of 16% after revision surgery, which results in a number needed to harm of 6. This means that every sixth patient with isolated liner exchange can expect to experience dislocation due to wear.

Conclusion
In conclusion, isolated exchange of the polyethylene liner because of wear showed a high risk of dislocation and further cup revision. Our results suggest that the threshold for revising well-fixed components in the case of liner wear should be lowered.

Trial Registration number and date of registration
Number: 20140710-1012 and Date: 2016-03-09.
Basolateral activation with TLR agonists induces polarized cytokine release and reduces barrier function in RPE in vitro
Authors: Terheyden Laura , Roider Johann , Klettner Alexa 
Published: September 2020

Abstract
Purpose
Systemic inflammation may be of importance in the development of AMD. RPE cells can recognize danger signals with toll-like receptors (TLR) and may react in a pro-inflammatory manner. In this study, we evaluated the basal and apical secretions of TNFα, IL-6, and IL-1β in primary RPE cells and RPE/choroid explant cells under basolateral stimulation of TLR2, 3, and 4; the effects on barrier function; and their influence on neuronal cell viability.

Methods
RPE/choroid tissue explants were prepared from porcine eyes and cultivated in modified Ussing chambers; primary porcine RPE cells on transwell plates. Cells were basally stimulated with agonists Pam2CSK4 (Pam; TLR2), polyinosinic/polycytidylic acid (Poly I:C; TLR3), and lipopolysaccharide (LPS; TLR4) for 24 h. Supernatants were evaluated with ELISA for cytokines TNFα, IL-6, and IL-1β. Apical supernatants were applied to SHSY-5Y cells, and cell viability was evaluated in MTT assay. Barrier function was tested by measuring transepithelial electrical resistance (TER) and occludin immunostaining.

Results
None of the tested TLR agonists was toxic on RPE cells after 24 h of exposure. Unstimulated RPE cells secreted hardly any cytokines. Pam induced IL-6, IL-1ß, and TNFα on the basal and apical sides at all concentrations tested. Poly I:C induced IL-6 and TNFα primarily at the basal side at lower but on both sides at higher concentrations. LPS induced IL-6, IL-1ß, and TNFα apically and basally at all concentrations tested. In the RPE/choroid, a strong difference between apical and basal secretions could be found. IL-6 was constitutively secreted basally, but not apically, but was induced by all agonists on both sides. IL-1ß and TNFα alpha were strongly induced on the basal side by all agonists. TER was reduced by all agonists, with Pam and LPS being effective in all concentrations tested. Occludin expression was unaltered, but the distribution was influenced by the agonists, with a less distinct localization at the cell borders after treatment. None of the agonists or supernatants of treated RPE and RPE/choroid organ cultures exerted any effect on viability of SHSY-5Y cells.

Conclusions
Danger signals activating TLRs can induce polarized cytokine expression and contribute to the loss of barrier function in the RPE.
Lung ultrasound features predict admission to the neonatal intensive care unit in infants with transient neonatal tachypnoea or respiratory distress syndrome born by caesarean section
Authors: Poerio Antonio , Galletti Silvia , Baldazzi Michelangelo , Martini Silvia , Rollo Alessandra , Spinedi Sofia , Raimondi Francesco , Zompatori Maurizio , Corvaglia Luigi , Aceti Arianna 
Published: September 2020

AbstractWe aimed to evaluate the reliability of lung ultrasound (LU) to predict admission to the neonatal intensive care unit (NICU) for transient neonatal tachypnoea or respiratory distress syndrome in infants born by caesarean section (CS). A prospective, observational, single-centre study was performed in the delivery room and NICU of Sant’Orsola-Malpighi Hospital in Bologna, Italy. Term and late-preterm infants born by CS were included. LU was performed at 30’ and 4 h after birth. LU appearance was graded according to a previously validated three-point scoring system (3P-LUS: type-1, white lung; type-2, black/white lung; type-3, normal lung). Full LUS was also calculated. One hundred infants were enrolled, and seven were admitted to the NICU. The 5 infants with bilateral type-1 lung at birth were all admitted to the NICU. Infants with type-2 and/or type-3 lung were unlikely to be admitted to the NICU. Mean full-LUS was 17 in infants admitted to the NICU, and 8 in infants not admitted. In two separate binary logistic regression models, both the 3P- and the full LUS proved to be independently associated with NICU admission (OR [95% CI] 0.001 [0.000–0.058], P = .001, and 2.890 [1.472–5.672], P = .002, respectively). The ROC analysis for the 3P-LUS yielded an AUC of 0.942 (95%CI, 0.876–0.979; P<.001), while ROC analysis for the full LUS yielded an AUC of 0.978 (95%CI, 0.926–0.997; P<.001). The AUCs for the two LU scores were not significantly different (p = .261).Conclusion: the 3P-LUS performed 30 min after birth proved to be a reliable tool to identify, among term and late preterm infants born to CS, those who will require NICU admission for transient neonatal tachypnoea or respiratory distress syndrome.

What is known• Lung ultrasound (LU) has become an attractive diagnostic tool in neonatal settings, and guidelines on point-of-care LU in the neonatal intensive care unit (NICU) have been recently issued.• LU is currently used for diagnosing several neonatal respiratory morbidities and has been also proposed for predicting further intervention, such as NICU admission, need for surfactant treatment or mechanical ventilation in preterm infants.

What is new• LU performed 30′ after birth and evaluated through a simple three-point scoring system represents a reliable tool to identify, among term and late preterm infants born to caesarean section, those with transient neonatal tachypnoea or respiratory distress syndrome who will require NICU admission.• LU performed in the neonatal period confirms its potential role in ameliorating routine neonatal clinical management.
Hybrid bio-inspired algorithm and convolutional neural network for automatic lung tumor detection
Authors: Vijh Surbhi , Gaurav Prashant , Pandey Hari Mohan 
Published: September 2020

AbstractIn this paper, we have proposed a hybrid bio-inspired algorithm which takes the merits of whale optimization algorithm (WOA) and adaptive particle swarm optimization (APSO). The proposed algorithm is referred as the hybrid WOA_APSO algorithm. We utilize a convolutional neural network (CNN) for classification purposes. Extensive experiments are performed to evaluate the performance of the proposed model. Here, pre-processing and segmentation are performed on 120 lung CT images for obtaining the segmented tumored and non-tumored region nodule. The statistical, texture, geometrical and structural features are extracted from the processed image using different techniques. The optimized feature selection plays a crucial role in determining the accuracy of the classification algorithm. The novel variant of whale optimization algorithm and adaptive particle swarm optimization, hybrid bio-inspired WOA_APSO, is proposed for selecting optimized features. The feature selection grouping is applied by embedding linear discriminant analysis which helps in determining the reduced dimensions of subsets. Twofold performance comparisons are done. First, we compare the performance against the different classification techniques such as support vector machine, artificial neural network (ANN) and CNN. Second, the computational cost of the hybrid WOA_APSO is compared with the standard WOA and APSO algorithms. The experimental result reveals that the proposed algorithm is capable of automatic lung tumor detection and it outperforms the other state-of-the-art methods on standard quality measures such as accuracy (97.18%), sensitivity (97%) and specificity (98.66%). The results reported in this paper are encouraging; hence, these results will motivate other researchers to explore more in this direction.
Effect of endodontic treatment on periodontal healing of grade 3 endo-periodontal lesions without root damage in periodontally compromised patients—a retrospective pilot study
Authors: Ruetters Maurice , Kim Ti-Sun , Krisam Johannes , El-Sayed Shirin , ElSayed Nihad 
Published: September 2020

Abstract
Objectives
There is little evidence about the effect of different treatment protocols for grade 3 endo-periodontal lesions without root damage in patients with periodontitis according to the new classification of periodontal disease. The aim of this study is to evaluate the impact of endodontic treatment on the achievement of periodontal healing.

Materials and methods
Teeth with the initial diagnosis endo-periodontal lesion without root damage grade 3, treated with a standardized endodontic treatment protocol, were included in this study. A retrospective analysis was performed to assess the impact on periodontal healing by evaluating probing pocket depth (PPD), clinical attachment gain (CAL), and periapical index score (PAI).

Results
Nineteen teeth and 13 patients were included. A mean reduction of 3.19 ± 3.41 mm in PPD was recorded. The mean CAL gain was 2.33± 3.75 mm. Five teeth (45.4%) showed an improvement of PAI and were classified as treatment success.

Conclusions
The results failed to show a highly predictable treatment outcome for endo-periodontal lesion grade 3 without root damage in patients with periodontitis. However, endodontic therapy alone resulted in treatment success for some of the teeth, which would otherwise have had a poor prognosis.

Clinical relevance
Endo-periodontal lesions can often be challenging for dentists in daily clinical practice. To date, there is not much evidence for practitioners to rely on. Therefore, this study aims to strengthen the evidence for the management and treatment of endo-periodontal lesions. Although the outcome is not highly predictable yet, teeth with the initial diagnosis endo-periodontal lesion without root damage grade 3 can benefit from an endodontic treatment.
High-resolution taxonomic examination of the oral microbiome after oil pulling with standardized sunflower seed oil and healthy participants: a pilot study
Authors: Griessl Tim , Zechel-Gran Silke , Olejniczak Stefan , Weigel Markus , Hain Torsten , Domann Eugen 
Published: September 2020

AbstractObjectivesWe aimed at the high-resolution examination of the oral microbiome depending on oil pulling, compared it with saline pulling, and analyzed whether the method is capable of reducing the overall microbial burden of the oral cavity.Materials and methodsThe study was a cohort study with three healthy subjects. Oil pulling samples, saline pulling samples, and saliva samples were microscoped and cultured under microaerophilic and anaerobic conditions; colony-forming units were counted; and cultivated bacteria were identified employing MALDI-TOF MS. The oral microbiomes (saliva) and the microbiota incorporated in oil and saline pulling samples were determined in toto by using 16S rDNA next-generation sequencing (NGS) and bioinformatics.ResultsMicroscopy revealed that oral epithelial cells are ensheathed with distinct oil droplets during oil pulling. Oil pulling induced a higher production of saliva and the oil/saliva emulsion contained more bacteria than saline pulling samples. Oil pulling resulted in a significant and transient reduction of the overall microbial burden in comparison to saliva examined prior to and after pulling. Both oil and saline pulling samples mirrored the individual oral microbiomes in saliva.ConclusionsWithin the limitations of this pilot study, it might be concluded that oil pulling is able to reduce the overall microbial burden of the oral cavity transiently and the microbiota in oil pulling samples are representative to the oral microbiome.Clinical relevanceWithin the limitations of this pilot study, it might be concluded that oil pulling can be considered as an enlargement of standard oral hygiene techniques since it has the characteristic of an oral massage, enwrapping epithelial cells carrying bacteria in oil vesicles and reaching almost all unique habitats in oral cavity.
Modulation of benzofuran structure as a fluorescent probe to optimize linear and nonlinear optical properties and biological activities
Authors: Krawczyk Przemysław 
Published: September 2020

AbstractThe study presents the influence of structure modulation by introducing selected donor and acceptor substituents on optical properties of benzofuran used in biological imaging. As the starting form, 2-(5-formylbenzofuran-2-yl)acetamide described experimentally was used. This molecule contains an aldehyde group as reactive site, through which conjugation with protein occurs. Structure modulation was carried out by attaching additional electron-donating and electron-withdrawing substituents to the amino group, namely -NH2, -NHCH3, -NO2, -OH, and -OCH3. Studies have shown that the -NH2, -NHCH3, -OH, and -OCH3 substituents do not induce a significant change in the position of maximum absorption and fluorescence relative to each other. They also do not change the parameters describing the nonlinear response. Only the presence of the -NO2 substituent results in significant solvatochromic shifts. Changing substituents also does not significantly affect the LD50 value, and all tested fluorescent probes should not be considered toxic to humans. Modulation of the benzofuran derivative structure also does not change the active center in which the biocomplex with the protein is formed. In each case, the conjugation takes place via LYS114. In addition, the study was prompted to analyze the linear and nonlinear optical properties of conjugates formed after the reaction with Concanavalin A.Graphical abstract