bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autonomous Reboot: Kant, the categorical imperative, and contemporary challenges for machine ethicists
Authors: White Jeffrey 
Published: January 2021

AbstractRyan Tonkens (2009) has issued a seemingly impossible challenge, to articulate a comprehensive ethical framework within which artificial moral agents (AMAs) satisfy a Kantian inspired recipe—"rational" and "free"—while also satisfying perceived prerogatives of machine ethicists to facilitate the creation of AMAs that are perfectly and not merely reliably ethical. This series of papers meets this challenge by landscaping traditional moral theory in resolution of a comprehensive account of moral agency. The first paper established the challenge and set out autonomy in Aristotelian terms. The present paper interprets Kantian moral theory on the basis of the preceding introduction, argues contra Tonkens that an engineer does not violate the categorical imperative in creating Kantian AMAs, and proposes that a Kantian AMA is not only a possible goal for Machine ethics research, but a necessary one.
Accuracy of Electrode Placement in IRE Treatment with Navigated Guidance
Authors: Stillström David , Sandu Raluca-Maria , Freedman Jacob 
Published: January 2021

Abstract
Purpose
Evaluate the accuracy of multiple electrode placements in IRE treatment of liver tumours using a stereotactic CT-based navigation system.

Method
Analysing data from all IRE treatments of liver tumours at one institution until 31 December 2018. Comparing planned with validated electrode placement. Analysing lateral and angular errors and parallelism between electrode pairs

Results
Eighty-four tumours were treated in 60 patients. Forty-six per cent were hepatocellular carcinoma, and 36% were colorectal liver metastases. The tumours were located in all segments of the liver. Data were complete from 51 treatments. Two hundred and six electrodes and 336 electrode pairs were analysed. The median lateral and angular error, comparing planned and validated electrode placement, was 3.6 mm (range 0.2–13.6 mm) and 3.1° (range 0°–16.1°). All electrodes with a lateral error >10 mm were either re-positioned or excluded before treatment. The median angle between the electrode pairs was 3.8° (range 0.3°–17.2°). There were no electrode placement-related complications.

Conclusion
The use of a stereotactic CT-based system for navigation of electrode placement in IRE treatment of liver tumours is safe, accurate and user friendly.
Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis
Authors: Little M. W. , Gibson M. , Briggs J. , Speirs A. , Yoong P. , Ariyanayagam T. , Davies N. , Tayton E. , Tavares S. , MacGill S. , McLaren C. , Harrison R. 
Published: January 2021

Abstract
Purpose
Planned interim analysis of GENESIS; a prospective pilot study investigating the role of genicular artery embolization (GAE) in patients with mild to moderate osteoarthritis of the knee using permanent microspheres.

Methods
Thirty-eight patients, median age = 60 (45–83), attended for GAE using 100–300 μm permanent microspheres. All patients had mild to moderate knee OA, resistant to conservative treatments over 6 months. Knee MRI was performed at baseline, and 12 months, enabling semi-quantitative analysis using Whole-Organ Magnetic Resonance Imaging Score (WORMS). Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS) (0–100 mm) were completed at baseline, 6 weeks, 3 months (n = 32), and 1-year (n = 16). Adverse events were recorded prospectively.

Results
Technical success of accessing and embolizing the target genicular arteries was 84%. Six patients were not embolized: four due to a presumed risk of non-target embolization, and two due to a lack of hyperaemic target. Mean VAS improved from 60 (SD = 20, 95% CI 53–66) at baseline to 36 (SD = 24, 95% CI 28–44) at 3 months (p < 0.001) and 45 (SD = 30, 95% CI 30–60) at 1-year (p < 0.05). All KOOS subscales showed a significant improvement at 6-weeks, 3-months, and 1-year follow-up, except function in daily living, which reached borderline significance (p = 0.06) at 1-year. Four patients experienced mild self-limiting skin discoloration over the embolized territory. One patient experienced a small self-limiting groin haematoma. WORMS scores at 1-year follow-up showed significant improvement in synovitis (p < 0.05). There were no cases of osteonecrosis.

Conclusion
GAE using permanent microspheres in patients with mild to moderate knee OA is safe, with potential efficacy at early follow-up.
Dreimuskelchirurgie bei großwinkliger Esotropie
Authors: Gräf Michael , Röhm Julia , Wassill Heiko 
Published: January 2021

Zusammenfassung
Hintergrund
Zur Korrektur großwinkliger Esotropie sind die kombinierte Konvergenzoperation und die beidseitige Medialisrücklagerung ohne und mit Myopexie verbreitet. Nur wenige Berichte liegen zu Dreimuskeleingriffen (3 ME) vor. Wir analysierten die Ergebnisse von 3 ME.

Patienten und Methoden
Von Juni 2016 bis Mai 2020 erhielten 61 Patienten einen 3 ME wegen Esotropie ≥ 27°. Schrägschielen wurde mitbehandelt. Die Schielwinkel wurden in 5 m und 0,3 m im simultanen (SPCT) und alternierenden Prismenabdecktest (APCT) gemessen. Die Dosierung betrug 0,51 mm/° (APCT, 5 m). Die Ergebnisse von 57 Patienten waren auswertbar.

Ergebnisse
Die Mediane und Streubreiten (min-max) betrugen: Alter: 6 Jahre (3–56). APCT präoperativ: fern 34° (27–45), nah 36° (27–50). Operationsdosis: 17 mm (15–21), 21 Fälle mit Obliquuschirurgie. APCT 5 Monate (3–24) postoperativ: fern 2° (−10–18), nah 2° (−8–18). Einen Restwinkel im Betrag ≤ 6° (≈ 10 PD) wiesen (APCT) fern 39 (68 %), nah 38 (67 %) und (SPCT) fern 45 (79 %), nah 42 Patienten (74 %) auf. Eine konsekutive Exotropie > 6° im APCT hatten fern 4 (7 %), nah 3 (5 %), eine Esotropie > 6° hatten 14 (25 %) bzw. 16 Patienten (28 %).

Schlussfolgerung
Die 3 ME ist als Ersteingriff bei großwinkliger Esotropie gut geeignet.
Volume electron microscopy: analyzing the lung
Authors: Schneider Jan Philipp , Hegermann Jan , Wrede Christoph 
Published: January 2021

AbstractSince its entry into biomedical research in the first half of the twentieth century, electron microscopy has been a valuable tool for lung researchers to explore the lung’s delicate ultrastructure. Among others, it proved the existence of a continuous alveolar epithelium and demonstrated the surfactant lining layer. With the establishment of serial sectioning transmission electron microscopy, as the first “volume electron microscopic” technique, electron microscopy entered the third dimension and investigations of the lung’s three-dimensional ultrastructure became possible. Over the years, further techniques, ranging from electron tomography over serial block-face and focused ion beam scanning electron microscopy to array tomography became available. All techniques cover different volumes and resolutions, and, thus, different scientific questions. This review gives an overview of these techniques and their application in lung research, focusing on their fields of application and practical implementation. Furthermore, an introduction is given how the output raw data are processed and the final three-dimensional models can be generated.
Studying molecular interactions in the intact organism: fluorescence correlation spectroscopy in the living zebrafish embryo
Authors: Dawes Michael L. , Soeller Christian , Scholpp Steffen 
Published: January 2021

AbstractCell behaviour and function is determined through the interactions of a multitude of molecules working in concert. To observe these molecular dynamics, biophysical studies have been developed that track single interactions. Fluorescence correlation spectroscopy (FCS) is an optical biophysical technique that non-invasively resolves single molecules through recording the signal intensity at the femtolitre scale. However, recording the behaviour of these biomolecules using in vitro-based assays often fails to recapitulate the full range of variables in vivo that directly confer dynamics. Therefore, there has been an increasing interest in observing the state of these biomolecules within living organisms such as the zebrafish Danio rerio. In this review, we explore the advancements of FCS within the zebrafish and compare and contrast these findings to those found in vitro.
Potential functions of embryonic cardiac macrophages in angiogenesis, lymphangiogenesis and extracellular matrix remodeling
Authors: Gula Grzegorz , Rumiński Sławomir , Niderla-Bielińska Justyna , Jasińska Agnieszka , Kiernozek Ewelina , Jankowska-Steifer Ewa , Flaht-Zabost Aleksandra , Ratajska Anna 
Published: January 2021

AbstractThe role of cardiac tissue macrophages (cTMs) during pre- and postnatal developmental stages remains in many aspects unknown. We aimed to characterize cTM populations and their potential functions based on surface markers. Our in situ studies of immunostained cardiac tissue specimens of murine fetuses (from E11to E17) revealed that a significant number of embryonic cTMs (phenotyped by CD45, CD68, CD64, F4/80, CD11b, CD206, Lyve-1) resided mostly in the subepicardial space, not in the entire myocardial wall, as observed in adult individuals. cTMs accompanied newly developed blood and lymphatic vessels adhering to vessel walls by cellular processes. A subpopulation of CD68-positive cells was found to form accumulations in areas of massive apoptosis during the outflow tract remodeling and shortening. Flow cytometry analysis at E14 and E17 stages revealed newly defined three subpopulations:CD64low, CD64highCD206-and CD64highCD206+. The levels of mRNA expression for genes related to regulation of angiogenesis (VEGFa, VEGFb, VEGFc, bFGF), lymphangiogenesis (VEGFc) and extracellular matrix (ECM) remodeling (MMP13, Arg1, Ym1/Chil3, Retlna/FIZZ1) differed among the selected populations and/or embryonic stages. Our results demonstrate a diversity of embryonic cTMs and their tissue-specific locations, suggesting their various potential roles in regulating angiogenesis, lymphangiogenesis and ECM remodeling.
Human amniotic fluid stem cells are able to form embryoid body-like aggregates which performs specific functions: morphological evidences
Authors: Centurione Lucia , Centurione Maria Antonietta , Antonucci Ivana , Sancilio Silvia , Stati Gianmarco , Stuppia Liborio , Di Pietro Roberta 
Published: January 2021

AbstractHuman second trimester Amniotic Fluid Stem Cells (hAFSCs) harbour the potential to differentiate into cells of each of the three germ layers and to form Embryoid Body (EB)-like aggregates, without inducing teratoma formation and with no ethical concerns. However, in spite of the number of reports on hAFSCs-EBs and their characterization, a thorough evaluation in light and electron microscopy of morphological and morphometric features of hAFSCs-EBs development in vitro has not been reported yet. Apart from a superficial layer of epithelial-like flat cells, displaying rare microvilli on the free surface, hAFSCs-EBs enclose inner material, abundant in vesicles and secretory granules, showing early characteristics of connective extracellular matrix dispersed among different types of inner cells. The observation of a number of microvesicles mainly represented by microparticles and, to a lower extent, by exosomes indicates the presence of a complex cellular communication system within this structure. According to morphological analysis, after 7 days of in vitro culture hAFSCs-EB appears as a well-organized corpuscle, sufficiently young to be a carrier of stemness and at the same time, when appropriately stimulated, able to differentiate. In fact, 7-day hAFSCs-EB represents itself an initial cellular transformation towards a specialized structure both in recording and in providing different stimuli from the surrounding environment, organizing structures and cells towards a differentiation fate.
miR-96-5p, miR-134-5p, miR-181b-5p and miR-200b-3p heterogenous expression in sites of prostate cancer versus benign prostate hyperplasia—archival samples study
Authors: Pełka Kacper , Klicka Klaudia , Grzywa Tomasz M. , Gondek Agata , Marczewska Janina M. , Garbicz Filip , Szczepaniak Kinga , Paskal Wiktor , Włodarski Paweł K. 
Published: January 2021

AbstractMicroRNAs are involved in various pathologies including cancer. The aim of the study was to assess the level of expression of miR-96-5p, -134-5p, -181b-5p, -200b-3p in FFPE samples of prostate cancer, adjacent cancer-free tissue, and benign prostatic hyperplasia. Samples of 23 FFPE prostate cancer and 22 benign prostatic hyperplasias were dissected and HE stained. Compartments of tumor tissue and adjacent healthy glandular tissue were isolated from each sample using Laser Capture Microdissection. Total RNA was isolated from dissected tissues. Expression of miR-96-5p, miR-134-5p, 181b-5p, and miR-200b-3p was determined by real-time RT-qPCR method. The expression of miR-200b-3p was significantly higher in cancerous prostate: both in adenocarcinomatous glands and in the adjacent, apparently unaffected glands compared to BPH samples. The expression of miR-181b-5p was lower in in both prostate cancer tissues and adjacent tissue compared to BPH samples. Expression of miR-96-5p and miR-134-5p was lower in prostate cancer tissues compared to BPH. Levels of miR-96-5p, miR-134-5p, and 181b-5p negatively correlated with the Gleason score. Given further studies, miR-96-5p, miR-134-5p and especially miR-200b-3p and miR-181b-5p may differentiate BPH and PC.
Effect of lead exposure from electronic waste on haemoglobin synthesis in children
Authors: Wang Hongwu , Huang Peng , Zhang Ruibiao , Feng Xueyong , Tang Qiulin , Liu Sixi , Wen Feiqiu , Zeng Li , Liu Yufeng , Wang Tianyou , Ma Lian 
Published: January 2021

Abstract
Background
Primitive electronic waste (e-waste) recycling is ongoing in Guiyu, so toxic heavy metals may continue to threaten the health of children in the area.

Objective
This study primarily aimed to evaluate the effect of e-waste exposure on haemoglobin (Hb) synthesis in preschool children.

Methods
Medical examinations were conducted with the permission of children’s guardians and the approval of the Ethics Committee of the Medical College of Shantou University. This study recruited 224 children (aged 3–6 years, exposed group) who lived in Guiyu and 204 children (aged 3–6 years, control group) who lived in a town free of e-waste pollution. Blood levels of lead, Hb, ferritin, folate and vitamin B12 were tested in all children. Furthermore, all children were assessed for thalassemia, and their parents were asked to fill in questionnaires.

Results
There were no significant differences in the level of ferritin, folate, or vitamin B12 between the exposed and control groups (P > 0.05). No children were identified as having thalassemia in all study participants. Blood lead level (BLL) and the risk of children with BLL ≥ 10 µg/dL in the exposed group were significantly higher than those in the control group (all P < 0.01). Three subgroups of each group were created according to BLL (Group A: < 5.0 µg/dL; Group B: 5.0–9.9 µg/dL; Group C: ≥ 10.0 µg/dL). Hb level decreased with elevated BLL in the exposed group (P = 0.03), but not in the control group (P = 0.14). Hb levels in group B and group C were also significantly lower in the exposed group than in the control group (Group B: 122.6 ± 9.5 g/L versus 125.8 ± 8.2 g/L, P = 0.01; Group C: 120.3 ± 7.3 g/L versus 123.6 ± 8.3 g/L, P = 0.03). In addition, the prevalence of anaemia associated with BLLs above 10 µg/dL and between 5.0 and 9.9 µg/dL were both significantly higher in the exposed group than in the control group (4.0% vs. 0.5%, 5.4% vs. 1.5%, respectively, both P < 0.05).

Conclusion
Lead exposure more significantly inhibits Hb synthesis in children who live in e-waste dismantling areas than in those who live in non-e-waste dismantling areas. Other toxins released from e-waste may also contribute to the inhibition of Hb synthesis and may lead to anaemia in local children. Further investigations are needed to provide evidence for the development of relevant protective measures.
Impact of pasireotide on postoperative pancreatic fistulas following distal resections
Authors: Vuorela Tiina , Mustonen H. , Kokkola A. , Haglund C. , Seppanen H. 
Published: January 2021

Abstract
Purpose
Postoperative pancreatic fistula (POPF), a difficult complication after surgery, can cause peripancreatic fluid collection and infections in the operative area. In addition, pancreatic fluid is corrosive and can lead to postoperative bleeding. Clinically significant grade B and C fistulas (CR-POPF) increase postoperative morbidity, resulting in a prolonged hospital stay. Delaying adjuvant therapy due to fistula formation in cancer patients can affect their prognosis. In this study, we aimed to determine if pasireotide affects fistula formation, and the severity of other complications in patients following pancreatic distal resections.

Data and methods
Between 2000 and 2016, 258 distal pancreatectomies were performed at Helsinki University Hospital and were included in our analysis. Pasireotide was administered to patients undergoing distal resections between July 2014 and December 2016. Patients received 900-μg pasireotide administered twice daily perioperatively. Other patients who received octreotide treatment were analyzed separately. Complications such as fistulas (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), reoperations, and mortality were recorded and analyzed 90 days postoperatively.

Results
Overall, 47 (18%) patients received pasireotide and 31 (12%) octreotide, while 180 patients (70%) who received neither constituted the control group. There were 40 (16%) clinically relevant grade B and C POPFs: seven (15%) in the pasireotide group, three (10%) in the octreotide group, and 30 (17%) in the control group (p = 0.739). Severe complications categorized as Clavien–Dindo grade III or IV were recorded in 64 (25%) patients: 17 (27%) in the pasireotide group, 4 (6%) in the octreotide group, and 43 (67%) in the control group (p = 0.059). We found no 90-day mortality.

Conclusions
In this study, pasireotide did not reduce clinically relevant POPFs or severe complications following pancreatic distal resection.
Effects of practice on visuo-spatial attention in a wayfinding task
Authors: Geisen Mai , Kim Kyungwan , Klatt Stefanie , Bock Otmar 
Published: January 2021

AbstractSeveral studies have evaluated the distribution of visuo-spatial attention in a wayfinding task, using gaze direction as an indicator for the locus of attention. We extended that work by evaluating how visuo-spatial attention is modified by wayfinding practice. Young and older participants followed prescribed routes through a virtual city on six trials. Each trial was followed by a route recall test, where participants saw screenshots of intersections encountered, and had to indicate which way to proceed. Behavioral and gaze data were registered in those tests. Wayfinding accuracy increased from trial to trial, more so in young than in older persons. Total gaze time, mean fixation time, and the vertical scatter of fixations decreased from trial to trial, similarly in young and older persons. The horizontal scatter of fixations did not differ between trials and age groups. The incidence of fixations on the subsequently chosen side also did not differ between trials, but it increased in older age. We interpret these findings as evidence that as wayfinding practice increased, participants gradually narrowed their attentional focus to the most relevant screenshot area, processed information within this focus more efficiently, reduced the total time in which attention dwelled on the rejected side of the screenshot, but maintained the total time on the chosen side. These dynamic changes of visuo-spatial attention were comparable in young and older participants. However, it appears that decision-making differed between age groups: older persons’ attention dwelled longer on the chosen side before they made their choice.
Resveratrol induces PD-L1 expression through snail-driven activation of Wnt pathway in lung cancer cells
Authors: Yang Mengmeng , Li Zongyu , Tao Jianping , Hu Hao , Li Zilin , Zhang Zhijian , Cheng Feng , Sun Yihang , Zhang Yao , Yang Jianke , Wei Huijun , Wu Zhihao 
Published: January 2021

Abstract
Purpose
Recent clinical trials with agents targeting immune checkpoint pathway have emerged as an important therapeutic approach for a broad range of cancer types. Resveratrol has been shown to possess cancer preventive and therapeutic effects and has potential to be chemotherapeutic agent/adjuvant. Here, we assessed the effect of resveratrol on immune checkpoint pathways.

Methods
The expression patterns of Wnt components and PD-L1 were examined by Western blot, Chromatin immunoprecipitation (ChIP) was used for analysis of DNA–protein interaction, the promoter activity was determined by luciferase reporter assay, apoptosis was analyzed by flow cytometry and the ability of the resveratrol to modulate T cell function was assessed in a co-culture system.

Results
Although the dose-, and cell-type dependent effects of resveratrol on PD-L1 expression have been reported, we show here that resveratrol dose-dependently upregulates PD-L1 expression at the range of pharmacologic-achievable concentrations in lung cancer cells and that is essential for suppression of T-cell-mediated immune response. We also found that Wnt pathway is critical for mediating resveratrol-induced PD-L1 upregulation. Mechanistically, resveratrol activates SirT1 deacetylase to deacetylate and stabilize transcriptional factor Snail. Snail in turn inhibits transcription of Axin2, which leads in disassembly of destruction complex and enhanced binding of β-catenin/TCF to PD-L1 promoter.

Conclusion
We conclude that resveratrol is capable to suppress anti-tumor immunity by controlling mainly PD-L1 expression. This finding will extend the understanding of resveratrol in regulation of tumor immunity and is relevant to the debate on resveratrol supplements for lung cancer patients.
Model-assisted DoE software: optimization of growth and biocatalysis in Saccharomyces cerevisiae bioprocesses
Authors: Moser André , Kuchemüller Kim B. , Deppe Sahar , Hernández Rodríguez Tanja , Frahm Björn , Pörtner Ralf , Hass Volker C. , Möller Johannes 
Published: January 2021

AbstractBioprocess development and optimization are still cost- and time-intensive due to the enormous number of experiments involved. In this study, the recently introduced model-assisted Design of Experiments (mDoE) concept (Möller et al. in Bioproc Biosyst Eng 42(5):867, 10.1007/s00449-019-02089-7, 2019) was extended and implemented into a software (“mDoE-toolbox”) to significantly reduce the number of required cultivations. The application of the toolbox is exemplary shown in two case studies with Saccharomyces cerevisiae. In the first case study, a fed-batch process was optimized with respect to the pH value and linearly rising feeding rates of glucose and nitrogen source. Using the mDoE-toolbox, the biomass concentration was increased by 30% compared to previously performed experiments. The second case study was the whole-cell biocatalysis of ethyl acetoacetate (EAA) to (S)-ethyl-3-hydroxybutyrate (E3HB), for which the feeding rates of glucose, nitrogen source, and EAA were optimized. An increase of 80% compared to a previously performed experiment with similar initial conditions was achieved for the E3HB concentration.