bluuebunny/crossref_metadata_2025 huggingface dataset:
Incentive spirometry to prevent pulmonary complications after chest trauma: a retrospective observational study
Authors: Dote Hisashi , Homma Yohichiro , Sakuraya Masaaki , Funakoshi Hiraku , Tanaka Shigeru , Atsumi Takahiro
Published: January 2021

Aim

Pulmonary complications (PCs) are a major cause of poor prognosis in chest trauma. Evidence on the effectiveness of incentive spirometry (IS) in trauma is scarce. This study investigated the effectiveness of IS in preventing PCs in patients with chest trauma with rib fractures.

Methods

This retrospective observational study analyzed the data obtained from the electronic medical records of patients with chest trauma with rib fractures admitted between 2011 and 2019. We included patients 18 years of age or older with risk of worsening respiratory failure. Early IS was the primary exposure and PCs (pulmonary infection or respiratory failure requiring escalating oxygen therapy) were the primary outcomes. Secondary outcomes were length of hospital stay, duration of oxygenation therapy, and adverse events of IS. Logistic regression analysis with a propensity score was used.

Results

We extracted 514 patients from the electronic medical records; 299 patients were included. The early IS group had a higher proportion of hypoxemia at admission, opioid analgesia use, invasive positive pressure ventilation, and respiratory physiotherapy. The severity of trauma was higher in the early IS group. There was no significant difference in the occurrence of the PCs between groups (adjusted odds ratio 0.71; 95% confidence interval, 0.24–2.16). No statistical differences were seen in the secondary outcomes.

Conclusion

For patients with chest trauma with rib fractures at risk of worsening respiratory failure, IS early after injury did not reduce the rate of PCs. No adverse event of IS was observed and IS was shown to be safe.
MOF‐derived Core‐Shell CoP@NC@TiO2 Composite as a High‐Performance Anode Material for Li‐ion Batteries
Authors: Chen Kai , Guo Hui‐nan , Li Wei‐qin , Wang Yi‐jing
Published: January 2021

Transition‐metal phosphides have been regarded as promising anode materials for high‐energy lithium‐ion batteries (LIBs) due to their high capacity and low cost. However, the mechanical pulverization and resultant capacity fade critically limit their further development. Here, we have designed an innovative core‐shell CoP@NC@TiO2 composite with an exotic rhombic dodecahedral morphology derived from ZIF‐67 precursor, which combines both advantages from TiO2 with excellent cycling stability and CoP with high capacity. The additional MOF‐derived N‐doped carbon framework is considered to improve the electrical conductivity and accommodate the volume expansion of CoP particles. Moreover, the outer TiO2 shell can also buffer the mechanical stress and maintain the integrity of composite. With the unique structure, the core‐shell CoP@NC@TiO2 composite material exhibits excellent electrochemical performance with a considerable discharge specific capacity of 706.3 mAh g−1 at a current density of 100 mA g−1 after 200 cycles and outstanding rate capacity. Hence, our work demonstrates that this core‐shell structure strategy combined with MOF‐derived carbon framework could provide a practical pathway towards enhanced electrode materials for energy storage and conversion.
The EGFR‐P38 MAPK axis up‐regulates PD‐L1 through miR‐675‐5p and down‐regulates HLA‐ABC via hexokinase‐2 in hepatocellular carcinoma cells
Authors: Liu Zongcai , Ning Fen , Cai Yanna , Sheng Huiying , Zheng Ruidan , Yin Xi , Lu Zhikun , Su Ling , Chen Xiaodan , Zeng Chunhua , Wang Haifang , Liu Li
Published: January 2021

Background

Immunotherapy has been shown to be a promising strategy against human cancers. A better understanding of the immune regulation in hepatocellular carcinoma (HCC) could help the development of immunotherapy against HCC. The epidermal growth factor receptor (EGFR) signaling is frequently activated in HCC and plays important roles in tumorigenesis. However, its role in HCC immunity is still largely unknown. This study aimed to investigate the impact of EGFR signaling on programmed death‐ligand 1 (PD‐L1) and human leukocyte antigen class‐I (HLA‐I) expression in HCC cells and its underlying mechanisms.

Methods

The expression of phosphorylated EGFR (p‐EGFR), PD‐L1, and HLA‐I (HLA‐ABC) in HCC specimens was detected by immunohistochemistry, and their correlations were analyzed. PD‐L1 and HLA‐ABC expression in EGFR‐activated HCC cells were detected by quantitative real‐time PCR, Western blotting, and flow cytometry, and T cell‐mediated lysis was performed to test the immunosuppressive effects of PD‐L1 and HLA‐ABC alterations in HCC cells. Furthermore, the underlying mechanisms of EGFR activation‐induced PD‐L1 up‐regulation and HLA‐ABC down‐regulation were explored by animal experiments, luciferase reporter assay, and gene gain‐ and loss‐of‐function studies.

Results

p‐EGFR was positively correlated with PD‐L1 and negatively correlated with HLA‐ABC expression in HCCs. EGFR activation by its ligand EGF up‐regulated PD‐L1 and down‐regulated HLA‐ABC in HCC cells, which was functionally important and could be abolished by the EGFR inhibitor, gefitinib, both in vitro and in vivo. Mechanistically, enhanced P38 mitogen‐activated protein kinase (MAPK) activation down‐regulated microRNA‐675‐5p (miR‐675‐5p) and up‐regulated glycolysis‐related enzyme hexokinase 2 (HK2); miR‐675‐5p down‐regulation enhanced the stability of PD‐L1 mRNA probably via the 3’‐untranslated region (3’‐UTR) of PD‐L1 and thereby caused PD‐L1 accumulation, and HK2 up‐regulation enhanced aerobic glycolysis and mediated a decrease in HLA‐ABC.

Conclusions

The EGFR‐P38 MAPK axis could up‐regulate PD‐L1 through miR‐675‐5p and down‐regulate HLA‐ABC via HK2 in HCC cells. Our study reveals a novel signaling network that may cause immune suppression in HCC and suggests that EGFR signaling can be targeted for HCC immunotherapy.
Ecthyma gangrenosum mimicking cellulitis
Authors: Ishihara Toru , Ozawa Hideki
Published: January 2021

This report has strong implications for carefully examining the common skin signs of cancer patients receiving chemotherapy. These signs can warn clinicians of the potential for severe infections such as fatal sepsis.
Multiply Charged Helium Droplet Anions
Authors: Laimer Felix , Zappa Fabio , Scheier Paul , Gatchell Michael
Published: January 2021

The detection of multiply charged helium droplet anions is reported for the first time. By ionizing droplets of superfluid helium with low energy electrons (up to 25 eV), it was possible to produce droplets containing up to five negative charges, which remain intact on the timescale of the experiment. The appearance sizes for different charge states are determined and are found to be orders of magnitude larger than for the equivalent cationic droplets, starting at 4 million He atoms for dianions. Droplets with He*− as charge carriers show signs of being metastable, but this effect is quenched by the pickup of water molecules.
Solution adaptive refinement of cut‐cell Cartesian meshes can improve FDA nozzle computational fluid dynamics efficiency
Authors: Pewowaruk Ryan , Li Yanheng , Rowinski David , Roldán‐Alzate Alejandro
Published: January 2021

To be an effective tool in studying cardiovascular disease and designing new treatments, computational fluid dynamics (CFD) needs to move from the realm of “high performance” to “high throughput” computing by improving efficiency while retaining accuracy. Solution adaptive mesh refinement (AMR) has the potential to decrease simulation time and benefits would be greater if the mesh could dynamically adapt throughout a heartbeat. This study used cut‐cell Cartesian grids with AMR at each time step. The refinement criteria was based on subgrid scale (SGS). The potential efficiency improvements from AMR were investigated with the FDA nozzle benchmark case at Re 500, 3500 and 6500. Using AMR with SGS = 1% mean throat velocity simulations could be performed in under 24 h on 16 CPUs with high accuracy compared to both FDA particle image velocimetry experiments and refined uniform grid CFD. This was an efficiency improvement of over an order of magnitude compared to uniform grids and other AMR SGS values. Using AMR with SGS = 5 or 0.2% mean throat velocity did not result in large efficiency improvements. Lastly, simulations of pulsatile flow suggest that performance improvements for typical cardiovascular flows may be even greater than were found simulating the statistically stationary FDA nozzle experiments.
Bioequivalence Analysis of 2 Dapoxetine Hydrochloride Formulations in Healthy Chinese Male Volunteers Under Fed and Fasting Conditions: A Randomized, Open‐Label, 2‐Sequence, 2‐Period, 2‐Way Crossover Study
Authors: Yan Keyu , Ju Gehang , Tan Qiong , Zeng Lijiao , Qiu Wen
Published: January 2021

This study assessed whether the reference and test formulations of dapoxetine hydrochloride were bioequivalent under fed and fasting conditions postadministration of a single dose as well as evaluated the safety profile of these 2 formulations. This study was a randomized, single‐center, 2‐period, open‐label, 2‐way crossover design study with a washout period of 7 days between each period. The study included 80 subjects, 40 under fed and 40 under fasting conditions. During each study period, the subjects were administered a single oral dose of either the reference or the test formulation, followed by collection of plasma samples 70 hours postdose. High‐performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) was performed to determine the concentrations of dapoxetine in plasma samples along with the calculation of Cmax, AUC0‐t, and AUC0‐inf. In addition, adverse events were monitored to determine the safety of these formulations. The geometric mean ratio (90%CI) for the reference and test formulations was 86% to 100%, 89% to 103%, and 89% to 103% under fasting conditions and 92% to 107%, 91% to 100%, and 92% to 101% under fed conditions for Cmax, AUC0‐t, and AUC0‐inf, respectively. The 90%CIs for the test/reference ratio for AUC and Cmax were within the acceptable limits of bioequivalence, thus demonstrating bioequivalence for these 2 dapoxetine hydrochloride formulations.
Toward a unified analysis of cerebellum maturation and aging across the entire lifespan: A MRI analysis
Authors: Romero José E. , Coupe Pierrick , Lanuza Enrique , Catheline Gwenaelle , Manjón José V. ,   Alzheimer's Disease Neuroimaging Initiative
Published: January 2021

Previous literature about the structural characterization of the human cerebellum is related to the context of a specific pathology or focused in a restricted age range. In fact, studies about the cerebellum maturation across the lifespan are scarce and most of them considered the cerebellum as a whole without investigating each lobule. This lack of study can be explained by the lack of both accurate segmentation methods and data availability. Fortunately, during the last years, several cerebellum segmentation methods have been developed and many databases comprising subjects of different ages have been made publically available. This fact opens an opportunity window to obtain a more extensive analysis of the cerebellum maturation and aging. In this study, we have used a recent state‐of‐the‐art cerebellum segmentation method called CERES and a large data set (N = 2,831 images) from healthy controls covering the entire lifespan to provide a model for 12 cerebellum structures (i.e., lobules I‐II, III, IV, VI, Crus I, Crus II, VIIB, VIIIA, VIIIB, IX, and X). We found that lobules have generally an evolution that follows a trajectory composed by a fast growth and a slow degeneration having sometimes a plateau for absolute volumes, and a decreasing tendency (faster in early ages) for normalized volumes. Special consideration is dedicated to Crus II, where slow degeneration appears to stabilize in elder ages for absolute volumes, and to lobule X, which does not present any fast growth during childhood in absolute volumes and shows a slow growth for normalized volumes.
Astrocytes deliver CK1 to neurons via extracellular vesicles in response to inflammation promoting the translation and amyloidogenic processing of APP
Authors: Li Zhigang , Moniruzzaman Mohammed , Dastgheyb Raha M. , Yoo Seung‐Wan , Wang Meina , Hao Hongbo , Liu Jia , Casaccia Patrizia , Nogueras‐Ortiz Carlos , Kapogiannis Dimitrios , Slusher Barbara S. , Haughey Norman J.
Published: January 2021

Chronic inflammation is thought to contribute to the early pathogenesis of Alzheimer's disease (AD). However, the precise mechanism by which inflammatory cytokines promote the formation and deposition of Aβ remains unclear. Available data suggest that applications of inflammatory cytokines onto isolated neurons do not promote the formation of Aβ, suggesting an indirect mechanism of action. Based on evidence astrocyte derived extracellular vesicles (astrocyte derived EVs) regulate neuronal functions, and data that inflammatory cytokines can modify the molecular cargo of astrocyte derived EVs, we sought to determine if IL‐1β promotes the formation of Aβ indirectly through actions of astrocyte derived EVs on neurons. The production of Aβ was increased when neurons were exposed to astrocyte derived EVs shed in response to IL‐1β (astrocyte derived EV‐IL‐1β). The mechanism for this effect involved an enrichment of Casein kinase 1 (CK1) in astrocyte derived EV‐IL‐1β. This astrocyte derived CK1 was delivered to neurons where it formed a complex with neuronal APC and GSK3 to inhibit the β‐catenin degradation. Stabilized β‐catenin translocated to the nucleus and bound toHnrnpcgene at promoter regions. An increased cellular concentration of hnRNP C promoted the translation of APP by outcompeting the translational repressor fragile X mental retardation protein (FMRP) bound to APP mRNA. An increased amount of APP protein became co‐localized with BACE1 in enlarged membrane microdomains concurrent with increased production of Aβ. These findings identify a mechanism whereby inflammation promotes the formation of Aβ through the actions of astrocyte derived EV‐IL‐1β on neurons.
Better modulation for risk decision‐making after optimized magnetic stimulation
Authors: Wang Lu , Wu Xingqi , Ji Gong‐Jun , Xiao Guixian , Xu Feifei , Yan Yibing , Wu Yang , Xi Chunhua , Chen Xingui , Wang Kai
Published: January 2021

Traditional repetitive transcranial magnetic stimulation can only produce a significant but weak effect on the cortex while theta burst stimulation (TBS), a patterned accelerated form of stimulation, can produce a stronger poststimulation effect, which may improve decision‐making abilities. We designed a comparative assessment of the effect of intermittent TBS (iTBS), 20 Hz, in two risk decision‐making tasks on healthy controls. Participants were randomized and assigned to the iTBS (n = 29), 20 Hz (n = 29), or sham (n = 29) groups. The effects of the different methods of left dorsolateral prefrontal cortex stimulation on risk decision‐making functions were compared based on subjects’ performance in the Game of Dice Task (GDT) and Risky Gains Task (RGT). The main indicators were positive and negative feedback utilization rates of GDT and RGT. Both iTBS and 20 Hz stimulation resulted in significant improvements upon negative feedback in the GDT, with increases in safe options and reductions in risky options; iTBS stimulation increased subjects’ use of positive feedback in the GDT and RGT (all p < 0.05). Furthermore, the iTBS group had a stronger feedback risk reduction effect than the 20 Hz or sham group following RGT negative feedback (p < 0.05). Individuals would integrate positive and negative information more efficiently, leading to them making rational choices after excitatory transcranial magnetic stimulation. Moreover, iTBS has a stronger risk reduction effect following negative feedback than the 20Hz stimulation did. In summary, iTBS might have clinical value in decision promotion.
Leading associations commit to agenda calling for transformation of care
Authors: Enos Gary
Published: January 2021

As leading mental health advocacy organizations closed 2020 by uniting around an effort to transform the system of care (see MHW, Dec. 21, 2020), the question remains: Can 2021 mark the realization of the kind of collective vision that revolutionized the nation's response to cancer in the 1970s and HIV/AIDS in the 1980s?
A rare opportunity for mental health in 2021
Authors: Gionfriddo Paul
Published: January 2021

A year ago, no one imagined how deeply we would all be affected by the pandemic. And no one predicted the incredible toll it would take on our mental health.
Readers reflect on opportunities, challenges following COVID
Authors: Canady Valerie A.
Published: January 2021

We asked our readers to send us their thoughts on the challenges and opportunities awaiting the field in 2021. Here are some of the comments we received. More to come next week.
Im Sauren überdauern
Authors: Vogt Oliver , Ukrainczyk Neven , Koenders Eddie
Published: January 2021

Bei optimaler Rohstoffzusammensetzung sind Geopolymere säurebeständiger als zementgebundene Baustoffe. Damit eignen sie sich als Bindemittel für stark korrosionsbeanspruchte Bauteile. Wie lange diese Bindemittel halten, hängt nicht nur von der für Geopolymere typischen Porosität ab.
Trendbericht Anorganische Chemie: Nebengruppen, Koordinationschemie, Bioanorganik und mehr
Authors: Becker Sabine , Rosca Dragos‐Adrian
Published: January 2021

Hauptgruppen: Beryllium radikalisiert sich, wohingegen das Bor seinen Zauber zeigt und Stickstoff in Ammoniak verwandelt. Silicium nimmt CO auf, und die Pnikogene vereinen sich erstmals alle in einer Verbindung. Nebengruppen und Koordinationschemie: das erste metallbasierte antiaromatische System, kristallisiertes UN2 und der erstmals isolierte kobaltbasierte σ‐Alkan‐Komplex.
Mit Kältemaschinen bis zum Nullpunkt
Authors: Ehrensberger Christian
Published: January 2021

Temperiersysteme für Chemielabore, Biotech oder Pharmaproduktion sollen umweltfreundlicher und effizienter werden. Als Innovationstreiber wirken dabei gesetzliche Vorgaben und die Neugier auf Quantencomputer.
Trendbericht Anorganische Chemie: Hauptgruppen
Authors: Sindlinger Christian , Hering‐Junghans Christian
Published: January 2021

Hauptgruppen: Beryllium radikalisiert sich, wohingegen das Bor seinen Zauber zeigt und Stickstoff in Ammoniak verwandelt. Silicium nimmt CO auf, und die Pnikogene vereinen sich erstmals alle in einer Verbindung. Nebengruppen und Koordinationschemie: das erste metallbasierte antiaromatische System, kristallisiertes UN2 und der erstmals isolierte kobaltbasierte σ‐Alkan‐Komplex.
Im Dunkeln schwimmen
Authors: Ziller Birgit , Leusmann Eliza
Published: January 2021

Künstliche Mikroschwimmer brauchen Energie, um voranzukommen, und nutzen dafür Licht. Eine neue Materialkombination speichert nun die Energie, sodass die Partikel sich auch im Dunkeln fortbewegen.
Verflixt verschachtelt
Authors: Groß Michael
Published: January 2021

Der Boden als funktionierendes Ökosystem ist wichtig für die Landwirtschaft und für natürliche Prozesse wie die Zersetzung von Pflanzenmaterialien und den Kohlenstoffkreislauf. Eine Metastudie zeigt, wie die Biodiversität im Boden eine Schlüsselrolle spielt und wie Schadstoffeinträge wirken.
50 Jahre Mitgliedschaft in der CG/GDCh – wir gratulieren!
Authors: Schreiner Peter R. , Koch Wolfram
Published: January 2021

Wir gratulieren herzlich unseren Kolleginnen und Kollegen zu ihren Goldenen Jubiläen in der GDCh bzw. zu ihren 50‐jährigen Mitgliedschaften in der Chemischen Gesellschaft der DDR (CG) und nach der Wiedervereinigung in der GDCh:
Salzwand und Plastikbaustein
Authors: Bulmahn Maren
Published: January 2021

Zum Wettbewerb zu nachhaltigem Bauen und Wohnen lieferten junge Unternehmen aus aller Welt Material‐ und Recyclingneuheiten.
Über Solarzellen
Authors: Leusmann Eliza
Published: January 2021

Alterungsprotokolle und Lösungsmitteleinfluss bei Perowskit‐Solarzellen sowie höherer und höchster Wirkungsgrad bei Chalcopyrit‐ beziehungsweise Tandemsolarzellen.
Improving management of psoriasis patients receiving biological treatment: A qualitative approach
Authors: Trettin Bettina , Feldman Steven , Andersen Flemming , Danbjørg Dorthe B. , Agerskov Hanne
Published: January 2021

Aim

To investigate psoriasis patients’ and healthcare professionals’ experiences and perspectives of follow‐up consultations.

Design

A qualitative study with a phenomenological‐hermeneutic approach.

Method

Participant observations of consultations and semi‐structured interviews were conducted with patients receiving biological treatment, together with two focus groups with healthcare professionals, from June 2018–January 2019. Data were analysed using a qualitative structured approach based on Paul Ricoeur's philosophy of interpretation.

Results

Consultations had a strong biomedical and corrective approach focusing on lifestyle behaviour change, measurements and permanent routines. Healthcare professionals felt the need for enhanced competencies providing lifestyle behaviour change support and the possibility of providing patients more specific strategies. They were faced with a dilemma between lacking the right skills and having a professional duty. The frequent follow‐up visits did not fit in with the patients’ everyday lives.
Knowledge-Based Innovations and Social Coordination
Authors: Leydesdorff Loet
Published: January 2021

Three themes have been central to my research program: (1) the dynamics of science, tech-nology, and innovation; (2) the scientometric operationalization and measurement of these dynamics; and (3) the Triple Helix (TH) of university-industry-government relations. In this introductory chapter, I relate these three themes first from an autobiographical perspective to (i)) Luhmann’s sociological theory about meaning-processing in communications with (ii) information-theoretical operationalizations of the possible synergies in Triple-Helix relations, and with (iii) anticipation as a selection mechanism in cultural evolutions different from “natural selection.” Interacting selection mechanisms can drive the development of redundancy; that is, options that are available, but have not yet been used. An increasing number of options is crucial for the viability of innovation systems more than is past performance. A calculus of redundancy different from and complementary to information calculus is envisaged.
Cultural and Biological Evolution
Authors: Leydesdorff Loet
Published: January 2021

Although there is no necessary relation between “big data” and “monism”—the program of reducing cultural and mental processes to computational and biological principles—both these programs reject a dualism between res extensa and res cogitans. Opposing this philosophy of science, I have argued in the above chapter that a second contingency of possible relations and expectations feeds back on the manifest relations. This second contingency cannot be studied from a natural-science or life-sciences perspective, but is the proper domain of the social sciences, where the focus is on what things mean as different from what they are. Next-order selection mechanisms can take evolutionary control. The complexity of the communication evolves against the arrow of time in terms of interacting codes, which generate redundancies and therefore new options. As human beings, we can follow the potentially unintended consequences of the communication dynamics reflexively. Both consciousness and communication are self-organizing and thus resilient against steering.
The Communication Turn in Philosophy of Science
Authors: Leydesdorff Loet
Published: January 2021

Whereas knowledge has often been attributed to individuals or, from a sociological perspective, to communities, a communications perspective on the sciences enables us to proceed to the measurement of the discursive knowledge contents. Knowledge claims are organized into texts which are entrained in evolving structures. The aggregated citation relations among journals, for example, can be used to visualize disciplinary structures. The structures are reproduced as “ecosystems” which differ among them in terms of using specific codes in the communications (e.g., jargons). Unlike biological DNA, these codes are not hard-wired; they can be changed in the communication. The sciences develop historically along trajectories embedded in regimes of expectations. Regimes exert selection pressure on the historical manifestations. The evolutionary dynamics at the regime level induce crises, bifurcations, etc., as historical events.
Scientific Communication and Codification
Authors: Leydesdorff Loet
Published: January 2021

In the sociology of scientific knowledge and the sociology of translation, heterogeneous networks have been studied in terms of practices and so-calledactor-networks. However, scientific practices are intellectually structured by codes. Cognitive structures interact and co-construct the organization of scholars and discourses into research programs, specialties, and disciplines. The intellectual organization of the sciences adds to and feeds back on the configurations of authors and texts. The social, textual, and cognitive sub-dynamicsselectupon each otherasymmetrically. Selections can further be selected for stabilization along trajectories and then also be globalized—symbolically generalized—into regimes of expectations.
Towards a Calculus of Redundancy
Authors: Leydesdorff Loet
Published: January 2021

In this chapter, I extend Shannon’s linear model of communication into a model in which communication is differentiated both vertically and horizontally (Simon, 1973). Following Weaver (1949), three layers are distinguished operating in relation to one another: (i) at level A, the events are sequenced historically along the arrow of time, generating Shannon-type information (that is, uncertainty); (ii) the incursion of meanings at level B is referential to (iii) horizons of meaning spanned by codes in the communication at level C. In other words, relations at level A are first distinguished fromcorrelationsamong patterns of relations and non-relations at level B. The correlations span a vector space on top of the network of relations.Relations are positionedin this vector space and can then be provided with meaning. Different positions provide other perspectives and horizons of meaning. Perspectives can overlap, for example, in Triple-Helix relations. Overlapping perspectives can generate redundancies—that is, new options—as a result of synergies.
Evolutionary and Institutional Triple Helix Models
Authors: Leydesdorff Loet
Published: January 2021

The institutional TH model focuses on relations of universities, industries, and governments in networks. Institutional arrangements develop over time along trajectories. The Triple-Helix metaphor of university-industry-government relations can also be elaborated into a neo-evolutionary model combining the vertical differentiation among the levels (in terms of relations, correlations, perspectives, and horizons of meaning) with the options for horizontal differentiation among the codes (e.g., markets, technologies, politics, etc., oper-ating in parallel). The neo-evolutionary model focuses on the interactions among selection mechanisms (markets, technologies, endowments) at the regime level. The historical and evolutionary dynamics feedback on each other. The relative weights of the historical versus evolutionary dynamics can be measured as a trade-off. Among three or more selection environments, synergy can be generated as redundancy on top of the aggregates of bilateral and unilateral contributions to the information flows. The number of new options available to an innovation system for realization may be as decisive for its survival more than the historical record of past performance.
Regions, Innovations, and the North–South Divide in Italy
Authors: Leydesdorff Loet
Published: January 2021

Using firm-level data collected by Statistics Italy for 2008, 2011, and 2015, the Triple-Helix synergy among geographical and size distributions of firms and technology classes is analyzed both regionally and nationally. The Italian system is both knowledge-based and knowledge-intensive, and therefore an interesting case. The contributions to national synergy of the twenty regions in Italy have increased between 2008 and 2015, but synergy generation at levels above the regions has remained relatively stable at approximately 45%. As against the statistical classification into twenty regions, or into Northern, Central, and Southern Italy, the greatest synergy is retrieved by defining the country in terms of Northern and Southern Italy as two sub-systems, with Tuscany included as part of Northern Italy. Different innovation strategies could be developed for these two parts of the country. However, the current focus on twenty regions for innovation policies may to some extent be an artefact of the statistics and EU policies. In terms of sectors, both medium- and high-tech manufacturing (MHTM) and knowledge-intensive services (KIS) are integrated proportionally in the various regions.
The Measurement of Synergy
Authors: Leydesdorff Loet
Published: January 2021

When policy-makers call for “interdisciplinarity,” they often mean “synergy.” Problem-solving requires crossing boundaries, such as those between disciplines. However, synergy can also be generated ininter-sectorial or geographical collaborations. Synergy is indicated when the whole offers more possibilities than the sum of its parts; “interdisciplinarity” can be an instrument for creating “synergy.” Synergy can be measured as an increase of redundancy; that is, the number of options which are available, but not-yet used. Instead of asking for the synergy among pre-defined categories, such as regions, sectors, size-classes, or nations, etc., I propose to let the most synergetic combinations among (potentially heterogenous) variables emerge from the data matrix. A synergy map can be drawn showing (cluster of) available but not-yet-realized options. A computer routine is made available at https://www.leydesdorff.net/software/synergy.triads which compares all possible triads in a data matrix in terms of their contributions to the synergy in a configuration.
Anticipation and the Dynamics of Expectations
Authors: Leydesdorff Loet
Published: January 2021

The operationalization of socio-cognitive structures in terms of observables such as texts (e.g., in discourse analysis and scientometrics) or the behavior of agents (e.g., in the sociology of scientific knowledge) may inadvertedly lead to reification. The dynamics of knowledge are not directly observable, but knowledge contents can be reconstructed. The reconstructions have the status of hypotheses; hypotheses can be tested against observations. Whereas agent-based modelling (ABM) focuses on observable behavior, simulations based on algorithms developed in the theory and computation of anticipatory systems (CASYS) enable us to visualize the incursive and recursive dynamics of knowledge at the individual level as different from the potentially hyper-incursive dynamics at the intersubjective level. The sciences can be considered as “strongly anticipatory” at this supra-individual level: expectations are discursively reconstructed in terms of next generations of expectations. This reflexive restructuring is embedded in historical dynamics on which it feeds back as a selection environment. The agents and texts entertain discursive models and thus be considered “weakly anticipatory” participants in the communication.
Subdynamics in Knowledge-Based Systems
Authors: Leydesdorff Loet
Published: January 2021

Using a set of six equations, I propose to model “interactions,” the “organization of meaning,” and “self-organization” as three coordination mechanisms among expectations; three further equations can be derived to operationalize “double contingency,” “identity,” and “reflection.” One can expect that the subdynamics update one another in co-evolutions as feedbacks and feed-forwards. Interfaces among two (sub)dynamics can be expected to operate with time differences (At). Interactions among horizontal and vertical time differences can generate hyper-incursivity in interhuman communications. Hyper-incursion enables us to reconstruct expectations. The social system is probably the only system which can be expected to carry “strong” anticipation while being reproduced as expectations. A system of expectations is not alive, is not constrained by a life-cycle, and does not need to “exist” otherwise than as expectations. The dynamics against the arrow of time are “cultural”: they rest on codes as the pillars of discursive knowledge driven upward into horizons of meaning.
Predicting the prognosis of hepatocellular carcinoma with the treatment of transcatheter arterial chemoembolization combined with microwave ablation using pretreatment MR imaging texture features
Authors: Liu Jun , Pei Yigang , Zhang Yu , Wu Yifan , Liu Fuquan , Gu Shanzhi
Published: January 2021

Objective

To investigate the prognostic value of baseline magnetic resonance imaging (MRI) texture analysis of hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA).

Methods

MRI was performed on 102 patients with HCC before receiving TACE combined with MWA in this retrospective study. The best 10 texture features were screened as a feature group for each MRI sequence by MaZda software using mutual information coefficient (MI), nonlinear discriminant analysis (NDA) and other methods. The optimal feature group with the lowest misdiagnosis rate was achieved on one MRI sequence between two groups dichotomized by 3-year survival, which was used to optimize the significant texture features with the optimal cutoff values. The Cox proportional hazards model was generated for the significant texture features and clinical variables to determine the independent predictors of overall survival (OS). The predictive performance of the model was further evaluated by the area under the ROC curve (AUC). Kaplan–Meier and log-rank tests were performed for disease-free survival (DFS) and Local recurrence-free survival (LRFS).

Results

The optimal feature group with the lowest misdiagnosis rate of 8.82% was obtained on T2WI using MI combined with NDA feature analysis. For Cox proportional hazards regression models, the independent prognostic factors associated with OS were albumin (P = 0.047), BCLC stage (P = 0.001), Correlat(1,− 1)T2 (P = 0.01) and SumEntrp(3,0)T2 (P = 0.015), and the prediction efficiency of multivariate model is AUC = 0.876, 95%CI = 0.803–0.949. Kaplan–Meier analyses further demonstrated that BCLC (P < 0.001), Correlat(1,− 1)T2 (P = 0.023) and SumEntrp(3,0)T2 (P < 0.001) were associated with DFS, and BCLC (P = 0.007) related to LRFS.

Conclusions

MR imaging texture features may be used to predict the prognosis of HCC treated with TACE combined with MWA.
Ideal Surgical Margin to Prevent Early Recurrence After Hepatic Resection for Hepatocellular Carcinoma
Authors: Nitta Hidetoshi , Allard Marc‐Antoine , Sebagh Mylène , Golse Nicolas , Ciacio Oriana , Pittau Gabriella , Vibert Eric , Sa Cunha Antonio , Cherqui Daniel , Castaing Denis , Bismuth Henri , Baba Hideo , Adam René
Published: January 2021

Backgrounds and Aims

Postoperative early recurrence after hepatic resection for hepatocellular carcinoma (HCC) poses a challenge to surgeons, and the effect of a surgical margin is still controversial. This study aimed to identify an ideal margin to prevent early recurrence.

Methods

A total of 226 consecutive patients who underwent primary curative hepatic resection for solitary and primary HCC were enrolled. The definition of early recurrence was determined using the minimum P value approach. Logistic regression analysis was used to identify the risk factors of early recurrence. The receiver‐operating characteristic (ROC) curve was used to identify the optimal cut‐off of the surgical margin and early recurrence.

Results

Recurrence within 8 months induced the poorest overall survival (P = 2×10−15). ROC analysis showed that the optimal cut‐off value of the surgical margin was 7 mm. The risk factors of early recurrence (≤ 8‐month recurrence) were preoperative alpha‐fetoprotein levels ≥ 100 ng/ml (Odds ratio [OR] 4.92 [2.28–10.77], P < 0.0001) and a surgical margin < 7 mm (OR 3.09 [1.26–8.85], P = 0.01) by multivariable analysis. The probability of early recurrence ranged from 5.0% in the absence of any factors to 43.5% in the presence of both factors. Among patients with alpha‐fetoprotein levels ≥ 100 ng/ml, non‐capsule formation, or microvascular invasion, there was a significant difference in 5‐year overall survival between surgical margins of < 7 mm and ≥ 7 mm.

Conclusions

A > 7‐mm margin is important to prevent early recurrence. Patients with HCC and alpha‐fetoprotein levels > 100 ng/ml, non‐capsule formation, or microvascular invasion may have a survival benefit from a ≥ 7‐mm margin.
An anatomy of Arctic sea ice forecast biases in the seasonal prediction system with EC-Earth
Authors: Cruz-García Rubén , Ortega Pablo , Guemas Virginie , Acosta Navarro Juan C. , Massonnet François , Doblas-Reyes Francisco J.
Published: January 2021

The quality of initial conditions (ICs) in climate predictions controls the level of skill. Both the use of the latest high-quality observations and of the most efficient assimilation method are of paramount importance. Technical challenges make it frequent to assimilate observational information independently in the various model components. Inconsistencies between the ICs obtained for the different model components can cause initialization shocks. In this study, we identify and quantify the contribution of the ICs inconsistency relative to the model inherent bias (in which the Arctic is generally too warm) to the development of sea ice concentration forecast biases in a seasonal prediction system with the EC-Earth general circulation model. We estimate that the ICs inconsistency dominates the development of forecast biases for as long as the first 24 (19) days of the forecasts initialized in May (November), while the development of model inherent bias dominates afterwards. The effect of ICs inconsistency is stronger in the Greenland Sea, in particular in November, and mostly associated to a mismatch between the sea ice and ocean ICs. In both May and November, the ICs inconsistency between the ocean and sea ice leads to sea ice melting, but it happens in November (May) in a context of sea ice expansion (shrinking). The ICs inconsistency tend to postpone (accelerate) the November (May) sea ice freezing (melting). Our findings suggest that the ICs inconsistency might have a larger impact than previously suspected. Detecting and filtering out this signal requires the use of high frequency data.
The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan
Authors: Sunami Kuniko , Naito Yoichi , Aimono Eriko , Amano Toraji , Ennishi Daisuke , Kage Hidenori , Kanai Masashi , Komine Keigo , Koyama Takafumi , Maeda Takahiro , Morita Sachi , Sakai Daisuke , Kohsaka Shinji , Tsuchihara Katsuya , Yoshino Takayuki
Published: January 2021

Background

Since June 2019, cancer genomic profiling (CGP) tests have been reimbursed by the National Health Insurance system in Japan, with restrictions for government-designated hospitals with a molecular tumor board composed of multidisciplinary specialists, known as an expert panel (EP). The standardization of EPs is a critical challenge for implementing precision oncology in the clinical setting.

Methods

Data on consecutive cases who underwent the CGP tests at 11 core hospitals between June 2019 and January 2020 were collected. We evaluated the proportions of cases that received genomically matched treatments, including investigational new drugs (INDs) based on CGP results, and/or for which genetic counseling was recommended. Two simulated cases were annotated by each EP. The annotated reports were then centrally assessed.

Results

Each EP mainly discussed the applicability to genomically matched treatments and the necessity of performing genetic counseling. A pre-review of the report by key members in each EP reportedly made the EP conference more interactive and efficient, and thereby saved time. A total of 747 cases underwent CGP tests, 28 cases (3.7%) received genomically matched treatment, and 17 cases (2.3%) were referred for genetic counseling. Annotated reports for the simulated cases varied across the EPs, particularly the number of recommended IND trials, which seemed to be associated with the actual number of participants in IND trials.

Conclusions

This investigation provides reference data for the application of precision oncology in a clinical setting. Further investigations on the standardization of clinical annotations are warranted.
The Empirical Under-Determination Argument Against Scientific Realism for Dual Theories
Authors: De Haro Sebastian
Published: January 2021

This paper explores the options available to the anti-realist to defend a Quinean empirical under-determination thesis using examples of dualities. I first explicate a version of the empirical under-determination thesis that can be brought to bear on theories of contemporary physics. Then I identify a class of examples of dualities that lead to empirical under-determination . But I argue that the resulting under-determination is benign, and is not a threat to a cautious scientific realism. Thus dualities are not new ammunition for the anti-realist. The paper also shows how the number of possible interpretative options about dualities that have been considered in the literature can be reduced, and suggests a general approach to scientific realism that one may take dualities to favour.
Effectiveness of VR Head Mounted Displays in Professional Training: A Systematic Review
Authors: Renganayagalu Sathiya kumar , Mallam Steven C. , Nazir Salman
Published: January 2021

Over the past decade, virtual reality (VR) has re-emerged as a popular technology trend. This is mainly due to the recent investments from technology companies that are improving VR systems while increasing consumer access and interest. Amongst many applications of VR, one area that is particularly promising is for pedagogy. The immersive, experiential learning offered by VR provides new training and learning opportunities driven by the latest versions of affordable, highly immersive and easy to use head mounted display (HMD) systems. VR has been tested as a tool for training across diverse settings with varying levels of success in the past. However, there is a lack of recent review studies that investigates the effectiveness, advantages, limitations, and feasibility of using VR HMDs in training. This review aims to investigate the extent to which VR applications are useful in training, specifically for professional skill and safety training contexts. In this paper, we present the results from a systematic review of the effectiveness of VR-based simulation training from the past 30 years. As a secondary aim, the methodological trends of application and practical challenges of implementing VR in training curriculum were also assessed. The results suggest that there is generally high acceptance amongst trainees for VR-based training regardless of the technology limitations, usability challenges and cybersickness. There is evidence that VR is useful for training cognitive skills, such as spatial memory, learning and remembering procedures and psychomotor skills. VR is also found to be a good alternative where on the job training is either impossible or unsafe to implement. However, many training effectiveness studies reviewed lack experimental robustness due to limited study participants and questionable assessment methods. These results map out the current known strengths and weaknesses of VR HMDs and provide insight into required future research areas as the new era of VR HMD’s evolve.
Identification and validation of suitable reference genes for quantitative real-time PCR gene expression analysis in pregnant human myometrium
Authors: Arrowsmith Sarah
Published: January 2021

Accurate quantification of quantitative PCR (qPCR) data requires a set of stable reference genes (RGs) for normalisation. Despite its importance to mechanistic studies, no evaluation of RG stability has been conducted for pregnant human myometrium. A systematic search of the literature was performed to identify the most used RGs in human myometrial gene expression studies. The stability of these genes, and others, was then evaluated using geNorm and NormFinder algorithms, in samples of myometrium from singleton or twin pregnancies (n = 7 per group) delivering at term or preterm. The most frequently cited RGs wereGAPDH, ACTB, B2M and 18s.There was strong agreement between algorithms on the most and least stable genes: Both indicatedCYC1, YWHAZandATP5Bwere the most stably expressed. Despite being some of the most used RGs,B2M,18sandACTBexpression was least stable and was too variable for use as accurate normalisation factors. Pairwise variation analysis determined that the optimal number of RGs for accurate normalisation is two. Validation of the choice of RGs by comparing relative expression of oxytocin receptors (OXTR)using the least stable18sandB2M, with the most stable,CYC1andYWHAZ, erroneously demonstrated significantly increasedOXTRexpression in myometrium in singleton pregnancies compared to twins. This study demonstrates the importance of appropriate RG selection for accurate quantification of relative expression in pregnant human myometrium qPCR studies. For normalisation, the geometric mean ofCYC1andYWHAZ or ATP5Bis suggested. The use ofACTB, 18sandB2M, is not recommended.
PIK3CA somatic alterations in invasive breast cancers: different spectrum from Caucasians to Chinese detected by next generation sequencing
Authors: Jia Minghan , Liao Ning , Chen Bo , Zhang Guochun , Wang Yulei , Li Xuerui , Cao Li , Mok Hsiaopei , Ren Chongyang , Li Kai , Li Cheukfai , Wen Lingzhu , Lin Jiali , Wei Guangnan , Balch Charles M.
Published: January 2021

Purpose

Somatic alteration of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a crucial therapeutic target in breast cancer (BC) and PI3Kα-specific inhibitor Alpelisib has been used in clinics. This study investigates the PIK3CA alterations in Chinese and Caucasians BC patients for the purpose of selecting anti-PI3K therapy.

Methods

The molecular profile of the PIK3CA gene was analyzed in 412 Chinese patients with untreated invasive BC using a 540 gene next-generation sequencing panel. The results were compared with data of the Caucasian BC patients in The Cancer Genome Atlas (TCGA-white).

Results

PIK3CA alterations were frequently found in BC of estrogen receptor (ER) positive (49.3%, p = 0.024), low ki67 proliferation index (58.3%, p = 0.007) and low pathological grade (grade I/II/III 80%, 53.4%, 35.9%, p < 0.001). Compared to TCGA-white, Chinese BC patients had a higher alteration frequency (45.6% vs. 34.7%, p < 0.001) with larger proportion of p.H1047R mutation among three common mutation sites (p.E545K, p.E542K and p.H1047R) (66.1% vs. 43.7%, p = 0.01). Across four molecular subtypes, ER + /human epidermal growth factor receptor 2 positive (HER2 +) tumors harbored the most PIK3CA alterations (51.6%), while ER-/HER2- harbored the least alteration (30.0%) but the most copy number amplification (19.05%).

Conclusion

PIK3CA alterations prevail in Chinese BC patients and have different molecular features compared to that of Caucasians. The results provide precise annotations of PIK3CA genomic alterations of Chinese in the context of application of PIK3CA inhibitor.