bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of L‐thyroxine administration on long‐term potentiation and accompanying mitogen‐activated protein kinases in rats
Authors: Tan Burak , Babur Ercan , Aşçıoğlu Meral , Süer Cem
Published: February 2021

The present study investigated the differences in the activation of c‐Jun NH2‐terminal kinases (JNK), p38 mitogen‐activated protein kinases (p38MAPK), and extracellular signal‐regulated kinases 1/2 (Erk1/2) 1 hr after the induction of long‐term potentiation (LTP) between rats with hyperthyroidism that was produced at two different stages of development. Hyperthyroidism was produced in rats by daily injections of L‐thyroxine (T4, ip., 0.2 mg/kg) to their dams for lactation period or to the rats itself during the young adult period. LTP was induced by application of high‐frequency stimulation protocol. Five‐min averages of the excitatory postsynaptic potential (EPSP) slopes and population spike (PS) amplitudes at the end of recording were averaged to measure the magnitude of LTP. Total and phosphorylated levels of Erk1/2, JNK, and P38‐MAPK were assessed via western blotting in these hippocampi. LTP was found to be impaired in both groups of hyperthyroidisms, but this impairment observed together with increased expression and phosphorylation of ERK1/2, and increased phosphorylation of JNK in rats treated maternally with T4 compared to those treated adultly. These results suggest that excessiveness of thyroid hormone has longstanding effects on hippocampal function and may account for failed LTP in both early and relatively late stage of development depending on various molecular pathways, such as ERK1/2 and JNK.
Expansion of drylands in China with an additional half a degree warming
Authors: Yang Qing , Chen Liang , Duan Yawen , Jian Dongnan , Ma Zhuguo
Published: February 2021

To contribute a more ambitious target of Paris Agreement, that is, limiting global warming to 1.5°C instead of 2.0°C above preindustrial levels, it is essential to quantitatively reveal regional impacts of an additional 0.5°C warming to inform climate policymaking. Based on bias‐corrected simulations of four models from the half a degree additional warming, prognosis and projected impacts (HAPPI), we examine how dry–wet condition may change in China at 1.5 and 2.0°C warming levels, focusing on the projected changes in the area of drylands. Results showed that China is projected to be dominated by a decrease Surface Wetness Index (SWI), due to a larger increase in potential evapotranspiration (PET) than precipitation, implying a drying signal, in both 1.5 and 2.0°C warming levels against a present‐day scenario. Correspondingly, an expansion of drylands is expected, the larger expansion with the higher warming level, with changes approximately 0.77 ± 2.02% in 1.5°C level, and 2.29 ± 2.69% in 2.0°C level, although there exists considerable intermodel variability. For an additional warming of 0.5°C, there is high confidence of the projected decrease of SWI and expansion of drylands, approximately 1.52 ± 0.77%. That is to say, limiting global warming to 1.5°C is suggested to robustly reduce the likelihood of emerging aridification compared to 2°C, and China might obtain considerable benefits in term of socio‐economic impacts related to the reduction of aridification. Thus, it is necessary for continued efforts to limit global warming to 1.5°C.
Assessment of GCMs simulation performance for precipitation and temperature from CMIP5 to CMIP6 over the Tibetan Plateau
Authors: Lun Yurui , Liu Liu , Cheng Lei , Li Xiuping , Li Hao , Xu Zongxue
Published: February 2021

General circulation models (GCMs) are indispensable for climate change adaptive study over the Tibetan Plateau (TP), which is the potential trigger and amplifier in global climate fluctuations. With the release of Coupled Model Intercomparison Project Phase 6 (CMIP6), 24 GCMs from CMIP5 and CMIP6 were comparatively evaluated for precipitation and air temperature simulations based on the China Meteorological Forcing Dataset (CMFD). Rank score results showed that CMIP6 models generally performed better than CMIP5 for precipitation and surface air temperature over the TP. According to multimodel ensembles (MMEs) of the optimal GCMs for each climate variable, the overestimation of precipitation was both present in CMIP5 and CMIP6, but the results of CMIP6 MMEs were relatively lower in the mid‐west and northern edge of the TP. Furthermore, CMIP6 offered a better performance of precipitation in summer and autumn. For temperature, CMIP6 MMEs were able to reduce the relatively large cold bias that appeared in CMIP5 MMEs in northwest areas to about 1°C and had a smaller bias in spring and winter. Moreover, the investigation into the simulation effects of precipitation at different elevation zones demonstrated that the improved ability of CMIP6 MMEs to reduce bias was mainly concentrated in the elevation zones of 2,000–3,000 m and over 5,000 m, where the precipitation bias was more than 200%. Additionally, CMIP6 MMEs of temperature were able to reduce the bias to less than 2°C in each elevation zone, with the minimum bias of −0.22°C distributed in the region with altitudes from 3,000 to 4,000 m, while the biases of CMIP5 MMEs in the region of 4,000–5,000 m and over 5,000 m were smaller than those of CMIP6 MMEs. Findings obtained in this study could provide a scientific reference for related climate change research over the TP. GCMs of CMIP6 perform better than those of CMIP5 for precipitation and temperature over the TP. Multimodel ensembles (MMEs) of CMIP6 effectively reduce the overestimation of precipitation from CMIP5 MMEs by 40 mm at the annual scale. Improved ability of CMIP6 MMEs shows a significant elevation dependency, especially in elevation zones of 2,000–3,000 m and over 5,000 m for precipitation.
MeRef: Multivariable extrapolated reference values in motor nerve conduction studies
Authors: Nandedkar Sanjeev D. , Stålberg Erik V. , Barkhaus Paul E.
Published: February 2021

Introduction

In this study we describe a method called “multivariable extrapolated reference values” (MeRef) that derives reference values (RVs) using patient data and includes the dependence of these variables on multiple patient demographic variables, such as age and height.

Methods

Computer simulations were used to generate “normal” and “patient” nerve conduction data. Median, ulnar, and tibial motor nerve conduction data from 500 patients studied were tabulated. Data were analyzed using the MeRef method.

Results

The simulations showed great similarity between RVs obtained from MeRef of “patient” data and traditional analysis of “normal” data. In the real patient data, MeRef gave RVs as regression equations based on patient age and/or height.

Discussion

MeRef can provide RVs by including patient demographic data and does not require subject grouping. It provides parameters of multivariable linear regression and standard deviation, and requires a few hundred patient studies to define reference values.
Abundance, Movement, Population Dynamics, and Management Implications of Channel Catfish in a Mid-Atlantic River
Authors: Keplinger Brandon J.
Published: February 2021

Riverine Channel Catfish Ictalurus punctatus are largely unregulated in West Virginia, while recreational angling interest for the species is emerging. This study focuses on hoop-net assessments of the species’ size structure and abundance across a longitudinal continuum of the fifth-order, low- to moderate-gradient South Branch of the Potomac River (SBR). Population growth, annual mortality, angler exploitation, and angler-reported movement were also assessed. Five pools were sampled during June–September in 2012–2017. Channel Catfish were measured for TL, fin-clipped, and tagged with a T-bar anchor tag. Lapillar otoliths were collected during September samples for growth analyses. Multiple-census models and CPUE data were employed to estimate abundance. Channel Catfish CPUE and size structure increased downstream, and sexually dimorphic growth was documented. The oldest fish aged was a 19-year-old female. Annual mortality rate was estimated at 19.1%. Angler return data indicated that 36% of fish reported by anglers were harvested, but only 6% of tags were returned. Angler exploitation was estimated at 2.3%. Channel Catfish in the SBR were highly mobile. Two fish were captured by anglers 188 km downstream of their tagging location, and an upstream movement of 97 km was detected by hoop-net recapture between sites. Dynamic function estimates for this population do not indicate a need for regulatory management. However, population modeling could be useful to determine when angling impacts on density or size structure may develop.
Investigating the folding mechanism of the N‐terminal domain of ribosomal protein L9
Authors: Zhang Haozhe , Zhang Haomiao , Chen Changjun
Published: February 2021

Protein folding is a popular topic in the life science. However, due to the limited sampling ability of experiments and simulations, the general folding mechanism is not yet clear to us. In this work, we study the folding of the N‐terminal domain of ribosomal protein L9 (NTL9) in detail by a mixing replica exchange molecular dynamics method. The simulation results are close to previous experimental observations. According to the Markov state model, the folding of the protein follows a nucleation‐condensation path. Moreover, after the comparison to its 39‐residue β‐α‐β motif, we find that the helix at the C‐terminal has a great influence on the folding process of the intact protein, including the nucleation of the key residues in the transition state ensemble and the packing of the hydrophobic residues in the native state.
Humans Judged by Machines: The Rise of Artificial Intelligence in Finance, Insurance, and Real Estate
Authors: Pasquale Frank
Published: February 2021

There are opportunities but also worrisome trends as AI is applied in finance, insurance, and real estate. In these domains, persons are increasingly assessed and judged by machines. The financial technology (Fintech) landscape ranges from automation of office procedures, to new approaches for storing and transferring value, to the granting of credit. The Fintech landscape can be separated into “incrementalist Fintech” and “futurist Fintech.” Incrementalist Fintech uses data, algorithms, and software to complement professionals who perform traditional tasks of existing financial institutions. It promises financial inclusion, but this inclusion can be predatory, creepy, and subordinating. These forms of financial inclusion undermine their solvency, dignity, and political power of borrowers. Futurist Fintech’s promoters claim to be more equitable, but are likely to falter in their aspiration to substitute technology for key financial institutions. When used to circumvent or co-opt state monetary authorities, both incrementalist and futurist Fintech expose deep problems at the core of the contemporary digitization of finance.
Human–Robot Interactions and Affective Computing: The Ethical Implications
Authors: Devillers Laurence
Published: February 2021

The field of social robotics is fast developing and will have wide implications especially within health care, where much progress has been made towards the development of “companion robots.” Such robots provide therapeutic or monitoring assistance to patients with a range of disabilities over a long timeframe. Preliminary results show that such robots may be particularly beneficial for use with individuals who suffer from neurodegenerative pathologies. Treatment can be accorded around the clock and with a level of patience rarely found among human healthcare workers. Several elements are requisite for the effective deployment of companion robots. They must be able to detect human emotions and in turn mimic human emotional reactions as well as having an outward appearance that corresponds to human expectations about their caregiving role. This chapter presents laboratory findings on AI-systems that enable robots to recognize specific emotions and to adapt their behavior accordingly. Emotional perception by humans (how language and gestures are interpreted by us to grasp the emotional states of others) is being studied as a guide to programming robots so they can simulate emotions in their interactions with humans.
Could a Robot Be Conscious? Some Lessons from Philosophy
Authors: Gabriel Markus
Published: February 2021

In this chapter, the question whether robots could be conscious is evaluated from a philosophical perspective. The position taken is that the human being is the indispensable locus of ethical discovery. Questions concerning what we ought to do as morally equipped agents subject to normative guidance largely depend on our synchronically and diachronically varying answers to the question of “who we are.” It is argued here, that robots are not conscious and could not be conscious, where consciousness is understood as a systemic feature of the animal-environment relationship. It is suggested, that ethical reflection yields the result that we ought not to produce cerebral organoids implanted in a robotic “body.”
Robotics and AI in Food Security and Innovation: Why They Matter and How to Harness Their Power
Authors: Torero Maximo
Published: February 2021

From strawberry-picking robots to satellite remote sensing and GIS techniques that forecast crop yields, the integration of robotics and AI in agriculture will play a key role in sustainably meeting the growing food demand of the future. But it also carries the risk of alienating a certain population, such as smallholder farmers and rural households, as digital technologies tend to be biased toward those with higher-level skills. To ensure that digital technologies are inclusive and become a driver for development, countries should make technology affordable and invest in institutions and human capital, so that everyone can participate in the new digital economy. Digital agriculture also represents an opportunity for young people as agriculture value chains can be developed to create new service jobs in rural areas, making agriculture an attractive sector for youth.
Robotics in the Classroom: Hopes or Threats?
Authors: Léna Pierre
Published: February 2021

Artificial intelligence implemented in a great diversity of systems, such as smartphones, computers, or robots, is progressively invading almost all aspects of life. Education is already concerned by this revolution, as are medicine or care for elderly people. Education is indeed a special case, because it is fundamentally based on the relationship, involving love and emotions as well as knowledge, between a fragile child and an adult. But teachers are becoming rare and education expensive: The Earth demography is here an economical challenge. We examine some of the various modalities of teacher substitution, companionship or computer-resources which are already experimented, and discuss their ethical aspects. We conclude on the positive aspects of computer-aided education, which does not substitute the teacher, but may help and provide continued professional development.
Skyrmion interactions and lattices in chiral magnets: analytical results
Authors: Ross Calum , Sakai Norisuke , Nitta Muneto
Published: February 2021

Abstract

We study two-body interactions of magnetic skyrmions on the plane and apply them to a (mostly) analytic description of a skyrmion lattice. This is done in the context of the solvable line, a particular choice of a potential for magnetic anisotropy and Zeeman terms, where analytic expressions for skyrmions are available. The energy of these analytic single skyrmion solutions is found to become negative below a critical point, where the ferromagnetic state is no longer the lowest energy state. This critical value is determined exactly without the ambiguities of numerical simulations. Along the solvable line the interaction energy for a pair of skyrmions is repulsive with power law fall off in contrast to the exponential decay of a purely Zeeman potential term. Using the interaction energy expressions we construct an inhomogeneous skyrmion lattice state, which is a candidate ground states for the model in particular parameter regions. Finally we estimate the transition between the skyrmion lattice and an inhomogeneous spiral state.
Entanglement entropy for $$ \mathrm{T}\overline{\mathrm{T}} $$, $$ \mathrm{J}\overline{\mathrm{T}} $$, $$ \mathrm{T}\overline{\mathrm{J}} $$ deformed holographic CFT
Authors: Chakraborty Soumangsu , Hashimoto Akikazu
Published: February 2021

Abstract

We derive the geodesic equation for determining the Ryu-Takayanagi surface in AdS3 deformed by single trace $$ \mu T\overline{T} $$
μT

T
¯

+ $$ {\varepsilon}_{+}J\overline{T} $$

ε
+

J

T
¯

+ $$ {\varepsilon}_{-}T\overline{J} $$

ε
−

T

J
¯

deformation for generic values of (μ, ε+, ε−) for which the background is free of singularities. For generic values of ε±, Lorentz invariance is broken, and the Ryu-Takayanagi surface embeds non-trivially in time as well as spatial coordinates. We solve the geodesic equation and characterize the UV and IR behavior of the entanglement entropy and the Casini-Huerta c-function. We comment on various features of these observables in the (μ, ε+, ε−) parameter space. We discuss the matching at leading order in small (μ, ε+, ε−) expansion of the entanglement entropy between the single trace deformed holographic system and a class of double trace deformed theories where a strictly field theoretic analysis is possible. We also comment on expectation value of a large rectangular Wilson loop-like observable.
Loop effect in the coherent neutrino-nucleus scattering
Authors: Li Tong , Liao Jiajun
Published: February 2021

Abstract

A connection between the neutrino and an exotic fermion is described in the general neutrino model. In this model the neutrinos can convert into the new fermion and thus the interaction leads to novel recoil spectrum in the neutrino scattering experiments. We study the general neutrino interaction by evaluating both the tree-level and loop-level contributions to the coherent elastic neutrino-nucleus scattering. We illustrate the scattering by taking the framework of a simplified neutrino model with a Dirac fermion χ and a spin-0 mediator. For the CP phase in the quark sector being 0 and π/2, the detection processes are dominated by the tree-level and loop-level contribution, respectively. We investigate the constraints on the couplings between the mediator and the new particle χ or the quarks by fitting to the COHERENT data. The parameter space with mχ larger than the maximal energy of incoming neutrinos can be also constrained by including the loop-level contribution.
DK I = 0, $$ D\overline{K} $$ I = 0, 1 scattering and the $$ {D}_{s0}^{\ast } $$(2317) from lattice QCD
Authors:   for the Hadron Spectrum Collaboration, Cheung Gavin K. C. , Thomas Christopher E. , Wilson David J. , Moir Graham , Peardon Michael , Ryan Sinéad M.
Published: February 2021

Abstract

Elastic scattering amplitudes for I = 0 DK and I = 0, 1 $$ D\overline{K} $$
D

K
¯

are computed in S, P and D partial waves using lattice QCD with light-quark masses corresponding to mπ = 239 MeV and mπ = 391 MeV. The S-waves contain interesting features including a near-threshold JP = 0+ bound state in I = 0 DK, corresponding to the $$ {D}_{s0}^{\ast } $$

D

s
0

∗

(2317), with an effect that is clearly visible above threshold, and suggestions of a 0+ virtual bound state in I = 0 $$ D\overline{K} $$
D

K
¯

. The S-wave I = 1 $$ D\overline{K} $$
D

K
¯

amplitude is found to be weakly repulsive. The computed finite-volume spectra also contain a deeply-bound D* vector resonance, but negligibly small P -wave DK interactions are observed in the energy region considered; the P and D-wave $$ D\overline{K} $$
D

K
¯

amplitudes are also small. There is some evidence of 1+ and 2+ resonances in I = 0 DK at higher energies.
Therapie des nicht-fernmetastasierten CRPC
Authors: Hadaschik Boris , Hellmis Eva
Published: February 2021

Bei Patienten mit nicht-fernmetastasiertem kastrationsresistentem Prostatakarzinom (nmCRPC oder M0CRPC) und hohem Progressionsrisiko (definiert als PSA-Verdopplungszeit ≤ 10 Monate) stellen selektive Androgenrezeptorinhibitoren (ARI) der neuen Generation in Kombination mit fortgeführter Androgendeprivationstherapie (ADT) den neuen Therapiestandard dar. Zugelassen sind derzeit Apalutamid, Enzalutamid und Darolutamid, die im Vorfeld bereits in den jeweiligen großen Phase-III-Zulassungsstudien SPARTAN, PROSPER und ARAMIS ihren primären Endpunkt metastasenfreies Überleben (MFS) erreicht hatten und jetzt nach längerer Nachbeobachtungszeit auch einen statistisch signifikanten und klinisch relevanten Gesamtüberlebensvorteil gegenüber Placebo plus ADT zeigen konnten. Die bisherige Datenlage weist auf eine vergleichbar gute Effektivität aller drei Substanzen bei insgesamt guter Verträglichkeit hin. Auch die generell gute Lebensqualität dieser Patientenpopulation, die in der Regel noch keine tumorbedingten Symptome aufweist, konnte erhalten werden. Direkt vergleichende Head-to-head-Studien der drei zugelassenen Substanzen liegen bislang nicht vor.
Phosphodiesterases 2, 3 and 4 can decrease cardiac effects of H2-histamine-receptor activation in isolated atria of transgenic mice
Authors: Neumann Joachim , Voss Rafaela , Laufs Ulrich , Werner Christian , Gergs Ulrich
Published: February 2021

Histamine exerts cAMP-dependent positive inotropic effects (PIE) and positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic mice which overexpress the human H2-receptor in the heart (=H2-TG). To determine whether these effects are antagonized by phosphodiesterases (PDEs), contractile studies were done in isolated left and right atrial preparations of H2-TG. The contractile effects of histamine were tested in the additional presence of the PDE-inhibitorserythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA, 1 μM, PDE2-inhibitor) or cilostamide (1 μM, PDE3-inhibitor), rolipram (10 μM, a PDE4-inhibitor), and their combinations. Cilostamide (1 μM) and EHNA (1 μM), rolipram (1 μM), and EHNA (1 μM) and the combination of rolipram (0.1 μM) and cilostamide (1 μM) each increased the potency of histamine to elevate the force of contraction (FOC) in H2-TG. Cilostamide (1 μM) and rolipram (10 μM) alone increased and EHNA (1 μM) decreased alone, and their combination increased the potency of histamine to increase the FOC in H2-TG indicating that PDE3 and PDE4 regulate the inotropic effects of histamine in H2-TG. The PDE inhibitors (EHNA, cilostamide, rolipram) alone did not alter the potency of histamine to increase the heart beat in H2-TG whereas a combination of rolipram, cilostamide, and EHNA, or of rolipram and EHNA increased the potency of histamine to act on the beating rate. In summary, the data suggest that the PCE of histamine in H2-TG atrium involves PDE 2 and 4 activities, whereas the PIE of histamine are diminished by activity of PDE 3 and 4.
Can Left Atrioventricular Valve Reduction Index (LAVRI) Predict the Surgical Strategy for Repair of Atrioventricular Septal Defect?
Authors: Schleiger Anastasia , Kramer Peter , Schafstedde Marie , Yigitbasi Mustafa , Danne Friederike , Murin Peter , Cho Mi-Young , Photiadis Joachim , Berger Felix , Ovroutski Stanislav
Published: February 2021

Despite improved survival, surgical treatment of atrioventricular septal defect (AVSD) remains challenging. The optimal technique for primary left atrioventricular valve (LAVV) repair and prediction of suitability for biventricular approach in unbalanced AVSD are still controversial. We evaluated the ability of our recently developed echocardiographic left atrioventricular valve reduction index (LAVRI) in predicting LAVV reoperation rate and surgical strategy for unbalanced AVSD. Retrospective echocardiographic analysis was available in 352 of 790 patients with AVSD treated in our institution and included modified atrioventricular valve index (mAVVI), ventricular cavity ratio (VCR), and right ventricle/left ventricle (RV/LV) inflow angle. LAVRI estimates LAVV area after complete cleft closure and was analyzed with regard to surgical strategy in primary LAVV repair and unbalanced AVSD. Of the entire cohort, 284/352 (80.68%) patients underwent biventricular repair and 68/352 (19.31%) patients underwent univentricular palliation. LAVV reoperation was performed in 25/284 (8.80%) patients after surgical correction of AVSD. LAVRI was significantly lower in patients requiring LAVV reoperation (1.92 cm2/m2 [IQR 1.31] vs. 2.89 cm2/m2 [IQR 1.37], p = 0.002) and significantly differed between patients receiving complete and no/partial cleft closure (2.89 cm2/m2 [IQR 1.35] vs. 2.07 cm2/m2 [IQR 1.69]; p = 0.002). Of 82 patients diagnosed with unbalanced AVSD, 14 were suitable for biventricular repair (17.07%). mAVVI, LAVRI, VCR, and RV/LV inflow angle accurately distinguished between balanced and unbalanced AVSD and predicted surgical strategy (all p < 0.001). LAVRI may predict surgical strategy in primary LAVV repair, LAVV reoperation risk, and suitability for biventricular approach in unbalanced AVSD anatomy.
Host defence peptides identified in human apolipoprotein B as promising antifungal agents
Authors: Dell’Olmo Eliana , Gaglione Rosa , Cesaro Angela , Cafaro Valeria , Teertstra Wieke R. , de Cock Hans , Notomista Eugenio , Haagsman Henk P. , Veldhuizen Edwin J. A. , Arciello Angela
Published: February 2021

Therapeutic options to treat invasive fungal infections are still limited. This makes the development of novel antifungal agents highly desirable. Naturally occurring antifungal peptides represent valid candidates, since they are not harmful for human cells and are endowed with a wide range of activities and their mechanism of action is different from that of conventional antifungal drugs. Here, we characterized for the first time the antifungal properties of novel peptides identified in human apolipoprotein B. ApoB-derived peptides, here named r(P)ApoBLPro, r(P)ApoBLAla and r(P)ApoBSPro, were found to have significant fungicidal activity towards Candida albicans (C. albicans) cells. Peptides were also found to be able to slow down metabolic activity of Aspergillus niger (A. niger) spores. In addition, experiments were carried out to clarify the mechanism of fungicidal activity of ApoB-derived peptides. Peptides immediately interacted with C. albicans cell surfaces, as indicated by fluorescence live cell imaging analyses, and induced severe membrane damage, as indicated by propidium iodide uptake induced upon treatment of C. albicans cells with ApoB-derived peptides. ApoB-derived peptides were also tested on A. niger swollen spores, initial hyphae and branched mycelium. The effects of peptides were found to be more severe on swollen spores and initial hyphae compared to mycelium. Fluorescence live cell imaging analyses confirmed peptide internalization into swollen spores with a consequent accumulation into hyphae. Altogether, these findings open interesting perspectives to the application of ApoB-derived peptides as effective antifungal agents.

Key points

Human cryptides identified in ApoB are effective antifungal agents.

ApoB-derived cryptides exert fungicidal effects towards C. albicans cells.

ApoB-derived cryptides affect different stages of growth of A. niger.

Graphical abstract
PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung
Authors: Goldmann Torsten , Marwitz Sebastian , Nitschkowski Dörte , Krupar Rosemarie , Backman Max , Elfving Hedvig , Thurfjell Viktoria , Lindberg Amanda , Brunnström Hans , La Fleur Linnea , Mezheyeuski Artur , Mattsson Johanna Sofia Margareta , Botling Johan , Micke Patrick , Strell Carina
Published: February 2021

Gene amplification is considered to be one responsible cause for upregulation of Programmed Death Ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) and to represent a specific molecular subgroup possibly associated with immunotherapy response. Our aim was to analyze the frequency of PD-L1 amplification, its relation to PD-L1 mRNA and protein expression, and to characterize the immune microenvironment of amplified cases. The study was based on two independent NSCLC cohorts, including 354 and 349 cases, respectively. Tissue microarrays were used to evaluate PD-L1 amplification by FISH and PD-L1 protein by immunohistochemistry. Immune infiltrates were characterized immunohistochemically by a panel of immune markers (CD3, CD4, CD8, PD-1, Foxp3, CD20, CD138, CD168, CD45RO, NKp46). Mutational status was determined by targeted sequencing. RNAseq data was available for 197 patients. PD-L1 amplification was detected in 4.5% of all evaluable cases. PD-L1 amplification correlated only weakly with mRNA and protein expression. About  37% of amplified cases were negative for PD-L1 protein. PD-L1 amplification did not show any association with the mutational status. In squamous cell cancer, PD-L1 amplified cases were enriched among patients with high tumoral immune cell infiltration and showed gene expression profiles related to immune exhaustion. In conclusion, PD-L1 amplification correlates with PD-L1 expression in squamous cell cancer and was associated with an immune cell rich tumor phenotype. The correlative findings help to understand the role of PD-L1 amplification as an important immune escape mechanism in NSCLC and suggest the need to further evaluate PD-L1 amplification as predictive biomarker for checkpoint inhibitor therapy.
Regulatory T cells promote glioma cell stemness through TGF-β–NF-κB–IL6–STAT3 signaling
Authors: Liu Shasha , Zhang Chaoqi , Wang Boqiao , Zhang Huanyu , Qin Guohui , Li Congcong , Cao Ling , Gao Qun , Ping Yu , Zhang Kai , Lian Jingyao , Zhao Qitai , Wang Dan , Zhang Zhen , Zhao Xuan , Yang Li , Huang Lan , Yang Bo , Zhang Yi
Published: February 2021

Glioma stem cells (GSCs) contribute to the malignant growth of glioma, but little is known about the interaction between GSCs and tumor microenvironment. Here, we found that intense infiltration of regulatory T cells (Tregs) facilitated the qualities of GSCs through TGF-β secretion that helped coordinately tumor growth. Mechanistic investigations indicated that TGF-β acted on cancer cells to induce the core cancer stem cell-related genes CD133, SOX2, NESTIN, MUSASHI1 and ALDH1A expression and spheres formation via NF-κB–IL6–STAT3 signaling pathway, resulting in the increased cancer stemness and tumorigenic potential. Furthermore, Tregs promoted glioma tumor growth, and this effect could be abrogated with blockade of IL6 receptor by tocilizumab which also demonstrated certain level of therapeutic efficacy in xenograft model. Additionally, expression levels of CD133, IL6 and TGF-β were found to serve as prognosis markers of glioma patients. Collectively, our findings reveal a new immune-associated mechanism underlying Tregs-induced GSCs. Moreover, efforts to target this network may be an effective strategy for treating glioma.
Correction to: The Local Mission: Improving Access to Surgical Care in Middle‐Income Countries
Authors: Nagengast Eric S. , Munabi Naikhoba C. O. , Xepoleas Meredith , Auslander Allyn , Magee William P. , Chong David
Published: February 2021

The article “The Local Mission: Improving Access to Surgical Care in Middle‐Income Countries”, written by Nagengast et al., was originally published electronically on the publisher's internet portal on January 2, 2021, without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on January 26, 2021 to © The Author(s) 2021
Konstruktion, Intuition: algorithmisch
Authors: Nake Frieder
Published: February 2021

Konstruktion ist der starke Pfeiler aller Ingenieursarbeit, so auch der Arbeit des Programmierens. Konstruktives Handeln zieht jedoch explizit auch in Textgestaltung und Bildende Kunst des 20. Jahrhunderts ein. Intuition ist das Finden ohne Suchen, das künstlerisches Schaffen oft auszuzeichnen scheint. Sie steht aber gewiss auch bei manchem Programmiertrick Pate. Mit dem für informatisches Tun zentralen algorithmischen Denken werfen wir einen Blick zurück auf den Beginn ästhetischer Experimente mit Rechenmaschinen Ende der 1950er und Anfang der 1960er Jahre.
On L-Close Sperner Systems
Authors: Nagy Dániel T. , Patkós Balázs
Published: February 2021

For a set L of positive integers, a set system $${\mathcal F}\subseteq 2^{[n]}$$

F
⊆

2

[
n
]

is said to be L-close Sperner, if for any pair F, G of distinct sets in $${\mathcal F}$$
F
the skew distance $$sd(F,G)=\min \{|F\setminus G|,|G\setminus F|\}$$

s
d
(
F
,
G
)
=
min
{
|
F
\
G
|
,
|
G
\
F
|
}

belongs to L. We reprove an extremal result of Boros, Gurvich, and Milanič on the maximum size of L-close Sperner set systems for $$L=\{1\}$$

L
=
{
1
}

, generalize it to $$|L|=1$$

|
L
|
=
1

, and obtain slightly weaker bounds for arbitrary L. We also consider the problem when L might include 0 and reprove a theorem of Frankl, Füredi, and Pach on the size of largest set systems with all skew distances belonging to $$L=\{0,1\}$$

L
=
{
0
,
1
}

.
Effect of high intake of cod or salmon on serum total neopterin concentration: a randomised clinical trial
Authors: Helland Anita , Bratlie Marianne , Hagen Ingrid V. , Midttun Øivind , Sveier Harald , Mellgren Gunnar , Ueland Per Magne , Gudbrandsen Oddrun A.
Published: February 2021

Purpose

Primarily, to investigate the effect of high intake of cod (lean fish) or salmon (fatty fish) on serum concentration of total neopterin, a marker of cellular immune activation that is associated with cardiovascular disease. Second, to investigate effects of high cod/salmon intake on antioxidant vitamins and elements essential for activity of antioxidant enzymes.

Methods

In this randomised clinical trial, 63 participants with overweight/obesity consumed 750 g/week of either Atlantic cod (N = 22) or Atlantic salmon (N = 22) or were instructed to continue their normal eating habits but avoid fish intake (Control group, N = 19) for 8 weeks. Food intake was recorded, and fasting serum were collected at baseline and endpoint.

Results

Serum total neopterin concentration was reduced in the Cod group (median change − 2.65 (25th, 75th percentiles − 3.68, − 0.45) nmol/l, P = 0.018) but not in the Salmon group (median change 0.00 (25th, 75th percentiles − 4.15, 3.05) nmol/l, P = 0.59) when compared with the Control group after 8 weeks. The estimated daily intake of selenium, iron, magnesium and zinc were similar between all groups. Increased serum concentration of selenium was observed only after cod intake when compared to the Control group (P = 0.017). Changes in serum concentrations of copper, iron, magnesium, all-trans retinol, α-tocopherol and γ-tocopherol were similar between the groups.

Conclusion

A high intake of cod, but not of salmon, lowered serum total neopterin concentration when compared to the Control group.

Clinical trial registration

This trial was registered at clinicaltrials.gov as NCT02350595
Neighbourhood deprivation and obesity among 5656 pre-school children—findings from mandatory school enrollment examinations
Authors: Nguyen Thuy Ha , Götz Simon , Kreffter Katharina , Lisak-Wahl Stefanie , Dragano Nico , Weyers Simone
Published: February 2021

The risk of child obesity is strongly related to socioeconomic factors such as individual socioeconomic position (SEP) and neighbourhood deprivation. The present study analyses whether the relationship between neighbourhood deprivation and child obesity differs by child’s individual SEP. Data from 5656 children (5–7 years) from the mandatory school enrollment examinations of the pre-school cohorts 2017/2018 in Düsseldorf were analysed. Obesity was determined by the age- and gender-specific body mass index (BMI); neighbourhood deprivation by using the socio-spatial degree of deprivation of the children’s residential addresses; and individual SEP by the level of parental education. Using Poisson regression, we estimated prevalence ratios (PR with 95% confidence interval (CI)) of child obesity by neighbourhood deprivation and parental education. Interactions between neighbourhood deprivation and parental education were tested. The prevalence of child obesity increases with the degree of neighbourhood deprivation. Compared to children living in low deprivation neighbourhoods, the proportion of obese children was twice as high in high deprivation neighbourhoods (PR=2.02; CI=1.46–2.78). Likewise, children from families with medium and low education have twice the risk for obesity compared to children with high parental education (PR=2.05; CI=1.46–2.78). The relationship between neighbourhood deprivation and child obesity was significantly moderated by parental education; it was stronger for higher parental education than for medium and low parental education (p<.001).

Conclusion: Our findings suggest that children from deprived neighbourhoods and families with lower education have a higher risk for child obesity. The identification of particularly deprived neighbourhoods with structural interventions in combination with the strengthening of parental health literacy seems reasonable.

What is Known:• Studies show that children from disadvantaged neighbourhoods are more frequently obese.

What is New:• The relationship between neighbourhood deprivation and child obesity is significantly moderated by parental education. It is stronger for children with higher parental education than for children with medium and low parental education.
Total flavonoids of Radix Tetrastigma suppress inflammation-related hepatocellular carcinoma cell metastasis
Authors: Liu Zhendong , Ding Fangmi , Shen Xingyong
Published: February 2021

This study aimed to investigate the effects of the total flavonoids of Radix Tetrastigma (RTF) on inflammation-related hepatocellular carcinoma (HCC) development. Extracted RTF was diluted to different concentrations for subsequent experiments. HCC cells were cotreated with lipopolysaccharide (LPS) and RTF to investigate the effects of RTF on LPS-stimulated HCC cells. A CCK-8 kit was used to measure cell proliferation. Apoptosis was detected with a flow cytometer. Cell migration and invasion were quantified by wound healing and Transwell assays, respectively. The expression of TLR4 and COX-2 and activation of the NF-κB pathway were determined by Western blotting. Treatment with LPS significantly enhanced cell proliferation and decreased the apoptosis rate, while cell migration and invasion were notably upregulated. RTF suppressed the proliferation and invasion induced by LPS stimulation and promoted HCC cell apoptosis. The protein levels of Bax and cleaved caspase-3 were decreased and that of Bcl-2 was increased by LPS in HCC cells, which could be rescued by RTF. RTF significantly inhibited the LPS-induced expression of the proinflammatory mediators IL-6 and IL-8 in HCC cells. Mechanistically, with RTF treatment, the upregulated expression of TLR4 and COX-2 induced by LPS was obviously downregulated. Furthermore, the phosphorylation of NF-κB/p65 was significantly decreased in LPS-stimulated cells after supplementation with RTF. Our study suggests that RTF exerts a significant inhibitory effect on the LPS-induced enhancement of the malignant behaviors of HCC cells via inactivation of TLR4/NF-κB signaling. RTF may be a promising chemotherapeutic agent to limit HCC development and inflammation-mediated metastasis.
Differential assessment of fluid compartments by bioimpedance in pediatric patients with kidney diseases
Authors: Frey Sandra M. , Vogt Bruno , Simonetti Giacomo D. , Büscher Rainer , Habbig Sandra , Schaefer Franz
Published: February 2021

Background

The kidney is central for maintaining water balance. As a corollary, patients with impaired kidney function are prone to pathological fluid volumes. Total body water (TBW) is distributed between the extracellular (ECW) and intracellular fluid compartments (ICW). In clinical practice, the judgment of hydration status does not allow to distinguish between ECW and ICW. Here, we evaluate the hydration status in children with chronic kidney disease by analyzing TBW, ECW, and ICW.

Methods

Hydration was quantified using whole-body bioimpedance spectroscopy (BCM) in 128 outpatients (1–25 years, 52 girls). Forty-two were transplanted (TPL), 43 suffered from chronic kidney disease without kidney replacement therapy (CKD), 21 were on peritoneal dialysis (PD), and 22 on hemodialysis (HD). HD patients were investigated before, after, and sequentially during dialysis.

Results

The ECW and ICW values obtained by BCM were of the same magnitude as those from the literature using isotope dilution. When compared with a healthy control group, TBW was increased in 9 TPL, 9 CKD, 1 PD, and 11 HD patients before but in none after dialysis. The decline of overhydration during dialysis (p < 0.001, n = 22) correlated with the change in body weight (R2 = 0.62). The kinetics of fluid compartment changes assessed twice in six HD patients revealed a reproducible linear decay of the ECW/ICW ratio due to an increase of ICW and a decrease of ECW.

Conclusion

BCM quantifies TBW and acute changes of ECW and ICW in children with chronic kidney failure. The clinical utility of measuring TBW, ECW, and ICW should be defined in the future.
The Dirichlet problem for the Jacobian equation in critical and supercritical Sobolev spaces
Authors: Guerra André , Koch Lukas , Lindberg Sauli
Published: February 2021

We study existence and regularity of solutions to the Dirichlet problem for the prescribed Jacobian equation,$$\det D u =f$$detDu=f, wherefis integrable and bounded away from zero. In particular, we take$$f\in L^p$$f∈Lp, where$$p>1$$p>1, or in$$L\log L$$LlogL. We prove that for a Baire-genericfin either space there are no solutions with the expected regularity.
Assessment of crop risk due to climate change in Sao Tome and Principe
Authors: Costa Resende Ferreira Nicole , Martins Minella , da Silva Tavares Priscila , Chan Chou Sin , Monteiro Armando , Gomes Ludmila , Santana Adérito
Published: February 2021

Sao Tome and Principe is a small insular country in the west coast of Central Africa. The small dimensions of the islands and the limited natural resources put these islands under highly vulnerable to climate change. To assess the possible future impacts and risks on their agricultural activities, the high-resolution 4-km downscaled climate change projections using Eta regional climate model are used. A crop risk index (CRI) is proposed to assess the risk of climate change on cocoa (Theobroma cacaoL.), pepper (Piper nigrumL. andPiper guinesseL.), taro (Colocasia esculenta(L.) Schott), and maize (Zea maysL.). The index takes into account the vulnerability to climate conditions and the crop yield in the future, and it is classified intovery-high,high,moderate,low, andvery-low. The climate change projections indicate increase in the risk of taro crop, partly due to thermal stress and partly due to the susceptibility to the leaf blight crop disease in taro. The risk of production of the pepper crop is very-high, mainly due to water stress. In mountain regions, the greater risk is due to the thermal stress caused by low temperatures. The cocoa crop is at risk due to water stress, mainly in the northwestern part of the Sao Tome Island, where major local production occurs. The projection indicates increase of the area with very-high risk to maize crops due to the increase of thermal stress and susceptibility to rust. In addition, in parts of the coastal regions, the risk changed from very-low to high risk, due to the low productivity potential. In general, the risks of the four major crops of Sao Tome and Principe increase in the future climate conditions.
Training Image Free High-Order Stochastic Simulation Based on Aggregated Kernel Statistics
Authors: Yao Lingqing , Dimitrakopoulos Roussos , Gamache Michel
Published: February 2021

A training image free, high-order sequential simulation method is proposed herein, which is based on the efficient inference of high-order spatial statistics from the available sample data. A statistical learning framework in kernel space is adopted to develop the proposed simulation method. Specifically, a new concept of aggregated kernel statistics is proposed to enable sparse data learning. The conditioning data in the proposed high-order sequential simulation method appear as data events corresponding to the attribute values associated with the so-called spatial templates of various geometric configurations. The replicates of the data events act as the training data in the learning framework for inference of the conditional probability distribution and generation of simulated values. These replicates are mapped into spatial Legendre moment kernel spaces, and the kernel statistics are computed thereafter, encapsulating the high-order spatial statistics from the available data. To utilize the incomplete information from the replicates, which partially match the spatial template of a given data event, the aggregated kernel statistics combine the ensemble of the elements in different kernel subspaces for statistical inference, embedding the high-order spatial statistics of the replicates associated with various spatial templates into the same kernel subspace. The aggregated kernel statistics are incorporated into a learning algorithm to obtain the target probability distribution in the underlying random field, while preserving in the simulations the high-order spatial statistics from the available data. The proposed method is tested using a synthetic dataset, showing the reproduction of the high-order spatial statistics of the sample data. The comparison with the corresponding high-order simulation method using TIs emphasizes the generalization capacity of the proposed method for sparse data learning.
Do millennials value travel time differently because of productive multitasking? A revealed-preference study of Northern California commuters
Authors: Malokin Aliaksandr , Circella Giovanni , Mokhtarian Patricia L.
Published: February 2021

Millennials, the demographic cohort born in the last two decades of the twentieth century, are reported to adopt information and communication technologies (ICTs) in their everyday lives, including travel, to a greater extent than older generations. As ICT-driven travel-based multitasking influences travelers’ experience and satisfaction in various ways, millennials are expected to be affected at a greater scale. Still, to our knowledge, no previous studies have specifically focused on the impact of travel multitasking on travel behavior and the value of travel time (VOTT) of young adults. To address this gap, we use an original dataset collected among Northern California commuters (N = 2216) to analyze the magnitude and significance of individual and household-level factors affecting commute mode choice. We estimate a revealed-preference mode choice model and investigate the differences between millennials and older adults in the sample. Additionally, we conduct a sensitivity analysis to explore how incorporation of explanatory factors such as attitudes and propensity to multitask while traveling in mode choice models affects coefficient estimates, VOTT, and willingness to pay to use a laptop on the commute. Compared to non-millennials, the mode choice of millennials is found to be less affected by socio-economic characteristics and more strongly influenced by the activities performed while traveling. Young adults are found to have lower VOTT than older adults for both in-vehicle (15.0% less) and out-of-vehicle travel time (15.7% less), and higher willingness to pay (in time or money) to use a laptop, even after controlling for demographic traits, personal attitudes, and the propensity to multitask. This study contributes to better understanding the commuting behavior of millennials, and the factors affecting it, a topic of interest to transportation researchers, planners, and practitioners.