bluuebunny/crossref_metadata_2025 huggingface dataset:
Short self‐assembling peptides with a urea bond: A new type of supramolecular peptide hydrogel materials
Authors: Tsutsumi Hiroshi , Tanaka Kunifumi , Chia Jyh Yea , Mihara Hisakazu
Published: November 2020

There is an increasing need to develop short self‐assembling peptides (SAPs) that can form hydrogels for cell engineering and biomedical applications. In this study, we proposed new short self‐assembling peptides with a symmetric structure via a urea bond. (FFiO)2 and (FFiK)2 were designed as amphiphilic peptides with a hydrophobic domain inside of zwitterionic hydrophilic ends and a urea bond embedded in the hydrophobic domain. The two peptides were synthesized by a liquid‐phase method. The simple structural design of these peptides makes their synthesis on a large scale possible. Both (FFiO)2 and (FFiK)2 assembled into β‐sheet structure and formed stable hydrogels under physiological pH conditions in a pH‐responsive manner. The urea bond was important for the formation of transparent hydrogels. Since (FFiK)2 exhibited self‐assembling properties superior to those of (FFiO)2, (FFiK)2 hydrogels were used as scaffolds for cell culture. (FFiK)2 hydrogels supported cell proliferation without significant cytotoxicity. Therefore, (FFiK)2 is a beneficial supramolecular peptide hydrogelator for cell engineering.
An evaluation of the incremental impact of math intervention on early literacy performance
Authors: Nelson Peter M. , Klingbeil David A. , Parker David C.
Published: November 2020

This study examined spring literacy scores among at‐risk prekindergarten students exposed to supplemental support solely in literacy or a combination of literacy and math. Propensity scores were used to match students receiving combined support (n = 39) with an equivalent number of students receiving only literacy tutoring. Students were matched using fall math scores and fall literacy scores. After confirming baseline equivalence, we used a multilevel model to evaluate the association between support type and spring literacy scores, controlling for fall literacy scores, fall numeracy scores, and the total number of intervention sessions completed. In addition to a significant and positive association between fall and spring scores, students who received support in both literacy and math scored significantly better on the spring literacy assessment. More specifically, participating in both literacy and math support was associated with a 23.81 increase in spring literacy scores relative to participating in literacy support alone, explaining 5% of the student‐level variance.
Tree Forensics: Modern DNA barcoding and traditional anatomy identify roots threatening an ancient necropolis
Authors: Jakoby Gilad , Rog Ido , Shtein Ilana , Chashmonay Inbar , Ben‐Yosef Dror , Eshel Amram , Klein Tamir
Published: November 2020

Societal Impact Statement

Ancient burial caves represent some of the most important sources of information on human history. In a world heritage site in Israel, such caves are under threat due to tree root growth penetrating from the ceilings and causing a risk of cave collapse. To facilitate historical conservation, while avoiding cutting of the mixed forest above the caves, we identified the tree species responsible for the damage, facilitating their specific cutting. Accurate identification of tree roots balances the needs to protect human structures on one side, while conserving the majority of vegetation on the other. Our approach is applicable to the management of ancient sites, as well as to urban management more broadly.

Tree roots have penetrated the ceiling of burial caves in a ~1,800‐years‐old necropolis in the Galilee, Israel, damaging the antiquities and risking the catacombs with collapse. Root identification was needed to enable selective cutting (at the species level), facilitating the conservation of the world heritage site, while maintaining the majority of trees growing on top of the burial caves.

Samples of roots penetrating the cave ceilings were collected and identified both by using DNA barcoding, which has become a standard method for the reliable identification of organisms in their natural environment, and also by traditional morpho‐anatomical methods.

However, woody plant species of the Mediterranean region are under‐represented in DNA databases. Therefore, we added relevant species to the ITS2 database by sequencing the internal transcribed spacer (ITS)2 of the 18S‐26S rDNA from sampled leaves of 19 woody species of the Mediterranean maquis.

The identification of these tree species facilitated their selective removal, balancing antiquities, and nature conservation needs.
Examination of Physiologically‐Based Pharmacokinetic Models of Rosuvastatin
Authors: Bowman Christine M. , Ma Fang , Mao Jialin , Chen Yuan
Published: November 2020

Physiologically‐based pharmacokinetic (PBPK) modeling is increasingly used to predict drug disposition and drug–drug interactions (DDIs). However, accurately predicting the pharmacokinetics of transporter substrates and transporter‐mediated DDIs (tDDIs) is still challenging. Rosuvastatin is a commonly used substrate probe in DDI risk assessment for new molecular entities (NMEs) that are potential organic anion transporting polypeptide 1B or breast cancer resistance protein transporter inhibitors, and as such, several rosuvastatin PBPK models have been developed to try to predict the clinical DDI and support NME drug labeling. In this review, we examine five representative PBPK rosuvastatin models, discuss common challenges that the models have come across, and note remaining gaps. These shared learnings will help with the continuing efforts of rosuvastatin model validation, provide more information to understand transporter‐mediated drug disposition, and increase confidence in tDDI prediction.
The Doping of Si p‐Field‐Effect Transistor Devices by Gallium Focused Ion Beam Implantation Enabling Flexible Fabrication Routes at Moderate Temperatures
Authors: Winkler Felix , Strobel Carsten , Wenzel Christian , Bartha Johann W.
Published: November 2020

A maskless approach of forming p‐doped regions in Si wafers using the Ga source of a standard focused ion beam (FIB) system and the moderate activation temperatures of 400–700 °C is demonstrated in this work. This simple and flexible route is accessible to many research labs and is successfully used to fabricate Si‐based diodes and field‐effect transistors (FETs). For the diodes, tunneling is found to be the forward current transport mechanism. The fabricated p‐FET structures show excellent switching behavior with a high ID,ON/ID,OFF current ratio of 5 × 106.
Mechanistic insight into ligand‐promoted C–H alkenylation of arenes with alkynes: A computational study
Authors: Wu Weirong , Hou Hua , Yang Yan , Li Tingzhen
Published: November 2020

The ligand‐promoted palladium‐catalyzed arylation of alkynes with arenes without directing group is able to furnish alkenyl chlorides via a 1,4‐chlorine migration or trisubstituted alkenes. This reaction is challenging due to bidentate N, N ligand and electron‐neutral arenes have rarely been reported to afford good yields. Intrigued by the novel strategy, we carried out density functional theory calculations to unravel the ligand effects and origins of substituent‐controlled chemoselectivity of the C–H functionalization reactions. For the n‐propyl‐substituted alkyne system, CMD process is identified as the rate‐determining step. And the chemoselectivity is controlled by oxidative addition with the C–Cl bond cleavage and protonation process. While for 3,5‐dimethylphenyl‐substituented alkyne system, the dominant pathway turns to the protonation process. The electrostatic attractions, repulsive force and aryl substituent effects jointly result in reverse chemoselectivity. Compared with the L2 ligand, the bidentate ligand L1 reacts with palladium acetate to form a different stable square‐planer species. The steric repulsion are found to be mainly responsible for the absence of products using the L2 ligand, which is different from previous reports.
Fisher information of a vector potential for time‐dependent Feinberg–Horodecki equation
Authors: Onate Clement A. , Onyeaju Michael C.
Published: November 2020

The time‐dependent Feinberg–Horodecki equation in the presence of a special Mie‐type pseudoharmonic potential was solved and the quantized momentum with the corresponding wave functions were obtained with the supersymmetric approach. The Fisher information for both the time and the momentum space were calculated via expectation values of time and momentum. The effect of the dissociation energy, the equilibrium time point and the quantum number respectively on the Fisher information were studied in detail. The result was applied to five molecules. The results obtained for the time‐dependent Feinberg–Horodecki equation followed the trend of the results obtained for the time‐independent Schrödinger equation.
A systematic meta‐analysis of immune signatures in patients with COVID‐19
Authors: Liu Kun , Yang Tong , Peng Xue‐Fang , Lv Shou‐Ming , Ye Xiao‐lei , Zhao Tian‐Shuo , Li Jia‐Chen , Shao Zhong‐Jun , Lu Qing‐Bin , Li Jing‐Yun , Liu Wei
Published: November 2020

Currently severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission has been on the rise worldwide. Predicting outcome in COVID‐19 remains challenging, and the search for more robust predictors continues. We made a systematic meta‐analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non‐severe patients of COVID‐19, serum levels of Interleukins (IL)‐2, IL‐2R, IL‐4, IL‐6, IL‐8, IL‐10 and tumor necrosis factor α were significantly up‐regulated in severe patients, with the largest inter‐group differences observed for IL‐6 and IL‐10. In contrast, IL‐5, IL‐1β and Interferon (IFN)‐γ did not show significant inter‐group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+CD25+CD127‐ Treg, together with CD19+ B cells count and CD16+CD56+ NK cells were all consistently and significantly depressed in severe group than in non‐severe group. SARS‐CoV‐2 specific IgA and IgG antibodies were significantly higher in severe group than in non‐severe group, while IgM antibody in the severe patients was slightly lower than those in the non‐severe patients, and IgE antibody showed no significant inter‐group differences. The combination of cytokines, especially IL‐6 and IL‐10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS‐CoV‐2 infection.
Extensive Mucocutaneous, Oesophageal and Otic Lichen Planus Secondary to Nivolumab Therapy
Authors: Ferguson L. , Ho B. , Weir J. , Francis N. , West K. , Rathbone B. , Larkin J. , Heelan K.
Published: November 2020

We report a 73-year-old female with metastatic renal cell carcinoma who developed a widespread lichenoid reaction following nivolumab treatment. The timeline of the reaction strongly correlated with the nivolumab treatment and subsequent cessation. Our patient had cutaneous, mucosal, otic, ophthalmic and oesophageal involvement, demonstrating the potentially extensive nature of lichenoid reactions to anti-programmed cell death receptor-1 (anti-PD1) therapies. Although lichenoid reactions to anti-PD1 therapies are now well recognized, there have been no previous reports of otic or oesophageal involvement in the literature. Although cutaneous lichenoid reactions do not tend to be severe or treatment limiting, more widespread systemic lichenoid reactions are challenging to manage, particularly in the context of malignancy. This very unusual case highlights the importance of considering involvement beyond the skin in all lichenoid skin reactions.
Directed coping: A key to coping effectively?
Authors: Wright Robert R.
Published: November 2020

Directed coping, or the use of fewer coping strategies, represents attempts of the individual to effectively cope with stressors. As individuals engage in this process, health and wellness (e.g., physical and mental) generally improve, suggesting directed coping may be an effective technique. However, little specific information is known about the directed coping construct beyond the results of the single study by Wright et al. among nurses dealing with work stressors. Therefore, the current study seeks to examine the directed coping construct in more depth. Following a pre/post study design, 611 undergraduate students participated in a health behaviour change program, completing an online questionnaire regarding their health, wellness and general life stressors as well as an in‐person physical health assessment before and after the 6‐week program. Consistent with hypotheses, directed coping was associated with and predictive of improved health and wellness subjectively (e.g., affect and stress) and objectively (e.g., heart rate, blood pressure and grip strength) relative to coping with general life stressors. Moreover, directed coping demonstrated stability over time and was related to personality characteristics. Thus, the results suggest directed coping is an effective method of coping and may be stable across situations.
The cytosine methylation landscape of spring barley revealed by a new reduced representation bisulfite sequencing pipeline, WellMeth
Authors: Malinowska Marta , Nagy Istvan , Wagemaker Cornelis A. M. , Ruud Anja K. , Svane Simon F. , Thorup‐Kristensen Kristian , Jensen Christian S. , Eriksen Birger , Krusell Lene , Jahoor Ahmed , Jensen Jens , Eriksen Lars Bonde , Asp Torben
Published: November 2020

Patterns and level of cytosine methylation vary widely among plant species and are associated with genome size as well as the proportion of transposons and other repetitive elements in the genome. We explored epigenetic patterns and diversity in a representative proportion of the spring barley (Hordeum vulgare L.) genome across several commercial and historical cultivars. This study adapted a genotyping‐by‐sequencing (GBS) approach for the detection of methylated cytosines in genomic DNA. To analyze the data, we developed WellMeth, a complete pipeline for analysis of reduced representation bisulfite sequencing. WellMeth enabled quantification of context‐specific DNA methylation at the single‐base resolution as well as identification of differentially methylated sites (DMCs) and regions (DMRs). On average, DNA methylation levels were significantly higher than what is commonly observed in many plants species, reaching over 10‐fold higher levels than those in Arabidopsis thaliana (L.) Heynh. in the CHH methylation. Preferential methylation was observed within and at the edges of long‐terminal repeats (LTR) retrotransposons Gypsy and Copia. From a pairwise comparison of cultivars, numerous DMRs could be identified of which more than 5,000 were conserved within the analyzed set of barley cultivars. The subset of regions overlapping with genes showed enrichment in gene ontology (GO) categories associated with chromatin and cellular structure and organization. A significant correlation between genetic and epigenetic distances suggests that a considerable portion of methylated regions is under strict genetic control in barley. The data presented herein represents the first step in efforts toward a better understanding of genome‐level structural and functional aspects of methylation in barley.
Engineering spatiotemporal organization and dynamics in synthetic cells
Authors: Groaz Alessandro , Moghimianavval Hossein , Tavella Franco , Giessen Tobias W. , Vecchiarelli Anthony G. , Yang Qiong , Liu Allen P.
Published: November 2020

Constructing synthetic cells has recently become an appealing area of research. Decades of research in biochemistry and cell biology have amassed detailed part lists of components involved in various cellular processes. Nevertheless, recreating any cellular process in vitro in cell‐sized compartments remains ambitious and challenging. Two broad features or principles are key to the development of synthetic cells—compartmentalization and self‐organization/spatiotemporal dynamics. In this review article, we discuss the current state of the art and research trends in the engineering of synthetic cell membranes, development of internal compartmentalization, reconstitution of self‐organizing dynamics, and integration of activities across scales of space and time. We also identify some research areas that could play a major role in advancing the impact and utility of engineered synthetic cells.

This article is categorized under:

Biology‐Inspired Nanomaterials > Lipid‐Based Structures

Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures
Yet another lesson on the stability conditions in multi-Higgs potentials
Authors: Ivanov Igor P. , Vazão Francisco
Published: November 2020

Abstract

We discuss a rather common but often unnoticed pitfall which arises when deriving the bounded-from-below (BFB) conditions in multi-Higgs models with softly broken global symmetries. Namely, necessary and sufficient BFB conditions derived for the case with an exact symmetry can be ruined by introducing soft symmetry breaking terms. Using S4 and A4-symmetric three-Higgs-doublet models as an example, we argue that all published necessary and sufficient BFB conditions, even those which are correct for the exactly symmetric case, are no longer sufficient if soft symmetry breaking is added. Using the geometric formalism, we derive the exact necessary and sufficient BFB conditions for the 3HDM with the symmetry group S4, either exact or softly broken, and review the situation for the A4-symmetric case.
Post-Minkowskian effective field theory for conservative binary dynamics
Authors: Kälin Gregor , Porto Rafael A.
Published: November 2020

Abstract

We develop an Effective Field Theory (EFT) formalism to solve for the conservative dynamics of binary systems in gravity via Post-Minkowskian (PM) scattering data. Our framework combines a systematic EFT approach to compute the deflection angle in the PM expansion, together with the ‘Boundary-to-Bound’ (B2B) dictionary introduced in [1, 2]. Due to the nature of scattering processes, a remarkable reduction of complexity occurs both in the number of Feynman diagrams and type of integrals, compared to a direct EFT computation of the potential in a PM scheme. We provide two illustrative examples. Firstly, we compute all the conservative gravitational observables for bound orbits to 2PM, which follow from only one topology beyond leading order. The results agree with those in [1, 2], obtained through the ‘impetus formula’ applied to the classical limit of the one loop amplitude in Cheung et al. [3]. For the sake of comparison we reconstruct the conservative Hamiltonian to 2PM order, which is equivalent to the one derived in [3] from a matching calculation. Secondly, we compute the scattering angle due to tidal effects from the electric- and magnetic-type Love numbers at leading PM order. Using the B2B dictionary we then obtain the tidal contribution to the periastron advance. We also construct a Hamiltonian including tidal effects at leading PM order. Although relying on (relativistic) Feynman diagrams, the EFT formalism developed here does not involve taking the classical limit of a quantum amplitude, neither integrals with internal massive fields, nor additional matching calculations, nor spurious (‘super-classical’) infrared singularities. By construction, the EFT approach can be automatized to all PM orders.
Random boundary geometry and gravity dual of $$ T\overline{T} $$ deformation
Authors: Hirano Shinji , Shigemori Masaki
Published: November 2020

Abstract

We study the random geometry approach to the $$ T\overline{T} $$
T

T
¯

deformation of 2d conformal field theory developed by Cardy and discuss its realization in a gravity dual. In this representation, the gravity dual of the $$ T\overline{T} $$
T

T
¯

deformation becomes a straightforward translation of the field theory language. Namely, the dual geometry is an ensemble of AdS3 spaces or BTZ black holes, without a finite cutoff, but instead with randomly fluctuating boundary diffeomorphisms. This reflects an increase in degrees of freedom in the renormalization group flow to the UV by the irrelevant $$ T\overline{T} $$
T

T
¯

operator. We streamline the method of computation and calculate the energy spectrum and the thermal free energy in a manner that can be directly translated into the gravity dual language. We further generalize this approach to correlation functions and reproduce the all-order result with universal logarithmic corrections computed by Cardy in a different method. In contrast to earlier proposals, this version of the gravity dual of the $$ T\overline{T} $$
T

T
¯

deformation works not only for the energy spectrum and the thermal free energy but also for correlation functions.
Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro
Authors: Szychowski Konrad A. , Skóra Bartosz , Kryshchyshyn-Dylevych Anna , Kaminskyy Danylo , Rybczyńska-Tkaczyk Kamila , Lesyk Roman , Gmiński Jan
Published: November 2020

4-Thiazolidinones and related derivatives are regarded as privileged structures in medicinal chemistry and a source of new drug-like compounds. To date it is known that thiazolidinones are able to induce CYP1A1 activity in 3T3-L1 cells. Therefore, to extend the knowledge of the mechanism of thiazolidinones in the cell, four chemically synthesized heterocycles were tested on 3T3-L1 cells. The 3T3-L1 cells were exposed to Les-2194, Les-3640, Les-5935, and Les-6166. Our study showed that 1 μM βNF, Les-2194, and Les-6166 decreased the expression of Ahr mRNA. In turn, βNF, Les-2194, and Les-3640 increased the Cyp1a1 mRNA expression at the same time interval. On the other hand, Les-5935 was found to decrease the Cyp1a1 mRNA expression. Interestingly, the expression of Cyp1a2 mRNA was activated only by βNF and Les-2194. The expression of Cyp1b1 mRNA in the 3T3 cell line increased after the βNF and Les-2194 treatment but declined after the exposure to Les-5935 and Les-6166. Moreover, the Les-2194 and Les-5935 compounds were shown to increase the activity of EROD, MROD, and PROD. Les-3640 increased the activity of EROD and decreased the activity of PROD. In turn, the treatment with Les-6166 resulted in an increase in the activity of EROD and a decrease in the activity of MROD and PROD in the 3T3-L1 cells.
The eigenvalue problem of one-dimensional Dirac operator
Authors: Karwowski Jacek , Ishkhanyan Artur , Poszwa Andrzej
Published: November 2020

The properties of the eigenvalue problem of the one-dimensional Dirac operator are discussed in terms of the mutual relations between vector, scalar and pseudo-scalar contributions to the potential. Relations to the exact solubility are analyzed.
Comparison of DAFH and FALDI-like approaches
Authors: Cooper David L. , de Lange Jurgens H. , Ponec Robert
Published: November 2020

Two complementary methodologies for extracting useful insights into electronic structure and bonding from contemporary wavefunctions are compared. The first of these, known as the analysis of domain-averaged Fermi holes (DAFH), mostly provides visually appealing descriptions of the role and the extent of electron sharing in chemical bonding. The second one, known as the fragment, atom, localized, delocalized and interatomic (FALDI) charge density decomposition scheme, uses the partitioning of certain localization and delocalization indices to focus on highly visual contributions associated with individual domains and with pairs of domains, respectively. Four variants of a FALDI-like approach are investigated here in some detail, mostly to establish which of them are the most reliable and the most informative. In addition to ‘full’ calculations that use the correlated pair density, the consequences for the DAFH and FALDI-like procedures of using instead a popular one-electron approximation are explored. Additionally, the geometry dependence of the degree of acceptability of the errors that this introduces for delocalization indices is assessed for different formal bond multiplicities. The familiar molecular test systems employed for these various linked investigations are the breaking of the bonds in H2and in N2, as well as the nature of the bonding in B2H6, as a simple example of multicenter bonding. One of the key outcomes of this study is a clear understanding of how DAFH analysis and a particular variant of FALDI-like analysis could be most profitably deployed to extract complementary insights into more complex and/or controversial bonding situations.
Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases
Authors: Shi Hui , Yang Shiwei , Lin Ning , Huang Peng , Yu Rongbin , Chen Mei , Wang Lijuan , Jiang Zhixin , Sun Xiaoru
Published: November 2020

The aim of this study is to evaluate the relationship between maternal single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine (HCY) level and offspring congenital heart diseases (CHDs). 338 mothers with offspring CHDs as case group and 306 mothers of normal children as control group were recruited. Their pregnant histories were interviewed by questionnaire and the MTHFR rsl801133 and rsl801131 were genotyped. The case–control analysis was used to find out the relationship between maternal SNPs of MTHFR gene and offspring CHDs. And the plasma HCY concentration of the mothers of CHDs children was detected. This case–case study was intended to find out the relevance between maternal HCY level and SNPs of MTHFR gene. There were significant differences in the gender of children, occupation of mothers, family history with CHDs, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHDs group and control group (P < 0.05). MTHFR rs1801133 was significantly associated with their offspring CHDs in mothers. The polymorphism of maternal MTHFR rs1801133 increased plasma HCY level, especially the homozygous mutation. Besides the environmental factors, our results suggested that the maternal MTHFR rs1801133 polymorphism might be a risk factor of their offspring CHDs, which may be due to the hyperhomocysteinemia by abnormal metabolism of HCY.
Predicting tumor response and outcome of second-look surgery with 18F-FDG PET/CT: insights from the GINECO CHIVA phase II trial of neoadjuvant chemotherapy plus nintedanib in stage IIIc-IV FIGO ovarian cancer
Authors: Aide Nicolas , Fauchille Pauline , Coquan Elodie , Ferron Gwenael , Combe Pierre , Meunier Jérome , Alexandre Jerôme , Berton Dominique , Leary Alexandra , De Rauglaudre Gaétan , Bonichon Nathalie , Pujade Lauraine Eric , Joly Florence
Published: November 2020

Background

This ancillary study aimed to evaluate 18F-FDG PET parameter changes after one cycle of treatment compared to baseline in patients receiving first-line neoadjuvant anti-angiogenic nintedanib combined to paclitaxel-carboplatin chemotherapy or chemotherapy plus placebo and to evaluate the ability of 18F-FDG PET parameters to predict progression-free survival (PFS), overall survival (OS), and success of second-look surgery.

Materials and methods

Central review was performed by two readers blinded to the received treatment and to the patients’ outcome, in consensus, by computing percentage change in PET metrics within a volume of interest encompassing the entire tumor burden. EORTC and PERCIST criteria were applied to classify patients as responders (partial metabolic response and complete metabolic response) or non-responders (stable metabolic disease and progressive metabolic disease). Also analyzed was the percentage change in metabolic active tumor volume (MATV) and total lesion glycolysis (TLG).

Results

Twenty-four patients were included in this ancillary study: 10 received chemotherapy + placebo and 14 chemotherapy + nintedanib. PERCIST and EORTC criteria showed similar discriminative power in predicting PSF and OS. Variation in MATV/TLG did not predict PFS or OS, and no optimal threshold could be found for MATV/TLG for predicting survival. Complete cytoreductive surgery (no residual disease versus residual disease < 0.25 cm/0.25–2.5 cm/> 2.5 cm) was more frequent in responders versus non-responders (P = 0.002 for PERCIST and P = 0.02 for EORTC criteria). No correlation was observed between the variation of PET data and the variation of CA-125 blood level between baseline sample and that performed contemporary to the interim PET, but a statistically significant correlation was observed between ΔSULpeak and ΔCA-125 between baseline sample and that performed after the second cycle.

Conclusion

18F-FDG PET using EORTC or PERCIST criteria appeared to be a useful tool in ovarian cancer trials to analyze early tumor response, and predict second-look surgery outcome and survival. An advantage of PERCIST is the correlation of ΔSULpeak and ΔCA-125, PET response preceding tumor markers response by 1 month. Neither MATV nor TLG was useful in predicting survival.

Trial registration

NCT01583322 ARCAGY/ GINECO GROUP GINECO-OV119, 24 April 2012
Heterogeneity in populations of enterohaemorrhagic Escherichia coli undergoing d-serine adaptation
Authors: O’Boyle Nicky , Roe Andrew J.
Published: November 2020

Phenotypic and genetic heterogeneities are conserved features of prokaryotic populations. During periods of stress, this programmed diversity increases the likelihood that variants within the population will survive the adverse conditions, allowing for proliferation. Phenotypic heterogeneity can have a mutational or indeed a non-mutational basis as observed in bet-hedging strategies adopted by antibiotic-tolerant persister cells. Genetic variants can arise by phase variation (slip-strand mispairing, promoter inversions etc.), nucleotide polymorphisms resulting from replication errors or larger rearrangements such as deletions and insertions. In the face of selective pressures, these alterations may be neutral, beneficial or deleterious.

We recently described the genetic basis of tolerance to a normally toxic metabolite, d-serine (d-ser) in enterohaemorrhagic E. coli (EHEC). Here we summarize our work in the context of population dynamics, provide further discussion on the distinction between these tolerance mechanisms and the importance of heterogeneity for maximising adaptive potential.
Datasets for the CMIP6 Scenario Model Intercomparison Project (ScenarioMIP) Simulations with the Coupled Model CAS FGOALS-f3-L
Authors: Zhao Shuwen , Yu Yongqiang , Lin Pengfei , Liu Hailong , He Bian , Bao Qing , Guo Yuyang , Hua Lijuan , Chen Kangjun , Wang Xiaowei
Published: November 2020

The datasets for the tier-1 Scenario Model Intercomparison Project (ScenarioMIP) experiments from the Chinese Academy of Sciences (CAS) Flexible Global Ocean-Atmosphere-Land System model, finite-volume version 3 (CAS FGOALS-f3-L) are described in this study. ScenarioMIP is one of the core MIP experiments in phase 6 of the Coupled Model Intercomparison Project (CMIP6). Considering future CO2, CH4, N2O and other gases’ concentrations, as well as land use, the design of ScenarioMIP involves eight pathways, including two tiers (tier-1 and tier-2) of priority. Tier-1 includes four combined Shared Socioeconomic Pathways (SSPs) with radiative forcing, i.e., SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5, in which the globally averaged radiative forcing at the top of the atmosphere around the year 2100 is approximately 2.6, 4.5, 7.0 and 8.5 W m−2, respectively. This study provides an introduction to the ScenarioMIP datasets of this model, such as their storage location, sizes, variables, etc. Preliminary analysis indicates that surface air temperatures will increase by about 1.89°C, 3.07°C, 4.06°C and 5.17°C by around 2100 under these four scenarios, respectively. Meanwhile, some other key climate variables, such as sea-ice extension, precipitation, heat content, and sea level rise, also show significant long-term trends associated with the radiative forcing increases. These datasets will help us understand how the climate will change under different anthropogenic and radiative forcings.
Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis
Authors: Kiss Szabolcs , Gede Noémi , Hegyi Péter , Németh Dávid , Földi Mária , Dembrovszky Fanni , Nagy Bettina , Juhász Márk Félix , Ocskay Klementina , Zádori Noémi , Molnár Zsolt , Párniczky Andrea , Hegyi Péter Jenő , Szakács Zsolt , Pár Gabriella , Erőss Bálint , Alizadeh Hussain
Published: November 2020

Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = − 0.35 × 109/L [CI − 0.43, − 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention.
Patterns of care and follow-up care of patients with uveal melanoma in German-speaking countries: a multinational survey of the German Dermatologic Cooperative Oncology Group (DeCOG)
Authors:   the German Dermatologic Cooperative Oncology Group (DeCOG, committee ocular melanoma), Steeb Theresa , Wessely Anja , Alter Mareike , Bayerl Christiane , Bender Armin , Bruning Guido , Dabrowski Evelyn , Debus Dirk , Devereux Nina , Dippel Edgar , Drexler Konstantin , Dücker Pia , Dummer Reinhard , Emmert Steffen , Elsner Peter , Enk Alexander , Gebhardt Christoffer , Gesierich Anja , Goebeler Matthias , Goerdt Sergij , Goetze Steven , Gutzmer Ralf , Haferkamp Sebastian , Hansel Gesina , Hassel Jessica C. , Heinzerling Lucie , Kähler Katharina C. , Kaume Kjell M. , Krapf Wolfgang , Kreuzberg Nicole , Lehmann Percy , Livingstone Elisabeth , Löffler Harald , Loquai Carmen , Mauch Cornelia , Mangana Johanna , Meier Friedegund , Meissner Markus , Moritz Rose K. C. , Maul Lara Valeska , Müller Verena , Mohr Peter , Navarini Alexander , Van Nguyen Ahn , Pfeiffer Christiane , Pföhler Claudia , Posch Christian , Richtig Erika , Rompel Rainer , Sachse Michael M. , Sauder Stefanie , Schadendorf Dirk , Schatton Kerstin , Schulze Hans-Joachim , Schultz Erwin , Schilling Bastian , Schmuth Matthias , Simon Jan. C. , Streit Markus , Terheyden Patrick , Thiem Alexander , Tüting Thomas , Welzel Julia , Weyandt Gerhard , Wesselmann Ulrich , Wollina Uwe , Ziemer Mirjana , Zimmer Lisa , Zutt Markus , Berking Carola , Schlaak Max , Heppt Markus V.
Published: November 2020

Purpose

Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting.

Methods

A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated.

Results

44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures.

Conclusion

Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.
Short-term impact of COVID-19 lockdown on metabolic control of patients with well-controlled type 2 diabetes: a single-centre observational study
Authors: Biancalana Edoardo , Parolini Federico , Mengozzi Alessandro , Solini Anna
Published: November 2020

Aims/hypothesis

The strict rules applied in Italy during the recent COVID-19 pandemic, with the prohibition to attend any regular outdoor activity, are likely to influence the degree of metabolic control in patients with type 2 diabetes. We explored such putative effect immediately after the resolution of lockdown rules, in the absence of any variation of pharmacologic treatment.

Methods

One-hundred and fourteen patients with adequate metabolic control took part in this single-centre, prospective, observational study. The metabolic profile tested 1 week after the end of the lockdown was compared with the last value and the mean of the last three determinations performed before the pandemic emergency (from 6 months to 2 years before).

Results

After 8 weeks of lockdown, an increase of HbA1c > 0.3% (mean +0.7%) was observed in 26% of the participants; these were also characterized by a persistent elevation in serum triglycerides able to predict the worsening of glucose control.

Conclusions

Lockdown determined a relevant short-term metabolic worsening in approximately one-fourth of previously well-controlled type 2 diabetic individuals; pre-lockdown triglycerides were the only parameter able to predict such derangement of glucose control.
Factors influencing the fascial closure rate after open abdomen treatment: Results from the European Hernia Society (EuraHS) Registry
Authors: Willms A. G. , Schwab R. , von Websky M. W. , Berrevoet F. , Tartaglia D. , Sörelius K. , Fortelny R. H. , Björck M. , Monchal T. , Brennfleck F. , Bulian D. , Beltzer C. , Germer C. T. , Lock J. F. ,   EURAHS Open Abdomen Group, Güsgen C. , Schaaf S. , Anger F. , Fuhr S. , Kiesel M. , Schmidt R. , Kalff J. C. , Vilz T. O. , Galatioto C. , Cobuccio L. , Hoffmann A. , Schlitt H. J. , Heiss M. , Muysoms F. , Oldhafer K. , Dietz U. , Björck Martin , Vanlander A.
Published: November 2020

Purpose

Definitive fascial closure is an essential treatment objective after open abdomen treatment and mitigates morbidity and mortality. There is a paucity of evidence on factors that promote or prevent definitive fascial closure.

Methods

A multi-center multivariable analysis of data from the Open Abdomen Route of the European Hernia Society included all cases between 1 May 2015 and 31 December 2019. Different treatment elements, i.e. the use of a visceral protective layer, negative-pressure wound therapy and dynamic closure techniques, as well as patient characteristics were included in the multivariable analysis. The study was registered in the International Clinical Trials Registry Platform via the German Registry for Clinical Trials (DRK00021719).

Results

Data were included from 630 patients from eleven surgical departments in six European countries. Indications for OAT were peritonitis (46%), abdominal compartment syndrome (20.5%), burst abdomen (11.3%), abdominal trauma (9%), and other conditions (13.2%). The overall definitive fascial closure rate was 57.5% in the intention-to-treat analysis and 71% in the per-protocol analysis. The multivariable analysis showed a positive correlation of negative-pressure wound therapy (odds ratio: 2.496, p < 0.001) and dynamic closure techniques (odds ratio: 2.687, p < 0.001) with fascial closure and a negative correlation of intra-abdominal contamination (odds ratio: 0.630, p = 0.029) and the number of surgical procedures before OAT (odds ratio: 0.740, p = 0.005) with DFC.

Conclusion

The clinical course and prognosis of open abdomen treatment can significantly be improved by the use of treatment elements such as negative-pressure wound therapy and dynamic closure techniques, which are associated with definitive fascial closure.
Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study
Authors: Hanai Nobuhiro , Shimizu Yasushi , Kariya Shin , Yasumatsu Ryuji , Yokota Tomoya , Fujii Takashi , Tsukahara Kiyoaki , Yoshida Masafumi , Hanyu Kenji , Ueda Tsutomu , Hirakawa Hitoshi , Takahashi Shunji , Ono Takeharu , Sano Daisuke , Yamauchi Moriyasu , Watanabe Akihito , Omori Koichi , Yamazaki Tomoko , Monden Nobuya , Kudo Naomi , Arai Makoto , Sakurai Daiju , Asakage Takahiro , Doi Issei , Yamada Takayuki , Homma Akihiro
Published: November 2020

Background

To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice.

Methods

This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records.

Results

Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1–27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2–12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141.

Conclusions

The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141.

Trial registration number

UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)
Classification score approach for detecting adversarial example in deep neural network
Authors: Kwon Hyun , Kim Yongchul , Yoon Hyunsoo , Choi Daeseon
Published: November 2020

Deep neural networks (DNNs) provide superior performance on machine learning tasks such as image recognition, speech recognition, pattern analysis, and intrusion detection. However, an adversarial example, created by adding a little noise to an original sample, can cause misclassification by a DNN. This is a serious threat to the DNN because the added noise is not detected by the human eye. For example, if an attacker modifies a right-turn sign so that it misleads to the left, autonomous vehicles with the DNN will incorrectly classify the modified sign as pointing to the left, but a person will correctly classify the modified sign as pointing to the right. Studies are under way to defend against such adversarial examples. The existing method of defense against adversarial examples requires an additional process such as changing the classifier or modifying input data. In this paper, we propose a new method for detecting adversarial examples that does not invoke any additional process. The proposed scheme can detect adversarial examples by using a pattern feature of the classification scores of adversarial examples. We used MNIST and CIFAR10 as experimental datasets and Tensorflow as a machine learning library. The experimental results show that the proposed method can detect adversarial examples with success rates: 99.05% and 99.9% for the untargeted and targeted cases in MNIST, respectively, and 94.7% and 95.8% for the untargeted and targeted cases in CIFAR10, respectively.
Assessment of cetacean–fishery interactions in the marine food web of the Gulf of Taranto (Northern Ionian Sea, Central Mediterranean Sea)
Authors: Carlucci Roberto , Capezzuto Francesca , Cipriano Giulia , D’Onghia Gianfranco , Fanizza Carmelo , Libralato Simone , Maglietta Rosalia , Maiorano Porzia , Sion Letizia , Tursi Angelo , Ricci Pasquale
Published: November 2020

The exploitation of fishery resources acts as a driving force on cetaceans both directly, by determining their fishing mortality or injury as by-catch species, and indirectly, through the lowering the availability of their prey. This competitive overlap between fishing and cetaceans often results in inadequate solutions so that in some cases there have been cases of intentional cetacean culling to maximize fishing production. A modelling approach applied to investigate the ecological roles of cetaceans in the food web could prove more effective to integrate ecological and fishing aspects and to provide suggestions for management. The comparative analysis carried out in the Gulf of Taranto (Northern Ionian Sea, Central Mediterranean Sea) showed that fishing exploitation provides impacts on the investigated food web greater than those due to cetacean predation. Trawling was estimated to be the most negatively impacting fishing gear considering the mortality rates and consumption flows. On the other hand, the striped dolphin was the main impact on the food web due to its highest consumption flows. Analysis showed a negative and non-selective impact on the exploited species due to the fishing gears, while the odontocetes proved to select their prey species and provide a positive impact in the assemblage. In particular, while the fishing gears are primarily size selective, targeting mostly large and economically valuable fish, the odontocetes seem to follow a co-evolution process with their prey, developing a specialization in their resources, providing control of the meso-consumers and ensuring a trophic stability in the ecosystem.