bluuebunny/crossref_metadata_2025 huggingface dataset:
How the medical professionals impact ASL and English families’ language planning policy
Authors: Kite Bobbie Jo
Published: November 2019

This article explores the journey of eight hearing families of bimodal‐bilingual deaf children as they navigate the decision‐making process reflecting their beliefs and values about American Sign Language (ASL) and English through their family language policy framework. The resources offered to families with deaf children often reflect a medical view, rather than a cultural perspective of being deaf. Because medical professionals, educators, and specialists who work with deaf and hard‐of‐hearing children have a strong influence on family members’ opinions, beliefs, and attitudes about being deaf, it is even more crucial to correct misconceptions about ASL and empower families to develop a family language policy that is inclusive of their deaf and hard‐of‐hearing children. This article informs researchers, teachers, and other professionals about the potential benefits and challenges of supporting the families’ ASL and English language planning policy.
Estimating the stability and reactivity of cyclic tetrahalo substituted germylenes: A density functional theory investigation
Authors: Koohi Maryam
Published: November 2019

The largest unsaturated carbene, cyclonona‐3,5,7‐trienylidene (1H), emerges as a boat‐shaped transition state (TS) for having a negative force constant (FC). Following the quest for stable germylenes (2X, where X = H, F, Cl, Br, and I) with C8H6X4Ge: formula, the density functional theory (DFT) calculations are carried out to assay the substituent effect on their thermodynamic and kinetic possibilities. These singlet and triplet germylenes (2X‐S and 2X‐T, respectively) appear as boat‐shaped minima without imaginary frequencies and the order of their stability estimated by singlet (S)–triplet (T) energy difference (ΔES‐T = ET − ES) is 1H < 2H < 2F < 2Cl < 2I < 2Br. The purpose of the present work is to swiftly switch from T carbene to S germylenes through alteration of the substituents and assess the influence of different halogens on the stability and other properties. The 2Br‐S seems as the most stable species. From kinetic point of view, 2Cl, 2Br, and 2I are more stable than some of synthesized germylenes. The stabilization of the S state is essential to stabilize germylenes. This can be achieved by σ‐electron withdrawing and π‐electron donating substituents, of which stabilizing effect can be further increased in the order of steric effect < positive hyperconjugation < negative hyperconjugation < mesomeric effect. Applying suitable isodesmic reactions, we show the π‐donor/σ‐acceptor halogen substituents stabilize not only the S but also the T states, and these groups stabilize 2X‐S more than 2X‐T.
Sensitivity of tumor versus normal cell migration and morphology to cold atmospheric plasma‐treated media in varying culture conditions
Authors: Pranda Marina A. , Murugesan Brittney J. , Knoll Andrew J. , Oehrlein Gottlieb S. , Stroka Kimberly M.
Published: November 2019

Cold atmospheric plasma (CAP) produces reactive oxygen species and reactive nitrogen species, which may disproportionally damage tumor cells, resulting in potentially selective cancer therapy. Here, we compare the effects of two CAP sources, that is, the atmospheric pressure plasma jet and the surface micro discharge, on the selectivity of CAP‐treated cell‐culture media. CAP‐treated media were applied to metastatic breast tumor cells and their normal breast epithelial cell counterparts to assess treatment selectivity, while systematically varying common cell‐culture media and cell‐matrix binding moieties. We show that media compositions are crucial in a CAP‐treated media selectivity, while binding moieties (specifically, collagen I, fibronectin, and poly‐d‐lysine) play a lesser role. These data have further implications in the translation of CAP to in vivo use.
A study on the influence of gas mixtures on the property of plasma‐activated water
Authors: Lai Cheng‐Chun , Deng Yong‐Xin , Liao Ying‐Hao
Published: November 2019

The present study applying a plasma jet to activate water in a controllable environment is aimed to investigate the effect of a combination of (working/chamber gas) on the properties of plasma‐activated water. After 10 min of activation, results reveal that a significant decrease in solution pH is observed with the presence of N2. Hydrogen peroxide appears to be the major species for most gas mixtures, except [Ar + air/Ar] and [Ar + air/air], where nitrite and nitrate dominate. A gas mixture of [Ar + air/Ar] produces the maximum concentration of , while the maximum and H2O2 are observed for [Ar + air/air] and (Ar/Ar), respectively. Overall, the antibacterial efficacy correlates well with concentration.
Computational simulations of TNF receptor oligomerization on plasma membrane
Authors: Su Zhaoqian , Wu Yinghao
Published: November 2019

The interactions between tumor necrosis factors (TNFs) and their corresponding receptors (TNFRs) play a pivotal role in inflammatory responses. Upon ligand binding, TNFR receptors were found to form oligomers on cell surfaces. However, the underlying mechanism of oligomerization is not fully understood. In order to tackle this problem, molecular dynamics (MD) simulations have been applied to the complex between TNF receptor‐1 (TNFR1) and its ligand TNF‐α as a specific test system. The simulations on both all‐atom (AA) and coarse‐grained (CG) levels achieved the similar results that the extracellular domains of TNFR1 can undergo large fluctuations on plasma membrane, while the dynamics of TNFα‐TNFR1 complex is much more constrained. Using the CG model with the Martini force field, we are able to simulate the systems that contain multiple TNFα‐TNFR1 complexes with the timescale of microseconds. We found that complexes can aggregate into oligomers on the plasma membrane through the lateral interactions between receptors at the end of the CG simulations. We suggest that this spatial organization is essential to the efficiency of signal transduction for ligands that belong to the TNF superfamily. We further show that the aggregation of two complexes is initiated by the association between the N‐terminal domains of TNFR1 receptors. Interestingly, the cis‐interfaces between N‐terminal regions of two TNF receptors have been observed in the previous X‐ray crystallographic experiment. Therefore, we provide supportive evidence that cis‐interface is of functional importance in triggering the receptor oligomerization. Taken together, our study brings insights to understand the molecular mechanism of TNF signaling.
The expression and function of opsin genes related to the phototactic behavior of Asian citrus psyllid
Authors: Li Chaofeng , Tian Fajun , Lin Tao , Wang Zhengbing , Liu Jiali , Zeng Xinnian
Published: November 2019

BACKGROUND

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is a prominent pest of citrus because it transmits Candidatus Liberibacter asiaticus associated with huanglongbing. Phototactic behavior ubiquitously exists in insects and plays essential roles in host‐searching and mate‐searching in ACP. However, its mechanism has remained unclear to date. In this paper, molecular assays were performed to understand the relation between opsins and the phototactic behavior of ACP.

RESULTS

We cloned five opsin genes and analyzed their expression patterns. The main three opsin genes (Dc‐UV, Dc‐BW and Dc‐LW) displayed high expression levels in daytime, and the expression levels of the other two opsin genes (Dc‐UV‐like and Dc‐arthropsin) increased during nighttime. In constant darkness, the expression patterns and levels of opsin genes of ACP were altered. Under starvation, the expression levels of the main three opsins were reduced (53.89–84.10%). In contrast, the expression levels in females increased (27.55–60.58%). Feeding of double‐stranded RNA (Dc‐UV, Dc‐LW or Dc‐BW) have reduced the phototactic efficiency of ACP to ultraviolet light (44.79%), green light (54.81%) and blue light (43.00%), respectively.

CONCLUSION

The results suggest that the expression levels and patterns of opsins of ACP were influenced by photoperiod and the physiological status of ACP. Our research indicates that opsins play crucial roles in phototactic behavior in ACP. © 2019 Society of Chemical Industry
Population Pharmacokinetics of Ipilimumab in Combination With Nivolumab in Patients With Advanced Solid Tumors
Authors: Sanghavi Kinjal , Zhang Jason , Zhao Xiaochen , Feng Yan , Statkevich Paul , Sheng Jennifer , Roy Amit , Vezina Heather E.
Published: November 2019

Ipilimumab is a fully human monoclonal antibody approved for the treatment of melanoma as monotherapy and for the treatment of melanoma, renal cell carcinoma, and colorectal cancer in combination with nivolumab. Ipilimumab time‐varying clearance (CL) was assessed by a population pharmacokinetics (PPK) model developed using statistically significant covariates identified in a previous PPK analysis plus additional covariates. Data from 3,411 patients who received ipilimumab 0.3–10 mg/kg alone or in combination with nivolumab in 16 clinical trials were analyzed. Ipilimumab CL decreased over time; the change in CL was greater in patients treated with nivolumab combination than ipilimumab alone and in responders vs. nonresponders. Time‐varying covariates including body weight, lactate dehydrogenase, albumin, and performance status were evaluated on change in ipilimumab CL. In addition, ipilimumab CL was similar across different tumor types, nivolumab dosing regimens, and lines of therapy. These data suggest an association of ipilimumab CL with disease severity.
Convolvulus plant—A comprehensive review from phytochemical composition to pharmacy
Authors: Salehi Bahare , Krochmal‐Marczak Barbara , Skiba Dominika , Patra Jayanta Kumar , Das Swagat Kumar , Das Gitishree , Popović‐Djordjević Jelena B. , Kostić Aleksandar Ž. , Anil Kumar Nanjangud V. , Tripathi Ayushi , Al‐Snafi Ali Esmail , Arserim‐Uçar Dılhun Keriman , Konovalov Dmitry Alekseevich , Csupor Dezső , Shukla Ila , Azmi Lubna , Mishra Abhay Prakash , Sharifi‐Rad Javad , Sawicka Barbara , Martins Natália , Taheri Yasaman , Fokou Patrick Valere Tsouh , Capasso Raffaele , Martorell Miquel
Published: November 2019

Convolvulus genus is a representative of the family of Convolvulaceae. Convolvulus plants are broadly distributed all over the world and has been used for many centuries as herbal medicine. Convolvulus genus contains various phytochemicals such as flavonoids, alkaloids, carbohydrates, phenolic compounds, mucilage, unsaturated sterols or terpenes, resin, tannins, lactones, and proteins. This review highlights the phytochemical composition, antimicrobial and antioxidant activities, application as food preservative, traditional medicine use, anticancer activities, and clinical effectiveness in human of Convolvulus plants. All the parts of Convolvulus plants possess therapeutic benefits; preliminary pharmacological data validated their use in traditional medicine. However, further preclinical and clinical experiments are warranted before any application in human health.
Mast cell mediators in relation to dengue severity: A systematic review and meta‐analysis
Authors: Sherif Nourin Ali , Zayan Ahmad Helmy , Elkady Aya Hesham , Ghozy Sherief , Ahmed Ahmed Reda , Omran Esraa Salah , Taha Elsayed A. , Eldesoky Esraa Ali , Ebied Amr , Tieu Thuan , Maraie Noha , Kamel Mohamed Gomaa , Ngo Huyen Thi , Mattar Omar Mohamed , Hirayama Kenji , Huy Nguyen Tien
Published: November 2019

Background

Degranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines, which all have important roles in the severity of dengue infection. We aimed to investigate the role of MCs in severity of dengue.

Methods

We searched for relevant studies in 10 databases on 15 August 2016. Meta‐analysis (MA) was conducted by R version 3.5.0.

Results

We included 24 studies. in vivo and in vitro studies showed higher MC products released from infected mice/cells with dengue virus. In addition, when administering MC stabilizers or antihistaminic drugs, there was a decrease in vascular/capillary permeability. In human and at early stages, studies revealed an insignificant difference in VEGF levels in dengue fever (DF) versus dengue hemorrhagic fever (DHF) (standardized mean difference [SMD] 0.145; 95% confidence interval [CI], −0.348‐0.638). Meanwhile, at acute stages and compared with healthy controls, high heterogeneity with an inconclusive difference in VEGF levels were noted in DF and DHF. However, pooled serum and plasma levels of VEGF were increased significantly in dengue shock syndrome (DSS) versus healthy controls (SMD 0.65; 95% CI, 0.3‐0.95). There were also significantly higher chymase levels in DHF patients compared with DF during the acute phase (MD −6.531; 95% CI, −12.2 to −0.9).

Conclusion

VEGF and chymase levels are mediators in dengue pathogenesis. However, limited data were available to support their role in severe dengue cases. Further studies are needed to evaluate the function of other mediators in dengue severity.
Lyapunov‐Krasovskii stability analysis of delayed Filippov system: Applications to neural networks with switching control
Authors: Cai Zuowei , Huang Lihong
Published: November 2019

This paper gives the stability analysis of Filippov system with delay. Under the Filippov‐framework, we introduce a general type of Lyapunov‐Krasovskii functional (LKF) to derive the stability of delayed differential inclusions (DDIs), where the indefiniteness or positive definiteness of the derivative of LKF holds for almost everywhere along the trajectories of state solution. The proposed LKF of this paper generalizes the classic LKF whose derivative possesses negative definiteness or seminegative definiteness for everywhere. As a result, the stability, uniform stability, uniform asymptotic stability, and global exponential stability criteria of the trivial solution for DDI are established. Moreover, the developed LKF method is applied to solve the stabilization control issue of delayed neural networks, possessing discontinuous input‐output activation.
Autonomous maritime collision avoidance: Field verification of autonomous surface vehicle behavior in challenging scenarios
Authors: Kufoalor D. K. M. , Johansen T. A. , Brekke E. F. , Hepsø A. , Trnka K.
Published: November 2019

We present results from sea trials for an autonomous surface vehicle (ASV) equipped with a collision avoidance system based on model predictive control (MPC). The sea trials were performed in the North Sea as part of an ASV Challenge posed by Deltares through a Dutch initiative involving different authorities, including the Ministry of Infrastructure and Water Management, the Netherlands Coastguard, and the Royal Netherlands Navy. To allow an ASV to operate in a maritime environment governed by the International Regulations for Preventing Collisions at Sea (COLREGs), the ASV must be capable of complying with COLREGs. Therefore, the sea trials focused on verifying COLREGs‐compliant behavior of the ASV in different challenging scenarios using automatic identification system (AIS) data from other vessels. The scenarios cover situations where some obstacle vessels obey COLREGs and emergency situations where some obstacles make decisions that increase the risk of collision. The MPC‐based collision avoidance method evaluates a combined predicted collision and COLREGs‐compliance risk associated with each obstacle and chooses the ‘best’ way out of dangerous situations. The results from the verification exercise in the North Sea show that the MPC approach is capable of finding safe solutions in challenging situations, and in most cases demonstrates behaviors that are close to the expectations of an experienced mariner. According to Deltares’ report, the sea trials have shown in practice that the technical maturity of autonomous vessels is already more than expected.
Aerobic Oxidation of Thiols and In Situ Generated Thiols to Symmetrical Disulfides (Disulfanes) Catalyzed by Na2S4O6
Authors: Abbasi Mohammad , Nowrouzi Najmeh , Mousavi Saadat
Published: November 2019

A simple and efficient procedure for aerobic oxidation of thiols into symmetric disulfides using Na2S4O6 as catalyst in situ generated by reacting Na2S2O3 with I2 in poly ethylene glycol (PEG‐200) has been introduced. Using this catalyst system, convenient protocol for one‐pot achievement of symmetric disulfides via aerobic oxidation of thiols in situ generated by reacting alkyl halides with thiourea is introduced.
Highly Efficient Ionic Photocurrent Generation through WS2‐Based 2D Nanofluidic Channels
Authors: Jia Pan , Wen Qi , Liu Dan , Zhou Min , Jin Xiaoyan , Ding Liping , Dong Huanli , Lu Diannan , Jiang Lei , Guo Wei
Published: November 2019

The unique feature of nacre‐like 2D layered materials provides a facile, yet highly efficient way to modulate the transmembrane ion transport from two orthogonal transport directions, either vertical or horizontal. Recently, light‐driven active transport of ionic species in synthetic nanofluidic systems attracts broad research interest. Herein, taking advantage of the photoelectric semiconducting properties of 2D transition metal dichalcogenides, the generation of a directional and greatly enhanced cationic flow through WS2‐based 2D nanofluidic membranes upon asymmetric visible light illumination is reported. Compared with graphene‐based materials, the magnitude of the ionic photocurrent can be enhanced by tens of times, and its photo‐responsiveness can be 2–3.5 times faster. This enhancement is explained by the coexistence of semiconducting and metallic WS2 nanosheets in the hybrid membrane that facilitates the asymmetric diffusion of photoexcited charge carriers on the channel wall, and the high ionic conductance due to the neat membrane structure. To further demonstrate its application, photonic ion switches, photonic ion diodes, and photonic ion transistors as the fundamental elements for light‐controlled nanofluidic circuits are further developed. Exploring new possibilities in the family of liquid processable colloidal 2D materials provides a way toward high‐performance light‐harvesting nanofluidic systems for artificial photosynthesis and sunlight‐driven desalination.
Promising Applications of AIEgens in Animal Models
Authors: He Bairong , Situ Bo , Zhao Zujin , Zheng Lei
Published: November 2019

In vivo investigations using small animal models are of great significance for the comprehensive understanding of biological and physiological functions—seeing is believing. Fluorescence imaging can provide real‐time and dynamic information of living systems. During the past few years, aggregation‐induced emission luminogens (AIEgens) are widely and rapidly developed for biological detection, imaging, and medicine, owing to their distinct advantages of structural variety, easy functionalization, strong luminescence, large Stokes shift, high photobleaching‐resistance, good biocompatibility, and so forth. In this review, recent advances in applying AIEgens in living animals are highlighted, including in vivo vascular and tumor‐targeted imaging, monitoring biological processes, disease diagnosis, and image‐guided therapy. The aim of this review is to provide a well‐rounded view of the potential applications of AIEgens for biomedical research at the preclinical animal level for researchers and clinicians, and to inspire more practical inventions that will improve or assist clinical techniques.
Dynamic experimental and numerical study of double beam–column joints in modern traditional‐style steel buildings with viscous damper
Authors: Wu Zhanjing , Xue Jianyang , Ke Xiaojun , Sui Yan , Dong Jinshuang
Published: November 2019

Modern traditional‐style steel (MTS) structure is an innovative architecture structure that is widely used in China. This paper explores the possibility of using viscous damper, which can be conveniently installed between beam and column, to replace “sparrow brace” at beam–column joints to improve its seismic capability. Three 1/2.6 scaled MTS double beam–column joints, one without viscous damper and two with viscous damper, were fabricated and tested under dynamic cyclic loading. The results indicated that the primary failure modes were cracking of base metal and local bucking at the beam ends. The hysteretic curve of specimens with viscous dampers was more plump than the common specimen without viscous dampers, indicating better energy dissipation capacity. The displacement ductility ratio was about 1.79–1.96, indicating the viscous damper has little effect on the ductility, whereas in plastic stage, the energy dissipation of specimens and viscous damper increased rapidly, indicating great energy dissipating function of viscous damper. Meanwhile, the results also proved that finite element analysis may stimulate and predict the mechanical behavior of MTS double beam joints with viscous dampers.
Medical needs for translational biophotonics with the focus on Raman‐based methods
Authors: Krafft Christoph , Popp Jürgen
Published: November 2019

This report summarizes state‐of‐the‐art biophotonic approaches for unmet needs in medicine with the focus on spontaneous and coherent Raman methods since 2017. Numerous proof‐of‐principle studies demonstrated how Raman spectroscopy and imaging were applied to classify tissues, delineate tumor borders and detect tumor cells in various disciplines such as histopathology, cytopathology and endoscopy. In some cases, Raman technologies were combined with other modalities such as fluorescence, optical coherence tomography, white light imaging, photoacoustic imaging, optoacoustics and multiphoton microscopy. However, the number of patients and specimens were usually small in these studies. It is concluded that preclinical biophotonic studies using high‐throughput instruments are required to collect big data from larger patient cohorts and develop robust classification algorithms for clinical translation.
Sparse separable 2‐D FIR filter design based on iterative reweighted ℓ1 norm and greedy searching techniques
Authors: Wang Hao , Li Weiqi , Zhao Zhijin , Sun Jian
Published: November 2019

A new separable 2‐D finite impulse response (FIR) filter design technique with sparse coefficients is proposed. This technique includes two stages. In the first stage, the iterative reweighted ℓ1 norm technique is utilized to design a sparse separable 2‐D FIR filter based on some initial design. In the second stage, the greedy searching technique is utilized to make more sparse coefficients based on the first stage design. Simulation experiment validates the effectiveness of the proposed technique. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
The impact of students’ English proficiency level and teacher education on L2 teachers’ pedagogical knowledge: A mixed‐methods study
Authors: Moradkhani Shahab , Rahimi Masoud
Published: November 2019

This article explores the impact of students’ proficiency level (i.e., beginning vs. advanced) and formal teacher education judged by academic credentials (i.e., BA vs. MA holders) on second/foreign language (L2) teachers' pedagogical knowledge base (PKB). To this end, eight L2 teachers teaching general English courses at four private language institutes in Iran participated in the study. Adopting an exploratory mixed‐methods approach, data were collected through stimulated recall and analyzed using both qualitative and quantitative procedures. The type and frequency of L2 teachers’ emerged PK categories were used to compare the repertoire of resources the L2 teachers had accumulated as knowledge across different groups. The results indicated no significant differences between the total PKB of L2 teachers teaching beginning L2 students and those teaching advanced L2 students. Regarding the PK categories, nevertheless, there were some slight differences in the rankings and significant differences in the frequency. On the other hand, no measurable difference was detected between L2 teachers holding a BA and those holding an MA. The results are interpreted based on the students’ proficiency level and the formal teacher education to which the participants were exposed. Suggestions are provided for designing proficiency level–specific teacher education programs and integrating university‐based teacher education with clinical experience.
Readability and types of questions in Chilean EFL high school textbooks
Authors: Cárcamo Morales Benjamín
Published: November 2019

This article evaluates the mandatory English as a foreign language textbooks provided by the government in Chile in terms of readability and types of questions. Three readability formulas are used to analyze the texts: Flesch Reading Ease, Flesch‐Kincaid Grade Level, and Coh‐Metrix L2 reading index (RDL2). To evaluate the cognitive demands that comprehension questions place on students, Day and Park’s (2005) taxonomy of questions is used. The findings of this study reveal that the readability of the texts used in textbooks for 10th and 12th graders is similar, but the texts used in the textbook for 11th graders are more difficult to read. Regarding the types of questions, literal comprehension questions are more used in 12th‐grade texts than in those for 10th and 11th grades. Consequently, there does not seem to be a progression either in readability or in cognitive demand across these grades.
Natural Pedagogy in Second Language Learning and Teaching
Authors: Atkinson Dwight , Shvidko Elena
Published: November 2019

This article introduces the concept ofnatural pedagogy(NP) as a tool for envisioning and enacting second language learning and teaching. Currently popular in the social and cognitive sciences, NP theory holds that much adaptive human behavior is too complex and nontransparent to learn via observation, imitation, and trial‐and‐error alone: Something extra is needed. NP employs humans’ remarkable “hyperprosocial” capacities/tools for interaction (e.g., gesture, gaze, facial expression, body movement, language) to effectteaching‐based learning. NP’s appearance in the hominin lineage likely predated humans; it is probably therefore the original form of teaching‐based learning. A much more recent invention—the classroom—is often portrayed as separated from the rest of the world in order to enable teaching‐based learning. Yet the interactional tools of NP occur pervasively in classrooms as well, making classrooms in this sense substantially continuous with the rest of the world. In both cases, according to the argument developed here, our evolved communicative toolkit underlies teaching‐based learning. This article is primarily conceptual in nature, representing a new departure in the TESOL field.
Correction to: Healthy Minds in the Twentieth Century
Authors: Taylor Steven J. , Brumby Alice
Published: November 2019

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Bag-of-gold spacetimes, Euclidean wormholes, and inflation from domain walls in AdS/CFT
Authors: Fu Zicao , Marolf Donald
Published: November 2019

Abstract

We use Euclidean path integrals to explore the set of bulk asymptotically AdS spacetimes with good CFT duals. We consider simple bottom-up models of bulk physics defined by Einstein-Hilbert gravity coupled to thin domain walls and restrict to solutions with spherical symmetry. The cosmological constant is allowed to change across the domain wall, modeling more complicated Einstein-scalar systems where the scalar potential has multiple minima. In particular, the cosmological constant can become positive in the interior. However, in the above context, we show that inflating bubbles are never produced by smooth Euclidean saddles to asymptotically AdS path integrals. The obstacle is a direct parallel to the well-known obstruction to creating inflating universes by tunneling from flat space. In contrast, we do find good saddles that create so-called “bag-of-gold” geometries which, in addition to their single asymptotic region, also have an additional large semi-classical region located behind both past and future event horizons. Furthermore, without fine-tuning model parameters, using multiple domain walls we find Euclidean geometries that create arbitrarily large bags-of-gold inside a black hole of fixed horizon size, and thus at fixed Bekenstein-Hawking entropy. Indeed, with our symmetries and in our class of models, such solutions provide the unique semi-classical saddle for appropriately designed (microcanonical) path integrals. This strengthens a classic tension between such spacetimes and the CFT density of states, similar to that in the black hole information problem.
Direct conversion of human fibroblasts into therapeutically active vascular wall-typical mesenchymal stem cells
Authors: Steens Jennifer , Unger Kristian , Klar Lea , Neureiter Anika , Wieber Karolin , Hess Julia , Jakob Heinz G. , Klump Hannes , Klein Diana
Published: November 2019

Cell-based therapies using adult stem cells are promising options for the treatment of a number of diseases including autoimmune and cardiovascular disorders. Among these, vascular wall-derived mesenchymal stem cells (VW-MSCs) might be particularly well suited for the protection and curative treatment of vascular damage because of their tissue-specific action. Here we report a novel method for the direct conversion of human skin fibroblasts towards MSCs using a VW-MSC-specific gene code (HOXB7,HOXC6andHOXC8) that directs cell fate conversion bypassing pluripotency. This direct programming approach using either a self-inactivating (SIN) lentiviral vector expressing the VW-MSC-specific HOX-code or a tetracycline-controlled Tet-On system for doxycycline-inducible gene expressions ofHOXB7,HOXC6andHOXC8successfully mediated the generation of VW-typical MSCs with classical MSC characteristics in vitro and in vivo. The induced VW-MSCs (iVW-MSCs) fulfilled all criteria of MSCs as defined by the International Society for Cellular Therapy (ISCT). In terms of multipotency and clonogenicity, which are important specific properties to discriminate MSCs from fibroblasts, iVW-MSCs behaved like primary ex vivo isolated VW-MSCs and shared similar molecular and DNA methylation signatures. With respect to their therapeutic potential, these cells suppressed lymphocyte proliferation in vitro, and protected mice against vascular damage in a mouse model of radiation-induced pneumopathy in vivo, as well as ex vivo cultured human lung tissue. The feasibility to obtain patient-specific VW-MSCs from fibroblasts in large amounts by a direct conversion into induced VW-MSCs could potentially open avenues towards novel, MSC-based therapies.
An artificial intelligence-based deep learning algorithm for the diagnosis of diabetic neuropathy using corneal confocal microscopy: a development and validation study
Authors: Williams Bryan M. , Borroni Davide , Liu Rongjun , Zhao Yitian , Zhang Jiong , Lim Jonathan , Ma Baikai , Romano Vito , Qi Hong , Ferdousi Maryam , Petropoulos Ioannis N. , Ponirakis Georgios , Kaye Stephen , Malik Rayaz A. , Alam Uazman , Zheng Yalin
Published: November 2019

Aims/hypothesis

Corneal confocal microscopy is a rapid non-invasive ophthalmic imaging technique that identifies peripheral and central neurodegenerative disease. Quantification of corneal sub-basal nerve plexus morphology, however, requires either time-consuming manual annotation or a less-sensitive automated image analysis approach. We aimed to develop and validate an artificial intelligence-based, deep learning algorithm for the quantification of nerve fibre properties relevant to the diagnosis of diabetic neuropathy and to compare it with a validated automated analysis program, ACCMetrics.

Methods

Our deep learning algorithm, which employs a convolutional neural network with data augmentation, was developed for the automated quantification of the corneal sub-basal nerve plexus for the diagnosis of diabetic neuropathy. The algorithm was trained using a high-end graphics processor unit on 1698 corneal confocal microscopy images; for external validation, it was further tested on 2137 images. The algorithm was developed to identify total nerve fibre length, branch points, tail points, number and length of nerve segments, and fractal numbers. Sensitivity analyses were undertaken to determine the AUC for ACCMetrics and our algorithm for the diagnosis of diabetic neuropathy.

Results

The intraclass correlation coefficients for our algorithm were superior to those for ACCMetrics for total corneal nerve fibre length (0.933 vs 0.825), mean length per segment (0.656 vs 0.325), number of branch points (0.891 vs 0.570), number of tail points (0.623 vs 0.257), number of nerve segments (0.878 vs 0.504) and fractals (0.927 vs 0.758). In addition, our proposed algorithm achieved an AUC of 0.83, specificity of 0.87 and sensitivity of 0.68 for the classification of participants without (n= 90) and with (n= 132) neuropathy (defined by the Toronto criteria).

Conclusions/interpretation

These results demonstrated that our deep learning algorithm provides rapid and excellent localisation performance for the quantification of corneal nerve biomarkers. This model has potential for adoption into clinical screening programmes for diabetic neuropathy.

Data availability

The publicly shared cornea nerve dataset (dataset 1) is available athttp://bioimlab.dei.unipd.it/Corneal%20Nerve%20Tortuosity%20Data%20Set.htmandhttp://bioimlab.dei.unipd.it/Corneal%20Nerve%20Data%20Set.htm.
Effects of temperature on carbon circulation in macroalgal food webs are mediated by herbivores
Authors: Ito Maysa , Scotti Marco , Franz Markus , Barboza Francisco R. , Buchholz Björn , Zimmer Martin , Guy-Haim Tamar , Wahl Martin
Published: November 2019

Warming is one of the most dramatic aspects of climate change and threatens future ecosystem functioning. It may alter primary productivity and thus jeopardize carbon sequestration, a crucial ecosystem service provided by coastal environments. Fucus vesiculosus is an important canopy-forming macroalga in the Baltic Sea, and its main consumer is Idotea balthica. The objective of this study is to understand how temperature impacts a simplified food web composed of macroalgae and herbivores to quantify the effect on organic carbon storage. The organisms were exposed to a temperature gradient from 5 to 25 °C. We measured and modeled primary production, respiration, growth and epiphytic load on the surface of Fucus and respiration, growth and egestion of Idotea. The results show that temperature affects physiological responses of Fucus and Idotea separately. However, Idotea proved more sensitive to increasing temperatures than the primary producers. The lag between the collapse of the grazer and the decline of Fucus and epiphytes above 20 °C allows an increase of carbon storage of the primary productivity at higher temperatures. Therefore, along the temperature gradient, the simplified food web stores carbon in a non-monotonic way (reaching minimum at 20 °C). Our work stresses the need of considering the combined metabolic performance of all organisms for sound predictions on carbon circulation in food webs.
Fish stable isotope community structure of a Bahamian coral reef
Authors: Zhu Yiou , Newman Steven P. , Reid William D. K. , Polunin Nicholas V. C.
Published: November 2019

Stable isotopes have provided important insight into the trophic structure and interaction in many ecosystems, but to date have scarcely been applied to the complex food webs of coral reefs. We sampled white muscle tissues from the fish species composing 80% of the biomass in the 4–512 g body mass range at Cape Eleuthera (the Bahamas) in order to examine isotopic niches characterised by δ13C and δ15N data and explore whether fish body size is a driver of trophic position based on δ15N. We found the planktivore isotopic niche was distinct from those of the other trophic guilds suggesting the unique isotopic baseline of pelagic production sources. Other trophic guilds showed some level of overlap among them especially in the δ13C value which is attributable to source omnivory. Surprising features of the isotopic niches included the benthivoreHalichoeres pictus, herbivoresAcanthurus coeruleusandCoryphopterus personatusand omnivoreThalassoma bifasciatumbeing close to the planktivore guild, while the piscivoreAulostomus maculatuscame within the omnivore and herbivore ellipses. These characterisations contradicted the simple trophic categories normally assigned to these species. δ15N tended to increase with body mass in most species, and at community level, the linear δ15N–log2body mass relationship pointing to a mean predator–prey mass ratio of 1047:1 and a relatively long food chain compared with studies in other aquatic systems. This first demonstration of a positive δ15N–body mass relationship in a coral reef fish community suggested that the Cape Eleuthera coral reef food web was likely supported by one main pathway and bigger reef fishes tended to feed at higher trophic position. Such finding is similar to other marine ecosystems (e.g. North Sea).
Stepwise Approach for Parathyroid Localisation in Primary Hyperparathyroidism
Authors: Korwar Vijay , Yuen Chang Fernando , Teasdale Ella , Suchett‐Kaye Ivo , Edwards Anusha , Morgan Justin
Published: November 2019

Introduction

Primary hyperparathyroidism (PHPT) is a relatively common condition in surgical practice. Availability of localisation studies has shifted the treatment from bilateral neck exploration to selective parathyroidectomy. Several imaging modalities, each with varying sensitivities, are available to detect abnormal parathyroid glands. Ultrasound is almost universally accepted as the first line radiological investigation however its sensitivity is particularly heterogeneous and operator‐dependent.

Material and methods

We studied 250 consecutive patients with PHPT who underwent parathyroidectomy in our hospital over a period of 33 months. Pre‐operative neck ultrasound, 99mTc‐sestamibi and single‐photon emission computed tomography (SPECT CT) were performed in 249, 237 and 198 patients respectively. Unilateral and bilateral neck exploration was performed in 190 and 60 patients, respectively. Sensitivity, positive predictive value (PPV) and accuracy were calculated comparing the results with surgical and pathology findings.

Results

Mean pre and postoperative PTH and adjusted calcium were, 11 ± 10.6 pmol/L, 1.9 ± 3.6, 2.81 ± 0.2 and 2.45 ± 0.2 mmol/L. There were 71 (29.95%) discordant results between US, compared to sestamibi and SPECT CT. An average of 1.9 parathyroid glands were removed with a mean weight of 0.92 g. Overall success rate based on postoperative PTH levels was 94.8%. Overall sensitivity, PPV and accuracy for US were 80.80%, 92.35%, and 75.73% respectively; for sestamibi were 71.82%, 94.61%, 69.00% and for SPECT CT were; 70.21%, 97.78%, 69.11% respectively.

Conclusion

Ultrasound performed by an experienced specialist sonographer is highly sensitive in localising abnormal parathyroid glands. It can be used as a main and sole investigation in the majority of patients. Sestamibi, SPECT CT and other investigations should be performed in a step‐wise manner and reserved for patients with negative US, failed primary procedure and recurrences.
Incidence and Risk Factors for Severity of Postoperative Ileus After Colorectal Surgery: A Prospective Registry Data Analysis
Authors: Venara A. , Meillat H. , Cotte E. , Ouaissi M. , Duchalais E. , Mor‐Martinez C. , Wolthuis A. , Regimbeau J. M. , Ostermann S. , Hamel J. F. , Joris J. , Slim K. ,   the GRACE Collaborative Group For Ileus Study, Chapuis O , Guignard B , Saint Denis M , Sirieix D , Arimont JM , Figuet S , Milou F , Hail K , Kothonidis K , Faucheron JL , Sage PY , Mauvais F , Rio D , Guiot JL , Poincenot J , Cuellar E , Luyer M , Boudewijn S , Aumont O , Dupre A , Poiblanc M , Sens N , Brigand C , Steinmetz JP , Plumereau F , Mathonnet M , Christou N , Ortega‐Deballon P , Vauclair E , Bozio G , Fernoux P , Massard JL , Bellouard A , de la Fontaine C , Finianos A , Michaud P , Bossard AE , Denet C , Grigoriu M , Kattou F , Gignoux B , Verrier JF , Raspado O , Arnalsteen L , Lamblin A , Dolbeau JB , Auvray S , Lammens S , Leporrier J , Sirisier F , Dileon S
Published: November 2019

Background

Defining severe postoperative ileus in terms of consequences could help physicians standardize the management of this condition. The recently described classification based on consequences requires further investigation. The aim of this study was to obtain a snapshot of postoperative ileus in patients undergoing colorectal surgery within enhanced recovery programs and to identify factors associated with non‐severe and severe postoperative ileus.

Methods

This prospective registry data analysis was conducted in 40 centers in five different countries. A total of 786 patients scheduled for colorectal surgery within enhanced recovery programs were included. The primary endpoint was the incidence rate of postoperative ileus as defined by Vather et al.

Results

A total of 121 patients experienced postoperative ileus (15.4%). Non‐severe POI occurred in 48 patients (6.1%), and severe postoperative ileus occurred in 73 patients (9.3%). In multivariate analysis, the male gender and intra‐abdominal complications were associated with severe postoperative ileus: odd ratio (OR) = 2.03 [95% confidence interval (CI) 1.14–3.59], p = 0.01 and OR = 3.60 [95% CI 1.75–7.40], p < 0.0001, respectively. Conversely, open laparotomy and urinary retention were associated with non‐severe POI: OR = 3.03 [95% CI 1.37–6.72], p = 0.006 and OR = 2.70 [95% CI 0.89–8.23], p = 0.08, respectively.

Conclusions

Postoperative ileus occurred in 15% of patients after colorectal surgery within enhanced recovery programs. For 60% of patients, this was considered severe. The physiopathology of these two entities could be different, severe POI being linked to intraabdominal complication, while non‐severe POI being linked with risk factors for “primary” POI. The physician should pay attention to male patients having POI after colorectal surgery and look for features evocating intraabdominal complications.
All’s well? Comparing on- and off-site pollen samples and exploring the potential of pollen from man-made contexts
Authors: van Amerongen Yvonne F.
Published: November 2019

Pollen analysis has long been used as a tool to make an assessment of regional vegetation. On-site pollen samples are taken for the same purpose at some excavations, because they are often the only available contexts with good preservation conditions. This paper shows that the analysis of on- and off-site pollen samples from the same region (West Frisia, the Netherlands) and time period (Dutch Bronze Age; ca. 2000–800 bc) can give very conflicting results on the type and amount of regional vegetation, in this case forest cover. Reasons for this discrepancy are discussed in relation to the use of on-site contexts by people in the past, as well as their location within a settlement. Furthermore, the potential of these contexts for the assessment of locally performed subsistence-related activities is outlined. New research directions are required to test this potential, so that wells and other man-made pollen traps can become a valuable future tool for reconstructing the past.
Using micro-computed tomography to examine the larynx in cases of suspected strangulation—a comparison of case findings and control images
Authors: Baier Waltraud , Burnett Brian A. , Payne Mark , Warnett Jason M. , Williams Mark A.
Published: November 2019

The examination of strangulation is one of the most challenging causes of death diagnoses encountered in forensic pathology. The injuries are often subtle and difficult to detect, especially in cases that lack superficial marks. Fractures of the laryngeal skeleton are commonly regarded as evidence of strangulation but these can be too subtle to be detected during autopsy. Micro-CT is a novel imaging technique that achieves a spatial resolution 1 μm or less which lends itself to the examination of small and delicate structures such as the larynx. However, there is little information to date regarding the appearance of the larynx at this scale, thus complicating the interpretation of the micro-CT images. This study therefore uses micro-CT to examine ten larynges from strangulation deaths and to compare them to nineteen samples from donor individuals in order to distinguish between naturally occurring features and actual trauma. It was found that there are several features which mimic damage in the donor group. Using associated case information, initial trends and patterns of different strangulation methods were established.
Functional outcome after recurrent patellar dislocation
Authors: Keilani Mohammad , Palma Stefano , Crevenna Richard , Gaudart Camilla , Hasenöhrl Timothy , Reschl Martin , Huto Nadine , Hajdu Stefan , Widhalm Harald K.
Published: November 2019

Background

There is no final consensus regarding the ideal surgical technique for the treatment of patellar dislocation. The aim of this retrospective pilot study was to describe muscle strength, body composition, self-reported physical performance, and pain in male patients after patellar dislocation treatment with two different surgical techniques: medial patellofemoral ligament (MPFL) reconstruction vs. the Elmslie-Trillat procedure.

Methods

Isokinetic testing of knee extensor muscles was performed using a Biodex System 3 pro dynamometer at an angular velocity of 60°/s. Body composition was measured with bioelectrical impedance analysis (Nutribox). Self-reported physical performance and pain were assessed by the SF-36 subscales of physical functioning, role physical and bodily pain. The outcome variables of peak torque normalized to participant’s body mass (Nm/kg), lean body mass, phase angle, self-reported physical performance, and pain were compared between the study groups.

Results

Of the 12 included male patients, 6 had been treated with MPFL reconstruction (age: median = 33 years, range = 18–38 years; BMI: median = 26 kg/m2, range = 23–29) and 6 with the Elmslie-Trillat procedure (age: median = 26 years, range = 19–32 years; BMI: median = 23 kg/m2, range = 19–28). No statistically significant differences were found between the groups in any outcome parameter of muscle strength, body composition, self-reported physical performance, or pain.

Conclusions

The results of the present pilot study revealed that MPFL reconstruction shows equal results to the Elmslie-Trillat procedure, with respect to isokinetic knee muscle strength, body composition, self-reported physical performance and pain in male patients suffering from recurrent patellar dislocation.
Viability of pico- and nanophytoplankton in the Baltic Sea during spring
Authors: Vanharanta Mari , Elovaara Samu , Franklin Daniel J. , Spilling Kristian , Tamelander Tobias
Published: November 2019

Phytoplankton cell death is an important process in marine food webs, but the viability of natural phytoplankton communities remains unexplored in many ecosystems. In this study, we measured the viability of natural pico- and nanophytoplankton communities in the central and southern parts of the Baltic Sea (55°21′ N, 17°06′ E–60°18′ N, 19°14′ E) during spring (4th–15th April 2016) to assess differences among phytoplankton groups and the potential relationship between cell death and temperature, and inorganic nutrient availability. Cell viability was determined by SYTOX Green cell staining and flow cytometry at a total of 27 stations representing differing hydrographic regimes. Three general groups of phytoplankton (picocyanobacteria, picoeukaryotes, and nanophytoplankton) were identified by cytometry using pigment fluorescence and light scatter characteristics. The picocyanobacteria and picoeukaryotes had significantly higher cell viability than the nanophytoplankton population at all depths throughout the study area. Viability correlated positively with the photosynthetic efficiency (Fv/Fm, maximum quantum yield of photosystem II) as measured on the total phytoplankton community. However, an anticipated correlation with dissolved organic carbon was not observed. We found that the abiotic factors suggested to affect phytoplankton viability in other marine ecosystems were not as important in the Baltic Sea, and other biotic processes, e.g. processes related to species succession could have a more pronounced role.