bluuebunny/crossref_metadata_2025 huggingface dataset:
An accurate and noninvasive skin cancer screening based on imaging technique
Authors: Rajput Gunjan , Agrawal Shashank , Raut Gopal , Vishvakarma Santosh Kumar
Published: June 2021

In the last decade, the public health problem is the primary consciousness worldwide, and cancer is especially the central issue. Further, skin cancer comes in the top‐3 of the world's most common cancer. We have proposed an efficient convolutional neural network (CNN) model that identifies skin cancer problems accurately. Although dataset HAM10K is used for the classification problem, its samples for each class are highly imbalanced and therefore are accountable for lower training accuracy. The AlexNet model is customized for the HAM10K data classification to address this problem. In addition, this work has presented an activation function that overcomes the vanishing gradient problem, and it is verified using the used dataset at multiple benchmark architectures. The results show better accuracy compared to the state‐of‐the‐art activation function. Our customized CNN architecture with the proposed activation function has 98.20% accuracy for HAM10K, which is better than any other state‐of‐the‐art models currently present. Further, precision, recall, and F‐score results are also improved, which are also 98.20%.
Existence, uniqueness, and Hyers–Ulam stability of solutions to nonlinear p‐Laplacian singular delay fractional boundary value problems
Authors: Aslam Muhammad , Gómez‐Aguilar José Francisco , ur‐Rahman Ghaus , Murtaza Rashid
Published: June 2021

In this article, we study existence, uniqueness, and stability analysis in Hyer–Ulam settings of delay fractional differential equations with nonlinear singular p‐Laplacian operator ϕp. The fractional operators are taken in the Caputo sense. The fractional differential equation is converted into an integral form with the Green's theorem, also a fixed point approach is studied for this article. We include an example with specific parameter and assumptions to show the results of the proposal. Our results generalize some of the works in the literature.
Optimal control of a crop irrigation model under water scarcity
Authors: Boumaza Kenza , Kalboussi Nesrine , Rapaport Alain , Roux Sébastien , Sinfort Carole
Published: June 2021

We consider a simple crop irrigation model and study the optimal control which consists of maximizing the biomass production at harvesting time. A specificity of this work is to impose a quota on the water used for irrigation, in a context of limited resources. The model is written as a 2d non‐autonomous dynamical system with a state constraint, and a non‐smooth right member given by threshold‐based soil and crop water stress functions. We show that when the water quota is below the threshold giving the largest possible production, the optimal strategy consists of irrigating once. We then show that the optimal solution can have one or several singular arcs, and therefore be better than simple bang‐bang controls, as commonly used. The gains over the best bang‐bang controls are illustrated on numerical simulations. These new feedback controls that we obtain are a promising first step towards the concrete application of control theory to the problem of optimal irrigation scheduling under water scarcity.
Geniposide downregulates the VEGF/SphK1/S1P pathway and alleviates angiogenesis in rheumatoid arthritis in vivo and in vitro
Authors: Wang Yan , Wu Hong , Deng Ran , Dai Xue‐jing , Bu Yan‐hong , Sun Ming‐hui , Zhang Heng , Wang Meng‐die , Wang Rong‐hui
Published: June 2021

The VEGF/SphK1/S1P pathway is closely related to angiogenesis in rheumatoid arthritis (RA), but the precise underlying mechanisms are unclear at present. Here, we explored the involvement of the VEGF/SphK1/S1P cascade in RA models and determined the effects of GE intervention. Our results showed abnormal expression of proteins related to this pathway in RA synovial tissue. Treatment with GE effectively regulated the signal axis, inhibited angiogenesis, and alleviated RA symptoms. In vitro, TNF‐ɑ enhanced the VEGF/SphK1/S1P pathway in a co‐culture model of fibroblast‐like synoviocytes (FLS) and vascular endothelial cells (VEC). GE induced downregulation of VEGF in FLS, restored the dynamic balance of pro‐/antiangiogenic factors, and suppressed SphK1/S1P signaling in VEC, resulting in lower proliferation activity, migration ability, tube formation ability, and S1P secretion ability of VEC cells. Additionally, SphK1‐specific small interfering RNA (siRNA) blocked the VEGF/SphK1/S1P cascade, which can effectively alleviate the stimulatory effect of FLS on VEC and further enhanced the therapeutic effect of GE. Taken together, our results demonstrate that GE suppresses the VEGF/SphK1/S1P pathway and alleviates the stimulation of VEC by FLS, thereby preventing angiogenesis and promoting therapeutic effects against RA.
Output feedback fuzzy control of nonlinear dynamic systems: Event‐triggered case
Authors: Su Xiaojie , Chen Qianqian , Jiao Chunting , Dai Xin
Published: June 2021

The event‐triggered output feedback controller design problem is investigated in this article for a class of discrete‐time Takagi–Sugeno fuzzy systems. We focus on constructing a closed‐loop system by considering the event generator communication mechanism, interval time‐varying delays, and packet dropouts. Under this newly established system, a less conservative stability condition is obtained using the Wirtinger‐based inequality and reciprocally convex approach, which guarantees that the corresponding augmented system is asymptotically stable in the mean‐squared sense with a prespecified – performance. The solution of the designed output feedback controller parameters can then be obtained by variable substitution method and by conversion of the controller parameters. Finally, two examples are presented to demonstrate the effectiveness of the proposed controller design technique.
Electrochemical Installation of CFH2−, CF2H−, CF3−, and Perfluoroalkyl Groups into Small Organic Molecules
Authors: Kisukuri Camila M. , Fernandes Vitor A. , Delgado José A. C. , Häring Andreas P. , Paixão Márcio W. , Waldvogel Siegfried R.
Published: June 2021

Electrosynthesis can be considered a powerful and sustainable methodology for the synthesis of small organic molecules. Due to its intrinsic ability to generate highly reactive species under mild conditions by anodic oxidation or cathodic reduction, electrosynthesis is particularly interesting for otherwise challenging transformations. One such challenge is the installation of fluorinated alkyl groups, which has gained significant attention in medicinal chemistry and material science due to their unique physicochemical features. Unsurprisingly, several electrochemical fluoroalkylation methods have been established. In this review, we survey recent developments and established methods in the field of electrochemical mono‐, di‐, and trifluoromethylation, and perfluoroalkylation of small organic molecules.
Atractylodin attenuates the expression of MUC5AC and extracellular matrix in lipopolysaccharide‐induced airway inflammation by inhibiting the NF‐κB pathway
Authors: Dong Yanpeng , Zhang Xiao , Yao Chuan , Xu Rui , Tian Xiaohong
Published: June 2021

This study aimed to explore the effects of atractylodin (ATR) on lipopolysaccharide (LPS)‐induced inflammatory response in human airway epithelial cells. The cytotoxicity was assessed by CCK‐8 assay. The mRNA expression and concentration of interleukin (IL)‐6, IL‐8, and mucin 5AC (MUC5AC) were measured by qRT‐PCR and ELISA, respectively. Western blotting was performed to determine protein expression. We found that LPS stimulation increased the mRNA expression and concentrations of IL‐6, IL‐8, and MUC5AC, as well as the expression of Col‐I and FN in 16HBE cells, but this effect of LPS was attenuated by ATR treatment. Mechanistically, ATR suppressed LPS‐induced activation of the NF‐κB pathway in 16HBE cells. Moreover, ATR repressed ovalbumin‐induced airway inflammation and NF‐kB pathway in mice. In conclusion, ATR attenuated the expression of MUC5AC and ECM in LPS‐induced airway inflammation by inhibiting the NF‐κB pathway.
Pitfalls and advances in morphometric sexing: insights from the Adélie penguin Pygoscelis adeliae
Authors: Fattorini Niccolò , Olmastroni Silvia
Published: June 2021

Sexing weakly/criptically dimorphic birds requires invasive techniques or molecular analysis. Alternatively, sexing can be based upon morphometric analysis, which remains invaluable in remote field conditions such as Polar regions. Nevertheless, discriminatory power may be affected by methodological issues hampering comparison between/within studies, e.g. considering alternative analytical techniques or measurements taken by different researchers. We investigated the sexing potential of bill length, bill depth and body mass in adult Adélie penguinsPygoscelis adeliaeof known sex. We performed discriminant analysis on a large dataset of measurements (237 males; 264 females) taken from penguins marked between 1994 and 2001, at Edmonson Point (Ross Sea, Antarctica). In a second step, we accounted for measurements collected by different researchers through permuted discriminant analysis. We found moderate support for sex discrimination through bill measurements (77%). Considering body mass did not improve classification power substantially (78.2%), possibly because of confounding inter/intra-annual oscillations in body condition. Discriminant rate decreased when controlling the researcher effect (72.7% and 71.4%, respectively). Results were also confirmed by logistic (mixed) models. Simulations showed that reduction in sample size markedly increased uncertainty in classification power. Differences with previous studies achieving a slightly greater classification power for sexing Adélie penguins through morphometrics could be related to (i) our higher sample size and/or (ii) geographical, population-specific differences, e.g. lower degree of sexual dimorphism. Our work emphasises key-factors influencing performance of morphometric sexing in avian species, advocating population-specific validation with large sample size as well as the necessity to account for the researcher effect prior to apply morphometric sexing.
Saltmarsh archives of vegetation and land use change from Big River Marsh, SW Newfoundland, Canada
Authors: Selby Katherine A. , Roe Helen M. , Wright Alexander J. , van de Plassche Orson , Derrett Sally R.
Published: June 2021

Pollen and plant macrofossils are often well-preserved in coastal sediments, providing a palaeoenvironmental record of sea-level and landscape change. In this study, we examine the pollen and plant macrofossil assemblages of a well-dated saltmarsh sediment core from southwest Newfoundland, Canada, to establish recent coastal vegetation and land use change, to increase the knowledge of anthropogenic activities in the area and develop pollen chronozones for reconstructing marsh accumulation rates and to examine the representation of plant macrofossil remains in the wetland pollen profile. Grouping the pollen record into upland and wetland assemblages allows local events related to hydrological change to be separated from landscape-scale changes. The wetland pollen and plant macrofossil records indicate a general acceleration in sea-level rise ca. ad 1700. The sedge pollen and plant macrofossil records attest to multiple phases of rhizome encroachment during inferred periods of marine regression. Two chronozones are identified from the upland pollen profile; the first associated with the settlement of St. George’s Bay ca. ad 1800, signalled by increases in Plantago lanceolata and Ambrosia pollen; the second with the permanent settlement of the Port au Port peninsula ca. ad 1850, indicated by increased P. lanceolata and Rumex pollen. Comparison of the plant macrofossil and wetland pollen profiles highlights the underrepresentation of grass pollen preserved in the saltmarsh sediments and a need for further analysis of the zonation, pollen dispersal and macrofossil representation of sedge species in saltmarshes.
Wie viele Patienten mit entzündlich rheumatischen Erkrankungen haben die technischen Voraussetzungen für Videosprechstunden und sind bereit, fachärztliche Visiten so durchzuführen?
Authors: Baraliakos X. , Alshakaki F. , Bühring B. , Andreica I. , Kiltz U. , Braun J.
Published: June 2021

Hintergrund

Die aktuell grassierende SARS-CoV-2-Pandemie und begrenzte Kapazitäten in der ambulanten rheumatologischen Versorgung werfen, auch angesichts der digitalen Revolution, Fragen nach möglichen Alternativen zu klinischen Visiten auf. Ob und inwieweit Patienten mit entzündlich rheumatischen Erkrankungen bereit und in der Lage sind, mit den neuen Medien wie etwa Videosprechstunden (VSS) umzugehen, ist unklar.

Methoden

Mitten in der Pandemie wurden im Mai 2020 ambulante Patienten mit einem standardisierten Fragebogen systematisch befragt, um ihre Möglichkeiten und die Bereitschaft für die Teilnahme an VSS zu ermitteln. Der behandelnde Arzt gab an, ob er die Durchführung einer VSS für möglich und auch für sinnvoll hielt.

Ergebnisse

Insgesamt wurden 232 Patienten mit entzündlich rheumatischen Erkrankungen befragt (64,7 % weiblich, mittleres Alter 54,0 ± 15,2 Jahre), seropositive (n = 58) und seronegative (n = 51) rheumatoide Arthritis (RA), Spondyloarthritis (SpA) (n = 77) inklusive der axialen SpA (axSpA) und der Psoriasisarthritis (PsA) sowie Kollagenosen und Vaskulitiden (KoV) (n = 46). Die mittlere Krankheitsdauer betrug 5,5 ± 8,2 Jahre, bei 75 Patienten (32,3 %) handelte es sich um eine Erstdiagnose. Die mittlere Krankheitsaktivität (0–10, subjektive Patienteneinschätzung) lag bei 4,7 ± 2,5. Insgesamt wussten 176 Patienten grundsätzlich über die Möglichkeit der Durchführung von VSS Bescheid (75,9 %), und 166 sahen sich technisch in der Lage, daran teilzunehmen (71,6 %), aber nur 131 waren grundsätzlich auch bereit dazu (56,5 %). Die logistische Regressionsanalyse zeigte, dass die Bereitschaft zur Teilnahme an VSS mit zunehmendem Alter abnahm (β = 0,28, p = 0,01). Nach ärztlicher Einschätzung wurden VSS bei 161 Patienten aus technischen (69,4 %) und bei 127 aus medizinischen Gründen (54,7 %) prinzipiell für möglich gehalten. Die Durchführung von VSS im Rahmen der Versorgung wurde vom Arzt aber nur bei 76 Patienten (32,8 %) für sinnvoll gehalten.

Nicht alle Patienten können oder wollen an VSS teilnehmen, mit zunehmendem Alter nimmt die Bereitschaft dazu ab. Auch die ärztliche Einschätzung der Sinnhaftigkeit von VSS beschränkte sich auf etwa ein Drittel der befragten Patienten. Dies ist für zukünftige Planungen von VSS zu berücksichtigen.
Imitating evolution’s tinkering by protein engineering reveals extension of human galectin-7 activity
Authors: Ludwig Anna-Kristin , Michalak Malwina , Gabba Adele , Kutzner Tanja J. , Beckwith Donella M. , FitzGerald Forrest G. , García Caballero Gabriel , Manning Joachim C. , Kriegsmann Mark , Kaltner Herbert , Murphy Paul V. , Cudic Maré , Kopitz Jürgen , Gabius Hans-Joachim
Published: June 2021

Wild-type lectins have distinct types of modular design. As a step to explain the physiological importance of their special status, hypothesis-driven protein engineering is used to generate variants. Concerning adhesion/growth-regulatory galectins, non-covalently associated homodimers are commonly encountered in vertebrates. The homodimeric galectin-7 (Gal-7) is a multifunctional context-dependent modulator. Since the possibility of conversion from the homodimer to hybrids with other galectin domains, i.e. from Gal-1 and Gal-3, has recently been discovered, we designed Gal-7-based constructs, i.e. stable (covalently linked) homo- and heterodimers. They were produced and purified by affinity chromatography, and the sugar-binding activity of each lectin unit proven by calorimetry. Inspection of profiles of binding of labeled galectins to an array-like platform with various cell types, i.e. sections of murine epididymis and jejunum, and impact on neuroblastoma cell proliferation revealed no major difference between natural and artificial (stable) homodimers. When analyzing heterodimers, acquisition of altered properties was seen. Remarkably, binding properties and activity as effector can depend on the order of arrangement of lectin domains (from N- to C-termini) and on the linker length. After dissociation of the homodimer, the Gal-7 domain can build new functionally active hybrids with other partners. This study provides a clear direction for research on defining the full range of Gal-7 functionality and offers the perspective of testing applications for engineered heterodimers.
FFT phase-field model combined with cohesive composite voxels for fracture of composite materials with interfaces
Authors: Chen Yang , Gélébart Lionel , Marano Aldo , Marrow James
Published: June 2021

A framework for damage modelling based on the fast Fourier transform (FFT) method is proposed to combine the variational phase-field approach with a cohesive zone model. This combination enables the application of the FFT methodology in composite materials with interfaces. The composite voxel technique with a laminate model is adopted for this purpose. A frictional cohesive zone model is incorporated to describe the fracture behaviour of the interface including frictional sliding. Representative numerical examples demonstrate that the proposed model is able to predict complex fracture behaviour in composite microstructures, such as debonding, frictional sliding of interfaces, crack deviation and coalescence of interface cracking and matrix cracking.
Gland cell responses to feeding in Drosera capensis, a carnivorous plant
Authors: Lichtscheidl Irene , Lancelle Sue , Weidinger Marieluise , Adlassnig Wolfram , Koller-Peroutka Marianne , Bauer Sonja , Krammer Stefanie , Hepler Peter K.
Published: June 2021

Glands of Drosera absorb and transport nutrients from captured prey, but the mechanism and dynamics remain unclear. In this study, we offered animal proteins in the form of fluorescent albumin (FITC-BSA) and observed the reactions of the glands by live cell imaging and fluorescence microscopy. The ultrastructure of these highly dynamic processes was also assessed in high-pressure frozen and freeze substituted (HPF-FS) cells. HPF-FS yielded excellent preservation of the cytoplasm of all cell types, although the cytosol looked different in gland cells as compared to endodermoid and stalk cells. Especially prominent were the ER and its contacts with the plasma membrane, plasmodesmata, and other organelles as well as continuities between organelles. Also distinct were actin microfilaments in association with ER and organelles. Application of FITC-BSA to glands caused the formation of fluorescent endosomes that pinched off the plasma membrane. Endosomes fused to larger aggregates, and accumulated in the bulk cytoplasm around the nucleus. They did not fuse with the cell sap vacuole but remained for at least three days; in addition, fluorescent vesicles also proceeded through endodermoid and transfer cells to the epidermal and parenchymal cells of the tentacle stalk.
Arbitrary-order intrinsic virtual element method for elliptic equations on surfaces
Authors: Bachini Elena , Manzini Gianmarco , Putti Mario
Published: June 2021

We develop a geometrically intrinsic formulation of the arbitrary-order Virtual Element Method (VEM) on polygonal cells for the numerical solution of elliptic surface partial differential equations (PDEs). The PDE is first written in covariant form using an appropriate local reference system. The knowledge of the local parametrization allows us to consider the two-dimensional VEM scheme, without any explicit approximation of the surface geometry. The theoretical properties of the classical VEM are extended to our framework by taking into consideration the highly anisotropic character of the final discretization. These properties are extensively tested on triangular and polygonal meshes using a manufactured solution. The limitations of the scheme are verified as functions of the regularity of the surface and its approximation.
Local regularity for concave homogeneous complex degenerate elliptic equations dominating the Monge–Ampère equation
Authors: Abja Soufian , Olive Guillaume
Published: June 2021

In this paper, we establish a local regularity result for $$W^{2,p}_{{\mathrm {loc}}}$$

W
loc

2
,
p

solutions to complex degenerate nonlinear elliptic equations $$F(D^2_{\mathbb {C}}u)=f$$

F
(

D
C
2

u
)
=
f

when they dominate the Monge–Ampère equation. Notably, we apply our result to the so-called k-Monge–Ampère equation.
Effects of La2O3 Addition into CaO-SiO2 Slag: Structural Evolution and Impurity Separation from Si-Sn Alloy
Authors: Zhu Mengyi , Wu Guixuan , Azarov Alexander , Monakhov Eduard , Tang Kai , Müller Michael , Safarian Jafar
Published: June 2021

Boron (B) and phosphorus (P) are the most problematic impurities to be removed in the production of solar-grade silicon by the metallurgical process. In this work, the distribution of B and P between CaO-(La2O3)-SiO2 slags and Si-10 mass pct Sn melt was experimentally studied. B distribution coefficient increased from 2.93 in binary CaO-SiO2 slag to 3.33 and 3.65 with 2 and 10 mass pct La2O3 additions, respectively. In the followed acid-leaching experiments, the slag-treated Si-Sn alloys exhibited higher B and P removal than that of the initial alloy without slag treatment. Molecular dynamics simulations were performed to study the effect of La2O3 addition on the slag structural and transport properties. A novel oxygen classification method was proposed to distinguish the different structural roles of La and Ca in the CaO-La2O3-SiO2 system. It was found that La3+ prefers to stay in the depolymerized region, mostly connects with 6-7 non-bridging oxygen, and requires a weak charge compensation with Ca2+. Possible silicothermic reduction was evaluated to discuss the slag chemistry and the mass transfer between slag and metal phase. A thermodynamic model was derived to theoretically study the alloying effect on impurity distribution in slag refining where positive interaction coefficient and high alloying concentration were found most beneficial to improve the impurity removal.
Behaviorally targeted location-based mobile marketing
Authors: Bernritter Stefan F. , Ketelaar Paul E. , Sotgiu Francesca
Published: June 2021

Marketers increasingly use behavioral targeting in location-based mobile marketing (LBMM). However, highly personalized marketing messages like this may backfire by eliciting consumer reactance. We suggest that LBMM efficacy depends on its potential to minimize consumer reactance, which can be achieved by effectively combining location targeting (in-store vs. out-store), behavioral targeting (based on consumers’ product category involvement [PCI]), and the type of promotion offered (price vs. non-price promotion). Results of a field study, a virtual reality experiment, and two online experiments show that although in-store mobile ads are generally more effective in increasing sales than out-store mobile ads, this is only the case if consumers have low PCI with the advertised product category, because this decreases their reactance. To attract consumers to stores by out-store LBMM, we show that firms should offer price promotions to consumers with low PCI and non-price promotions to consumers with high PCI, because these combinations of location targeting, behavioral targeting, and type of promotion elicit the least reactance and therefore result in a higher probability to buy.
Air pollution perception in ten countries during the COVID-19 pandemic
Authors: Lou Baowen , Barbieri Diego Maria , Passavanti Marco , Hui Cang , Gupta Akshay , Hoff Inge , Lessa Daniela Antunes , Sikka Gaurav , Chang Kevin , Fang Kevin , Lam Louisa , Maharaj Brij , Ghasemi Navid , Qiao Yaning , Adomako Solomon , Foroutan Mirhosseini Ali , Naik Bhaven , Banerjee Arunabha , Wang Fusong , Tucker Andrew , Liu Zhuangzhuang , Wijayaratna Kasun , Naseri Sahra , Yu Lei , Chen Hao , Shu Benan , Goswami Shubham , Peprah Prince , Hessami Amir , Abbas Montasir , Agarwal Nithin
Published: June 2021

As largely documented in the literature, the stark restrictions enforced worldwide in 2020 to curb the COVID-19 pandemic also curtailed the production of air pollutants to some extent. This study investigates the perception of the air pollution as assessed by individuals located in ten countries: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the USA. The perceptions towards air quality were evaluated by employing an online survey administered in May 2020. Participants (N = 9394) in the ten countries expressed their opinions according to a Likert-scale response. A reduction in pollutant concentration was clearly perceived, albeit to a different extent, by all populations. The survey participants located in India and Italy perceived the largest drop in the air pollution concentration; conversely, the smallest variation was perceived among Chinese and Norwegian respondents. Among all the demographic indicators considered, only gender proved to be statistically significant.
Do commodity prices incentivize exploration permit application? An explorative study of an anecdotal relation
Authors: Olofsson Tobias
Published: June 2021

Do commodity prices drive exploration permit applications? In a recent qualitative study on mineral exploration and risk management in Sweden, a number of respondents representing mineral exploration organizations and governmental agencies expressed how mineral exploration permit applications increase with rising commodity prices. This paper seeks to investigate this alleged correlation quantitatively. In doing so, the study uses time series analysis and ARIMA models to analyze the covariation of applications for exploration permits filed with the Mining Inspectorate of Sweden and annual average copper, lead, zinc, silver, and gold prices in the period 2000 to 2018. Contrary to the anecdotal evidence given by actors in the exploration and mining industry, the paper cannot show any significant covariation between the majority of mineral prices and applications filed. Contrary to expectations, there appear therefore not to be any correlation between copper, lead, silver, and gold prices and the volume of permit applications filed annually. Moreover, the study also shows that the correlation between annual average zinc prices and permit applications appears to be the reverse of what was first believed as the annual change in application volume occurs before the rise or fall in zinc prices.
Unifying the Hepatopancreatobiliary Surgery Fellowship Curriculum via Delphi Consensus
Authors: Park Keon Min , Rashidian Nikdokht , Mohamedaly Sarah , Brasel Karen J. , Conroy Patricia , Glencer Alexa C. , He Jin , Passeri Michael J. , Katariya Nitin N. , Alseidi Adnan
Published: June 2021

BACKGROUND:

Hepatopancreatobiliary (HPB) Fellowship training in the Americas consists of 3 distinctive routes with variable curricula: Surgical Oncology Fellowship via the Society of Surgical Oncology (SSO), Abdominal Transplant Surgery Fellowship via the American Society of Transplant Surgeons (ASTS), and HPB Fellowship via the Americas Hepato-Pancreato-Biliary Association (AHPBA). Our objective was to establish a pan-American consensus among HPB surgeons, surgical oncologists, abdominal transplant surgeons, and general surgery residency program directors (GSPDs) on a core knowledge curriculum for HPB fellowship, and to identify topics appropriate for general surgery residency and subspecialty beyond HPB fellowship.

STUDY DESIGN:

A 3-round modified Delphi process was used. Baseline statements were developed by the Education and Training Committee of the AHPBA, in collaboration with representatives of the SSO, ASTS, and GSPDs. The expert panel, consisting of members of the 3 societies together with GSPDs, rated the statements on a 5-point Likert scale and suggested editing or adding new statements. A statement was included in the final curriculum when Cronbach's alpha value was ≥ 0.8 and ≥ 80% of the panel agreed on inclusion.

RESULTS:

The response rate was 100% for the first round, and 98% for the second and third rounds. Eighty-nine of 138 proposed statements were included in the final HPB fellowship curriculum. Curricula for general surgery residency and subspecialty beyond HPB fellowship included 50 and 29 statements, respectively.

CONCLUSIONS:

A multinational consensus on core knowledge for an HPB fellowship curriculum was achieved via the modified Delphi method. This core curriculum may be used to standardize HPB fellowship training across different pathways in the Americas.
Status as a Reward
Authors: Johnstone Ian
Published: June 2021

Rewarding in International Law foregrounds a topic that has been in the compliance literature for years but, as Anne van Aaken and Betül Simsek point out, tends to get treated as the mirror opposite of penalizing and therefore of little distinct analytical significance. In this essay, I seek to engage with their argument not by way of critique but rather to highlight some gaps and build on their insights. I introduce the notion of “status” as a reward and identify institutional mechanisms for conferring status, arguing that this is especially important in the multilateral context where institutions tend to be more prominent than in bilateral, transactional relations.
Primary Adult-Onset Hemophagocytic Lymphohistiocytosis with Neurologic Presentation
Authors: Southam Cormac , Grossman Jennifer , Hahn Chris
Published: June 2021

Hemophagocytic lymphohistiocytosis (HLH) is a rare immune deregulatory disorder that predominantly presents in children. Here we describe three patients with adult-onset primary HLH whose initial presentations were characterized by neurological features, and we review the literature of published cases. These cases ranged in age from 17 to 30 and presented with a variety of neurological symptoms. One of our cases demonstrated numerous microhemorrhages on MR brain. This is the first published case of adult-onset HLH presenting with cerebral microhemorrhages. In addition, literature review identified five additional patients with isolated central nervous system presentation of primary HLH.
Simulations of ionospheric refraction on radio interferometric data
Authors: Chege J. Kariuki , Jordan C. H. , Lynch C. , Line J. L. B. , Trott C. M.
Published: June 2021

The Epoch of Reionisation (EoR) is the period within which the neutral universe transitioned to an ionised one. This period remains unobserved using low-frequency radio interferometers, which target the 21 cm signal of neutral hydrogen emitted in this era. The Murchison Widefield Array (MWA) radio telescope was built with the detection of this signal as one of its major science goals. One of the most significant challenges towards a successful detection is that of calibration, especially in the presence of the Earth’s ionosphere. By introducing refractive source shifts, distorting source shapes, and scintillating flux densities, the ionosphere is a major nuisance in low-frequency radio astronomy. We introducesivio, a software tool developed for simulating observations of the MWA through different ionospheric conditions, which is estimated using thin screen approximation models and propagated into the visibilities. This enables us to directly assess the impact of the ionosphere on observed EoR data and the resulting power spectra. We show that the simulated data captures the dispersive behaviour of ionospheric effects. We show that the spatial structure of the simulated ionospheric media is accurately reconstructed either from the resultant source positional offsets or from parameters evaluated during the data calibration procedure. In turn, this will inform on the best strategies of identifying and efficiently eliminating ionospheric contamination in EoR data moving into the Square Kilometre Array era.
The Italian State's Active Support for the Aeronautical Industry: The Case of the Caproni Group, 1910–1951
Authors: Fauri Francesca
Published: June 2021

Based on Italian and foreign archival sources, this study shows how Italy's active assistance to its industrial apparatus soon included the newly born aircraft industry, including the Caproni Group. However, after World War II the Group went bankrupt along with most aircraft manufacturers. The suspension of aircraft development, the preference for importing allied (American and British) aircraft for civil airlines, and the denial of international assistance were the ensuing political and economic costs of defeat. In the end, Italy nationalized what was left of its aviation firms. Also, nationalization was consistent with its industrial history and represented the only way to help this sector survive.
Inflammatory bowel disease and the gut microbiota
Authors: Wu Nan , Mah Cassandra , Koentgen Sabrina , Zhang Leo , Grimm Michael C. , El-Omar Emad , Hold Georgina L.
Published: June 2021

Inflammatory bowel disease (IBD) is a group of immune-mediated disorders characterised by a chronic, relapsing-remitting inflammation predominantly affecting the gastrointestinal tract. IBD is incurable, affecting people in their most productive years. IBD is historically seen as a disease of Westernised nations although in recent times other countries have seen an exponential rise in cases. Although the exact pathogenesis remains unclear, evidence suggests that microbiota changes play a critical role in IBD pathogenesis. Over the past two decades, IBD has become one of the most studied human conditions linked to the gut microbiota. However, deciphering the intricate link between the gut microbiota and therapeutic efficacy remains elusive. This review will summarise the current evidence relating to the gut microbiota and its involvement in IBD pathogenesis as well as the impact of IBD treatments including pharmaceutical-, nutraceutical- and microbial-focused regimens on the gut microbiota.
Trisomy 21, transposition of the great arteries and abnormal myelopoiesis
Authors: Mishra Chandan , Kadiyani Lamk , Ramakrishnan Sivasubramanian , Sehgal Tushar
Published: June 2021

Down syndrome is a well-recognised genetic condition associated with several comorbidities. Although CHD is common in Down syndrome, transposition of the great arteries is exceptionally rare. We describe a neonate with Down syndrome who presented with transient abnormal myelopoiesis and transposition of the great arteries. Down syndrome may accelerate pulmonary hypertension in transposition of the great arteries and is associated with poor outcomes.
Treatment of refractory obsessive–compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study
Authors: Sarris Jerome , Byrne Gerard J. , Oliver Georgina , Cribb Lachlan , Blair-West Scott , Castle David , Dean Olivia M. , Camfield David A. , Brakoulias Vlasios , Bousman Chad , Dowling Nathan , Ee Carolyn , Murphy Jenifer , Menon Ranjit , Berk Michael , Chamoli Suneel , Boschen Mark , Ng Chee H.
Published: June 2021

Background

Obsessive–compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach.

Objective

To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD:N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5′ phosphate, and selenium.

Methods

A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive–Compulsive Scale (YBOCS), administered every 4 weeks.

Results

An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of −7.13 (95% confidence interval = −9.24, −5.01), with a mean reduction of −1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered “responders” (YBOCS ≥35% reduction and “very much” or “much improved” on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD.

Conclusions

While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.
Overestimation of body weight and its association with parental, teacher and peer support: evidence from the Israeli Health Behaviours in Schools survey
Authors: Ben-Yaish Shir , Tesler Riki , Boaz Mona , Harel Fisch Yossi , Kaufman-Shriqui Vered
Published: June 2021

Objective:

To investigate the association between family, teachers and peer support patterns on gaps in adolescent’s weight perceptions.

Design:

A cross-sectional, school-based survey collected information on weight and height, weight perception, socio-economic and family characteristics and social support. Principal component analysis (PCA) was performed to capture social support patterns (SSP). Multivariable logistic regression was used to model adolescent weight perception, including SSP adjusted for demographic variables.

Setting:

The 2014 Israeli Health Behaviours in School-Aged Children (HBSC) survey.

Participants:

Adolescents aged 11–18 years (n 7563).

Results:

In total, 16·1 % of the boys and 10·7 % of the girls were overweight or obese. Most participants perceived their size accurately. Body size was underestimated by 25·6 % of the boys and 15·1 % of the girls, while 15·2 % of the boys and 27·7 % of the girls overestimated their body size. PCA generated three SSP accounting for 81·9 % of the variance in social support. Female sex and higher SES increased odds of overestimating body size. Students in the top quartile (Q4 v. Q1–Q3) of family support and teacher support were less likely to overestimate their body size. Good parental communication reduced the odds of body size overestimation in middle school students. Male sex and higher family support increased odds of underestimation.

Conclusions:

Significant support from parents and teachers was associated with accurate weight perceptions; thus, support skills may be amenable to intervention. Efforts should be made to educate adolescents on healthy weight.
Impact of early response on outcomes in AL amyloidosis following treatment with frontline Bortezomib
Authors: Ravichandran Sriram , Cohen Oliver C. , Law Steven , Foard Darren , Fontana Marianna , Martinez-Naharro Ana , Whelan Carol , Gillmore Julian D. , Lachmann Helen J. , Sachchithanantham Sajitha , Mahmood Shameem , Hawkins Philip N. , Wechalekar Ashutosh D.
Published: June 2021

The outcomes in systemic AL amyloidosis are dependent on the depth of haematologic response. However, there is limited data on the impact of the speed of response on outcomes. Here we report the impact of speed of response in a cohort of AL patients treated with upfront Bortezomib. Patients seen from February 2010 until August 2019 are included in the present analysis. 1194 & 1133 patients comprised the ITT and 1-month landmark cohorts. In the landmark cohort, 137 (11.5%), 270 (22.6%), 252 (21.1%) and 352 (31.1%) patients had a CR, VGPR, PR and NR at 1-month. Patients with ≥ VGPR at 1-month had significantly better survival (median not reached; at the end of 1, 2, 5,10 years, 87%/92%, 83%/87%, 68%/72% and 63%/58% of patients in CR/VGPR, respectively, were alive) compared to those with a PR (median OS 60 months) or NR (median OS 32 months) (p < 0.005). At 1-month, patients with CR and iFLC < 20 mg/l had a significantly better survival compared to CR and iFLC > 20 mg/l (p = 0.005). Reaching ≥ VGPR at 1-month significantly improved survival in all Mayo disease stages. In conclusion, patients achieving an early deep haematologic response have a significantly superior survival irrespective of cardiac involvement.
Media and strain studies for the scaled production of cis-enone resorcylic acid lactones as feedstocks for semisynthesis
Authors: Al Subeh Zeinab Y. , Raja Huzefa A. , Obike Jennifer C. , Pearce Cedric J. , Croatt Mitchell P. , Oberlies Nicholas H.
Published: June 2021

Resorcylic acid lactones (RALs) with a cis-enone moiety, represented by hypothemycin (1) and (5Z)-7-oxozeaenol (2), are fungal secondary metabolites with irreversible inhibitory activity against protein kinases, with particularly selective activity for inhibition of TAK1 (transforming growth factor beta-activated kinase 1). Gram-scale quantities of these compounds were needed as feedstock for semi-synthesizing RAL-analogues in a step-economical fashion. To do so, this study had three primary goals: identifying fungi that biosynthesized 1 and 2, enhancing their production by optimizing the fermentation conditions on the lab scale, and developing straight forward purification processes. After evaluating 536 fungal extracts via an in-house dereplication protocol, three strains were identified as producing cis-enone RALs (i.e., MSX78495, MSX63935, MSX45109). Screening these fungal strains on three grain-based media revealed enhanced production of 1 by strain MSX78495 on oatmeal medium, while rice medium increased the biosynthesis of 2 by strain MSX63935. Furthermore, the purification processes were improved, moving away from HPLC purification to utilizing two to four cycles of resuspension and centrifugation in small volumes of organic solvents, generating gram-scale quantities of these metabolites readily. In addition, studying the chemistry profiles of strains MSX78495 and MSX63935 resulted in the isolation of ten other RALs (3-12), two radicinin analogues (13-14), and six benzopyranones (15-20), with 19 and 20 being newly described chlorinated benzopyranones.
A transgenic female killing system for the genetic control of Drosophila suzukii
Authors: Schetelig Marc F. , Schwirz Jonas , Yan Ying
Published: June 2021

The spotted wing Drosophila (Drosophila suzukii) is an invasive pest of soft-skinned fruit crops. It is rapidly transmitted in Europe and North America, causing widespread agricultural losses. Genetic control strategies such as the sterile insect technique (SIT) have been proposed as environment-friendly and species-restricted approaches for this pest. However, females are inefficient agents in SIT programs. Here we report a conditional female-killing (FK) strategy based on the tetracycline-off system. We assembled sixteen genetic constructs for testing in vitro and in vivo. Twenty-four independent transgenic strains of D. suzukii were generated and tested for female-specific lethality. The strongest FK effect in the absence of tetracycline was achieved by the construct containing D. suzukii nullo promoter for early gene expression, D. suzukii pro-apoptotic gene hidAla4 for lethality, and the transformer gene intron from the Mediterranean fruit fly Ceratitis capitata for female-specific splicing. One strain carrying this construct eliminated 100% of the female offspring during embryogenesis and produced only males. However, homozygous females from these FK strains were not viable on a tetracycline-supplemented diet, possibly due to the basal expression of hidAla4. Potential improvements to the gene constructs and the use of such FK strains in an SIT program are discussed.
Changes in eating habits and food preferences in breast cancer patients undergoing adjuvant chemotherapy
Authors: Pedersini Rebecca , di Mauro Pierluigi , Bosio Sara , Zanini Barbara , Zanini Alessandra , Amoroso Vito , Turla Antonella , Vassalli Lucia , Ardine Mara , Monteverdi Sara , Zamparini Manuel , Gurizzan Cristina , Cosentini Deborah , Ricci Chiara , Simoncini Edda Lucia , Berruti Alfredo
Published: June 2021

Change in eating habits in early breast cancer (EBC) patients during chemotherapy has been poorly studied in the literature. The primary aim of this study was to prospectively evaluate food preferences and weight change in EBC patients before and after adjuvant chemotherapy. From April 2014 to June 2018, 205 EBC patients underwent a dietary assessment according to the following timeline: baseline evaluation (one week before starting chemotherapy, T0); first follow-up (approximately 2–3 months after starting chemotherapy, T1); final follow-up (one week after chemotherapy end, T2). A statistically significant reduction of the following foods was reported after the start of chemotherapy: pasta or rice, bread, breadsticks/crackers, red meat, fat and lean salami, fresh and aged cheese, milk, yogurt, added sugar, soft drinks, alcoholic beverages (wine, beer, and schnapps), and condiments (oil and butter). Conversely, fruit consumption consistently increased. As a result of these changes, a Healthy Eating Index (HEI) specifically developed for this study and suggestive of a balanced diet, significantly increased. Body weight did not increase, despite reduction in physical activity. This prospective study shows that EBC patients tend to adopt “healthier dietary patterns” during adjuvant chemotherapy, leading to a non-change in weight, despite reduction in physical activity.
Altered spontaneous activity in the frontal gyrus in dry eye: a resting-state functional MRI study
Authors: Yu Kang , Guo Yu , Ge Qian-Min , Su Ting , Shi Wen-Qing , Zhang Li-Juan , Shu Hui-Ye , Pan Yi-Cong , Liang Rong-Bin , Li Qiu-Yu , Shao Yi
Published: June 2021

This study investigated neurologic changes in patients with dry eye (DE) by functional magnetic resonance imaging (fMRI) and to used regional homogeneity (ReHo) analysis to clarify the relationship between these changes and clinical features of DE. A total of 28 patients with DE and 28 matched healthy control (HC) subjects (10 males and 18 females in each group) were enrolled. fMRI scans were performed in both groups. We carried out ReHo analysis to assess differences in neural activity between the 2 groups, and receiver operating characteristic curve (ROC) analysis was performed to evaluate the performance of ReHo values of specific brain areas in distinguishing DE patients from HCs. The relationship between average ReHo values and clinical characteristics was assessed by correlation analysis. ReHo values of the middle frontal gyrus, inferior frontal gyrus, and superior frontal gyrus were significantly lower in DE patients compared to HCs. The ROC analysis showed that ReHo value had high accuracy in distinguishing between DE patients and HCs (P < 0.0001). The ReHo values of the middle frontal gyrus and dorsolateral superior frontal gyrus were correlated to disease duration (P < 0.05). Symptoms of ocular surface injury in DE patients are associated with dysfunction in specific brain regions, which may underlie the cognitive impairment, psychiatric symptoms, and depressive mood observed in DE patients. The decreased ReHo values of some brain gyri in this study may provide a reference for clinical diagnosis and determination of treatment efficacy.