bluuebunny/crossref_metadata_2025 huggingface dataset:
Heads in the clouds: On the carbon footprint of conference‐seeded publications in the advancement of knowledge
Authors: Seuront Laurent , Nicastro Katy R. , Zardi Gerardo I.
Published: October 2021

The carbon footprint of flying overseas to conferences, meetings, and workshops to share and build knowledge has been increasingly questioned over the last two decades, especially in environmental and climate sciences, due to the related colossal carbon emissions. Here, we infer the value of scientific meetings through the number of publications produced either directly or indirectly after attending a scientific conference, symposium, or workshop (i.e., the conference‐related production) and the number of publications produced per meeting (i.e., the conference‐related productivity) as proxies for the academic value of these meetings, and relate them to both the number of meetings attended and the related carbon emissions. We show that conference‐related production and productivity, respectively, increase and decay with the number of meetings attended, and noticeably that the less productive people exhibit the largest carbon footprint. Taken together, our results imply that a twofold decrease in the carbon footprint of a given scientist would result in a twofold increase in productivity through a fivefold decrease in the number of meeting attended. In light of these figures, we call for both the implementation of objective and quantitative criteria related to the optimum number of conferences to attend in an effort to maximize scientific productivity while minimizing the related carbon footprint, and the development of a rationale to minimize the carbon emission related to scientific activities.
The effect of deep feature concatenation in the classification problem: An approach on COVID‐19 disease detection
Authors: Cengil Emine , Çınar Ahmet
Published: October 2021

In image classification applications, the most important thing is to obtain useful features. Convolutional neural networks automatically learn the extracted features during training. The classification process is carried out with the obtained features. Therefore, obtaining successful features is critical to achieving high classification success. This article focuses on providing effective features to enhance classification performance. For this purpose, the success of the process of concatenating features in classification is taken as basis. At first, the features acquired by feature transfer method are extracted from AlexNet, Xception, NASNETLarge, and EfficientNet‐B0 architectures, which are known to be successful in classification problems. Concatenating the features results in the creation of a new feature set. The method is completed by subjecting the features to various classification algorithms. The proposed pipeline is applied to the three datasets: “COVID‐19 Image Dataset,” “COVID‐19 Pneumonia Normal Chest X‐ray (PA) Dataset,” and “COVID‐19 Radiography Database” for COVID‐19 disease detection. The whole datasets contain three classes (normal, COVID, and pneumonia). The best classification accuracies for the three datasets are 98.8%, 95.9%, and 99.6%, respectively. Performance metrics are given such as: sensitivity, precision, specificity, and F1‐score values, as well. Contribution of paper is as follows: COVID‐19 disease is similar to other lung infections. This situation makes diagnosis difficult. Furthermore, the virus's rapid spread necessitates the need to detect cases as soon as possible. There has been an increased curiosity in computer‐aided deep learning models to provide the requirements. The use of the proposed method will be beneficial as it provides high accuracy.
Hemostatic Electrospun Nanocomposite Containing Poly(lactic acid)/Halloysite Nanotube Functionalized by Poly(amidoamine) Dendrimer for Wound Healing Application: In Vitro and In Vivo Assays
Authors: Delyanee Mahsa , Solouk Atefeh , Akbari Somaye , Daliri Morteza
Published: October 2021

The main challenge in treating injuries is excessive bleeding whereas intervention is required if the body's hemostatic systems fail to control the bleeding. Herein, a novel nanocomposite consisting of poly(lactic acid) (PLA) and poly(amidoamine) (PAMAM) dendrimer functionalized halloysite nanotube (HNT) with a highly porous structure via electrospinning is developed. HNT is functionalized by PAMAM via divergent synthetic routes from zero to third‐generation numbers. The effect of different percentages and generation numbers of PAMAM dendrimer (G1, G2, and G3) functionalized HNT on PLA is studied using physicochemical nanocomposite characteristics. These resultant nanocomposites provide a nanofibrous structure with appropriate physicochemical characteristics such as mechanical properties, surface wettability, and water permeability. The hemostatic assays indicate that nanocomposite with PAMAM G3 functionalized HNT have the quickest blood clotting time due to the abundant amino functional group. Furthermore, the nanocomposites with 10 wt% of nanoparticles significantly promote cellular behavior in vitro. The in vivo study demonstrates that PLA/PAMAM G3 functionalized HNT promotes angiogenesis, collagen deposition, and re‐epithelialization in the wound sites of the rat model, as well as inhibiting inflammatory response. The findings indicate that nanofibrous structure and the presence of dendrimer functionalized HNT have a synergetic effect on the enhanced nanocomposite wound healing performance.
The current status of preclinical proton FLASH radiation and future directions
Authors: Diffenderfer Eric S. , Sørensen Brita S. , Mazal Alejandro , Carlson David J.
Published: October 2021

We review the current status of proton FLASH experimental systems, including preclinical physical and biological results. Technological limitations on preclinical investigation of FLASH biological mechanisms and determination of clinically relevant parameters are discussed. A review of the biological data reveals no reproduced proton FLASH effect in vitro and a significant in vivo FLASH sparing effect of normal tissue toxicity observed with multiple proton FLASH irradiation systems. Importantly, multiple studies suggest little or no difference in tumor growth delay for proton FLASH when compared to conventional dose rate proton radiation. A discussion follows on future areas of development with a focus on the determination of the optimal parameters for maximizing the therapeutic ratio between tumor and normal tissue response and ultimately clinical translation of proton FLASH radiation.
Analytic hierarchy process‐technique for order preference by similarity to ideal solution: A multi criteria decision‐making technique to select the best dental restorative composite materials
Authors: Yadav Ramkumar
Published: October 2021

The purpose of this paper is to investigate the optimal selection of a variety of dental composites using a hybrid analytic hierarchy process (AHP) and technique for order preference by similarity to ideal solution (TOPSIS) technique as a multi criteria decision‐making (MCDM) technique under a set of conflict Performance Defining Criteria (PDCs). The resinous matrix of the dental composite was fabricated by Bis‐GMA (51 wt%), TEGDMA (48 wt%), CQ (0.2 wt%), and EDMAB (0.8 wt%). Five dental composite compositions were created utilizing hybrid nTiO2‐Al2O3 particles with varying nTiO2 content (0, 2, 4, 6, 8 wt%). According to AHP, the following PDCs are listed in order: Cost (PDC‐13) > Vickers hardness (PDC‐4) > compressive strength (PDC‐1) > depth of cure (PDC‐5) > flexural modulus (PDC‐3) > flexural strength (PDC‐2) > degree of conversion (PDC‐11) > material stability (PDC‐12) > void content (PDC‐8) > water sorption (PDC‐9) > Density (PDC‐7) (PDC‐6). According to TOPSIS, the following are the rankings: nT2 > nT0 > nT4 > nT6 > nT8. The experimental results are connected to the ranking of several sets of dental formulations. As a result, the AHP‐TOPSIS method is one of the finest MCDM strategies for ranking under diverse PDCs.
Recent advances in intermixed phase of organic solar cells: Characterization, regulating strategies and device applications
Authors: Liang Qiuju , Hu Zhangbo , Yao Jianhong , Yin Yukai , Wei Puxin , Chen Zhikang , Li Wangchang , Liu Jiangang
Published: October 2021

Organic solar cells (OSCs) have unique advantages of low‐cost solution processing, light weight, flexibility, and semitransparency, which is a promising photovoltaic technology. The intermixed phase plays a key role in determining the power conversion efficiencies (PCE) of OSCs. The intermixed phase is an amorphous region, where the donor and acceptor mix at the molecular level. Great efforts have been devoted to optimize the content and the composition of the intermixed phase. This perspective focuses on the functions of intermixed phase and elaborates the relationship between intermixed phase behavior and photophysical process, in particular, the exciton dissociation and charge transport. Then the characterization methods, including quantitative and qualitative characterizations, for the content and composition of intermixed phases are introduced. Meanwhile, this review also introduces the strategies to control the intermixed phase behavior, such as adjusting the miscibility between donor and acceptor, changing the ratio of donor to acceptor, regulating the crystallinity and so on. Moreover, representative examples are given and discussed to understand the key parameters on tuning the intermixed phase behavior. Finally, a future controlling and development of intermixed phase behavior is briefly outlooked, which may help to achieve high PCE of OSCs.
Spiropyran‐Appended Cucurbit[6]uril Enabling Direct Generation of 2D Materials inside Living Cells
Authors: Hou Delong , Pu Liping , Zhou Shuai , Wang Rui , Xu Yong , Zhang Wenle , Wang Zhonghui , Zeng Qi , Xu Zhou , Fan Haojun , Chen Yi
Published: October 2021

The unique structural advantage and physicochemical properties render some 2D materials emerging platforms for intracellular bioimaging, biosensing, or disease theranostics. Despite recent advances in this field, one major challenge lies in bypassing the endocytic uptake barrier to allow internalization of very large 2D materials that have longer retention time in cells, and hence greater potency as intracellular functional platforms than small, endocytosable counterparts. Here, an engineered cucurbit[6]uril carrying at its periphery multiple spiropyran pendants that readily translocates into cytosol, and then polymerizes laterally and non‐covalently in a controlled manner, enabling direct generation of 2D materials inside living cells, is reported. The resultant 2D materials are single‐monomer‐thick and can in situ grow up to 0.8–1.2 µm in lateral size, experimentally proved too large to be endocytosed from outside the cells even after surface engineered with biorecognition entities. A Förster resonance energy transfer assay is further devised for real‐time visualization of the polymerization dynamics in vivo, clearly demonstrating the rationale in this study. With the otherwise non‐endocytosable large 2D materials gaining access to cytosol, potent intracellular signaling or theranostic platform that surpasses the intrinsic performance limit of conventional small counterparts are in sight.
Emerging Single‐Photon Detectors Based on Low‐Dimensional Materials
Authors: Wang Hailu , Guo Jiaxiang , Miao Jinshui , Luo Wenjin , Gu Yue , Xie Runzhang , Wang Fang , Zhang Lili , Wang Peng , Hu Weida
Published: October 2021

Single‐photon detectors (SPDs) that can sense individual photons are the most sensitive instruments for photodetection. Established SPDs such as conventional silicon or III–V compound semiconductor avalanche diodes and photomultiplier tubes have been used in a wide range of time‐correlated photon‐counting applications, including quantum information technologies, in vivo biomedical imaging, time‐of‐flight 3D scanners, and deep‐space optical communications. However, further development of these fields requires more sophisticated detectors with high detection efficiency, fast response, and photon‐number‐resolving ability, etc. Thereby, significant efforts have been made to improve the performance of conventional SPDs and to develop new photon‐counting technologies. In this review, the working mechanisms and key performance metrics of conventional SPDs are first summarized. Then emerging photon‐counting detectors (in the visible to infrared range) based on 0D quantum dots, 1D quantum nanowires, and 2D layered materials are discussed. These low‐dimensional materials exhibit many exotic properties due to the quantum confinement effect. And photodetectors built from these nD‐materials (n = 0, 1, 2) can potentially be used for ultra‐weak light detection. By reviewing the status and discussing the challenges faced by SPDs, this review aims to provide future perspectives on the research directions of emerging photon‐counting technologies.
Timing Selector: Using Transient Switching Dynamics to Solve the Sneak Path Issue of Crossbar Arrays
Authors: Rao Mingyi , Song Wenhao , Kiani Fatemeh , Asapu Shiva , Zhuo Ye , Midya Rivu , Upadhyay Navnidhi , Wu Qing , Barnell Mark , Lin Peng , Li Can , Wang Zhongrui , Xia Qiangfei , Joshua Yang J.
Published: October 2021

Sneak path current is a fundamental issue and a major roadblock to the wide application of memristor crossbar arrays. Traditional selectors such as transistors compromise the 2D scalability and 3D stack‐ability of the array, while emerging selectors with highly nonlinear current–voltage relations contradict the requirement of a linear current–voltage relation for efficient multiplication by directly using Ohm's law. Herein, the concept of a timing selector is proposed and demonstrated, which addresses the sneak path issue with a voltage‐dependent delay time of its transient switching behavior, while preserving a linear current–voltage relationship for computation. Crossbar arrays with silver‐based diffusive memristors as the timing selectors are built and the operation principle and operational windows are experimentally demonstrated. The timing selector enables large memristor crossbar arrays that can be used to solve large‐dimension real‐world problems in machine intelligence and neuromorphic computing.
Research Progress on Control Strategy of Intermetallic Compounds in Welding Process of Heterogeneous Materials
Authors: Lu WenBin , Zhang Yan , Yu DeShui , Sun DaQian , Li HongMei
Published: October 2021

The welding of dissimilar metals is widely used in various industries and is also generally recognized by the industry. The welding of dissimilar metals is of great significance. It can not only obtain higher‐strength composite joints but also save the excessive use of rare metals and effectively expand the profit margin. The weldability of dissimilar metals is closely related to their own physical and chemical properties. Usually when the physical and chemical properties of the two metals differ greatly, their weldability is generally poor, and complex intermetallic compounds (IMCs) are easily generated during the welding process. The deterioration of joint performance is very serious. Welding of dissimilar metals is widely used in many fields such as aerospace, automobile manufacturing, and medical equipment, solving the problems of low strength, high cost, and poor corrosion resistance of the same metal joints. Regarding the welding of dissimilar metals, the current existing methods include fusion welding, pressure welding, brazing, etc. Each welding method has its own advantages and disadvantages. To obtain an effective and reliable welding joint, the simplest method is to adjust the welding parameters, but the effect is not obvious. A large amount of IMCs are generated in the weld, which has a serious impact on the joint performance. To obtain a stronger composite joint, a third transition metal can be introduced to inhibit the formation of IMCs. Under the same conditions, the introduction of the third metal can significantly optimize the performance of the composite joint. In the weld, significantly reducing the number of IMCs to a large extent reduces the deterioration of the joint performance of the newly formed IMCs, but there is still a small amount of IMCs formation. To completely avoid the formation of IMCs, special joint composite intermediate layer is introduced, which completely avoids the influence of newly generated IMCs on joint performance. In the welding process of dissimilar metals, selecting the appropriate welding method and welding process can obtain a composite joint with excellent performance.
Are the CKM anomalies induced by vector-like quarks? Limits from flavor changing and Standard Model precision tests
Authors: Belfatto B. , Berezhiani Z.
Published: October 2021

Abstract

Recent high precision determinations of Vus and Vud indicate towards anomalies in the first row of the CKM matrix. Namely, determination of Vud from beta decays and of Vus from kaon decays imply a violation of first row unitarity at about 3σ level. Moreover, there is tension between determinations of Vus obtained from leptonic Kμ2 and semileptonic Kℓ3 kaon decays. These discrepancies can be explained if there exist extra vector-like quarks at the TeV scale, which have large enough mixings with the lighter quarks. In particular, extra vector-like weak singlets quarks can be thought as a solution to the CKM unitarity problem and an extra vector-like weak doublet can in principle resolve all tensions. The implications of this kind of mixings are examined against the flavour changing phenomena and SM precision tests. We consider separately the effects of an extra down-type isosinglet, up-type isosinglet and an isodoublet containing extra quarks of both up and down type, and determine available parameter spaces for each case. We find that the experimental constraints on flavor changing phenomena become more stringent with larger masses, so that the extra species should have masses no more than few TeV. Moreover, only one type of extra multiplet cannot entirely explain all the discrepancies, and some their combination is required, e.g. two species of isodoublet, or one isodoublet and one (up or down type) isosinglet. We show that these scenarios are testable with future experiments. Namely, if extra vector-like quarks are responsible for CKM anomalies, then at least one of them should be found at scale of few TeV, and anomalous weak isospin violating Z-boson couplings with light quarks should be detected if the experimental precision on Z hadronic decay rate is improved by a factor of 2 or so.
Iterative Metal Artifact Reduction (iMAR) of the Non-adhesive Liquid Embolic Agent Onyx in Computed Tomography
Authors: Schmitt Niclas , Weyland Charlotte S. , Wucherpfennig Lena , Herweh Christian , Bendszus Martin , Möhlenbruch Markus A. , Vollherbst Dominik F.
Published: October 2021

Background

A drawback of Onyx, one of the most used embolic agents for endovascular embolization of intracranial arteriovenous malformations (AVM), is the generation of imaging artifacts (IA) in computed tomography (CT). Since these artifacts can represent an obstacle for the detection of periprocedural bleeding, this study investigated the effect of artifact reduction by an iterative metal artifact reduction (iMAR) software in CT in a brain phantom.

Methods

Two different in vitro models with two-dimensional tube and three-dimensional AVM-like configuration were filled with Onyx 18. The models were inserted into a brain imaging phantom and images with (n = 5) and without (n = 10) an experimental hemorrhage adjacent were acquired. Afterwards, the iMAR algorithm was applied for artifact reduction. The IAs of the original and the post-processed images were graded quantitatively and qualitatively. Moreover, qualitative definition of the experimental hemorrhage was investigated.

Results

Comparing the IAs of the original and the post-processed CT images, quantitative and qualitative analysis showed a lower degree of IAs in the post-processed images, i.e. quantitative analysis: 2D tube model: 23.92 ± 8.02 Hounsfield units (HU; no iMAR; mean ± standard deviation) vs. 5.93 ± 0.43 HU (with iMAR; p < 0.001); qualitative analysis: 3D AVM model: 4.93 ± 0.18 vs. 3.40 ± 0.48 (p < 0.001). Furthermore, definition of the experimental hemorrhage was better in the post-processed images of both in vitro models (2D tube model: p = 0.004; 3D AVM model: p = 0.002).

Conclusion

The iMAR algorithm can significantly reduce the IAs evoked by Onyx 18 in CT. Applying iMAR could thus improve the accuracy of postprocedural CT imaging after embolization with Onyx in clinical practice.
Bayesian tests of symmetry for the generalized Von Mises distribution
Authors: Salvador Sara , Gatto Riccardo
Published: October 2021

Bayesian tests on the symmetry of the generalized von Mises model for planar directions (Gatto and Jammalamadaka in Stat Methodol 4(3):341–353, 2007) are introduced. The generalized von Mises distribution is a flexible model that can be axially symmetric or asymmetric, unimodal or bimodal. A characterization of axial symmetry is provided and taken as null hypothesis for one of the proposed Bayesian tests. The Bayesian tests are obtained by the technique of probability perturbation. The prior probability measure is perturbed so to give a positive prior probability to the null hypothesis, which would be null otherwise. This allows for the derivation of simple computational formulae for the Bayes factors. Numerical results reveal that, whenever the simulation scheme of the samples supports the null hypothesis, the null posterior probabilities appear systematically larger than their prior counterpart.
Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation
Authors: van der Stel Wanda , Yang Huan , Vrijenhoek Nanette G. , Schimming Johannes P. , Callegaro Giulia , Carta Giada , Darici Salihanur , Delp Johannes , Forsby Anna , White Andrew , le Dévédec Sylvia , Leist Marcel , Jennings Paul , Beltman Joost B. , van de Water Bob , Danen Erik H. J.
Published: October 2021

Mitochondrial perturbation is a key event in chemical-induced organ toxicities that is incompletely understood. Here, we studied how electron transport chain (ETC) complex I, II, or III (CI, CII and CIII) inhibitors affect mitochondrial functionality, stress response activation, and cell viability using a combination of high-content imaging and TempO-Seq in HepG2 hepatocyte cells. CI and CIII inhibitors perturbed mitochondrial membrane potential (MMP) and mitochondrial and cellular ATP levels in a concentration- and time-dependent fashion and, under conditions preventing a switch to glycolysis attenuated cell viability, whereas CII inhibitors had no effect. TempO-Seq analysis of changes in mRNA expression pointed to a shared cellular response to CI and CIII inhibition. First, to define specific ETC inhibition responses, a gene set responsive toward ETC inhibition (and not to genotoxic, oxidative, or endoplasmic reticulum stress) was identified using targeted TempO-Seq in HepG2. Silencing of one of these genes, NOS3, exacerbated the impact of CI and CIII inhibitors on cell viability, indicating its functional implication in cellular responses to mitochondrial stress. Then by monitoring dynamic responses to ETC inhibition using a HepG2 GFP reporter panel for different classes of stress response pathways and applying pathway and gene network analysis to TempO-Seq data, we looked for downstream cellular events of ETC inhibition and identified the amino acid response (AAR) as being triggered in HepG2 by ETC inhibition. Throughin silicoapproaches we provide evidence indicating that a similar AAR is associated with exposure to mitochondrial toxicants in primary human hepatocytes. Altogether, we (i) unravel quantitative, time- and concentration-resolved cellular responses to mitochondrial perturbation, (ii) identify a gene set associated with adaptation to exposure to active ETC inhibitors, and (iii) show that ER stress and an AAR accompany ETC inhibition in HepG2 and primary hepatocytes.
Deformations of higher-page analogues of $$\partial {{\bar{\partial }}}$$-manifolds
Authors: Popovici Dan , Stelzig Jonas , Ugarte Luis
Published: October 2021

We extend the notion of small essential deformations of Calabi–Yau complex structures from the case of the Iwasawa manifold, for which they were introduced recently by the first-named author, to the general case of page-1-$$\partial {{\bar{\partial }}}$$

∂

∂

¯

-manifolds that were jointly introduced very recently by all three authors. We go on to obtain an analogue of the unobstructedness theorem of Bogomolov, Tian and Todorov for Calabi–Yau page-1-$$\partial {{\bar{\partial }}}$$

∂

∂

¯

-manifolds. As applications of this discussion, we study the small deformations of certain Nakamura solvmanifolds and reinterpret the cases of the Iwasawa manifold and its 5-dimensional analogue from this standpoint.
Combined transarterial iodized oil injection and computed tomography-guided thermal ablation for hepatocellular carcinoma: utility of the iodized oil retention pattern
Authors: Tan Jie , Mathy René Michael , Chang De-Hua , Tang Tian , Zhang Zi-Shu , Xiao Yu-Dong
Published: October 2021

Purpose

To investigate whether the iodized oil (Lipiodol, Guerbet Group, Villepinte, France) retention pattern influences the treatment efficacy of combined transarterial Lipiodol injection (TLI) and thermal ablation in patients with hepatocellular carcinoma (HCC).

Methods

Data of 198 patients (280 HCC lesions), who underwent TLI plus computed tomography (CT)-guided thermal ablation at three separate medical institutions between June 2014 and September 2020, were reviewed and analyzed. The Lipiodol retention pattern was classified as complete or incomplete based on non-enhanced CT at the time of ablation. The primary outcome was local recurrence-free survival (LRFS) for lesions; the secondary outcome was overall survival (OS) for patients. Propensity score matching (PSM) was performed using a caliper width of 0.1 between the two groups. Differences in LRFS and OS between the two groups were compared using the log-rank test.

Results

A total of 133 lesions exhibited a complete Lipiodol retention pattern, while 147 exhibited an incomplete pattern. After PSM analysis of baseline characteristics of the lesions, 121 pairs of lesions were matched. LRFS was significantly longer for lesions exhibiting complete retention than for those exhibiting incomplete retention (P = 0.030). After PSM analysis of patient baseline characteristics, 74 pairs of patients were matched. There was no significant difference in OS between the two groups (P = 0.456).

Conclusion

Lipiodol retention patterns may influence the treatment efficacy of combined TLI and thermal ablation for HCC lesions. However, a survival benefit for the Lipiodol retention pattern among HCC patients was not observed and needs further confirmation.
Regulation of STAT3 and its role in cardioprotection by conditioning: focus on non-genomic roles targeting mitochondrial function
Authors: Comità Stefano , Femmino Saveria , Thairi Cecilia , Alloatti Giuseppe , Boengler Kerstin , Pagliaro Pasquale , Penna Claudia
Published: October 2021

Ischemia–reperfusion injury (IRI) is one of the biggest challenges for cardiovascular researchers given the huge death toll caused by myocardial ischemic disease. Cardioprotective conditioning strategies, namely pre- and post-conditioning maneuvers, represent the most important strategies for stimulating pro-survival pathways essential to preserve cardiac health. Conditioning maneuvers have proved to be fundamental for the knowledge of the molecular basis of both IRI and cardioprotection. Among this evidence, the importance of signal transducer and activator of transcription 3 (STAT3) emerged. STAT3 is not only a transcription factor but also exhibits non-genomic pro-survival functions preserving mitochondrial function from IRI. Indeed, STAT3 is emerging as an influencer of mitochondrial function to explain the cardioprotection phenomena. Studying cardioprotection, STAT3 proved to be crucial as an element of the survivor activating factor enhancement (SAFE) pathway, which converges on mitochondria and influences their function by cross-talking with other cardioprotective pathways. Clearly there are still some functional properties of STAT3 to be discovered. Therefore, in this review, we highlight the evidence that places STAT3 as a promoter of the metabolic network. In particular, we focus on the possible interactions of STAT3 with processes aimed at maintaining mitochondrial functions, including the regulation of the electron transport chain, the production of reactive oxygen species, the homeostasis of Ca2+and the inhibition of opening of mitochondrial permeability transition pore. Then we consider the role of STAT3 and the parallels between STA3/STAT5 in cardioprotection by conditioning, giving emphasis to the human heart and confounders.
Neuroendocrine neoplasms of the pancreas: diagnosis and pitfalls
Authors: Konukiewitz Björn , Jesinghaus Moritz , Kasajima Atsuko , Klöppel Günter
Published: October 2021

Common to neuroendocrine neoplasms of the pancreas is their expression of synaptophysin, chromogranin A, and/or INSM1. They differ, however, in their histological differentiation and molecular profile. Three groups can be distinguished: well-differentiated neuroendocrine neoplasms (neuroendocrine tumors), poorly differentiated neuroendocrine neoplasms (neuroendocrine carcinomas), and mixed neuroendocrine-non-neuroendocrine neoplasms. However, the expression of synaptophysin and, to a lesser extent, also chromogranin A is not restricted to the neuroendocrine neoplasms, but may also be in a subset of non-neuroendocrine epithelial and non-epithelial neoplasms. This review provides the essential criteria for the diagnosis of pancreatic neuroendocrine neoplasms including diagnostic clues for the distinction of high-grade neuroendocrine tumors from neuroendocrine carcinomas and an algorithm avoiding diagnostic pitfalls in the delineation of non-neuroendocrine neoplasms with neuroendocrine features from pancreatic neuroendocrine neoplasms.
Vitamin D in Gambian children with discordant tuberculosis (TB) infection status despite matched TB exposure: a case control study
Authors: Stockdale Lisa , Sambou Basil , Sissoko Muhamed , Egere Uzochukwu , Sillah Abdou K. , Kampmann Beate , Basu Roy Robin
Published: October 2021

Using a matched case control design conducted at MRC Gambia in 2015, we measured vitamin D levels in pairs of asymptomatic children with discordant tuberculin skin test status despite the same sleeping proximity to the same adult TB index case. Median ages of groups (infected; 10.0 years, uninfected 8.8 years) were not significantly different (p = 0.13). Mean vitamin D levels were 2.05 ng/mL (95% CI − 0.288 to 4.38) higher in 24 highly TB-exposed uninfected children compared with 24 matched highly TB-exposed infected children (p = 0.08). The findings warrant further investigation in larger studies to understand the implications and significance.

Conclusion: Vitamin D levels were higher in TB-uninfected children compared with TB-infected despite equal high exposure to a TB case.

What is Known:• Paediatrics TB represents one of the leading causes of child death globally.• Current literature shows an inconsistent relationship between vitamin D deficiency and increased risk of TB disease however a large Phase 3 trial of vitamin D supplementation in (largely vitamin D deficient) Mongolian children did not find any association with TB infection rates.

What is New:• This study adds to the literature in a vitamin D sufficient paediatric population whereby children with equal exposure to a household TB case with no evidence of TB infection have higher levels of vitamin D compared with matched children with TB infection.
Onchocerciasis drug development: from preclinical models to humans
Authors: Ngwewondo Adela , Scandale Ivan , Specht Sabine
Published: October 2021

Twenty diseases are recognized as neglected tropical diseases (NTDs) by World Health Assembly resolutions, including human filarial diseases. The end of NTDs is embedded within the Sustainable Development Goals for 2030, under target 3.3. Onchocerciasis afflicts approximately 20.9 million people worldwide with > 90% of those infected residing in Africa. Control programs have made tremendous efforts in the management of onchocerciasis by mass drug administration and aerial larviciding; however, disease elimination is not yet achieved. In the new WHO roadmap, it is recognized that new drugs or drug regimens that kill or permanently sterilize adult filarial worms would significantly improve elimination timelines and accelerate the achievement of the program goal of disease elimination. Drug development is, however, handicapped by high attrition rates, and many promising molecules fail in preclinical development or in subsequent toxicological, safety and efficacy testing; thus, research and development (R&D) costs are, in aggregate, very high. Drug discovery and development for NTDs is largely driven by unmet medical needs put forward by the global health community; the area is underfunded and since no high return on investment is possible, there is no dedicated drug development pipeline for human filariasis. Repurposing existing drugs is one approach to filling the drug development pipeline for human filariasis. The high cost and slow pace of discovery and development of new drugs has led to the repurposing of “old” drugs, as this is more cost-effective and allows development timelines to be shortened. However, even if a drug is marketed for a human or veterinary indication, the safety margin and dosing regimen will need to be re-evaluated to determine the risk in humans. Drug repurposing is a promising approach to enlarging the pool of active molecules in the drug development pipeline. Another consideration when providing new treatment options is the use of combinations, which is not addressed in this review. We here summarize recent advances in the late preclinical or early clinical stage in the search for a potent macrofilaricide, including drugs against the nematode and against its endosymbiont, Wolbachia pipientis.
Plasticity in induced resistance to sequential attack by multiple herbivores in Brassica nigra
Authors: de Bobadilla Maite Fernández , Van Wiechen Roel , Gort Gerrit , Poelman Erik H.
Published: October 2021

In nature, plants interact with multiple insect herbivores that may arrive simultaneously or sequentially. There is extensive knowledge on how plants defend themselves against single or dual attack. However, we lack information on how plants defend against the attack of multiple herbivores that arrive sequentially. In this study, we investigated whether Brassica nigra L. plants are able to defend themselves against caterpillars of the late-arriving herbivore Plutella xylostella L., when plants had been previously exposed to sequential attack by four other herbivores (P. xylostella, Athalia rosae, Myzus persicae and Brevicoryne brassicae). We manipulated the order of arrival and the history of attack by four herbivores to investigate which patterns in sequential herbivory determine resistance against the fifth attacker. We recorded that history of sequential herbivore attack differentially affected the capability of B. nigra plants to defend themselves against caterpillars of P. xylostella. Caterpillars gained less weight on plants attacked by a sequence of four episodes of attack by P. xylostella compared to performance on plants that were not previously damaged by herbivores. The number of times the plant was attacked by herbivores of the same feeding guild, the identity of the first attacker, the identity and the guild of the last attacker as well as the order of attackers within the sequence of multiple herbivores influenced the growth of the subsequent herbivory. In conclusion, this study shows that history of sequential attack is an important factor determining plant resistance to herbivores.
Immune function differs among tropical environments but is not downregulated during reproduction in three year-round breeding equatorial lark populations
Authors: Ndithia Henry K. , Matson Kevin D. , Muchai Muchane , Tieleman B. Irene
Published: October 2021

Seasonal variation in immune function can be attributed to life history trade-offs, and to variation in environmental conditions. However, because phenological stages and environmental conditions co-vary in temperate and arctic zones, their separate contributions have not been determined. We compared immune function and body mass of incubating (female only), chick-feeding (female and male), and non-breeding (female and male) red-capped larksCalandrella cinereabreeding year-round in three tropical equatorial (Kenya) environments with distinct climates. We measured four immune indices: haptoglobin, nitric oxide, agglutination, and lysis. To confirm that variation in immune function between breeding (i.e., incubating or chick-feeding) and non-breeding was not confounded by environmental conditions, we tested if rainfall, average minimum temperature (Tmin), and average maximum temperature (Tmax) differed during sampling times among the three breeding statuses per location.TminandTmaxdiffered between chick-feeding and non-breeding, suggesting that birds utilized environmental conditions differently in different locations for reproduction. Immune indices did not differ between incubating, chick-feeding and non-breeding birds in all three locations. There were two exceptions: nitric oxide was higher during incubation in cool and wet South Kinangop, and it was higher during chick-feeding in the cool and dry North Kinangop compared to non-breeding birds in these locations. For nitric oxide, agglutination, and lysis, we found among-location differences within breeding stage. In equatorial tropical birds, variation in immune function seems to be better explained by among-location climate-induced environmental conditions than by breeding status. Our findings raise questions about how within-location environmental variation relates to and affects immune function.
Thrombosis associated with ventriculoatrial shunts
Authors: Wu Dengjun , Guan Zhengyan , Xiao Limin , Li Donghai
Published: October 2021

Ventriculoatrial shunts are the most common second-line procedure for cases in which ventriculoperitoneal shunts are unsuitable. Shunting-associated thrombosis is a potentially life-threatening complication after ventriculoatrial shunt insertion. The overall prevalence of this complication is still controversial because of substantial differences in the numbers found in studies using clinical data and in those analyzing postmortem findings. The etiology of thrombosis may be multifactorial, including shunt catheter itself, contents of cerebrospinal fluid, shunt infection, and genetic disorder. The clinical presentation can vary widely, ranging from asymptomatic to a life-threatening condition. Timely recognition of thromboembolic lesions is critical for treatment. However, early diagnosis and management is still challenging because of a relatively long asymptomatic latency and lack of clear guideline recommendations. The purpose of this review is to provide an overview of ventriculoatrial shunt thrombosis, especially to focus on its etiopathogenesis, diagnosis, treatment, and prevention.
Dexmedetomidine attenuates haemorrhage-induced thalamic pain by inhibiting the TLR4/NF-κB/ERK1/2 pathway in mice
Authors: Huang Tianfeng , Li Yong , Hu Wenqing , Yu Dapeng , Gao Ju , Yang Fan , Xu Yingying , Wang Zehua , Zong Liang
Published: October 2021

Background

Thalamic pain, a neuropathic pain syndrome, frequently occurs after stroke. This research aimed to investigate the effect of dexmedetomidine (DEX) on thalamic pain.

Methods

The cellular localization of the TLR4 protein was determined by immunostaining. The expression of Iba1, GFAP and protein associated with the TLR4/NF-κB/ERK1/2 pathway was measured by Western blotting. Continuous pain hypersensitivity was evaluated by behavioural tests. The results were analysed by one-way ANOVA, two-way ANOVA and Tukey’s post hoc test.

Results

The results demonstrated that DEX obviously alleviated thalamic pain induced by haemorrhage on the ipsilateral side and delayed the development of pain hypersensitivity. Furthermore, the expression levels of Iba1, GFAP and proteins associated with the TLR4/NF-κB/ERK1/2 signalling pathway were greatly increased in mice with thalamic pain, but these effects were reversed by DEX.

Conclusion

Our findings suggest that DEX alleviates the inflammatory response during thalamic pain through the TLR4/NF-κB/ERK1/2 signalling pathway and might be a potential therapeutic agent for thalamic pain.
Let’s Connect to Keep the Distance: How SMEs Leverage Information and Communication Technologies to Address the COVID-19 Crisis
Authors: Wendt Charlotte , Adam Martin , Benlian Alexander , Kraus Sascha
Published: October 2021

COVID-19 caused significant challenges for small and medium-sized enterprises (SMEs) in the event industry. To address these challenges, many SMEs leveraged information and communication technologies (ICTs), with some even emerging strengthened from the crisis. Drawing on the technology-organization-environment framework and technology-affordances-and-constraints theory, we investigate the adoption of ICTs as a crisis response strategy in 10 SMEs in the German business event (e.g., corporate events, conferences) industry. Our findings reveal that ICT adoption not only depends on rational decisions based on organizational, environmental, and technological characteristics, but also on these dimensions’ interrelationship and the specific ICTs’ affordances and constraints. Introducing readily available ICTs (e.g., video-conferencing) has significant potential in addressing physical distancing in the short and medium term, while more sophisticated ICTs (e.g., virtual reality) are more likely to gain importance in the long term. Thus, we expand our understanding of organizational technology adoption and ICT-enabled crisis response strategies in SMEs.
The Mediating Effects of Alexithymia, Intolerance of Uncertainty, and Anxiety on the Relationship Between Sensory Processing Differences and Restricted and Repetitive Behaviours in Autistic Adults
Authors: Moore Heather L. , Brice Samuel , Powell Lauren , Ingham Barry , Freeston Mark , Parr Jeremy R. , Rodgers Jacqui
Published: October 2021

Distress caused by sensory processing differences for autistic individuals may be reduced by repetitive behaviours (RRB), including repetitive motor (RMB) and insistence on sameness (ISB) behaviours. Intolerance of uncertainty (IU) and anxiety mediate the relationship between sensory processing and RRB in autistic children. We replicated this model in autistic adults, extending it to include alexithymia. Serial mediation, using data from 426 autistic adults, identified significant direct effects from sensory processing to RMB and ISB, and indirect effects through alexithymia-IU-anxiety for RMB, and IU alone, and alexithymia-IU for ISB. Different mechanisms may underpin RMB and ISB. Alexithymia alongside, IU and anxiety, should be considered when understanding the relationship between sensory processing and RRB, and when offering interventions to support autistic people.
Proof Complexity of Modal Resolution
Authors: Sigley Sarah , Beyersdorff Olaf
Published: October 2021

We investigate the proof complexity of modal resolution systems developed by Nalon and Dixon (J Algorithms 62(3–4):117–134, 2007) and Nalon et al. (in: Automated reasoning with analytic Tableaux and related methods—24th international conference, (TABLEAUX’15), pp 185–200, 2015), which form the basis of modal theorem proving (Nalon et al., in: Proceedings of the twenty-sixth international joint conference on artificial intelligence (IJCAI’17), pp 4919–4923, 2017). We complement these calculi by a new tighter variant and show that proofs can be efficiently translated between all these variants, meaning that the calculi are equivalent from a proof complexity perspective. We then develop the first lower bound technique for modal resolution using Prover–Delayer games, which can be used to establish “genuine” modal lower bounds for size of dag-like modal resolution proofs. We illustrate the technique by devising a new modal pigeonhole principle, which we demonstrate to require exponential-size proofs in modal resolution. Finally, we compare modal resolution to the modal Frege systems of Hrubeš (Ann Pure Appl Log 157(2–3):194–205, 2009) and obtain a “genuinely” modal separation.
Regret, Self-regulatory Abilities, and Well-Being: Their Intricate Relationships
Authors: Sijtsema Jelle J. , Zeelenberg Marcel , Lindenberg Siegwart M.
Published: October 2021

Emotions, like regret, have been heralded as instruments of self-regulation, by instigating reflection, learning and feedback for betterment and thus increasing well-being. Yet, this view neglects taking the frequency of regret into consideration. Frequently experiencing regret may instead be a sign of repeatedly failing to achieve betterment. Previous work has shown that people who experience regret often have lower life satisfaction. We suggest that, by itself, the reflective function of regret is not enough to lead to betterment. Rather, in addition to regret, self-regulatory abilities are needed. In the absence of these abilities, the reflective function of regret does not turn off but is likely to lead to frequent episodes of regret and turn into counter-productive rumination, reducing rather than increasing well-being. We tested these possibilities in two studies. In Study 1, reports were administered about regret frequency, self-regulatory abilities, and life satisfaction in 388 US adults (54.6% males;Mage = 35,SD = 10). In the preregistered Study 2, the same instruments were administered in a replication sample of 470 British adults (22.1% males;Mage = 36,SD = 12). In both studies, low self-regulatory abilities were associated with higher regret frequency, which in turn, was associated with poorer life satisfaction. Moreover, in both studies, the negative association between regret frequency and life satisfaction was explained by ruminative brooding styles. In sum, the positive reflective function of regret for well-being cannot stand alone, but needs self-regulatory abilities. Without these abilities, regret experience is frequent and its reflective function turns into brooding rumination that negatively affects well-being.
Interactive teaching environment for diagnostic radiography with real-time X-ray simulation and patient positioning
Authors: Sujar Aaron , Kelly Graham , García Marcos , Vidal Franck P.
Published: October 2021

Purpose

Traditional undergraduate radiographer training mixes academic lectures and clinical practice. Our goal is to bridge the current disconnection between theory and practice in a safe environment, avoiding the risk of radiation for both practitioners and patients. To this end, this research proposes a new software to teach diagnostic radiography using real-time interactive X-ray simulation and patient positioning.

Methods

The proposed medical simulator is composed of three main modules. A fast and accurate character animation technique is in charge of simulating the patient positioning phase and adapts their internal anatomy accordingly. gVirtualXRay is an open-source X-ray simulation library and generates the corresponding radiographs in real time. Finally, the courseware allows going through all the diagnostic radiology steps from the patient positioning and the machine configuration to the final image enhancing.

Results

A face and content validation study has been conducted; 18 radiology professionals were recruited to evaluate our software using a questionnaire. The results show that our tool is realistic in many ways (72% of the participants agreed that the simulations are visually realistic), useful (67%) and suitable (78%) for teaching X-ray radiography.

Conclusions

The proposed tool allows simulating the most relevant steps of the projectional radiography procedure. The virtual patient posing system and X-ray simulation module execute at interactive rates. These features enable the lectures to show their students the results of good and bad practices in a classroom environment, avoiding radiation risk.