bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen-substituted graphdiyne encapsulated cuprous oxide photocathode for efficient and stable photoelectrochemical water reduction
Authors: Zhou Xue , Fu Baihe , Li Linjuan , Tian Zheng , Xu Xiankui , Wu Zihao , Yang Jing , Zhang Zhonghai
Published: October 2022

Photoelectrochemical (PEC) water splitting is an appealing approach for “green” hydrogen generation. The natural p-type semiconductor of Cu2O is one of the most promising photocathode candidates for direct hydrogen generation. However, the Cu2O-based photocathodes still suffer severe self-photo-corrosion and fast surface electron-hole recombination issues. Herein, we propose a facile in-situ encapsulation strategy to protect Cu2O with hydrogen-substituted graphdiyne (HsGDY) and promote water reduction performance. The HsGDY encapsulated Cu2O nanowires (HsGDY@Cu2O NWs) photocathode demonstrates a high photocurrent density of −12.88 mA cm−2 at 0 V versus the reversible hydrogen electrode under 1 sun illumination, approaching to the theoretical value of Cu2O. The HsGDY@Cu2O NWs photocathode as well as presents excellent stability and contributes an impressive hydrogen generation rate of 218.2 ± 11.3 μmol h−1cm−2, which value has been further magnified to 861.1 ± 24.8 μmol h−1cm−2 under illumination of concentrated solar light. The in-situ encapsulation strategy opens an avenue for rational design photocathodes for efficient and stable PEC water reduction.
Wien effect in interfacial water dissociation through proton-permeable graphene electrodes
Authors: Cai J. , Griffin E. , Guarochico-Moreira V. H. , Barry D. , Xin B. , Yagmurcukardes M. , Zhang S. , Geim A. K. , Peeters F. M. , Lozada-Hidalgo M.
Published: October 2022

Strong electric fields can accelerate molecular dissociation reactions. The phenomenon known as the Wien effect was previously observed using high-voltage electrolysis cells that produced fields of about 107 V m−1, sufficient to accelerate the dissociation of weakly bound molecules (e.g., organics and weak electrolytes). The observation of the Wien effect for the common case of water dissociation (H2O $$\leftrightarrows$$
⇆
H+ + OH−) has remained elusive. Here we study the dissociation of interfacial water adjacent to proton-permeable graphene electrodes and observe strong acceleration of the reaction in fields reaching above 108 V m−1. The use of graphene electrodes allows measuring the proton currents arising exclusively from the dissociation of interfacial water, while the electric field driving the reaction is monitored through the carrier density induced in graphene by the same field. The observed exponential increase in proton currents is in quantitative agreement with Onsager’s theory. Our results also demonstrate that graphene electrodes can be valuable for the investigation of various interfacial phenomena involving proton transport.
Energy landscape reshaped by strain-specific mutations underlies epistasis in NS1 evolution of influenza A virus
Authors: Kim Iktae , Dubrow Alyssa , Zuniga Bryan , Zhao Baoyu , Sherer Noah , Bastiray Abhishek , Li Pingwei , Cho Jae-Hyun
Published: October 2022

Elucidating how individual mutations affect the protein energy landscape is crucial for understanding how proteins evolve. However, predicting mutational effects remains challenging because of epistasis—the nonadditive interactions between mutations. Here, we investigate the biophysical mechanism of strain-specific epistasis in the nonstructural protein 1 (NS1) of influenza A viruses (IAVs). We integrate structural, kinetic, thermodynamic, and conformational dynamics analyses of four NS1s of influenza strains that emerged between 1918 and 2004. Although functionally near-neutral, strain-specific NS1 mutations exhibit long-range epistatic interactions with residues at the p85β-binding interface. We reveal that strain-specific mutations reshaped the NS1 energy landscape during evolution. Using NMR spin dynamics, we find that the strain-specific mutations altered the conformational dynamics of the hidden network of tightly packed residues, underlying the evolution of long-range epistasis. This work shows how near-neutral mutations silently alter the biophysical energy landscapes, resulting in diverse background effects during molecular evolution.
Fitness consequences of chronic exposure to different light pollution wavelengths in nocturnal and diurnal rodents
Authors: Vardi-Naim Hagar , Benjamin Ava , Sagiv Tali , Kronfeld-Schor Noga
Published: October 2022

Use of artificial at night (ALAN) exposes the world to continuously increasing levels and distribution of light pollution. Our understanding of the adverse effects of ALAN is based mostly on observational or laboratory studies, and its effects are probably underestimated. Demonstration of direct experimental fitness consequences of ALAN on mammals is missing. We studied the effects of chronic light pollution at different wavelengths on fitness and glucocorticoid hormone levels under semi-natural conditions in two closely related species: the nocturnal common spiny mouse (Acomys cahirinus) and the diurnal golden spiny mouse (Acomys russatus). Our results clearly demonstrate the adverse effects of ALAN exposure on the fitness of both nocturnal and diurnal species, manifested by changes in cortisol levels and reproductive timing, reduced reproductive output and reduced survival, which differed between species and wavelengths. In A. russatus exposure to blue ALAN had the strongest effect on fitness, followed by white and yellow ALAN exposure. In A. cahirinus the results are more complex and suggest it suffered from the combined effects of ALAN and competition. Our research shows that light pollution presents a real threat to both nocturnal and diurnal species, affecting the species fitness directly and through interspecific interactions. Worryingly, these effects are probably not limited to spiny mice. The clear adverse effects we documented, as well as the differences between wave lengths, contribute to our ability to present science-based recommendations to decision makers regarding the use of artificial light at night. Such information and guidelines are highly important nowadays when lighting systems are being replaced to promote energy efficiency.
Single-shot off-axis digital holographic system with extended field-of-view by using multiplexing method
Authors: Kumar Manoj , Pensia Lavlesh , Kumar Raj
Published: October 2022

We propose a new configuration of single-shot off-axis digital holographic system to realize double the camera field-of-view (FOV) of the existing off-axis Mech-Zehnder type holographic setup. The double FOV is obtained by double spatial frequency multiplexing of two different areas of an object beam by inserting a Fresnel bi-prism in it, which divides the object beam into two, both carrying different object information. The image sensor is placed at the plane where these two different FOVs overlap so as to record simultaneously two parts of the wavefront of the object in a single-shot. The multiplexed hologram is carrying two interferometric images corresponding to two different FOVs of the object which are modulated with two different spatial carrier frequencies. The feasibility of the proposed digital holographic system is experimentally demonstrated by imaging two different areas of a resolution test target. The limitation of the proposed system and a method to overcome it, are also discussed. The proposed system is useful in a wide range of applications including microscopy and optical metrology.
Urtica dioica and Dodonaea viscosa leaf extracts as eco-friendly bioagents against Alternaria alternata isolate TAA-05 from tomato plant
Authors: Behiry Said I. , Philip Bassant , Salem Mohamed Z. M. , Amer Mostafa A. , El-Samra Ibrahim A. , Abdelkhalek Ahmed , Heflish Ahmed
Published: October 2022

One of the tomato’s acutely devastating diseases is Alternaria leaf spot, lowering worldwide tomato production. In this study, one fungal isolate was isolated from tomatoes and was assigned to Alternaria alternata TAA-05 upon morphological and molecular analysis of the ITS region and 18SrRNA, endoPG, Alt a1, and gapdh genes. Also, Urtica dioica and Dodonaea viscosa methanol leaf extracts (MLEs) were utilized as antifungal agents in vitro and compared to Ridomil, a reference chemical fungicide. The in vitro antifungal activity results revealed that Ridomil (2000 µg/mL) showed the highest fungal growth inhibition (FGI) against A. alternata (96.29%). Moderate activity was found against A. alternata by D. viscosa and U. dioica MLEs (2000 µg/mL), with an FGI value of 56.67 and 54.81%, respectively. The abundance of flavonoid and phenolic components were identified by HPLC analysis in the two plant extracts. The flavonoid compounds, including hesperidin, quercetin, and rutin were identified using HPLC in D. viscosa MLE with concentrations of 11.56, 10.04, and 5.14 µg/mL of extract and in U. dioica MLE with concentrations of 12.45, 9.21, and 5.23 µg/mL, respectively. α-Tocopherol and syringic acid, were also identified in D. viscosa MLE with concentrations of 26.13 and 13.69 µg/mL, and in U. dioica MLE, with values of 21.12 and 18.33 µg/mL, respectively. Finally, the bioactivity of plant extracts suggests that they play a crucial role as antifungal agents against A. alternata. Some phenolic chemicals, including coumaric acid, caffeic acid, ferulic acid, and α-tocopherol, have shown that they may be utilized as environmentally friendly fungicidal compounds.
Fractal features of soil grain-size distribution in a typical Tamarix cones in the Taklimakan Desert, China
Authors: Dong Zhengwu , Mao Donglei , Ye Mao , Li Shengyu , Ma Xiaodong , Liu Suiyunhao
Published: October 2022

Tamarix cones play key roles in preventing sand erosion and maintaining regional ecosystem stability. This study aimed to explore the characteristics of soil grain size distribution (GSD) in Tamarix cones across the Taklimakan Desert, verify the relationships between soil grain composition and the fractal dimension, and analyze the relationships between soil GSD and environmental factors. Soils of the Tamarix cones from 0 to 500 cm soil depth were sampled every 20 cm at four sites (Qiemo, Qira, Aral, and Tazhong) along the periphery to the hinterland of the Taklimakan Desert. A total of 300 soil samples were collected to measure soil grain sizes and soil properties. Soil grain size composition was dominated by silt and very fine sand, and the fraction of fine particles decreased and that of the coarse particles increased with soil depth, except for at Tazhong. This suggested that suspension-size particles are the main component of the soil GSD and decrease with the increasing depth in the profiles at the Tamarix cones. The soils were poorly and moderately poorly sorted. Kurtosis generally showed a mesokurtic peak, and the GSD was negatively skewed towards the coarser particles. The fractal dimensions of GSD decreased in the following order Qiemo (2.30) > Qira (2.07) > Aral (1.99) > Tazhong (1.96) because of the increase of coarse particles. The fractal dimension had a strong positive correlation with the clay and silt fractions, and a strong negative correlation with the sand fraction, indicating that the fractal dimension can reflect the characteristics of the soil GSD. The strong relationships between the fractal dimensions and selected soil properties indicate that the fractal dimension can not only quantify changes in soil properties, but also reflect the degree of desertification and degradation in the desert region. Considering the strong wind activities and different deposition sources in the Taklimakan Desert, this study provides a deep insight into the soil formation processes of Tamarix cones within extreme arid desert ecosystems.
Flapping and powering characteristics of a flexible piezoelectric nanogenerator at Reynolds number range simulating ocean current
Authors: Moon Joonkyeong , Kang Giho , Im Busi , Kim Jihoon , Cho Dae-Hyun , Byun Doyoung
Published: October 2022

For effective ocean energy harvesting, it is necessary to understand the coupled motion of the piezoelectric nanogenerator (PENG) and ocean currents. Herein, we experimentally investigate power performance of the PENG in the perspective of the fluid–structure interaction considering ocean conditions with the Reynolds number (Re) values ranging from 1 to 141,489. A piezoelectric polyvinylidene fluoride micromesh was constructed via electrohydrodynamic (EHD) jet printing technique to produce the β-phase dominantly that is desirable for powering performance. Water channel was set to generate water flow to vibrate the flexible PENG. By plotting theRevalues as a function of nondimensional bending rigidity (KB) and the structure-to-fluid mass ratio (M*), we could find neutral curves dividing the stable and flapping regimes. Analyzing the flow velocities between the vortex and surroundings via a particle image velocimetry, the larger displacement of the PENG in the chaotic flapping regime than that in the flapping regime was attributed to the sharp pressure gradient. By correlatingM*,Re,KB, and the PENG performance, we conclude that there is criticalKBthat generate chaotic flapping motion for effective powering. We believe this study contributes to the establishment of a design methodology for the flexible PENG harvesting of ocean currents.
Increased Type I interferon signaling and brain endothelial barrier dysfunction in an experimental model of Alzheimer’s disease
Authors: Jana Arundhati , Wang Xinge , Leasure Joseph W. , Magana Lissette , Wang Li , Kim Young-Mee , Dodiya Hemraj , Toth Peter T. , Sisodia Sangram S. , Rehman Jalees
Published: October 2022

Blood–brain barrier (BBB) dysfunction is emerging as a key pathogenic factor in the progression of Alzheimer’s disease (AD), where increased microvascular endothelial permeability has been proposed to play an important role. However, the molecular mechanisms leading to increased brain microvascular permeability in AD are not fully understood. We studied brain endothelial permeability in female APPswe/PS1∆E9 (APP/PS1) mice which constitute a transgenic mouse model of amyloid-beta (Aβ) amyloidosis and found that permeability increases with aging in the areas showing the greatest amyloid plaque deposition. We performed an unbiased bulk RNA-sequencing analysis of brain endothelial cells (BECs) in female APP/PS1 transgenic mice. We observed that upregulation of interferon signaling gene expression pathways in BECs was among the most prominent transcriptomic signatures in the brain endothelium. Immunofluorescence analysis of isolated BECs from female APP/PS1 mice demonstrated higher levels of the Type I interferon-stimulated gene IFIT2. Immunoblotting of APP/PS1 BECs showed downregulation of the adherens junction protein VE-cadherin. Stimulation of human brain endothelial cells with interferon-β decreased the levels of the adherens junction protein VE-cadherin as well as tight junction proteins Occludin and Claudin-5 and increased barrier leakiness. Depletion of the Type I interferon receptor in human brain endothelial cells prevented interferon-β-induced VE-cadherin downregulation and restored endothelial barrier integrity. Our study suggests that Type I interferon signaling contributes to brain endothelial dysfunction in AD.
Comparison of concentrations of chemical species and emission sources PM2.5 before pandemic and during pandemic in Krakow, Poland
Authors: Rys Anna , Samek Lucyna , Stegowski Zdzislaw , Styszko Katarzyna
Published: October 2022

Observations of air pollution in Krakow have shown that air quality has been improved during the last decade. In the presented study two factors affecting the physicochemical characteristic of PM2.5 fraction at AGH station in Krakow were observed. One is the ban of using solid fuels for heating purposes and the second is COVID-19 pandemic in Krakow. The PM2.5 fraction was collected during the whole year every 3rd day between 2nd March 2020 and 28th February 2021 at AGH station in Krakow. In total 110 PM2.5 fraction samples were collected. The chemical composition was determined for these samples. The elemental analysis was performed by energy dispersive X-ray fluorescence (EDXRF) technique, ions analysis was performed by ion chromatography (IC) and black carbon by optical method. In order to identify the emission sources the positive matrix factorization (PMF) was used. The results of such study were compared to similar analysis performed for PM2.5 for the period from June 2018 to May 2019 at AGH station in Krakow. The PM2.5 concentration dropped by 25% in 2020/2021 in comparison to 2018/2019 at this station. The concentrations of Si, K, Fe, Zn and Pb were lowering by 43–64% in the year 2020/2021 in comparison to 2018/2019. Cu, Mn, Zn and Pb come from mechanical abrasion of brakes and tires while Ti, Fe, Mn and Si are crustal species. They are the indicators of road dust (non-exhaust traffic source). Moreover, the annual average contribution of traffic/industrial/soil/construction work source was reduced in 2020/2021 in comparison to 2018/2019. As well the annual average contribution of fuels combustion was declining by 22% in 2020/2021 in comparison to 2018/2019. This study shows that the ban and lockdown, during COVID-19 pandemic, had significant impact on the characteristic of air pollution in Krakow.
A data‐driven inertia adequacy‐based approach for sustainable expansion planning in distributed generations‐penetrated power grids
Authors: Golpîra Hêmin , Amini Shiva , Atarodi Azin , Bevrani Hassan
Published: October 2022

Reduced rotational inertia in power grids due to increasing penetration levels of distributed generations (DGs) may lead to degraded performance of the traditional frequency control scheme. In response to this challenge, inertia adequacy has recently emerged as a new research area in modern power systems. Accordingly, an attempt is made in this paper to tackle inertia adequacy in the generation expansion planning (GEP) problem. This in turn helps to realize sustainable economic development. For this purpose, the inertia adequacy constraint is tied to the frequency stability metrics. In other words, minimum permissible inertia that satisfies frequency dynamic standards is defined as an inertia adequacy constraint in the GEP formulation. Further, an experimentally validated model of a cluster of DGs is employed to realize a penetrated power grid to deal with sustainable planning development. Finally, an iterative‐based algorithm is proposed to expand the system with minimum cost and with the highest permissible penetration level of DGs. The effectiveness of the proposed algorithm is examined in the Garver test system.
Multi‐similarity based hyperrelation network for few‐shot segmentation
Authors: Shi Xiangwen , Cui Zhe , Zhang Shaobing , Cheng Miao , He Lian , Tang Xianghong
Published: October 2022

Few‐shot semantic segmentation aims at recognizing the object regions of unseen categories with only a few annotated examples as supervision. The key to few‐shot segmentation is to establish a robust semantic relationship between the support and query images and to prevent overfitting. In this paper, an effective multi‐similarity hyperrelation network (MSHNet) is proposed to tackle the few‐shot semantic segmentation problem. In MSHNet, a new generative prototype similarity (GPS) is proposed, which, together with cosine similarity, establishes a strong semantic relationship between supported images and query images. In addition, a symmetric merging block (SMB) in MSHNet is proposed to efficiently merge multi‐layer, multi‐shot, multi‐similarity features to generate hyperrelation features for semantic segmentation. Experimenting on two benchmark semantic segmentation datasets (Pascal − 5i and COCO − 20i) shows that this method achieves a mean intersection‐over‐union score of 72.3% and 56.0%, respectively, which outperforms the state‐of‐the‐art methods by 1.9% and 6.5%.
Guest editorial: Biomass conversion for energy: Process intensification and economics
Authors: Patience Gregory S. , Villasana Yanet , Boffito Daria C.
Published: October 2022

The symposium Biomass Conversion for Energy: Process Intensification and Economics held at the Canadian Chemical Engineering Conference 2022 corresponds to several United Nations Sustainable Development Goals (SDG): SDG7—produce more affordable and cleaner energy; SDG9—build small‐scale industrial enterprises and domestic technologies; SDG12—improve the management and efficient use of natural resources; SDG13—integrate climate change measures into national strategies. Cooking fuel remains scarce in many regions around the world as three billion people rely on polluting systems while 800 million people have no electricity. The energy density of renewable resources is low, compared to petroleum, which makes transporting bio‐feedstocks to centralized stations prohibitively expensive. Process intensification (PI) and distributed manufacturing are strategies that reduce costs and serve these markets equitably. PI reduces the size of equipment while maintaining productivity by maximizing thermal, electrical, mechanical, and catalytic driving forces. These technologies must be coupled with mass manufacturing (numbering up manufacturing rather than scaling up) to achieve economic parity with centralized power facilities. They apply to converting biomass to electricity, thermo‐processing of lignocellulosics, and producing liquid fuels, butane, and propane from flared and vented natural gas, landfill gas, and biogas, via gas‐to‐liquids technology.
Design and implementation of an adaptive fuzzy sliding mode controller for drug delivery in treatment of vascular cancer tumours and its optimisation using genetic algorithm tool
Authors: Ghasemabad Ehsan Sadeghi , Zamani Iman , Tourajizadeh Hami , Mirhadi Mahdi , Zarandi Zahra Goorkani
Published: October 2022

In this paper, the side effects of drug therapy in the process of cancer treatment are reduced by designing two optimal non‐linear controllers. The related gains of the designed controllers are optimised using genetic algorithm and simultaneously are adapted by employing the Fuzzy scheduling method. The cancer dynamic model is extracted with five differential equations, including normal cells, endothelial cells, cancer cells, and the amount of two chemotherapy and anti‐angiogenic drugs left in the body as the engaged state variables, while double drug injection is considered as the corresponding controlling signals of the mentioned state space. This treatment aims to reduce the tumour cells by providing a timely schedule for drug dosage. In chemotherapy, not only the cancer cells are killed but also other healthy cells will be destroyed, so the rate of drug injection is highly significant. It is shown that the simultaneous application of chemotherapy and anti‐angiogenic therapy is more efficient than single chemotherapy. Two different non‐linear controllers are employed and their performances are compared. Simulation results and comparison studies show that not only adding the anti‐angiogenic reduce the side effects of chemotherapy but also the proposed robust controller of sliding mode provides a faster and stronger treatment in the presence of patient parametric uncertainties in an optimal way. As a result of the proposed closed‐loop drug treatment, the tumour cells rapidly decrease to zero, while the normal cells remain healthy simultaneously. Also, the injection rate of the chemotherapy drug is very low after a short time and converges to zero.
A metamaterial lens traps atoms
Authors: Miller Johanna L.
Published: October 2022

Compact, finely textured metasurface optics are coming to a new field of physics.
The race to cut methane emissions ramps up worldwide
Authors: Lopatka Alex
Published: October 2022

Governments, private companies, and nongovernmental organizations are teaming up to eliminate methane leaks and flaring from the oil and gas industry.
Sex and Gender Multidimensionality in Epidemiologic Research
Authors: Bauer Greta R
Published: October 2022

Along with age and race, sex has historically been a core stratification and control variable in epidemiologic research. While in recent decades research guidelines and institutionalized requirements have incorporated an approach differentiating biological sex from social gender, neither sex nor gender is itself a unidimensional construct. The conflation of dimensions within and between sex and gender presents a validity issue wherein proxy measures are used for dimensions of interest, often without explicit acknowledgement or evaluation. Here, individual-level dimensions of sex and gender are outlined as a guide for epidemiologists, and 2 case studies are presented. The first case study demonstrates how unacknowledged use of a sex/gender proxy for a sexed dimension of interest (uterine status) resulted in decades of cancer research misestimating risks, racial disparities, and age trends. The second illustrates how a multidimensional sex and gender framework may be applied to strengthen research on coronavirus disease 2019 incidence, diagnosis, morbidity, and mortality. Considerations are outlined, including: 1) addressing the match between measures and theory, and explicitly acknowledging and evaluating proxy use; 2) improving measurement across dimensions and social ecological levels; 3) incorporating multidimensionality into research objectives; and 4) interpreting sex, gender, and their effects as biopsychosocial.
Adaptive Federated Learning With Non-IID Data
Authors: Zeng Yan , Mu Yuankai , Yuan Junfeng , Teng Siyuan , Zhang Jilin , Wan Jian , Ren Yongjian , Zhang Yunquan
Published: October 2022

With the widespread use of Internet of things(IoT) devices, it generates an enormous volume of data, and it is a challenge to mine the IoT data value while ensuring security and privacy. Federated learning is a decentralized approach for training data located on edge devices, such as mobile phones and IoT devices, while keeping privacy, efficiency, and security. However, the Non-IID (non-independent and identically distributed) data, always greatly impacts the performance of the global model. In this paper, we propose a FedDynamic algorithm to solve the statistical challenge of federated learning caused by Non-IID. As Non-IID data can lead to significant differences in model parameters between edge devices, we set different weights for different devices during model aggregation to get a high-performance global model. We analyze and exact key indices (local model accuracy, local data quality, and model difference between local models and the global model), which can reflect the quality of the model, and calculate the aggregation weight for edge devices based on the key indices. Furthermore, we dynamically adjust aggregation weight based on accuracy’s variety to solve weight staleness during the training process. Experiments on the MNIST, FMNIST, EMNIST, CINIC-10 and CIFAR-10 datasets show that the FedDynamic algorithm has better accuracy and convergence performance, compared to the FedAvg, FedProx and Scaffold algorithms.
An Efficient Deep Learning Approach To IoT Intrusion Detection
Authors: Cao Jin , Lin Liwei , Ma Ruhui , Guan Haibing , Tian Mengke , Wang Yong
Published: October 2022

With the rapid development of the Internet of Things (IoT), network security challenges are becoming more and more complex, and the scale of intrusion attacks against the network is gradually increasing. Therefore, researchers have proposed Intrusion Detection Systems and constantly designed more effective systems to defend against attacks. One issue to consider is using limited computing power to process complex network data efficiently. In this paper, we take the AWID dataset as an example, propose an efficient data processing method to mitigate the interference caused by redundant data and design a lightweight deep learning-based model to analyze and predict the data category. Finally, we achieve an overall accuracy of 99.77% and an accuracy of 97.95% for attacks on the AWID dataset, with a detection rate of 99.98% for the injection attack. Our model has low computational overhead and a fast response time after training, ensuring the feasibility of applying to edge nodes with weak computational power in the IoT.
Reverse-Payment Settlements Under EU and US Patent Law: Convergence in Remedies
Authors: Signoretta Camilla
Published: October 2022

This paper investigates the existing case law on reverse-payment settlements from a comparative perspective, focusing on the US and EU panoramas. In this respect, we will illustrate the emergence of patent-related proxies in the anticompetitive assessment, which contaminate the antitrust benchmarks in a problematic way, with the effect of hampering patent law and policy. Primarily we will delve into seminal decisions in the EU framework. In this regard we will observe how the Court of Justice of the European Union (CJEU) shifted from a quick-look approach towards a case-by-case antitrust analysis of patent settlements, progressively neglecting, but not eliminating, patent-related presumptions. Then we will look at the fragmented US case law scenario. We will explore the various benchmarks deployed to challenge these agreements, highlighting the differences and similarities with the EU approaches. It will be concluded that a strong IP-law-based perspective about these agreements has arisen in both legal systems. This perspective orientates the anticompetitive assessment through quasi-absolute presumptions, hindering the consistency of competition law remedies and misrecognising the cruciality of patent law and policy. Therefore, we will try to outline that the intermingling of criteria adopted to scrutinise reverse-payment settlements and similar over-exclusionary strategies is pernicious under both antitrust and patent law.
Poppy Seed Consumption May Be Associated with Codeine-Only Urine Drug Test Results
Authors: Reisfield Gary M , Teitelbaum Scott A , Jones Joseph T
Published: October 2022

Consumption of poppy seed-containing food products can result in opiate-positive urine drug test results and may pose challenges in distinguishing poppy seed consumption from opiate administration. In this context, guidance has suggested that codeine concentrations exceeding 300 ng/mL coupled with morphine-to-codeine ratios <2 are indicative of codeine consumption and, therefore, exclude poppy seed consumption as a legitimate explanation for the test result. In recent years, we performed independent medical examinations of three individuals who produced codeine-positive/morphine-negative (300 ng/mL) forensic urine drug test results but denied codeine administration, attributing their test results to the consumption of specific poppy seed-containing food products. In the present study, 11 participants consumed one of the 10 unique poppy seed-containing food products, including the three implicated food products. Six of 33 non-baseline urine samples (18%)—representing three food products—were positive for codeine and negative for morphine at 300 ng/mL cut-offs (and therefore featured morphine-to-codeine ratios <2). This study adds to a small literature indicating that consumption of poppy seed-containing food products cannot reliably be distinguished from codeine administration based on previously published urinary opiate concentrations and ratios. An important caveat is that in none of these cases did maximum urinary codeine concentrations exceed 1,300 µg/g creatinine.
On-grid labeling method for freeze-fracture replicas
Authors: Osakada Hiroko , Fujimoto Toyoshi
Published: October 2022

Sodium dodecyl sulfate–treated freeze-fracture replica labeling (SDS-FRL) is an electron microscopic (EM) method that can define the two-dimensional distribution of membrane proteins and lipids in a quantitative manner. Despite its unsurpassed merit, SDS-FRL has been adopted in a limited number of labs, probably because it requires a laborious labeling process as well as equipment and technique for freeze-fracture. Here, we present a method that reduces the manual labor significantly by mounting freeze-fracture replicas on EM grids prior to labeling. This was made possible by the discovery that freeze-fracture replicas invariably adhere to the carbon-coated formvar membrane with their platinum–carbon side, ensuring that the membrane molecules retained in replicas are accessible to labeling solutions. The replicas mounted on EM grids can be stored dry until labeling, checked by light microscopy before labeling and labeled in the same manner as tissue sections. This on-grid method will make SDS-FRL easier to access for many researchers.
Recurrent vaginal vault dehiscence and evisceration following total laparoscopic hysterectomy, successfully repaired with polypropylene mesh and sacrocolpopexy
Authors: Rathigashini R , Wanniarachchi W A D P , De Silva A , Herath R P
Published: October 2022

Recurrent vault dehiscence is a rare and potentially serious complication following hysterectomy. We report a rare case of recurrent vault dehiscence and evisceration following a total laparoscopic hysterectomy (TLH) which was successfully repaired with polypropylene mesh and sacro-colpopexy. A 47-year-old multiparous woman underwent TLH for adenomyosis. During the surgery, vaginal wall was incised with monopolar diathermy and sutured with synthetic absorbable barbed suture in a single layer. She presented 12 weeks later with vault dehiscence and evisceration of omentum. Laparoscopically, eviscerated omental part was removed and the vaginal cuff was repaired vaginally with absorbable synthetic suture. She came with a recurrence in 3 months with vault dehiscence and a vault prolapse without any evisceration. She underwent laparoscopic mesh repair of the vault combined with laparoscopic Sacro-colpopexy with complete recovery. Incidence of vault dehiscence is found to be higher in TLH than abdominal or vaginal hysterectomy. Treatment options for recurrent vault dehiscence involve strengthening the vault with tissues, or with a prosthesis.
Molecular and Developmental Signatures of Genital Size Macro-Evolution in Bugs
Authors: Genevcius Bruno C , Calandriello Denis C , Torres Tatiana T
Published: October 2022

Our understanding of the genetic architecture of phenotypic traits has experienced drastic growth over the last years. Nevertheless, the majority of studies associating genotypes and phenotypes have been conducted at the ontogenetic level. Thus, we still have an elusive knowledge of how these genetic-developmental architectures evolve themselves and how their evolution is mirrored in the phenotypic change across evolutionary time. We tackle this gap by reconstructing the evolution of male genital size, one of the most complex traits in insects, together with its underlying genetic architecture. Using the order Hemiptera as a model, spanning over 350 million years of evolution, we estimate the correlation between genitalia and three features: development rate, body size, and rates of DNA substitution in 68 genes associated with genital development. We demonstrate that genital size macro-evolution has been largely dependent on body size and weakly influenced by development rate and phylogenetic history. We further revealed significant correlations between mutation rates and genital size for 19 genes. Interestingly, these genes have diverse functions and participate in distinct signaling pathways, suggesting that genital size is a complex trait whose fast evolution has been enabled by molecular changes associated with diverse morphogenetic processes. Our data further demonstrate that the majority of DNA evolution correlated with the genitalia has been shaped by negative selection or neutral evolution. Thus, in terms of sequence evolution, changes in genital size are predominantly facilitated by relaxation of constraints rather than positive selection, possibly due to the high pleiotropic nature of the morphogenetic genes.
Hull’s Magic Box: Keeping Brain Tumour Biopsies “Alive” in the Lab Brings Research Opportunities for New Therapies and Earlier Diagnosis of Brain Tumour
Authors: Barry Antonia , Samuel Sabrina , Moursi Amr , Deepak Srihari , Achawal Shailendra , Rajaraman Chittoor , Feugere Lauric , Iles Alexander , Green Vicky , Wade Mark , Stead Lucy , Greenman John , Beltran-Alvarez Pedro
Published: October 2022

AIMS

Assess/evaluate apoptosis in GBM samples maintained on a microfluidics system in response to GSK3368715 and other PRMT inhibitors, currently in clinical trials, with the ultimate goal of synergising with personalised patient care and precision medicine. Investigate the effect of treating GBM biopsies on-chip with PRMT inhibitors at the molecular level, including RNA and protein modifications.

METHOD

GBM biopsies are received from Hull Royal Infirmary and maintained on-chip for 8-days. They are perfused with media, at a rate of 3 μl/min, mimicking the in vivo environment and allowing real-time analysis of tumour behaviour. PRMT inhibitors, such as GSK3368715, are added to the media, in conjunction with TMZ, to determine their efficacy ex vivo using a range of techniques, such as: immunohistochemistry, cell viability assays, protein analysis and RNA-sequencing.

RESULTS

We show that PRMT inhibition increases apoptosis five-fold above the control, untreated GBM-on-chip samples. This is compounded by cell viability assays, which have indicated that cell viability in these post-chip tissues is reduced by 30% upon treatment with 1μM GSK3368715. Additionally, western blot analysis has indicated that PRMT inhibition with GSK3368715 appears to switch the methylation status of fused-in-sarcoma (FUS) protein in GBM biopsies.

CONCLUSION

These results indicate that PRMT inhibition may not only be a viable target for GBM therapy, but could also highlight a mechanism for re-sensitising MGMT-negative GBM to TMZ. This data produces an exciting argument for further research into the use of this novel inhibitor for improving prognosis for patients diagnosed with this devastating disease.
Novel Application of Polygenic Risk Scores Identifies Biomarkers for Early Detection of Glioma
Authors: Andrews Lily , Robinson Jamie , Kurian Kathreena , Kar Siddhartha
Published: October 2022

AIMS

In the UK, brain, other CNS and intracranial tumours incidence rates are increasing with over 12,200 new cases diagnosed each year. The overall survival rate over 5 years in these tumours is approximately 12%. There is a need for predictive biomarkers to detect the presence of gliomas to improve prognosis for such patients. A novel modified Mendelian randomization (MR)-based technique has been proposed to discover predictive biomarkers for diagnostic applications. The aim of this project is to identify circulating blood biomarkers that are genetically liable to all gliomas, glioblastoma (GB), or non-GBs.

METHOD

We generated polygenic scores for genetic liability to glioma and a separate GWAS of plasma protein levels from the INTERVAL study. We used sensitivity analyses methods to further assess our findings. The results were then validated by the plasma pQTL GWAS data from the Fenland cohort.

RESULTS

We identified a potential blood biomarker called erythroblast membrane associated protein (ERMAP) which showed consistent results across all sensitivity analyses in our discovery cohort [β: -0.0778, P-value: 2.1E-04]. We identified that decreased levels of ERMAP [β: -0.078 SD of ERMAP abundance per SD increase in glioma risk, 95% confidence interval (CI) 0.037 to 0.119, P-value: 2.1E-04] in the blood are associated with increased risk of glioma.

CONCLUSION

ERMAP protein is found to have a potential genetic liability for all gliomas. Predictive biomarkers are novel to glioma research and could be important for diagnostic applications and population screening in early detection. However, further clinical research is required to validate these findings.
Systemic Inflammation Is Implicated in De Novo Seizures Following Meningioma Resection
Authors: Bakhsh Ali , Gillespie Conor , Kumar Siddhant , Richardson George , Mustafa Arish , Mirza Nasir , Jenkinson Michael
Published: October 2022

AIMS

To investigate the association between perioperative peripheral blood inflammatory markers and seizures in patients who have undergone meningioma resection.

METHOD

A single neurosurgery tertiary centre blood bank database was screened to extract pre-operative and post-operative white cell count (WCC), neutrophils, lymphocytes, monocytes, platelets and neutrophil-lymphocyte ratio (NLR) and derived NLR (dNLR). All patients who underwent resection of meningioma from 2012 to 2020 were eligible. Patients were excluded if they had an inflammatory condition, peri-operative infection, medical illness or operative complication.

RESULTS

30 patients suffered pre-operative seizures only, 16 experienced de novo post-operative seizures within 1 year and 42 patients did not experience seizures throughout their treatment timeline. In those who had never had a seizure, there was a significant increase in WCC post-operatively (15.2 vs. 10.6 × 109/L (95% CI 2.1-8.2), p=0.02). Patients who suffered de novo seizures had a significantly higher post-operative day 1 to 4 WCC than those with no seizures (21.1 vs. 14.8 × 109/L (2.1-12.6), p=0.48). However, this difference of WCC was poorly predictive of de novo seizures at one year (AUC 0.61). There was no difference in pre-operative inflammatory markers between pre-operative seizure patients, de novo seizure or never seizure patients.

CONCLUSION

There is a significantly higher post-operative systemic inflammatory response in patients who suffered de novoseizures after meningioma resection. Peripheral blood markers have the potential to predict seizures in patients with meningioma.
CLIC1 and CLIC4 Ion Channel Deficiency Confers Increased Sensitivity to Tumour Treating Fields and Improved Survival in Paediatric Glioblastoma
Authors: Griffin Michaela , Basu Surajit , Khan Raheela , Smith Stuart
Published: October 2022

AIMS

(1) To determine if specific and unique chloride intracellular channel (CLIC) expression patterns exist in paediatric glioblastoma. (2) To assess if these expression patterns can be exploited as a treatment strategy. (3) To assess the combination of ion channel manipulation with Tumour Treating Fields (TTFields).

METHOD

CLIC channel expression patterns were identified via multivariate analysis of in-house and publicly available data sets and RNA sequencing of in-house patient tumour samples. siRNA depletion or inhibition via IAA94 of CLIC1 and CLIC4 was assessed using cell cycle, clonogenic, migration and proliferation assays, alone and in combination with TTFields. Whole transcriptome gene expression analysis (Human Clairom™ Array) of pGBM cells treated with TTFields was carried out.

RESULTS

Clinical correlation determined that CLIC4 and CLIC1 deficiency was associated with increased overall survival, with siRNA depletion propagating a reduction in the proliferation, migration and invasion of pHGG cell lines associated with cell cycle arrest. Furthermore, CLIC1 and CLIC4 deficiency exacerbated the killing capacity of TTFields, reducing clonogenic and proliferative capabilities. Whole transcriptome gene expression analysis of paediatric GBM cell lines treated with TTFields and found that cells treated with TTfields exhibited a down-regulation in CLIC1 and CLIC4 compared to untreated cells.

CONCLUSION

These data provide rationale that genetic, electrical, and pharmacological manipulation of ion channels can reduce the capacity of childhood brain tumours to proliferate and invade. CLIC channels may be a suitable target for combination therapy to enhance the treatment efficacy of TTfields and help bring this non-invasive therapy to paediatric patients.
Health-Related Quality of Life in Patients With High-Grade Glioma: A Systematic Review
Authors: Sanpher Elen , Mitchell Layla , Keshwara Sumirat , Islim Abdurrahman , Jenkinson Michael , Millward Christopher
Published: October 2022

AIMS

Several studies have evaluated health-related quality of life (HRQoL) through patient-reported outcomes (PROs) in high-grade glioma (HGG) patients. No systematic review has summarised this increasingly important research area.

METHOD

Seven electronic databases were systematically searched. Primary research articles evaluating HRQoL in HGG patients through PRO assessment were included. Global, physical, mental, and social health were summarised descriptively. Risk of bias (RoB) of included studies was assessed using The Joanna Briggs Institute Critical Appraisal tool or Newcastle Ottawa Scale. Quality of study reporting was assessed using a modified ISOQOL checklist.

RESULTS

Twenty-six studies were included (4,451 patients): cross-sectional (n=14), longitudinal (n=12). RoB and quality of reporting were satisfactory. Ten PRO measurement instruments were identified, of which EORTC-QLQ-C30 (n=15) was utilised most frequently. Fatigue significantly impacted both physical and global health. HRQoL improved after surgery but recurrence, fatigue, and difficulties with activities of daily living were associated with worsening HRQoL. HGG patients had higher anxiety and depression scores than the general population, negatively impacting overall HRQoL. Social health was superior for patients with good supportive networks, but a majority do not return to full-time employment post-diagnosis. Long-term survivors reported improvements in their physical, social and emotional functioning over time.

CONCLUSION

With HGG life expectancy less than 12 months post-diagnosis, HRQoL is of paramount importance to patients. PRO assessment of HRQoL can be used to evaluate self-reported functioning and well-being in both routine practice and clinical trial settings and provide opportunities for timely intervention.
Usability of Mixed Reality in Awake Craniotomy Planning
Authors: Moon Richard , Barua Neil
Published: October 2022

AIMS

This study aimed to describe our institutional use of a commercially available mixed reality viewer within a multi-disciplinary planning workflow for awake craniotomy surgery and to report an assessment of its usability.

METHOD

Three Tesla MRI scans, including 32-direction diffusion tensor sequences, were reconstructed with BrainLab Elements auto-segmentation software. Magic Leap mixed reality viewer headsets were registered to a shared virtual viewing space to display image reconstructions. System Usability Scale was used to assess the usability of the mixed reality system.

RESULTS

The awake craniotomy planning workflow utilises the mixed reality viewer to facilitate a stepwise discussion through four progressive anatomical layers; skin, cerebral cortex, subcortical white matter tracts and tumour with surrounding vasculature. At each stage relevant members of the multi-disciplinary team reviewed key operative considerations, including patient positioning, cortical and subcortical speech mapping protocols and surgical approaches to the tumour. The mixed reality system was used in 10 consecutive awake craniotomy procedures over a 5-month period. Ten participants (2 Anaesthetists, 5 Neurosurgical trainees, 2 Speech therapists, 1 Neuropsychologist) completed System Usability Scale assessments, reporting a mean score of 71.5. Feedback highlighted the benefit of being able to rehearse important steps in the procedure, including patient positioning and anaesthetic access and visualising the testing protocol for cortical and subcortical speech mapping.

CONCLUSION

This study supports the use of mixed reality for multi-disciplinary planning for awake craniotomy surgery, with an acceptable degree of interface usability. We highlight the need to consider the requirements of non-technical, non-neurosurgical team members when involving mixed reality activities.