bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective observational study to evaluate the clinical and biological safety profile of pyronaridine–artesunate in a rural health district in Burkina Faso
Authors: Rouamba Toussaint , Sondo Paul , Yerbanga Isidore W. , Compaore Adelaide , Traore‐Coulibaly Maminata , Hien Franck S. , Diande Nassirou A. , Valea Innocent , Tahita Marc Christian , Baiden Rita , Binka Fred , Tinto Halidou
Published: July 2022

The assessment in real‐life conditions of the safety and efficacy of new antimalarial drugs is of greatest interest. This study aimed to monitor and evaluate both clinical and biological safety of pyronaridine‐artesunate (PA) in real‐life conditions in Burkina Faso's health system. This was a single‐arm, open‐label study, where patients attending Nanoro health facilities with uncomplicated malaria were consented to be part of a cohort event monitoring (CEM). At inclusion (day‐0), PA was administered orally once a day for 3 days. Patients spontaneous reported any clinical adverse events (AEs) occurring within 28 days following the treatment. Additionally, the study focused on AEs of special interest (AESI), namely clinical signs related to hepatotoxicity and increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). A nested subset of patients with blood sample collection at day‐0 and day‐7 were monitored to investigate the effect of PA on biochemistry parameters. From September 2017 to October 2018, 2786 patients were treated with PA. About 97.8% (2720/2786) of patients did not report any AE. The most commonly reported events were respiratory, thoracic, and mediastinal disorders (8.3 per 1000), infections and infestations (7.9 per 1000), and gastrointestinal disorders (7.2 per 1000). No clinical or biological hepatotoxicity event related to PA was reported during the follow‐up. Changes in biochemistry parameters remained within laboratory reference ranges. The study showed that PA is a well‐tolerated drug and should be considered as a good option by malaria control programs in countries where existing first‐line antimalarial drugs are continuously threatened by the emergence of drug resistance.
Safe prescribing and withdrawal of dependence‐forming medicines
Authors: Chaplin Steve
Published: July 2022

NICE has recently published a guideline on the safe prescribing and withdrawal of medicines associated with dependence or withdrawal symptoms (NG215), including benzodiazepines, Z‐drugs, opioids, gabapentinoids and antidepressants. This article summarises the guidance, which recommends a supportive and collaborative approach.
Bimekizumab for the treatment of plaque psoriasis
Authors: Chaplin Steve
Published: July 2022

Bimekizumab (Bimzelx) is an anti‐IL‐17A and ‐17F monoclonal antibody for the treatment of moderate to severe plaque psoriasis. This article summarises its efficacy, adverse effects and place in therapy.
Evaluating response‐adaptive randomization procedures for recurrent events and terminal event data using a composite endpoint
Authors: Mau Yu‐Lin , Su Pei‐Fang
Published: July 2022

Recurrent event and terminal event data commonly arise in clinical and observational studies. To evaluate the efficacy of a treatment effect for both types of events, a composite endpoint has been used as a possible assessment, particularly when faced with high costs and a longer follow‐up study. To model recurrent event processes complicated by the existence of a terminal event, joint frailty modeling has been typically employed. In this study, the objective was to develop some target‐driven response adaptive randomization strategies using a composite endpoint based on joint frailty modeling. We first implemented a balanced randomized design and then investigated the response adaptive randomization. The former is intuitively first adopted while the latter is expected to be desirable and ethical in terms of allocating more subjects to the more effective treatment. The results show that the proposed procedures using a composite endpoint are capable of reducing the number of trial participants who receive inferior treatment while simultaneously reaching a desired optimal target as compared to a balanced randomized design. The R shiny application for calculating the sample size and allocation probabilities is also available. Finally, two clinical trials were used as pilot datasets to introduce the proposed procedures.
Gas source localization and mapping with mobile robots: A review
Authors: Francis Adam , Li Shuai , Griffiths Christian , Sienz Johann
Published: July 2022

Within the last couple of decades, there has been increasing research into the use of mobile robots for gas sensing applications. This has led to many different branches of research, most notably on the topics of gas distribution mapping and source localization. This paper aims to provide an up to date and comprehensive overview of the research on these topics for both controlled and uncontrolled environments with ground‐based or aerial robots. To complement other review papers, a greater focus is placed on recent probabilistic algorithms developed for both single robot and multirobot applications.
Application of DLLME‐SFO as a Green Analytical Tool for Determination of Trace Amounts of Cadmium and Lead in Vegetables and Fruits using FAAS: Optimization Using Box‐Behnken Design**
Authors: Mahmoudian Masoumeh , Sarrafi Amir Hossein Mohsen , Konoz Elaheh , Niazi Ali
Published: July 2022

In this study, dispersive liquid‐liquid microextraction method based on solidification of floating organic drop (DLLME‐SFO) was developed for the preconcentration of trace amount of Pb(II) and Cd(II) in vegetable and fruit extracts (DIW, Apple, Kiwi, Banana, Orange, Mint, Dill, Savory, and Thyme) and determination of these ions by flame atomic absorption spectroscopy (FAAS). The proposed method is based on the formation of an ion association Pb‐ 4‐(2‐thiazolylazo) resorcinol (TAR) ‐ zephiramine chloride (ZCl) and Cd‐4‐(2‐thiazolylazo) resorcinol (TAR) ‐ zephiramine chloride (ZCl) and then extraction of the resulting complex in micro‐droplets of the extraction solvent. Response surface methodology (RSM) based on the Box‐Behnken Design (BBD) was applied to optimize the experimental variables and evaluate the effect of factors. Optimal conditions were obtained with pH=6, 0.6 mL of the ligand solution 4‐(2‐thiazolylazo) resorcinol 0.2 %, 221 μL of 0.2 % zephiramine chloride, 130 μL of 1‐undecanol as solvent extraction, and 530 μL of acetonitrile. The linear range was 3.8‐200 and 1.0–160.0 μg L−1 with a coefficient of determination (R2) of 0.9976 and 0.9985 for Pb (II) and Cd(II), respectively. The limit of detection (LOD) was found to be 1.2 and 0.3 μg L−1 for Pb (II) and Cd(II), respectively. According to the results of market samples, the recovery (%) of the interday and intraday related to the Pb(II) were in the range of 94.67 % to 103.33 % and 95.33 % to 104.00 % for fruits and vegetables, respectively. Also, the relative standard deviation (RSD%) values of Pb(II) corresponding to the interday and intraday were found to be 1.52 % to 4.36 % and 2.15 % to 4.54 % for fruits and vegetables, respectively. In addition, the recoveries of Cd(II) were obtained 96.33 % to 104.00 % and 97.33 % to 103.33 % for fruits and vegetables, respectively. The RSD values of Cd(II) were 2.09 % to 4.19 % and 2.15 % to 4.54 % for fruits and vegetables, respectively. DLLME‐SFO uses an extraction solvent with lower toxicity instead of highly toxic solvents in other methods and high extraction recovery within a short period of time is possible.
A Polyethylenimine‐Functionalized Protic Ionic Liquid (PolyE‐IL) Catalyst for Conversion of Aqueous 2,3‐Butanediol into Methyl Ethyl Ketone (MEK)
Authors: Mahale Jyoti S. , Pawar Hitesh S.
Published: July 2022

The dehydration of C6 sugars derived 2, 3‐butane diol (2, 3‐BDO) into Methyl Ethyl Ketone (MEK) is an emerging, and green alternative for production of green platform chemicals. In the present manuscript polyethyleneimine (PEI) functionalized protic ionic liquid (PolyE‐IL) has been integrated as a selective, recyclable, robust and efficient catalyst for dehydration of aqueous 2, 3‐BDO into MEK. The exploration of PolyE‐IL catalyst provides selective dehydration of aqueous 2,3‐BDO with significantly higher yield (>70 %) of MEK and conversion (>80 %) of 2,3‐BDO. PolyE‐ILs with different counter ions were synthesized and tested for 2,3‐BDO dehydration. Of the tested catalyst, PolyE‐IL‐1 with sulfonic acid counter ion ([PEI]+[HSO4]−) showed excellent performance for obtaining high MEK yield (77 %) and 2,3‐BDO conversion (85 %) at 220 °C. Moreover, the [PEI]+[HSO4]− catalyst showed excellent performance in term of TON (4.16) and TOF (0.14) with E‐Factor (0.33) and PMI (28.3). The recyclability study for five consecutive runs showed the consistency in yield (>70 %) and conversion (>80 %). Thus, PolyE‐IL catalyst found to be robust and stable under optimized reaction conditions. The present process provides several environmental and process economical benefits of low operating temperature, pressure, reaction time, and catalyst recycle. The use of PolyE‐IL shall contribute to development of economically and industrially feasible process.
Synthesis of Nitrogen‐doped Carbon Nanodots from Tri‐isopropanolamine and the Application in Cell Imaging
Authors: Yang Jing , Fan Xuexue , Cao Yongqian , Liu Jianxin , Wang Yunfang , Zhang Xiaochao , Li Rui , Zhang Changming , Fan Caimei , Wang Yawen
Published: July 2022

As an emerging nano‐functional material, fluorescent carbon nanodots (CDs) have made breakthroughs in many fields. In our research, graphite‐like nitrogen‐doped carbon nanodots (N‐CDs) with excellent down‐ and up‐conversion fluorescent properties were synthesized by a facile one‐step solvothermal method using tri‐isopropanolamine (TIPA) as carbon and nitrogen sources. Mean particle diameter from 2.85 to 5.62 nm can be obtained by controlling the amount of HNO3 during synthesis. With low cytotoxicity and excellent fluorescence properties, the prepared N‐CDs can well label HeLa cells, which has great potential in the field of cell imaging. This work could enrich the research on the preparation and application of N‐CDs.
Synthesis and Properties of Bis(nitrocarbamoylethyl) Nitramine ‐ A New Energetic Open‐Chain Nitrocarbamate
Authors: Klapötke Thomas M. , Krumm Burkhard , Lechner Jasmin T. , Riedelsheimer Christian
Published: July 2022

The nitrocarbamate derivative of the well‐known and intensively investigated nitro ester DINA was prepared and studied. Starting with bis(hydroxyethyl) nitramine obtained from DINA, the corresponding carbamate was obtained by treatment with chlorosulfonyl isocyanate (CSI). Using fuming nitric acid only as nitration reagent, the target compound bis(nitrocarbamoylethyl) nitramine was synthesized. Furthermore, a route to the salt bis(nitrocarbamoylethyl)ammonium nitrate by a simple two step synthesis starting from diethanolamine was revealed. The compounds were fully characterized by NMR spectroscopy, X‐ray diffraction, differential thermal analysis, vibrational analysis and elemental analysis. The sensitivities towards impact and friction of the energetic compounds were measured, as well as their energetic properties determined by using the energies of formation, calculated on the CBS4‐M level of theory, with the EXPLO5 computer code.
Toxin‐Enabled “On‐Demand” Liposomes for Enhanced Phototherapy to Treat and Protect against Methicillin‐Resistant Staphylococcus aureus Infection
Authors: Zhuge Deli , Chen Mengchun , Yang Xuewei , Zhang Xufei , Yao Lulu , Li Li , Wang Haonan , Chen Hao , Yin Qingqing , Tian Dongyan , Weng Cuiye , Liu Shuangshuang , Xue Pengpeng , Lin Yijing , Sun Yiruo , Huang Zhuoying , Ye Cen Jie‐Nuo , Shen Lan , Huh Joo Young , Xia Weiliang , Zhao Yingzheng , Chen Yijie
Published: July 2022

An effective therapeutic strategy against methicillin‐resistant Staphylococcus aureus (MRSA) that does not promote further drug resistance is highly desirable. While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off‐target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore‐forming toxins trigger on‐demand payload release. Upon subsequent near‐infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on‐demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high‐priority pathogens.
Recent advances in the molecular basis of chemotherapy resistance and potential application of epigenetic therapeutics in chemorefractory renal cell carcinoma
Authors: Acharya Narayan , Singh Kamaleshwar P.
Published: July 2022

Among various types of cancers, kidney cancer is unique with respect to a low frequency of mutations and a relatively higher level of chemotherapy resistance. Resistance to chemotherapy is a major challenge in kidney cancer treatment in the clinic. Tremendous progress has been made in identifying the molecular changes associated with chemotherapy resistance in RCC. However, the exact contribution of these molecular changes to the acquisition of chemotherapy resistance is not fully understood. In addition to genetic changes, epigenetic alterations have been shown to contribute to various pathways associated with chemotherapy resistance, such as increased cell proliferation and survival, regulation of drug influx and efflux transporters, increased DNA repair, loss of DNA‐damage‐dependent apoptotic potential, cellular dedifferentiation to cancer stem cell, and epithelial–mesenchymal transitions (EMT). Moreover, recent studies suggest that epigenetic aberrations that can be reversed by epigenetic therapeutics can potentially be targeted to restore chemosensitivity in chemorefractory kidney cancer. This review article highlights current knowledge of the role of genetic and epigenetic aberrations as well as the physiological and metabolic changes associated with chemotherapeutic resistance. Additionally, current approaches and future directions for overcoming chemotherapeutic resistance including the potential of epigenetic therapeutic in chemorefractory kidney cancer have also been discussed.

This article is categorized under:

Cancer > Genetics/Genomics/Epigenetics
Moral Psychology of Emotion in Korean Neo-Confucianism and Its Philosophical Debates on the Affective Nature of the Mind
Authors: Seok Bongrae
Published: July 2022

This chapter discusses the Four-Seven Debate and the Horak Debate, the two major philosophical debates of Korean Neo-Confucianism and analyzes how Korean Neo-Confucians in the Joseon dynasty understood and explained emotions in their theories of the mind, morality, and human nature. Although the Korean thinkers respected and followed the philosophical framework of the Cheng-Zhu Neo-Confucianism, they also developed their own theories of emotions. The philosophical significance of Korean Neo-Confucianism lies in its unique moral psychology, the moral psychology of the emotional mind with its dedication to the moral nature of human beings and the regulative principle of the universe.
The UN Food Systems Summit: Disaster Capitalism and the Future of Food
Authors: Ferrando Tomaso
Published: July 2022

COVID-19 has brought to light the multiple cracks in the logistically integrated, financialized and commodity-based capitalist food system. As with other aspects of social life thrown into disruption amid the global health, economic and environmental downturn, the early weeks of the pandemic seemed to offer the hope of transformative possibility, a “portal” towards different food systems. The time seemed ripe for the kinds of radical transitions that social movements and peasants’ organizations have requested for decades: subverting the “conventional” food system without going back to “corporate normality”. However, when the multiple crises are characterized as exceptional rather than structural, a narrative of emergency and urgency is deployed to reinforce the power of the incumbents. The overlap between the pandemic and the climate crisis can be an opportunity, but hardly for peasants and indigenous people. As in Naomi Klein’s Shock Doctrine, corporate actors and billionaire philanthropists are using the rhetoric of urgency to push for changes that reinforce the status quo and do not address the root causes that have brought us here. In order to spark debate and reflections, my contribution engages with one example of ongoing co-optation of the state of climate and sanitary emergency: the 2021 United Nations Food Systems Summit as a new food policy arena where decisions are distanced from peasants, indigenous communities and citizens and put in the hands of corporations, financial investors and billionaire philanthropists.
Against Consumer Ethics
Authors: Mayes Christopher , Sassano Angie
Published: July 2022

Consumer food ethics has re-emerged over the past 30 years as a popular form of activism to address concerns with the dominance of corporate interests in the global food system. Proponents of consumer ethics contend that informing consumers about injustices in the food system via labels or awareness campaigns will lead to collective rejection of unethical food corporations and the embrace of ethical products. This approach has been criticized on a variety of grounds, including its reliance on and eventual co-optation by market mechanisms. In response to these criticisms, food activists and scholars have promoted a consumer ethic that embraces local and alternative food systems, thereby producing an alternative consumer ethic purportedly outside of market logics. While these alternative practices have much to commend them, we argue that alternative food systems are invariably oriented towards consumer interests and thereby run into similar problems faced by earlier iterations of consumer-based ethics. We argue against the persistent focus on consumer ethics as means of substantially disrupting food systems, whether global, local or alternative.
Going Against the Grain in the West Australian Wheatbelt
Authors: Donati Kelly
Published: July 2022

The vast wheatbelt of Western Australia marks a disruptive force on an ancient landscape, an upheaval wrought by the dispossessive ecologies of sheep and wheat (Mayes, Unsettling Food Politics: Agriculture, Dispossession and Sovereignty. London: Rowman & Littlefield, 2018). This chapter asks what transformational possibilities might emerge in this context through a case study of a broad-acre regenerative-farming couple, Di and Ian Haggerty, and their experiments with new ways of knowing, living and farming in the wheatbelt. The Haggertys seek to reconfigure ecological relations within regimes of large-scale production. On the one hand, these regimes of production look much like their neighbours’, as they use the same logistical chains, infrastructure and financial systems as other wheatbelt producers. On the other, their farming practice—informed by a probiotic and more-than-human epistemology the Haggertys call “natural intelligence”—suggests a potential disruption to extractivist commodity agriculture in the wheatbelt and the hegemony of its technoscientific institutions. While regenerative farming at scale could be dismissed as a greener form of settler-colonial agriculture, this case study suggests, or at least creates space for, a cautious optimism that more diverse ways of knowing and doing food might be constructed from within the cracks of global supply chains and that new alliances might emerge from the ground up.
Reviving Community Agrarianism in Post-socialist China
Authors: Leung Daren Shi-Chi
Published: July 2022

Tasked with feeding 1.4 billion people, China often promotes its success in food security in relation to its self-sufficient grain production. In the post-socialist context, the reformist state has been pursuing a capital-based vertical model to integrate millions of smallholding producers into the market. Yet, the introduction of high-yield hybrid rice to increase production has resulted in a set of related crises, including widespread environmental pollution, food-safety issues and adverse impacts on rural life. However, agrarian communities are challenging these state-imposed practices of food production. This chapter explores an endogenous form of regenerative agriculture that has emerged in South China since the early 2000s, a Chinese form of food and farming activism for reviving community agrarianism. I argue that the revitalization of “traditional” farming practices as a form of xaingtu (rural) knowledge has evolved with and through local peasants’ experience and struggle over the decades. One example that combines diverse aspects of such knowledge is the “fish-duck-rice paddy”, a well-known symbiotic method of pest control that also works with native varieties, organic manure and cooperative labour. This method revives peasants’ experience of the Mao era as a cultural reference for community agrarianism. The revival of community agrarianism allows farming to be narrated as an evolving social and historical practice, not “wasting” peasants’ knowledge, in contrast to the capitalist agrarian transformation.
Fantasies of Logistics in Aotearoa New Zealand
Authors: Henry Matthew , Morris Carolyn
Published: July 2022

Logistics is a form of calculative reasoning and set of material practices framed by the fantasy of perpetual, seamless circulation. This fantasy is built on ideas of universal connection and fungibility that sit beyond the teeming messiness of lived, unpacified life. The fantasy of connection is, however, continually haunted by an anxiety that an irruption of liveliness will disrupt material flows and expectations of plenitude. In this chapter, we draw on two case studies of food disruption from Aotearoa New Zealand—pork and flour—to interrogate these promises. The two cases take the form of vignettes when the regular operation of logistics relationships was in some way affected by the COVID-19 response of the Aotearoa New Zealand government and other actors. We argue that the character and impact of the disruption experienced in each case study are specific to its material and cultural particularities and that the particularities of disruption themselves provide a valuable analytical entry point for understanding the fragility and contingency of logistics. This leads us to show that the critical analysis of logistics relationships needs to move beyond a mirroring of claims to universality and is more insightful when it is attentive to the specific materialities of things and their liveliness.
Reproducing Hunger in Pandemic America
Authors: Dickinson Maggie
Published: July 2022

The COVID-19 pandemic has precipitated a significant rise in hunger in the United States, especially among caretakers of children, people who are unemployed or insecurely employed, undocumented immigrants and other racialized marginalized groups. The gaping holes in the public response to growing hunger are the inevitable result of decades of welfare state transformation in which policymakers have withdrawn assistance for caregivers and reframed public benefits as a subsidy to low-wage jobs. In the face of mass unemployment and life-threatening risks for frontline food workers, hunger is once again being deployed as a tool to push people into unsafe jobs that prop up a racist and ecologically destructive food system.
Line defects in three dimensional mirror symmetry beyond linear quivers
Authors: Dey Anindya
Published: July 2022

Abstract

The map of half-BPS line defects under mirror symmetry has previously been worked out for 3d $$ \mathcal{N} $$
N
= 4 linear quivers with unitary gauge groups, where these defects have a clear realization in terms of a brane picture in Type IIB String Theory. In this work, we initiate the study of line defects and the associated mirror maps for more general 3d $$ \mathcal{N} $$
N
= 4 quiver gauge theories from a QFT approach, using the S-type operations introduced in [1]. In particular, our construction does not rely on any String Theory realization of the quiver gauge theories and the defects. After discussing the general framework for the construction of these line defects and their mirror maps, we focus on quiver gauge theories of the D-type and the affine D-type with unitary gauge groups, as a concrete set of examples. Some of the line defects we study admit a Hanany-Witten description and we show that the associated mirror maps predicted by the Type IIB construction in these cases agree with the QFT computation. In addition, we study an example involving defects in an affine D-type theory, for which the dual theory is not directly realized by the Type IIB description. In a companion paper, we will discuss defects in infinite families of non-ADE quivers using the general construction developed in this paper.
BIonic membranes and AdS instabilities
Authors: Marchesano Fernando , Prieto David , Quirant Joan
Published: July 2022

Abstract

We study 4d membranes in type IIA flux compactifications of the form AdS4× X6, whereX6admits a Calabi-Yau metric. These models feature scale separation and D6-branes/O6-planes on three-cycles ofX6. When the latter are treated as localised sources, explicit solutions to the 10d equations of motion and Bianchi identities are known in 4d$$ \mathcal{N} $$N= 1 settings, valid at first order in an expansion parameter related to the AdS4cosmological constant. We extend such solutions to a family of perturbatively stable$$ \mathcal{N} $$N= 0 vacua, and analyse their non-perturbative stability by looking at 4d membranes. Up to the accuracy of the solution, we find that either D4-branes or anti-D4-branes on holomorphic curves feel no force in both$$ \mathcal{N} $$N= 1 and$$ \mathcal{N} $$N= 0 AdS4. Differently, D8-branes wrappingX6and with D6-branes ending on them can be superextremal 4d membranes attracted towards the$$ \mathcal{N} $$N= 0 AdS4boundary. The sources of imbalance are the curvature ofX6and the D8/D6 BIon profile, with both comparable terms as can be checked forX6a (blown-up) toroidal orbifold. We then show that simple$$ \mathcal{N} $$N= 0 vacua with space-time filling D6-branes are unstable against bubble nucleation, decaying to$$ \mathcal{N} $$N= 0 vacua with less D6-branes and larger Romans mass.
Model-independent constraints on non-unitary neutrino mixing from high-precision long-baseline experiments
Authors: Agarwalla Sanjib Kumar , Das Sudipta , Giarnetti Alessio , Meloni Davide
Published: July 2022

Abstract

Our knowledge on the active 3νmixing angles (θ12,θ13, andθ23) and the CP phaseδCPis becoming accurate day-by-day enabling us to test the unitarity of the leptonic mixing matrix with utmost precision. Future high-precision long-baseline experiments are going to play an important role in this direction. In this work, we study the impact of possible non-unitary neutrino mixing (NUNM) in the context of next-generation long-baseline experiments DUNE and T2HKK/JD+KD having one detector in Japan (T2HK/JD) and a second detector in Korea (KD). We estimate the sensitivities of these setups to place direct, model-independent, and competitive constraints on various NUNM parameters. We demonstrate the possible correlations between the NUNM parameters,θ23, andδCP. Our numerical results obtained using only far detector data and supported by simple approximate analytical expressions of the oscillation probabilities in matter, reveal that JD+KD has better sensitivities for|α21|andα22as compared to DUNE, due to its larger statistics in the appearance channel and less systematic uncertainties in the disappearance channel, respectively. For|α31|,|α32|, andα33, DUNE gives better constraints as compared to JD+KD, due to its larger matter effect and wider neutrino energy spectrum. Forα11, both DUNE and JD+KD give similar bounds. We also show how much the bounds on the NUNM parameters can be improved by combining the prospective data from DUNE and JD+KD setups. We find that due to zero-distance effects, the near detectors alone can also constrainα11,|α21|, andα22in both these setups. Finally, we observe that theντappearance sample in DUNE can improve the constraints on|α32|andα33.
Ataluren suppresses a premature termination codon in an MPS I-H mouse
Authors: Wang Dan , Xue Xiaojiao , Gunn Gwen , Du Ming , Siddiqui Amna , Weetall Marla , Keeling Kim M.
Published: July 2022

Abstarct

Suppressing translation termination at premature termination codons (PTCs), termed readthrough, is a potential therapy for genetic diseases caused by nonsense mutations. Ataluren is a compound that has shown promise for clinical use as a readthrough agent. However, some reports suggest that ataluren is ineffective at suppressing PTCs. To further evaluate the effectiveness of ataluren as a readthrough agent, we examined its ability to suppress PTCs in a variety of previously untested models. Using NanoLuc readthrough reporters expressed in two different cell types, we found that ataluren stimulated a significant level of readthrough. We also explored the ability of ataluren to suppress a nonsense mutation associated with Mucopolysaccharidosis I-Hurler (MPS I-H), a genetic disease that is caused by a deficiency of α-L-iduronidase that leads to lysosomal accumulation of glycosaminoglycans (GAGs). Using mouse embryonic fibroblasts (MEFs) derived from Idua-W402X mice, we found that ataluren partially rescued α-L-iduronidase function and significantly reduced GAG accumulation relative to controls. Two-week oral administration of ataluren to Idua-W402X mice led to significant GAG reductions in most tissues compared to controls. Together, these data reveal important details concerning the efficiency of ataluren as a readthrough agent and the mechanisms that govern its ability to suppress PTCs.

Key messages

Ataluren promotes readthrough of PTCs in a wide variety of contexts.

Ataluren reduces glycosaminoglyan storage in MPS I-H cell and mouse models.

Ataluren has a bell-shaped dose–response curve and a narrow effective range.
A novel phenotype in an Italian family with a rare progranulin mutation
Authors: Russillo Maria Claudia , Sorrentino Cristiano , Scarpa Alfonso , Vinciguerra Claudia , Cicarelli Giulio , Cuoco Sofia , Gagliardi Monica , Talarico Mariagrazia , Procopio Radha , Quattrone Andrea , Barone Paolo , Pellecchia Maria Teresa
Published: July 2022

Introduction

Progranulin (PGRN) is a secreted glycoprotein encoded in humans by the GRN gene, located on chromosome 17q21. Several nonsense and missense pathogenetic GRN mutations have been described.

Objective

We herein describe two sisters carrying a rare GRN mutation with extremely different clinical features and family history of dementia and behavioral disorders, with a novel presentation with stridor and dysphonia.

Methods

Patients underwent a multidimensional assessment including neurological and neuropsychological evaluation, structural and functional imaging, and genetic screening.

Results

The younger sister presented at the age of 64 with inspiratory stridor, dysphonia and exercise-induced dyspnea. Transnasal fiberoptic laryngoscopy showed bilateral adduction of the vocal cords at rest and paradoxical further adduction of the vocal cords during forced inspiration, suggesting the hypothesis of an adductor laryngeal dystonia. The older sister presented at the age of 63 with a rapidly progressive corticobasal syndrome. The only clinical feature common to both sisters was a dysexecutive syndrome. The c.893G > A mutation in exon 9 of GRN was found in heterozygosis in both sisters, causing a missense Arginine to Histidine substitution in position 298 of the protein (p.R298H).

Conclusions

Our report supports the pathogenicity of the GRN p.R298H mutation, which is first detected in two members from the same family, showing an extremely different phenotypes. Moreover, we report the first case of an FTD-associated mutation presenting with inspiratory stridor and dysphonia linked to adductor laryngeal dystonia, thus expanding the clinical spectrum of GRN-related disorders.
Ex situ arterial reconstruction prior normothermic machine perfusion of liver grafts
Authors: Becker Felix , Kneifel Felicia , Riegel Arne , Katou Shadi , Wagner Tristan , Flammang Isabelle , Juratli Mazen , Vogel Thomas , Radunz Sonia , Morgul Haluk , Pascher Andreas , Houben Philipp , Brockmann Jens G.
Published: July 2022

Purpose

Atypical variants of the hepatic artery are common and pose a technical challenge for normothermic machine perfusion (NMP). The transplant surgeon has three options when confronted with hepatic arterial variation in a liver graft to be subjected to NMP: to perform arterial reconstruction (i) prior, (ii) during, or (iii) following NMP.

Methods

Herein, we report our experience and technical considerations with pre-NMP reconstruction. Out of 52 livers, 9 had an atypical hepatic artery (HA): 3 replaced right HA, 3 replaced left HA, 1 accessory left HA, 1 accessory left and right HA, and 1 replaced left and right HA.

Results

Reconstruction was conducted during back-table preparation. A single vascular conduit was created in all grafts to allow single arterial cannulation for NMP, necessitating only one arterial anastomosis within the recipient. All grafts were subjected to NMP and subsequently successfully transplanted.

Conclusion

Our approach is being advocated for as it preserves the ability to alter the reconstruction in case of problems resulting from the reconstruction itself, thereby allowing functional evaluation of the reconstruction prior transplantation, permitting simultaneous reperfusion in the recipient, and providing the shortest possible duration for vascular reconstruction once the graft is rewarming non-perfused within the recipient. In addition, in light of the frequency of technically demanding reconstructions with very small vessels, we consider our technique beneficial as the procedure can be performed under ideal conditions at the back-table.
Expert opinion on NSCLC small specimen biomarker testing — Part 1: Tissue collection and management
Authors: Penault-Llorca Frédérique , Kerr Keith M. , Garrido Pilar , Thunnissen Erik , Dequeker Elisabeth , Normanno Nicola , Patton Simon J. , Fairley Jenni , Kapp Joshua , de Ridder Daniëlle , Ryška Aleš , Moch Holger
Published: July 2022

Biomarker testing is crucial for treatment selection in advanced non-small cell lung cancer (NSCLC). However, the quantity of available tissue often presents a key constraint for patients with advanced disease, where minimally invasive tissue biopsy typically returns small samples. In Part 1 of this two-part series, we summarise evidence-based recommendations relating to small sample processing for patients with NSCLC. Generally, tissue biopsy techniques that deliver the greatest quantity and quality of tissue with the least risk to the patient should be selected. Rapid on-site evaluation can help to ensure sufficient sample quality and quantity. Sample processing should be managed according to biomarker testing requirements, because tissue fixation methodology influences downstream nucleic acid, protein and morphological analyses. Accordingly, 10% neutral buffered formalin is recommended as an appropriate fixative, and the duration of fixation is recommended not to exceed 24–48 h. Tissue sparing techniques, including the ‘one biopsy per block’ approach and small sample cutting protocols, can help preserve tissue. Cytological material (formalin-fixed paraffin-embedded [FFPE] cytology blocks and non-FFPE samples such as smears and touch preparations) can be an excellent source of nucleic acid, providing either primary or supplementary patient material to complete morphological and molecular diagnoses. Considerations on biomarker testing, reporting and quality assessment are discussed in Part 2.
Different standing postures are the influencing factors for the efficacy of laminoplasty in the treatment of K-Line (−) patients with ossification of the posterior longitudinal ligament
Authors: Xue Rui , Liu Dai , Li Yao , Zhang Di
Published: July 2022

Objective

To investigate the relationship between different standing postures and surgical outcomes of K-Line (−) ossification of the posterior longitudinal ligament (OPLL) patients after laminoplasty with a titanium basket.

Summary of Background Data

There is a lack of data evaluating the relationship between the postoperative satisfaction of K-Line (−) patients and their standing postures.

Methods

OPLL patients enrolled in the study were divided into a K-Line (+) group (Group A) and a K-Line (− group (Group B) in natural and relaxed standing positions. We compared the postoperative outcomes after cervical laminoplasty with titanium basket surgery using the Japanese Orthopaedic Association score (JOA), recovery rate and the degree of improvement in the six JOA score items. The degree of satisfaction with the outcome was assessed at the 1-year follow-up using a 7-point numerical rating scale.

Results

A total of 34 K-Line (+) patients with OPLL (age 61.9 ± 2.9 years) in Group A and 40 K-Line (−)patients with OPLL (age 60.4 ± 3.5 years) in Group B in natural and relaxed standing positions were recruited. In Group A, the mean preoperative and postoperative JOA scores were 10.1 ± 1.4 and 13.1 ± 0.8 points, respectively, and in Group B, the mean preoperative and postoperative JOA scores were 9.7 ± 1.3 and 11.1 ± 0.9 points, respectively. A significant improvement in the JOA score was seen in both groups postoperatively, but the recovery rate of the patients’ JOA scores was significantly lower in Group B. In Group A, significant improvements were seen in all JOA score items, but in Group B, improvements were seen only in upper- and lower-extremity sensory functions.

Conclusion

Different standing postures are risk factors in the treatment of K-Line (−) patients, and therefore, natural and relaxed standing positions should be given more attention before devising the surgical plan.
Allopolyploidisation in a geological collision zone: on the origin of the tetraploid Anthemis cupaniana Nyman (Compositae, Anthemideae) in Sicily
Authors: Oberprieler Christoph , Verkhoturova Elena , Domina Gianniantonio
Published: July 2022

The genus Anthemis has a circum-Mediterranean distribution and comprises c. 175 annual, biennial, and perennial species with polyploid species and species complexes found in its section A. sect. Hiorthia. In Sicily, the genus is represented by 13 species, one of these being the tetraploid A. cupaniana, which is endemic to the island and is distributed throughout the limestone mountains at elevations between 500 and 1800 m a.s.l. Discordant positions in phylogenetic trees based on two plastid regions (psbA-trnH and trnC-petN) and on one nuclear marker (nrDNA ITS1 + 5.8S + ITS2) reveal that the species is of allopolyploid origin, with the maternal parent from the species group around A. cretica and the paternal one from a monophyletic group comprising mostly N African representatives around A. pedunculata. Owing to the fact that the latter group also comprises the Sicilian perennial and diploid A. ismelia and that A. cretica has been found with diploid populations in the C Sicilian Madonie Mts, these two species are considered being the most probable parental diploids of A. cupaniana. The close relationship of A. ismelia with the N African A. pedunculata group supports the biogeographical interpretation of A. cupaniana being the result of a ‘collision’ between diploids from the southern (African) and northern (Eurasian) platforms after dispersal along a Pleistocene corridor in the Sicilian channel.
Edge computing
Authors: Pérez Jorge , Díaz Jessica , Berrocal Javier , López-Viana Ramón , González-Prieto Ángel
Published: July 2022

IoT edge computing is a new computing paradigm “in the IoT domain” for performing calculations and processing at the edge of the network, closer to the user and the source of the data. This paradigm is relatively recent, and, together with cloud and fog computing, there may be some confusion about its meaning and implications. This paper aims to help practitioners and researchers better understand what the industry thinks about what IoT edge computing is, and the expected benefits and challenges associated with this paradigm. We conducted a survey using a semi-structured in-depth questionnaire to collect qualitative data from relevant stakeholders from 29 multinational companies and qualitatively analyzed these data using the Constructivist Grounded Theory (Charmaz) method. Several researchers participated in the coding process (collaborative coding). To ensure consensus on the constructs that support the theory and thus improve the rigor of qualitative research, we conducted an intercoder agreement analysis. From the analysis, we have derived a substantive and analytic theory of what companies perceive about IoT edge computing, its benefits and challenges. The theory is substantive in that the scope of validity refers to the 29 surveys processed and analytic in that it analyzes “what is” rather than explaining causality or attempting predictive generalizations. A public repository with all the data related to the information capture process and the products resulting from the analysis of this information is publicly available. This study aims to strengthen the evidence and support practitioners in making better informed decisions about why companies are adopting edge computing and the current challenges they face. Additionally, the testing theory phase shows that the results are aligned with the ISO/IEC TR 30164 standard.
PDGFD switches on stem cell endothelial commitment
Authors: Lu Weisi , Xu Peipei , Deng Boxiong , Zhang Jianing , Zhan Ying , Lin Xianchai , Xu Xiangzhong , Xia Zhaoxia , Yang Xiaoxi , Zeng Xiaoling , Huang Lijuan , Xie Bingbing , Wang Chenghu , Wang Shasha , Kuang Haiqing , Han Xianjing , Mora Antonio , Cao Yihai , Jiang Qin , Li Xuri
Published: July 2022

The critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.
Predicting Housing Related Delayed Discharge from Mental Health Inpatient Units: A Case Control Study
Authors: Honey Anne , Arblaster Karen , Nguyen Jenny , Heard Robert
Published: July 2022

The aims of this study were to identify factors that a) predict whether people experience housing related discharge delay (HRDD) from a mental health inpatient unit; and b) predict the length of HRDD for people affected. By identifying the groups most affected by HRDD, clinicians and policy makers can prioritise and address barriers to timely discharge at both an individual and systemic level. A case control study using a detailed medical record review was conducted in one Australian mental health service. Demographic, clinical, contextual and systemic variables were collected for patients with HRDD in one calendar year (n = 55) and a random comparison sample (n = 55). Logistical and multiple regression analyses were conducted to identify variables that predict HRDD and length of HRDD. A model that correctly predicted 92% of HRDD and 78% of non-HRDD cases using five variables was developed. These variables were: diagnosis of schizophrenia or other psychotic disorder, physical comorbidity, having a history of violence or aggressive behaviour, being employed and being involved as a defendant in the justice system. The first three variables increased the likelihood of HRDD, while the second two reduced the likelihood of HRDD. For people who experienced HRDD, the only variable that predicted length of delay was staff reported difficulty finding appropriate support services. This model can be used to rapidly identify patients who might be at risk of HRDD and commence coordinated actions to secure appropriate housing and supports to facilitate timely discharge, thereby addressing a current practice gap. These findings highlight the intersection between health, housing and disability services in the lives of people with serious mental illness, and the need for a whole of government approach to investment and integration to address systemic barriers to suitable housing and supports.
Vehicle trajectory prediction on highways using bird eye view representations and deep learning
Authors: Izquierdo Rubén , Quintanar Álvaro , Llorca David Fernández , Daza Iván García , Hernández Noelia , Parra Ignacio , Sotelo Miguel Ángel
Published: July 2022

This work presents a novel method for predicting vehicle trajectories in highway scenarios using efficient bird’s eye view representations and convolutional neural networks. Vehicle positions, motion histories, road configuration, and vehicle interactions are easily included in the prediction model using basic visual representations. The U-net model has been selected as the prediction kernel to generate future visual representations of the scene using an image-to-image regression approach. A method has been implemented to extract vehicle positions from the generated graphical representations to achieve subpixel resolution. The method has been trained and evaluated using the PREVENTION dataset, an on-board sensor dataset. Different network configurations and scene representations have been evaluated. This study found that U-net with 6 depth levels using a linear terminal layer and a Gaussian representation of the vehicles is the best performing configuration. The use of lane markings was found to produce no improvement in prediction performance. The average prediction error is 0.47 and 0.38 meters and the final prediction error is 0.76 and 0.53 meters for longitudinal and lateral coordinates, respectively, for a predicted trajectory length of 2.0 seconds. The prediction error is up to 50% lower compared to the baseline method.