bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes for the first four lines of therapy in patients with HER2-positive advanced breast cancer: results from the SONABRE registry
Authors: Ibragimova Khava I. E. , Geurts Sandra M. E. , Meegdes Marissa , Erdkamp Frans , Heijns Joan B. , Tol Jolien , Vriens Birgit E. P. J. , Dercksen Marcus W. , Aaldering Kirsten N. A. , Pepels Manon J. A. E. , van de Winkel Linda , Peters Natascha A. J. B. , Teeuwen-Dedroog Nathalie J. A. , Vriens Ingeborg J. H. , Tjan-Heijnen Vivianne C. G.
Published: January 2023

Purpose

We assessed the systemic treatment choices and outcomes in patients diagnosed with human epidermal growth factor receptor-2-positive (HER2 +) advanced breast cancer (ABC), for the first four lines of systemic therapy and by hormone receptor (HR) status.

Methods

We identified 330 patients diagnosed with HER2 + ABC in 2013–2018 in the Southeast of The Netherlands, of whom 64% with HR + /HER2 + and 36% with HR-/HER2 + disease. Overall survival (OS) from start of therapy was calculated using the Kaplan–Meier method.

Results

In real world, 95% of patients with HR + /HER2 + and 74% of patients with HR-/HER2 + disease received systemic therapy. In HR + /HER2 + disease, use of endocrine, chemo- and HER2-targeted therapy was , respectively, 64%, 46% and 60% in first line, and 39%, 64% and 75% in fourth line. In HR-/HER2 + disease, 91–96% of patients received chemotherapy and 77–91% HER2-targeted therapy, irrespective of line of therapy. In patients with HR + /HER2 + disease, median OS was 34.9 months (95%CI:25.8–44.0) for the first line and 12.8 months (95%CI:10.7–14.9) for the fourth line. In HR-/HER2 + disease, median OS was 39.9 months (95%CI:23.9–55.8) for the first line and 15.2 months (95%CI:10.9–19.5) for the fourth line. For patients treated with first-line pertuzumab, trastuzumab plus chemotherapy, median OS was not reached at 56.0 months in HR + /HER2 + disease and 48.4 months (95%CI:32.6–64.3) in HR-/HER2 + disease.

Conclusion

Survival times for later lines of therapy are surprisingly long and justify the use of multiple lines of systemic therapy in well-selected patients with HER2 + ABC. Our real-world evidence adds valuable observations to the accumulating evidence that within HER2 + ABC, the HR status defines two distinct disease subtypes.
Variation of compounds in leaves of susceptible and resistant alternate hosts of Cronartium pini and C. ribicola
Authors: Piispanen Juha , Bergmann Ulrich , Karhu Jouni , Kauppila Tuomas , Kaitera Juha
Published: January 2023

Leaf compounds may contribute to plant defense againstCronartiumrusts. Secondary compounds are either natural or induced in leaves. We studied the variation of compounds in leaves of six alternate hosts ofCronartium piniand two ofC. ribicolathat represented either susceptible or resistant species to these rusts. Extracts from the plant leaves were analyzed using LC-MSMS (liquid chromatography tandem mass spectrometry) and compounds were compared between susceptible and resistant species of the same plant genera to identify significant differences between resistant and susceptible species. Also, LC–MS (liquid chromatography mass spectrometry) with external calibration was used to quantify 12 candidate compounds known from the literature. Among these compounds, the most abundant significant ones inC. pini-resistantMelampyrum pratensewere chlorogenic acid and quercitrin, inVeronica chamaedrysferulic acid, quercitrin and luteolin and inImpatiens glanduliferaquercitrin, ferulic acid, kaempferol, rutin and hyperoside. InC. ribicola-resistantRibes rubrumthe most abundant significant compounds were caffeic acid, p-coumaric acid and quercitrin. Among all extracted leaf compounds, concentrations of three compounds were over 1000 times greater in rust-resistantM. pratense, three compounds inV. chamaedrys, eight compounds inI. glandulifera, and one compound inR. rubrumthan in rust-susceptible species. Among the compounds, the most promising possibly linked to rust resistance were chlorogenic acid and quercitrin.
Far Transfer Effects of Trainings on Executive Functions in Neurodevelopmental Disorders: A Systematic Review and Metanalysis
Authors: Bombonato Clara , Del Lucchese Benedetta , Ruffini Costanza , Di Lieto Maria Chiara , Brovedani Paola , Sgandurra Giuseppina , Cioni Giovanni , Pecini Chiara
Published: January 2023

Executive Functions are a set of interrelated, top-down processes essential for adaptive goal-directed behaviour, frequently impaired across different neurodevelopmental disorders with variable degrees of severity. Many executive-function-training studies in children with neurodevelopmental disorders have focused on near effects, investigating post-treatment improvements on directly trained processes, while enhancements of skills not directly trained, defined as far effects, are less considered, albeit these could be extremely relevant for reducing the negative impact of a disorder’s core symptomatology. This systematic review and metanalysis aims to investigate the far effect outcomes after EF training in children with different types of neurodevelopmental disorders. 17 studies met the inclusion criteria for the systematic review, while 15 studies were selected in the metanalysis. An overall statistically significant effect size was found in the majority of far effect outcome measures considered in the studies. In particular, trainings on executive functions determine significant far effects on daily life functioning (0.46, 95% CI: [0.05–0.87]) and clinical symptoms (0.33, 95% CI: [0.15–0.51]). Despite a high variability of the results, intensity, frequency and the laboratory/life contexts dimension seem to be the most influential variables in determining far effects. This systematic review and metanalysis highlights the need to measure far effects of executive function training in neurodevelopmental disorders, selecting treatments not only on directly targeted processes, but also according to far impacts on the functional weakness of the disorder.
Differentiation in Protest Politics: Participation by Political Insiders and Outsiders
Authors: Borbáth Endre
Published: January 2023

The political participation literature has documented a long-term trend of the normalization of noninstitutional participation that is often equated with the conventionalization of engagement in protest politics. Less is known on the extent to which noninstitutional forms are differentiated by their mobilization context. Population surveys find it difficult to contextualize individual engagement, and on-site surveys point to effects that are hard to generalize. This study fills this gap by emphasizing differentiation and distinguishing participation according to the issue of engagement. It introduces a conceptual distinction between political insiders and outsiders, defined based on the extent to which they are embedded in the organizational landscape of the dominant cleavage dimension. Using an original survey conducted in Germany during the Covid-19 crisis, the analysis demonstrates that general-population surveys are fit to examine issue-specific participation patterns. The results expose an insider and outsider divide, captured by the effect of attitudinal and behavioral indicators, and demonstrates that the two groups are equally likely to participate in noninstitutional forms. However, insiders engage on the established issues of climate and anti-racism, whereas outsiders engage on the new issues of Covid-19 related economic assistance and civil liberties restrictions. In addition, dynamic models reveal that noninstitutional participation is rooted in volatile issue preferences. Overall, the paper argues that participation during the Covid-19 crisis has furthered the trend towards a differentiated protest arena.
Removal of Contaminants of Emerging Concern from a Wastewater Effluent by Solar-Driven Heterogeneous Photocatalysis: A Case Study of Pharmaceuticals
Authors: Pérez-Lucas Gabriel , Aatik Abderrazak El , Aliste Marina , Navarro Ginés , Fenoll José , Navarro Simón
Published: January 2023

The occurrence of emerging micropollutants (pharmaceuticals, pesticides, personal care products, industrial compounds, etc.) in the environment is considered a major threat to human health and aquatic ecosystems. These micropollutants enter the environment through anthropogenic actions and have been identified in surface, ground, waste, and even in drinking water, in quantities ranging from ng L−1 to µg L−1. Currently, the pollution of the global water cycle with persistent organic pollutants remains one of the major challenges of the twenty-first century. Most of these organic substances are only partially removed by conventional wastewater treatment plants. Particularly, considerable amounts of pharmaceuticals are used in human and veterinary medicine, which are not efficiently removed during conventional wastewater treatments and subsequently continuously enter freshwater systems and even agricultural crops. Accordingly, we have evaluated the effectivity of TiO2 as a photocatalyst in tandem with Na2S2O8 as an oxidant for the treatment of a wastewater effluent polluted with pharmaceutical (atenolol, carbamazepine, clarithromycin, erythromycin, irbesartan, and ketoprofen) residues. Results show that the use of solar heterogeneous photocatalysis by means of band-gap semiconductor materials, especially TiO2 in combination with a strong oxidant such as Na2S2O8, significantly enhances their disappearance from the wastewater effluent. However, the selected pharmaceuticals show a slow degradation in wastewater effluent compared to pure water indicating that the occurrence of dissolved salts and organic carbon in wastewater effluent noticeably slows down the efficiency of the treatment. A single first-order model satisfactorily explains the photocatalytic degradation of the compounds studied for both, pure and wastewater. In the case of wastewater effluent, the highest DT50 values were observed for macrolides (13 and 16 min for erythromycin and clarithromycin, respectively), while the other compounds studied showed DT50 values below 10 min. This methodology has a notorious interest in some areas of the Mediterranean basin with water shortage, such as SE of Spain, where more than 3000 h of sunlight per year are recovered.
Retzius-sparing robot-assisted radical prostatectomy in a medium size oncological center holds adequate oncological and functional outcomes
Authors: Fonseca Jorge , Moraes-Fontes Maria Francisca , Rebola Jorge , Lúcio Rui , Almeida Miguel , Muresan Ciprian , Palmas Artur , Gaivão Ana , Matos Celso , Santos Tiago , Dias Daniela , Sousa Inês , Oliveira Francisco , Ribeiro Ricardo , Lopez-Beltran Antonio , Fraga Avelino
Published: January 2023

Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has emerged as a surgical option for patients with prostatic cancer in high-volume centers. The objective is to assess oncological and functional outcomes when implementing RS-RARP in a medium-volume center without previous experience of robotic surgery. This is a prospective observational single-center study. Patients operated between July 2017 and April 2020 were divided into two consecutive groups, A and B, each with 104 patients. The surgeons had prior experience in laparoscopic surgery and underwent robotic training. Positive surgical margin (PSM) status, urinary continence, and erectile function projected by Kaplan–Meier curves, together with patient reported quality of life outcomes at 12 months post-surgery were documented. Median patient age was 63 years (IQR = 59–67), overall PSM rate were 33%, 28% for pT2 disease. Pre-operative values showed no significant difference between both groups. The rate of urinary continence dropped from 81 to 78% (SE = 5.7) (Group A) and from 90 to 72% (SE = 6.3) (Group B) using the International Consultation on Incontinence Questionnaire-Short Form. Baseline sexual function was regained in 41% (Group A) and 47% (Group B) of patients. The median Expanded Prostate Index Composite-26 total score decreased from 86 to 82. These outcomes relate favorably to prior reports. There was a clinically significant decrease in median operative time in the successive groups with post-operative complications occurring in less than 2% of surgical procedures overall. A 12-month follow-up suggests that RS-RARP may be safely introduced in a medium-volume center without previous experience of robotic surgery.
Can Robots have Personal Identity?
Authors: Alonso Marcos
Published: January 2023

This article attempts to answer the question of whether robots can have personal identity. In recent years, and due to the numerous and rapid technological advances, the discussion around the ethical implications of Artificial Intelligence, Artificial Agents or simply Robots, has gained great importance. However, this reflection has almost always focused on problems such as the moral status of these robots, their rights, their capabilities or the qualities that these robots should have to support such status or rights. In this paper I want to address a question that has been much less analyzed but which I consider crucial to this discussion on robot ethics: the possibility, or not, that robots have or will one day have personal identity. The importance of this question has to do with the role we normally assign to personal identity as central to morality. After posing the problem and exposing this relationship between identity and morality, I will engage in a discussion with the recent literature on personal identity by showing in what sense one could speak of personal identity in beings such as robots. This is followed by a discussion of some key texts in robot ethics that have touched on this problem, finally addressing some implications and possible objections. I finally give the tentative answer that robots could potentially have personal identity, given other cases and what we empirically know about robots and their foreseeable future.
Comparison of bio-oils derived from crop digestate treated through conventional and microwave pyrolysis as an alternative route for further waste valorization
Authors: Diaz Perez Nidia , Lindfors Christian , van den Broek Lambertus A. M. , van der Putten Jacinta , Meredith William , Robinson John
Published: January 2023

A total of 120,000 tonnes per year of crop waste from contaminated land has been used as a feedstock for anaerobic digestion (AD). This produces only around 20% of biogas from the total crop and results in a large amount of digestate with heavy metal content. This crop digestate was analyzed across a calendar year to identify the variation in composition, and any potential high-value components that could be targeted for recovery. The chemical characterization revealed that approximately 65% of this residual waste is lignocellulosic material (20% hemicellulose, 24% cellulose, 24% lignin) and about 10% is ash, with no observable difference across the seasons. Three different pyrolysis technologies were studied with the same crop digestate as alternative route to maximize the value of this solid residue by transforming this lignocellulosic material into further bio-based products. Slow pyrolysis at operating temperatures between 355 and 530 °C resulted in bio-oil yields of 35–46% wt, fast pyrolysis at 460–560 °C produced 36–40% wt, and microwave pyrolysis using a power input of 500 and 700 W generated 8–27% wt from the digestate. Chemical compounds found in these bio-oils were categorized into seven chemical groups: acids, aldehydes and ketones, alcohols, furans, sugars, phenolics, and others. This analytical study opens other scenarios to explore the upgrading of these pyrolytic bio-oils for green product generation from the same waste.

Graphical Abstract
Existence of classical solutions for a class of nonlinear impulsive evolution partial differential equations
Authors: Cherfaoui Saïda , Georgiev Svetlin Georgiev , Kheloufi Arezki , Mebarki Karima
Published: January 2023

This paper is devoted to the study of a class of impulsive nonlinear evolution partial differential equations. We give new results about existence and multiplicity of global classical solutions. The method used is based on the use of fixed points for the sum of two operators. Our main results will be illustrated by an application to an impulsive Burgers equation.
Visibility and Well-Being in School Environments: Children’s Reflections on the “New Normal” of Teaching and Learning during the Covid-19 Pandemic
Authors: Fegter Susann , Kost Miriam
Published: January 2023

This paper aims to contribute to the theory on school-related well-being by applying a qualitative approach that focuses on children’s experiences during the Covid-19 pandemic and conceptualizes them as an epistemic opportunity to reconstruct aspects of school-related well-being from children’s perspectives. Within the framework of the multinational qualitative study Children’s Understandings of Well-being (CUWB), it conceptualizes well-being as a cultural construct and argues for including children’s voices in the process of knowledge production. By drawing on statements from online interviews with 11- to 14-year-old children from Berlin, Germany in spring 2021 during school lockdown and by using a discourse analytical approach, the paper outlines the findings on visibility as a central feature of well-being in school environments that children make relevant for experiences of agency, security, and self. Visibility in school is constructed as a medium of control that subjects their bodies to norms of the school, exposes the individual to the gaze of others, and provides security in the context of the digital sphere and its temptations. The paper argues to systematically include these reflections and assessments of new digital learning arrangements during the Covid-19 pandemic into theoretical concepts on school-related well-being.
A Comprehensive Review on Ensemble Solar Power Forecasting Algorithms
Authors: Rahimi Negar , Park Sejun , Choi Wonseok , Oh Byoungryul , Kim Sookyung , Cho Young-ho , Ahn Sunghyun , Chong Chulho , Kim Daewon , Jin Cheong , Lee Duehee
Published: January 2023

With increasing demand for energy, the penetration of alternative sources such as renewable energy in power grids has increased. Solar energy is one of the most common and well-known sources of energy in existing networks. But because of its non-stationary and non-linear characteristics, it needs to predict solar irradiance to provide more reliable Photovoltaic (PV) plants and manage the power of supply and demand. Although there are various methods to predict the solar irradiance. This paper gives the overview of recent studies with focus on solar irradiance forecasting with ensemble methods which are divided into two main categories: competitive and cooperative ensemble forecasting. In addition, parameter diversity and data diversity are considered as competitive ensemble forecasting and also preprocessing and post-processing are as cooperative ensemble forecasting. All these ensemble forecasting methods are investigated in this study. In the end, the conclusion has been drawn and the recommendations for future studies have been discussed.
Sustainable Husbandry?—A Comparative LCA of Three Lamb Breeding Systems in Turkey
Authors: Geß Andreas , Hazar Kalonya Dalya
Published: January 2023

The agricultural sector has historically been the forefront economic sector in Turkey and is crucial for the rural sustainability and the pastures that are critical for biodiversity. However, inadequate policies and factors such as climate change and malpractices result in brittle pastures, rural–urban migration, and a declining agricultural sector. Also, pastures have been left without function and appropriated to other land uses such as quarries, energy power plants, and mines. Although the husbandry sector produces significant greenhouse gas emissions, pastures have a significant capacity of CO2 sequestration. In this study, Life cycle assessment (LCA) is applied to quantify the advantages and disadvantages of the transition between extensive and intensive production. The methodology presents a holistic analysis of the several impact categories and amounts of relevant products, services, and resource emissions along their life cycles. In order to assess the environmental effects of the lamb meat production, three sheep breeding systems in Turkey are evaluated. The study aims to promote a sustainable use of natural resources/assets without compromising the quality, competitiveness, or animal welfare and obtain recommendations for the future husbandry systems and rural development in Turkey. As an overall result, it can be stated that the intensification of sheep farming can lead to a decrease of greenhouse gas emissions per kg of meat. However, extensive sheep farming shows less impacts on soil acidification or eutrophication and can even be beneficial for erosion resistance or biodiversity if properly managed.
Design and performance of directional rectification control system in an aircraft with a novel type of wheel-ski landing gear
Authors: Yin Q. , Sun H. , Li T. , Wei X. , Song J.
Published: January 2023

For a hypersonic-speed aircraft with a flat fuselage structure that has narrow space for a traditional wheel-type landing gear retraction, a novel type of wheel-ski landing gear is designed, which is different from traditional landing gears in force distribution and actuation methods. In order to capture the direction control performance of an aircraft with the wheel-ski landing gear, the aircraft ground taxiing nonlinear dynamic mathematical model is built based on a certain type of aircraft data. The experiment of the wheel-ski landing gear actuator and the differential brake control system is carried out to verify that the electric wheel-ski actuator model with the pressure sensor is in good agreement with the test results, indicating the model validity and the speediness of the differential brake response. Then a new fuzzy combined direction rectifying control law is designed based on the optimisation method and the fuzzy control theory. Comparing with the PD wheel-ski differential brake control, the direction rectifying efficiencies increase higher than 140% during the whole taxiing process. In addition, the combined control law can also decrease the overshoots of the yaw angle responses effectively. Finally, the stability and robustness of the designed combined direction control law are verified under various working conditions.
Invariant Galton–Watson trees: metric properties and attraction with respect to generalized dynamical pruning
Authors: Kovchegov Yevgeniy , Xu Guochen , Zaliapin Ilya
Published: January 2023

The invariant Galton–Watson (IGW) tree measures are a one-parameter family of critical Galton–Watson measures invariant with respect to a large class of tree reduction operations. Such operations include the generalized dynamical pruning (also known as hereditary reduction in a real tree setting) that eliminates descendant subtrees according to the value of an arbitrary subtree function that is monotone nondecreasing with respect to an isometry-induced partial tree order. We show that, under a mild regularity condition, the IGW measures are attractors of arbitrary critical Galton–Watson measures with respect to the generalized dynamical pruning. We also derive the distributions of height, length, and size of the IGW trees.
Improved assessment of the statistical stability of turbulent flows using extended Orr–Sommerfeld stability analysis
Authors: Markeviciute Vilda K. , Kerswell Rich R.
Published: January 2023

The concept of statistical stability is central to Malkus's 1956 attempt to predict the mean profile in shear flow turbulence. Here we discuss how his original attempt to assess this – an Orr–Sommerfeld (OS) analysis on the mean profile – can be improved by considering a cumulant expansion of the Navier–Stokes equations. Focusing on the simplest non-trivial closure (commonly referred to as CE2) that corresponds to the quasilinearized Navier–Stokes equations, we develop an extended OS analysis that also incorporates information about the fluctuation field. A more practical version of this – minimally extended OS analysis – is identified and tested on a number of statistically steady and, therefore, statistically stable turbulent channel flows. Beyond the concept of statistical stability, this extended stability analysis should also improve the popular approach of mean flow linear analysis in time-dependent shear flows by including more information about the underlying flow in its predictions as well as for other flows with additional physics such as convection.
Supplementation of hydrogenated fat-embedded calcium gluconate improves milk fat content and yield in multiparous Holstein dairy cattle
Authors: Seymour Dave J. , Winia Pieter A. , Uittenbogaard Gera , Carson Michelle , Doelman John
Published: January 2023

This research communication reports the responses to supplementing dairy cattle with a hydrogenated fat-embedded calcium gluconate feed additive. The role of hindgut health in ruminant performance and wellbeing is an area of growing interest. Various prebiotic compounds have been used to promote lower gut health in various non-ruminant species. Calcium gluconate, a prebiotic compound, has previously been observed to increase milk fat yield when fed to ruminants in a form capable of resisting fermentation in the rumen, though the mechanism(s) behind this response remain unclear. The objective of this study was to compare the responses of lactating cattle to two different supplementation levels of a hydrogenated fat-embedded calcium gluconate (HFCG) product to evaluate a potential linear dose response. Forty-six lactating Holstein dairy cattle were used in a 3 × 3 replicated Latin square design with 28 d periods to evaluate a previously used dose of HFCG (approximately 16 g/d) with both a negative control and a dose of 25 g/d. Supplementation of multiparous animals with 16 g/d HFCG significantly (P < 0.05) increased milk fat yield and content relative to the negative control, and subsequently improved gross feed efficiency (P < 0.05); additionally, the presence of a potential non-linear dose response was observed for these parameters. Responses when supplemented with 25 g/d HFCG did not differ from the negative control. No production responses were observed in primiparous animals. The mode of action of HFCG, in addition to the potential differential response in primiparous animals remains unclear and warrants further investigation.
Does Main Street Benefit from What Benefits Wall Street?
Authors: Flynn Sean J. , Ghent Andra
Published: January 2023

Yes. We show that aggregate stock returns predict aggregate U.S. employment, despite the industrial composition of publicly traded firms differing markedly from that of all firms, and the representativeness of public firms declining over time. We also show that appropriately reweighted stock returns predict industry and local labor market outcomes. We find the strongest evidence of an alignment of interests between shareholders and workers in the manufacturing sector, despite its declining labor share of output. Our findings suggest that at quarterly frequencies, product demand shocks are more important drivers of industry- and city-level stock returns than technology shocks.
How to use natural history collections to resurrect information on historical parasite abundances
Authors: Wood C. L. , Leslie K. L. , Claar D. , Mastick N. , Preisser W. , Vanhove M. P.M. , Welicky R.
Published: January 2023

Many of the most contentious questions that concern the ecology of helminths could be resolved with data on helminth abundance over the past few decades or centuries, but unfortunately these data are rare. A new sub-discipline – the historical ecology of parasitism – is resurrecting long-term data on the abundance of parasites, an advancement facilitated by the use of biological natural history collections. Because the world's museums hold billions of suitable specimens collected over more than a century, these potential parasitological datasets are broad in scope and finely resolved in taxonomic, temporal and spatial dimensions. Here, we set out best practices for the extraction of parasitological information from natural history collections, including how to conceive of a project, how to select specimens, how to engage curators and receive permission for proposed projects, standard operating protocols for dissections and how to manage data. Our hope is that other helminthologists will use this paper as a reference to expand their own research programmes along the dimension of time.
A century of parasitology in fisheries and aquaculture
Authors: Timi J.T. , Buchmann K.
Published: January 2023

Fish parasitological research associated with fisheries and aquaculture has expanded remarkably over the past century. The application of parasites as biological tags has been one of the fields in which fish parasitology has generated new insight into fish migration and stock assessments worldwide. It is a well-established discipline whose methodological issues are regularly reviewed and updated. Therefore, no concepts or case-studies will be repeated here; instead, we summarize some of the main recent findings and achievements of this methodology. These include the extension of its use in hosts other than bony fishes; the improvements in the selection of parasite tags; the recognition of the host traits affecting the use of parasite tags; and the increasingly recognized need for integrative, multidisciplinary studies combining parasites with classical methods and modern techniques, such as otolith microchemistry and genetics. Archaeological evidence points to the existence of parasitic problems associated with aquaculture activities more than a thousand years ago. However, the main surge of research within aquaculture parasitology occurred with the impressive development of aquaculture over the past century. Protozoan and metazoan parasites, causing disease in domesticated fish in confined environments, have attracted the interest of parasitologists and, due to their economic importance, funding was made available for basic and applied research. This has resulted in a profusion of basic knowledge about parasite biology, physiology, parasite–host interactions, life cycles and biochemistry. Due to the need for effective control methods, various solutions targeting host–parasite interactions (immune responses and host finding), genetics and pharmacological aspects have been in focus.
A new cryptic species of Echinostoma (Trematoda: Echinostomatidae) closely related to Echinostoma paraensei found in Brazil
Authors: Valadão Marisa C. , Alves Philippe V. , López-Hernández Danimar , Assis Jordana C. A. , Coelho Paulo R. S. , Geiger Stefan M. , Pinto Hudson A.
Published: January 2023

Echinostoma paraensei, described in Brazil at the end of the 1960s and used as a biological model for a range of studies, belongs to the ‘revolutum’ complex of Echinostoma comprising species with 37 collar spines. However, molecular data are available only for a few isolates maintained under laboratory conditions, with molecular prospecting based on specimens originating from naturally infected hosts virtually lacking. The present study describes Echinostoma maldonadoi Valadão, Alves & Pinto n. sp., a species cryptically related to E. paraensei found in Brazil. Larval stages (cercariae, metacercariae and rediae) of the new species were found in the physid snail Stenophysa marmorata in the State of Minas Gerais, Brazil, the same geographical area where E. paraensei was originally described. Adult parasites obtained experimentally in Meriones unguiculatus were used for morphological (optical microscopy) and molecular [28S, internal transcribed spacer (ITS), nad1 and cox1] characterization. The morphology of larval and adult parasites (most notable the small-sized dorsal spines in the head collar), associated with low (0–0.1%) molecular divergence for 28S gene or ITS region, and only moderate divergence for the mitochondrial cox1 gene (3.83%), might suggest that the newly collected specimens should be assigned to E. paraensei. However, higher genetic divergence (6.16–6.39%) was found in the mitochondrial nad1, revealing that it is a genetically distinct, cryptic lineage. In the most informative phylogenetic reconstruction, based on nad1, E. maldonadoi n. sp. exhibited a strongly supported sister relationship with E. paraensei, which may indicate a very recent speciation event giving rise to these 2 species.
Contrasting the population genetic structure of a specialist (Hexaglandula corynosoma: Acanthocephala: Polymorphidae) and a generalist parasite (Southwellina hispida) distributed sympatrically in Mexico
Authors: García-Varela Martín , López-Jiménez Alejandra , González-García Marcelo Tonatiuh , Sereno-Uribe Ana Lucia , Andrade-Gómez Leopoldo
Published: January 2023

Polymorphidae is a monophyletic group of acanthocephalans distributed worldwide. Within this family,Hexaglandula corynosomais a specialist species that uses a single bird species as a definitive host.Southwellina hispidais a generalist species that uses a broad spectrum of definitive hosts to complete its life cycle. In the current research, sequences of cytochrome c oxidase subunit 1 (cox1) from mitochondrial DNA were generated from 44 specimens ofH. corynosomaand 76 ofS. hispidadistributed sympatrically in 6 biogeographic provinces of Mexico with the objective of characterizing and comparing the population genetic structure of 2 acanthocephalan species with opposing life strategies. The phylogeographic studies indicated that the populations of both species lacked a phylogeographic structure and exhibited high haplotype diversity, low nucleotide diversity and lowFstvalues among the biogeographic provinces; in combination with negative values on the neutrality test, this suggests that the populations of acanthocephalans are expanding. Paratenic hosts are key for the transmission from intermediate to definitive hosts in the generalist species. However, the inclusion of paratenic hosts does not play a principal role in the population genetic structure ofS. hispidawithin its distribution along the coasts of Mexico.
In vitro and in silico analysis of imatinib analogues as anti-Trypanosoma cruzi drug candidates
Authors: Nesic de Freitas Luca S. F. , da Silva Cristiane França , Intagliata Sebastiano , Amata Emanuele , Salerno Loredana , Soeiro Maria de Nazaré Correia
Published: January 2023

Chagas disease (CD) is a neglected tropical disease caused by the intracellular protozoan Trypanosoma cruzi that remains a serious public health issue affecting more than 6 million people worldwide. The available treatment includes 2 nitro derivatives, benznidazole (BZ) and nifurtimox, that lack in efficacy in the later chronic phase and when administered against the several naturally resistant parasite strains and present several side-effects, demanding new therapeutic options. One strategy is based on repurposing by testing drugs already used for other illness that may share similar targets. In this context, our previous data on imatinib (IMB) and derivatives motivated the screening of 8 new IMB analogues. Our findings showed that all except 1 were active against bloodstream trypomastigotes reaching drug concentration capable of inducing a 50% of parasite lysis (EC50) values < 12 μm after 2 h while BZ was inactive. After 24 h, all derivatives were more potent than BZ, exhibiting EC50 values 1.5–5.5 times lower. Against intracellular forms, 7 out of 8 derivatives presented high activity, with EC50 values ≤ BZ. LS2/89 stood out as one of the most promising, reaching EC90 values of 1.68 and 4.9 μm on intracellular and trypomastigote forms, respectively, with the best selectivity index (>60) towards the proliferative forms. Physicochemical parameters as well as the absorption, distribution, metabolism, excretion and toxicity properties were predicted to be acceptable and with good chance of a favourable oral bioavailability. The promising results motivate further studies such as in vivo and combinatory assays aiming to contribute for a novel safer and effective therapy for CD.
In the native speaker’s eye: Online processing of anomalous learner syntax
Authors: Søby Katrine Falcon , Milburn Evelyn Arko , Kristensen Line Burholt , Vulchanov Valentin , Vulchanova Mila
Published: January 2023

How do native speakers process texts with anomalous learner syntax? Second-language learners of Norwegian, and other verb-second (V2) languages, frequently place the verb in third position (e.g., *Adverbial-Subject-Verb), although it is mandatory for the verb in these languages to appear in second position (Adverbial-Verb-Subject). In an eye-tracking study, native Norwegian speakers read sentences with either grammatical V2 or ungrammatical verb-third (V3) word order. Unlike previous eye-tracking studies of ungrammaticality, which have primarily addressed morphosyntactic anomalies, we exclusively manipulate word order with no morphological or semantic changes. We found that native speakers reacted immediately to ungrammatical V3 word order, indicated by increased fixation durations and more regressions out on the subject, and subsequently on the verb. Participants also recovered quickly, already on the following word. The effects of grammaticality were unaffected by the length of the initial adverbial. The study contributes to future models of sentence processing which should be able to accommodate various types of “noisy” input, that is, non-standard variation. Together with new studies of processing of other L2 anomalies in Norwegian, the current findings can help language instructors and students prioritize which aspects of grammar to focus on.
Good practice in needs-based post-diagnostic support for people with young onset dementia: findings from the Angela Project
Authors: Stamou Vasileios , Oyebode Jan , La Fontaine Jenny , O'Malley Mary , Parkes Jacqueline , Carter Janet
Published: January 2023

Evidence on post-diagnostic support for people with young onset dementia is scarce. Previous studies have employed a problem-focused approach; however, evidence on ‘what works’ in real-life practice is essential to develop recommendations for service design and delivery. This study aimed to provide insight into ‘what works’ from the perspectives of people with young onset dementia and their supporters. We gathered free-text responses on positive service experiences via a UK cross-sectional survey. Inductive thematic analysis was used to identify the objectives of positive services and the needs these met. Follow-up interviews enabled in-depth insights from people with diverse diagnoses, ages and social situations. These were analysed using a template drawn from the survey. The 233 survey respondents gave 856 examples of positive support. Analysis of 24 follow-up interviews led to 16 themes clustered under three superordinate themes: ‘maintaining autonomy’, ‘being myself’ and ‘togetherness’. We found that positive services address the disruptions to sense of agency, selfhood and meaningful relationships that are experienced by those with young onset dementia. The study provides an in-depth understanding of the needs met by positive services for younger people with dementia. Our nuanced findings on good practice can inform age-specific guidelines for young onset dementia and indicate how personalisation can work in practice to help people with young onset dementia to maintain identity, autonomy and connections.
Multiplicative extended Kalman filter ignoring initial conditions for attitude estimation using vector observations
Authors: Chang Lubin
Published: January 2023

In this paper, the well-known multiplicative extended Kalman filter (MEKF) is re-investigated for attitude estimation using vector observations. From the Lie group theory, it is shown that the attitude estimation model is group-affine and its error state model should be trajectory-independent. Moreover, with such a trajectory-independent error state model, the linear Kalman filter is still effective for large initialisation errors. However, the measurement model of the traditional MEKF is dependent on the attitude prediction, which is therefore trajectory-dependent. This is also the main reason why the performance of traditional MEKF is degraded for large initialisation errors. Through substitution of the attitude prediction related term with vector observations in the body frame, a trajectory-independent measurement model is derived for MEKF. Meanwhile, MEKFs with reference attitude error definition and with global state formulating on special Euclidean group have also been studied, with the main focus on derivation of the trajectory-independent measurement models. Extensive Monte Carlo simulations of spacecraft attitude estimation implementations demonstrate that the performance of MEKFs can be much improved with trajectory-independent measurement models.
Cognitive behavioural therapy and medication for treatment of adolescent depression: a network meta-analysis
Authors: Dardas Latefa Ali , Xu Hanzhang , Franklin Michelle Scotton , Scott Jewel , Vance Ashlee , van de Water Brittney , Pan Wei
Published: January 2023

Background:

Cognitive behavioural therapy (CBT) and medication are widely accepted and useful interventions for individuals with depression. However, a gap remains in our current understanding of how CBT directly benefits adolescents with depression.

Aims:

The purpose of this study was to examine the short- and long-term effectiveness of CBT only, CBT+Medication, or Medication alone in reducing the duration of major depressive episodes, lessening internalizing and externalizing symptoms and improving global functioning.

Methods:

Data were extracted from 14 unique studies with a total of 35 comparisons. Network meta-analysis was conducted and p-scores, a measure of the extent of certainty that one treatment is better than another, were used to rank treatments.

Results:

There was no significant difference between any two treatments for depression, nor internalizing or externalizing symptoms. For global functioning, CBT had significantly greater effect at the longest follow-up than CBT+Medication. CBT+Medication had the highest p-score for depression, short- and long-term effects, and internalizing and externalizing symptoms long-term effects. No indication of publication bias was found.

Conclusions:

Neither modality, CBT nor medication, is superior for treating adolescent depression. However, CBT was superior in improving global functioning, which is essential for meeting developmental goals.
On the Scale‐Dependence of Fault Surface Roughness
Authors: Beeler N. M.
Published: January 2023

Defining roughness as the ratio of height to length, the standard approach to characterize amplitudes of single fault, joint and fracture surfaces is to measure average height as a function of profile length. Empirically, this roughness depends strongly on scale. The ratio is approximately 0.01 at a few mm but 10× smaller at a few tens of meters. Surfaces are rougher at small scales. However, these conclusions are metric‐dependent. If instead height is averaged over wavelength, roughness is nearly Brown spatial noise, having almost scale‐independent apparent surface height to wavelength ratio. The small deviation from scale‐independence is of the opposite sense than found using the standard metric; surfaces are slightly rougher at long wavelengths. Some natural surfaces may be Brownian within the measurement uncertainties. These contradictions are curiosities of surfaces that have Hurst exponents between 0.5 and 1, as natural fault surfaces do. The wavelength‐based analysis of roughness and how it changes with scale are straight‐forward; a normalized Fourier transform approximately preserves amplitude and its scale dependence in the wavelength domain. Among the conclusions from reconsideration of scale dependence are that the scale dependence is weak and much smaller than that of other fault and shear zone properties. Background and aftershock seismicity, jogs and step‐overs indicate strong localization (smoothing) with slip and scale. The lack of strong scale dependence to surface roughness suggests it is not the dominant control on brittle shear zone evolution.
Two Phases of Crustal Shortening in Northeastern Tibet as a Result of a Stronger Qaidam Lithosphere During the Cenozoic India–Asia Collision
Authors: Xie Renxian , Chen Lin , Yin An , Xiong Xiong , Chen Yongshun John , Guo Zhen , Wang Kai
Published: January 2023

Although two phases of Cenozoic crustal deformation in the Qilian Shan thrust belt of northeastern Tibet has been documented, their dynamic causes remain unclear. To address this issue, we investigate whether the mechanical strength of the Qaidam Basin, which is located between the Eastern Kunlun Range and the Qilian Shan, was a controlling factor for the observed deformation history by performing 2‐D thermal–mechanical simulations. Our models consider the division of the Tibetan terranes (i.e., Qilian arc, Kunlun‐Qaidam, Songpan‐Ganzi, Qiangtang, and Lhasa, from north to south) bounded by suture zones. Simulation results show that weak suture zones in central Tibet can lead to peeling off and sinking of the mantle lithosphere beneath the Qiangtang and Songpan–Ganzi terranes. After lithospheric delamination, varying north‐south width, thickness and strength of the Qaidam crust creates three end‐member model results: (a) the mantle lithosphere of the Lhasa terrane delaminates while the mantle lithosphere beneath Eastern Kunlun‐Qaidam terrane and the Qilian Shan thrust belt (KQQ) remains undeformed, (b) the Lhasa mantle lithosphere moves northward while the KQQ mantle lithosphere subducts southward, and (c) the Lhasa mantle lithosphere moves northward while lithospheric thickening occurs north of the Qaidam Basin. Our simulations show that pre‐existing weaknesses in northeastern Tibet can be activated and deformed shortly after the onset of collision, and a second wave of deformation sweeps across northeastern Tibet after lithospheric delamination in northern Tibet.
USP15 promotes pulmonary vascular remodeling in pulmonary hypertension in a YAP1/TAZ-dependent manner
Authors: Wu Zhuhua , Zhu Li , Nie Xinran , Wei Li , Qi Yong
Published: January 2023

Pulmonary hypertension (PH) is a life-threatening cardiopulmonary disease characterized by pulmonary vascular remodeling. Excessive growth and migration of pulmonary artery smooth muscle cells (PASMCs) are believed to be major contributors to pulmonary vascular remodeling. Ubiquitin-specific protease 15 (USP15) is a vital deubiquitinase that has been shown to be critically involved in many pathologies. However, the effect of USP15 on PH has not yet been explored. In this study, the upregulation of USP15 was identified in the lungs of PH patients, mice with SU5416/hypoxia (SuHx)-induced PH and rats with monocrotaline (MCT)-induced PH. Moreover, adeno-associated virus-mediated functional loss of USP15 markedly alleviated PH exacerbation in SuHx-induced mice and MCT-induced rats. In addition, the abnormal upregulation and nuclear translocation of YAP1/TAZ was validated after PH modeling. Human pulmonary artery smooth muscle cells (hPASMCs) were exposed to hypoxia to mimic PH in vitro, and USP15 knockdown significantly inhibited cell proliferation, migration, and YAP1/TAZ signaling in hypoxic hPASMCs. Rescue assays further suggested that USP15 promoted hPASMC proliferation and migration in a YAP1/TAZ-dependent manner. Coimmunoprecipitation assays indicated that USP15 could interact with YAP1, while TAZ bound to USP15 after hypoxia treatment. We further determined that USP15 stabilized YAP1 by inhibiting the K48-linked ubiquitination of YAP1. In summary, our findings reveal the regulatory role of USP15 in PH progression and provide novel insights into the pathogenesis of PH.