bluuebunny/crossref_metadata_2025 huggingface dataset:
Indolent Lymphomas
Authors: Morschhauser Franck , Zinzani Pier Luigi
Published: February 2022

Indolent non-Hodgkin lymphoma (iNHL), including follicular (FL) and marginal zone (MZL) lymphoma, now enjoy durable disease control with first-line immunochemotherapy, with a median overall survival (OS) of over 15 years in most series (Kahl and Yang 2016). However, iNHL is still widely considered incurable in most cases, and disease history remains characterized by a relapsing and remitting course, with each remission period shorter than the previous one, and OS and progression-free survival (PFS) decrease with each subsequent line of conventional therapy (Batlevi et al. 2020). Patients with unmet needs include approximately 20% of FL patients who experience disease progression within 24 months (POD24) after initial chemoimmunotherapy (with a 5-year OS of 48% (Casulo et al. 2015)—although it remains unclear how much this worse outcome is driven by misdiagnosed transformed follicular lymphoma (Freeman et al. 2019)) and those who fail multiple regimens (5-year PFS of 23%) (Rivas-Delgado et al. 2019) have double refractory disease (Gopal et al. 2017) or experience relapse after autologous stem cell transplantation (ASCT) (Sesques et al. 2020). Although promising results were obtained with an immunomodulatory regimen combining anti-C20 Moab and lenalidomide (Leonard et al. 2019; Morschhauser et al. 2019), most current approved therapies do not overcome incremental disease resistance, resulting in multiple lines of treatment with cumulative toxicity over a patient’s lifetime. The autologous anti-CD19 chimeric antigen receptor T cell (CAR-T) therapies tisa-cel and axi-cel, which are now approved for patients with relapsed/refractory (r/r) large B cell lymphoma (LBCL), have also been tested in iNHL, with promising results.
Bridging Chemotherapy: Adult Acute Lymphoblastic Leukaemia
Authors: Boissel Nicolas , Ciceri Fabio
Published: February 2022

Bridging therapy can be given after leukapheresis and before lymphodepletion during CAR-T cell manufacturing. The primary goal of bridging therapies is to prevent uncontrolled progression of the underlying disease during the manufacturing period before CAR-T cell infusion. Several studies indicate that a high tumour burden is associated with an increased risk of complications after CAR-T cell infusion (Cohen et al. 2019). Therefore, controlling the disease and even possibly decreasing the tumour burden is critical during the manufacturing period. The choice of bridging therapies is essential for the success of the procedure.
Bridging Chemotherapy: Follicular Lymphoma, Mantle Cell Lymphoma, and CLL
Authors: Gagelmann Nico , Gribben John , Kröger Nicolaus
Published: February 2022

While lisocabtagene maraleucel (liso-cel) is the only product that is specifically approved to treat grade 3B follicular lymphoma (FL), specifically in aggressive lymphoma indications, to date, axi-cel is the first and only approved CAR-T product for indolent NHL.
Management of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Authors: Rees Jeremy H.
Published: February 2022

A common and challenging side effect associated with CAR-T cell therapy is immune cell-associated neurotoxicity syndrome (ICANS), which occurs in 20–60% of patients, of whom 12–30% have severe (≥ grade 3) symptoms.
Management of Hypogammaglobulinaemia and B-Cell Aplasia
Authors: Topp Max , Feuchtinger Tobias
Published: February 2022

The development and regulatory approval of CAR-T cell therapies targeting B-lineage surface antigens (Maude et al. 2018), such as CD19 or CD22, represents a major milestone in cancer immunotherapy. This treatment results in the depletion of malignant and normal B cells and is associated with hypogammaglobulinaemia. These on-target, off-tumour toxicities may result in an increased risk of infection. Careful long-term follow-up assessment of patients receiving CAR-T cell therapy is important. Management of these on-target, off-tumour effects should be well coordinated between treatment and referring centres if the patient returns to local providers following therapy. Aims of this toxicity management:
ICU
Authors: Holtick Udo , Azoulay Elie
Published: February 2022

CAR-T cell treatment comes with significant side effects that challenge the structure and capacity of haematology wards and will regularly necessitate intermittent patient transfer to the ICU. Life-threatening adverse events include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which can occur within hours or days after administration. Sepsis might also require ICU admission within the days that follow CAR-T infusion in these high-risk immunocompromised patients.
Educational Needs for Physicians
Authors: Kröger Nicolaus , Gribben John , Sánchez-Ortega Isabel
Published: February 2022

CAR-T cells are novel therapies associated with promising and potentially curative outcomes in patients with high-risk relapsed disease. In Europe, there are currently three approved products (tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel) for patients with acute lymphoblastic leukaemia, aggressive B-cell lymphoma, and mantle cell lymphoma, although expanded haematologic and nonhaematologic indications are expected soon.
Tumour Escape from CAR-T Cells
Authors: Rasche Leo , Vago Luca , Mutis Tuna
Published: February 2022

Over the past decade, CAR-T cells have emerged as one of the most powerful cellular immune therapy approaches in the battle against haematological malignancies. Nonetheless, similar to other immunotherapeutic approaches, tumour cells develop strategies to evade CAR-T cell therapy, often with the support of a highly immunosuppressive and protective tumour microenvironment. To date, antigen loss, immune dysfunction, exhaustion and (microenvironment-mediated) upregulation of antiapoptotic pathways have been identified as major modes of tumour escape from CAR-T cell therapy. This chapter will focus on our current understanding of these modes of immune escape from CAR-T cells.
Education Needs for Nurses in Adult and Paediatric Units
Authors: Kenyon Michelle , Murray John , Ellard Rose , Hutt Daphna
Published: February 2022

Complex nursing care for patients on the CAR-T cell therapy pathway involves many different nursing roles that have important functions at different stages in the pathway. Within the multiprofessional team, nurse education is critical to safe and competent care and to the patient’s treatment experience. As we consider the education needs of the nursing workforce throughout the entire patient pathway, including the supply chain, chain of custody, and clinical care delivery, we recognize the important roles of expert nurses, practice educators, and the wider multiprofessional team in sharing their knowledge and experience. Nurse education strategies should include referring nursing teams to facilitate seamless patient care throughout referral, treatment, and follow-up to optimize communication and appropriately meet patient and caregiver information needs.
CART Initiatives in Europe
Authors: Urbano-Ispizua Alvaro , Hudecek Michael
Published: February 2022

The efficacy of chimeric antigen receptor T cells (CARTs) in B cell neoplasms, ALL, large B cell lymphoma, and now multiple myeloma has been one of the great achievements in the fight against cancer in recent decades (Porter et al. 2011). However, there is still a need to increase the proportion of responses (especially in NHL) (Locke et al. 2019) and to decrease the proportion of relapse (especially in ALL) (Grupp et al. 2013). More importantly, currently, commercial CAR-T products are not available for T cell neoplasms, myeloid malignant haemopathies, or solid tumours. As a reflection of the necessary efforts to expand the efficacy of CARTs, more than 500 clinical trials are currently underway worldwide, mostly led by American or Chinese groups. Unfortunately, European institutions are underrepresented in these initiatives. It is our duty to push and harmonize European academic clinical trials. We identified 35 early clinical trials promoted by European groups in Eudract and ClinTrialsGov (20 February 2021). Among them, 20 are initiatives from academic institutions, and 15 are initiatives from European companies allied with European academic institutions. In this summary, CART clinical trials promoted by European academic centres or by small to medium European companies are listed. The aim is to inform European groups treating haemato-oncology diseases of the current situation in this field, facilitating the inclusion of patients in these clinical trials. We aim to support the groups promoting these studies to increase collaboration.
Point-of-Care Production of CAR-T Cells
Authors: Delgado Julio , Roddie Claire , Schmitt Michael
Published: February 2022

CAR-T cells for clinical application are classified as advanced therapy medicinal products (ATMPs), and their manufacture is subject to laws and regulations governed by the European Medicines Agency (EMA) and by federal and regional authorities. CAR-T cells must be manufactured to achieve good manufacturing practice (GMP) compliance and are defined as potent products manufactured safely according to standardized methods under closely controlled, reproducible, and auditable conditions. BioPharma supplies the vast majority of CAR-T products for patients, but some academic centres have developed point-of-care cGMP CAR-T manufacturing capability, striving to uphold the same stringency of product quality while improving patient access to CAR-T cells and streamlining the costs of therapy. Point-of-care CAR-T manufacturing can only be performed in facilities with the appropriate regulatory approvals in place.
Off-the-Shelf Allogeneic CAR-T Cells or Other Immune Effector Cells
Authors: Depil Stephane , Qasim Waseem
Published: February 2022

“Off-the-shelf” allogeneic CAR TCRab T cells and other immune effector cells, such as natural killer (NK) or gamma delta (gd) T cells, can be premanufactured from healthy donors and may offer alternatives to autologous strategies. However, major barriers, namely HLA disparity resulting in graft versus host disease (GvHD) and host-mediated rejection, must be addressed.
Organisational Contexts of Energy Cybersecurity
Authors: Wallis Tania , Paul Greig , Irvine James
Published: February 2022

The energy system is going through huge transformation to integrate distributed renewable generation and to achieve the goals of net-zero carbon emissions. This involves a significant adjustment to how the system is controlled and managed, with increasing digitalisation of technology and growing complexities across interconnected systems. Traditionally electricity networks adjusted their supply of energy in response to changes in demand. The future energy system will require more flexible demand to be able to use or store energy when renewables are generating. This change is exacerbated by additional demand for electricity for heat and transport uses.

Utility organisations hold responsibility for securing their networks and assuring the supply of electricity. This paper describes a full investigation of cybersecurity issues and concerns for utilities. This industry review was carried out to create a clear organisational context for the ongoing design of cybersecurity improvements. The assessment of potential impact and consequences of cyber-attack is recommended to direct necessary preparations towards protecting essential functions and processes. Improving resilience across interdependent actors is discussed and resilience measures suggested to guide the contributions of different actors towards whole system resilience.
The top quark electro-weak couplings after LHC Run 2
Authors: Miralles Víctor , López Marcos Miralles , Llácer María Moreno , Peñuelas Ana , Perelló Martin , Vos Marcel
Published: February 2022

Abstract

Recent measurements at the Large Hadron Collider allow for a robust and precise characterisation of the electro-weak interactions of the top quark. We present the results of a global analysis at next-to-leading order precision including LHC, LEP/SLD and Tevatron data in the framework of the Standard Model Effective Field Theory. We include a careful analysis of the impact of correlations among measurements, as well as of the uncertainties in the Effective Field Theory setup itself. We find remarkably robust global fit results, with central values in good agreement with the Standard Model prediction, and 95% probability bounds on Wilson coefficients that range from ±0.35 to ±8 TeV−2. This result represents a considerable improvement over previous studies, thanks to the addition of differential cross-section measurements in associated production processes of top quarks and neutral gauge bosons.
Abfall von Sauerstoffsättigung und Blutdruck sowie Anstieg des zentralen Venendrucks im Rahmen eines Mitralklappenclippings bei einer 81-Jährigen
Authors: Volz Martin J. , Aurich Matthias , Konstandin Mathias , Katus Hugo A. , Frey Norbert , Kreusser Michael M. , Raake Philip W.
Published: February 2022

Hintergrund

Atriumseptumdefekte (ASD) im Rahmen eines endovaskulären Mitralklappenclippings sind potenziell hämodynamisch relevante Komplikationen. Ein sofortiger Verschluss mittels Okkluder kann eine sichere und effektive Therapie darstellen.

Fallzusammenfassung

Eine 81-jährige Patientin mit schwerer Dyspnoe bei vorbekannter hochgradiger Mitralklappeninsuffizienz wurde zum elektiven Mitralklappenclipping vorgestellt. Die Clipimplantation verlief komplikationslos. Nach Entfernung der transseptalen Schleuse kam es zu einem plötzlichen Abfall der Sauerstoffsättigung und des Blutdrucks sowie zu einem sofortigen Anstieg des zentralen Venendrucks. Es zeigte sich ein iatrogener Links-rechts-Shunt auf Vorhofebene mit relevantem Shuntvolumen. Daraufhin erfolgte der sofortige Verschluss mittels Vorhofseptumokkluder, was zu einer unmittelbaren Besserung der Kreislaufparameter und der Sauerstoffsättigung führte.

Schlussfolgerung

Ein Anstieg des zentralen Venendrucks, ein Blutdruckabfall oder Sättigungsabfall nach Rückzug der transseptalen steuerbaren Schleuse im Rahmen des Mitralklappenclippings sollte bezüglich eines möglichen ASD abgeklärt werden.
Early Cambrian highly metalliferous black shale in South China: Cu and Zn isotopes and a short review of other non-traditional stable isotopes
Authors: Lehmann Bernd , Pašava Jan , Šebek Ondřej , Andronikov Alexandre , Frei Robert , Xu Lingang , Mao Jingwen
Published: February 2022

Early Cambrian black shales on the Yangtze Platform host a regionally distributed highly metalliferous sulfide-rich carbonaceous unit which has been the subject of extensive debate. This marker unit, with a few centimeters or tens of centimeters in thickness, displays extreme enrichment in Mo and Ni (wt% range), and in a broad spectrum of other metals such as As, Au, PGE, Re, Cu, Zn, Cd, Ag, Sb, Se, Tl, and Hg, and occurs discontinuously along the western passive margin of the Yangtze Platform. It grades laterally in stratigraphically equivalent meter-thick vanadium-rich shale and tens-of-meter-thick sapropelite (combustible shale). New Cu and Zn isotope data, combined with existing Cd, Cr, Ni, Mo, Hg, and Se isotope and other chemical data, allow to attempt an integrated view on the formation of this intriguing unit of hyper-enriched metalliferous black shale. The authigenic Cu enrichment in the 1000-ppm range has produced no or little Cu isotope fractionation (0.03 ± 0.26 ‰ δ65Cu) beyond the lithogenic background. Heavy zinc and cadmium isotope enrichment in the sulfidic samples (1.11 ± 0.18 ‰ δ66Zn, 0.31 ± 0.10 ‰ δ114Cd) is controlled by sulfide fractionation and contrasts with V-rich and barren shale (0.60 ± 0.18 ‰ δ66Zn, 0.00 ± 0.14 ‰ δ114Cd). The distinctly negative Ni isotope composition of the metalliferous unit (−0.84 ± 0.05 ‰ δ60Ni) with Ni in the percent range has been interpreted as due to hydrothermal activity related to the leaching of mafic rocks and their sulfides. Sorption processes (Fe-oxyhydroxides) and redox cycling in the water column and the bottom sediment with microbial activity could be an alternative interpretation. The extreme metal enrichment can be understood as due to a process chain, from high biological productivity in the oxic photic zone to sulfate reduction in the deeper sulfidic water column and upper sediment layer. Key to the metal enrichment seems to be extremely low clastic sedimentation and advanced carbon destruction by anaerobic oxidation. Hydrothermal input of basinal brines along the rifted margin of the Yangtze Platform was likely a part of this scenario.
Nonlinear nexus between corruption and tourism arrivals: a global analysis
Authors: Maria Krambia-Kapardis , Ioanna Stylianou , Salomi Demetriou
Published: February 2022

The relationship between corruption and tourism has been sporadically examined over the years. According to the existing theory, there is an inverted U relationship which implies that tourism demand initially increases as corruption increases (greasing the wheels) and after a certain threshold level of corruption, tourism demand decreases (sanding the wheels). Empirical studies so far concentrated on capturing the nonlinear relationship, by applying a simple linear model and by including corruption as a quadratic term. In the current paper, the authors revisit the “greasing and sanding the wheels” hypothesis by applying an advanced econometric technique, the threshold regression model, which deals with a key element of model uncertainty, namely parameter heterogeneity. In particular, using a sample of 83 countries from 2001 to 2018, the authors firstly examine if there is a nonlinear relationship between corruption and tourism, and then, they estimate the threshold value of corruption. According to the results, the null hypothesis of a linear model against the alternative of a threshold model with two regimes is strongly rejected. Furthermore, while the effect of corruption on tourism is positive in the low corruption regime and negative in the high corruption regime, a heterogeneous relationship is also found between other politico-socio-economic variables and tourism demand in the low and high corruption regimes.
From inside to outside: CT scanning as a tool to link internal knot structure and external branch diameter as a prerequisite for quality assessment
Authors: Longo Bruna L. , Brüchert Franka , Becker Gero , Sauter Udo H.
Published: February 2022

Branches are as essential for tree growth as knots are detrimental from the wood quality point of view. To bridge the gap between tree growth and the quality toward end-use, this study aims to establish a relationship between internal and external diameters of Douglas-fir whorl branches. The data comprised 102 trees of a wide age range (30–80 years old) from nine study sites in Southwest Germany. External branch measurements were performed in the field following an established protocol. Logs were scanned on a MiCROTEC CT.LOG, and knots were detected by applying an automated algorithm. Obvious detection artefacts by the CT algorithm were excluded to reveal the relationship between inner-outer branch diameters as clear as possible. Results showed a significant mean difference of 13.8 (± 10.0) mm between the methods (external diameter being larger), with a model indicating an offset of 9.75 mm and angular shift of 0.53 (RMSE = 7.12 mm;R2 = 0.57) between the methods. Separate calculations of sound and dead datasets did not reveal a statistically significant difference. By linking the internal knot structure to external branch measurements, the findings of this study constitute a first step toward the incorporation of CT data into growth models, providing a meaningful prediction of the maximum internal knot diameter at an early stage in the wood supply chain.
Klang der Depression
Authors: Shugaley Alisa , Altmann Uwe , Brümmel Maria , Meier Julija , Strauß Bernhard , Schönherr Désirée
Published: February 2022

Hintergrund

Die Depression ist neben kognitiven, emotionalen, sozialen und psychomotorischen Beeinträchtigungen durch spezifische stimmliche Merkmale gekennzeichnet. Bisher existieren erst wenige Studien, die diese in klinischen Kontexten und in Abgrenzung zu Gesunden untersuchten.

Fragestellung

Untersucht wurde der Zusammenhang zwischen Depressivität und paraverbalen Merkmalen bei depressiven Patient_innen und gesunden Probanden.

Methode

In einem mehrschrittigen Verfahren wurden die Audioinhalte von Anamneseinterviews mit Depressiven (n = 15) und Gesunden (n = 15) mit einer Software annotiert und transkribiert. Die paraverbalen Merkmale Grundfrequenz der Stimme, Spannweite der Stimme, Sprechgeschwindigkeit und Pausenlänge wurden automatisiert bestimmt. Mithilfe hierarchisch linearer Modelle wurde der Einfluss der Gruppenzugehörigkeit, Depressivität, Ängstlichkeit sowie psychischer und körperlicher Gesundheit auf die paraverbalen Merkmale analysiert.

Ergebnisse

Es zeigte sich ein Zusammenhang zwischen Depressivität und der Sprechgeschwindigkeit. Zwischen der Spannweite der Grundfrequenz, der Pausenlänge und Depressivität konnten tendenzielle Zusammenhänge gefunden werden. Depressive Patient_innen sind im Vergleich zu Gesunden durch eine monotone Sprache, eine geringe Sprechgeschwindigkeit und längere Pausen gekennzeichnet. Sprechgeschwindigkeit und Pausenlänge waren ebenfalls mit Ängstlichkeit assoziiert.

Diskussion

Sprechgeschwindigkeit, Pausenlänge und Spannweite der Grundfrequenz scheinen relevante Indikatoren für Depressivität/ggf. Ängstlichkeit zu sein. Die Spannweite der Grundfrequenz ist eher depressionsspezifisch, während Pausenlänge und Sprechgeschwindigkeit mit Depressivität und Ängstlichkeit assoziiert sind. Zukünftige Studien sollten die Zusammenhänge in größeren Stichproben verschiedener klinischer Störungsbilder untersuchen.
Coupled climate response to Atlantic Multidecadal Variability in a multi-model multi-resolution ensemble
Authors: Hodson Daniel L. R. , Bretonnière Pierre-Antoine , Cassou Christophe , Davini Paolo , Klingaman Nicholas P. , Lohmann Katja , Lopez-Parages Jorge , Martín-Rey Marta , Moine Marie-Pierre , Monerie Paul-Arthur , Putrasahan Dian A. , Roberts Christopher D. , Robson Jon , Ruprich-Robert Yohan , Sanchez-Gomez Emilia , Seddon Jon , Senan Retish
Published: February 2022

North Atlantic sea surface temperatures (SSTs) underwent pronounced multidecadal variability during the twentieth and early twenty-first century. We examine the impacts of this Atlantic Multidecadal Variability (AMV), also referred to as the Atlantic Multidecadal Oscillation (AMO), on climate in an ensemble of five coupled climate models at both low and high spatial resolution. We use a SST nudging scheme specified by the Coupled Model Intercomparision Project’s Decadal Climate Prediction Project Component C (CMIP6 DCPP-C) to impose a persistent positive/negative phase of the AMV in the North Atlantic in coupled model simulations; SSTs are free to evolve outside this region. The large-scale seasonal mean response to the positive AMV involves widespread warming over Eurasia and the Americas, with a pattern of cooling over the Pacific Ocean similar to the Pacific Decadal Oscillation (PDO), together with a northward displacement of the inter-tropical convergence zone (ITCZ). The accompanying changes in global atmospheric circulation lead to widespread changes in precipitation. We use Analysis of Variance (ANOVA) to demonstrate that this large-scale climate response is accompanied by significant differences between models in how they respond to the common AMV forcing, particularly in the tropics. These differences may arise from variations in North Atlantic air-sea heat fluxes between models despite a common North Atlantic SST forcing pattern. We cannot detect a widespread effect of increased model horizontal resolution in this climate response, with the exception of the ITCZ, which shifts further northwards in the positive phase of the AMV in the higher resolution configurations.
Long-term follow-up for monovision surgery by Implantable Collamer Lens V4c implantation for myopia correction in early presbyopia
Authors: Ye Yuhao , Zhao Jing , Zhang Zhe , Niu Lingling , Shi Wanru , Wang Xiaoying , Zhou Xingtao
Published: February 2022

Purpose

To investigate the long-term safety and efficacy of monovision surgery using implantable collamer lens V4c (ICL V4c) implantation in myopic patients with early presbyopia.

Setting

Eye and ENT Hospital of Fudan University, Shanghai, China.

Design

Prospective case series study.

Methods

This study included 64 eyes of 32 patients with early presbyopia, who underwent bilateral ICL V4c implantation for myopia correction. Parameters, including mean spherical equivalent (SE), uncorrected distance visual acuity, corrected distance visual acuity, intraocular pressure, endothelial cell density, presbyopic add power, visual acuity (logMAR) of dominant eyes (D-eye), nondominant (nD-eye) eyes, and both eyes (Bi) at 0.4 m, 0.8 m, and 5 m were recorded at the last follow-up.

Results

All surgeries were uneventful. At the last follow-up, the safety indices were 1.23 ± 0.18 (D-eyes) and 1.21 ± 0.18 (nD-eyes) (p > 0.05); the efficacy indices were 0.95 ± 0.27 (D-eyes) and 0.92 ± 0.28 (nD-eyes) (p < 0.05), the SE was -0.62 ± 0.47 D (D-eyes); and − 1.21 ± 0.78D (nD-eyes) (p < 0.05), presbyopic add power was 1.31 ± 0.58 D. The visual acuity (logMAR) of D-eyes, nD-eyes, and binocular (Bi) at 5.0 m were: 0.06 ± 0.15 (D-eye), 0.21 ± 0.18 (nD-eye), (p < 0.01), and 0.04 ± 0.13 (Bi); 0.8 m: 0.03 ± 0.18 (D-eye), 0.08 ± 0.16 (nD-eye), (p > 0.05), and − 0.02 ± 0.11 (Bi); 0.4 m: 0.08 ± 0.09 (D-eye), − 0.02 ± 0.08 (nD-eye), (p < 0.001), and − 0.03 ± 0.09 (Bi). Subjects were very satisfied or felt excellent with their visual acuity at near (81.25%) and far distances (87.50%), respectively (versus preoperative, p < 0.001).

Conclusion

Monovision surgery using ICL V4c implantation is safe and practicable for correction of myopes with presbyopia, with long-term efficacy at near and far distances and patient satisfaction.
Replacing vertical actions by mouse movements: a web-suited paradigm for investigating vertical spatial associations
Authors: Schütt Emanuel , Mackenzie Ian Grant , Kaup Barbara , Dudschig Carolin
Published: February 2022

The number of web-based studies in experimental psychology has been growing tremendously throughout the last few years. However, a straightforward web-based implementation does not exist for all types of experimental paradigms. In the current paper, we focus on how vertical response movements—which play a crucial role in spatial cognition and language research—can be translated into a web-based setup. Specifically, we introduce a web-suited counterpart of the vertical Stroop task (e.g., Fox & Shor, in Bull Psychon Soc 7:187–189, 1976; Lachmair et al., in Psychon Bull Rev 18:1180–1188, 2011; Thornton et al., in J Exp Psychol Hum Percept Perform 39:964–973, 2013). We employed nouns referring to entities typically located in lower or upper vertical space (e.g., “worm” and “bird”, respectively) in Experiments 1 and 2, and emotional valence words associated with a crouched or an upward bodily posture (e.g., “sadness” and “excitement”, respectively) in Experiment 3. Depending on the font color, our participants used their mouse to drag the words to the lower or upper screen location. Across all experiments, we consistently observed congruency effects analogous to those obtained with the lab paradigm using actual vertical arm movements. Consequently, we conclude that our web-suited paradigm establishes a reliable approach to examining vertical spatial associations.
Molecular assessment of Theileria equi and Babesia caballi prevalence in horses and ticks on horses in southeastern France
Authors: Rocafort-Ferrer Gloria , Leblond Agnès , Joulié Aurélien , René-Martellet Magalie , Sandoz Alain , Poux Valérie , Pradier Sophie , Barry Séverine , Vial Laurence , Legrand Loïc
Published: February 2022

Equine piroplasmosis (EP) is a tick-borne disease caused by Babesia caballi and Theileria equi that is potentially emerging in non-endemic countries. We conducted a descriptive study to investigate EP prevalence and spatial distribution in an endemic region: the Camargue and the Plain of La Crau in France. In spring 2015 and 2016, we carried out sampling at stables (total n = 46) with a history of horses presenting chronic fever or weight loss. Overall, we collected blood from 632 horses, which were also inspected for ticks; these horses had been housed in the target stables for at least 1 year. We obtained 585 ticks from these horses and described land use around the stables. Real-time PCR was employed to assess T. equi and B. caballi prevalence in the horses and in the ticks found on the horses. For the horses, T. equi and B. caballi prevalence was 68.6% and 6.3%, respectively. For the ticks found on the horses, prevalence was 28.8% for T. equi and 0.85% for B. caballi. The most common tick species were, in order of frequency, Rhipicephalus bursa, R. sanguineus sl., Hyalomma marginatum, Haemaphysalis punctata, and Dermacentor sp. Horses bearing Rhipicephalus ticks occurred in wetter zones, closer to agricultural areas, permanent crops, and ditches, as well as in drier zones, in the more northern countryside. Compared to horses bearing R. bursa, horses bearing R. sanguineus sl. more frequently occurred near the Rhone River. Prevalence of T. equi in the ticks was as follows: Hyalomma marginatum (43%), Dermacentor sp. (40%), R. bursa (33%), R. sanguineus sl. (19%), and Haemaphysalis punctata (17%). In contrast, B. caballi only occurred in Dermacentor sp. (20%) and R. bursa (1%).
Anti-tubulin-alpha-1c antibody as a marker of value in Behçet syndrome
Authors: Amin Mariam Maged , Abdel Latif Osama M.
Published: February 2022

Background

Behçet’s syndrome (BS) is a multi-systemic vasculitis characterized by recurrent oral ulcers, genital ulcers, ocular lesions, and other systemic manifestations. As there is no laboratory diagnostics of BS, the diagnosis is mainly clinical.

Objective

To investigate the utility of the autoantibody against tubulin-α-1c in diagnosis of BS and its clinical significance.

Methods

Sixty BS patients and sixty healthy controls were enrolled in this study. We assessed all patients by Behçet disease current activity form (BDCAF), routine laboratory investigations, and immunological markers (ANA, anti-DNA, ANCA). Anti-endothelial cell antibodies (AECA) and anti-tubulin-alpha-1c antibodies were performed for all participants.

Results

Regarding duration of illness, Birmingham Vasculitis Activity Score (BVAS), and BDCAF, the mean value was 4.77 ± 4.239, 19.80 ± 10.020, and 9.52 ± 5.476, respectively. On comparing laboratory investigations, there was only significant increase in anti-tubulin-alpha-1c antibody in BS patients compared to healthy controls. Regarding AECA, there was no any significant correlation except with CRP. Anti-tubulin-alpha-1c detected significant direct correlation with the presence of posterior uveitis, panuveitis, and venous thrombosis as well as BVAS, C4, and protein/creatinine ratio. Regarding diagnostic performance of both AECA and anti-tubulin-alpha-1c, the cutoff value of AECA for diagnosis was 27.250, with sensitivity and specificity of 93.3% and 96.7%, respectively. The cutoff value of the anti-tubulin-alpha-1c for diagnosis was 22.300, with sensitivity and specificity of 100% and 96.7% respectively.

Conclusion

Anti-tubulin-α-1c antibodies are of diagnostic value in BS and are indicative of activity with 100% sensitivity and 96.7% specificity.

Key Points•There is lack of specific laboratory, radiological, or histological diagnostics for Behcet syndrome.•We aimed to evaluate the significance of tubulin-α-1c autoantibody in diagnosis of Behcet syndrome.•There is elevation of tubulin-α-1c autoantibody with sensitivity and specificity of 100% and 96.7%, respectively.
Should administrative costs in health insurance be included in the risk-equalization? An analysis of five countries
Authors: Douven Rudy , Kauer Lukas , Demme Sylvia , Paolucci Francesco , van de Ven Wynand , Wasem Jürgen , Zhao Xiaoxi
Published: February 2022

Most countries that apply risk-equalization in their health insurance market(s) perform risk-equalization on medical claims but do not include other components of the insurance premium, such as administrative costs. Using fixed effects panel regressions from individual insurers in Australia, Germany, the Netherlands, Switzerland, and the US, we find evidence that health insurers with a high morbidity population on average have higher administrative costs. We argue that administrative costs should also be included in risk-equalization and we show that such equalization results in additional equalization payments nontrivial in size. Using examples from Germany and the US, we show how in practice policymakers can include administrative costs in risk-equalization. We are skeptical about applying risk-equalization to other components of the insurance premium, such as profits or costs related to solvency requirements of insurers.
Selecting Environmental Water Tracers to Understand Groundwater around Mines: Opportunities and Limitations
Authors: Kurukulasuriya Devmi , Howcroft William , Moon Ellen , Meredith Karina , Timms Wendy
Published: February 2022

Underground mining operations have the potential to alter groundwater systems and facilitate hydraulic connections between surface water and groundwater. The nature and degree of these interactions need to be evaluated to identify mining risks to surrounding water resources and to predict potential operational effects and environmental impacts, such as hydraulic stress on local surface waters. Environmental water tracers (EWTs) are commonly used to study such interactions in mine water and hydrogeological studies. However, the opportunities presented by EWTs could be more widely utilised to benefit the mining industry and the environment. Some of the challenges faced include the lack of practical frameworks, the need for more examples of EWTs applications in mining, and the possibility of complex interpretation of tracer results. This paper reviews previous studies that have applied EWTs in groundwater systems within or near mine sites, mostly from Australia, China, and India. The EWTs used in these studies include water quality parameters, major ions, stable isotopes, radioisotopes, and dissolved gases. The opportunities of applying multiple EWTs to identify water sources, mixing, and determine recharge rates and groundwater residence times are discussed. Limitations of different EWTs in terms of their capabilities, reliability, cost of analysis, effort, and processing times are reviewed. Steps for selecting suitable EWTs for specific mine hydrogeology assessments should be commensurate with the risks. Finally, this paper provides an overview of suitable EWTs that will be a useful contribution to appropriate water resource management decisions around mines.
Order theory for discrete gradient methods
Authors: Eidnes Sølve
Published: February 2022

The discrete gradient methods are integrators designed to preserve invariants of ordinary differential equations. From a formal series expansion of a subclass of these methods, we derive conditions for arbitrarily high order. We derive specific results for the average vector field discrete gradient, from which we get P-series methods in the general case, and B-series methods for canonical Hamiltonian systems. Higher order schemes are presented, and their applications are demonstrated on the Hénon–Heiles system and a Lotka–Volterra system, and on both the training and integration of a pendulum system learned from data by a neural network.
Probing Environmental Sustainability Through the Diversity-Pollution Nexus—a Global Perspective via PM2.5 and NO2
Authors: Amin Saqib , Khan Mujahid Ameen , Mehmood Waqas
Published: February 2022

This paper analyzes the effects of ethnic and religious diversity on air pollution for 187 countries around the world (categorized into high-income, middle-income and low-income countries) from 1990 to 2020. We determine the long-run relationship between the variables using panel-fixed effects and GMM models. Air pollution emission factors are spatially explicit into emissions of particulate matter (PM2.5) and nitrogen dioxide (NO2) and the Alesina’s fragmentation index has been used to calculate ethnic and religious diversity. The results show that ethnic and religious diversity both have significant negative impacts on air pollution (PM2.5 and NO2). Furthermore, the results are more significant for high-income and middle-income countries and vice versa for low-income countries. This study suggests that diversity is a natural phenomenon; however, its disastrous effects may be curtailed by providing equal opportunities and promoting a peaceful society, as done in high-income countries, to ensure the well-being of the people through cohesiveness. Policymakers need to promote collective action and communication among different groups while acknowledging that investment for public benefits often requires broad social consensus and solidarity.
Genomic breeding values’ prediction including populational selfing rate in an open-pollinated Eucalyptus globulus breeding population
Authors: Quezada Marianella , Aguilar Ignacio , Balmelli Gustavo
Published: February 2022

In forest tree breeding programs, open-pollinated families are frequently used to estimate genetic parameters and evaluate genetic merit of individuals. However, the presence of selfing events not documented in the pedigree affects the estimation of these parameters. In this study, 194 open-pollinated families of Eucalyptus globulus Labill. trees were used to compare the precision of estimated genetic parameters and accuracies of predicted breeding values with the conventional pedigree-based model (ABLUP) and the pedigree-genomic single-step model (ssGBLUP). The available genetic information for pairwise parent-offspring allows us to estimate an actual populational selfing rate of 5.4%. For all the growth and disease resistance traits evaluated, the inclusion of selfing rate was effective in reducing the upward bias, between 7 and 30%, in heritability estimates. The predictive abilities for ssGBLUP models were always higher than those for ABLUP models. In both cases, a considerable reduction of predictive abilities was observed when relatedness between training and validation populations was removed. We proposed a straightforward approach for the estimation of the actual selfing rate in a breeding population. The incorporation of this parameter allows for more reliable estimation of genetic parameters. Furthermore, our results proved that ssGBLUP was effective for the accurate estimation of genetic parameters and to improve the prediction of breeding values in presence of selfing events, thus a valuable tool for genomic evaluations in Eucalyptus breeding programs.
A systematic comparison of generative models for medical images
Authors: Uzunova Hristina , Wilms Matthias , Forkert Nils D. , Handels Heinz , Ehrhardt Jan
Published: February 2022

Purpose

This work aims for a systematic comparison of popular shape and appearance models. Here, two statistical and four deep-learning-based shape and appearance models are compared and evaluated in terms of their expressiveness described by their generalization ability and specificity as well as further properties like input data format, interpretability and latent space distribution and dimension.

Methods

Classical shape models and their locality-based extension are considered next to autoencoders, variational autoencoders, diffeomorphic autoencoders and generative adversarial networks. The approaches are evaluated in terms of generalization ability, specificity and likeness depending on the amount of training data. Furthermore, various latent space metrics are presented in order to capture further major characteristics of the models.

Results

The experimental setup showed that locality statistical shape models yield best results in terms of generalization ability for 2D and 3D shape modeling. However, the deep learning approaches show strongly improved specificity. In the case of simultaneous shape and appearance modeling, the neural networks are able to generate more realistic and diverse appearances. A major drawback of the deep-learning models is, however, their impaired interpretability and ambiguity of the latent space.

Conclusions

It can be concluded that for applications not requiring particularly good specificity, shape modeling can be reliably established with locality-based statistical shape models, especially when it comes to 3D shapes. However, deep learning approaches are more worthwhile in terms of appearance modeling.
Inland-coastal demographic transformations in a karst area: a case study of the surroundings of Krka National Park (Croatia)
Authors: Telbisz Tamás , Radeljak Kaufmann Petra , Bočić Neven
Published: February 2022

According to geographic possibilism, environment does not determine socio-economic development. However, the environment sets certain constraints and limitations for development. How do natural settings influence population dynamics? In this study, we examine this question using the example of Šibenik-Knin County, which includes Krka National Park (NP) with a GIS-based statistical approach. The following parameters represent natural factors: elevation, slope, distance from water, and proportion of karst areas. In addition, distance from Krka NP was also added as an independent semi-natural factor (despite the fact that it is a social construction). The dependent social parameters are population density for selected historical dates, population change, year of maximum population, natural increase, migration, and age index. The analysis units are the 199 settlements found in the county, and the 20 local administrative units (LAU2). The study period can be divided into five phases: from the first census in 1857 to 1921, there was a slow increase in most settlements; then a relatively constant phase up to 1961 (some settlements began shrinking in this period); a slow decrease until 1991; a rapid decrease during the next decade; and relative stabilisation to present day. These processes were also accompanied by significant inner and outer migrations. As for the relationships between natural and demographic factors, we found that although the coastal-inland area dichotomy is dominant in the study area, elevation has the highest correlation with most population parameters. However, distance from water is also significantly correlated with population change and migration in certain periods. In the inland areas, there are statistically significant differences between the demographic processes of fully-karstic and partially-karstic areas, while in the coastal zone, the karst effect is overshadowed by other social processes. The impact of Krka NP on the demographic characteristics of the surrounding settlements was statistically not detectable. Our final conclusion is that correlations between natural and population parameters are low or moderately strong but statistically significant in many cases, thus the basic principles of geographic possibilism are valid for the area.
Quasi-Non-destructive Characterization of Carburized Case Depth by an Application of Centerless X-ray Diffractometers
Authors: Sepsi Mate , Szobota Peter , Mertinger Valeria
Published: February 2022

A new application of a centerless x-ray diffractometer was proposed that goes beyond residual stress measurements during the regular operation of such equipment. During depth residual stress measurement, it is possible to fit the measured interference function of the ferrite (211) with a different number of curves as a function of depth. The different curves corresponded with the appearance of ferrite fractions with different grain sizes and concentrations in ferrite, perlite, bainite, or martensite. Accordingly, different microstructures were non-destructively detected through the thickness of the carburized layer, and a good correlation was found with results from metallography and hardness testing. This novel method was validated on solid and gas carburized samples, but more work is needed to apply it to other microstructures.
Enhancing Gender
Authors: Zohny Hazem , Earp Brian D. , Savulescu Julian
Published: February 2022

Transgender healthcare faces a dilemma. On the one hand, access to certain medical interventions, including hormone treatments or surgeries, where desired, may be beneficial or even vital for some gender dysphoric trans people. But on the other hand, access to medical interventions typically requires a diagnosis, which, in turn, seems to imply the existence of a pathological state—something that many transgender people reject as a false and stigmatizing characterization of their experience or identity. In this paper we argue that developments from the human enhancement debate can help clarify or resolve some of the conceptual and ethical entanglements arising from the apparent conflict between seeking medicine while not necessarily suffering from a pathology or disorder. Specifically, we focus on the welfarist account of human enhancement and argue it can provide a useful conceptual framework for thinking about some of the more contentious disagreements about access to transgender healthcare services.
Local and systemic effect of azadirachtin on host choice and feeding activity of Macrosiphum rosae on rose plants
Authors: Bartelsmeier Imke , Kilian Michael , ten Broeke Cindy J. M. , Mertens Daan , Dicke Marcel
Published: February 2022

Many studies in the last decades addressed the antifeedant and repellent effects of neem (Azadirachta indica)-based pesticides on arthropod herbivores with azadirachtin as the leading active ingredient. However, results for aphids regarding repellence and feeding were often contradictory and mainly based on laboratory studies with self-made neem extracts in high concentrations. Moreover, no data are available on the presence of azadirachtin in the phloem of treated plants—the tissue that most aphids feed on. We investigated how the application of the commercial neem product NeemAzal-T/S onto only one plant half (upper or lower) affects nymphs of the aphidMacrosiphum rosaein clip cages on the untreated plant half. Results for aphid mortality indicate that active ingredients of NeemAzal-T/S are translocated both upwards and downwards in rose plants and that active ingredients are transported in the phloem. Furthermore, we investigated whether NeemAzal-T/S has a repellent or antifeedant effect onM. rosae. A choice test in the greenhouse as well as the quantification of honeydew excretion and electrical penetration graph analysis do not show differences in settling or feeding on untreated and NeemAzal-T/S-treated rose plants. Collectively, our data show that the effect of approved concentrations of NeemAzal-T/S onM. rosaeis based on the toxicity after feeding on treated plants, not on starvation.
Neuromodulation for Chronic Daily Headache
Authors: Coppola Gianluca , Magis Delphine , Casillo Francesco , Sebastianelli Gabriele , Abagnale Chiara , Cioffi Ettore , Di Lenola Davide , Di Lorenzo Cherubino , Serrao Mariano
Published: February 2022

Purpose of Review

We reviewed the literature that explored the use of central and peripheral neuromodulation techniques for chronic daily headache (CDH) treatment.

Recent Findings

Although the more invasive deep brain stimulation (DBS) is effective in chronic cluster headache (CCH), it should be reserved for extremely difficult-to-treat patients. Percutaneous occipital nerve stimulation has shown similar efficacy to DBS and is less risky in both CCH and chronic migraine (CM). Non-invasive transcutaneous vagus nerve stimulation is a promising add-on treatment for CCH but not for CM. Transcutaneous external trigeminal nerve stimulation may be effective in treating CM; however, it has not yet been tested for cluster headache. Transcranial magnetic and electric stimulations have promising preventive effects against CM and CCH.

Although the precise mode of action of non-invasive neuromodulation techniques remains largely unknown and there is a paucity of controlled trials, they should be preferred to more invasive techniques for treating CDH.