bluuebunny/crossref_metadata_2025 huggingface dataset:
Quadripartite bond length rule applied to two prototypical aromatic and antiaromatic molecules
Authors: Wolański Łukasz , Grochala Wojciech
Published: March 2023

Context

In 2000, a remarkably simple relationship was introduced, which connected the calculated geometries of isomolecular states of three different multiplicities. These encompass a ground single state, the first excited triplet state, as well as related radical anion and radical cation. The rule allows the prediction of the geometry of one of the species if the three remaining ones are known. Here, we verify the applicability of this bond length rule for two small planar cyclic organic molecules, i.e., benzene and cyclobutadiene, which stand as prototypical examples of, respectively, aromatic and antiaromatic systems. We see that the rule works fairly well to benzene, and it works independently for quinoid as well as for anti-quinoid minima, despite the fact that radical anion species poses challenges for correct theoretical description.

Methods

To obtain chosen electronic state equilibrium geometries, three types of computational approaches were utilized: fast and efficient density functional theory DFT, the coupled cluster method CC2, the complete active space self-consistent field (CASSCF) approach, and the most accurate but also resource-consuming perturbation theory with multireference wavefunction (CASPT2) with a default value and without IPEA-shift. Dunning and co-workers correlation-consistent basis sets (aug-)cc-pVXZ (X = D, T, Q) were employed. Gaussian 16 revision A.03, Turbomole 7.1, and Molcas 8.0 computational software were used.
Adoption of additive manufacturing in oral and maxillofacial surgery among university and non-university hospitals in Sweden: findings from a nationwide survey
Authors: Zheng Xuewei , Wang Ruilin , Brantnell Anders , Thor Andreas
Published: March 2023

Purpose

Additive manufacturing (AM) is an innovative printing technology that can manufacture 3-dimensional solid objects by adding layers of material from model data. AM in oral and maxillofacial surgery (OMFS) provides several clinical applications such as surgical guides and implants. However, the adoption of AM in OMFS is not well covered. The purpose was to study the adoption of AM in OMFS in university and non-university hospitals in Sweden. Three research questions were addressed: What is the degree of using AM solutions in university and non-university hospitals?; What are AM solutions used?; How are the AM solutions accessed (production mode) in university hospitals and non-university hospitals?

Methods

A survey was distributed to OMF surgeons in Sweden. The questionnaire consisted of 16 questions. Data were analyzed through descriptive and content analysis.

Results

A total of 14 university and non-university hospitals were captured. All 14 hospitals have adopted AM technology and 11 of the hospitals adopted AM in OMFS. Orthognathic and trauma surgery are two major types of surgery that involve AM technology where material extrusion and vat polymerization are the two most used AM technologies in OMFS. The primary application of AM was in medical models and guides.

Conclusion

Majority of Swedish university hospitals and non-university hospitals have adopted AM in OMFS. The type of hospital (university or non-university hospital) has no impact on AM adoption. AM in OMFS in Sweden can be perceived to be a mature clinical application.
Combining rule- and SMT-based reasoning for verifying floating-point Java programs in KeY
Authors: Abbasi Rosa , Schiffl Jonas , Darulova Eva , Ulbrich Mattias , Ahrendt Wolfgang
Published: March 2023

Deductive verification has been successful in verifying interesting properties of real-world programs. One notable gap is the limited support for floating-point reasoning. This is unfortunate, as floating-point arithmetic is particularly unintuitive to reason about due to rounding as well as the presence of the special values infinity and ‘Not a Number’ (NaN). In this article, we present the first floating-point support in a deductive verification tool for the Java programming language. Our support in the KeY verifier handles floating-point arithmetics, transcendental functions, and potentially rounding-type casts. We achieve this with a combination of delegation to external SMT solvers on the one hand, and KeY-internal, rule-based reasoning on the other hand, exploiting the complementary strengths of both worlds. We evaluate this integration on new benchmarks and show that this approach is powerful enough to prove the absence of floating-point special values—often a prerequisite for correct programs—as well as functional properties, for realistic benchmarks.
Der Einfluss von Frequent Usern auf das Rettungsfachpersonal: Ergebnisse einer Umfrage
Authors: Schodlok Mia , Langeloh Jule , Kreinfeldt Hanna , Scheel Arlene , Kubacki Saskia , Kroll Anna , Ludwig Christoph , Möckel Luis , Hofmann Thomas
Published: March 2023

Hintergrund

Frequent User (FU) nutzen den Rettungsdienst vermehrt in kürzester Zeit und können so direkten Einfluss auf Einsatzaufkommen und -charakter nehmen. Aus diesem Grund war das Ziel dieser Studie, die Wahrnehmung von Rettungskräften zu FU in Deutschland zu untersuchen.

Methoden

Es wurde eine deutschlandweite Querschnittstudie als Befragung von Rettungskräften durchgeführt. Die Auswertung der Daten erfolgte deskriptiv unter Berechnung von Häufigkeiten. Unterschiede zu FU im ländlichen und städtischen Bereich wurden mittels Chi2-Test und unter Berechnung von Odds Ratios (OR) und dazugehörigen 95 %-Konfidenzintervallen (95 %-KI) ermittelt.

Ergebnisse

Insgesamt wurden 1142 Rettungskräfte (36,69 % Frauen, 62,87 % Männer) in die Studie eingeschlossen. Die beiden häufigsten wahrgenommenen Einsatzorte im Zusammenhang mit FU waren bestimmte Privatadressen (32,75 %) und Pflegeheime (29,99 %), so wie die häufigsten Ursachen für Rettungsdiensteinsätze Versorgungsprobleme (44,66 %) und Intoxikationen (24,34 %) sind. Auf dem Land waren ebenfalls bestimmte Privatadressen (42,51 %) die häufigsten Einsatzorte, wohingegen in der Stadt bestimmte Stadtteile im Vordergrund standen (34,94 %). FU hatten einen negativen Einfluss auf das Verhalten, die Stimmung und die Geduld der Rettungskräfte. Im ländlichen Raum war zudem die Tendenz zu einer weniger sorgfältigen Untersuchung der FU niedriger (OR: 0,61 [95 %-KI: 0,48; 0,78]) und dass FU keine Versorgung wünschen, da die Alarmierung durch Dritte erfolgte (OR: 0,67 [95 %-KI: 0,53; 0,84]). Dagegen schätzen die FU ihre Symptome auf dem Land häufiger bedrohlicher ein als notwendig (OR: 1,95 [95 %-KI: 1,37; 2,77]) und Einsätze zu FU waren häufiger außerhalb der Öffnungszeiten von Versorgungseinrichtungen (OR: 1,65 [95 %-KI: 1,30; 2,09]).

Schlussfolgerung

Diese Studie zeigt, dass Frequent User sich negativ auf die Stimmung sowie die Arbeitsweise der Rettungskräfte auswirken und dass sowohl in dieser Hinsicht als auch bezogen auf die häufigsten Einsatzorte Unterschiede in der Stadt- und Landrettung bestehen.
Staphylococcus aureus bacteraemia, cardiac implantable electronic device, and the risk of endocarditis: a retrospective population–based cohort study
Authors: Berge Andreas , Carlsén Casper , Petropoulos Alexandros , Gadler Fredrik , Rasmussen Magnus
Published: March 2023

Patients with cardiac implantable electronic device (CIED) and Staphylococcus aureus bacteraemia (SAB) are at risk of having infective endocarditis (IE). The objectives were to describe a Swedish population-based cohort of patients with CIED and SAB, to identify risk factors, and to construct a predictive score for IE. Patients over 18 years old in the Stockholm Region identified to have SAB in the Karolinska Laboratory database from January 2015 through December 2019 were matched to the Swedish Pacemaker and Implantable Cardioverter-Defibrillator ICD Registry to identify the study cohort. Data were collected from study of medical records. A cohort of 274 patients with CIED and SAB was identified and in 38 episodes (14%) IE were diagnosed, 19 with changes on the CIED, and 35 with changes on the left side of the heart. The risk factors predisposition for IE, community acquisition, embolization, time to positivity of blood cultures, and growth in blood culture after start of therapy in blood cultures were independently associated to IE. A score to identify patients with IE was constructed, the CTEPP score, and the chosen cut-off generated a sensitivity of 97%, specificity of 25%, and a negative predictive value of 98%. The score was externally validated in a population-based cohort of patients with CIED and SAB from another Swedish region. We found that 14% of patients with CIED and SAB had definite IE diagnosed. The CTEPP-score can be used to predict the risk of IE and, when negative, the risk is negligible.
Should fiscal policies be centralized in a monetary union? A dynamic game approach
Authors: Blueschke Dmitri , Blueschke-Nikolaeva Viktoria , Neck Reinhard
Published: March 2023

In this paper we analyze dynamic interactions in a monetary union with three fiscal players (the governments of the countries concerned) and a common central bank in the presence of exogenous shocks. The model is calibrated for the euro area and includes a fiscally more solid core block denoted as country 1 as well as a fiscally less solid periphery block represented by countries 2 and 3. Introducing two periphery countries allows us to capture different attitudes of the periphery countries towards the goal of sustainable fiscal performance. Moreover, different coalition scenarios are modelled in this study including a fiscal union, a coalition of periphery countries and a coalition of fiscal-stability oriented countries. The exogenous shocks are calibrated in such a way as to describe the last major crises in the euro area, namely the financial crisis, the European sovereign debt crisis, the Covid-19 crisis, and the Ukraine war (energy price) crisis. Using the OPTGAME algorithm we calculate a cooperative Pareto and non-cooperative feedback Nash equilibrium solutions for the modelled scenarios. The fully cooperative solution yields the best results. The different non-cooperative scenarios allow insights into the underlying trade-off between economic growth, price stability and fiscal stability.
Automated database design for document stores with multicriteria optimization
Authors: Hewasinghage Moditha , Nadal Sergi , Abelló Alberto , Zimányi Esteban
Published: March 2023

Document stores have gained popularity among NoSQL systems mainly due to the semi-structured data storage structure and the enhanced query capabilities. The database design in document stores expands beyond the first normal form by encouraging de-normalization through nesting. This hinders the process, as the number of alternatives grows exponentially with multiple choices in nesting (including different levels) and referencing (including the direction of the reference). Due to this complexity, document store data design is mostly carried out in trial-and-error or ad-hoc rule-based approaches. However, the choices affect multiple, often conflicting, aspects such as query performance, storage space, and complexity of the documents. To overcome these issues, in this paper, we apply multicriteria optimization. Our approach is driven by a query workload and a set of optimization objectives. First, we formalize a canonical model to represent alternative designs and introduce an algebra of transformations that can systematically modify a design. Then, using these transformations, we implement a local search algorithm driven by a loss function that can propose near-optimal designs with high probability. Finally, we compare our prototype against an existing document store data design solution purely driven by query cost, where our proposed designs have better performance and are more compact with less redundancy.
Clinical outcomes of patients diagnosed with cancer of unknown primary or malignancy of undefined primary origin who were referred to a regional cancer center
Authors: Ando Masashi , Honda Kazunori , Hosoda Waki , Matsubara Yuki , Kumanishi Ryosuke , Nakazawa Taiko , Ogata Takatsugu , Nakata Akinobu , Kodama Hiroyuki , Masuishi Toshiki , Narita Yukiya , Taniguchi Hiroya , Kadowaki Shigenori , Muro Kei
Published: March 2023

Background

A regional cancer hospital has been identified to be crucial in the management of malignancies of undefined primary origin (MUO) and cancer of unknown primary (CUP). This hospital primarily consists of oncologists with expertise in CUP, pathologists, and interventional radiologists. Early consultation or referral of MUO and CUP to a cancer hospital is deemed important.

Methods

This study retrospectively collected and analyzed the clinical, pathological, and outcome data of all patients (n = 407) referred to the Aichi Cancer Center Hospital (ACCH) in Japan over an 8-year period.

Results

In total, 30% of patients were referred for a second opinion. Among 285 patients, 13% had non-neoplastic disease or confirmed primary site and 76% had confirmed CUP (cCUP), with 29% of cCUP being identified as favorable risk. In 155 patients with unfavorable-risk CUP, 73% had primary sites predicted by immunohistochemistry (IHC) and distribution of metastatic sites, whereas 66% of them received site-specific therapies based on the predicted primary sites. The median overall survival (OS) was found to be poor in patients with MUO (1 month) and provisional CUP (6 months). In addition, the median OS of 206 patients with cCUP treated at the ACCH was 16 months (favorable risk, 27 months; unfavorable risk, 12 months). No significant difference was noted in OS between patients with non-predictable and predictable primary-sites (13 vs 12 months,p = 0.411).

Conclusion

The outcome of patients with unfavorable-risk CUP remains to be poor. Site-specific therapy based on IHC is not recommended for all patients with unfavorable-risk CUP.
A novel frame switching model based on virtual MAC in SDN
Authors: Song Guangjia , Hu Jianhua , Wang Hui
Published: March 2023

MAC address spoofing has plagued LAN communication for a long time. Many attacks use it as a springboard to carry out subsequent attacks. The main reason for this kind of attack is the exposure of MAC address. If the source MAC address of the node can be hidden during frame forwarding, this kind of attack can be effectively prevented. This study proposes virtual MAC switching (VMS) as a solution to this problem. VMS uses multi-address hopping technology to make the MAC address of the frame change continuously in the forwarding process. Its unique address generation format makes other nodes unable to record or speculate the real MAC address of the node, so it cannot launch an attack. Experiments show that VMS is close to typical SDN switches in terms of delay, throughput, and overhead and has a higher security level.
The effect of different kinematics on apical debris extrusion with a single-file system
Authors: Al Omari Taher M. N. , La Rosa Giusy Rita Maria , Albanna Rami Haitham Issa , Tabnjh Abedelmalek , Papale Flavia , Pedullà Eugenio
Published: March 2023

To compare the amount of extruded debris caused by different motions using a single-file system. Fifty mandibular first molar teeth were randomized into 5 groups (n = 10) according to the motion tested: Optimize Torque Reverse (OTR), TF Adaptive Motion (TFA), continuous rotation (CR), reciprocation motion (+ 150°, −30°) (REC), and Jeni motion (Jeni). One Curve single file 25/06 (Micro-Mega, Besançon, France) was used in all experimental groups. The root canals were irrigated with 2.5% NaOCl, and the extruded debris were collected at pre-weighted glass vials. The glass vials were kept inside an incubator for one week at 70 °C to dry out the irrigating solution. The extruded debris was quantified by subtracting the pre-instrumentation from the post-instrumentation weight of the glass vials. The time required for each instrumentation procedure was digitally recorded. All data were analyzed statistically with one way ANOVA and post hoc Tukey test (P < 0.05). All the motions extruded apically debris with Jeni mode caused significantly less debris extrusion than TFA, REC, and CR (P < 0.05) while no significant difference emerged with OTR. Preparation time was not significantly different in all groups. Within the limits of the present study, all the kinematics produced apically debris extrusion, with Jeni reporting a similar amount of debris compared with OTR and significantly less than TFA, REC, and CR. Preparation time was similar among the tested kinematics.
Deep Learning Body Region Classification of MRI and CT Examinations
Authors: Raffy Philippe , Pambrun Jean-François , Kumar Ashish , Dubois David , Patti Jay Waldron , Cairns Robyn Alexandra , Young Ryan
Published: March 2023

This study demonstrates the high performance of deep learning in identification of body regions covering the entire human body from magnetic resonance (MR) and computed tomography (CT) axial images across diverse acquisition protocols and modality manufacturers. Pixel-based analysis of anatomy contained in image sets can provide accurate anatomic labeling. For this purpose, a convolutional neural network (CNN)–based classifier was developed to identify body regions in CT and MRI studies. Seventeen CT (18 MRI) body regions covering the entire human body were defined for the classification task. Three retrospective datasets were built for the AI model training, validation, and testing, with a balanced distribution of studies per body region. The test datasets originated from a different healthcare network than the train and validation datasets. Sensitivity and specificity of the classifier was evaluated for patient age, patient sex, institution, scanner manufacturer, contrast, slice thickness, MRI sequence, and CT kernel. The data included a retrospective cohort of 2891 anonymized CT cases (training, 1804 studies; validation, 602 studies; test, 485 studies) and 3339 anonymized MRI cases (training, 1911 studies; validation, 636 studies; test, 792 studies). Twenty-seven institutions from primary care hospitals, community hospitals, and imaging centers contributed to the test datasets. The data included cases of all sexes in equal proportions and subjects aged from 18 years old to + 90 years old. Image-level weighted sensitivity of 92.5% (92.1–92.8) for CT and 92.3% (92.0–92.5) for MRI and weighted specificity of 99.4% (99.4–99.5) for CT and 99.2% (99.1–99.2) for MRI were achieved. Deep learning models can classify CT and MR images by body region including lower and upper extremities with high accuracy.
From RTK to PPP-RTK: towards real-time kinematic precise point positioning to support autonomous driving of inland waterway vessels
Authors: An Xiangdong , Ziebold Ralf , Lass Christoph
Published: March 2023

PPP-RTK is Precise Point Positioning (PPP) using corrections from a ground reference network, which enables single-receiver users with integer ambiguity resolution thereby improving its performance. However, most of the PPP-RTK studies are investigated and evaluated in a static situation or a post-processing mode because of the complexity of implementation in real-time practical applications. Moreover, although PPP-RTK achieves a faster convergence than PPP, it typically needs 30 s or even longer to derive high-accuracy results. We have implemented a real-time PPP-RTK approach based on undifferenced observations and State-Space Representation corrections with a fast convergence of less than 30 s to support autonomous driving of inland waterway vessels. The PPP-RTK performances and their feasibility to support autonomous driving have been evaluated and validated in a real-time inland waterway navigation. It proves the PPP-RTK approach can realize a precise positioning of less than 10 cm in horizontal with a rapid convergence. The convergence time is within 10 s after a normal bridge passing and less than 30 s after a complicated bridge passing. Moreover, the PPP-RTK approach can be extended to outside of the GNSS station network. Even if the location is 100 km away from the border of the GNSS station network, the PPP-RTK convergence time after a bridge passing is also normally less than 30 s. We have realized the first automated entry into a waterway lock for a vessel supported by PPP-RTK and taken the first step toward autonomous driving of inland vessels based on PPP-RTK.
Assessing flank instability of Stromboli volcano (Italy) by reappraising the 30 December 2002 tsunamigenic landslides
Authors: Di Traglia F. , Calvari S. , Borselli L. , Cassanego L. , Giudicepietro F. , Macedonio G. , Nolesini T. , Casagli N.
Published: March 2023

Bearing in mind the destructive potential of tsunamis induced by volcanic landslides, the tsunamigenic event occurring at Stromboli volcano in Italy on 30 December 2002 has been re-examined here, by means of visible images and slope stability analysis. This was one of the few examples in the world of a flank collapse occurring at a volcano that was directly observed. We present the results of stability analyses, together with a sequence of photos collected from a helicopter a few minutes before the collapse. The result of this study is that the sequence of landslides triggering the 2002 Stromboli tsunami can be defined as the final stage of a lateral magma intrusion that exerted a high thrust at high altitude, destabilizing the entire slope. This study allows a more complete understanding of the event that took place on Stromboli on 30 December 2002. Furthermore, the approach used here, if appropriately modified, can be used in other contexts, contributing to the understanding of the condition that leads to tsunamigenic landslides.
Musculotendon Parameters in Lower Limb Models: Simplifications, Uncertainties, and Muscle Force Estimation Sensitivity
Authors: Chen Ziyu , Franklin David W.
Published: March 2023

Musculotendon parameters are key factors in the Hill-type muscle contraction dynamics, determining the muscle force estimation accuracy of a musculoskeletal model. Their values are mostly derived from muscle architecture datasets, whose emergence has been a major impetus for model development. However, it is often not clear if such parameter update indeed improves simulation accuracy. Our goal is to explain to model users how these parameters are derived and how accurate they are, as well as to what extent errors in parameter values might influence force estimation. We examine in detail the derivation of musculotendon parameters in six muscle architecture datasets and four prominent OpenSim models of the lower limb, and then identify simplifications which could add uncertainties to the derived parameter values. Finally, we analyze the sensitivity of muscle force estimation to these parameters both numerically and analytically. Nine typical simplifications in parameter derivation are identified. Partial derivatives of the Hill-type contraction dynamics are derived. Tendon slack length is determined as the musculotendon parameter that muscle force estimation is most sensitive to, whereas pennation angle is the least impactful. Anatomical measurements alone are not enough to calibrate musculotendon parameters, and the improvement on muscle force estimation accuracy will be limited if the source muscle architecture datasets are the only main update. Model users may check if a dataset or model is free of concerning factors for their research or application requirements. The derived partial derivatives may be used as the gradient for musculotendon parameter calibration. For model development, we demonstrate that it is more promising to focus on other model parameters or components and seek alternative strategies to further increase simulation accuracy.
Efficient and certified solution of parametrized one-way coupled problems through DEIM-based data projection across non-conforming interfaces
Authors: Zappon Elena , Manzoni Andrea , Quarteroni Alfio
Published: March 2023

One of the major challenges of coupled problems is to manage nonconforming meshes at the interface between two models and/or domains, due to different numerical schemes or domain discretizations employed. Moreover, very often complex submodels depend on (e.g., physical or geometrical) parameters, thus making the repeated solutions of the coupled problem through high-fidelity, full-order models extremely expensive, if not unaffordable. In this paper, we propose a reduced order modeling (ROM) strategy to tackle parametrized one-way coupled problems made by a first,mastermodel and a second,slavemodel; this latter depends on the former through Dirichlet interface conditions. We combine a reduced basis method, applied to each subproblem, with the discrete empirical interpolation method to efficiently interpolate or project Dirichlet data across either conforming or non-conforming meshes at the domains interface, building a low-dimensional representation of the overall coupled problem. The proposed technique is numerically verified by considering a series of test cases involving both steady and unsteady problems, after deriving a posteriori error estimates on the solution of the coupled problem in both cases. This work arises from the need to solve staggered cardiac electrophysiological models and represents the first step towards the setting of ROM techniques for the more general two-way Dirichlet-Neumann coupled problems solved with domain decomposition sub-structuring methods, when interface non-conformity is involved.
Effects of M-DEPTH Model of Depression Care on Maternal HIV Viral Suppression and Adherence to the PMTCT Care Continuum Among HIV-Infected Pregnant Women in Uganda: Results from a Cluster Randomized Controlled Trial at Pregnancy Completion
Authors: Wagner Glenn J. , Gwokyalya Violet , Faherty Laura , Akena Dickens , Nakigudde Janet , Ngo Victoria , McBain Ryan , Ghosh-Dastidar Bonnie , Beyeza-Kashesya Jolly , Nakku Juliet , Kyohangirwe Leticia , Nabitaka Linda Kisaakye , Lukwata Hafsa , Mukasa Barbara , Wanyenze Rhoda K.
Published: March 2023

Perinatal depression has been shown to impede adherence to antiretroviral therapy (ART) and the prevention of mother-to-child transmission (PMTCT) care continuum; therefore, treating perinatal depression may result in increased viral suppression and PMTCT adherence. We examined the effects of the M-DEPTH (Maternal Depression Treatment in HIV) depression care model (including antidepressants and individual Problem Solving Therapy) on depression, maternal viral suppression and adherence to PMTCT care processes in an ongoing cluster-randomized controlled trial of 391 HIV-infected pregnant women (200 usual care; 191 intervention) with at least mild depressive symptoms enrolled across 8 antenatal care clinics in Uganda. At baseline, 68.3% had clinical depression and 41.7% had detectable HIV viral load. Adjusted repeated-measures multivariable regression models found that the intervention group was nearly 80% less likely to be clinically depressed [Adjusted OR (95% CI) 0.22 (0.05, 0.89)] at the 2-month post-pregnancy assessment, compared to the control group. However, the intervention and control groups did not differ meaningfully on maternal viral suppression, ART adherence, and other PMTCT care processes and outcomes. In this sample of women who were mostly virally suppressed and ART adherent at baseline, the depression care model had a strong effect on depression alleviation, but no downstream effects on viral suppression or other PMTCT care processes.

Trial Registration NIH Clinical Trial Registry NCT03892915 (clinicaltrials.gov).
Reconceiving Argument Schemes as Descriptive and Practically Normative
Authors: Larson Brian N. , Morrison David Seth
Published: March 2023

We propose a revised definition of “argument scheme” that focuses on describing argumentative performances and normative assessments that occur within an argumentative context, the social context in which the scheme arises. Our premise-and-conclusion structure identifies the typical instantiation of an argument in the argumentative context, and our critical framework describes a set of normative assessments available to participants in the context, what we call practically normative assessments. We distinguish this practical normativity from the rationally or universally normative assessment that might be imposed from outside the argumentative context. Thus, the practical norms represented in an argument scheme may still be subject to rational critique, and the scheme avoids the is/ought fallacy. We ground our theoretical discussion and observations in an empirical study of US district court opinions resolving legal questions about copyright fair use and the lawyers’ briefs that led to them, instantiating our definition of argument scheme in the “argument for classification by precedent.” Our definition addresses some criticisms the argument-scheme construct has received. For example, using our data, we show that a minimally well formed instance of this type of argument does not shift any conventional burden from the proponent of the argument to its skeptics. We also argue that these argument schemes need not be seen as dialogical.
Negative frequency dependent prey selection by two canid predators and its implications for the conservation of a threatened rodent in arid Australia
Authors: Sheldon Elizabeth L. , Feit Benjamin , Feit Anna , Letnic Mike
Published: March 2023

Unprecedented anthropogenic changes to biodiversity and biogeography demand a greater understanding of the consequences of altered faunal composition for ecosystem functioning. Selective predation has important, yet poorly understood effects on ecosystem stability, and can be strongly influenced by the relative frequencies of different prey types in the environment. Yet, how predators adjust their selection for prey according to their environmental frequency is often overlooked. Here, we assessed frequency dependent selection of prey by dingoes and foxes in the Australian desert, biannually, across a nine-year period (2007–2016). Both predators exhibited potentially destabilizing, negative frequency dependent selection for prey. Foxes persisted to preferentially consume a threatened, native rodent (Notomys fuscus) when it was environmentally scarce. Bolstered by the observation that N.fuscus occurs at low densities in areas where foxes are common, our results suggest that N.fuscus is particularly vulnerable to predation by this predator; possibly because it is naïve and/or lacks adaptations to avoid or escape predation by the relatively recently introduced fox. Dingoes tended to consume reptiles when they were scarce; potentially constituting a conservation concern if selected reptilian taxa are threatened. Foxes avoided, thus were unlikely to control populations of overabundant kangaroos, while both foxes and dingoes showed a preference for, and may therefore control populations of invasive rabbits. The integration of our results into the relative suites of (de)stabilizing influences exerted by dingoes and foxes is important to provide a more dynamic insight into how each predator impacts their naturally fluctuating ecosystems.
Remnant habitat patches provide high value for a wide range of insect species in a timber plantation mosaic
Authors: van der Mescht Aileen C , Pryke James S , Gaigher René , Samways Michael J
Published: March 2023

Species present in transformed landscapes utilise resources from either the transformed patches, natural patches, or both. Depending on the degree to which species are specialised, species-specific responses to landscape transformation is both varied and dynamic. Understanding species-specific responses across a landscape is therefore essential to make informed conservation decisions. We investigate how spillover of stenotopic, cultural, and ubiquitous insect species respond to the different edge combinations present in a timber plantation mosaic. We use a multi-taxon approach, sampling two distinct insect assemblages (ground and foliage) across four different biotopes in a grassland-forest-plantation landscape in the Midlands of KwaZulu-Natal, South Africa, which forms part of the Maputaland-Pondoland-Albany biodiversity hotspot. We show that in this landscape, ecological networks consisting of natural grassland and forest supported high insect diversity in both ground and foliage assemblages. The foliage assemblage displayed stronger responses to the different biotope combinations than the ground assemblage. There was remarkably little spillover of habitat specialist species of either the ground or foliage assemblages from grassland or forest into the plantation stands. The few species associated with plantation stands (cultural species) had consistent levels of spillover across different types of plantation blocks, but not into the natural areas. Natural biotopes in this landscape conserved many habitat specialists, whereas plantations maintained low levels of diversity. Thus, we recommend that conservation practitioners consider the fidelity and spillover of the species present in the local landscape before designing conservation plans in these dynamic production landscapes.
Using Oncotype DX breast recurrence score® assay to define the role of neoadjuvant endocrine therapy in early-stage hormone receptor-positive breast cancer
Authors: Taylor Caitlin , Meisel Jane , Foreman Aimee J. , Russell Christy , Bandyopadhyay Dipankar , Deng Xiaoyan , Floyd Lisa , Zelnak Amelia , Bear Harry , O’Regan Ruth
Published: March 2023

Purpose

The role of neoadjuvant endocrine therapy in the treatment of patients with early-stage, hormone receptor-positive (HR +) breast cancer is not well defined. Tools to better determine which patients may benefit from neoadjuvant endocrine therapy versus chemotherapy or upfront surgery remain an unmet need.

Methods

We assessed the rate of clinical and pathologic complete response (cCR, pCR) among a pooled cohort of patients with early-stage HR + breast cancer who had been randomized to neoadjuvant endocrine therapy or neoadjuvant chemotherapy in two earlier studies to understand better how outcomes varied by Oncotype DX Breast Recurrence Score® assay.

Results

We observed that patients with intermediate RS results had no statistically significant differences in pathologic outcomes at the time of surgery based on whether they received neoadjuvant endocrine therapy or neoadjuvant chemotherapy, suggesting that a subgroup of women with a RS 0–25 may omit chemotherapy without compromising outcomes.

Conclusion

These data suggest that Recurrence Score® (RS) results may serve as a useful tool in treatment decision-making in the neoadjuvant setting.
Antitumor activity of the PI3K δ-sparing inhibitor MEN1611 in PIK3CA mutated, trastuzumab-resistant HER2 + breast cancer
Authors: Fiascarelli Alessio , Merlino Giuseppe , Capano Stefania , Talucci Simone , Bisignano Diego , Bressan Alessandro , Bellarosa Daniela , Carrisi Corrado , Paoli Alessandro , Bigioni Mario , Tunici Patrizia , Irrissuto Clelia , Salerno Massimiliano , Arribas Joaquin , de Stanchina Elisa , Scaltriti Maurizio , Binaschi Monica
Published: March 2023

Purpose

Dysregulation of the PI3K pathway is one of the most common events in breast cancer. Here we investigate the activity of the PI3K inhibitor MEN1611 at both molecular and phenotypic levels by dissecting and comparing its profile and efficacy in HER2 + breast cancer models with other PI3K inhibitors.

Methods

Models with different genetic backgrounds were used to investigate the pharmacological profile of MEN1611 against other PI3K inhibitors. In vitro studies evaluated cell viability, PI3K signaling, and cell death upon treatment with MEN1611. In vivo efficacy of the compound was investigated in cell line- and patient-derived xenografts models.

Results

Consistent with its biochemical selectivity, MEN1611 demonstrated lower cytotoxic activity in a p110δ-driven cellular model when compared to taselisib, and higher cytotoxic activity in the p110β-driven cellular model when compared to alpelisib. Moreover, MEN1611 selectively decreased the p110α protein levels in PIK3CA mutated breast cancer cells in a concentration- and proteasome-dependent manner. In vivo, MEN1611 monotherapy showed significant and durable antitumor activity in several trastuzumab-resistant PIK3CA-mutant HER2 + PDX models. The combination of trastuzumab and MEN1611 significantly improved the efficacy compared to single agent treatment.

Conclusions

The profile of MEN1611 and its antitumoral activity suggest an improved profile as compared to pan-inhibitors, which are limited by a less than ideal safety profile, and isoform selective molecules, which may potentially promote development of resistance mechanisms. The compelling antitumor activity in combination with trastuzumab in HER2 + trastuzumab-resistant, PIK3CA mutated breast cancer models is at the basis of the ongoing B-Precise clinical trial (NCT03767335).
Implications for surveillance for breast cancer patients based on the internally and externally validated BRENDA-metastatic recurrence score
Authors: Ebner Florian , Salmen Jessica , Dayan Davut , Kiesel Matthias , Wolters Regine , Janni Wolfgang , Wöckel Achim , Wischnewsky Manfred
Published: March 2023

Purpose

Although the incidence of distant relapse is decreasing, 20–30% of patients with early breast cancer die of metastasis. The aim of this study is to characterize patients with metastasis-free survival(MFS) less than 5 years, to analyze the most probable site of metastases according to the internally and externally validated BRENDA-score. The BRENDA-score is a combination of the biological subtype and clinical staging.

Method

3832 patients with primary diagnosis of breast cancer and either distant metastatic recurrence within 5 years or MFS ≥ 5 years were assigned to this study. Patients were classified for metastatic recurrence according to the BRENDA-score. 1765 patients were in a validation set. Statistical methods were Kaplan–Meier curves, Cox regression analysis, Exhausted CHAID, likelihood-ratio tests and the Nearest Neighbor Estimation method.

Results

There was a significant(p < 0.001) difference between the Kaplan–Meier MFS-functions of M0-patients stratified by BRENDA-score. The BRENDA score outperforms intrinsic subtypes and the Nottingham prognostic score. It fits the original data and the validation set equally well (p = 0.179).There was a significant(p < 0.001) difference between mean BRENDA-Index for patients with MFS < 5y(21.0 ± 9.0) and patients with MFS ≥ 5y(mean BRENDA-Index 11.7 ± 8.2). 55.6% of the very high risk patients(BRENDA-Index ≥ 27) had metastases within 5 years. The most likely primary metastatic site was bone(30%) followed by liver(19%) and lung(18%). The discriminatory ability(areas under the time dependent ROC curve) of the BRENDA score is good to acceptable for the first 5 years. In the very low/low risk (intermediate, high/very high) risk group 50% of all metastases were diagnosed within 26 months. Guideline adherence had a highly significant influence on outcome independent of the risk group.

Conclusion

The evaluation showed that the BRENDA-Score is a robust predictive tool for breast cancer recurrence and site of metastases in the first five years after diagnosis. It outperforms intrinsic subtypes and the Nottingham prognostic score. The BRENDA-score could be a tool for a risk orientated and targeted follow up.
Goal-Based Private Sustainability Governance and Its Paradoxes in the Indonesian Palm Oil Sector
Authors: Grabs Janina , Garrett Rachael D.
Published: March 2023

In response to stakeholder pressure, companies increasingly make ambitious forward-looking sustainability commitments. They then draw on corporate policies with varying degrees of alignment to disseminate and enforce corresponding behavioral rules among their suppliers and business partners. This goal-based turn in private sustainability governance has important implications for its likely environmental and social outcomes. Drawing on paradox theory, this article uses a case study of zero-deforestation commitments in the Indonesian palm oil sector to argue that goal-based private sustainability governance’s characteristics set the stage for two types of paradoxes to emerge: performing paradoxes between environmental, social, and economic sustainability goals, and organizing paradoxes between cooperation and competition approaches. Companies’ responses to these paradoxes, in turn, can explain the lack of full goal attainment and differential rates of progress between actors. These results draw our attention to the complexities hidden behind governance through goal setting in the corporate space, and raise important questions about the viability of similar strategies such as science-based targets and net-zero goals.
Pharmacological Inhibition of P-Rex1/Rac1 Axis Blocked Angiotensin II-Induced Cardiac Fibrosis
Authors: Pan Jianyuan , Liu Ming , Su Huimin , Hu Hao , Chen Hongwu , Ma Likun
Published: March 2023

Purpose

Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor-1 (P-Rex1), as one of the members of Rac-GEFs, has been proven to play a critical role in cancer progression and metastasis. Nonetheless, its role in cardiac fibrosis remains elusive. In the present study, we aimed to investigate whether and how the P-Rex1 mediates AngII-induced cardiac fibrosis.

Method

A cardiac fibrosis mouse model was established by chronic AngII perfusion. The heart structure, function, pathological changes of myocardial tissues, oxidative stress, and cardiac fibrotic protein expression were determined in an AngII induced mouse model. To provide a molecular mechanism for P-Rex1 involvement in cardiac fibrosis, a specific inhibitor or siRNA was used to block P-Rex1, and target the relationship between Rac1-GTPase and its downstream effector.

Results

Blocking P-Rex1 showed down-regulation of its downstream effectors such as the profibrotic transcriptional regulator Paks, ERK1/2, and ROS generation. Intervention treatment with P-Rex1 inhibitor 1A-116 ameliorated AngII-induced abnormalities in heart structure and function. Moreover, pharmacological inhibition of the P-Rex1/Rac1 axis showed a protective effect in AngII-induced cardiac fibrosis through the down-regulation of collagen1, CTGF, and α-SMA expression.

Conclusion

Our findings demonstrated for the first time that P-Rex1 was an essential signaling mediator in CFs activation and subsequent cardiac fibrosis, and 1A-116 could be a potential pharmacological development drug.
Effect of pretreated cow dung fiber on rheological and fatigue properties of asphalt binder
Authors: Niu Dongyu , Zhang Zhao , Gao Yangming , Li Yuanxiao , Yang Zhengxian , Niu Yanhui
Published: March 2023

Cow dung waste has caused severe environmental pollution and public health issues in China. In this study, the cow dung residues were used as a cheap renewable fiber to modify asphalt binder, providing a new solution for the proper disposal of cow dung waste. Three cow dung fibers with two lengths were prepared using different treatments, including original cow dung fiber (CDF), surface treatments of cow dung fiber (STCDF) and alkali treatments of cow dung fiber (ATCDF). The physicochemical properties of CDF, STCDF and ATCDF were analyzed by scanning electron microscope (SEM) and thermogravimetry (TG). The viscidity, rheological properties and fatigue characteristics of CDF modified asphalt binders (CDFMA) were evaluated using Brookfield viscometer and dynamic shear rheometer. The results showed that the rough surfaces of STCDF and ATCDF improved their thermal stability. STCDF and ATCDF enhanced the resistance to permanent deformation under high temperature conditions of modified asphalt binder. STCDF modified asphalt binders exhibited the best viscosity and rheological performance. The increase of fiber length was positively correlated with the high temperature deformation resistance of CDFMA. CDF, STCDF and ATCDF inhibited fatigue cracking of modified asphalt binders compared to base asphalt binders. ATCDF modified asphalt binders exhibited higher fatigue life and smaller crack under the same cyclic loading. The increase in fiber length had a slight improvement on the fatigue resistance of modified asphalt binders.
Sense of Belonging at School and on Social Media in Adolescence: Associations with Educational Achievement and Psychosocial Maladjustment
Authors: Fabris Matteo Angelo , Settanni Michele , Longobardi Claudio , Marengo Davide
Published: March 2023

Belongingness is a key factor in the psychological development and school adjustment of children and adolescents. Going beyond the existing literature, the present study evaluated the association between two sources of belongingness, namely sense of belonging at school (SOBAS) and on social media (SOBOSM), and both psychological maladjustment and educational achievement. Sample consisted of 698 early-to-late adolescents (52.3% female, mean age = 13.79 ± 2.09). Both SOBAS and SOBOSM showed negative direct associations with psychological maladjustment. SOBOSM showed a negative direct association with educational achievement. Social media addiction mediated the links between both SOBAS and SOBOSM and psychological maladjustment and education achievement. Overall, findings suggest that adolescents reporting high sense of belonging both at school and on social media may at lower risk for psychological maladjustment. However, adolescents reporting low SOBAS and high SOBOSM may also be a greater risk of SMA, possibly impacting their psychological health and school adjustement.
Incorporating Indigenous voices in regional climate change adaptation: opportunities and challenges in the U.S. Pacific Northwest
Authors: Dent Lauren A. , Donatuto Jamie , Campbell Larry , Boardman Marnie , Hess Jeremy J. , Errett Nicole A.
Published: March 2023

As the impacts of climate change increasingly and disproportionately affect indigenous peoples, equitable approaches to regional climate change adaptation must center the voices, needs, and priorities of Indigenous communities. Although the tribal climate change principles identify actionable recommendations to address the unique needs of Indigenous peoples in the contexts of climate change adaptation efforts undertaken at the Federal level in the United States (U.S.), there has yet to be exploration of how such principles might be applied at the regional level. Through semi-structured qualitative interviews with 18 representatives from inter-Tribal organizations and non-Tribal organizations engaged in regional climate adaptation in the U.S. Pacific Northwest, this research sought to describe challenges faced by, and opportunities available to, non-Tribal entities when engaging with Tribes on regional climate adaptation initiatives. All respondents reported high levels of motivation to work with Tribes on climate adaptation and identified several perceived benefits of integrating Tribal partnerships and indigenous ways of knowing into regional climate adaptation initiatives. Respondents underscored the need for strong, trusted relationships that respect the sovereignty and priorities of Tribal nations to guide engagement. However, non-Tribal organizations’ own capacity constraints, perceived Tribal capacity constraints, and institutional cultures rooted in colonialism and structural racism were discussed as obstacles to meaningful engagement. As such, we identify an urgent need to prioritize sustained investments in both Tribal and non-Tribal actors’ partnership capacities and climate change adaptation capabilities to place Indigenous voices and needs at the forefront of regional climate change adaptation planning and implementation.