bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase I trial of the pan-ERBB inhibitor neratinib combined with the MEK inhibitor trametinib in patients with advanced cancer with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation or KRAS mutation
Authors: Piha-Paul Sarina A. , Tseng Chieh , Tran Hai T. , Gao Meng , Karp Daniel D. , Subbiah Vivek , Tsimberidou Apostolia Maria , Kawedia Jitesh D. , Fu Siqing , Pant Shubham , Yap Timothy A. , Morris Van K. , Kee Bryan K. , Blum Murphy Mariela , Lim JoAnn , Meric-Bernstam Funda
Published: June 2023

Purpose

Aberrant alterations of ERBB receptor tyrosine kinases lead to tumorigenesis. Single agent therapy targeting EGFR or HER2 has shown clinical successes, but drug resistance often develops due to aberrant or compensatory mechanisms. Herein, we sought to determine the feasibility and safety of neratinib and trametinib in patients with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation and KRAS mutation.

Methods

Patients with actionable somatic mutations or amplifications in ERBB genes or actionable KRAS mutations were enrolled to receive neratinib and trametinib in this phase I dose escalation trial. The primary endpoint was determination of the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Secondary endpoints included pharmacokinetic analysis and preliminary anti-tumor efficacy.

Results

Twenty patients were enrolled with a median age of 50.5 years and a median of 3 lines of prior therapy. Grade 3 treatment-related toxicities included: diarrhea (25%), vomiting (10%), nausea (5%), fatigue (5%) and malaise (5%). The MTD was dose level (DL) minus 1 (neratinib 160 mg daily with trametinib 1 mg, 5 days on and 2 days off) given 2 DLTs of grade 3 diarrhea in DL1 (neratinib 160 mg daily with trametinib 1 mg daily). The treatment-related toxicities of DL1 included: diarrhea (100%), nausea (55.6%) and rash (55.6%). Pharmacokinetic data showed trametinib clearance was significantly reduced leading to high drug exposures of trametinib. Two patients achieved stable disease (SD) ≥ 4 months.

Conclusion

Neratinib and trametinib combination was toxic and had limited clinical efficacy. This may be due to suboptimal drug dosing given drug–drug interactions.

Trial registration ID: NCT03065387.
Promoting genotype-independent plant transformation by manipulating developmental regulatory genes and/or using nanoparticles
Authors: Yan Tingwei , Hou Quancan , Wei Xun , Qi Yuchen , Pu Aqing , Wu Suowei , An Xueli , Wan Xiangyuan
Published: June 2023

Key message

This review summarizes the molecular basis and emerging applications of developmental regulatory genes and nanoparticles in plant transformation and discusses strategies to overcome the obstacles of genotype dependency in plant transformation.

Plant transformation is an important tool for plant research and biotechnology-based crop breeding. However, Plant transformation and regeneration are highly dependent on species and genotype. Plant regeneration is a process of generating a complete individual plant from a single somatic cell, which involves somatic embryogenesis, root and shoot organogeneses. Over the past 40 years, significant advances have been made in understanding molecular mechanisms of embryogenesis and organogenesis, revealing many developmental regulatory genes critical for plant regeneration. Recent studies showed that manipulating some developmental regulatory genes promotes the genotype-independent transformation of several plant species. Besides, nanoparticles penetrate plant cell wall without external forces and protect cargoes from degradation, making them promising materials for exogenous biomolecule delivery. In addition, manipulation of developmental regulatory genes or application of nanoparticles could also bypass the tissue culture process, paving the way for efficient plant transformation. Applications of developmental regulatory genes and nanoparticles are emerging in the genetic transformation of different plant species. In this article, we review the molecular basis and applications of developmental regulatory genes and nanoparticles in plant transformation and discuss how to further promote genotype-independent plant transformation.
The importance of wild plant resources in the Neolithic: a case study of the Late Neolithic lakeshore settlement of Grandson-Corcelettes, Les Pins (Switzerland)
Authors: Vandorpe Patricia , Akeret Örni , Kühn Marlu , Wick Lucia
Published: June 2023

The site of Grandson-Corcelettes, Les Pins is located at Lake Neuchâtel, Switzerland and was occupied during several phases of the Late Neolithic (between roughly 3000 and 2500 bc). Archaeobotanical analyses of the cultural layers revealed that, besides the cultivation of food plants, the inhabitants of Grandson used wild plant resources for many purposes. An estimation of the proportion of a selection of collected wild plants within the plant diet – based on calories – showed that they accounted for more than half of the calorific intake. This is in line with similar calculations performed for other Neolithic circum-Alpine settlements. The wild food plant spectrum indicates that most of them were gathered in the woodlands and semi-open habitats close to the village, whereas the riparian forest only seemed to play a marginal role. The analysis of macrofossils and pollen from dung pellets of goat and/or sheep showed that wild plants were also important as food for domestic animals, and that grazing took place in a variety of places, including forests, fallow fields and grassland-like habitats outside the village and throughout the year. Besides, there are indications that the nearby Jura mountains (reaching 1,600 m a.s.l. near the lakeshore villages) were exploited.
Depiction of an external classical field effects on a four-level W-configuration atom embedded in a coherent cavity field
Authors: Ali S. I.
Published: June 2023

This paper examines the dynamics of a W-configuration four-level atom in a quantized cavity field and the system driven by an external classical field. By applying some canonical transformations, we derive analytical solutions to the Schrödinger equation for the corresponding Hamiltonian. We have analyzed the impact of the external field and detuning parameters on the system’s relative entropy of coherence, Wigner function, and Pancharatnam phase. Our findings suggest that the external field parameter greatly affects the coherence of the system, whereas the detuning parameters may increase its maximum bounds. Furthermore, we have utilized the Wigner function as a tool to measure the quantumness and classicality of the system in its phase space. Our results indicate that the external field has a greater impact on the classicality of the system than the detuning parameters. Additionally, we have observed rapid oscillations in the dynamics of the Pancharatnam phase for large detuning values. It is worth noting that the external field reduces the number of phase jumps in the system.
Limb salvage in traumatic hemipelvectomy: case series with surgical management and review of the literature
Authors: Herold J. , Notov D. , Reeps C. , Schaser K. D. , Kamin K. , Mäder M. , Kleber C.
Published: June 2023

Background

Traumatic hemipelvectomies are rare and serious injuries. The surgical management was described in several case studies, with primary amputation often performed to save the patient's life.

Methods

We report of two survivors with complete traumatic hemipelvectomy resulting in ischemia and paralyzed lower extremity. Due to modern emergency medicine and reconstructive surgery, limb salvage could be attained. Long-term outcome with quality of life was assessed one year after the initial accident.

Results and conclusions

The patients were able to mobilize themselves and live an independent life. The extremities remained without function and sensation. Urinary continence and sexual function were present and the colostomy could be relocated in both patients. Both patients support limb salvage, even having difficulties and follow-up treatments. Concomitant cases are required to consolidate the findings.

Level of evidence

IV.
LAG3 in gastric cancer: it’s complicated
Authors: Ulase Dita , Behrens Hans-Michael , Krüger Sandra , Heckl Steffen M. , Ebert Ulrike , Becker Thomas , Röcken Christoph
Published: June 2023

Purpose

Lymphocyte activation gene 3 (LAG3) is thought to contribute to T cell exhaustion within the tumor microenvironment of solid tumors. This study aimed to analyze the spatial distribution of LAG3 + cells in relation to clinicopathological and survival data in a large set of 580 primary resected and neoadjuvantly treated gastric cancers (GC).

Methods

LAG3 expression was evaluated in tumor center and invasive margin using immunohistochemistry and whole-slide digital image analysis. Cases were divided into LAG3-low and LAG3-high expression groups based on (1) median LAG3 + cell density, (2) cut-off values adapted to cancer-specific survival usingCutoff Finderapplication.

Results

Significant differences in spatial distribution of LAG3 + cells were observed in primarily resected GC, but not in neoadjuvantly treated GC. LAG3 + cell density showed evident prognostic value at following cut-offs: in primarily resected GC, 21.45 cells/mm2in tumor center (17.9 vs. 10.1 months,p = 0.008) and 208.50 cells/mm2in invasive margin (33.8 vs. 14.7 months,p = 0.006); and in neoadjuvantly treated GC, 12.62 cells/mm2(27.3 vs. 13.2 months,p = 0.003) and 123.00 cells/mm2(28.0 vs. 22.4 months,p = 0.136), respectively. Significant associations were found between LAG3 + cell distribution patterns and various clinicopathological factors in both cohorts. In neoadjuvantly treated GC, LAG3 + immune cell density was found to be an independent prognostic factor of survival (HR = 0.312, 95% CI 0.162–0.599,p < 0.001).

Conclusion

In this study, a higher density of LAG3 + cells was associated with favorable prognosis. Current results support the need for extended analysis of LAG3. Differences in the distribution of LAG3 + cells should be considered, as they could influence clinical outcomes and treatment responses.

Graphical abstract
Widespread distribution and altered pain processing in head and neck cancer survivors at long-term after treatment
Authors: Hernández Sofía Hernández , Guía Vanessa Gabriela Jerviz , Núñez Javier Martín , Ciuró Alejandro Heredia , Otero Alba Navas , Mohedo Esther Díaz , Valenza Marie Carmen
Published: June 2023

Purpose

Radiotherapy (RT) treatment in head and neck cancer (HNC) patients may induce long-term sequels as pain, which nowadays is not fully understand. Therefore, there is a need of characterization of pain features in HNC to enhance after oncology treatment management. Head and neck cancer survivors develop chronic pain after radiotherapy treatment. The purpose of the current study is to evaluate the presence of pain, pain distribution, and pain processing by means of patient reported outcomes and quantitative sensory testing.

Methods

Pain pressure threshold (PPT), temporal summation (TS), Brief Pain Inventory (BPI), Widespread Pain Index (WPI), The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, and EuroQol5D5L were assessed in 20 head and neck cancer survivors (sHNC) and 20 health-related sex and age-matched controls.

Results

The sHNC present lower PPT values in both the affected and non-affected side than did the healthy controls, especially in the widespread pain in the body, an altered TS in both affected and non-affected side and lower scores in quality of life and arm dysfunction.

Conclusions

Following radiotherapy treatment after 1 year, sHNC present widespread pain, hypersensitivity in the radiated area, altered pain processing, upper limb affection, and a QoL diminution. These data provide evidence that a peripheral and central sensitization is happening in sHNC. Future efforts should focus on preventing pain after oncologic treatment. The comprehension about pain and its features in sHNC enhance health professional understanding and allows to tailor an optimal patient-targeted pain treatment.
Histone modification as a drug resistance driver in brain tumors ⁎
Authors: Xi Guifa , Mania-Farnell Barbara , Lei Ting , Tomita Tadanori
Published: June 2023

Patients with brain tumors, specifically, malignant forms such as glioblastoma, medulloblastoma and ependymoma, exhibit dismal survival rates despite advances in treatment strategies. Chemotherapeutics, the primary adjuvant treatment for human brain tumors following surgery, commonly lack efficacy due to either intrinsic or acquired drug resistance. New treatments targeting epigenetic factors are being explored. Post-translational histone modification provides a critical regulatory platform for processes such as chromosome condensation and segregation, apoptosis, gene transcription, and DNA replication and repair. This work reviews how aberrant histone modifications and alterations in histone-modifying enzymes can drive the acquisition of drug resistance in brain tumors. Elucidating these mechanisms should lead to new treatments for overcoming drug resistance.
Penguin Huddling: A Continuum Model
Authors: Harris Samuel J. , McDonald N. R.
Published: June 2023

Penguins huddling in a cold wind are represented by a two-dimensional, continuum model. The huddle boundary evolves due to heat loss to the huddle exterior and through the reorganisation of penguins as they seek to regulate their heat production within the huddle. These two heat transfer mechanisms, along with area, or penguin number, conservation, gives a free boundary problem whose dynamics depend on both the dynamics interior and exterior to the huddle. Assuming the huddle shape evolves slowly compared to the advective timescale of the exterior wind, the interior temperature is governed by a Poisson equation and the exterior temperature by the steady advection-diffusion equation. The exterior, advective wind velocity is the gradient of a harmonic, scalar field. The conformal invariance of the exterior governing equations is used to convert the system to a Polubarinova-Galin type equation, with forcing depending on both the interior and exterior temperature gradients at the huddle boundary. The interior Poisson equation is not conformally invariant, so the interior temperature gradient is found numerically using a combined adaptive Antoulas-Anderson and least squares algorithm. The results show that, irrespective of the starting shape, penguin huddles evolve into an egg-like steady shape. This shape is dependent on the wind strength, parameterised by the Péclet number Pe, and a parameter $\beta $
β
which effectively measures the strength of the interior self-generation of heat by the penguins. The numerical method developed is applicable to a further five free boundary problems.
Processing societal expectations: entrepreneurship initiative decision-making at a research university
Authors: Tuunainen Juha , Kantasalmi Kari
Published: June 2023

Deploying systems-theoretical conceptuality, this paper improves understanding of the organisational consequences of the intensified societal engagement of a research university. Aligning its work with Luhmannian organisational analysis, it addresses the dynamic interplay between two modes of administrative decision-making communication, namely, the traditional professional administration and the New-Public-Management-oriented (NPM) managerial techniques. Our research observes how the politico-economic conditions of the society translate into the university’s decisions concerning an initiative to engage in start-up entrepreneurship. The article contributes to higher education literature by showing that the university’s professional administration is a discrete organisational function internally differentiated into specialised administrative branches, each of which operates according to a sense-making regime associated with its primary societal system reference, such as education, science and the economy. The article also demonstrates the structurally conditioned differences in branch-specific temporalisations of the entrepreneurial initiative during decision-making. Inspired by the Luhmannian view on temporality, we demonstrate how administrative decisions synchronise the varied structural time horizons within the university’s professional administration. Focus on temporality in decision-making thus allows us to see how the NPM-inspired managerial techniques are operationalised in administrative communication at universities. Consequently, the paper argues that university administration is a complex dynamic entity, which varyingly aligns itself to national policy scripts, and only selectively enacts features of a global trend known as NPM.
Combinatorics and preservation of conically stable polynomials
Authors: Codenotti Giulia , Gardoll Stephan , Theobald Thorsten
Published: June 2023

Given a closed, convex cone $$K\subseteq \mathbb {R}^n$$

K
⊆

R

n

, a multivariate polynomial $$f\in \mathbb {C}[\textbf{z}]$$

f
∈
C
[
z
]

is called K-stable if the imaginary parts of its roots are not contained in the relative interior of K. If K is the nonnegative orthant, K-stability specializes to the usual notion of stability of polynomials. We develop generalizations of preservation operations and of combinatorial criteria from usual stability toward conic stability. A particular focus is on the cone of positive semidefinite matrices (psd-stability). In particular, we prove the preservation of psd-stability under a natural generalization of the inversion operator. Moreover, we give conditions on the support of psd-stable polynomials and characterize the support of special families of psd-stable polynomials.
Sales prices, social rigidity and the second home property market
Authors: Hjalager Anne-Mette , Sørensen Michael Tophøj , Steffansen Rasmus Nedergård , Staunstrup Jan Kloster
Published: June 2023

Second homes are much valued as recreational resources and also as important commodities on the property market. This study examines the trading patterns and regional price development of Danish second homes from 1992 to 2020. Second home sales volumes and prices reflect the general economic booms and busts and also the possibilities to rent out the property on sharing platforms. However, across regional clusters and over time, property price developments suggest a significant social rigidity in preferences and prospects. The investment and financialization logics and the underlying guiding conspicuous consumption behavior has not changed as an effect of the increased demand during the early phases of the COVID-19 pandemic. When controlling for factors such as house and land plot size, building year, location attractiveness the strong social class and spatial rigidity is reproduced in the data. The shifting of wealth accumulated in the second homes between generations supports the same tendency, and taxation does not rebalance regional effects. Accordingly, only to a limited extent does owning a second home contribute to social equality, even if some second-home owners and policy makers tend to think otherwise. Economic measures in planning and governance portfolios are found to be negligible.
Parity Violation Energy Difference Calculation of Atropisomers
Authors: Vadivel Dhanalakshmi , Dondi Daniele
Published: June 2023

Enantiomers have a different energy due to the parity violation effects. Up to now, these effects are difficult to calculate and their final effect on the choice of one enantiomer in the homochirality issue is still a matter of debate. Nevertheless, many scientists support the role of this tiny energy difference in the triggering of homochirality. In this work, we studied the energy difference in atropisomers, a class of stereoisomers in which the chirality is given by the block of rotation around one bond. Atropisomers might have a low energy barrier for the interconversion and this is interesting for the equilibration of the two enantiomers and the choice of the most stable enantiomer. Moreover, structures might be extended like in the case of polymers or crystals having helical framework and thus giving an additive effect on the parity violation energy of the whole structure. The parity violation energy difference here is discussed with the correlation on the general structure of the final molecule giving a qualitative model to predict the sign of local contributions of atoms.
Fineness of grain and the hylomorphism of experience
Authors: Settegast Sascha
Published: June 2023

A central objection to McDowell’s conceptualism about empirical content concerns the fine-grained phenomenology of experience, which supposedly entails that the actual content of experience cannot be matched in its particularity by our concepts. While McDowell himself has answered this objection in recourse to the possibility of demonstrative concepts, his reply has engendered a plethora of further objections and is widely considered inadequate. I believe that McDowell’s critics underestimate the true force of his reply because they tend to read unrecognized empiricist presuppositions into his account of experience. To show this, I introduce a new hylomorphic reading of McDowell’s account of experience and argue that the objections to his reply all rest on a specific empiricist assumption, which is untenable because it conflates the form of experience with its content. Consequently, conceptualism so understood can resist all of these objections, as I attempt to show by systematizing and answering them.
Construction of prediction model for KRAS mutation status of colorectal cancer based on CT radiomics
Authors: Cao Yuntai , Zhang Jing , Huang Lele , Zhao Zhiyong , Zhang Guojin , Ren Jialiang , Li Hailong , Zhang Hongqian , Guo Bin , Wang Zhan , Xing Yue , Zhou Junlin
Published: June 2023

Background

In this study, we used computed tomography (CT)-based radiomics signatures to predict the mutation status of KRAS in patients with colorectal cancer (CRC) and to identify the phase of radiomics signature with the most robust and high performance from triphasic enhanced CT.

Methods

This study involved 447 patients who underwent KRAS mutation testing and preoperative triphasic enhanced CT. They were categorized into training (n = 313) and validation cohorts (n = 134) in a 7:3 ratio. Radiomics features were extracted using triphasic enhanced CT imaging. The Boruta algorithm was used to retain the features closely associated with KRAS mutations. The Random Forest (RF) algorithm was used to develop radiomics, clinical, and combined clinical–radiomics models for KRAS mutations. The receiver operating characteristic curve, calibration curve, and decision curve were used to evaluate the predictive performance and clinical usefulness of each model.

Results

Age, CEA level, and clinical T stage were independent predictors of KRAS mutation status. After rigorous feature screening, four arterial phase (AP), three venous phase (VP), and seven delayed phase (DP) radiomics features were retained as the final signatures for predicting KRAS mutations. The DP models showed superior predictive performance compared to AP or VP models. The clinical–radiomics fusion model showed excellent performance, with an AUC, sensitivity, and specificity of 0.772, 0.792, and 0.646 in the training cohort, and 0.755, 0.724, and 0.684 in the validation cohort, respectively. The decision curve showed that the clinical–radiomics fusion model had more clinical practicality than the single clinical or radiomics model in predicting KRAS mutation status.

Conclusion

The clinical–radiomics fusion model, which combines the clinical and DP radiomics model, has the best predictive performance for predicting the mutation status of KRAS in CRC, and the constructed model has been effectively verified by an internal validation cohort.
Impact-Dissipating Capacity of Fiber-Reinforced Polymer Samples, Fabricated by Fused Filament Fabrication
Authors: Tsamos Dimitris , Zyganitidis Ioannis , Fasnakis Dimitris , Ganatsios Stavros , Ntinas Nikolaos , Maropoulos Stergios , Tsouknidas Alexander
Published: June 2023

The use of additive manufacturing for the fabrication of sacrificial cladding is becoming increasingly popular as it facilitates the production of complex yet space-saving protective structures. Despite this, the effect of several structural parameters on their capacity to mitigate high-velocity impacts remains elusive. Toward this end, the shock-mitigating capacity of various short fiber-reinforced polymer samples was evaluated regarding impact velocity and mass (raging from 1 to 8.3 m/s and 5.5 to 7.5 Kg, respectively). Among the assessed parameters were peak force (measured to vary by up to 46.6%), max. and mean deceleration values (with max. differences documented at 29.5% and 48.2%, respectively) and cushion factor. As expected, the progressive crushing modes differed significantly across the spectrum of the tested samples. Structural failure involved the growth of inter- and intra-laminar cracks, fiber-matrix de-bonding and de-lamination, which was dependent on equivalent pore volume fraction and compressive strength. Increasing infill density led in most cases to higher peak forces during impact, as did the deposition of more solid peripheral layers, with the latter producing a superior deceleration plateau. Evaluated collectively, the results indicate that an infill density of 37% with 4 solid external (protective) layers exhibited the superior impact response among the tested samples.
Die proximale Humerusfraktur: Ist die Operation immer die beste Wahl
Authors: Fenwick Annabel , Schreiner Sabine , Bund Theresa , Gilbert Fabian , Reichel Thomas , Meffert Rainer , Eden Lars
Published: June 2023

Hintergrund

Proximale Humerusfrakturen gehören zu den dritthäufigsten, osteoporotischen Verletzungen mit steigender Inzidenz. Die Indikationsstellung wird weiterhin kontrovers diskutiert. Ziel unserer Studie war es herauszufinden, ob der Trend zur konservativen Therapie gerechtfertigt ist und sich hiermit v. a. beim geriatrischen Patienten vergleichbare, reproduzierbare Ergebnisse erreichen lassen.

Material und Methoden

In die retrospektive Single-center-Studie wurden 128 Patienten mit konservativer und kopferhaltender operativer Therapie zwischen 2013 und 2015 eingeschlossen und davon wurden 91 nachuntersucht. Demografische Daten, operative Versorgung sowie Komplikationen wurden erhoben. Eine Follow-up-Untersuchung fand statt, in der Subjective Shoulder Value (SSV), visuelle Analogskala (VAS), Disability of Arm, Shoulder and Hand Questionnaire (DASH), Constant Murley Score (CMS) und Bewegungsausmaß erhoben wurden. Eine radiologische Auswertung wurde durchgeführt.

Ergebnisse

In den Scores wurden folgende Ergebnisse für konservative und operative Therapie erzielt (konservativ: VAS Schmerz 0,89 Punkte, CMS abs. 70,7 Punkte, DASH: 16,5 Punkte; operativ: VAS Schmerz 1,7 Punkte, CMS abs. 63,5 Punkte, DASH: 24,2 Punkte). Es zeigte sich kein signifikanter Unterschied zwischen Nagel- und Plattenosteosynthese. Die Komplikationsrate betrug 20 %. Die konservative Gruppe erzielte ein besseres Bewegungsausmaß. Die dislozierten Frakturen waren auffallend, wenngleich nicht statistisch signifikant schlechter im Vergleich zu den Neer-1-Frakturen und nur leichtgradig schlechter als die operativ versorgten Patienten.

Schlussfolgerung

Die Behandlung der proximalen Humerusfraktur bleibt weiterhin eine individuelle Entscheidung abhängig von Funktionsanspruch, Alter und Komorbiditäten. Die konservative Therapie kann in Erwägung gezogen werden, teils auch bei formell bestehender Operationsindikation (v. a. 2‑ und 3‑Part-Frakturen), da sich hiermit vergleichbare Langzeitergebnisse mit hoher Patientenzufriedenheit und reduziertem (perioperativem) Risiko erzielen lassen.
Layout optimization of steel reinforcement in concrete structure using a truss-continuum model
Authors: Chen Anbang , Lin Xiaoshan , Zhao Zi-Long , Xie Yi Min
Published: June 2023

Owing to advancement in advanced manufacturing technology, the reinforcement design of concrete structures has become an important topic in structural engineering. Based on bi-directional evolutionary structural optimization (BESO), a new approach is developed in this study to optimize the reinforcement layout in steel-reinforced concrete (SRC) structures. This approach combines a minimum compliance objective function with a hybrid truss-continuum model. Furthermore, a modified bi-directional evolutionary structural optimization (M-BESO) method is proposed to control the level of tensile stress in concrete. To fully utilize the tensile strength of steel and the compressive strength of concrete, the optimization sensitivity of steel in a concrete–steel composite is integrated with the average normal stress of a neighboring concrete. To demonstrate the effectiveness of the proposed procedures, reinforcement layout optimizations of a simply supported beam, a corbel, and a wall with a window are conducted. Clear steel trajectories of SRC structures can be obtained using both methods. The area of critical tensile stress in concrete yielded by the M-BESO is more than 40% lower than that yielded by the uniform design and BESO. Hence, the M-BESO facilitates a fully digital workflow that can be extremely effective for improving the design of steel reinforcements in concrete structures.
Rethinking Vulnerability as a Radically Ethical Device: Ethical Vulnerability Analysis and the EU’s “Migration Crisis”
Authors: Da Lomba Sylvie , Vermeylen Saskia
Published: June 2023

We reinvigorate vulnerability theory as a radically ethical device — ethical vulnerability analysis. We bring together fuller vulnerability analysis as theorized by Fineman and Grear in conversation with Levinas and Derrida’s radical vulnerability and the ethics of hospitality to construct a theoretical framework that is firmly anchored in the realities of the everyday that are vulnerability and migration. This novel framework offers a thinking space to subvert approaches to migrants and migration as it compels us to come face-to face with the “other”, which in turn renders the political accountable by her.

We deploy ethical vulnerability analysis to deconstruct the EU’s “migration crisis” and investigate whether the activation of temporary protection for displaced persons from Ukraine signifies a humanizing turn in the EU’s asylum and migration policies. In this regard, we submit that this hospitable moment constitutes an “exception to the rule” rather than a paradigm shift.
Basic psychological needs and suicidal ideation: testing an integrative model in referred and non-referred adolescents
Authors: Nieto-Casado Francisco J. , Vansteenkiste Maarten , Brenning Katrijn , Oliva Alfredo , Rodríguez-Meirinhos Ana , Antolín-Suárez Lucía
Published: June 2023

This study tested an integrative model linking experiences of need frustration and need satisfaction with suicidal ideation through a risk-enhancing (via anxious-depressive symptoms) and a risk-reducing pathway (via positive cognitions) in adolescents. The generalizability of the model based on the clinical status of the participants was also explored. A matched sample of referred (n = 210) and non-referred (n = 210) adolescents aged between 12 and 17 years old completed self-report measures of psychological need-based experiences, suicidal ideation, positive cognitions, and anxious-depressive symptoms. Structural equation modeling was used to explore the proposed model. Mediation analysis showed that need frustration was positively associated with suicidal ideation through anxious-depressive symptoms, while need satisfaction was negatively associated with suicidal ideation through positive cognitions. Invariance analysis pointed to limited differences in the model associations as a function of clinical status. These initial findings suggest the relevance of consider need frustration and need satisfaction in explaining suicidal ideation. The integration of risk and protective factors and the study of the generalizability of the data across the clinical status of adolescents provide preliminary implications for the development of interventions to prevent suicidal ideation.
Anthropic Vulnerability of a Hydrothermal Mineral Deposit and Related Mining Heritage, a Case Study from a Medieval Gold-Silver Mining Area, Telkibánya, Hungary
Authors: Szepesi János , Sütő László , Novák Tibor József , Ésik Zsuzsanna , Benkó Zsolt , Gruber Péter , Mcintosh Richard William , Harangi Szabolcs , Lukács Réka
Published: June 2023

The movable geoheritage elements (minerals, fossils, rocks) are important part of geodiversity. Their anthropic vulnerability includes collection by geo-amateurs and professionals which has become a very popular activity in the last decades. The in situ protection of such geoheritage elements preserves their authenticity and integrity, but needs detailed inventory and assessment providing recommendation for geoconservation. The aim of this study is to investigate a medieval mining site of the Carpathians (Telkibánya, Hungary) where recent anthropic vulnerability related to mineral collecting. Earlier works emphasized the scientific, aesthetic, and geo-educational potential of the mineral association and mining heritage of the study area. Our field survey gives a review of medieval mining works and the current state of the surviving infrastructure identifies the major areas of mineral collecting disturbances and the integrity of the main and additional geological elements. Based on the degradation risk assessment, further conservation management initiatives are proposed by open collecting outcrops (exposure sites) and declared protection with controlled collecting (finite sites).
MOB kinase activator 1A acts as an oncogene by targeting PI3K/AKT/mTOR in ovarian cancer
Authors: Lei Jian , Xu Jing-Ying , Hu Min , Wu San-Gang , Zhou Juan
Published: June 2023

Background

To illuminate the precise roles of MOB Kinase Activator 1 A (MOB1A) in the development of ovarian cancer (OC).

Methods

MOB1A expression and clinical data of OC were obtained from the public database on gene expression and proteomics. Meanwhile, verification of expression was carried out in Gene Expression Omnibus, the Human Protein Atlas, and OC cell lines. The prognosis of MOB1A was explored in the Kaplan-Meier plotter. RNA interference and lentivirus vectors were applied to construct knockdown and overexpressed cell models. Changes in the malignant behaviors of OC cells were detected by cholecystokinin octopeptide cell counting kit, wound healing, colony formation assay, transwell, flow cytometry assays, and in vivo experiments. Changes in proteins in the PI3K and autophagy-related makers were detected by western blot analysis.

Results

The expression of MOB1A was significantly upregulated and accompanied by an inferior survival rate in OC. Knockdown of MOB1A inhibited the proliferation, invasion, migration, and cell cycle of OC cells, whereas induced cell autophagy. MOB1A upregulation had the opposite effects. In addition, bioinformatics analysis and western blot experiments showed that MOB1A plays an important role in the PI3K/AKT/mTOR pathway.

Conclusions

Our findings indicated that MOB1A is highly expressed and related to poor prognosis in OC. MOB1A plays a role in promoting the malignant biological behavior of tumor cells through PI3K/AKT/mTOR signaling pathway.
A Recommender Approach to Enable Effective and Efficient Self-Service Analytics in Data Lakes
Authors: Stach Christoph , Eichler Rebecca , Schmidt Simone
Published: June 2023

As a result of the paradigm shift away from rather rigid data warehouses to general-purpose data lakes, fully flexible self-service analytics is made possible. However, this also increases the complexity for domain experts who perform these analyses, since comprehensive data preparation tasks have to be implemented for each data access. For this reason, we developed BARENTS, a toolset that enables domain experts to specify data preparation tasks as ontology rules, which are then applied to the data involved. Although our evaluation of BARENTS showed that it is a valuable contribution to self-service analytics, a major drawback is that domain experts do not receive any semantic support when specifying the rules. In this paper, we therefore address how a recommender approach can provide additional support to domain experts by identifying supplementary datasets that might be relevant for their analyses or additional data processing steps to improve data refinement. This recommender operates on the set of data preparation rules specified in BARENTS—i.e., the accumulated knowledge of all domain experts is factored into the data preparation for each new analysis. Evaluation results indicate that such a recommender approach further contributes to the practicality of BARENTS and thus represents a step towards effective and efficient self-service analytics in data lakes.
Investigation of the optimal indocyanine green dose in real-time fluorescent cholangiography during laparoscopic cholecystectomy with an ultra-high-definition 4K fluorescent system: a randomized controlled trial
Authors: Liu Hui , Kuang Jiao , Xu Yujie , Li Tianyang , Li Peilin , Huang Zisheng , Zhang Shuai , Weng Jiefeng , Lai Yueyuan , Wu Zhaofeng , Lin Fan , Gu Weili , Huang Yu
Published: June 2023

This study aimed to investigate the indocyanine green (ICG) dose in real‐time fluorescent cholangiography during laparoscopic cholecystectomy (LC) with a 4K fluorescent system. A randomized controlled clinical trial was conducted in patients who underwent LC for treatment of cholelithiasis. Using the OptoMedic 4K fluorescent endoscopic system, we compared four different doses of ICG (1, 10, 25, and 100 µg) administered intravenously within 30 min preoperatively and evaluated the fluorescence intensity (FI) of the common bile duct and liver background and the bile-to-liver ratio (BLR) of the FI at three timepoints: before surgical dissection of the cystohepatic triangle, before clipping the cystic duct, and before closure. Forty patients were randomized into four groups, and 33 patients were fully analyzed, with 10 patients in Group A (1 µg), 7 patients in Group B (10 µg), 9 patients in Group C (25 µg), and 7 patients in Group D (100 µg). The preoperative baseline characteristics were compared among groups (p > 0.05). Group A showed no or minimal FI in the bile duct and liver background, while Group D showed extremely high FIs in the bile duct and in the liver background at the three timepoints. Groups B and C presented with visible FI in the bile duct and low FI in the liver background. With increasing ICG doses, the FIs in the liver background and bile duct gradually increased at the three timepoints. The BLR, however, showed no increasing trend with an increasing ICG dose. A relatively high BLR on average was found in Group B, without a significant difference compared to the other groups (p > 0.05). An ICG dose ranging from 10 to 25 µg by intravenous administration within 30 min preoperatively was appropriate for real‐time fluorescent cholangiography in LC with a 4K fluorescent system. Registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR No: ChiCTR2200064726).
AI-Based Estimation of Swelling Stress for Soils in South Africa
Authors: Aneke Frank I. , Onyelowe Kennedy C. , Ebid Ahmed M.
Published: June 2023

Soil swelling is one of the major causes of structural failure, due to excessive moisture saturation and desaturation moisture. In situ measurement of swelling stress is somewhat impossible and requires tedious routine site observation. The use of artificial intelligence to predict the swelling stress of in situ soil is highly recommended, because of the complex behavior of soil upon moisture absorption. Because of this challenge, this study is channeled towards the prediction of swelling stress using basic geotechnical properties to save the challenges of repeating geotechnical experimental tests. In this study, the swelling stress of soils collected from 15 locations in 5 sites across South Africa has been predicted by using the artificial neural network (ANN), genetic programming (GP), and evolutionary polynomial regression (EPR)-based intelligent techniques. Multiple data were collected through laboratory experiments on the predictors: gravimetric moisture content (GMC), plasticity index (Ip), dry density (γd), free swell index (FSI), degree of saturation (S), matric suction (Ψm) and the target, and swelling stress (Psm). This predictive model was aimed at proposing models, which will help earthwork designers and constructors in South Africa overcome the rampant visit to the laboratory in search of soil data needed for geotechnical engineering designs. The soils showed their potential for swelling, which was eventually confirmed by the sensitivity analysis of the intelligent models. The performance indices of the models showed that ANN outclassed the other techniques with a performance accuracy of 93.6% at an error of 1.9%. Also, the sensitivity analysis showed that the plasticity index and matric suction were the most influential to the models. With the predicted models, future earthworks in South Africa can quickly forecast swelling stress prior to designs and construction more so in hydraulically bound environments.
Erythropoiesis in Cushing syndrome: sex-related and subtype-specific differences. Results from a monocentric study
Authors: Detomas M. , Deutschbein T. , Tamburello M. , Chifu I. , Kimpel O. , Sbiera S. , Kroiss M. , Fassnacht M. , Altieri B.
Published: June 2023

Context

Cushing syndrome (CS) is associated with different hematological abnormalities. Nevertheless, conflicting data about erythropoiesis in CS have been reported. Furthermore, it is unclear whether CS sex and subtype-specific alterations in red blood cells (RBC) parameters are present.

Objective

To investigate sex and subtype-specific changes in RBC in patients with CS at initial diagnosis and after remission.

Design

Retrospective, monocentric study including 210 patients with CS (women, n = 162) matched 1:1 for sex and age to patients with pituitary microadenomas or adrenal incidentalomas (both hormonally inactive). RBC parameters were evaluated at initial diagnosis and after remission.

Results

Women with CS had higher hematocrit (median 42.2 vs 39.7%), hemoglobin (14.1 vs 13.4 g/dl) and mean corpuscular volume (MCV) (91.2 vs 87.9 fl) compared to the controls (all p < 0.0001). Women with Cushing disease (CD) showed higher hematocrit, RBC and hemoglobin levels than those with ectopic Cushing (ECS) (all p < 0.005). Men with CS had lower hematocrit (42.9 vs 44.7%), RBC count (4.8 vs 5.1n*106/µl) and hemoglobin (14.2 vs 15.4 g/dl), but higher MCV (90.8 vs 87.5 fl) than controls (all p < 0.05). In men with CS, no subtype-specific differences were identified. Three months after remission hemoglobin decreased in both sexes.

Conclusion

CS is characterized by sexual and subtype-specific differences in RBC parameters. Compared to controls, women with CS showed higher hematocrit/hemoglobin levels, whereas men had lower hematocrit/hemoglobin, which further decreased directly after remission. Therefore, anemia should be considered as complication of CS in men. In women, differences in RBC parameters may help to differentiate CD from ECS.
A problem-specific parallel pareto local search for the reactive decision support of a special RCPSP extension
Authors: Cai Junqi , Peng Zhihong , Ding Shuxin , Wang Zhiguo , Wei Yue
Published: June 2023

The disaster information collection mission should be executed after the disaster occurs to provide details for the decision-makers. During the execution of the information collection mission, some disruptions may occur and prevent the resource used for information collection from completing the mission as planned. It is difficult for decision-makers to make reactive resource scheduling plan that optimize the mission’s execution time, quality, and cost at the same time under such circumstances. This article focuses on designing the reactive decision support algorithm for the disaster information collection resource scheduling, which aims to provide multi high-quality scheduling plans for decision-makers to choose. The problem studied in this article is modeled as an extension of Resource-Constrained Project Scheduling Problem (RCPSP). First, the basic problem formulation for a normal schedule and two disruption recovery models are presented. Second, a novel framework of a parallel pareto local search based on decomposition is designed to repair the schedule within the time limit. Third, two solution acceptance criteria based on constraint handling and negative correlation are specially designed to maintain high-quality population with diversity. The experiments show that the proposed method outperforms the other competitors with respect to Inverted Generational Distance, Spacing, and Hypervolume, which means that the proposed method can help decision-makers to make better decisions.
$${L_1}$$-2-Type Surfaces in 3-Dimensional De Sitter and Anti De Sitter Spaces
Authors: García-Martínez S. Carolina , Lucas Pascual , Ramírez-Ospina H. Fabián
Published: June 2023

Let $$M_s^2$$

M
s
2

be an orientable surface immersed in the De Sitter space $$\mathbb {S}_1^3\subset \mathbb {R}^4_1$$

S
1
3

⊂

R

1
4

or anti de Sitter space $$\mathbb {H}_1^3\subset \mathbb {R}^4_2$$

H
1
3

⊂

R

2
4

. In the case that $$M_s^2$$

M
s
2

is of $$L_1$$

L
1

-2-type we prove that the following conditions are equivalent to each other: $$M_s^2$$

M
s
2

has a constant principal curvature; $$M_s^2$$

M
s
2

has constant mean curvature; $$M_s^2$$

M
s
2

has constant second mean curvature. As a consequence, we also show that an $$L_1$$

L
1

-2-type surface is either an open portion of a standard pseudo-Riemannian product, or a B-scroll over a null curve, or else its mean curvature, its Gaussian curvature and its principal curvatures are all non-constant.
ResNetFed: Federated Deep Learning Architecture for Privacy-Preserving Pneumonia Detection from COVID-19 Chest Radiographs
Authors: Riedel Pascal , von Schwerin Reinhold , Schaudt Daniel , Hafner Alexander , Späte Christian
Published: June 2023

Personal health data is subject to privacy regulations, making it challenging to apply centralized data-driven methods in healthcare, where personalized training data is frequently used. Federated Learning (FL) promises to provide a decentralized solution to this problem. In FL, siloed data is used for the model training to ensure data privacy. In this paper, we investigate the viability of the federated approach using the detection of COVID-19 pneumonia as a use case. 1411 individual chest radiographs, sourced from the public data repository COVIDx8 are used. The dataset contains radiographs of 753 normal lung findings and 658 COVID-19 related pneumonias. We partition the data unevenly across five separate data silos in order to reflect a typical FL scenario. For the binary image classification analysis of these radiographs, we propose ResNetFed, a pre-trained ResNet50 model modified for federation so that it supports Differential Privacy. In addition, we provide a customized FL strategy for the model training with COVID-19 radiographs. The experimental results show that ResNetFed clearly outperforms locally trained ResNet50 models. Due to the uneven distribution of the data in the silos, we observe that the locally trained ResNet50 models perform significantly worse than ResNetFed models (mean accuracies of 63% and 82.82%, respectively). In particular, ResNetFed shows excellent model performance in underpopulated data silos, achieving up to +34.9 percentage points higher accuracy compared to local ResNet50 models. Thus, with ResNetFed, we provide a federated solution that can assist the initial COVID-19 screening in medical centers in a privacy-preserving manner.