bluuebunny/crossref_metadata_2025 huggingface dataset:
Ameliorating and Therapeutic Impact of Curcumin Nanoparticles Against Aluminum Oxide Nanoparticles Induced Kidney Toxicity, DNA Damage, Oxidative Stress, PCNA and TNFα Alteration in Male Rats
Authors: Tousson Ehab , El‐Sayed Ibrahim E. T. , Elsharkawy Hebatalla Nashaat , Ahmed Amira S.
Published: August 2024

Aluminum oxide nanoparticles (Al2O3 NPs) are among the most extensively utilized nanoparticles in nanotechnology and that have negative impacts on the environment. Therefore, the intention of this work is to investigate the protective and therapeutic effects of curcumin in nanoform (Cur NPs) against Al2O3 NPs induced kidney toxicity, oxidative stress, DNA damage, and changes in necrosis factor alpha (TNFα) and proliferating cell nuclear antigen (PCNA) expressions in male rats. Fifty healthy adult male were divided into five groups [G1, control; G2, received 50 mg/kg/day for 4 weeks of Cur NPs orally; G3, received 6 mg/kg BW orally for 4 weeks of Al2O3 NPs; G4, (Cur NPs + Al2O3 NPs) received Cur NPs and Al2O3 NPs at a dose similar to G2 and G3, respectively for 4 weeks; G5, (Al2O3 NPs + Cur NPs) received Al2O3 NPs at a dose similar to G3 for 4 weeks then received Cur NPs at a dose similar to G2 for another 4 weeks]. Current results revealed that Al2O3 NPs induced a significant elevation in serum urea, creatinine, chloride, calcium, kidney malondialdehyde (MDA), DNA damage, injury, TNFα and PCNA expressions and a significant depletion in serum potassium, kidney superoxide dismutase (SOD), glutathione (GSH) as compared to control. On the other hand, treatments of Al2O3 NPs with Cur NPs induced modulation in all altered parameters and improved kidney functions and structure, with best results for the Al2O3 NPs + Cur NPs than Cur NPs + Al2O3 NPs. In conclusion, Cur NPs has the capacity to mitigate the renal toxicity induced by Al2O3 NPs in male albino rats.
Protective Effects of Carvacrol on Mercuric Chloride‐Induced Lung Toxicity Through Modulating Oxidative Stress, Apoptosis, Inflammation, and Autophagy
Authors: Eriten Berna , Kucukler Sefa , Gur Cihan , Ayna Adnan , Diril Halit , Caglayan Cuneyt
Published: August 2024

Mercuric chloride (HgCl2) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl2 can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl2. Intraperitoneal injections of HgCl2 at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue's oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl2‐induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co‐administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF‐κB, IκB, NLRP3, TNF‐α, IL‐1β, IL6, COX‐2, and iNOS were all reduced by CRV. When exposed to HgCl2, the levels of apoptotic Bax, caspase‐3, Apaf1, p53, caspase‐6, and caspase‐9 increased, but the levels of antiapoptotic Bcl‐2 reduced after CRV treatment. CRV decreased levels of Beclin‐1, LC3A, and LC3B, which in turn decreased HgCl2‐induced autophagy damage. After HgCl2 treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl2‐induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative.
Evaluating the winter diet of elk using DNA metabarcoding analysis
Authors: Metts Dailee L. , Miller Bradley F. , Kurth Katherine A. , Watson Eryn M. , Brown Veronica A. , Debruyn Jennifer M. , Kwit Charles , Muller Lisa I.
Published: August 2024

North American elk Cervus canadensis inhabited portions of the eastern United States until extirpation in the mid‐1800s. From 2000 to 2008, 201 elk were reintroduced to the North Cumberland Wildlife Management Area (NCWMA), Tennessee. The stocking source was Elk Island National Park, Alberta Canada where there are two distinct genetic populations isolated from the north and south. This genetic structure has largely persisted in the population after translocation. Food habits were evaluated in the early stages of restoration, but the population has had approximately 20 years to adapt to the landscape, and current food habits are unknown. To assess diet composition using DNA metabarcoding, we collected fecal pellets of elk from 65 openings within the 79 318 ha NCWMA weekly from February to April of 2019. We targeted the ITS2 region of the nuclear ribosomal DNA to amplify vegetation sequences found in the internal portion of the elk feces. DNA metabarcoding of feces was linked to results from an accompanying elk population genetics study to investigate food habits between sexes from the two different genetic groups. The majority (80.298%) of sequences matched plants from 21 genera. The top genera (> 5.000%) represented were Vaccinium (15.216%), Festuca (8.446%), Rosa (6.358%), Robinia (5.793%), and Eleagnus (5.186%). Elk heavily used woody plants before and after spring green‐up (> 50% of diet). However, the quantity of forbs in their diet more than doubled after emergence in the spring. The sex‐genetic groups consumed similar vegetation in approximately proportionate amounts. Diversity analyses revealed a significant difference in plant genera sequence detection between males from the two genetic groups, although this finding is likely explained by limited sample size. NCWMA elk used a variety of forage in the winter and DNA metabarcoding analysis allows for a comprehensive analysis of food habits useful for monitoring how elk respond dietarily to habitat management.
Auslegung der Vorgaben des DRS 20 zur Konzernlageberichterstattung im Hinblick auf erwartbare Angaben zur digitalen Transformation von Unternehmen
Authors: Pelster Clemens
Published: August 2024

Der (Konzern-)Lagebericht wurde in den vorangegangenen Kapiteln bereits als das vielversprechendste bzw. geeignetste Berichtsinstrument identifiziert, in welchem über digitale Transformation von Unternehmen berichtet werden könnte bzw. wird. Zwar sind keine expliziten Vorgaben zur Berichterstattung über digitale Transformation in den Vorschriften des HGB und DRS 20 zur Aufstellung von Konzernlageberichten enthalten. Da jedoch viele Inhalte gefordert werden, die gem. den in Kapitel 3 interviewten Experten auch für eine Berichterstattung über digitale Transformation von Bedeutung sind und zudem die gesetzlich vorgegebenen Mindestinhalte – unter Beachtung der Grundsätze ordnungsmäßiger (Konzern-)Lageberichterstattung – um weitere relevante Inhalte ergänzt werden können bzw. dies unter bestimmten Umständen sogar geboten erscheint, stellt sich die Frage, an welchen Stellen im (Konzern-)Lagebericht am ehesten eine Berichterstattung zur digitalen Transformation zu erwarten ist und wie diese aussehen könnte. In diesem Kapitel wurden die Vorgaben zur (Konzern-)Lageberichterstattung im Hinblick auf mögliche Angaben zur digitalen Transformation ausgelegt, um auf dieser Grundlage und in Kombination mit den zuvor erhobenen Anforderungen das Kategoriensystem zur anschließenden Analyse der Konzernlageberichterstattung zu entwickeln (Kapitel 5) und eine Grundlage für das Berichtskonzept zur entscheidungsnützlichen externen Berichterstattung über digitale Transformation zu schaffen (Kapitel 6). Mit Blick auf die in den Experteninterviews identifizierten Erkenntnisziele potenzieller Adressaten der Berichterstattung über digitale Transformation (Abschnitt 3.5.6) eignen sich die zu den Grundlagen des Unternehmens/Konzerns vorgesehenen Inhalte vor allem, um einen Überblick und/oder eine zusammenfassende Beurteilung zur Bedeutung der digitalen Transformation für den zukünftigen Erfolg des Geschäftsmodells zu vermitteln sowie die bisherige und in Zukunft geplante Handhabung des Themas aufzuzeigen. Angaben zu den bisherigen und voraussichtlichen Auswirkungen der digitalen Transformation passen inhaltlich insb. in den Wirtschaftsbericht sowie den Prognose-, Chancen- und Risikobericht. Eine gänzlich trennscharfe Abgrenzung der Aspekte innerhalb der Konzernlageberichterstattung ist aufgrund der Abhängigkeiten der Aspekte sowie aufgrund der unterschiedlichen Möglichkeiten zur Platzierung bestimmter Informationen oder Möglichkeiten zur Kombination inhaltsverwandter Angaben allerdings nicht zu erwarten. So können u. a. zur Beurteilung der Bedeutung der digitalen Transformation auch Erwartungen hinsichtlich künftiger Entwicklungen mit den damit einhergehenden Chancen und Risiken eine Rolle spielen oder zur digitalen Transformation des Geschäftsmodells ergriffene Maßnahmen zugleich als Ereignis anzusehen sein, welches für den Geschäftsverlauf ursächlich ist und dementsprechend im Wirtschaftsbericht thematisiert werden könnte.
$$ \mathcal{N} $$ = 5 SCFTs and quaternionic reflection groups
Authors: Deb Anirudh , Zafrir Gabi
Published: August 2024

Abstract

It was previously noted that for 3d SCFTs with $$ \mathcal{N} $$
N
≥ 6 the moduli space has the form of ℂ4r/Γ, where Γ is a complex reflection group, at least following suitable gauging of finite symmetries. Here we argue that this observation can be extended also to 3d SCFTs with $$ \mathcal{N} $$
N
≥ 5 SUSY, where Γ is now a quaternionic reflection group. To do this, we study the moduli space of the known 3d $$ \mathcal{N} $$
N
= 5 SCFTs. For Lagrangian cases, the results for the moduli space are further checked using the superconformal index.
Supermassive gauginos in supergravity inflation with high-scale SUSY breaking
Authors: Jang Hun , Porrati Massimo
Published: August 2024

Abstract

A model of supergravity inflation we recently proposed can produce slow roll inflation and a realistic spectrum of particles even without F-term supersymmetry breaking. Supersymmetry is broken only by a D-term induced by a recently discovered new type of Fayet-Iliopoulos (FI) term. Almost all supersymmetric partners of the standard model fields can get masses as high as the inflationary Hubble scale. The exception is gauginos, for which the vanishing of F-terms implies an exact cancellation that keeps their masses exactly zero. To cure this problem without spoiling the simplicity of our model we introduce a new term that further enlarges the space of supergravity effective actions. It is an F-term that, similarly to the new FI term, becomes singular in the supersymmetric limit. We show that this term can produce large gaugino masses without altering the spectrum of other states and without lowering the cutoff of the effecive theory.
Brane expansions for anti-symmetric line operator index
Authors: Imamura Yosuke , Inoue Masato
Published: August 2024

Abstract

Based on the D5-brane realization of Wilson line operators in anti-symmetric representations, we propose brane expansion formulas for IN,k, the Schur index of $$ \mathcal{N} $$
N
= 4 U(N) SYM decorated by line operators in the anti-symmetric representation of rank k. For the large N index I∞,k we propose a double-sum expansion, and for finite N index IN,k we propose a quadruple-sum expansion. Objects causing finite k and finite N corrections are disk D3-branes ending on the D5-brane.
Baryogenesis via QCD preheating with nonadiabatic baryon chemical potential
Authors: Wang Jimin , Wang Xin-Ru , Matsuzaki Shinya
Published: August 2024

Abstract

The chiral phase transition in QCD can be supercooled in the thermal history of the universe to be instantaneously out-of equilibrium, if QCD is coupled to a dark QCD sector exhibiting the dark chiral phase transition of the first order. In that case the QCD sigma meson field (as the chiral order parameter, or the light quark condensate) starts to roll in a nonadiabatic way down to the true QCD vacuum. Meanwhile a dynamic baryonic chemical potential can be generated solely within QCD, which is governed by the dynamic motion of the QCD sigma meson field, analogously to the spontaneous baryogenesis or the leptogenesis via the Higgs or axionlike relaxation scenario. When QCD is further allowed to communicate with a dark fermion with mass of order of 1 GeV and the baryon number violating coupling to neutron, the nonadiabatic QCD sigma motion along with the nonadiabatic baryon chemical potential can trigger the preheating and produce the baryon number asymmetry. We discuss this scenario in details to find that the QCD-induced dynamic baryon chemical potential plays a significant role for the QCD preheating and the baryogenesis, which yields the desired amount of the asymmetry today consistently with current astrophysical, cosmological, and terrestrial experimental constraints. Cosmological and phenomenological consequences characteristic to the present scenario are also addressed.
Resummation of Glauber phases in non-global LHC observables for large Nc
Authors: Böer Philipp , Hager Patrick , Neubert Matthias , Stillger Michel , Xu Xiaofeng
Published: August 2024

Abstract

The Glauber series for non-global jet observables at hadron colliders simultaneously includes the super-leading logarithms alongside an arbitrary number of Glauber phases. Building on the formalism of [1], it is shown that the leading terms in this series for large Nc can be resummed in closed form in renormalization-group improved perturbation theory. This remarkable observation suggests that large-Nc methods might also be helpful to study other aspects of non-global logarithms at hadron colliders, and to combine our analytic results with amplitude-level parton showers.
Principles of artificial intelligence in radiooncology
Authors: Huang Yixing , Gomaa Ahmed , Höfler Daniel , Schubert Philipp , Gaipl Udo , Frey Benjamin , Fietkau Rainer , Bert Christoph , Putz Florian
Published: August 2024

Purpose

In the rapidly expanding field of artificial intelligence (AI) there is a wealth of literature detailing the myriad applications of AI, particularly in the realm of deep learning. However, a review that elucidates the technical principles of deep learning as relevant to radiation oncology in an easily understandable manner is still notably lacking. This paper aims to fill this gap by providing a comprehensive guide to the principles of deep learning that is specifically tailored toward radiation oncology.

Methods

In light of the extensive variety of AI methodologies, this review selectively concentrates on the specific domain of deep learning. It emphasizes the principal categories of deep learning models and delineates the methodologies for training these models effectively.

Results

This review initially delineates the distinctions between AI and deep learning as well as between supervised and unsupervised learning. Subsequently, it elucidates the fundamental principles of major deep learning models, encompassing multilayer perceptrons (MLPs), convolutional neural networks (CNNs), recurrent neural networks (RNNs), transformers, generative adversarial networks (GANs), diffusion-based generative models, and reinforcement learning. For each category, it presents representative networks alongside their specific applications in radiation oncology. Moreover, the review outlines critical factors essential for training deep learning models, such as data preprocessing, loss functions, optimizers, and other pivotal training parameters including learning rate and batch size.

Conclusion

This review provides a comprehensive overview of deep learning principles tailored toward radiation oncology. It aims to enhance the understanding of AI-based research and software applications, thereby bridging the gap between complex technological concepts and clinical practice in radiation oncology.
Vergleich der präklinischen Analgesiequalität von Notarzt und Notfallsanitäter anhand traumatologischer Patienten
Authors: Thomas Julian , Kleinschmidt Stefan , Mörsdorf Philipp , Conrad David , Berwanger Ulrich , Armbruster Werner
Published: August 2024

Hintergrund

Die präklinische Schmerztherapie ist ein wesentlicher Bestandteil der Notfallmedizin. Mit Einführung des Berufsbildes des Notfallsanitäters wurden nicht ärztlichen Rettungskräften erweiterte medizinische Kompetenzen zuerkannt. Diese Studie evaluiert die Qualität der Analgesie durch Notfallsanitäter im Vergleich zu Notärzten anhand traumatologischer Patienten.

Material und Methoden

Erfasst wurden Patienten mit Verletzungen, die nach einer präklinisch durchgeführten Analgetikagabe, durch Notärzte oder Notfallsanitäter, in der zentralen Notaufnahme des Universitätsklinikums des Saarlandes aufgenommen wurden. In einem Erfassungsbogen wurden sowohl aus dem Notfalleinsatzprotokoll als auch initial in der Sichtung/Notaufnahme erhobene Daten und Messwerte erfasst. Die deskriptive Auswertung erfolgte anhand statistischer Standardverfahren. Eingeschlossen wurden 207 komplette Datensätze. Als primärer Endpunkt wurde die Reduktion der Schmerzen bei Übergabe in der zentralen Notaufnahme festgelegt.

Ergebnisse

Beide Berufsgruppen erreichen eine signifikante Reduktion der Schmerzen und erfüllen das Ziel einer effektiven Schmerztherapie (Schmerzdifferenz: Notarzt 5,5 ± 2,0/Notfallsanitäter 4,4 ± 2,1/p < 0,001). Notärzte erzielten eine höhere Reduktion der NRS-Werte und verabreichten häufiger Sauerstoff. Unterschiede zeigten sich v. a. im Spektrum der verwendeten Pharmaka.

Schlussfolgerung

Bei korrekter Indikationsstellung und Beachtung der Handlungsanweisungen können Notfallsanitäter eine effektive Analgosedierung durchführen. Hinsichtlich Sicherheit und Qualität lässt sich die Therapie mit der eines Notarztes vergleichen.
A framework for simulating genotype-by-environment interaction using multiplicative models
Authors: Bančič J. , Gorjanc G. , Tolhurst D. J.
Published: August 2024

Key message

The simulation of genotype-by-environment interaction using multiplicative models provides a general and scalable framework to generate realistic multi-environment datasets and model plant breeding programmes.

Abstract

Plant breeding has been historically shaped by genotype-by-environment interaction (GEI). Despite its importance, however, many current simulations do not adequately capture the complexity of GEI inherent to plant breeding. The framework developed in this paper simulates GEI with desirable structure using multiplicative models. The framework can be used to simulate a hypothetical target population of environments (TPE), from which many different multi-environment trial (MET) datasets can be sampled. Measures of variance explained and expected accuracy are developed to tune the simulation of non-crossover and crossover GEI and quantify the MET-TPE alignment. The framework has been implemented within the R package FieldSimR, and is demonstrated here using two working examples supported by R code. The first example embeds the framework into a linear mixed model to generate MET datasets with low, moderate and high GEI, which are used to compare several popular statistical models applied to plant breeding. The prediction accuracy generally increases as the level of GEI decreases or the number of environments sampled in the MET increases. The second example integrates the framework into a breeding programme simulation to compare genomic and phenotypic selection strategies over time. Genomic selection outperforms phenotypic selection by $$\sim $$
∼
50–70% in the TPE, depending on the level of GEI. These examples demonstrate how the new framework can be used to generate realistic MET datasets and model plant breeding programmes that better reflect the complexity of real-world settings, making it a valuable tool for optimising a wide range of breeding methodologies.
Ethical approaches in designing autonomous and intelligent systems: a comprehensive survey towards responsible development
Authors: Jedličková Anetta
Published: August 2024

Over the past decade, significant progress in artificial intelligence (AI) has spurred the adoption of its algorithms, addressing previously daunting challenges. Alongside these remarkable strides, there has been a simultaneous increase in model complexity and reliance on opaque AI models, lacking transparency. In numerous scenarios, the systems themselves may necessitate making decisions entailing ethical dimensions. Consequently, it has become imperative to devise solutions to integrate ethical considerations into AI system development practices, facilitating broader utilization of AI systems across various domains. Research endeavors should explore innovative approaches to enhance ethical principles in AI systems, fostering greater transparency, accountability, and trustworthiness. Upholding fundamental individual rights, human dignity, autonomy, privacy, equality, and fairness, while mitigating potential harm, remains paramount. Considering ethical values and ensuring compliance with ethical requirements throughout the development lifecycle of autonomous and intelligent systems nurture trust and reliability in their utilization. Ethical considerations should be ingrained within organizational procedures guiding AI research activities, establishing robust frameworks that address ethical concerns and reflect the ethical implications of AI-based systems. This paper presents an overview of ethical approaches and processes aimed at integrating ethical considerations into AI system development practices. It underscores the significance of ethical frameworks in fostering ethical AI implementation and ensuring the ethical integrity of AI technologies.
Mathematical modelling of stability problems for thin transversally graded cylindrical shells
Authors: Tomczyk B. , Gołąbczak M. , Kubacka E. , Bagdasaryan V.
Published: August 2024

The objects of consideration are thin linearly elastic Kirchhoff–Love-type open circular cylindrical shells having a functionally graded macrostructure and a tolerance-periodic microstructure in circumferential direction. The first aim of this contribution is to formulate and discuss a new mathematical averaged non-asymptotic model for the analysis of selected stability problems for such shells. As a tool of modelling we shall apply the tolerance averaging technique. The second aim is to derive and discuss a new mathematical averaged asymptotic model. This model will be formulated using the consistent asymptotic modelling procedure. The starting equations are the well-known governing equations of linear Kirchhoff–Love second-order theory of thin elastic cylindrical shells. For the functionally graded shells under consideration, the starting equations have highly oscillating, non-continuous and tolerance-periodic coefficients in circumferential direction, whereas equations of the proposed models have continuous and slowly-varying coefficients. Moreover, some of coefficients of the tolerance model equations depend on a microstructure size. It will be shown that in the framework of the tolerance model not only the fundamental cell-independent, but also the new additional cell-dependent critical forces can be derived and analysed.
Calibrated representations of the double Dyck path algebra
Authors: González Nicolle , Gorsky Eugene , Simental José
Published: August 2024

The double Dyck path algebra $$\mathbb {A}_{q,t}$$

A

q
,
t

and its polynomial representation first arose as a key figure in the proof of the celebrated Shuffle Theorem of Carlsson and Mellit. A geometric formulation for an equivalent algebra $$\mathbb {B}_{q,t}$$

B

q
,
t

was then given by the second author and Carlsson and Mellit using the K-theory of parabolic flag Hilbert schemes. In this article, we initiate the systematic study of the representation theory of the double Dyck path algebra $$\mathbb {B}_{q,t}$$

B

q
,
t

. We define a natural extension of this algebra and study its calibrated representations. We show that the polynomial representation is calibrated, and place it into a large family of calibrated representations constructed from posets satisfying certain conditions. We also define tensor products and duals of these representations, thus proving (under suitable conditions) the category of calibrated representations is generically monoidal. As an application, we prove that tensor powers of the polynomial representation can be constructed from the equivariant K-theory of parabolic Gieseker moduli spaces.
Impact of the interval between neoadjuvant immunotherapy and surgery on prognosis in esophageal squamous cell carcinoma (ESCC): a real-world study
Authors: Yang Guozhen , Hong Yutong , Zhang Xiaomin , Zeng Chufeng , Tan Linyu , Zhang Xu
Published: August 2024

Background

The time interval between neoadjuvant immunotherapy and surgery is 6 weeks for esophageal squamous cell carcinoma (ESCC), but whether delayed surgery affects prognosis remains unclear.

Methods

Clinical data of locally advanced ESCC who underwent neoadjuvant immunotherapy followed by esophagectomy from November 2019 to December 2022 were collected. The surgery outcomes and prognosis were compared between short-interval (time to surgery ≤ 6 weeks) and long-interval groups (time to surgery > 6 weeks).

Results

152 patients were enrolled totally, with a ratio of 91:61 between short-interval and long-interval groups. The rate of pathological complete response in the short-interval and long-interval groups were 34.1% and 24.6% (P = 0.257). Delayed surgery did not have a significantly impact on the number of lymph node dissections (P = 0.133), operative duration (P = 0.689), blood loss (P = 0.837), hospitalization duration (P = 0.293), chest drainage duration (P = 0.886) and postoperative complications (P > 0.050). The 3-year Overall survival (OS) rates were 85.10% in the short-interval group, and 82.07% in the long-interval group (P = 0.435). The 3-year disease-free survival (DFS) rates were 83.41% and 70.86% in the two groups (P = 0.037). Subgroup analysis revealed that patients with a favorable response to immunotherapy (tumor regression grade 0) exhibited inferior 3-year OS (long-interval vs. short-interval: 51.85% vs. 91.08%, P = 0.035) and DFS (long-interval vs. short-interval: 47.40% vs. 91.08%, P = 0.014) in the long-interval group.

Conclusions

Delayed surgery after neoadjuvant immunotherapy does not further improve pathological response; instead, it resulted in a poorer DFS. Especially for patients with a favorable response to immunotherapy, delayed surgery increases the risk of mortality and recurrence.
Safety and clinical activity of JNJ-78306358, a human leukocyte antigen-G (HLA-G) x CD3 bispecific antibody, for the treatment of advanced stage solid tumors
Authors: Geva Ravit , Vieito Maria , Ramon Jorge , Perets Ruth , Pedregal Manuel , Corral Elena , Doger Bernard , Calvo Emiliano , Bardina Jorge , Garralda Elena , Brown Regina J. , Greger James G. , Wu Shujian , Steinbach Douglas , Yao Tsun-Wen Sheena , Cao Yu , Lauring Josh , Chaudhary Ruchi , Patel Jaymala , Patel Bharvin , Moreno Victor
Published: August 2024

Background

JNJ-78306358 is a bispecific antibody that redirects T cells to kill human leukocyte antigen-G (HLA-G)-expressing tumor cells. This dose escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of JNJ-78306358 in patients with advanced solid tumors.

Methods

Adult patients with metastatic/unresectable solid tumors with high prevalence of HLA-G expression were enrolled. Dose escalation was initiated with once-weekly subcutaneous administration with step-up dosing to mitigate cytokine release syndrome (CRS).

Results

Overall, 39 heavily pretreated patients (colorectal cancer: n = 23, ovarian cancer: n = 10, and renal cell carcinoma: n = 6) were dosed in 7 cohorts. Most patients (94.9%) experienced ≥ 1 treatment-emergent adverse events (TEAEs); 87.2% had ≥ 1 related TEAEs. About half of the patients (48.7%) experienced CRS, which were grade 1/2. Nine patients (23.1%) received tocilizumab for CRS. No grade 3 CRS was observed. Dose-limiting toxicities (DLTs) of increased transaminases, pneumonitis and recurrent CRS requiring a dose reduction were reported in 4 patients, coinciding with CRS. No treatment-related deaths reported. No objective responses were noted, but 2 patients had stable disease > 40 weeks. JNJ-78306358 stimulated peripheral T cell activation and cytokine release. Anti-drug antibodies were observed in 45% of evaluable patients with impact on exposure. Approximately half of archival tumor samples (48%) had expression of HLA-G by immunohistochemistry.

Conclusion

JNJ-78306358 showed pharmacodynamic effects with induction of cytokines and T cell activation. JNJ-78306358 was associated with CRS-related toxicities including increased transaminases and pneumonitis which limited its dose escalation to potentially efficacious levels.

Trial registration number ClinicalTrials.gov (No. NCT04991740).
Rethinking Urban Water Management Through Drivers-Pressures-States-Impacts-Responses Framework Application in Chennai, India
Authors: Rosado Daniel , Fárez-Román Valeria , Müller Felix , Nambi Indumathi , Fohrer Nicola
Published: August 2024

Cities suffering water scarcity are projected to increase in the following decades. However, the application of standardized indicator frameworks for assessing urban water resource management problems is on an early stage. India is expected to have the highest urban population facing water scarcity in the world by 2050. In this study, the authors assess how the Drivers-Pressures-States-Impacts-Responses framework, a causal framework adopted by the European Environment Agency, can contribute to evaluate water management challenges in cities and apply it to Chennai, India´s fourth-largest urban agglomeration. The framework proved to be a helpful tool for the evaluation of water management challenges in cities by disentangling relationships between environmental indicators and structuring dispersed data that allows a better understanding for policymakers. The main drivers identified in Chennai were population growth and economic development which generated impacts such as loss of aquatic ecosystems, low water table, low water quality, and reduction of biodiversity and human health. As a response, better urban planning, projects for new water infrastructure, and water bodies restoration have been implemented. Nevertheless, Chennai keeps facing difficulties to achieve proper water management. The severe hit of the COVID-19 pandemic on the Indian economy and its future management will be key for achievements related to water management.
The impact of anastomotic leakage characteristics on the occurrence of anastomotic stenosis after colorectal resection, a retrospective cohort study
Authors: Abdelhadi Schaima , Tzatzarakis Emmanouil , Hermann Maike , Orth Vanessa , Vedder Katharina , Briscoe Jannis , Reissfelder Christoph , Șandra-Petrescu Flavius
Published: August 2024

Introduction

Anastomotic stenosis (AS) is a common complication after colorectal resection. However, the predisposing factors for stricture formation are not fully understood. Previous studies have shown anastomotic leakage (AL) to be a risk factor for the occurrence of AS. Therefore, we aim to investigate the impact of anastomotic leakage characteristics on the occurrence of anastomotic stenosis after colorectal resection.

Methods

Consecutive patients with AL following elective, sphincter preserving, colorectal resection, with or without diversion ostomy, between January 2009 and March 2023 were identified from a prospectively collected database. The characteristics of the anastomotic leakage, patient baseline and operative characteristics as well as the postoperative outcomes were analyzed using univariate and multivariate logistic regression to identify factors associated with the occurrence of post-leakage AS.

Results

A total of 129 patients developed AL and met the inclusion criteria. Among these, 28 (21.7%) patients were diagnosed with post-leakage AS. There was a significantly higher frequency of patients with neoadjuvant radiotherapy (18% vs 3%; p = .026) and hand-sewn anastomoses (39% vs 17%; p = .011) within the AS group. Furthermore, the extent of the anastomotic defect was significantly higher in the AS group compared with the non-AS group (50%, IQR 27–71 vs. 20%, IQR 9–40, p = 0.011). Similar findings were observed between the study groups regarding age, sex, BMI, ASA score, medical comorbidities, diagnosis, surgical procedure, surgical approach (open vs. minimally invasive), and anastomotic fashioning (side-to-end vs. end-to-end). On multivariate analysis, the extent of the anastomotic defect (OR 1.01; 95% CI 1.00–1.03; p = 0.034) and hand-sewn anastomoses (OR 2.68; 95% CI 1.01–6.98; p = 0.043) were confirmed as independent risk factors for post-leakage AS. No correlation could be observed between the occurrence of post-leakage AS and the ISREC grading of AL, the anastomotic height or the management of AL. Time to ostomy reversal was significantly longer in the AS group (202d, IQR 169–275 vs. 318d IQR 192–416, p = 0.014).

Conclusion

The extent of the anastomotic defect and hand-sewn anastomoses were confirmed as independent risk factors for the occurrence of post-leakage AS. No correlation could be observed between the ISREC grading of AL, the anastomotic height or AL management, and the occurrence of post-leakage AS.
Outcomes of patients admitted with malignant small bowel obstruction: a subgroup multicentre observational cohort analysis
Authors: Hupfeld N. B. , Burcharth J. , Jensen T. K. , Lolle I. , Nielsen L. B. J. , Tolver M. A. , Skovsen A. P. , Smith H. G.
Published: August 2024

Introduction and purpose of the study

Small bowel obstruction (SBO) accounts for a substantial proportion of emergency surgical admissions. Malignancy is a common cause of obstruction, either due to a primary tumour or intra-abdominal metastases. However, little is known regarding the current treatment or outcomes of patients with malignant SBO. This study aimed to characterise the treatment of malignant SBO and identify areas for potential improvement and compare overall survival of patients with malignant SBO to patients with non-malignant SBO.

Materials and methods

This was a subgroup analysis of a multicentre observational study of patients admitted with SBO. Details regarding these patients’ diagnoses, treatments, and outcomes up to 1-year after admission were recorded. The primary outcome was overall survival in patients with malignant SBO.

Results

A total of 316 patients with small bowel obstruction were included, of whom 33 (10.4%) had malignant SBO. Out of the 33 patients with malignant SBO, 20 patients (60.6%) were treated with palliative intent although only 7 patients were seen by a palliative team during admission. Nutritional assessments were performed on 12 patients, and 11 of these patients received parenteral nutrition. 23 patients underwent surgery, with the most common surgical interventions being loop ileostomies (9 patients) and gastrointestinal bypasses (9 patients). 4 patients underwent right hemicolectomies, with a primary anastomosis formed and 1 patient had a right hemicolectomy with a terminal ileostomy. Median survival was 114 days, and no difference was seen in survival between patients treated with or without palliative intent.

Conclusion

Malignant SBO is associated with significant risks of short-term complications and a poor prognosis. Consideration should be given to the early involvement of senior decision-makers upon patient admission is essential for optimal management and setting expectation for a realistic outcome.
Advancements in triple-negative breast cancer sub-typing, diagnosis and treatment with assistance of artificial intelligence : a focused review
Authors: Batool Zahra , Kamal Mohammad Amjad , Shen Bairong
Published: August 2024

Triple negative breast cancer (TNBC) is most aggressive type of breast cancer with multiple invasive sub-types and leading cause of women’s death worldwide. Lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) causes it to spread rapidly making its treatment challenging due to unresponsiveness towards anti-HER and endocrine therapy. Hence, needing advanced therapeutic treatments and strategies in order to get better recovery from TNBC. Artificial intelligence (AI) has been emerged by giving its high inputs in the automated diagnosis as well as treatment of several diseases, particularly TNBC. AI based TNBC molecular sub-typing, diagnosis as well as therapeutic treatment has become successful now days. Therefore, present review has reviewed recent advancements in the role and assistance of AI particularly focusing on molecular sub-typing, diagnosis as well as treatment of TNBC. Meanwhile, advantages, certain limitations and future implications of AI assistance in the TNBC diagnosis and treatment are also discussed in order to fully understand readers regarding this issue.

Graphical Abstract
Balint groups’ possible role in self-care and job satisfaction of general practitioners—A qualitative study
Authors: Schweiger Karina , Hofbaur Benedikt , Rabady Susanne
Published: August 2024

Background

Concerns are growing when it comes to the shortage of primary care physicians, therefore it seems necessary to take a closer look at job satisfaction and self-care as one of many influences on career choice. A higher job satisfaction reduces the risk to experience burnout and job-related stress and in addition it will contribute to staying in the profession. The objective of this study is to investigate the impact of regular participation in Balint groups on job satisfaction and self-care among general practitioners.

Methods

Descriptive qualitative study with semi-structured expert interviews of 7 general practitioners. Thematical analysis of data and narrative summary.

Results

A total of 402 coded segments were categorized into 8 main themes and 39 subthemes. Interviewees emphasized changes in self-care and job satisfaction as a result of Balint work and mentioned Balint work as a burnout prophylaxis for themselves. Competences that were learnt or improved through Balint work were described as well as aspects such as feedback and connection with colleagues or professional challenges and difficulties.

Conclusion

The results of the study give rise to the assumption that regular participation in Balint groups might help to improve self-care, resilience, and contribute to job satisfaction. Further research is needed before a general recommendation can be made. Many positive aspects were described by the experts, while no harmful negative influences of Balint work were identified.
On-site extraction of benzophenones from swimming pool water using hybrid tapes based on the integration of hydrophilic-lipophilic balance microparticles and an outer magnetic nanometric domain
Authors: Belhameid Ahmed , Casado-Carmona Francisco Antonio , Megriche Adel , López-Lorente Ángela Inmaculada , Lucena Rafael , Cárdenas Soledad
Published: August 2024

An on-site extraction device is presented consisting of scotch tape modified with concentric domains of micrometric hydrophilic-lipophilic balance (HLB) particles surrounded by a ring of nanometric magnetic ones. On the one hand, HLB microparticles are readily available at the surface of the tape, exposed to interact with the target analytes, being responsible for the extraction capacity of the sorptive phase. On the other hand, the presence of magnetic nanoparticles enables the attachment of the modified tape onto a metallic screw via a magnet, which is then coupled to a wireless drill, enabling the stirring of the microextraction device. Both are simply fixed to the cost-effective, flexible, and versatile support, i.e., scotch tape, owing to their adhesive properties. The microextraction device has been applied to the determination of six benzophenones in swimming pool water samples. The variables that may affect the extraction process have been evaluated. Under the optimum conditions and using liquid chromatography-tandem mass spectrometry as the instrumental technique, the method provided a limit of detection of 0.03 µg L−1. The intra-day precision, evaluated at three different concentration levels and expressed as relative standard deviation, was lower than 10%, which also comprises the variability within single-use sorptive tapes. The accuracy, calculated with spiked samples and expressed as relative recovery, ranged from 71 to 138%. The method was applied to the analysis of swimming pool water, revealing the presence of such compounds.

Graphical Abstract
Elektronische Patientenakte und Freigabe von Gesundheitsdaten
Authors: Haug Sonja , Altenbuchner Amelie , Weber Karsten
Published: August 2024

Hintergrund

In Deutschland wird die elektronische Patientenakte (ePA) eingeführt.

Fragestellung

Untersucht werden Nutzungsbereitschaft der ePA, Einstellung zu Gesundheitsdaten und Datenübermittlung bei Personen mit und ohne Kinder.

Methoden

Telefonbefragung bei einer Zufallsstichprobe der Bevölkerung in Deutschland (2022, n = 1308).

Ergebnisse

Die ePA ist bei Haushalten mit Kindern mehrheitlich unbekannt. Ihre Nutzungsbereitschaft der ePA und die Zustimmung zur Speicherung von Gesundheitsdaten ist geringer, aber sie sind häufiger als Haushalte ohne Kinder bereit zur Freigabe ihrer Gesundheitsdaten für die Forschung.

Schlussfolgerung

Es besteht Aufklärungsbedarf über die Speicherung von Gesundheitsdaten. Gewünscht wird zunehmend eine digitale Arzt-Patienten-Kommunikation.
Electrochemical goniometry: keystone reactivity at the three-phase boundary
Authors: Varley Thomas S. , Lawrence Nathan S. , Wadhawan Jay D.
Published: August 2024

Contact angles of liquid, spherical cap droplets immobilised on an electrode surface and bathed by a fluid are important, quantifiable measures of the liquid/fluid interfacial tension. Optical goniometry, even if computer assisted, suffers when the contact angle is 10° or less. In this work, an alternative method of measurement is considered: electrochemical techniques (voltammetry and chronoamperometry), which rely on the transport of material from within the droplet to the conductive surface. As a result of the reactions that take place at the triple phase boundary, these are demonstrated to provide information on the size and the shape of the droplet, including its contact angle, for the cases when the droplets have a redox analyte and either have a supporting electrolyte, or not. The voltammetric behaviour is seen to change from exhaustive, thin film characteristics, to quasi-steady-state signals as the droplet becomes bigger, or the scan rate becomes larger, or diffusion of the redox material inside the droplet becomes slower. One of the surprising outcomes is that there is a zone of planar diffusion only in the case of the supported droplets, with both the droplet size and its contact angle determining whether this is seen at conventional combinations of scan rates and diffusion coefficients. Experimental data are provided which emphasize key features pertaining to the nature of the redox system and illustrate the facile nature of the contact angle estimation process, albeit to within 10% uncertainty.
The effect of imbrication on the porosity value of uniform gravel bed
Authors: Xu Wenjia , Brüll Catrina , Schüttrumpf Holger , Frings Roy M. , Vollmer Stefan
Published: August 2024

Existing empirical relations used to predict the porosity of gravel beds are mainly derived from laboratory-generated sediment beds with random grain packing. However, such relations could not adequately describe beds with non-random grain arrangements that occur widely in fluvial deposits. In this work, the effect of grain imbrication on gravel-bed porosity has been quantified using beds with variable strengths of imbrication generated by flume experiments. Mono-sized ellipsoids with specific shapes were used in experiments to remove particle size and sorting effects on porosity. Random bed packings were generated by settling of ellipsoids in still water whilst imbricated beds generated under flowing water. Beds were frozen using liquid nitrogen before extraction. A new relatively simple and time-saving workflow was developed to measure the orientation of particles and quantify the degree of grain imbrication in frozen beds from X-ray Computed Tomography images. Beds with the strongest grain fabric display a ca. 0.03 absolute reduction of porosity value on average (8–10% relative reduction) compared to that of random packing for undisturbed beds. Further, results were obtained for beds deposited under still-water conditions subject to disturbance by shaking, to mimic the potential effect of vibrations from currents, waves or other sources in the environment. A reduction in bed porosity of ca. 0.014–0.018 (ca. 5% relative reduction) is observed between beds with the strongest grain fabric and those with random packing that had undergone shaking after deposition. Hence, a significant proportion (> 50%) of the porosity loss observed for imbricated beds may be attributable to tighter packing due to turbulence-related vibrations from the flow. The small decrease in porosity value despite the formation of strong imbrication is considered to be due to the limited improvement in grain organization, as the results show that the flat shape of the ellipsoids and the uniformity of their size promote the formation of a stacking structure under gravity, leading to a similarly highly ordered grain organization in random packings compared to the imbricated packings.

Graphical abstract
Lack of association between TRPV1 gene polymorphisms and risk of migraine chronification: a case-control study and meta-analysis
Authors: Giacon Martina , Cargnin Sarah , Allena Marta , Greco Rosaria , Zanaboni Anna Maria , Facchetti Sara , De Icco Roberto , Sances Grazia , Ghiotto Natascia , Guaschino Elena , Martinelli Daniele , Tassorelli Cristina , Terrazzino Salvatore
Published: August 2024

Objective

To confirm a previously reported association of TRPV1 rs8065080 with the risk of transformation from episodic (EM) to chronic migraine (CM) and to extend knowledge about the role of other TRPV1 single nucleotide polymorphisms (SNPs), we first investigated the impact of three TRPV1 SNPs (rs8065080, rs222747 and rs222749) on the risk of migraine chronification in a case-control study. A systematic review and meta-analysis were then conducted to summarize the accumulated findings.

Methods

Genotyping of the selected TRPV1 SNPs was performed using TaqMan real-time PCR in 167 EM and 182 CM participants. Crude and adjusted odds ratios with associated 95% confidence intervals were calculated in the log-additive, dominant, and recessive genetic models. A comprehensive literature search was performed in PubMed, Web of Knowledge, Cochrane Library, and OpenGrey until February 2024.

Results

In our case-control study, no association was found between TRPV1 SNPs and the risk of migraine chronification, both in the unadjusted logistic regression models and after adjustment for confounding clinical variables. The results of the meta-analysis with a total of 241 participants with EM and 223 with CM confirmed no association between TRPV1 SNPs and the risk of migraine chronification in any of the genetic models tested.

Conclusion

The results of the present case-control study and meta-analysis exclude a major role of TRPV1 rs8065080, rs222747, and rs222749 as risk factors for migraine chronification. However, further research is needed to investigate the gene-gene and gene-environment interactions of TRPV1 SNPs on the risk of transformation from episodic to chronic migraine.