bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of Iron Homeostasis to Induce Ferroptosis with Albumin‐Encapsulated Pt(IV) Nanodrug for the Treatment of Non‐Small Cell Lung Cancer
Authors: Tian Hui‐Xiang , Mei Jie , Cao Lei , Song Jianan , Rong Dingchao , Fang Man , Xu Zhe , Chen Juan , Tang Jie , Xiao Haihua , Liu Zhaoqian , Wang Peng‐Yuan , Yin Ji‐Ye , Li Xiang‐Ping
Published: August 2023

Non‐small cell lung cancer (NSCLC) is the most common pathological type of lung cancer , accounting for approximately 85% of lung cancers. For more than 40 years, platinum (Pt)‐based drugs are still one of the most widely used anticancer drugs even in the era of precision medicine and immunotherapy. However, the clinical limitations of Pt‐based drugs, such as serious side effects and drug resistance, have not been well solved. This study constructs a new albumin‐encapsulated Pt(IV) nanodrug (HSA@Pt(IV)) based on the Pt(IV) drug and nanodelivery system. The characterization of nanodrug and biological experiments demonstrate its excellent drug delivery and antitumor effects. The multi‐omics analysis of the transcriptome and the ionome reveals that nanodrug can activate ferroptosis by affecting intracellular iron homeostasis in NSCLC. This study provides experimental evidence to suggest the potential of HSA@Pt(IV) as a nanodrug with clinical application.
Biosynthesis of Multifunctional Transformable Peptides for Inducing Tumor Cell Apoptosis
Authors: Di Yufei , Shen Qi , Yang Zhiwen , Song Gang , Fang Tiantian , Liu Yazhou , Liu Yamei , Luo Qun , Wang Fuyi , Yan Xuehai , Bai Haotian , Huang Yiming , Lv Fengting , Wang Shu
Published: August 2023

Engineered nanomaterials hold great promise to improve the specificity of disease treatment. Herein, a fully protein‐based material is obtained from nonpathogenic Escherichia coli (E. coli), which is capable of morphological transformation from globular to fibrous in situ for inducing tumor cell apoptosis. The protein‐based material P1 is comprised of a β‐sheet‐forming peptide KLVFF, pro‐apoptotic protein BAK, and GFP along with targeting moieties. The self‐assembled nanoparticles of P1 transform into nanofibers in situ in the presence of cathepsin B, and the generated nanofibrils favor the dimerization of functional BH3 domain of BAK on the mitochondrial outer membrane, leading to efficient anticancer activity both in vitro and in vivo via mitochondria‐dependent apoptosis through Bcl‐2 pathway. To precisely manipulate the morphological transformation of biosynthetic molecules in living cells, a spatiotemporally controllable anticancer system is constructed by coating P1‐expressing E. coli with cationic conjugated polyelectrolytes to release the peptides in situ under light irradiation. The biosynthetic peptide‐based enzyme‐catalytic transformation strategy in vivo would offer a novel perspective for targeted delivery and shows great potential in precision disease therapeutics.
Carbonized Platycladus orientalis Derived Carbon Dots Accelerate Hemostasis through Activation of Platelets and Coagulation Pathways
Authors: Liang Pan , Bi Tao , Zhou Yanan , Wang Chengmei , Ma Yining , Xu Houping , Shen Hongping , Ren Wei , Yang Sijin
Published: August 2023

Achieving rapid and effective hemostasis remains a multidisciplinary challenge. Here, distinctive functional carbon dots derived from carbonized Platycladus orientalis (CPO‐CDs) are developed using one‐step hydrothermal method. The negatively charged surface of CPO‐CDs retains partial functional groups from CPO precursor, exhibiting excellent water solubility and high biocompatibility. Both rat liver injury model and tail amputation model have confirmed the rapid and effective hemostatic performance of CPO‐CDs on exogenous hemorrhage. Further, on endogenous blood‐heat hemorrhage syndrome rat model, CPO‐CDs could inhibit hemorrhage and alleviate inflammation response. Interestingly, the excellent hemostasis performance of CPO‐CDs is ascribed to activate exogenous coagulation pathway and common coagulation pathway. More importantly, metabolomics of rat plasma suggests that the hemostasis effect of CPO‐CDs is closely related to platelet functions. Therefore, the designed in vitro experiments are performed and it is discovered that CPO‐CDs significantly promote platelets adhesion, activation, and aggregation. Further, the underlying mechanism investigation suggests that Src/Syk signal pathway plays a key role in platelets activation triggered by CPO‐CDs. Overall, CPO‐CDs with rapid and excellent hemostatic performance are discovered for the first time, which could be an excellent candidate for the treatment of hemorrhagic diseases.
Black women faculty and administrators leveraging Black feminist consciousness to enhance the experiences of postsecondary college students
Authors: West Nicole M.
Published: August 2023

This article reports findings from semi‐structured, individual interviews with 14 Black women faculty and administrators to decipher the ways Black feminist thought (BFT) informed and was evident in their work with students.
What English language in‐service teachers think, know, and do about writing instruction: Iranian teachers' stated attitudes vs. actual practice
Authors: Bozorgian Hossein , Nemati Narges , Shamsi Esmat , Yaqubi Baqer
Published: August 2023

This study explored second language (L2) in‐service teachers' (ISTs') attitudes toward writing, probed any discrepancy between their attitudes and practice, and investigated the extent to which writing skill is included in L2 classrooms compared to the other three macro skills, namely listening, speaking, and reading. To conduct this mixed‐methods study, 100 Iranian L2 ISTs who teach English in language institutes filled out a validated questionnaire on teachers' attitudes toward writing. Before filling out the questionnaire, a sample of 10 L2 ISTs was randomly selected to participate in nonparticipant observation sessions throughout a semester. They were finally invited for semi‐structured interviews. The result indicated that teachers had positive attitudes toward teaching writing. However, there was a mismatch between their stated attitudes and their actual practice—less than 3% of their class time was allotted to actual writing compared to the other three macro skills (speaking = 45%; listening = 17%; reading = 13%; writing and grammar = 14%; other activities = 11%). Furthermore, teachers reported on some factors such as insufficient payment for additional writing tasks including feedback, and lack of allotted time for writing. Implications of these findings for teachers and stakeholders are discussed further.
A study of programmed death‐1/programmed death ligand and iodine‐induced autoimmune thyroiditis in NOD.H‐2h4 mice
Authors: Li Fan , Zhou Zheng , Wang Lingbo , Li Baoxiang , Jin Meihui , Liu Jinjin , Chen Yun , He Yanhong , Ren Bingxuan , Shen Hongmei , Liu Lixiang
Published: August 2023

Excess iodine will trigger the occurrence of autoimmune thyroiditis (AIT), and programmed death‐1 (PD‐1)/programmed death ligand (PD‐L) will also contribute to the development of AIT. The purpose of this study was to explore the role that negative regulatory signals mediated by PD‐1/PD‐L play in the development of spontaneous autoimmune thyroiditis (SAT) in NOD.H‐2h4 mice when they are exposed to iodine. Programmed death ligand 1 (PD‐L1) antibody was administered intraperitoneally to NOD.H‐2h4 mice. The relevant indicators were determined by flow cytometry, real‐time quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, immunohistochemistry, pathological hematoxylin and eosin staining, and arsenic–cerium catalytic spectrophotometry. Results showed that the level of urinary iodine, the level of thyroid lymphocyte infiltration, the level of thyroglobulin antibodies (TgAb) and interferon (IFN‐γ)/tumor necrosis factor (TNF‐α)/interleukin (IL‐2)/IL‐17, and the relative expression of PD‐1/PD‐L1/programmed death‐2 (PD‐L2) increased with the intervention of excess iodine. After the intervention of the PD‐L1 antibody, the expression of PD‐1/PD‐L1/PD‐L2 in different degrees was inhibited, but the level of thyroid lymphocyte infiltration and serum TgAb/IFN‐γ/TNF‐α/ IL‐2/IL‐17 did not decrease. Collectively, although PD‐1/PD‐L participates in the occurrence of SAT and induces inflammation, administration of the PD‐L1 antibody does not effectively improve the pathological process of SAT. More research is needed to determine whether PD‐1/PD‐L intervention can treat autoimmune thyroid disease.
Integrating de novo QTL‐seq and linkage mapping to identify quantitative trait loci conditioning physiological resistance and avoidance to white mold disease in dry bean
Authors: Roy Jayanta , Soler‐Garzón Alvaro , Miklas Phillip N. , Lee Rian , Clevenger Josh , Myers Zachary , Korani Walid , McClean Phillip E.
Published: August 2023

White mold (WM), caused by the ubiquitous fungus Sclerotinia sclerotiorum, is a devastating disease that limits production and quality of dry bean globally. In the present study, classic linkage mapping combined with QTL‐seq were employed in two recombinant inbred line (RIL) populations, “Montrose”/I9365‐25 (M25) and “Raven”/I9365‐31 (R31), with the initial goal of fine‐mapping QTL WM5.4 and WM7.5 that condition WM resistance. The RILs were phenotyped for WM reactions under greenhouse (straw test) and field environments. The general region of WM5.4 and WM7.5 were reconfirmed with both mapping strategies within each population. Combining the results from both mapping strategies, WM5.4 was delimited to a 22.60–36.25 Mb interval in the heterochromatic regions on Pv05, while WM7.5 was narrowed to a 0.83 Mb (3.99–4.82 Mb) region on the Pv07 chromosome. Furthermore, additional QTL WM2.2a (3.81–7.24 Mb), WM2.2b (11.18–17.37 Mb, heterochromatic region), and WM2.2c (23.33–25.94 Mb) were mapped to a narrowed genomic interval on Pv02 and WM4.2 in a 0.89 Mb physical interval at the distal end of Pv04 chromosome. Gene models encoding gibberellin 2‐oxidase proteins regulating plant architecture are likely candidate genes associated with WM2.2a resistance. Nine gene models encoding a disease resistance protein (quinone reductase family protein and ATWRKY69) found within the WM5.4 QTL interval are putative candidate genes. Clusters of 13 and 5 copies of gene models encoding cysteine‐rich receptor‐like kinase and receptor‐like protein kinase‐related family proteins, respectively, are potential candidate genes associated with WM7.5 resistance and most likely trigger physiological resistance to WM. Acquired knowledge of the narrowed major QTL intervals, flanking markers, and candidate genes provides promising opportunities to develop functional molecular markers to implement marker‐assisted selection for WM resistant dry bean cultivars.
Five questions with Lehigh's Carina Sitkus
Authors: Talarico Donna
Published: August 2023

On occasion, our marketing column will profile a communications professional to give you an inside look at what's happening in departments across the country.
Hydrogel and aerogel‐based flame‐retardant polymeric materials: A review
Authors: Vahabi Henri , Gholami Fatemeh , Tomas Martin , Movahedifar Elnaz , Yazdi Mohsen Khodadadi , Saeb Mohammad Reza
Published: August 2023

Hydrogels are multifunctional engineering materials best known for their promising characteristics such as toughness, flexibility, water absorption capacity, and porosity. These features can support fire protection missions. Application of hydrogels as flame‐retardant materials is receiving much attention, such that several research and industrial projects have been devoted to design, manufacturing, and optimization of flame‐retardant hydrogels—taking a unique position among advanced multifunctional materials and strategies. Likewise, aerogels (derived from gels) due to their porous structure filled with a gas, usually air, rather than water in the case of hydrogels, have shown superior thermal insulation potential. Correspondingly, they have been used in fire and flame protection applications. In this work, the flame‐retardant hydrogels and aerogels along with mechanisms underlying their flame retardancy are reviewed. Besides classifying and interpreting the open literature on flame‐retardant hydrogels and aerogels, challenging aspects of future developments ahead of these advanced materials are highlighted.

Highlights

Briefly overviewed general features of hydrogels including synthesis and applications.

Briefly overviewed principles of flame retardancy and flame‐retardant polymers.

Reviewed and classified flame‐retardant hydrogels and aerogels as advanced materials.

Summarized the latest advancements in flame‐retardant hydrogels and aerogels.

Highlighted future fire protection by flame‐retardant hydrogels and aerogels.
Set up: The European Parliament
Authors: Berthet Valentine , Gaweda Barbara , Kantola Johanna , Miller Cherry , Ahrens Petra , Elomäki Anna
Published: August 2023

Prior to conducting any research, it is crucial to understand and familiarise oneself with the research context and setting. The chapter provides an overview of the existing research on the European Parliament and its political groups, as well as key information on the Parliament as a setting for qualitative research. Following the step-by-step approach of the book, Chapter 2 provides the readers with key preliminary insights about the European Parliament with regard to conducting qualitative research. It engages with key concepts in qualitative research on parliaments and discusses them in light of the uniqueness of the European Parliament. Specifically, the cultural and linguistic diversity and its highly technical legislative process and complex institutional context make the European Parliament a rich albeit challenging site of qualitative research. The chapter stresses the high level of informality in the parliamentary work of the European Parliament and highlights the contributions qualitative research makes to a field still largely dominated by quantitative research. The study of everyday dynamics and informal practices reinforces the importance of utilising a qualitative toolkit and data, like interviews and ethnography, and that of broadening the range of research participants to parliamentary staff from political elites only.
How Was the Data Gathered? Doing Research Interviews and Ethnography
Authors: Berthet Valentine , Gaweda Barbara , Kantola Johanna , Miller Cherry , Ahrens Petra , Elomäki Anna
Published: August 2023

The chapter describes the process of gathering data for research interviews and ethnography in the context of the European Parliament. First, the ethical review process is reviewed and discussed in light of the impact of the General Data Protection Regulation on interviews and ethnography. This chapter provides a detailed overview of how the interviews were conducted, outlines the selection and recruitment of interviewees and describes the preparatory steps ahead of the interview. It also offers various ethnographic practices that researchers can use in parliamentary research. Simultaneously, the chapter discusses the specificities of the research site that influenced data gathering. For example, in the European Parliament Strasbourg site, the long hours and close-knit community provided unique opportunities for building relationships and gaining credibility as ‘insiders’ through informal dialogues and shared experiences. However, the intense schedule and overlapping meetings made it challenging to secure interviews. Finally, the impact of Covid-19 on how the interviews were conducted and how the European Parliament operated, in general, is also discussed.
Ok Google or Not Ok Google?—Voice Assistants and the Protection of Privacy in Families
Authors: Backes Christina , Jungfleisch Julia , Pültz Sebastian
Published: August 2023

Voice assistants, such as Alexa, Siri or the Google Assistant have become a fixed component in the everyday life of many. However, their use gives rise to several questions in the context of data protection. This chapter provides an overview of the function of voice assistants and the international, European and national legal framework that regulates them. The focus lies on the implications of the use of voice assistants, especially when considering the right to privacy of children towards their parents, as a special case of horizontal effects of fundamental rights between private individuals. In the context of a possible future and existing state regulation, the right of parents to educate their children, as well as the fundamentally required restraint of the state in family matters must be taken into account. New legislation in the area of digital services and AI could help to improve the protection of personal data in this area in the future. Evaluations from other, at first glance similar, cases such as smart toys or dash cams, can only be transferred to a limited extent.
Reevaluating Main Concepts of Intellectual Property in the Light of AI-Challenges
Authors: Mešević Iza Razija
Published: August 2023

This paper examines the impact of Artificial Intelligence (AI) systems on some of the main principles of Intellectual Property, specifically those inherent to copyright and patent law. Particular attention is dedicated to the concept of authorship in relation to AI-assisted and AI-generated creations in the field of art. The chapter also examines the potential need, or a lack thereof, to re-evaluate the anthropocentric foundations of copyright embedded in the acquis communautaire, copyright laws of the Member States and the case law of CJEU. Taking into consideration the AI’s inability to act as an autonomous agent, attention is drawn to possible legislative interventions to introduce legal certainty, whilst honoring and maintaining core values of copyright law.
Theory of Second Language Acquisition
Authors: Krüger Maleika
Published: August 2023

The scientific field of second language acquisition (SLA), as it emerged in the 1970s, is concerned with the conditions and circumstances in which second and foreign language learning occurs. Although sometimes used synonymously, the terms second language and foreign language describe two different aspects: a second language refers to the official language within the country of residence, which is not a person’s mother tongue. This is, for example, the case for immigrant children who learn the language of their parents’ homeland before or while learning the language of their country of residence as a second language in school or kindergarten.
Remembrance of things past
Authors: Woodard R. P. , Yesilyurt B.
Published: August 2023

Abstract

Nonlinear sigma models on de Sitter background have proved a useful prototype for quantum gravity in summing the large logarithms which arise from loop corrections. We consider a model whose evolution is described, at leading logarithm order, by the trace of the coincident, doubly differentiated scalar propagator. An analytic approximation for this quantity on an arbitrary expansion history is applied to generalize the resummed de Sitter result to any cosmological background which has experienced primordial inflation. In addition to analytic expressions, we present explicit numerical results for the evolution in a plausible expansion history. The large scales of primordial inflation are transmitted to late times.
Scalar-fermion fixed points in the ε expansion
Authors: Pannell William H. , Stergiou Andreas
Published: August 2023

Abstract

The one-loop beta functions for systems of Ns scalars and Nf fermions interacting via a general potential are analysed as tensorial equations in 4 − ε dimensions. Two distinct bounds on combinations of invariants constructed from the couplings are derived and, subject to an assumption, are used to prove that at one-loop order the anomalous dimensions of the elementary fields are universally restricted by γϕ ⩽ $$ \frac{1}{2} $$

1
2

Nsε and γψ ⩽ Nsε. For each root of the Yukawa beta function there is a number of roots of the quartic beta function, giving rise to the concept of ‘levels’ of fixed points in scalar-fermion theories. It is proven that if a stable fixed point exists within a certain level, then it is the only such fixed point at that level. Solving the beta function equations, both analytically and numerically, for low numbers of scalars and fermions, well-known and novel fixed points are found and their stability properties are examined. While a number of fixed points saturate one out of the two bounds, only one fixed point is found which saturates both of them.
Fermionic dark matter in Dynamical Scotogenic Model
Authors: Chun Eung Jin , Roy Abhishek , Mandal Sanjoy , Mitra Manimala
Published: August 2023

Abstract

In the Dynamical Scotogenic Model, the global B − L symmetry is supposed to be broken spontaneously resulting in a massless Goldstone boson called majoron, and massive right handed neutrinos which participate in the generation of light neutrino massses at one-loop. One of them being the lightest stable particle can be a thermal dark matter candidate. We discuss how the dark matter phenomenology differs from the original Scotogenic model, taking into account all the constraints coming from the observed neutrino masses and mixing, lepton flavor violations such as μ → eγ, μ → eJ, astrophysical and cosmological observations of stellar cooling and Neff, as well as collider signatures such as Higgs invisible decays. We find that the dark matter annihilation to majorons plays an important role to produce the right relic abundance.
Path-integral quantization of tensionless (super) string
Authors: Chen Bin , Hu Zezhou , Yu Zhe-fei , Zheng Yu-fan
Published: August 2023

Abstract

In this work, we study the tensionless (super)string in the formalism of path-integral quantization. We introduce BMS bc and βγ ghosts intrinsically by accounting for the Faddeev-Popov determinants appeared in fixing the gauges. We then do canonical quantization and obtain the critical dimensions for different tensionless strings. We find that among four kinds of tensionless superstrings, the 𝒩 = 2 homogeneous and inhomogeneous doublet tensionless superstrings have the same critical dimension as the usual superstrings. Taking the BMS bc and βγ ghosts as new types of BMS free field theories, we find that their enhanced underlying symmetries are generated by BMS-Kac-Moody algebras, with the Kac-Moody subalgebras being built from a three-dimensional non-abelian and non-semi-simple Lie algebra.
Three-dimensional orbifolds by 2-groups
Authors: Perez-Lona Alonso , Sharpe Eric
Published: August 2023

Abstract

In this paper we generalize previous work on decomposition in three-dimensional orbifolds by 2-groups realized as analogues of central extensions, to orbifolds by more general 2-groups. We describe the computation of such orbifolds in physics, state a version of the decomposition conjecture, and then compute in numerous examples, checking that decomposition works as advertised.
Temporal adaptation of sensory attenuation for self-touch
Authors: Fritz Clara , Zimmermann Eckart
Published: August 2023

The sensory consequences of our actions appear attenuated to us. This effect has been reported for external sensations that are evoked by auditory or visual events and for body-related sensations which are produced by self-touch. In the present study, we investigated the effects of prolonged exposure to a delay between an action and the generated sensation on sensory attenuation for self-touch. Previously, it has been shown that after being presented to a systematic exposure delay, artificially delayed touch can feel more intense and non-delayed touches can appear less intense. Here, we investigated the temporal spread of the temporal recalibration effect. Specifically, we wondered whether this temporal recalibration effect would affect only the delay that was used during exposure trials or if it would also modulate longer test delays. In the first two experiments, we tested three test delays (0, 100 and 400 ms) either in randomized or in blocked order. We found sensory attenuation in all three test intervals but no effect of the exposure delay. In Experiment 3, we replicated the experiment by Kilteni et al. (ELife 8:e42888, 2019. https://doi.org/10.7554/eLife.42888) and found evidence for temporal recalibration by exposure delay. Our data show that the temporal selectivity of sensory attenuation of self-touch depends on presenting a singular test delay only. Presenting multiple test delays leads to a temporally broad spread of sensory attenuation.
Systematic Analysis of Diverse Polynucleotide Kinase Clp1 Family Proteins in Eukaryotes: Three Unique Clp1 Proteins of Trypanosoma brucei
Authors: Saito Motofumi , Inose Rerina , Sato Asako , Tomita Masaru , Suzuki Haruo , Kanai Akio
Published: August 2023

The Clp1 family proteins, consisting of the Clp1 and Nol9/Grc3 groups, have polynucleotide kinase (PNK) activity at the 5′ end of RNA strands and are important enzymes in the processing of some precursor RNAs. However, it remains unclear how this enzyme family diversified in the eukaryotes. We performed a large-scale molecular evolutionary analysis of the full-length genomes of 358 eukaryotic species to classify the diverse Clp1 family proteins. The average number of Clp1 family proteins in eukaryotes was 2.3 ± 1.0, and most representative species had both Clp1 and Nol9/Grc3 proteins, suggesting that the Clp1 and Nol9/Grc3 groups were already formed in the eukaryotic ancestor by gene duplication. We also detected an average of 4.1 ± 0.4 Clp1 family proteins in members of the protist phylum Euglenozoa. For example, in Trypanosoma brucei, there are three genes of the Clp1 group and one gene of the Nol9/Grc3 group. In the Clp1 group proteins encoded by these three genes, the C-terminal domains have been replaced by unique characteristics domains, so we designated these proteins Tb-Clp1-t1, Tb-Clp1-t2, and Tb-Clp1-t3. Experimental validation showed that only Tb-Clp1-t2 has PNK activity against RNA strands. As in this example, N-terminal and C-terminal domain replacement also contributed to the diversification of the Clp1 family proteins in other eukaryotic species. Our analysis also revealed that the Clp1 family proteins in humans and plants diversified through isoforms created by alternative splicing.
Hydrogel capsules as new approach for increasing drying survival of plant biostimulant gram-negative consortium
Authors: Chaparro-Rodríguez Martha , Estrada-Bonilla German , Rosas-Pérez Jaiver , Gómez-Álvarez Martha , Cruz-Barrera Mauricio
Published: August 2023

Several plant growth–promoting bacteria (PGPB) are gram-negative, and their cell viability is affected during the bio-inoculant production. Hence, formulation-drying processes provide challenges that limit the adoption of these beneficial microorganisms in sustainable agricultural production. Among delivery system strategies for gram-negative PGPB, the encapsulating cells in biopolymeric materials are emerging as a promising alternative. This research aims to evaluate the effect of additives and crosslinking agents on the survival of the consortium of Herbaspirillum frisingense AP21, Azospirillum brasilense D7, and Rhizobium leguminosarum T88 in hydrogel capsules. Three crosslinkers and diverse potential drying protectors were tested. Calcium gluconate provides notable consortium survival advantages regarding colony-forming units (CFUs) (losses of up to 4 log CFU) compared to calcium lactate and calcium chloride (up to 6 log CFU). Additives such as skimmed milk, whey protein, and Gelita® EC improve the recovery of viable cells after the drying process, demonstrating an increase in cell survival of the three bacteria by up to 4 log CFU. The combination of these substances into a capsule prototype extends the storage stability of bacterial consortium up to 3 months at 18 ± 2 °C. This study expands the knowledge for formulating gram-negative PGPB consortium, regarding the crosslinker and drying protector relationship on encapsulation processes with drying survival and further storage stability performance.

Key points

• Hydrogel immobilization formulation approach for PGPB consortium

• Enhancing drying survival of gram-negative PGPB consortium

• Increasing storage stability of PGPB consortium at 18 °C
Immune checkpoint inhibitor-induced neurotoxicity is not associated with seroprevalence of neurotropic infections
Authors: Schmitt C. , Hoefsmit E. P. , Fangmeier T. , Kramer N. , Kabakci C. , Vera González J. , Versluis J. M. , Compter A. , Harrer T. , Mijočević H. , Schubert S. , Hundsberger T. , Menzies A. M. , Scolyer R. A. , Long G. V. , French L. E. , Blank C. U. , Heinzerling L. M.
Published: August 2023

Background

Immune checkpoint inhibitors (ICI) substantially improve outcome for patients with cancer. However, the majority of patients develops immune-related adverse events (irAEs), which can be persistent and significantly reduce quality of life. Neurological irAEs occur in 1–5% of patients and can induce severe, permanent sequelae or even be fatal. In order to improve the diagnosis and treatment of neurological irAEs and to better understand their pathogenesis, we assessed whether previous neurotropic infections are associated with neurological irAEs.

Methods

Neurotropic infections that might predispose to ICI-induced neurological irAEs were analyzed in 61 melanoma patients from 3 countries, the Netherlands, Australia and Germany, including 24 patients with neurotoxicity and 37 control patients. In total, 14 viral, 6 bacterial, and 1 protozoal infections previously reported to trigger neurological pathologies were assessed using routine serology testing. The Dutch and Australian cohorts (NL) included pre-treatment plasma samples of patients treated with neoadjuvant ICI therapy (OpACIN-neo and PRADO trials; NCT02977052). In the Dutch/Australian cohort a total of 11 patients with neurological irAEs were compared to 27 control patients (patients without neurological irAEs). The German cohort (LMU) consisted of serum samples of 13 patients with neurological irAE and 10 control patients without any documented irAE under ICI therapy.

Results

The association of neurological irAEs with 21 possible preceding infections was assessed by measuring specific antibodies against investigated agents. The seroprevalence of all the tested viral (cytomegalovirus, Epstein-Barr-Virus, varicella-zoster virus, measles, rubella, influenza A and B, human herpes virus 6 and 7, herpes simplex virus 1 and 2, parvovirus B19, hepatitis A and E and human T-lymphotropic virus type 1 and 2), bacterial (Borrelia burgdorferi sensu lato, Campylobacter jejuni, Mycoplasma pneumoniae, Coxiella burnetti, Helicobacter pylori, Yersinia enterocolitica and Y. pseudotuberculosis) and protozoal (Toxoplasma gondii) infections was similar for patients who developed neurological irAEs as compared to control patients. Thus, the analysis provided no evidence for an association of described agents tested for seroprevalence with ICI induced neurotoxicity.

Conclusion

Previous viral, bacterial and protozoal neurotropic infections appear not to be associated with the development of neurological irAEs in melanoma patients who underwent therapy with ICI across 3 countries. Further efforts are needed to unravel the factors underlying neurological irAEs in order to identify risk factors for these toxicities, especially with the increasing use of ICI in earlier stage disease.
A new method to estimate the histological stage of primary biliary cholangitis
Authors: Zhang Yuan , Hu Xing , Chang Jing , Li Weihua , Huang Chunyang , Zhang Haiping , Shen Jianjun , Shang Ning , Meng Fankun
Published: August 2023

Objective

To analyze the diagnostic efficacy of the periportal hypoechoic band (PHB) in the histological stage of patients with primary biliary cholangitis (PBC).

Methods

We prospectively included 77 cases of PBC pathologically or clinically confirmed, and high-frequency ultrasound (HFUS) measurements of the PHB were performed in all included patients. Ludwig staging system of histopathology was used as the gold standard.

Results

The width of the PHB was positively correlated with histological staging (r = 0.844, p < 0.001). By area under the receiving operating characteristic curve (AUROC), the best cutoff value for PHB for advanced stage (≥ stage 3) was 2.4 mm (AUROC: 0.934; 95%CI: 0.841–0.981) and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The correct rate for early-stage PBC was 87.9% and for the progressive stage was 93.1%. After multi-factor regression analysis, the PHB (OR = 1.331, CI = 1.105–1.603, p = 0.003) and total bilirubin (OR = 1.156, CI = 1.041–1.285, p = 0.007) were independent influencing factors for progressive PBC.

Conclusions

Measurement of the PHB to assess advanced PBC is a simple and effective method. This method may complement current methods for the histological staging assessment of patients with PBC.

Registration

Clinical trial registration: ChiCTR 2000032053, 2020/04/19.

Clinical relevance statement

The measurement of periportal hypoechoic band (PHB) provides a simple and easy assessment of the degree of disease progression in patients with PBC and provides an important clinical reference in predicting the histological staging of PBC from an ultrasound perspective.

Key Points

• The PHB is correlated with histological staging in the patient with PBC.

• The area under the ROC curves of PHB for detecting advanced stage (≥ stage 3) were 0.934 and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The application of PHB can better assess the advanced PBC.

• Measurement of the PHB to assess advanced PBC is a simple and effective method that can significantly reduce the need for liver biopsy.
Glycaemic control and insulin therapy are significant confounders of the obesity paradox in patients with heart failure and diabetes mellitus
Authors: Fröhlich Hanna , Bossmeyer Anna , Kazmi Syed , Goode Kevin M. , Agewall Stefan , Atar Dan , Grundtvig Morten , Frey Norbert , Cleland John G. F. , Frankenstein Lutz , Clark Andrew L. , Täger Tobias
Published: August 2023

Background

A high body mass index (BMI) confers a paradoxical survival benefit in patients with heart failure (HF) or diabetes mellitus (DM). There is, however, controversy whether an obesity paradox is also present in patients with HF and concomitant DM. In addition, the influence of glycaemic control and diabetes treatment on the presence or absence of the obesity paradox in patients with HF and DM is unknown.

Methods

We identified 2936 patients with HF with reduced ejection fraction (HFrEF) in the HF registries of the universities of Heidelberg, Germany, and Hull, UK (general sample). Of these, 598 (20%) were treated for concomitant DM (DM subgroup). The relationship between BMI and all-cause mortality was analysed in both the general sample and the DM subgroup. Patients with concomitant DM were stratified according to HbA1c levels or type of diabetes treatment and analyses were repeated.

Results

We found an inverse BMI-mortality relationship in both the general sample and the DM subgroup. However, the obesity paradox was less pronounced in patients with diabetes treated with insulin and it disappeared in those with poor glycaemic control as defined by HbA1c levels > 7.5%.

Conclusion

In patients with HFrEF, a higher BMI is associated with better survival irrespective of concomitant DM. However, insulin treatment and poor glycaemic control make the relationship much weaker.

Graphical abstract
Functional, biological, and radiological evaluation of the pancreaticojejunal anastomosis 1 year after pancreatoduodenectomy: a prospective study
Authors: Joliat Gaëtan-Romain , Allemann Pierre , Labgaa Ismail , Demartines Nicolas , Vietti Violi Naik , Schmidt Sabine , Schäfer Markus
Published: August 2023

Purpose

This prospective study aimed to analyze the functional, biological, and radiological aspects of the pancreatic anastomosis 1 year after pancreatoduodenectomy (PD).

Methods

From 2016 to 2019, patients with PD indication were screened. Questionnaires about pancreas insufficiency, fecal elastase tests, and magnetic resonance imaging (MRI) were performed before and 1 year after PD.

Results

Twenty patients were prospectively included. The only difference between pre- and postoperative questionnaires was constipation (less frequent 1 year after PD). Median pre- and postoperative fecal elastase levels were 96 μg/g (IQR 15–196, normal value > 200) and 15 μg/g (IQR 15–26, p = 0.042). There were no significant differences in terms of main pancreatic duct (MPD) size (4, IQR 3–5 vs. 4 mm, IQR 3–5, p = 0.892), border regularity, stenosis, visibility, image improvement, and secondary pancreatic duct dilation before and after secretin injection. All patients but one (2 refused and 2 were lost to follow-up, 15/16, 94%) had a patent pancreaticojejunal anastomosis on 1-year MRI.

Conclusion

Although median 1-year fecal elastase was significantly lower than preoperatively, suggesting that exocrine secretion was altered, the anatomical outcome as assessed by MRI was excellent showing high patency rate (15/16, 94%) at 1 year. This emphasizes the difference between anatomy and function.
Regeneration of starfish radial nerve cord restores animal mobility and unveils a new coelomocyte population
Authors: Magalhães Filipe , Andrade Claúdia , Simões Beatriz , Brigham Fredi , Valente Ruben , Martinez Pedro , Rino José , Sugni Michela , Coelho Ana Varela
Published: August 2023

The potential to regenerate a damaged body part is expressed to a different extent in animals. Echinoderms, in particular starfish, are known for their outstanding regenerating potential. Differently, humans have restricted abilities to restore organ systems being dependent on limited sources of stem cells. In particular, the potential to regenerate the central nervous system is extremely limited, explaining the lack of natural mechanisms that could overcome the development of neurodegenerative diseases and the occurrence of trauma. Therefore, understanding the molecular and cellular mechanisms of regeneration in starfish could help the development of new therapeutic approaches in humans. In this study, we tackle the problem of starfish central nervous system regeneration by examining the external and internal anatomical and behavioral traits, the dynamics of coelomocyte populations, and neuronal tissue architecture after radial nerve cord (RNC) partial ablation. We noticed that the removal of part of RNC generated several anatomic anomalies and induced behavioral modifications (injured arm could not be used anymore to lead the starfish movement). Those alterations seem to be related to defense mechanisms and protection of the wound. In particular, histology showed that tissue patterns during regeneration resemble those described in holothurians and in starfish arm tip regeneration. Flow cytometry coupled with imaging flow cytometry unveiled a new coelomocyte population during the late phase of the regeneration process. Morphotypes of these and previously characterized coelomocyte populations were described based on IFC data. Further studies of this new coelomocyte population might provide insights on their involvement in radial nerve cord regeneration.
Steinmetzwerkzeuge aus dem römischen Marmorsteinbruchrevier Spitzelofen (Österreich)
Authors: Karl Stephan
Published: August 2023

Im Zuge eines archäologischen Surveys im römischen Marmorsteinbruchrevier Spitzelofen im Jahr 2021 wurden unter anderen zwei Steinmetzwerkzeuge gefunden, welche die bisherige Anzahl von über 30 Steinbruchwerkzeugen von dieser Lagerstätte erweitern. Bei den Neufunden handelt es sich um Werkzeuge für die eigentliche Steinbearbeitung, d. h. für das Zurichten der abgekeilten bzw. herausgebrochenen Steinblöcke zu Roh- bzw. Halbfertigprodukten: ein zweibahniger Hammer mit ausschwingenden Enden und ein schmaler Breitmeißel. Der Hammer (lat. malleus) kann einem Hammertyp zugewiesen werden, der als archäologisches Fundstück rar, jedoch in einigen Reliefdarstellungen, zumeist auf Grabdenkmalen, von der Zeitenwende bis zum Ende des 3. Jahrhunderts n. Chr. nachzuweisen ist. Auf diesen Grabdenkmalen erscheint dieser Hammertyp stets als Teil eines Werkzeugsets, zumeist mit Messwerkzeugen und Meißeln (lat. scalpra) kombiniert. Die dargestellten Werkzeuge kennzeichnen – in einem Fall auch durch die Grabinschrift belegt – das berufliche Umfeld des Verstorbenen als Marmorarius, als eine mit Marmor arbeitende Person, dessen Arbeitsbereich sich von der Steingewinnung bis zur Herstellung von Objekten und Bauten aus Marmor erstrecken kann. Entgegen der häufigen Annahme, dass sich Werkzeuge der Steinbearbeitung bis zur Neuzeit kaum verändert haben, zeigen sie doch charakteristische Eigenschaften ihrer Zeit.
Li–Yau type inequality for curves in any codimension
Authors: Miura Tatsuya
Published: August 2023

For immersed curves in Euclidean space of any codimension we establish a Li–Yau type inequality that gives a lower bound of the (normalized) bending energy in terms of multiplicity. The obtained inequality is optimal for any codimension and any multiplicity except for the case of planar closed curves with odd multiplicity; in this remaining case we discover a hidden algebraic obstruction and indeed prove an exhaustive non-optimality result. The proof is mainly variational and involves Langer–Singer’s classification of elasticae and André’s algebraic-independence theorem for certain hypergeometric functions. We also discuss applications to elastic flows, networks, and knots.
Association between lesion location and sensorimotor rhythms in stroke – a systematic review with narrative synthesis
Authors: Kancheva Ivana , van der Salm Sandra M. A. , Ramsey Nick F. , Vansteensel Mariska J.
Published: August 2023

Background

Stroke causes alterations in the sensorimotor rhythms (SMRs) of the brain. However, little is known about the influence of lesion location on the SMRs. Understanding this relationship is relevant for the use of SMRs in assistive and rehabilitative therapies, such as Brain-Computer Interfaces (BCIs)..

Methods

We reviewed current evidence on the association between stroke lesion location and SMRs through systematically searching PubMed and Embase and generated a narrative synthesis of findings.

Results

We included 12 articles reporting on 161 patients. In resting-state studies, cortical and pontine damage were related to an overall decrease in alpha (∼8–12 Hz) and increase in delta (∼1–4 Hz) power. In movement paradigm studies, attenuated alpha and beta (∼15–25 Hz) event-related desynchronization (ERD) was shown in stroke patients during (attempted) paretic hand movement, compared to controls. Stronger reductions in alpha and beta ERD in the ipsilesional, compared to contralesional hemisphere, were observed for cortical lesions. Subcortical stroke was found to affect bilateral ERD and ERS, but results were highly variable.

Conclusions

Findings suggest a link between stroke lesion location and SMR alterations, but heterogeneity across studies and limited lesion location descriptions precluded a meta-analysis.

Significance

Future research would benefit from more uniformly defined outcome measures, homogeneous methodologies, and improved lesion location reporting.
Debiasing SHAP scores in random forests
Authors: Loecher Markus
Published: August 2023

Black box machine learning models are currently being used for high-stakes decision making in various parts of society such as healthcare and criminal justice. While tree-based ensemble methods such as random forests typically outperform deep learning models on tabular data sets, their built-in variable importance algorithms are known to be strongly biased toward high-entropy features. It was recently shown that the increasingly popular SHAP (SHapley Additive exPlanations) values suffer from a similar bias. We propose debiased or "shrunk" SHAP scores based on sample splitting which additionally enable the detection of overfitting issues at the feature level.
Audio description in video games? Persons with visual disabilities weigh in
Authors: Larreina-Morales María Eugenia , Mangiron Carme
Published: August 2023

In recent years, important advances have taken place to improve game accessibility for all types of players. However, audio description (AD), the access service that translates images into words, is yet to be widely implemented in mainstream games. This paper presents part of the results of the Researching Audio Description Project: Translation, Delivery and New Scenarios (RAD). One of the main objectives of the project is to investigate the potential inclusion of AD in video games in order to improve their accessibility and to contribute to a more enjoyable experience for persons with visual disabilities. First, the evolution of game accessibility is discussed, including the latest developments in the field, both from the industry and research perspectives. Secondly, the RAD Project is presented. Thirdly, the data collected from a survey addressed to blind and low vision persons in Spain is described, for which 106 valid answers were received. Survey topics include the game accessibility barriers encountered by participants, their desired solutions, and their interest in the potential application of AD. Finally, results are discussed regarding similar studies, limitations, and future research. Survey participants are interested in including AD in video games, particularly in non-interactive sections such as cutscenes. Other pressing issues for the game industry regarding accessibility are improving screen reader compatibility, enhancing sounds, and exploring the technical feasibility of game AD in real-time action.
The relationshipbetween anxiety and social outcomes in autistic children and adolescents: A meta-analysis
Authors: Adams Dawn , Ambrose Kathryn , Simpson Kate , Malone Stephanie , Dargue Nicole
Published: August 2023

Anxiety is one of the most frequently reported co-occurring conditions for autistic children and adolescents. The relationship between anxiety and social outcomes in autistic youth has been the focus of a range of studies, with mixed results. This meta-analysis aimed to identify the strength of the association between anxiety and a frequently researched social outcome (social competence) in autistic young people and whether that association is influenced by individual or research design factors. A previous preregistered systematic review was updated with a search of the same three databases (CINAHL, ERIC, and PsycINFO) as the original review. Through this, 20 studies with sufficient data on a neurotypically-defined measure of social competence and anxiety were identified. Results were synthesised using a mixed effects model. The meta-analysis on 2,321 participants (from 22 samples) highlighted wide heterogeneity in results. The findings show that anxiety has a significant, small negative impact on social competence (d = − 0.48; 95% CI = − 0.71, − 0.26), meaning that as scores on measures of anxiety increase, scores on measures of social competence decrease. This relationship between anxiety and social competence was moderated by age, becoming weaker as age increased. Whilst this is an important finding for supporting mental health and well-being of autistic young people, the large amount of variance left unexplained suggests that multiple factors, including the use of measures designed for neurotypical people and the potential impact of camouflaging on such measures, need to be considered in future designs.