bluuebunny/crossref_metadata_2025 huggingface dataset:
The monodromic axion-photon coupling
Authors: Agrawal Prateek , Platschorre Arthur
Published: January 2024

Abstract

We consider the general form of the axion coupling to photons in the axion-Maxwell theory. On general grounds this coupling takes the form of a monodromic function of the axion, which we call g(a), multiplying the Chern-Pontryagin density $$ F\overset{\sim }{F} $$
F

F
~

of the photon. We show that the non-linearity of g(a) is a spurion for the shift symmetry of the axion. In this context, when g(a) ≠ ℤa, the linearized coupling of the axion g′(a) is not quantized and there is a correlated mass term for the axion. Singularities in g(a) due to the fast rearrangement of degrees of freedom are shown to have corresponding cusps and singularities in the axion potential. We derive the general form of g(a) for the QCD axion, axions with perturbatively broken shift symmetries and axions descending from extra dimensions. In all cases, we show that there is a uniform general form of the monodromic function g(a) and it is connected to the axion potential.
What is the Simplest Linear Ramp?
Authors: Das Suman , Garg Sumit K. , Krishnan Chethan , Kundu Arnab
Published: January 2024

Abstract

We discuss conditions under which a deterministic sequence of real numbers, interpreted as the set of eigenvalues of a Hamiltonian, can exhibit features usually associated to random matrix spectra. A key diagnostic is the spectral form factor (SFF) — a linear ramp in the SFF is often viewed as a signature of random matrix behavior. Based on various explicit examples, we observe conditions for linear and power law ramps to arise in deterministic spectra. We note that a very simple spectrum with a linear ramp is En ~ log n. Despite the presence of ramps, these sequences do not exhibit conventional level repulsion, demonstrating that the lore about their concurrence needs refinement. However, when a small noise correction is added to the spectrum, they lead to clear level repulsion as well as the (linear) ramp. We note some remarkable features of logarithmic spectra, apart from their linear ramps: they are closely related to normal modes of black hole stretched horizons, and their partition function with argument s = β + it is the Riemann zeta function ζ(s). An immediate consequence is that the spectral form factor is simply −ζ|(it)|2. Our observation that log spectra have a linear ramp, is closely related to the Lindelöf hypothesis on the growth of the zeta function. With elementary numerics, we check that the slope of a best fit line through |ζ(it)|2 on a log-log plot is indeed 1, to the fourth decimal. We also note that truncating the Riemann zeta function sum at a finite integer N causes the would-be-eternal ramp to end on a plateau.
Hypoxia-driven deSUMOylation of EXOSC10 promotes adaptive changes in the transcriptome profile
Authors: Filippopoulou Chrysa , Thomé Chairini C. , Perdikari Sofia , Ntini Evgenia , Simos George , Bohnsack Katherine E. , Chachami Georgia
Published: January 2024

Reduced oxygen availability (hypoxia) triggers adaptive cellular responses via hypoxia-inducible factor (HIF)-dependent transcriptional activation. Adaptation to hypoxia also involves transcription-independent processes like post-translational modifications; however, these mechanisms are poorly characterized. Investigating the involvement of protein SUMOylation in response to hypoxia, we discovered that hypoxia strongly decreases the SUMOylation of Exosome subunit 10 (EXOSC10), the catalytic subunit of the RNA exosome, in an HIF-independent manner. EXOSC10 is a multifunctional exoribonuclease enriched in the nucleolus that mediates the processing and degradation of various RNA species. We demonstrate that the ubiquitin-specific protease 36 (USP36) SUMOylates EXOSC10 and we reveal SUMO1/sentrin-specific peptidase 3 (SENP3) as the enzyme-mediating deSUMOylation of EXOSC10. Under hypoxia, EXOSC10 dissociates from USP36 and translocates from the nucleolus to the nucleoplasm concomitant with its deSUMOylation. Loss of EXOSC10 SUMOylation does not detectably affect rRNA maturation but affects the mRNA transcriptome by modulating the expression levels of hypoxia-related genes. Our data suggest that dynamic modulation of EXOSC10 SUMOylation and localization under hypoxia regulates the RNA degradation machinery to facilitate cellular adaptation to low oxygen conditions.
Functional role of Ash2l in oxLDL induced endothelial dysfunction and atherosclerosis
Authors: Su Zhenghua , Wang Jinghuan , Xiao Chenxi , Zhong Wen , Liu Jiayao , Liu Xinhua , Zhu Yi Zhun
Published: January 2024

Endothelial injury and dysfunction in the artery wall fuel the process of atherosclerosis. As a key epigenetic regulator, Ash2l (Absent, small, or homeotic-Like 2) is involved in regulating vascular injury and its complications. However, the role of Ash2l in atherosclerosis has not yet been fully elucidated. Here, we found increased Ash2l expression in high-cholesterol diet-fed ApoE−/− mice and oxidized LDL (oxLDL) treated endothelial cells (ECs). Furthermore, Ash2l promoted the scavenger receptors transcription by catalyzing histone H3 lysine 4 (H3K4) trimethylation at the promoter region of transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) and triggered the activation of the pro-inflammatory nuclear factor-kappa B (NF-κB) by enhancing interaction between CD36 and toll-like receptor 4 (TLR4). Meanwhile, enhanced expression of scavenger receptors drove more oxLDL uptake by ECs. In vivo studies revealed that ECs-specific Ash2l knockdown reduced atherosclerotic lesion formation and promoted fibrous cap stability in the aorta of ApoE−/− mice, which was partly associated with a reduced endothelial activation by suppressing scavenger receptors and the uptake of lipids by ECs. Collectively, our findings identify Ash2l as a novel regulator that mediates endothelial injury and atherosclerosis. Targeting Ash2l may provide valuable insights for developing novel therapeutic candidates for atherosclerosis.

Graphical Abstract
Shuffling Algorithm for Coupled Tilings of the Aztec Diamond
Authors: Keating David , Nicoletti Matthew
Published: January 2024

In this article, we define a generalization of the domino shuffling algorithm for tilings of the Aztec diamond to the interacting k-tilings recently introduced by S. Corteel, A. Gitlin, and the first author. We describe the algorithm both in terms of dynamics on a system of colored particles and as operations on the dominos themselves.
Understanding via exemplification in XAI: how explaining image classification benefits from exemplars
Authors: Mann Sara
Published: January 2024

Artificial intelligent (AI) systems that perform image classification tasks are being used to great success in many application contexts. However, many of these systems are opaque, even to experts. This lack of understanding can be problematic for ethical, legal, or practical reasons. The research field Explainable AI (XAI) has therefore developed several approaches to explain image classifiers. The hope is to bring about understanding, e.g., regarding why certain images are classified as belonging to a particular target class. Most of these approaches use visual explanations. Drawing on Elgin’s work (True enough. MIT Press, Cambridge, 2017), I argue that analyzing what those explanations exemplify can help to assess their suitability for producing understanding. More specifically, I suggest to distinguish between two forms of examples according to their suitability for producing understanding. I call these forms samples and exemplars, respectively. Samples are prone to misinterpretation and thus carry the risk of leading to misunderstanding. Exemplars, by contrast, are intentionally designed or chosen to meet contextual requirements and to mitigate the risk of misinterpretation. They are thus preferable for bringing about understanding. By reviewing several XAI approaches directed at image classifiers, I show that most of them explain with samples. If my analysis is correct, it will be beneficial if such explainability methods use explanations that qualify as exemplars.
Socratic nudges, virtual moral assistants and the problem of autonomy
Authors: Lara Francisco , Rodríguez-López Blanca
Published: January 2024

Many of our daily activities are now made more convenient and efficient by virtual assistants, and the day when they can be designed to instruct us in certain skills, such as those needed to make moral judgements, is not far off. In this paper we ask to what extent it would be ethically acceptable for these so-called virtual assistants for moral enhancement to use subtle strategies, known as “nudges”, to influence our decisions. To achieve our goal, we will first characterise nudges in their standard use and discuss the debate they have generated around their possible manipulative character, establishing three conditions of manipulation. Secondly, we ask whether nudges can occur in moral virtual assistants that are not manipulative. After critically analysing some proposed virtual assistants, we argue in favour of one of them, given that by pursuing an open and neutral moral enhancement, it promotes and respects the autonomy of the person as much as possible. Thirdly, we analyse how nudges could enhance the functioning of such an assistant, and evaluate them in terms of their degree of threat to the subject’s autonomy and their level of transparency. Finally, we consider the possibility of using motivational nudges, which not only help us in the formation of moral judgements but also in our moral behaviour.
The sociotechnical entanglement of AI and values
Authors: Johnson Deborah G. , Verdicchio Mario
Published: January 2024

Scholarship on embedding values in AI is growing. In what follows, we distinguish two concepts of AI and argue that neither is amenable to values being ‘embedded’. If we think of AI as computational artifacts, then values and AI cannot be added together because they are ontologically distinct. If we think of AI as sociotechnical systems, then components of values and AI are in the same ontologic category—they are both social. However, even here thinking about the relationship as one of ‘embedding’ is a mischaracterization. The relationship between values and AI is best understood as a dimension of the relationship between technology and society, a relationship that can be theorized in multiple ways. The literature in this area is consistent in showing that technology and society are co-productive. Within the co-production framework, the relationship between values and AI is shown to be generative of new meaning. This stands in stark contrast to the framework of ‘embedding’ values which frames values as fixed things that can be inserted into technological artifacts.
Effects of base plate temperature on microstructure evolution and high-temperature mechanical properties of IN718 processed by laser powder bed fusion using simulation and experiment
Authors: Kakehi Koji , Chowdhury Hasina Tabassum , Shinoda Yusuke , Naidu Palleda Thaviti , Kakuta Naoto , Ishisako Shohei
Published: January 2024

Base plate preheating is a relatively new strategy to influence the mechanical properties and microstructure of IN718. Base plate preheating was studied to reduce Niobium (Nb) segregation in the interdendritic region of IN718 superalloy and to improve mechanical properties through the laser powder bed fusion (L-PBF) process. Here, we compared experimental results for high-temperature (650℃) mechanical properties of specimens built with 200℃ (PH200) and 600℃ (PH600) preheated base plates. The as-built PH200 and PH600 specimens had relatively similar grain morphologies and orientations along the building direction. The PH200 specimen showed a cellular structure and higher Nb segregation at the interdendritic region, whereas the PH600 specimen had a dendritic structure and lower Nb segregation. The lower amount of Nb segregation in the PH600 specimen is mainly because of the cooling rate difference between specimens during the L-PBF process. The PH600 specimen exhibited slightly better tensile properties, longer creep life, and elongation than the PH200 specimen in both the as-built and heat-treated conditions. These differences mainly occurred due to differences in Laves and δ-phase fractions between the PH200 and PH600 specimens. The simulation result indicates that the temperature distribution in the block remains relatively uniform during the building process.
Evaluation of picture change effects on fractional occupation number states in noble gas atoms
Authors: Takashima Chinami , Nakai Hiromi
Published: January 2024

In the two-component relativistic density functional theory, the picture change error (PCE), which originates from insufficient transformation of operators, should be corrected. In this study, we examine the PCE in the fractional occupation number (FON) state based on the spin-free infinite-order two-component Hamiltonian. The PCE for the total and orbital energy changes is estimated with respect to the FON electrons of the highest occupied molecular orbital and 1s core orbital in noble gas atoms. PCE is significant in core orbitals in heavy elements but relatively small in light elements and valence orbitals. The delocalization error, which can be represented by the total energy deviation from the behavior of the exact energy, is overestimated by the lack of picture change correction of the two-electron operator and underestimated by that of the density operator. Corresponding to these results, the PCE influences the value of orbital energies and slope of orbital energy change to FON.
Novel method for rapid monitoring of OPFRs by LLE and GC–MS as a tool for assessing biodegradation: validation and applicability
Authors: Losantos Diana , Palacios Oscar , Berge María Jesús , Sarrà Montserrat , Caminal Gloria , Eustaquio Alba
Published: January 2024

Organophosphate flame retardants (OPFRs) are high-production volume chemicals widely present in environmental compartments. The presence of water-soluble OPFRs (tri-n-butyl phosphate (TnBP), tris(2-butoxyethyl) phosphate (TBEP), tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCPP), and triethyl phosphate (TEP)) in water compartments evidences the struggle of conventional wastewater treatment plants (WWTPs) to effectively eliminate these toxic compounds. This study reports for the first time the use of white-rot fungi as a promising alternative for the removal of these OPFRs. To accomplish this, a simple and cost-efficient quantification method for rapid monitoring of these contaminants’ concentrations by GC–MS while accounting for matrix effects was developed. The method proved to be valid and reliable for all the tested parameters. Sample stability was examined under various storage conditions, showing the original samples to be stable after 60 days of freezing, while post-extraction storage techniques were also effective. Finally, a screening of fungal degraders while assessing the influence of the glucose regime on OPFR removal was performed. Longer chain organophosphate flame retardants, TBP and TBEP, could be easily and completely removed by the fungus Ganoderma lucidum after only 4 days. This fungus also stood out as the sole organism capable of partially degrading TCEP (35% removal). The other chlorinated compound, TCPP, was more easily degraded and 70% of its main isomer was removed by T. versicolor. However, chlorinated compounds were only partially degraded under nutrient-limiting conditions. TEP was either not degraded or poorly degraded, and it is likely that it is a transformation product from another OPFR’s degradation. These results suggest that degradation of chlorinated compounds is dependent on the concentration of the main carbon source and that more polar OPFRs are less susceptible to degradation, given that they are less accessible to radical removal by fungi. Overall, the findings of the present study pave the way for further planned research and a potential application for the degradation of these contaminants in real wastewaters.

Graphical Abstract
Where Charged Sectors are Localizable: A Viewpoint from Covariant Cohomology
Authors: Ciolli Fabio , Ruzzi Giuseppe , Vasselli Ezio
Published: January 2024

Given a Haag–Kastler net on a globally hyperbolic spacetime, one can consider a family of regions where quantum charges are supposed to be localized. Assuming that the net fulfils certain minimal properties (factoriality of the global observable algebra and relative Haag duality), we give a geometric criterion that the given family must fulfil to have a superselection structure with charges localized on its regions. Our criterion is fulfilled by all the families used in the theory of sectors (double cones, spacelike cones, diamonds, hypercones). In order to take account of eventual spacetime symmetries, our superselection structures are constructed in terms of covariant charge transporters, a novel cohomological approach generalizing that introduced by J. E. Roberts. In the case of hypercones, with the forward light cone as an ambient spacetime, we obtain a superselection structure with Bose–Fermi parastatistics and particle-antiparticle conjugation. It could constitute a candidate for a different description of the charged sectors introduced by Buchholz and Roberts for theories including massless particles.
Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice
Authors: Cervantes-Torres Jacquelynne , Cabello-Gutiérrez Carlos , Ayón-Núñez Dolores-Adriana , Soldevila Gloria , Olguin-Alor Roxana , Diaz Georgina , Acero Gonzalo , Segura-Velázquez René , Huerta Leonor , Gracia-Mora Isabel , Cobos Laura , Pérez-Tapia Mayra , Almagro Juan C. , Suárez-Güemes Francisco , Bobes Raúl J. , Fragoso Gladis , Sciutto Edda , Laclette Juan Pedro
Published: January 2024

Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31–61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFNγ-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs.

Key points

• ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity

• A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice

• Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice
CD74 is associated with inflamed tumor immune microenvironment and predicts responsiveness to PD-1/CTLA-4 bispecific antibody in patients with solid tumors
Authors: Wang Jianghua , Li Xiaoting , Xiao Guanxi , Desai Jayesh , Frentzas Sophia , Wang Zhongmin Maxwell , Xia Yu , Li Baiyong
Published: January 2024

Introduction

Cadonilimab (AK104) is a first-in-class tetravalent bispecific antibody that targets both PD-1 and CTLA-4, showing a manageable safety profile and favorable clinical benefits. This study aimed to identify the biomarkers of clinical response and explore the immune response within the tumor microenvironment upon the AK104 therapy in advanced solid tumors.

Material and methods

Gene expression profiles of paired pre- and post-treatment tumor tissues from twenty-one patients were analyzed. The association of gene expression levels with either clinical efficacy or prognosis was evaluated and subsequently validated with published datasets using log-rank for Kaplan–Meier estimates. Comparative immune profile analyses of tumor microenvironment before and after AK104 treatment were conducted. The visualization of tumor-infiltrating lymphocytes was performed using multiplex immunohistochemistry. The predictive value of CD74 was further validated with protein expression by immunohistochemistry.

Results

Baseline CD74 gene expression was associated with favorable patient outcomes (overall survival [OS], HR = 0.33, 95% CI 0.11–1.03, p = 0.0463), which was further confirmed with the published datasets. Tumors with high CD74 gene expression at baseline were more likely to exhibit an immune-inflamed microenvironment. AK104 efficiently enhanced the infiltration of immune cells in the tumor microenvironment. Additionally, high CD74 protein expression (≥ 10% of the tumor area occupied by CD74 stained immune cells) at baseline was associated with better progressive-free survival (HR = 0.21, 95% CI 0.06–0.68, p = 0.0065) and OS (HR = 0.35, 95% CI 0.12–1.08, p = 0.0615).

Conclusions

Our findings demonstrate that CD74 is a promising predictive biomarker for AK104 therapeutic response in advanced solid tumors.

Trial registration number NCT03261011.
Targeting CD24/Siglec-10 signal pathway for cancer immunotherapy: recent advances and future directions
Authors: Li Xingchen , Tian Wenzhi , Jiang Zhongxing , Song Yongping , Leng Xiangyang , Yu Jifeng
Published: January 2024

The small, heavily glycosylated protein CD24 is primarily expressed by many immune cells and is highly expressed mostly in cancer cells. As one of the most crucial biomarkers of cancers, CD24 is frequently highly expressed in solid tumors, while tumor-associated macrophages express Siglec-10 at high levels, Siglec-10 and CD24 can interact on innate immune cells to lessen inflammatory responses to a variety of disorders. Inhibiting inflammation brought on by SHP-1 and/or SHP-2 phosphatases as well as cell phagocytosis by macrophages, the binding of CD24 to Siglec-10 can prevent toll-like receptor-mediated inflammation. Targeted immunotherapy with immune checkpoint inhibitors (ICI) has lately gained popularity as one of the best ways to treat different tumors. CD24 is a prominent innate immune checkpoint that may be a useful target for cancer immunotherapy. In recent years, numerous CD24/Siglec-10-related research studies have made tremendous progress. This study discusses the characteristics and workings of CD24/Siglec-10-targeted immunotherapy and offers a summary of current advances in CD24/Siglec-10-related immunotherapy research for cancer. We then suggested potential directions for CD24-targeted immunotherapy, basing our speculation mostly on the results of recent preclinical and clinical trials.
Butyricimonas is a key gut microbiome component for predicting postoperative recurrence of esophageal cancer
Authors: Otsuka Koji , Isobe Junya , Asai Yoshiyuki , Nakano Tomohisa , Hattori Kouya , Ariyoshi Tomotake , Yamashita Takeshi , Motegi Kentaro , Saito Akira , Kohmoto Masahiro , Hosonuma Masahiro , Kuramasu Atsuo , Baba Yuta , Murayama Masakazu , Narikawa Yoichiro , Toyoda Hitoshi , Funayama Eiji , Tajima Kohei , Shida Midori , Hirasawa Yuya , Tsurui Toshiaki , Ariizumi Hirotsugu , Ishiguro Tomoyuki , Suzuki Risako , Ohkuma Ryotaro , Kubota Yutaro , Sambe Takehiko , Tsuji Mayumi , Wada Satoshi , Kiuchi Yuji , Kobayashi Shinichi , Horiike Atsushi , Goto Satoru , Murakami Masahiko , Kim Yun-Gi , Tsunoda Takuya , Yoshimura Kiyoshi
Published: January 2024

Background

Recently, intestinal bacteria have attracted attention as factors affecting the prognosis of patients with cancer. However, the intestinal microbiome is composed of several hundred types of bacteria, necessitating the development of an analytical method that can allow the use of this information as a highly accurate biomarker. In this study, we investigated whether the preoperative intestinal bacterial profile in patients with esophageal cancer who underwent surgery after preoperative chemotherapy could be used as a biomarker of postoperative recurrence of esophageal cancer.

Methods

We determined the gut microbiome of the patients using 16S rRNA metagenome sequencing, followed by statistical analysis. Simultaneously, we performed a machine learning analysis using a random forest model with hyperparameter tuning and compared the data obtained.

Results

Statistical and machine learning analyses revealed two common bacterial genera, Butyricimonas and Actinomyces, which were abundant in cases with recurrent esophageal cancer. Butyricimonas primarily produces butyrate, whereas Actinomyces are oral bacteria whose function in the gut is unknown.

Conclusion

Our results indicate that Butyricimonas spp. may be a biomarker of postoperative recurrence of esophageal cancer. Although the extent of the involvement of these bacteria in immune regulation remains unknown, future research should investigate their presence in other pathological conditions. Such research could potentially lead to a better understanding of the immunological impact of these bacteria on patients with cancer and their application as biomarkers.
Novel mechanism of drug resistance triggered by tumor-associated macrophages through Heat Shock Factor-1 activation
Authors: Nikotina Alina D. , Vladimirova Snezhana A. , Kokoreva Nadezhda E. , Nevdakha Valeria A. , Lazarev Vladimir F. , Kuznetcova Liubov S. , Komarova Elena Y. , Suezov Roman V. , Efremov Sergei , Leonova Elizaveta , Kartsev Viktor G. , Aksenov Nikolay D. , Margulis Boris A. , Guzhova Irina V.
Published: January 2024

Macrophages constitute a major part of tumor microenvironment, and most of existing data demonstrate their ruling role in the development of anti-drug resistance of cancer cell. One of the most powerful protection system is based on heat shock proteins whose synthesis is triggered by activated Heat Shock Factor-1 (HSF1); the inhibition of the HSF1 with CL-43 sensitized A549 lung cancer cells to the anti-cancer effect of etoposide. Notably, analyzing A549 tumor xenografts in mice we observed nest-like pattern of co-localization of A549 cells demonstrating enhanced expression of HSF1 with macrophages, and decided to check whether the above arrangement has a functional value for both cell types. It was found that the incubation of A549 or DLD1 colon cancer cells with either human monocytes or THP1 monocyte-like cells activated HSF1 and increased resistance to etoposide. Importantly, the same effect was shown when primary cultures of colon tumors were incubated with THP1 cells or with human monocytes. To prove that HSF1 is implicated in enhanced resistance caused by monocytic cells, we generated an A549 cell subline devoid of HSF1 which did not respond to incubation with THP1 cells. The pharmacological inhibition of HSF1 with CL-43 also abolished the effect of THP1 cells on primary tumor cells, highlighting a new target of tumor-associated macrophages in a cell proteostasis mechanism.
Incidence of brain injuries in a large cohort of very preterm and extremely preterm infants at term-equivalent age: results of a single tertiary neonatal care center over 10 years
Authors: Drommelschmidt Karla , Mayrhofer Thomas , Hüning Britta , Stein Anja , Foldyna Borek , Schweiger Bernd , Felderhoff-Müser Ursula , Sirin Selma
Published: January 2024

Objectives

Cerebral magnetic resonance imaging (cMRI) at term-equivalent age (TEA) can detect brain injury (BI) associated with adverse neurological outcomes in preterm infants. This study aimed to assess BI incidences in a large, consecutive cohort of preterm infants born < 32 weeks of gestation, the comparison between very (VPT, ≥ 28 + 0 to < 32 + 0 weeks of gestation) and extremely preterm infants (EPT, < 28 + 0 weeks of gestation) and across weeks of gestation.

Methods

We retrospectively analyzed cMRIs at TEA of VPT and EPT infants born at a large tertiary center (2009–2018). We recorded and compared the incidences of BI, severe BI, intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhage (CBH), cystic periventricular leukomalacia (cPVL), and punctate white matter lesions (PWML) between VPTs, EPTs, and across weeks of gestation.

Results

We included 507 preterm infants (VPT, 335/507 (66.1%); EPT, 172/507 (33.9%); mean gestational age (GA), 28 + 2 weeks (SD 2 + 2 weeks); male, 52.1%). BIs were found in 48.3% of the preterm infants (severe BI, 12.0%) and increased with decreasing GA. IVH, PVHI, CBH, cPVL, and PWML were seen in 16.8%, 0.8%, 10.5%, 3.4%, and 18.1%, respectively. EPT vs. VPT infants suffered more frequently from BI (59.3% vs. 42.7%, p < 0.001), severe BI (18.6% vs. 8.7%, p = 0.001), IVH (31.9% vs. 9.0%, p < 0.001), and CBH (18.0% vs. 6.6%, p < 0.001).

Conclusion

Brain injuries are common cMRI findings among preterm infants with a higher incidence of EPT compared to VPT infants. These results may serve as reference values for clinical management and research.

Clinical relevance statement

Our results with regard to gestational age might provide valuable clinical insights, serving as a key reference for parental advice, structured follow-up planning, and enhancing research and management within the Neonatal Intensive Care Unit.

Key Points

• Brain injury is a common cMRI finding in preterm infants seen in 48.3% individuals.

• Extremely preterm compared to very preterm infants have higher brain injury incidences driven by brain injuries such as intraventricular and cerebellar hemorrhage.

• Reference incidence values are crucial for parental advice and structured follow-up planning.
Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases
Authors: Aguero Cinthya , Dhaynaut Maeva , Amaral Ana C. , Moon S.-H. , Neelamegam Ramesh , Scapellato Margaret , Carazo-Casas Carlos , Kumar Sunny , El Fakhri Georges , Johnson Keith , Frosch Matthew P. , Normandin Marc D. , Gómez-Isla Teresa
Published: January 2024

We and others have shown that [18F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to tau aggregates in Alzheimer's (AD) but has relatively low affinity for tau aggregates in non-AD tauopathies and exhibits off-target binding to neuromelanin- and melanin-containing cells, and to hemorrhages. Several second-generation tau tracers have been subsequently developed. [18F]-MK-6240 and [18F]-PI-2620 are the two that have garnered most attention. Our recent data indicated that the binding pattern of [18F]-MK-6240 closely parallels that of [18F]-Flortaucipir. The present study aimed at the direct comparison of the autoradiographic binding properties and off-target profile of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 in human tissue specimens, and their potential binding to monoamine oxidases (MAO). Phosphor-screen and high resolution autoradiographic patterns of the three tracers were studied in the same postmortem tissue material from AD and non-AD tauopathies, cerebral amyloid angiopathy, synucleopathies, transactive response DNA-binding protein 43 (TDP-43)-frontotemporal lobe degeneration and controls. Our results show that the three tracers show nearly identical autoradiographic binding profiles. They all strongly bind to neurofibrillary tangles in AD but do not seem to bind to a significant extent to tau aggregates in non-AD tauopathies pointing to their limited utility for the in vivo detection of non-AD tau lesions. None of them binds to lesions containing β-amyloid, α-synuclein or TDP-43 but they all show strong off-target binding to neuromelanin and melanin-containing cells, as well as weaker binding to areas of hemorrhage. The autoradiographic binding signals of the three tracers are only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline suggesting that MAO enzymes do not appear to be a significant binding target of any of them. These findings provide relevant insights for the correct interpretation of the in vivo behavior of these three tau PET tracers.
Long-term medication for ADHD (LMA) trial: 2-year prospective observational study in children and adolescents. Core symptoms, daily functioning, and comorbidity outcomes
Authors: Johnson M. , Johnels J. Åsberg , Östlund S. , Jakobsson K. , Högstedt J. , Larsson P. Javid , Gillberg C. , Billstedt E.
Published: January 2024

More knowledge is needed about long-term ADHD medication and symptom, daily functioning, comorbidity, and tolerability outcomes. This “Long-term Medication for ADHD (LMA) trial” was a prospective observational 2-year trial in children and adolescents aged 6–18 years (extension of 1-year trial). Participants met criteria for DSM-5 ADHD (inattentive or combined), with complex comorbidities; autism spectrum disorder (31%), autistic traits (24%), oppositional symptoms (59%), anxiety (32%), dyslexia/language disorder (16%), borderline intellectual functioning (17%). Medication was individually tailored and followed-up at clinical visits (1, 2, 3, 6, 12, 18, 24 months). Primary outcome: Clinical Global Impression-Severity and Improvement scales (CGI-S, CGI-I). Secondary outcomes: Investigator-rated ADHD-Rating Scale, Weiss Functional Impairment Rating Scale-Parent report (WFIRS-P; Family, School Learning and Behavior, Life Skills, Self-Concept, Social Activities, and Risky Activities domains), comorbidity symptoms and adverse events (AEs). One hundred twenty-eight participants were enrolled (1-year trial onlyn = 27, LMA trialn = 101). Of these 29 (23%) discontinued, mainly due to AEs (n = 7), moving (n = 7), or no longer needing medication (n = 6). Main AEs were poor appetite, low mood, anxiety, irritability, fatigue. Improvements from baseline to 2 years were large in CGI-S (effect size (ES) 2.28), ADHD-RS (ES 2.06), and moderate to large in WFIRS-P (ES total 0.73, learning 0.4, family 0.67). Overall, the trial showed robust and sustained improvements in ADHD symptom severity and daily functioning over a period of 2 years of ADHD medication in children and adolescents with ADHD and complex comorbidities. Most AEs were mild. Comorbidity symptoms were improved after 1 year, particularly oppositional symptoms, depression, and anxiety.
Abnormal vestibular-evoked myogenic potentials as a risk factor for unpredicted falls in spinocerebellar ataxia: a preliminary study
Authors: Choi Seo-Young , Choi Kwang-Dong , Choi Jae-Hwan , Kim Ji-Soo
Published: January 2024

Objective

This study aimed to correlate the symptoms and signs with the findings of laboratory vestibular function tests in patients with spinocerebellar ataxia (SCA).

Method

We retrospectively recruited 26 patients with SCA (9 men, median age: 52, age range: 21–67). Assessments included Dizziness Handicap Inventory, EuroQoL Five-Dimension, symptom questionnaires manifesting during walking in daily life, the Scale for the Assessment and Rating of Ataxia (SARA), and vestibular function tests including 3D video-oculography, video head impulse test, subjective visual vertical, and cervical and ocular vestibular evoked myogenic potentials (VEMP).

Results

Cross-analyses revealed that the patients with VEMP abnormalities showed higher SARA (p = 0.014) and prevalence of unpredictable falls (p = 0.046). The patients with SCA1 more frequently had unpredictable falls (75%, p = 0.038) and VEMP abnormalities (88%, p = 0.001) compared to SCA2 (29% falls, 17% VEMP abnormalities) and SCA6 (no falls or VEMP abnormalities).

Conclusion

Abnormal VEMPs are strongly associated with unpredicted falls in patients with SCA, particularly in those with SCA1. Impaired processing of otolithic information may contribute to falls in SCAs, and VEMP may help identifying the patients with a risk for unpredicted falls and preventing fall-related injuries in SCA. Limited number of patients with lower SARA scores warrant further confirmatory studies.
How to activate the glutes best? Peak muscle activity of acceleration-specific pre-activation and traditional strength training exercises
Authors: Goller Maximilian , Quittmann Oliver J. , Alt Tobias
Published: January 2024

Purpose

Isometric training and pre-activation are proven to enhance acceleration performance. However, traditional strength training exercises do not mirror the acceleration-specific activation patterns of the gluteal muscles, characterized by ipsilateral hip extension during contralateral hip flexion. Therefore, the aim of the study was to determine gluteal muscle activity of acceleration-specific exercises compared to traditional strength training exercises.

Methods

In a cross-sectional study design, the peak electromyographic activity of two acceleration-specific exercises was investigated and compared to two traditional strength training exercises each for the gluteus maximus and medius. Twenty-four participants from various athletic backgrounds (13 males, 11 females, 26 years, 178 cm, 77 kg) performed four gluteus maximus [half-kneeling glute squeeze (HKGS), resisted knee split (RKS), hip thrust (HT), split squat (SS)] and four gluteus medius [resisted prone hip abduction (RPHA), isometric clam (IC), side-plank with leg abduction (SP), resisted side-stepping (RSS)] exercises in a randomized order.

Results

The RKS (p = 0.011,d = 0.96) and the HKGS (p = 0.064,d = 0.68) elicited higher peak gluteus maximus activity than the SS with large and moderate effects, respectively. No significant differences (p > 0.05) were found between the HT, RKS and HKGS. The RPHA elicited significantly higher gluteus medius activity with a large effect compared to RSS (p < 0.001,d = 1.41) and a moderate effect relative to the SP (p = 0.002,d = 0.78).

Conclusion

The acceleration-specific exercises effectively activate the gluteal muscles for pre-activation and strength training purposes and might help improve horizontal acceleration due to their direct coordinative transfer.
Mononuclear phagocyte system-related multi-omics features yield head and neck squamous cell carcinoma subtypes with distinct overall survival, drug, and immunotherapy responses
Authors: Zhang Cong , Deng Jielian , Li Kangjie , Lai Guichuan , Liu Hui , Zhang Yuan , Xie Biao , Zhong Xiaoni
Published: January 2024

Background

Recent research reported that mononuclear phagocyte system (MPS) can contribute to immune defense but the classification of head and neck squamous cell carcinoma (HNSCC) patients based on MPS-related multi-omics features using machine learning lacked.

Methods

In this study, we obtain marker genes for MPS through differential analysis at the single-cell level and utilize “similarity network fusion” and “MoCluster” algorithms to cluster patients’ multi-omics features. Subsequently, based on the corresponding clinical information, we investigate the prognosis, drugs, immunotherapy, and biological differences between the subtypes. A total of 848 patients have been included in this study, and the results obtained from the training set can be verified by two independent validation sets using “the nearest template prediction”.

Results

We identified two subtypes of HNSCC based on MPS-related multi-omics features, with CS2 exhibiting better predictive prognosis and drug response. CS2 represented better xenobiotic metabolism and higher levels of T and B cell infiltration, while the biological functions of CS1 were mainly enriched in coagulation function, extracellular matrix, and the JAK-STAT signaling pathway. Furthermore, we established a novel and stable classifier called “getMPsub” to classify HNSCC patients, demonstrating good consistency in the same training set. External validation sets classified by “getMPsub” also illustrated similar differences between the two subtypes.

Conclusions

Our study identified two HNSCC subtypes by machine learning and explored their biological difference. Notably, we constructed a robust classifier that presented an excellent classifying prediction, providing new insight into the precision medicine of HNSCC.
Multi-omics and Multi-VOIs to predict esophageal fistula in esophageal cancer patients treated with radiotherapy
Authors: Guo Wei , Li Bing , Xu Wencai , Cheng Chen , Qiu Chengyu , Sam Sai-kit , Zhang Jiang , Teng Xinzhi , Meng Lingguang , Zheng Xiaoli , Wang Yuan , Lou Zhaoyang , Mao Ronghu , Lei Hongchang , Zhang Yuanpeng , Zhou Ta , Li Aijia , Cai Jing , Ge Hong
Published: January 2024

Objective

This study aimed to develop a prediction model for esophageal fistula (EF) in esophageal cancer (EC) patients treated with intensity-modulated radiation therapy (IMRT), by integrating multi-omics features from multiple volumes of interest (VOIs).

Methods

We retrospectively analyzed pretreatment planning computed tomographic (CT) images, three-dimensional dose distributions, and clinical factors of 287 EC patients. Nine groups of features from different combination of omics [Radiomics (R), Dosiomics (D), and RD (the combination of R and D)], and VOIs [esophagus (ESO), gross tumor volume (GTV), and EG (the combination of ESO and GTV)] were extracted and separately selected by unsupervised (analysis of variance (ANOVA) and Pearson correlation test) and supervised (Student T test) approaches. The final model performance was evaluated using five metrics: average area under the receiver-operator-characteristics curve (AUC), accuracy, precision, recall, and F1 score.

Results

For multi-omics using RD features, the model performance in EG model shows: AUC, 0.817 ± 0.031; 95% CI 0.805, 0.825; p < 0.001, which is better than single VOI (ESO or GTV).

Conclusion

Integrating multi-omics features from multi-VOIs enables better prediction of EF in EC patients treated with IMRT. The incorporation of dosiomics features can enhance the model performance of the prediction.
Lifetime risks of second primary malignancies after pediatric Hodgkin lymphoma and non-Hodgkin lymphoma
Authors: Wang Laduona , Zheng Yue , Luo Ren , Kang Kai , Niedermann Gabriele , Zhao Ailin , Wu Yijun
Published: January 2024

Objectives

Survivors after pediatric Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are with lifetime risk for second primary malignancy (SPM). This necessitates a thorough analysis to better understand the potential long-term health implications for these individuals.

Methods

We used a US-wide population-based cancer registry data to quantify the SPM risk and identify its incidence patterns among pediatric lymphoma patients.

Results

We observed 4.74-fold (95% CI 4.27–5.25) and 3.40-fold (95% CI 2.78–4.10) increased risks of SPM in survivors after pediatric HL and NHL, respectively. Through over 40 years’ follow-up, the cumulative incidence of SPM for pediatric lymphoma was persistently increasing, and here we firstly report the high 40-year cumulative incidence rates of SPM, 22.2% for HL and 12.6% for NHL, suggesting that SPM accounts for a great proportion of deaths among survivors. Of 6805 pediatric lymphomas, 462 (6.36%) developed a SPM, especially second breast and thyroid cancer, followed by hematologic neoplasms including leukemia and NHL. The competing risk analysis demonstrated gender, lymphoma subtype and radiotherapy were significantly associated with SPM. Different risk patterns of SPM were identified between pediatric HL and NHL. Chemotherapy accelerated SPM development but did not increase its incidence risk.

Conclusion

Overall, patients after pediatric lymphoma can be with high lifetime risk of SPM, and more attention should be paid to SPM-related signs for early detection and intervention.
3D-printed glenoid implant reconstruction, after partial scapulectomy for malignant tumors: a case series
Authors: Trikoupis Ioannis G. , Mavrodontis Ioannis I. , Papadopoulos Dimitrios V. , Goumenos Stavros D. , Georgoulis Dimitrios A. , Gavriil Panagiotis , Melissaridou Dimitra , Savvidou Olga D. , Kontogeorgakos Vasileios A. , Papagelopoulos Panayiotis J.
Published: January 2024

Purpose

Glenoid tumors are extremely rare, and reconstruction remains very challenging. The aim of this study is to present the clinical and functional outcomes, of a new glenoid reconstruction method using 3-dimensional-printed implant.

Methods

Four patients with primary glenoid tumors underwent reconstruction using 3-dimensional-printed glenoid implant linked with reverse shoulder arthroplasty. We retrospectively reviewed the clinical and functional outcome, using MSTS and DASH score, as well as complications’ rate.

Results

Wide excision was achieved in all patients. No local recurrence or distant metastasis was diagnosed at the follow-up period. The mean MSTS score was 80.5%, and DASH score was 15.2%. According to Hendersons’ classification, there were no postoperative complications.

Conclusion

The use of 3-dimensional-printed implants, can be a very reliable solution with satisfying clinical and functional outcomes for reconstruction, in patients with musculoskeletal malignancies of the glenoid.

Level of evidence IV Treatment Study.
Unraveling the multiplicity of geranylgeranyl reductases in Archaea: potential roles in saturation of terpenoids
Authors: Rao Alka , Driessen Arnold J. M.
Published: January 2024

The enzymology of the key steps in the archaeal phospholipid biosynthetic pathway has been elucidated in recent years. In contrast, the complete biosynthetic pathways for proposed membrane regulators consisting of polyterpenes, such as carotenoids, respiratory quinones, and polyprenols remain unknown. Notably, the multiplicity of geranylgeranyl reductases (GGRs) in archaeal genomes has been correlated with the saturation of polyterpenes. Although GGRs, which are responsible for saturation of the isoprene chains of phospholipids, have been identified and studied in detail, there is little information regarding the structure and function of the paralogs. Here, we discuss the diversity of archaeal membrane-associated polyterpenes which is correlated with the genomic loci, structural and sequence-based analyses of GGR paralogs.