bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractOrganophosphate 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

AbstractGiven 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

Abstract
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

Abstract
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

AbstractThe 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

Abstract
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

AbstractMacrophages 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

Abstract
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

AbstractWe 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

AbstractMore 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

Abstract
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.