bluuebunny/crossref_metadata_2025_split huggingface dataset:
A modular SU (5) littlest seesaw
Authors: de Medeiros Varzielas Ivo , King Steve F. , Levy Miguel 
Published: May 2024

Abstract
We extend the littlest modular seesaw to a Grand Unified scenario based on SU (5) endowed with three modular S4 symmetries. We leverage symmetry protected zeroes in the leptonic and down quark sectors to suppress deviations to the littlest modular seesaw predictions, but not contributions to the quark mixing. The model is supplemented by two weighton fields, such that the hierarchical nature of the charged-lepton masses, as well as the quark masses and mixing, stem from the content and symmetries of the model, rather than a hierarchical nature of the Yukawa coefficients.
Explanation of the hints for a 95 GeV Higgs boson within a 2-Higgs Doublet Model
Authors: Belyaev A. , Benbrik R. , Boukidi M. , Chakraborti M. , Moretti S. , Semlali S. 
Published: May 2024

Abstract
We suggest an explanation for and explore the consequences of the excess around 95 GeV in the di-photon and di-tau invariant mass distributions recently reported by the CMS collaboration at the Large Hadron Collider (LHC), together with the discrepancy that has long been observed at the Large Electron-Positron (LEP) collider in the $$ b\overline{b} $$
b

b
¯

invariant mass. Interestingly, the most recent findings announced by the ATLAS collaboration do not contradict, or even support, these intriguing observations. Their search in the di-photon final state similarly reveals an excess of events within the same mass range, albeit with a bit lower significance, thereby corroborating and somewhat reinforcing the observations made by CMS.We demonstrate that the lightest CP-even Higgs boson in the general 2-Higgs Doublet Model (2HDM) Type-III can explain simultaneously the observed excesses at approximately 1.3 σ C.L. while satisfying up-to-date theoretical and experimental constraints. Moreover, the 2HDM Type-III predicts an excess in the $$ pp\to t\overline{t}{H}_{\textrm{SM}} $$
pp
→
t

t
¯

H
SM

production channel of the 125 GeV Higgs boson, HSM. This effect is caused by a up to 12% enhancement of the HSMtt Yukawa coupling in comparison to that predicted by the Standard Model. Such an effect can be tested at the High Luminosity LHC (HL-LHC), which can either discover or exclude the scenario we suggest. This unique characteristic of the 2HDM Type-III makes this scenario with the 95 GeV resonance very attractive for further theoretical and experimental investigations at the (HL-)LHC and future colliders.
Mechanistic safety assessment via multi-omic characterisation of systemic pathway perturbations following in vivo MAT2A inhibition
Authors: Fogal Valentina , Michopoulos Filippos , Jarnuczak Andrew F. , Hamza Ghaith M. , Harlfinger Stephanie , Davey Paul , Hulme Heather , Atkinson Stephen J. , Gabrowski Piotr , Cheung Tony , Grondine Michael , Hoover Clare , Rose Jonathan , Bray Chandler , Foster Alison J. , Askin Sean , Majumder Muntasir Mamun , Fitzpatrick Paul , Miele Eric , Macdonald Ruth , Keun Hector C. , Coen Muireann 
Published: May 2024

AbstractThe tumour suppressor p16/CDKN2A and the metabolic gene, methyl-thio-adenosine phosphorylase (MTAP), are frequently co-deleted in some of the most aggressive and currently untreatable cancers. Cells with MTAP deletion are vulnerable to inhibition of the metabolic enzyme, methionine-adenosyl transferase 2A (MAT2A), and the protein arginine methyl transferase (PRMT5). This synthetic lethality has paved the way for the rapid development of drugs targeting the MAT2A/PRMT5 axis. MAT2A and its liver- and pancreas-specific isoform, MAT1A, generate the universal methyl donor S-adenosylmethionine (SAM) from ATP and methionine. Given the pleiotropic role SAM plays in methylation of diverse substrates, characterising the extent of SAM depletion and downstream perturbations following MAT2A/MAT1A inhibition (MATi) is critical for safety assessment. We have assessed in vivo target engagement and the resultant systemic phenotype using multi-omic tools to characterise response to a MAT2A inhibitor (AZ’9567). We observed significant SAM depletion and extensive methionine accumulation in the plasma, liver, brain and heart of treated rats, providing the first assessment of both global SAM depletion and evidence of hepatic MAT1A target engagement. An integrative analysis of multi-omic data from liver tissue identified broad perturbations in pathways covering one-carbon metabolism, trans-sulfuration and lipid metabolism. We infer that these pathway-wide perturbations represent adaptive responses to SAM depletion and confer a risk of oxidative stress, hepatic steatosis and an associated disturbance in plasma and cellular lipid homeostasis. The alterations also explain the dramatic increase in plasma and tissue methionine, which could be used as a safety and PD biomarker going forward to the clinic.
The Cold War in pharmacology: a bibliometric analysis of Berlin’s contributions to Naunyn‑Schmiedeberg’s Archives of Pharmacology (1947–1974)
Authors: Basol Mert Erkan , Seifert Roland 
Published: May 2024

AbstractAfter World War II, Berlin was divided into the West, controlled by The United States, the UK, and France, and the East, controlled by the Soviet Union, resulting in a Cold War for decades. This bibliometric study analyzes the influence of the Cold War on pharmacological research in Berlin by evaluating publication patterns in Naunyn-Schmiedeberg’s Archives of Pharmacology from 1947 to 1974 (n = 383). The publications highlight the political disparities in scientific output, exacerbated by the founding of the Free University of Berlin (FUB) as a countermeasure to Soviet repression, promoting academic freedom in West-Berlin. Researchers in West-Berlin published many more papers in Naunyn-Schmiedeberg’s Archives of Pharmacology than researchers in East-Berlin and received much more citations. West-Berlin adopted English as a scientific language much more rapidly than East-Berlin. West-Berlin and East-Berlin focused on totally different research topics. This paper demonstrates how political freedom, financial support, and internationalization boosted research productivity in West-Berlin. In contrast, political suppression, financial scarcity, and restricted international ties hindered scientific development in East-Berlin.
The later-line efficacy and safety of immune checkpoint inhibitors plus anlotinib in EGFR-mutant patients with EGFR-TKI-resistant NSCLC: a single-center retrospective study
Authors: Yin Xiaoyan , Liu Xinchao , Ren Fei , Meng Xiangjiao 
Published: May 2024

Abstract
Background
Effective treatment after EGFR-TKI resistance is of great clinical concern. We aimed to investigate the efficacy and safety of anlotinib in combination with an anti-PD-1/PD-L1 antibody in later-line therapy for EGFR-mutant NSCLC patients after TKI treatment failure and to explore the independent predictive factors of therapeutic efficacy.

Methods
A total of 71 patients with confirmed advanced EGFR-mutated NSCLC who progressed after previous standard EGFR-TKI therapy but still failed after multiline treatments were included retrospectively in this study. Most of the patients had previously received at least three lines of treatment. All were treated with anlotinib combined with anti-PD-1 or anti-PD-L1 therapy. The safety of this combined treatment was assessed by the incidence of adverse events. The efficacy of the regimens was evaluated by survival analysis (OS, PFS, ORR, DCR).

Results
The median follow-up period was 28.6 months (range: 2.3–54.0 months), and the median number of treatment lines was 4. The overall response rate (ORR) and disease control rate (DCR) were 19.7% and 77.5%, respectively. The median PFS was 5.8 months (95% CI 4.2–7.4 months), and the median OS was 17.1 months (95% CI 12.0–22.3 months). Patients who received immune checkpoint inhibitors plus anlotinib had an encouraging intracranial ORR of 38.5% and a DCR of 80.8%. ECOG performance status < 2 at baseline was independent protective factors of PFS. Metastatic organs and ECOG performance status were independent parameters in predicting OS. Treatment-related adverse events occurred in 66 (93.0%) patients; most of the adverse events were Grade 1–2, and no increase in adverse events was observed compared to monotherapy.

Conclusion
Anlotinib combined with an anti-PD-1/PD-L1-based regimen exhibited promising efficacy and tolerance in NSCLC patients with EGFR mutations after previous TKI failure. The efficacy of this combined regimen in patients with EGFR mutations should be further evaluated.
A nanogold sensor test for tire wear chemicals based on the plasmon ruler approach
Authors: Gagné François , Roubeau-Dumont Eva , André Chantale 
Published: May 2024

AbstractThe release of tire wear substances in the environment is raising concerns about potential impacts on aquatic ecosystems. The purpose of this study was to develop a quick and inexpensive screening test for the following tire wear substances: 6-phenylphenyldiamine quinone (6-PPD quinone), hexamethoxymethylmelamine (HMMM), 1–3-diphenylguanidine (1,3-DPG), and melamine. A dual strategy consisting of nanogold (nAu) signal intensity and the plasmonic ruler principle was used based on the spectral shift from the unaggregated free-form nAu from 525 nm to aggregated nAu at higher wavelengths. The shift in resonance corresponded to the relative sizes of the tire wear substances at the surface of nAu: 6-PPD (560 nm), HMMM (590 nm), 1,3-DPG (620 nm), and melamine (660 nm) in a concentration-dependent manner. When present in mixtures, a large indiscriminate band between 550 and 660 nm with a maximum corresponding to the mean intermolecular distance of 0.43 nm from the tested individual substances suggests that all compounds indiscriminately interacted at the surface of nAu. An internal calibration methodology was developed for mixtures and biological extracts from mussels and biofilms and revealed a proportional increase in absorbance at the corresponding resonance line for each test compound. Application of this simple and quick methodology revealed the increased presence of melamine and HMMM compounds in mussels and biofilms collected at urban sites (downstream city, road runoffs), respectively. The data also showed that treated municipal effluent decreased somewhat melamine levels in mussels.
Graphical Abstract
Comparative proteomic analysis of dental pulp from supernumerary and normal permanent teeth
Authors: Lertruangpanya Kritkamon , Roytrakul Sittiruk , Surarit Rudee , Horsophonphong Sivaporn 
Published: May 2024

Abstract
Objectives
To obtain and compare the protein profiles of supernumerary and normal permanent dental pulp tissues.

Materials and methods
Dental pulp tissues were obtained from supernumerary and normal permanent teeth. Proteins were extracted and analyzed by liquid chromatography-tandem mass spectrometry (LC/MS-MS). Protein identification and quantification from MS data was performed with MaxQuant. Statistical analysis was conducted using Metaboanalyst to identify differentially expressed proteins (DEPs) (P-value < 0.05, fold-change > 2). Gene Ontology enrichment analyses were performed with gProfiler.

Results
A total of 3,534 proteins were found in normal dental pulp tissue and 1,093 in supernumerary dental pulp tissue, with 174 DEPs between the two groups. This analysis revealed similar functional characteristics in terms of cellular component organization, cell differentiation, developmental process, and response to stimulus, alongside exclusive functions unique to normal permanent dental pulp tissues such as healing, vascular development and cell death. Upon examination of DEPs, these proteins were associated with the processes of wound healing and apoptosis.

Conclusions
This study provides a comprehensive understanding of the protein profile of dental pulp tissue, including the first such profiling of supernumerary permanent dental pulp. There are functional differences between the proteomic profiles of supernumerary and normal permanent dental pulp tissue, despite certain biological similarities between the two groups. Differences in protein expression were identified, and the identified DEPs were linked to the healing and apoptosis processes.

Clinical relevance
This discovery enhances our knowledge of supernumerary and normal permanent pulp tissue, and serves as a valuable reference for future studies on supernumerary teeth.
A journey with ASMETA from requirements to code: application to an automotive system with adaptive features
Authors: Arcaini Paolo , Bonfanti Silvia , Gargantini Angelo , Riccobene Elvinia , Scandurra Patrizia 
Published: May 2024

AbstractModern automotive systems with adaptive control features require rigorous analysis to guarantee correct operation. We report our experience in modeling the automotive case study from the ABZ2020 conference using the ASMETA toolset, based on the Abstract State Machine formal method. We adopted a seamless system engineering method: from an incremental formal specification of high-level requirements to increasingly refined ASMETA models, to the C++ code generation from the model. Along this process, different validation and verification activities were performed. We explored modeling styles and idioms to face the modeling complexity and ensure that the ASMETA models can best capture and reflect specific behavioral patterns. Through this realistic automotive case study, we evaluated the applicability and usability of our formal modeling approach.
Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis
Authors: Shen Yuqi , Wen Dan , Liang Zhenghua , Wan Li , Jiang Qingli , He Haiyan , He Mei 
Published: May 2024

AbstractTo assess whether monitoring brain tissue oxygen partial pressure (PbtO2) or employing intracranial pressure (ICP)/cerebral perfusion pressure (CCP)-guided management improves patient outcomes, including mortality, hospital length of stay (LOS), mean daily ICP and mean daily CCP during the intensive care unit(ICU)stay. We searched the Web of Science, EMBASE, PubMed, Cochrane Library, and MEDLINE databases until December 12, 2023. Prospective randomized controlled and cohort studies were included. A meta-analysis was performed for the primary outcome measure, mortality, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eleven studies with a total of 37,492 patients were included. The mortality in the group with PbtO2 was 29.0% (odds ratio: 0.73;95% confidence interval [CI]:0.56–0.96; P = 0.03; I = 55%), demonstrating a significant benefit. The overall hospital LOS was longer in the PbtO2 group than that in the ICP/CPP group (mean difference:2.03; 95% CI:1.03–3.02; P<0.0001; I = 39%). The mean daily ICP in the PbtO2 monitoring group was lower than that in the ICP/CPP group (mean difference:-1.93; 95% CI: -3.61 to -0.24; P = 0.03; I = 41%). Moreover, PbtO2 monitoring did not improve the mean daily CPP (mean difference:2.43; 95%CI: -1.39 to 6.25;P = 0.21; I = 56%).Compared with ICP/CPP monitoring, PbtO2 monitoring reduced the mortality and the mean daily ICP in patients with severe traumatic brain injury; however, no significant effect was noted on the mean daily CPP. In contrast, ICP/CPP monitoring alone was associated with a short hospital stay.
Early localization of tissue at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: blood distribution on initial imaging vs early CT perfusion
Authors: Malinova Vesna , Kranawetter Beate , Tuzi Sheri , Rohde Veit , Mielke Dorothee 
Published: May 2024

Abstract
Objective
Delayed cerebral ischemia (DCI) is a potentially reversible adverse event after aneurysmal subarachnoid hemorrhage (aSAH), when early detected and treated. Computer tomography perfusion (CTP) is used to identify the tissue at risk for DCI. In this study, the predictive power of early CTP was compared with that of blood distribution on initial CT for localization of tissue at risk for DCI.

Methods
A consecutive patient cohort with aSAH treated between 2012 and 2020 was retrospectively analyzed. Blood distribution on CT was semi-quantitatively assessed with the Hijdra-score. The vessel territory with the most surrounding blood and the one with perfusion deficits on CTP performed on day 3 after ictus were considered to be at risk for DCI, respectively.

Results
A total of 324 patients were included. Delayed infarction occurred in 17% (56/324) of patients. Early perfusion deficits were detected in 82% (46/56) of patients, 85% (39/46) of them developed infarction within the predicted vessel territory at risk. In 46% (25/56) a vessel territory at risk was reliably determined by the blood distribution. For the prediction of DCI, blood amount/distribution was inferior to CTP. Concerning the identification of “tissue at risk” for DCI, a combination of both methods resulted in an increase of sensitivity to 64%, positive predictive value to 58%, and negative predictive value to 92%.

Conclusions
Regarding the DCI-prediction, early CTP was superior to blood amount/distribution, while a consideration of subarachnoid blood distribution may help identify the vessel territories at risk for DCI in patients without early perfusion deficits.
IFN-α/β/IFN-γ/IL-15 pathways identify GBP1-expressing tumors with an immune-responsive phenotype
Authors: Wang Lei , Wei Yuxuan , Jin Zheng , Liu Fangfang , Li Xuchang , Zhang Xiao , Bai Xiumei , Jia Qingzhu , Zhu Bo , Chu Qian 
Published: May 2024

AbstractImmunotherapy is widely used in cancer treatment; however, only a subset of patients responds well to it. Significant efforts have been made to identify patients who will benefit from immunotherapy. Successful anti-tumor immunity depends on an intact cancer-immunity cycle, especially long-lasting CD8+ T-cell responses. Interferon (IFN)-α/β/IFN-γ/interleukin (IL)-15 pathways have been reported to be involved in the development of CD8+ T cells. And these pathways may predict responses to immunotherapy. Herein, we aimed to analyze multiple public databases to investigate whether IFN-α/β/IFN-γ/IL-15 pathways could be used to predict the response to immunotherapy. Results showed that IFN-α/β/IFN-γ/IL-15 pathways could efficiently predict immunotherapy response, and guanylate-binding protein 1 (GBP1) could represent the IFN-α/β/IFN-γ/IL-15 pathways. In public and private cohorts, we further demonstrated that GBP1 could efficiently predict the response to immunotherapy. Functionally, GBP1 was mainly expressed in macrophages and strongly correlated with chemokines involved in T-cell migration. Therefore, our study comprehensively investigated the potential role of GBP1 in immunotherapy, which could serve as a novel biomarker for immunotherapy and a target for drug development.
Earthworm, Perionyx excavatus as an alternate protein source for Nile tilapia: Effects on growth performance, blood biochemistry, erythrocyte morphology and intestinal health
Authors: Das Bethi , Islam S. M. Majharul , Nag Sudipta Kumar , Al-Azim  , Vatsos Ioannis N. , Siddik Muhammad A. B. 
Published: May 2024

AbstractRecently, an increasing disparity has emerged in the need for raw fish meal (FM) and its supply, along with the environmental and financial obstacles associated with its use. Therefore, increasing and elevating the diversity of alternative protein sources for aquaculture nutrition is imperative. The study investigated the impact of substituting FM protein with EW meal on the growth, haemato-biochemical response and intestinal histomorphology of Nile tilapia. Up to 20% fishmeal replacement with EW meal had no adverse effects on fish growth performance. A quadratic analysis of the final body weight and EW meal level indicated the best growth performance at 17.5% replacement. Fish fed the 40% replacement level had significantly decreased height and width of intestinal folds and number of mucosal goblet cells compared to the control. Although red and white blood cell counts were found unchanged between the control, the 10% and 20% replacement groups, a significantly higher number of white blood cells and a lower number of red blood cells were found in the 40% group compared to the control. Blood glucose level was the highest, while haemoglobin level was the lowest in the 40% group. In the same group, significantly higher frequencies of erythrocyte cellular and nuclear abnormalities were noted. Lipid droplet accumulation in the liver was significantly higher in the 40% group, whilst the 10% and 20% groups showed no significant difference compared to the control.
Endangered giant kelp forests support similar fish and macroinvertebrate communities to sympatric stipitate kelp forests
Authors: Forbes Hunter , Strain Elisabeth M. A. , Bennett Scott , Ling Scott D. , Layton Cayne 
Published: May 2024

AbstractKelp forests provide habitat for many species, but it remains uncertain whether specific kelp forest types support distinct biodiversity. Surface canopy-forming giant kelp (Macrocystis pyrifera) forests in Tasmania, Australia, have declined significantly due to climate change, and have been widely replaced by forests dominated by smaller stipitate kelps like Ecklonia radiata. However, there is limited knowledge of the community composition of Macrocystis forests and how this may differ from the stipitate kelp forest community. Underwater visual census surveys were conducted of the fishes and macroinvertebrates (> 2.5 cm length) in remnant Macrocystis forests in south-eastern Tasmania, and in adjacent stipitate kelp forests. 18 sites (9 of each forest type) were surveyed across two regions during the period of peak growth and canopy cover (i.e. winter-spring). Faunal community composition varied little between forest types, although Macrocystis forests supported more than double the abundance and biomass of mobile fishes, while cryptic fishes differed by forest type depending on region. Macroinvertebrate assemblages did not differ between forest types nor regions. Thus, for the taxa and time period examined, Tasmanian Macrocystis and stipitate kelp forests supported mostly similar faunal communities. Kelp forest communities showed spatial variation and were also likely influenced by a variety of other habitat characteristics, such as the relatively small patch sizes and/or ephemeral state of the remnant Macrocystis forests. Quantifying the community structure of these endangered communities informs the ecological changes that have occurred and will serve as an important reference for ongoing conservation and restoration activities.
Genetic erosion in a tropical tree species demonstrates the need to conserve wide-ranging germplasm amid extreme habitat fragmentation
Authors: Phang A. , Niissalo M.A. , Ruhsam M. , Pezzini F.F. , Neo W.L. , Burslem D.F.R.P. , Middleton D.J. , Wilkie P. , Khew G.S. 
Published: May 2024

AbstractComparing the genetic diversity across different generations within tropical tree populations is an understudied topic. To assess the potential genetic consequences and conservation implications of contemporary disturbances, a population genomic study of Palaquium obovatum across age classes was undertaken. Trees and juveniles were sampled from ten different localities (eight in Singapore, two in Peninsular Malaysia) and subjected to double digest restriction-site associated DNA-sequencing (ddRAD-seq) to assess intergenerational genetic differences and investigate population structure in a hexaploid lineage. Genetic erosion, characterised by reduced heterozygosity, was found to have occurred in almost all wild populations over time, the exceptions being in one isolated coastal population and some areas with cultivated occurences. Population structure was highly localised with the number of genetically distinct populations usually following geographically separated districts, which indicates limitations in pollen and seed dispersal between fragments, possibly due to declines in the associated assemblage of dispersers. For this reason, the germplasm for conserving species diversity in degraded habitats and forest fragments should be selected from a wide range of wild populations across the landscape.