bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personality disorder coverage, prevalence, and convergence: do the DSM-5's two models of personality disorder identify the same patients?
Authors: Clark Lee Anna , Ro Eunyoe , Nuzum Hallie , Vanderbleek Emily N. , Allen Xia 
Published: March 2024

AbstractBackgroundResearch on the Alternative DSM-5 Model for Personality Disorders (AMPD) in DSM-5's Section-III has demonstrated acceptable interrater reliability, a largely consistent latent structure, substantial correlations with theoretically and clinically relevant measures, and evidence for incremental concurrent and predictive validity after controlling for DSM-5's Section II categorical personality disorders (PDs). However, the AMPD is not yet widely used clinically. One clinician concern may be caseness – that the new model will diagnose a different set of PD patients from that with which they are familiar. The primary aim of this study is to determine whether this concern is valid, by testing how well the two models converge in terms of prevalence and coverage.MethodParticipants were 305 psychiatric outpatients and 302 community residents not currently in mental-health treatment who scored above threshold on the Iowa Personality Disorder Screen (Langbehn et al., 1999). Participants were administered a semi-structured interview for DSM-5 PD, which was scored for both Section II and III PDs.ResultsConvergence across the two PD models was variable for specific PDs, Good when specific PDs were aggregated, and Very Good for ‘any PD.’ConclusionsResults provide strong evidence that the AMPD yields the same overall prevalence of PD as the current model and, further, identifies largely the same overall population. It also addresses well-known problems of the current model, is more consistent with the ICD-11 PD model, and provides more complete, individualized characterizations of persons with PD, thereby offering multiple reasons for its implementation in clinical settings.
The non-religious and the European city in the nineteenth century: the development of crematories in Milan and Gotha
Authors: Kosuch Carolin 
Published: March 2024

AbstractWhile our knowledge of the entanglements of cities and religions is growing, the ‘other’ of religion and its impact on the city has not received the same level of attention in research so far. This article explores how this lacuna could start to be filled. Its focus is on the history of modern cremation that unfolded with strong secularist leanings during the long nineteenth century. I will look into the history of the first European crematories that were built in Milan and Gotha, the construction of the first cremation furnaces and the infrastructures necessary to make them work. My hypothesis is that what I call ‘worldview technologies’ and related infrastructures changed the faces of cities and were in turn influenced by these cities’ histories and self-images.
(-)-epicatechin treatment did not modify the thermogenic pathway in the gastrocnemius muscle of male rat offspring obeses by programming
Authors: Tejeda María Elena , De los Santos Sergio , Coral-Vázquez Ramón Mauricio , Álvarez-Chávez Ana , Palma Flores Carlos , Zambrano Elena , Méndez Juan Pablo , Canto Patricia 
Published: March 2024

Abstract
The aim of this study was to analyse the expression of genes related to the regulation of energy metabolism in skeletal muscle tissue by comparing male offspring in two age groups [at 110 and 245 postnatal days (pnd)] from a mother with obesity induced by a high-fat diet and (-)-epicatechin (Epi) administration. Four groups of six male offspring from different litters were randomly selected for the control groups [C and offspring of mothers with maternal obesity (MO)] or Epi intervention groups. We evaluated the effect of Epi on gastrocnemius tissue by analysing the mRNA and protein expression levels of Fndc5/irisin, Pgc-1α, Ucp3, and Sln. Epi significantly increased the Pgc-1α protein in the MO group of offspring at 110 pnd (p < 0.036, MO vs. MO+Epi), while at 245 pnd, Epi increased Fndc5/irisin mRNA expression in the MO+Epi group versus the MO group (p = 0.006).
No differences were detected in Fndc5/irisin, Ucp3 or Sln mRNA or protein levels (including Pgc-1α mRNA) in the offspring at 110 pnd or in Pgc-1α, Ucp3, or Sln mRNA or protein levels (including Fndc5/irisin protein) at 245 pnd among the experimental groups. In conclusion, (-)-epicatechin treatment increased Fndc5/irisin mRNA expression and Pgc-α protein levels in the gastrocnemius muscle of offspring at postnatal days 110 and 245. Furthermore, it is suggested that the flavonoid effect in a model of obesity and its impact on thermogenesis in skeletal muscle are regulated by a different pathway than Fndc5/irisin.
Comparative political process theory II
Authors: Gardbaum Stephen 
Published: March 2024

Abstract
This article aims to continue the recent neo-Elyean turn in comparative constitutional scholarship by further exploring the role of the courts in supporting and protecting democracy. In so doing, it refines and develops my previous work on the topic, and applies this fuller version to a highly visible current dispute. The article first examines the underlying conception of democracy that comparative political process theory is designed to protect; namely, constitutional democracy. It asks what this is and what role courts have in supporting it. The article then introduces the idea of ‘semi-substantive review’ as an integral and output-oriented part of a comprehensive comparative political process theory, alongside and in addition to the types of more purely procedural review I primarily emphasized in my previous work. Finally, the article employs the recent, highly controversial judicial reforms in Israel as a case study in applying the criteria for, and limits of, court intervention in my account. It analyses whether, why and how, in the event that the deeply contested bills become law (as so far one did), judges would be justified in acting to support and protect constitutional democracy.
Resonances of Fluid‐Filled Cracks With Complex Geometry and Application to Very Long Period (VLP) Seismic Signals at Mayotte Submarine Volcano
Authors: Liang Chao , Peng Junjun , Ampuero Jean‐Paul , Shauer Nathan , Dai Kaoshan 
Published: March 2024

AbstractFluid‐filled cracks sustain a slow guided wave (Krauklis wave or crack wave) whose resonant frequencies are widely used for interpreting long period (LP) and very long period (VLP) seismic signals at active volcanoes. Significant efforts have been made to model this process using analytical developments along an infinite crack or numerical methods on simple crack geometries. In this work, we develop an efficient hybrid numerical method for computing resonant frequencies of complex‐shaped fluid‐filled cracks and networks of cracks and apply it to explain the ratio of spectral peaks in the VLP signals from the Fani Maoré submarine volcano that formed in Mayotte in 2018. By coupling triangular boundary elements and the finite volume method, we successfully handle complex geometries and achieve computational efficiency by discretizing solely the crack surfaces. The resonant frequencies are directly determined through eigenvalue analysis. After proper verification, we systematically analyze the resonant frequencies of rectangular and elliptical cracks, quantifying the effect of aspect ratio and crack stiffness. We then discuss theoretically the contribution of fluid viscosity and seismic radiation to energy dissipation. Finally, we obtain a crack geometry that successfully explains the characteristic ratio between the first two modes of the VLP seismic signals from the Fani Maoré submarine volcano in Mayotte. Our work not only reveals rich eigenmodes in complex‐shaped cracks but also contributes to illuminating the subsurface plumbing system of active volcanoes. The developed model is readily applicable to crack wave resonances in other geological settings, such as glacier hydrology and hydrocarbon reservoirs.
Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together
Authors: Guo Hong-Li , Wu Dan-Dan , Fu Di , Li Yue , Wang Jie , Zhang Yuan-Yuan , Wang Wei-Jun , Huang Jian , Fang Wei-Rong , Xu Jing , Hu Ya-Hui , Liu Qian-Qi , Chen Feng 
Published: March 2024

AbstractIntegrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children’s Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including CYP2D6 genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, >60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while <40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, P = 0.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (q.m.) dosing regimen exhibited a more effective response to atomoxetine when their levels were ≥ 268 ng/mL (AUC = 0.710, P < 0.001). In addition, CYP2D6 IMs receiving q.m. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509 ng/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their CYP2D6 genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268 ng/mL might be requisite for q.m. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.
Post-traumatic stress disorder in a national sample of preadolescent children 9 to 10 years old: Prevalence, correlates, clinical sequelae, and treatment utilization
Authors: Levin Rachel Y. , Liu Richard T. 
Published: March 2024

AbstractAlthough posttraumatic stress disorder (PTSD) has been well characterized in adults, its epidemiology in children is unclear. The current study provides the first population-based examination of the prevalence of PTSD, sociodemographic and psychiatric correlates, clinical sequelae, and associations with psychiatric treatment in preadolescents 9-10 years old in the United States. Data from the Adolescent Brain and Cognitive Development (ABCD) Study (release 5.0) was analyzed. Participants (unweighted n = 11,875) were recruited from 21 sites across the United States. Current and lifetime PTSD prevalence were estimated, as was treatment use among children with PTSD. Sociodemographic, psychiatric correlates and sequelae of PTSD were analyzed using logistic regression, as was the association between PTSD and psychiatric treatment. After the application of propensity weights, lifetime prevalence of PTSD was 2.17%. Sexual minority status, being multiracial, having unmarried parents, and family economic insecurity were associated with greater odds of PTSD. Among psychiatric disorders, separation anxiety was most strongly associated with PTSD, although general comorbid psychopathology was associated with greater odds of PTSD. Prior history of PTSD predicted a new onset of other psychiatric disorders after PTSD remission. Nearly one in three children with lifetime PTSD did not receive psychiatric treatment, despite negative long-term outcomes of PTSD and significant psychiatric comorbidity. Even among preadolescents who experience full remission of PTSD, a significant risk for future psychiatric illness remains. Further, the current findings underscore the need for improved efforts to reduce unmet treatment needs among those with PTSD at this age.
Exemestane plus everolimus and palbociclib in metastatic breast cancer: clinical response and genomic/transcriptomic determinants of resistance in a phase I/II trial
Authors: Gómez Tejeda Zañudo Jorge , Barroso-Sousa Romualdo , Jain Esha , Jin Qingchun , Li Tianyu , Buendia-Buendia Jorge E. , Pereslete Alyssa , Abravanel Daniel L. , Ferreira Arlindo R. , Wrabel Eileen , Helvie Karla , Hughes Melissa E. , Partridge Ann H. , Overmoyer Beth , Lin Nancy U. , Tayob Nabihah , Tolaney Sara M. , Wagle Nikhil 
Published: March 2024

AbstractThe landscape of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) resistance is still being elucidated and the optimal subsequent therapy to overcome resistance remains uncertain. Here we present the final results of a phase Ib/IIa, open-label trial (NCT02871791) of exemestane plus everolimus and palbociclib for CDK4/6i-resistant metastatic breast cancer. The primary objective of phase Ib was to evaluate safety and tolerability and determine the maximum tolerated dose/recommended phase II dose (100 mg palbociclib, 5 mg everolimus, 25 mg exemestane). The primary objective of phase IIa was to determine the clinical benefit rate (18.8%, n = 6/32), which did not meet the predefined endpoint (65%). Secondary objectives included pharmacokinetic profiling (phase Ib), objective response rate, disease control rate, duration of response, and progression free survival (phase IIa), and correlative multi-omics analysis to investigate biomarkers of resistance to CDK4/6i. All participants were female. Multi-omics data from the phase IIa patients (n = 24 tumor/17 blood biopsy exomes; n = 27 tumor transcriptomes) showed potential mechanisms of resistance (convergent evolution of HER2 activation, BRAFV600E), identified joint genomic/transcriptomic resistance features (ESR1 mutations, high estrogen receptor pathway activity, and a Luminal A/B subtype; ERBB2/BRAF mutations, high RTK/MAPK pathway activity, and a HER2-E subtype), and provided hypothesis-generating results suggesting that mTOR pathway activation correlates with response to the trial’s therapy. Our results illustrate how genome and transcriptome sequencing may help better identify patients likely to respond to CDK4/6i therapies.
Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers
Authors: Iyer R. Sumanth , Needham Sarah R. , Galdadas Ioannis , Davis Benjamin M. , Roberts Selene K. , Man Rico C. H. , Zanetti-Domingues Laura C. , Clarke David T. , Fruhwirth Gilbert O. , Parker Peter J. , Rolfe Daniel J. , Gervasio Francesco L. , Martin-Fernandez Marisa L. 
Published: March 2024

AbstractThe Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Oncogenic EGFR has been successfully targeted by tyrosine kinase inhibitors, but acquired drug resistance eventually overcomes the efficacy of these treatments. Attempts to surmount this therapeutic challenge are hindered by a poor understanding of how and why cancer mutations specifically amplify ligand-independent EGFR auto-phosphorylation signals to enhance cell survival and how this amplification is related to ligand-dependent cell proliferation. Here we show that drug-resistant EGFR mutations manipulate the assembly of ligand-free, kinase-active oligomers to promote and stabilize the assembly of oligomer-obligate active dimer sub-units and circumvent the need for ligand binding. We reveal the structure and assembly mechanisms of these ligand-free, kinase-active oligomers, uncovering oncogenic functions for hitherto orphan transmembrane and kinase interfaces, and for the ectodomain tethered conformation of EGFR. Importantly, we find that the active dimer sub-units within ligand-free oligomers are the high affinity binding sites competent to bind physiological ligand concentrations and thus drive tumor growth, revealing a link with tumor proliferation. Our findings provide a framework for future drug discovery directed at tackling oncogenic EGFR mutations by disabling oligomer-assembling interactions.
The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome
Authors: Gersteuer Felix , Morici Martino , Gabrielli Sara , Fujiwara Keigo , Safdari Haaris A. , Paternoga Helge , Bock Lars V. , Chiba Shinobu , Wilson Daniel N. 
Published: March 2024

AbstractNascent polypeptide chains can induce translational stalling to regulate gene expression. This is exemplified by the E. coli secretion monitor (SecM) arrest peptide that induces translational stalling to regulate expression of the downstream encoded SecA, an ATPase that co-operates with the SecYEG translocon to facilitate insertion of proteins into or through the cytoplasmic membrane. Here we present the structure of a ribosome stalled during translation of the full-length E. coli SecM arrest peptide at 2.0 Å resolution. The structure reveals that SecM arrests translation by stabilizing the Pro-tRNA in the A-site, but in a manner that prevents peptide bond formation with the SecM-peptidyl-tRNA in the P-site. By employing molecular dynamic simulations, we also provide insight into how a pulling force on the SecM nascent chain can relieve the SecM-mediated translation arrest. Collectively, the mechanisms determined here for SecM arrest and relief are also likely to be applicable for a variety of other arrest peptides that regulate components of the protein localization machinery identified across a wide range of bacteria lineages.
Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer
Authors: Bi Guoshu , Liang Jiaqi , Bian Yunyi , Shan Guangyao , Huang Yiwei , Lu Tao , Zhang Huan , Jin Xing , Chen Zhencong , Zhao Mengnan , Fan Hong , Wang Qun , Gan Boyi , Zhan Cheng 
Published: March 2024

AbstractTargeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour’s metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine’s conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H2O2-dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal——iron overload——through WNT/MYC signalling, as well as the subsequent elevated polyamine synthesis, thus forming a ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H2O2 positive feedback loop that amplifies ferroptosis. Meanwhile, we notice that ferroptotic cells release enhanced polyamine-containing extracellular vesicles into the microenvironment, thereby further sensitizing neighbouring cells to ferroptosis and accelerating the “spread” of ferroptosis in the tumour region. Besides, polyamine supplementation also sensitizes cancer cells or xenograft tumours to radiotherapy or chemotherapy through inducing ferroptosis. Considering that cancer cells are often characterized by elevated intracellular polyamine pools, our results indicate that polyamine metabolism exposes a targetable vulnerability to ferroptosis and represents an exciting opportunity for therapeutic strategies for cancer.
A topographical atlas of α-synuclein dosage and cell type-specific expression in adult mouse brain and peripheral organs
Authors: Geertsma Haley M. , Fisk Zoe A. , Sauline Lillian , Prigent Alice , Kurgat Kevin , Callaghan Steve M. ,   aSCENT-PD Consortium, Arenkiel Benjamin R. , Mollenhauer Brit , Schlossmacher Michael G. , Stadelmann Christine , Tomlinson Julianna J. , Henderson Michael X. , Rousseaux Maxime W. C. 
Published: March 2024

AbstractParkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and presents pathologically with Lewy pathology and dopaminergic neurodegeneration. Lewy pathology contains aggregated α-synuclein (αSyn), a protein encoded by the SNCA gene which is also mutated or duplicated in a subset of familial PD cases. Due to its predominant presynaptic localization, immunostaining for the protein results in a diffuse reactivity pattern, providing little insight into the types of cells expressing αSyn. As a result, insight into αSyn expression-driven cellular vulnerability has been difficult to ascertain. Using a combination of knock-in mice that target αSyn to the nucleus (SncaNLS) and in situ hybridization of Snca in wild-type mice, we systematically mapped the topography and cell types expressing αSyn in the mouse brain, spinal cord, retina, and gut. We find a high degree of correlation between αSyn protein and RNA levels and further identify cell types with low and high αSyn content. We also find high αSyn expression in neurons, particularly those involved in PD, and to a lower extent in non-neuronal cell types, notably those of oligodendrocyte lineage, which are relevant to multiple system atrophy pathogenesis. Surprisingly, we also found that αSyn is relatively absent from select neuron types, e.g., ChAT-positive motor neurons, whereas enteric neurons universally express some degree of αSyn. Together, this integrated atlas provides insight into the cellular topography of αSyn, and provides a quantitative map to test hypotheses about the role of αSyn in network vulnerability, and thus serves investigations into PD pathogenesis and other α-synucleinopathies.