bluuebunny/crossref_metadata_2025_split huggingface dataset:
BMScope: A scoping review to chart the evolving clinical study landscape in brain and leptomeningeal metastasis
Authors: Cheng Vinton W T , Heywood Richard , Zakaria Rasheed , Burger Rebecca , Zucker Kieran , Kannan Siddarth , Putra Muhammad Alifian Remifta , Fitzpatrick Amanda , Doherty Gary , Sanghera Paul , Jenkinson Michael D , Palmieri Carlo 
Published: August 2024

Abstract

Background
Recent studies have challenged the notion that patients with brain metastasis (BM) or leptomeningeal metastasis (LM) should be excluded from systemic therapy clinical trials. This scoping study summarizes the BM/LM clinical studies published between 2010 and 2023.

Methods
MEDLINE, CINAHL, CAB Abstracts, PsycINFO, Cochrane Library, HINARI, International Pharmaceutical Abstracts, PubMed, Scopus, Web of Science, and EMBASE electronic databases were searched on June 21, 2021. An updated search was performed on February 21, 2023. Eligible studies investigated a therapeutic intervention in solid tumor patients with BM and/or LM and reported a patient outcome. Extracted study-level data, including study type, publication date, geographical location, number of BM/LM patients in the study, primary tumor type, and type of therapeutic intervention, were collected.

Results
4921 unique studies were eligible for analysis. The key finding is that BM/LM clinical research is expanding globally, both in observational studies and clinical trials. Despite the shift over time toward a higher proportion of systemic therapy trials, the majority still do not include patients with symptomatic disease and lack reporting of BM/LM-specific endpoints. Globally, there has been a trend to more international collaboration in BM/LM clinical studies.

Conclusions
Our analysis of the BM/LM literature charts the evolving landscape of studies involving this previously excluded population. Given the increasing clinical research activity, particularly involving late-stage systemic therapy trials, it is imperative that due consideration is given to the intracranial activity of new investigational agents. Wider adoption of standardized reporting of intracranial-specific endpoints will facilitate the evaluation of relative intracranial efficacy.
A low level of tumor necrosis factor α in tumor microenvironment maintains the self-renewal of glioma stem cells by Vasorin-mediated glycolysis
Authors: Zhang Yang , Kang Tianxu , Wang Yuxi , Song Chao , Li Huan , Mi Hailong , Li Yachao , Dong Minhai , Ma Xiaoyu , Zhu Hongtao , Cheng Lidong , Zhang Po , Chen Zhiye , Zhou Lin , Wu Qiulian , Mao Feng , Wang Baofeng , Zhang Suojun , Shu Kai , Wan Feng , Zhou Wenchao , Rich Jeremy N , Shen Jianying , Xiao Qungen , Yu Xingjiang 
Published: August 2024

Abstract

Background
Self-renewal of glioma stem cells (GSCs) is responsible for glioblastoma (GBM) therapy resistance and recurrence. Tumor necrosis factor α (TNFα) and TNF signaling pathway display an antitumor activity in preclinical models and in tumor patients. However, TNFα exhibits no significance for glioma clinical prognosis based on the Glioma Genome Atlas database. This study aimed to explore whether TNFα of tumor microenvironment maintains self-renewal of GSCs and promotes worse prognosis in glioma patients.

Methods
Spatial transcriptomics, immunoblotting, sphere formation assay, extreme limiting dilution, and gene expression analysis were used to determine the role of TNFα on GSC’s self-renewal. Mass spectrometry, RNA-sequencing detection, bioinformatic analyses, qRT-RNA, immunofluorescence, immunohistochemistry, single-cell RNA sequencing, in vitro and in vivo models were used to uncover the mechanism of TNFα-induced GSC self-renewal.

Results
A low level of TNFα displays a promoting effect on GSC self-renewal and worse glioma prognosis. Mechanistically, Vasorin (VASN) mediated TNFα-induced self-renewal by potentiating glycolysis. Lactate produced by glycolysis inhibits the TNFα secretion of tumor-associated macrophages (TAMs) and maintains TNFα at a low level.

Conclusions
TNFα-induced GSC self-renewal mediated by VASN provides a possible explanation for the failures of endogenous TNFα effect on GBM. A combination of targeting VASN and TNFα antitumor effect may be an effective approach for treating GBM.
Developmental pluripotency-associated 4 increases aggressiveness of pituitary neuroendocrine tumors by enhancing cell stemness
Authors: Chaudhary Shaista , Das Ujjal , Jabbar Shaima , Gangisetty Omkaram , Rousseau Bénédicte , Hanft Simon , Sarkar Dipak K 
Published: August 2024

Abstract

Background
Pituitary neuroendocrine tumors, PitNETs, are often aggressive and precipitate in distant metastases that are refractory to current therapies. However, the molecular mechanism in PitNETs’ aggressiveness is not well understood. Developmental pluripotency-associated 4 (DPPA4) is known as a stem cell regulatory gene and overexpressed in certain cancers, but its function in the context of PitNETs’ aggressiveness is not known.

Methods
We employed both rat and human models of PitNETs. In the rat pituitary tumor model, we used prenatal-alcohol-exposed (PAE) female Fischer rats which developed aggressive PitNETs following estrogen treatment, while in the human pituitary tumor model, we used aggressively proliferative cells from pituitary tumors of patients undergone surgery. Various molecular, cellular, and epigenetic techniques were used to determine the role of DPPA4 in PitNETs’ aggressiveness.

Results
We show that DPPA4 is overexpressed in association with increased cell stemness factors in aggressive PitNETs of PAE rats and of human patients. Gene-editing experiments demonstrate that DPPA4 increases the expression of cell stemness and tumor aggressiveness genes and promotes proliferation, colonization, migration, and tumorigenic potential of PitNET cells. ChIP assays and receptor antagonism studies reveal that DPPA4 binds to canonical WINTs promoters and increases directly or indirectly the WNT/β-CATENIN control of cell stemness, tumor growth, and aggressiveness of PitNETs. Epigenetic studies show the involvement of histone methyltransferase in alcohol activation of DPPA4.

Conclusions
These findings support a role of DPPA4 in tumor stemness and aggressiveness and provide a preclinical rationale for modulating this stemness regulator for the treatment of PitNETs.
Effects of Single Low-Carbohydrate, High-Fat Meal Consumption on Postprandial Lipemia and Markers of Endothelial Dysfunction: A Systematic Review of Current Evidence
Authors: Wilson Megan L , Lane Katie E , Fadel Abdulmannan , Dawson Ellen A , Moore Ella , Mazidi Mohsen , Webb Richard J , Davies Ian G 
Published: August 2024

Abstract

Context
Postprandial lipemia (PPL) is associated with increased risk of endothelial dysfunction (ED), a precursor of atherosclerotic cardiovascular disease (ASCVD). The effects of low-carbohydrate, high-fat (LCHF) diets on ASCVD risk are uncertain; therefore, gaining a greater understanding of LCHF meals on PPL may provide valuable insights.

Objective
The current systematic review investigated the effects of single LCHF meal consumption on PPL and markers of ED.

Data Sources
CINAHL Plus, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for key terms related to endothelial function, cardiovascular disease, glycemia, lipemia, and the postprandial state with no restriction on date.

Data Extraction
Full-text articles were independently screened by 2 reviewers, of which 16 studies were eligible to be included in the current review. All trials reported a minimum analysis of postprandial triglycerides (PPTG) following consumption of an LCHF meal (&lt;26% of energy as carbohydrate). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Data Analysis
Single-meal macronutrient composition was found to play a key role in determining postprandial lipid and lipoprotein responses up to 8 hours post-meal. Consumption of LCHF meals increased PPTG and may contribute to ED via reduced flow-mediated dilation and increased oxidative stress; however, energy and macronutrient composition varied considerably between studies.

Conclusion
Consumption of an LCHF meal had a negative impact on PPL based on some, but not all, single-meal studies; therefore, the contribution of LCHF meals to cardiometabolic health outcomes remains unclear. Further research is needed on specific categories of LCHF diets to establish a causal relationship between postprandial modulation of lipids/lipoproteins and impaired vascular endothelial function.

Systematic Review Registration
PROSPERO registration no. CRD 42023398774.
Testing for Blastomycosis, Coccidioidomycosis, and Histoplasmosis at a Major Commercial Laboratory, United States, 2019–2024
Authors: Benedict Kaitlin , Williams Samantha L , Smith Dallas J , Lindsley Mark D , Lockhart Shawn R , Toda Mitsuru 
Published: August 2024

Abstract

Background
Blastomycosis, coccidioidomycosis, and histoplasmosis are environmentally acquired fungal diseases that clinically resemble bacterial and viral community-acquired pneumonia and require laboratory testing for diagnosis. Patients frequently present to primary care and experience diagnostic delays when a fungal etiology is not initially suspected. Current national-level public health surveillance for these diseases is limited and does not include laboratory data, so nationwide testing practices are unknown.

Methods
We identified laboratory tests for blastomycosis, coccidioidomycosis, and histoplasmosis ordered during 1 March 2019–29 February 2024 and performed within a major national commercial laboratory system. We analyzed test results, patient and healthcare provider features, reasons for testing, and temporal trends.

Results
Results included 5693 Blastomyces complement fixation tests (of those, 12% were positive), 71 858 immunodiffusion tests (0.1% positive), and 1186 serum enzyme immunoassay (EIA) tests (11% positive); 154 989 Coccidioides EIA immunoglobulin M results (5% positive) and 154 968 immunoglobulin G results (8% positive); and 46 346 Histoplasma complement fixation tests (30% positive), 49 062 immunodiffusion tests (1% positive), 35 506 serum EIA tests (4% positive), and 82 489 urine EIA tests (2% positive). Most histoplasmosis (58%–74%) and blastomycosis (42%–68%) tests were ordered from hospitals, whereas coccidioidomycosis tests were most frequently ordered by primary care providers (40%). A yearly average of 2727 positive tests were ordered by healthcare providers in states without public health surveillance for these diseases.

Conclusions
Blastomycosis, coccidioidomycosis, and histoplasmosis are likely underdetected in primary care settings or by public health surveillance. Increased testing by primary care providers and expanded surveillance are needed to reduce disease burden.
Probing Bilin–Protein Interaction in the Protochromic Photocycle of Cyanobacteriochrome RcaE by Site-Directed Mutagenesis
Authors: Kamo Takanari , Matsushita Takaaki , Hamada Masako , Fujisawa Tomotsumi , Eki Toshihiko , Unno Masashi , Hirose Yuu 
Published: August 2024

Abstract
Cyanobacteriochromes (CBCRs) are members of the phytochrome superfamily of photosensor proteins that bind a bilin chromophore. CBCRs exhibit substantial diversity in their absorption wavelengths through a variety of bilin–protein interactions. RcaE is the first discovered CBCR as a regulator of chromatic acclimation, where cyanobacteria optimize the absorption wavelength of their photosynthetic antenna. RcaE undergoes a reversible photoconversion between green-absorbing (Pg) and red-absorbing (Pr) states, where the bilin chromophore adopts a deprotonated C15-Z,anti and a protonated C15-E,syn structures, respectively. This photocycle is designated as the ‘protochromic photocycle’ as the change in the bilin protonation state is responsible for the large absorption shift. With the guidance of recently determined Pg and Pr structures of RcaE, in this study, we investigated bilin–protein interaction by site-directed mutagenesis on three key residues referred to as a protochromic triad and also other conserved residues interacting with the bilin. Among the protochromic triad residues, Glu217 and Lys261 are critical for the formation of the Pr state, while Leu249 is critical for the formation of both Pg and Pr states. Substitution in other conserved residues, including Val218, Phe219 and Pro220 in the wind-up helix and Phe252, Phe214 and Leu209 in a part of the bilin-binding pocket, had less substantial effects on the spectral sensitivity in RcaE. These data provide insights into our understanding of the bilin–protein interaction in the protochromic photocycle and also its evolution in the CBCRs.
Thermodynamic Topology of Topological Black Hole in F(R)-ModMax Gravity’s Rainbow
Authors: Eslam Panah B , Hazarika B , Phukon P 
Published: August 2024

Abstract
In order to include the effect of high energy and topological parameters on black holes in $\mathrm{ F}(R)$ gravity, we consider two corrections to this gravity: energy-dependent spacetime with different topological constants, and a nonlinear electrodynamics field. In other words, we combine $\mathrm{ F}(R)$ gravity’s rainbow with ModMax nonlinear electrodynamics theory to see the effects of high energy and topological parameters on the physics of black holes. For this purpose, we first extract topological black hole solutions in $\mathrm{ F}(R)$-ModMax gravity’s rainbow. Then, by considering black holes as thermodynamic systems, we obtain thermodynamic quantities and check the first law of thermodynamics. The effect of the topological parameter on the Hawking temperature and the total mass of black holes is obvious. We also discuss the thermodynamic topology of topological black holes in $\mathrm{ F}(R)$-ModMax gravity’s rainbow using the off-shell free energy method. In this formalism, black holes are assumed to be equivalent to defects in their thermodynamic spaces. For our analysis, we consider two different types of thermodynamic ensembles. These are: fixed q ensemble and fixed $\phi$ ensemble. We take into account all the different types of curvature hypersurfaces that can be constructed in these black holes. The local and global topology of these black holes are studied by computing the topological charges at the defects in their thermodynamic spaces. Finally, in accordance with their topological charges, we classify the black holes into three topological classes with total winding numbers corresponding to $-1, 0$, and 1. We observe that the topological classes of these black holes are dependent on the value of the rainbow function, the sign of the scalar curvature, and the choice of ensembles.
The National Front and environmental politics, 1967–90
Authors: Bhargava Beth 
Published: August 2024

Abstract
The green entanglements of the inter-war British far right are well-documented. Martin Pugh has drawn attention to the predominantly rural, agricultural support base of the British Union of Fascists. We know that the aspiration to go ‘back to the land’ was deeply enmeshed with a politics of racial hygiene, which equated the urban with miscegenation and the rural with purity. However, in the post-war world, British far-right ecologism has typically been interpreted as a curious anomaly driven by cynical realpolitik. This article contends environmental themes as an intellectual staple of British fascism—running from the interwar far right, through the NF, and into the latter’s largest successor organization, the Flag Group. The Front’s preoccupation with the environment, and its racism, were mutually reinforcing, central pillars of its politics. Its environmentalism was alternately revolutionary and conservative, nostalgic and future oriented.
The use of modelling in the learning of differential equations in an economics course
Authors: Trigueros María , Martínez-Planell Rafael 
Published: August 2024

Abstract
This study examines the experience of using an open-ended modelling problem to introduce economics students to the mathematical subject of differential equations. We show the potential of such an approach in motivating students whilst at the same time helping them construct a new differential equations Schema that is coordinated with their developing understanding of economics. In a classroom context of collaborative group work, general class discussions and carefully chosen homework exercises, students showed that they could develop an interest in the relation between mathematics, specifically differential equations, and economics, and ‘discover’ uses of mathematics that are new to them whilst modelling the economics problem of diffusion of an innovation. Students were able to anticipate important mathematical ideas, like the phase plane qualitative analysis of dynamical systems, on their own. This was accompanied by activities that formalized the mathematical aspects of the course as students developed them.
Virome Scanning of Pear Germplasm Collections Identifies a New Velarivirus and Extends the Geographical Spread of Three Other Pear Viruses
Authors: Fontdevila Pareta Nuria , Gailly Carole , Blouin Arnaud G. , Buchmann Beatrix , Bünter Markus , Candresse Thierry , Dubuis Nathalie , Kutnjak Denis , Lateur Marc , Pecman Anja , Steyer Stéphan , Massart Sébastien 
Published: August 2024

In this study, an extensive virome investigation was performed on a germplasm collection of pear trees ( Pyrus communis L.) from the Walloon Agricultural Research Centre (Gembloux, Belgium). In total, 128 pear trees samples were analyzed as pools using high-throughput sequencing techniques and/or tested individually for targeted viruses by reverse transcription PCR (RT-PCR). During the virome survey, a novel velarivirus was identified in several asymptomatic trees, and four known viruses were detected. Bioinformatics tools were used to assemble the genome of the new virus. The pear germplasm collection from Kozjanski Park (Slovenia) and a viral collection from Agroscope (Nyon, Switzerland) were also surveyed for the new pear virus and for three known viruses (citrus virus A [CiVA], apple rubbery wood virus 1 [ARWV-1], and apple rubbery wood virus 2 [ARWV-2]) to study their prevalence and geographic distribution. In Belgium, the new velarivirus was detected by RT-PCR in 6 of the 99 sampled trees (6%) and CiVA in 49 (49%) of them; in Slovenia, four of the six trees sampled (67%) were positive for CiVA; and in Switzerland, four of the nine trees sampled (44%) were positive for CiVA and 1 (11%) for ARWV-1 and -2. This study combined pooled high-throughput sequencing analyses to maximize the amount of germplasm tested and targeted RT-PCR tests on individual samples for accurate detection. It reports and describes a new velarivirus discovered in pear trees and first detections of CiVA in Belgium, Switzerland, and Slovenia, as well as ARWV-1 and -2 in Switzerland. [Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium
Authors: Lian Zexuan , Chen Ruchong , Xian Mo , Huang Peiying , Xu Jiahan , Xiao Xiaojun , Ning Xiaoping , Zhao Jin , Xie Jianlei , Duan Jielin , Li Bizhou , Wang Wanjun , Shi Xu , Wang Xinru , Jia Nan , Chen Xuepeng , Li Jing , Yang Zhaowei 
Published: August 2024

AbstractEpithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity‐associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small‐molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO‐regulated transcriptome‐wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP‐seq) and RNA‐seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue‐specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL‐4/IL‐13‐treated epithelial cells and house dust mite (HDM)‐induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF‐α signaling via NF‐κB and epithelial–mesenchymal transition‐related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23‐induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM‐induced mice, potentially through diverse cellular processes and epithelial–mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.
The Inequitable Experiences of Left-Handed Medical Students in Surgical Education
Authors: Gilbert Timothy J. , Anderson Maia S. , Byrnes Mary E. , Kim Gloria Y. , Solano Quintin P. , Wan Julian H. , Sack Bryan S. 
Published: August 2024

Abstract

Purpose
Left-handed medical students contend with unique educational barriers within surgery, such as lack of educational resources, lack of left-handed–specific training, and widespread stigmatization of surgical left-handedness. This study aimed to highlight the surgical experiences of left-handed medical students so educators may be empowered to act with greater care and appreciation of these students’ circumstances.

Method
In this qualitative study, the authors conducted semistructured interviews on surgical experiences during medical school between January 31, 2021, and June 20, 2021, on 31 current surgical residents and fellows from 15 U.S. institutions and 6 surgical specialties. Left-handed trainees were included regardless of their surgical hand dominance.

Results
The authors identified 3 themes related to left-handed medical students’ surgical experience: (1) disorienting advice from faculty or residents, (2) discouraging right-handed pressures and left-handed stigmatization, and (3) educational wishes of left-handed medical students. Trainees describe dialogues during medical school in which their handedness was directly addressed by residents and faculty with disorienting and nonbeneficial advice. Often trainees were explicitly told which hand to use, neglecting any preferences of the left-handed student. Participants also described possible changes in future surgical clerkships, including normalization of left-handedness, tangible mentorship, or granular and meaningful instruction.

Conclusions
Left-handed medical students encounter unique challenges during their surgical education. These students report being disoriented by the variability of advice provided by mentors, discouraged by how pressured they feel to operate right-handed, and burdened by the need to figure things out by themselves in the absence of adequate left-handed educational resources. Surgical education leadership should detail the unique problems left-handed learners face, impartially elicit the learner’s current operative hand preference, take responsibility for their left-handed students, promote acceptance and accommodation strategies of left-handed surgical trainees, and endeavor to improve the breadth of left-handed surgical resources.