bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ACTIV-6 Stakeholder Advisory Committee: a model for virtual engagement in decentralized clinical trials
Authors: Hamm Megan E. , Arnold Jonathan , Denson Josh , Edwards Talethia , Merritt Greg , McCarthy Matthew , Nelson Danielle , Phillips Kirk T. , Thicklin Florence , Vasey Andrew , McTigue Kathleen 
Published: November 2023

Abstract

Introduction:
Engaging patients, caregivers, and other stakeholders to help guide the research process is a cornerstone of patient-centered research. Lived expertise may help ensure the relevance of research questions, promote practices that are satisfactory to research participants, improve transparency, and assist with disseminating findings.

Methods:
Traditionally engagement has been conducted face-to-face in the local communities in which research operates. Decentralized platform trials pose new challenges for the practice of engagement. We used a remote model for stakeholder engagement, relying on Zoom meetings and blog communications.

Results:
Here we describe the approach used for research partnership with patients, caregivers, and clinicians in the planning and oversight of the ACTIV-6 trial and the impact of this work. We also present suggestions for future remote engagement.

Conclusions:
The ACTIV-6 experience may inform proposed strategies for future engagement in decentralized trials.
Continuous gradient fusion class activation mapping: segmentation of laser-induced damage on large-aperture optics in dark-field images
Authors: Han Yueyue , Huang Yingyan , Dong Hangcheng , Chen Fengdong , Zeng Fa , Peng Zhitao , Zhu Qihua , Liu Guodong 
Published: November 2023

Abstract
Segmenting dark-field images of laser-induced damage on large-aperture optics in high-power laser facilities is challenged by complicated damage morphology, uneven illumination and stray light interference. Fully supervised semantic segmentation algorithms have achieved state-of-the-art performance but rely on a large number of pixel-level labels, which are time-consuming and labor-consuming to produce. LayerCAM, an advanced weakly supervised semantic segmentation algorithm, can generate pixel-accurate results using only image-level labels, but its scattered and partially underactivated class activation regions degrade segmentation performance. In this paper, we propose a weakly supervised semantic segmentation method, continuous gradient class activation mapping (CAM) and its nonlinear multiscale fusion (continuous gradient fusion CAM). The method redesigns backpropagating gradients and nonlinearly activates multiscale fused heatmaps to generate more fine-grained class activation maps with an appropriate activation degree for different damage site sizes. Experiments on our dataset show that the proposed method can achieve segmentation performance comparable to that of fully supervised algorithms.
The Interrelationship between Freedom of Thought, Conscience, and Religion and the Rule of Law
Authors: Giles Jessica 
Published: November 2023

AbstractThe article explores the connection between the rule of law and the right to freedom of thought, conscience, and religion from an empirical and theoretical perspective. The author posits that the two are not merely interdependent, but that freedom of thought, conscience, and religion is foundational for embedding the rule of law because a state needs to facilitate freedom of thought, conscience, and religion to encourage the exploration of virtue to inform consensus around society’s common norms. This virtue-building role of freedom of thought, conscience, and religion gives the human right its foundational role for creating the conditions required for embedding the rule of law. This conclusion is drawn from Martin Krygier’s analysis of the sociological conditions necessary to embed the rule of law and a comparison of the worldwide rule of law, religious freedom, and happiness indexes. To support a universal approach to the human right and to underpin the identified essentiality of it, the author proposes a theoretical approach grounded in the theory of common grace; Rowan Williams’s other-regarding communal approach to rights; and the framework for plural living together proposed by Herman Dooyeweerd. The author posits that this approach could be adapted with a plural metanarrative to accommodate dialogue around virtue building and dispute resolution within societies with very different outlooks.
How do adolescents classify foods as healthy and unhealthy?: A qualitative inquiry from rural India
Authors: Kansal Sangeeta , Raj Aryan , Smita Kumari , Worsley Anthony , Rathi Neha 
Published: November 2023

Abstract
Indian adolescents exhibit obesogenic dietary habits including low intake of fruits and vegetables and increasing consumption of fast food and carbonated beverages. Adolescents’ classification of healthy and unhealthy foods is likely to have significant implications for their dietary behaviour, and consequently, their health. However, there is limited evidence about the ways Indian adolescents classify foods as healthy or unhealthy. Hence, this qualitative study was designed to explore how Indian adolescents classify nutritious or non-nutritious food choices. Convenience sampling was used to recruit the study participants from Tikari village in Uttar Pradesh, India. Underpinned by the social constructivist lens, the adolescents were interviewed face-to-face in Hindi. All the interactions were digitally recorded, transcribed verbatim, and translated into English prior to data analysis. Transcribed data were analysed thematically using inductive as well as deductive coding, and subsequently, conceptual themes were extracted. A total of thirty-nine adolescents (twenty boys; nineteen girls) aged 10–19 years participated in this qualitative inquiry. The adolescents classified healthy and unhealthy foods based on the following six themes: (i) Food groups and nutrients; (ii) Health and immunity; (iii) Type of ingredient; (iv) Place and time of food preparation; (v) Packaging; and (vi) Parental influence. These findings can inform school-based food literacy interventions to foster healthy dietary habits and cooking skills among Indian adolescents.
Effects of pre-exercise high and low glycaemic index meals on substrate metabolism and appetite in middle-aged women
Authors: Sakazaki Miki , Yoshikawa Yoshie , Kamemoto Kayoko , Tataka Yusei , Yamada Yoshiki , Wu Ching-Lin , Miyashita Masashi 
Published: November 2023

Abstract
Few studies have examined the influence of pre-exercise meals with different glycaemic indices (GIs) on substrate oxidation and non-homeostatic appetite (i.e. food reward) in adults of various ages and ethnicities. We aimed to examine the effects of pre-exercise high and low GI meals on substrate oxidation and food reward in middle-aged Japanese women. This randomised crossover trial included fifteen middle-aged women (aged 40⋅9 ± 6⋅5 years, mean ± sd). The participants consumed a high or low GI breakfast at 09.00 and rested until 11.00. Thereafter, participants performed a 60-min walk at 50 % of their estimated maximum oxygen uptake (11.00–12.00) and rested until 13.00. Expired gas samples were collected every 30 min prior to walking, and samples were collected continuously throughout the walking and post-walking periods. Blood samples and subjective appetite ratings were collected every 30 min, except during walking. The Leeds Food Preference Questionnaire in Japanese (LFPQ-J) was used to assess food reward at 09.00, 10.00, and 13.00 h. The cumulative fat oxidation during exercise was higher in the low GI trial than in the high GI trial (P = 0⋅03). The cumulative carbohydrate oxidation during walking was lower in the low GI trial than in the high GI trial (P = 0⋅01). Trial-by-time interactions were not found for any food-reward parameters between trials. Low GI meals elicited enhanced fat oxidation during a subsequent 60-min walk in middle-aged women. However, meals with different GIs did not affect food reward evaluated over time in the present study.
Interplay between endocannabinoid and endovanilloid mechanisms in fear conditioning
Authors: Briânis Rayssa C. , Andreotti Julia P. , Moreira Fabrício A. , Iglesias Lia P. 
Published: November 2023

AbstractObjective:The transient receptor potential cation channel, subfamily V (vanilloid), member 1 (TRPV1) mediates pain perception to thermal and chemical stimuli in peripheral neurons. The cannabinoid receptor type 1 (CB1), on the other hand, promotes analgesia in both the periphery and the brain. TRPV1 and CB1 have also been implicated in learned fear, which involves the association of a previously neutral stimulus with an aversive event. In this review, we elaborate on the interplay between CB1 receptors and TRPV1 channels in learned fear processing.Methods:We conducted a PubMed search for a narrative review on endocannabinoid and endovanilloid mechanisms on fear conditioning.Results:TRPV1 and CB1 receptors are activated by a common endogenous agonist, arachidonoyl ethanolamide (anandamide), Moreover, they are expressed in common neuroanatomical structures and recruit converging cellular pathways, acting in concert to modulate fear learning. However, evidence suggests that TRPV1 exerts a facilitatory role, whereas CB1 restrains fear responses.Conclusion:TRPV1 and CB1 seem to mediate protective and aversive roles of anandamide, respectively. However, more research is needed to achieve a better understanding of how these receptors interact to modulate fear learning.
Systematic review and meta-analysis of laryngeal reinnervation techniques in adults with unilateral and bilateral vocal fold palsies
Authors: Onifade Anjola , Vincent Elizabeth , Tolley Neil 
Published: November 2023

AbstractObjectiveTo evaluate the outcomes of reinnervation techniques for the treatment of adult unilateral vocal fold paralysis and bilateral vocal fold paralysis.MethodsA literature review was conducted in the Embase and Medline databases in English, with no limitations on the publication date. The outcome parameters of interest included visual, subjective perceptual, acoustic, aerodynamic analysis and electromyography. A meta-analysis with a random-effects model and inverse variance was calculated.ResultsThe systematic Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach resulted in 27 studies, totalling 803 patients (747 unilateral cases and 56 bilateral cases). Thyroid cancer and/or surgery had caused unilateral vocal fold paralysis in 74.8 per cent of cases and bilateral vocal fold paralysis in 69.6 per cent of cases. Statistically significant improvements in patients were observed for voice, deglutition and decannulation (bilateral vocal fold paralysis). Meta-analysis of 10 reinnervation techniques was calculated for the maximum phonation time of 184 patients.ConclusionReinnervation was shown to improve voice, swallowing and decannulation, but studies lacked control groups, limiting generalisability. Larger studies with controls are needed.
Metabolic syndrome after childhood trauma: a 9-year longitudinal analysis
Authors: Souama Camille , Milaneschi Yuri , Lamers Femke , Vinkers Christiaan H. , Giltay Erik J. , Liemburg Edith J. , Penninx Brenda W. J. H. 
Published: November 2023

AbstractBackgroundChildhood trauma (CT) has been cross-sectionally associated with metabolic syndrome (MetS), a group of biological risk factors for cardiometabolic disease. Longitudinal studies, while rare, would clarify the development of cardiometabolic dysregulations over time. Therefore, we longitudinally investigated the association of CT with the 9-year course of MetS components.MethodsParticipants (N = 2958) from the Netherlands Study of Depression and Anxiety were assessed four times across 9 years. The CT interview retrospectively assessed childhood emotional neglect and physical, emotional, and sexual abuse. Metabolic outcomes encompassed continuous MetS components (waist circumference, triglycerides, high-density lipoprotein [HDL] cholesterol, blood pressure [BP], and glucose) and count of clinically elevated MetS components. Mixed-effects models estimated sociodemographic- and lifestyle-adjusted longitudinal associations of CT with metabolic outcomes over time. Time interactions evaluated change in these associations.ResultsCT was reported by 49% of participants. CT was consistently associated with increased waist (b = 0.32, s.e. = 0.10, p = 0.001), glucose (b = 0.02, s.e. = 0.01, p < 0.001), and count of MetS components (b = 0.04, s.e. = 0.01, p < 0.001); and decreased HDL cholesterol (b = −0.01, s.e.<0.01, p = .020) and systolic BP (b = −0.33, s.e. = 0.13, p = 0.010). These associations were mainly driven by severe CT and unaffected by lifestyle. Only systolic BP showed a CT-by-time interaction, where CT was associated with lower systolic BP initially and with higher systolic BP at the last follow-up.ConclusionsOver time, adults with CT have overall persistent poorer metabolic outcomes than their non-maltreated peers. Individuals with CT have an increased risk for cardiometabolic disease and may benefit from monitoring and early interventions targeting metabolism.
Are dynamic measurements of central venous pressure in Fontan circulation during exercise or volume loading superior to resting measurements?
Authors: Venna Alyssia , Deshpande Shriprasad , Downing Tacy , John Anitha , d’Udekem Yves 
Published: November 2023

AbstractBackground:The main objective measure to assess the health of the Fontan circulation is the pressure measurement of the superior vena cava or pulmonary arteries. We reviewed the literature for benefits of measuring resting pressure in the Fontan circuit and explored whether dynamic measurement by volume loading or exercise has the potential to refine this diagnostic tool.Methods:PubMed was searched for articles showing a relationship between resting post-operative central venous pressure or pulmonary artery pressure and Fontan failure. Relationships between post-operative central venous pressure or pulmonary artery pressure and volume loading changes, such as during exercise or volume loading during cardiac catheterization, were also queried.Results:A total of 44 articles mentioned relationships between resting central venous pressure or pulmonary artery pressure and Fontan failure. Only 26 included an analysis between the variables and only seven of those articles found pressure to be predictive of Fontan failure. Ten articles examined the relationship between exercise or volume loading and outcomes and demonstrated a large individual variation of pressures under these dynamic conditions.Conclusions:Based on current literature, there is not a lot of strong evidence to show that elevated resting central venous pressure or pulmonary artery pressure is predictive of Fontan failure. Some individuals experience dramatic increases in central venous pressure or pulmonary artery pressure under increased loading conditions with exercise or bolus fluid infusion, while others experience increases closer to that of a healthy control population. Further studies are needed to examine whether more dynamic and continuous monitoring of systemic venous pressures might better predict outcomes in patients with Fontan circulation.
Identifying a locus in super-enhancer and its resident NFE2L1/MAFG as transcriptional factors that drive PD-L1 expression and immune evasion
Authors: Shi Conglin , Chen Liuting , Pi Hui , Cui Henglu , Fan Chenyang , Tan Fangzheng , Qu Xuanhao , Sun Rong , Zhao Fengbo , Song Yihua , Wu Yuanyuan , Chen Miaomiao , Ni Wenkai , Qu Lishuai , Mao Renfang , Fan Yihui 
Published: November 2023

AbstractAlthough the transcriptional regulation of the programmed death ligand 1 (PD-L1) promoter has been extensively studied, the transcription factor residing in the PD-L1 super-enhancer has not been comprehensively explored. Through saturated CRISPR-Cas9 screening of the core region of the PD-L1 super-enhancer, we have identified a crucial genetic locus, referred to as locus 22, which is essential for PD-L1 expression. Locus 22 is a potential binding site for NFE2:MAF transcription factors. Although genetic silencing of NRF2 (NFE2L2) did not result in a reduction of PD-L1 expression, further analysis reveals that MAFG and NFE2L1 (NRF1) play a critical role in the expression of PD-L1. Importantly, lipopolysaccharides (LPS) as the major component of intratumoral bacteria could greatly induce PD-L1 expression, which is dependent on the PD-L1 super-enhancer, locus 22, and NFE2L1/MAFG. Mechanistically, genetic modification of locus 22 and silencing of MAFG greatly reduce BRD4 binding and loop formation but have minimal effects on H3K27Ac modification. Unlike control cells, cells with genetic modification of locus 22 and silencing of NFE2L1/MAFG failed to escape T cell-mediated killing. In breast cancer, the expression of MAFG is positively correlated with the expression of PD-L1. Taken together, our findings demonstrate the critical role of locus 22 and its associated transcription factor NFE2L1/MAFG in super-enhancer– and LPS-induced PD-L1 expression. Our findings provide new insight into understanding the regulation of PD-L1 transcription and intratumoral bacteria-mediated immune evasion.
RPL22L1, a novel candidate oncogene promotes temozolomide resistance by activating STAT3 in glioblastoma
Authors: Chen Yunping , Mu Yu , Guan Qing , Li Chenlong , Zhang Yangong , Xu Yinzhi , Zhou Chong , Guo Ying , Ma Yanan , Zhao Meiqi , Ji Guohua , Liu Peng , Sun Donglin , Sun Haiming , Wu Nan , Jin Yan 
Published: November 2023

AbstractAggressiveness and drug resistance are major challenges in the clinical treatment of glioblastoma (GBM). Our previously research reported a novel candidate oncogene ribosomal protein L22 like 1 (RPL22L1). The aim of this study was to elucidate the potential role and mechanism of RPL22L1 in progression and temozolomide (TMZ) resistance of GBM. Online database, tissue microarrays and clinical tissue specimens were used to evaluate the expression and clinical implication of RPL22L1 in GBM. We performed cell function assays, orthotopic and subcutaneous xenograft tumor models to evaluate the effects and molecular mechanisms of RPL22L1 on GBM. RPL22L1 expression was significantly upregulated in GBM and associated with poorer prognosis. RPL22L1 overexpression enhanced GBM cell proliferation, migration, invasion, TMZ resistance and tumorigenicity, which could be reduced by RPL22L1 knockdown. Further, we found RPL22L1 promoted mesenchymal phenotype of GBM and the impact of these effects was closely related to EGFR/STAT3 pathway. Importantly, we observed that STAT3 specific inhibitor (Stattic) significantly inhibited the malignant functions of RPL22L1, especially on TMZ resistance. RPL22L1 overexpressed increased combination drug sensitive of Stattic and TMZ both in vitro and in vivo. Moreover, Stattic effectively restored the sensitive of RPL22L1 induced TMZ resistance in vitro and in vivo. Our study identified a novel candidate oncogene RPL22L1 which promoted the GBM malignancy through STAT3 pathway. And we highlighted that Stattic combined with TMZ therapy might be an effective treatment strategy in RPL22L1 high-expressed GBM patients.
Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly
Authors: Houghton F. M. , Adams S. E. , Ríos A. S. , Masino L. , Purkiss A. G. , Briggs D. C. , Ledda F. , McDonald N. Q. 
Published: November 2023

AbstractGlial-cell line derived neurotrophic factor (GDNF) bound to its co-receptor GFRα1 stimulates the RET receptor tyrosine kinase, promoting neuronal survival and neuroprotection. The GDNF-GFRα1 complex also supports synaptic cell adhesion independently of RET. Here, we describe the structure of a decameric GDNF-GFRα1 assembly determined by crystallography and electron microscopy, revealing two GFRα1 pentamers bridged by five GDNF dimers. We reconsitituted the assembly between adhering liposomes and used cryo-electron tomography to visualize how the complex fulfils its membrane adhesion function. The GFRα1:GFRα1 pentameric interface was further validated both in vitro by native PAGE and in cellulo by cell-clustering and dendritic spine assays. Finally, we provide biochemical and cell-based evidence that RET and heparan sulfate cooperate to prevent assembly of the adhesion complex by competing for the adhesion interface. Our results provide a mechanistic framework to understand GDNF-driven cell adhesion, its relationship to trophic signalling, and the central role played by GFRα1.
Synaptic mechanisms for associative learning in the cerebellar nuclei
Authors: Broersen Robin , Albergaria Catarina , Carulli Daniela , Carey Megan R. , Canto Cathrin B. , De Zeeuw Chris I. 
Published: November 2023

AbstractAssociative learning during delay eyeblink conditioning (EBC) depends on an intact cerebellum. However, the relative contribution of changes in the cerebellar nuclei to learning remains a subject of ongoing debate. In particular, little is known about the changes in synaptic inputs to cerebellar nuclei neurons that take place during EBC and how they shape the membrane potential of these neurons. Here, we probed the ability of these inputs to support associative learning in mice, and investigated structural and cell-physiological changes within the cerebellar nuclei during learning. We find that optogenetic stimulation of mossy fiber afferents to the anterior interposed nucleus (AIP) can substitute for a conditioned stimulus and is sufficient to elicit conditioned responses (CRs) that are adaptively well-timed. Further, EBC induces structural changes in mossy fiber and inhibitory inputs, but not in climbing fiber inputs, and it leads to changes in subthreshold processing of AIP neurons that correlate with conditioned eyelid movements. The changes in synaptic and spiking activity that precede the CRs allow for a decoder to distinguish trials with a CR. Our data reveal how structural and physiological modifications of synaptic inputs to cerebellar nuclei neurons can facilitate learning.
Megakaryocyte- and erythroblast-specific cell-free DNA patterns in plasma and platelets reflect thrombopoiesis and erythropoiesis levels
Authors: Moss Joshua , Ben-Ami Roni , Shai Ela , Gal-Rosenberg Ofer , Kalish Yosef , Klochendler Agnes , Cann Gordon , Glaser Benjamin , Arad Ariela , Shemer Ruth , Dor Yuval 
Published: November 2023

AbstractCirculating cell-free DNA (cfDNA) fragments are a biological analyte with extensive utility in diagnostic medicine. Understanding the source of cfDNA and mechanisms of release is crucial for designing and interpreting cfDNA-based liquid biopsy assays. Using cell type-specific methylation markers as well as genome-wide methylation analysis, we determine that megakaryocytes, the precursors of anuclear platelets, are major contributors to cfDNA (~26%), while erythroblasts contribute 1–4% of cfDNA in healthy individuals. Surprisingly, we discover that platelets contain genomic DNA fragments originating in megakaryocytes, contrary to the general understanding that platelets lack genomic DNA. Megakaryocyte-derived cfDNA is increased in pathologies involving increased platelet production (Essential Thrombocythemia, Idiopathic Thrombocytopenic Purpura) and decreased upon reduced platelet production due to chemotherapy-induced bone marrow suppression. Similarly, erythroblast cfDNA is reflective of erythrocyte production and is elevated in patients with thalassemia. Megakaryocyte- and erythroblast-specific DNA methylation patterns can thus serve as biomarkers for pathologies involving increased or decreased thrombopoiesis and erythropoiesis, which can aid in determining the etiology of aberrant levels of erythrocytes and platelets.