bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep proteome investigation of high-grade gliomas reveals heterogeneity driving differential metabolism of 5-aminolevulinic acid
Authors: Ghantasala Saicharan , Bhat Amruth , Agarwal Unnati , Biswas Deeptarup , Bhattarai Prawesh , Epari Sridhar , Moiyadi Aliasgar , Srivastava Sanjeeva 
Published: June 2023

Abstract

Background
Fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) as adjunct for high-grade gliomas (HGGs) has been on the rise in recent years. Despite being largely effective, we observed multiple histologically similar sub-regions of the same tumor from a few individuals with varying protoporphyrin IX (PpIX) levels. The current study aims at understanding the proteomic changes driving differential metabolism of 5-ALA in HGGs.

Methods
Biopsies were histologically and biochemically assayed. Following this, a deep proteomics investigation was carried out using high resolution liquid chromatography—mass spectrometry (HR LC-MS) to identify protein expression in differentially fluorescing regions of HGGs.

Results
Our analysis identified 5437 proteins with high confidence. Differential analysis in the subgroup with HGGs carrying IDH mutation (IDH mt.) revealed 93 differentially regulated proteins (raw p-value ≤ 0.05 and absolute FC ≥ 1.5). Similar analysis in the IDH wild type (IDH wt.) subgroup revealed 20 differentially regulated proteins. Gene set enrichment analysis (GSEA) identified key pathways like ion channel transport, trafficking of AMPA receptors, and regulation of heme-oxygenase-1 in the IDH wt. subgroup. Pathways such as scavenging of heme, signaling by NOTCH4, negative regulation of PI3-AKT pathway, and iron uptake and transport were observed to be differentially regulated in the IDH mt. subgroup.

Conclusions
Tumor regions from the same patient exhibiting differential fluorescence following 5-ALA administration were observed to have different proteome profiles. Future studies aimed at a better molecular understanding of 5-ALA metabolism in HGGs hold the potential to increase the efficacy of FGS and the use of 5-ALA as a theragnostic tool.
Retrospective and Real-time Measures of the Quantity of E-cigarette Use: An Ecological Momentary Assessment Study
Authors: Yang James J , Ou Tzung-Shiang , Lin Hsien-Chang , Kyung Nam Joon , Piper Megan E , Buu Anne 
Published: June 2023

AbstractIntroductionQuantifying e-cigarette use is challenging because of the wide variety of products and the lack of a clear, objective demarcation of a use event. This study aimed to characterize the difference between retrospective and real-time measures of the quantity of e-cigarette use and identify the covariates that may account for discrepancies between the two types of measures.MethodsThis study analyzed data from 401 college student e-cigarette users in Indiana and Texas who responded to a web survey (retrospective) and 7-day ecological momentary assessments (EMA) (real-time) on their e-cigarette use behavior, dependence symptomatology, e-cigarette product characteristics, and use contexts from Fall 2019 to Fall 2021. Generalized linear mixed models were used to model the real-time measures of quantity offset by the retrospective average quantity.ResultsAlthough the number of times using e-cigarettes per day seems to be applicable to both retrospective and real-time measures, the number reported via EMA was 8.5 times the retrospective report. E-cigarette users with higher e-cigarette primary dependence motives tended to report more daily nicotine consumption via EMA than their retrospective reports (ie, perceived average consumption). Other covariates that were associated with discrepancies between real-time and retrospective reports included gender, nicotine concentration, using a menthol- or fruit-flavored product, co-use with alcohol, and being with others when vaping,ConclusionsThe study found extreme under-reporting of e-cigarette consumption on retrospective surveys. Important covariates identified to be associated with higher than average consumption may be considered as potential targets for future vaping interventions.ImplicationsThis is the first study that characterizes the direction and magnitude of the difference between retrospective and real-time measures of the quantity of e-cigarette use among young adults—the population most likely to use e-cigarettes. An average retrospective account of vaping events per day may significantly underestimate e-cigarette use frequency among young adults. The lack of insight into the degree of consumption among users with heavy primary dependence motives illustrates the importance of incorporating self-monitoring into cessation interventions.
Cash versus lottery video messages: online COVID-19 vaccine incentives experiment
Authors: Duch Raymond M , Barnett Adrian , Filipek Maciej , Espinosa-Brito Javier , Roope Laurence S J , Violato Mara , Clarke Philip M 
Published: June 2023

Abstract
During the COVID-19 pandemic, governments offered financial incentives to increase vaccine uptake. We evaluate the impact on COVID-19 vaccine uptake of cash equivalents versus being entered into lotteries. We randomly assign 1628 unvaccinated US participants into one of three 45-second informational videos promoting vaccination with messages about (a) health benefits of COVID-19 vaccines (control), (b) being entered into lotteries or (c) receiving cash equivalent vouchers. After seeing the control health information video, 16% of individuals wanted information on COVID-19 vaccination. This compared with 14% of those assigned to the lottery video (odds ratio of 0.82 relative to control: 95% credible interval, 0.58–1.17) and 22% of those assigned to the cash voucher video (odds ratio of 1.53 relative to control: 95% credible interval, 1.11–2.11). These results support greater use of cash vouchers to promote information seeking about COVID-19 vaccination and do not support the use of lottery incentives.
Age as a moderator in the interplay among locus of control, coping, and quality of life of people with chronic pain
Authors: Kłosowska Joanna , Farley Dominika , Brączyk Justyna , Buglewicz-Przewoźnik Ewa , Bąbel Przemysław 
Published: June 2023

Abstract

Objective
Identifying the factors that determine the quality of life of patients with chronic pain is an integral part of developing interventions to reduce the negative impact of persistent pain. Locus of control (LoC) could play an important role in adaptation to prolonged pain, but the results of studies are inconsistent. We examined the link between pain LoC and quality of life. Moreover, we investigated whether the relationship between LoC and quality of life is mediated by passive and active coping, and whether age moderates the LoC–coping relationship.

Methods
The study was cross-sectional, and variables (internal, chance and powerful-others LoC, pain coping strategies, average pain intensity, and quality of life) were assessed via questionnaires in a sample of 594 individuals (67% females) with chronic pain who were 18–72 (mean: 36) years of age.

Results
Mediation and moderated mediation analyses were conducted. Internal and external LoC were associated, respectively, with better and with worse quality of life. Passive coping mediated the association between the powerful-others dimension of LoC and poor quality of life. Additionally, indirect effects of internal LoC on quality of life via passive and active coping were found. The relationship between the powerful-others dimension of LoC and coping was stronger for middle-aged and older individuals than for younger individuals.

Conclusions
This study contributes to a better understanding of the mechanisms linking LoC with quality of life of patients with chronic pain. Depending on the age, control beliefs might translate differently into strategies used to cope with pain, and thus into quality of life.
Exploring the treatment burden of disease-modifying anti-rheumatic drug monitoring in people with rheumatoid arthritis
Authors: Ryan Sarah , Bullock Laurna , Manning Fay , A. Chew-Graham Carolyn , Paskins Zoe 
Published: June 2023

Abstract

Objectives
People with RA taking DMARDs require safety monitoring to identify potential side effects. The aim of this study was to explore the perspectives of patients and family members on DMARD monitoring and how the associated treatment burden could be minimized to optimize concordance and safety.

Methods
Thirteen adults with RA on DMARDs and three family members participated in semi-structured telephone interviews between July 2021 and January 2022. Data were analysed using a framework method. Findings were discussed with a group of stakeholders to develop implications for practice.

Results
Two main themes were identified: (i) making sense of drug monitoring; and (ii) work involved in drug monitoring. Participants perceived DMARDs as necessary to reduce symptoms, with drug monitoring providing an opportunity for a holistic assessment of wellbeing. Participants expressed a preference for face-to-face consultations, which allowed them to share their concerns, rather than remote, often transactional, care. The limited availability of convenient appointment times, travel requirements and parking increased the work involved for patients and family members.

Conclusion
Drug monitoring was accepted as a necessity of DMARD treatment, but increased the work for people with RA related to organizing and attending appointments. The potential for treatment burden needs to be assessed proactively by clinicians when a DMARD is commenced. Where identified, strategies for minimizing the treatment burden can form part of a shared management plan, including the offer of regular contact with health professionals, with an emphasis on person-centred care.
Azathioprine vs methotrexate in eosinophilic granulomatosis with polyangiitis: a monocentric retrospective study
Authors: Milanesi Alessandra , Delvino Paolo , Quaglini Silvana , Montecucco Carlomaurizio , Monti Sara 
Published: June 2023

Abstract

Objectives
To analyse the effectiveness, safety and steroid-sparing effect of AZA and MTX as induction of remission and maintenance treatment in eosinophilic granulomatosis with polyangiitis.

Methods
We retrospectively collected data from 57 patients divided into four groups according to treatment: MTX/AZA as first-line agents (MTX1/AZA1) in non-severe disease or as second-line maintenance therapy (MTX2/AZA2) in severe disease previously treated with CYC/rituximab. During the first 5 years of treatment with AZA/MTX we compared the groups according to: remission rate [defined as R1: BVAS = 0; R2: BVAS = 0 with prednisone ≤5 mg/day; R3 (MIRRA definition): BVAS = 0 with prednisone ≤3.75 mg/day], persistence on therapy, cumulative glucocorticoid (GC) dose, relapse and adverse events (AEs).

Results
There were no significant differences in remission rates (R1) in each group (63% in MTX1 vs 75% in AZA1, P = 0.53; 91% in MTX2 vs 71% in AZA2, P = 0.23). MTX1 allowed R2 more frequently in the first 6 months compared with AZA1 (54% vs 12%, P = 0.04); no patients receiving AZA1 achieved R3 up to the first 18 months (vs 35% in MTX1, P = 0.07). The cumulative GC dose was lower for MTX2 vs AZA2 (6 g vs 10.7 g at 5 years, P = 0.03). MTX caused more AEs compared with AZA (66% vs 30%, P = 0.004), without affecting the suspension rate. No differences emerged in time-to-first relapse, although fewer patients treated with AZA2 had asthma/ENT relapses (23% vs 64%, P = 0.04).

Conclusion
A significant proportion of patients achieved remission with both MTX and AZA. MTX1 had an earlier remission on a lower GC dose but MTX2 had a better steroid-sparing effect.
5Ecocriticism
Authors: Ryan John Charles 
Published: June 2023

AbstractThis review of ecocritical publications in 2022 is divided into six sections: 1. Introduction: Ecocriticism in the Anthropocene; 2. Eco-modernism: The Environmental Turn in Modernist Studies; 3. Climate Criticism: Narratives of Vulnerability; 4. Cryocriticism: Biographies of Ice; 5. More-than-Human Ecocriticism: The Heterogeneities of Nature; 6. Conclusion: Ecocriticism and Transformation.
Stem Cell Therapy Enriched Fat Grafting for the Reconstruction of Craniofacial Deficits
Authors: Bourne Debra A. , Egro Francesco M. , Bliley Jacqueline , James Isaac , Haas Gretchen L. , Meyer E. Michael , Donnenberg Vera , Donnenberg Albert D. , Branstetter Barton , Coleman Sydney , Rubin J. Peter 
Published: June 2023

Background:
Fat grafting is an effective treatment for craniofacial deformities. Stromal vascular fraction (SVF) is a concentrated form of adipose derived stem cells that can be isolated from fat. The aim of this clinical trial was to assess the impact of SVF enrichment on craniofacial fat grafting.

Methods:
Twelve subjects with at least two regions of craniofacial volume deficit were enrolled, and they underwent fat grafting with SVF-enriched or standard fat grafting to each area. All patients had bilateral malar regions injected with SVF-enriched graft on one side and control standard fat grafting to the contralateral side. Outcome assessments included demographic information, volume retention determined by CT scans, SVF cell populations assessed by flow cytometry, SVF cell viability, complications, and appearance ratings. Follow-up was 9 months.

Results:
All patients had improvement in appearance. There were no serious adverse events. There was no significant difference in volume retention between the SVF-enriched and control regions overall (50.3% versus 57.3%, P = 0.269) or comparing malar regions (51.4% versus 56.7%, P = 0.494). Patient age, smoking status, obesity, and diagnosis of diabetes did not impact volume retention. Cell viability was 77.4% ± 7.3%. Cellular subpopulations were 60.1% ± 11.2% adipose derived stem cells, 12.2 ± 7.0% endothelial cells, and 9.2% ± 4.4% pericytes. A strong positive correlation was found between CD146+ CD31-pericytes and volume retention (R = 0.863, P = 0.027).

Conclusions:
Autologous fat transfer for reconstruction of craniofacial defects is effective and safe, leading to reliable volume retention. However, SVF enrichment does not significantly impact volume retention.
Current status and practical considerations of artificial intelligence use in screening and diagnosing retinal diseases: Vision Academy retinal expert consensus
Authors: Chou Yu-Bai , Kale Aditya U. , Lanzetta Paolo , Aslam Tariq , Barratt Jane , Danese Carla , Eldem Bora , Eter Nicole , Gale Richard , Korobelnik Jean-François , Kozak Igor , Li Xiaorong , Li Xiaoxin , Loewenstein Anat , Ruamviboonsuk Paisan , Sakamoto Taiji , Ting Daniel S.W. , van Wijngaarden Peter , Waldstein Sebastian M. , Wong David , Wu Lihteh , Zapata Miguel A. , Zarranz-Ventura Javier 
Published: June 2023

Purpose of review
The application of artificial intelligence (AI) technologies in screening and diagnosing retinal diseases may play an important role in telemedicine and has potential to shape modern healthcare ecosystems, including within ophthalmology.

Recent findings
In this article, we examine the latest publications relevant to AI in retinal disease and discuss the currently available algorithms. We summarize four key requirements underlining the successful application of AI algorithms in real-world practice: processing massive data; practicability of an AI model in ophthalmology; policy compliance and the regulatory environment; and balancing profit and cost when developing and maintaining AI models.

Summary
The Vision Academy recognizes the advantages and disadvantages of AI-based technologies and gives insightful recommendations for future directions.
Longitudinal Assessment of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thicknesses in Patients With Large Optic Disc Cups and Normal Intraocular Pressure and Visual Fields
Authors: Kang Eun Jin , Jin Sang Wook 
Published: June 2023

Précis:
The thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and ganglion cell complex (GCC) did not change during 5 years in physiological large disc cupping.

Purpose:
We evaluated longitudinal changes in the thicknesses of the cpRNFL and GCC in large disc cupping with a normal intraocular pressure (IOP) (<21 mm Hg) and visual field.

Methods:
This retrospective, consecutive case series study included 269 eyes of 269 patients with large disc cupping and normal IOP. We analyzed patient demographics, IOP, central corneal thickness, vertical cup-to-disc ratios using color fundus photography, the thicknesses of the cpRNFL and GCC using RTVue-100, and mean deviation using visual field examinations.

Results:
The differences in IOP, vertical cup-to-disc ratios, and mean deviation between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the cpRNFL thickness were 106.5±8.5 and 105.1±9.3 μm, respectively; differences between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the GCC thickness were 82.8±9. and 81.5±9.2 μm, respectively; differences between baseline and each follow-up visit were not statistically significant.

Conclusions:
The thicknesses of the cpRNFL and GCC did not change in well-maintained optic nerve head findings with normal IOP and visual field during a 5-year follow-up period. Optical coherence tomography evaluations of the thicknesses of the cpRNFL and GCC help accurately diagnose physiological optic disc cupping.
Augmented pain-evoked primary sensorimotor cortex activation in adolescent girls with juvenile fibromyalgia
Authors: Tong Han , Maloney Thomas C. , Payne Michael F. , Suñol Maria , Dudley Jonathan A. , King Christopher D. , Ting Tracy V. , Kashikar-Zuck Susmita , Coghill Robert C. , López-Solà Marina 
Published: June 2023

Abstract
Juvenile fibromyalgia (JFM) is a chronic widespread pain condition that primarily affects adolescent girls. Previous studies have found increased sensitivity to noxious pressure in adolescents with JFM. However, the underlying changes in brain systems remain unclear. The aim of this study was to characterize pain-evoked brain responses and identify brain mediators of pain hypersensitivity in adolescent girls with JFM. Thirty-three adolescent girls with JFM and 33 healthy adolescent girls underwent functional magnetic resonance imaging scans involving noxious pressure applied to the left thumbnail at an intensity of 2.5 or 4 kg/cm2 and rated pain intensity and unpleasantness on a computerized Visual Analogue Scale. We conducted standard general linear model analyses and exploratory whole-brain mediation analyses. The JFM group reported significantly greater pain intensity and unpleasantness than the control group in response to noxious pressure stimuli at both intensities (P < 0.05). The JFM group showed augmented right primary somatosensory cortex (S1) activation to 4 kg/cm2 (Z > 3.1, cluster-corrected P < 0.05), and the peak S1 activation magnitudes significantly correlated with the scores on the Widespread Pain Index (r = 0.35, P = 0.048) with higher activation associated with more widespread pain. We also found that greater primary sensorimotor cortex activation in response to 4 kg/cm2 mediated the between-group differences in pain intensity ratings (P < 0.001). In conclusion, we found heightened sensitivity to noxious pressure stimuli and augmented pain-evoked sensorimotor cortex responses in adolescent girls with JFM, which could reflect central sensitization or amplified nociceptive input.
Morphine-induced osteolysis and hypersensitivity is mediated through toll-like receptor-4 in a murine model of metastatic breast cancer
Authors: Thompson Austen L. , Grenald Shaness A. , Ciccone Haley A. , Mohty Dieter , Smith Angela F. , Coleman Deziree L. , Bahramnejad Erfan , De Leon Erick , Kasper-Conella Logan , Uhrlab Jennifer L. , Margolis David S. , Salvemini Daniela , Largent-Milnes Tally M. , Vanderah Todd W. 
Published: June 2023

Abstract
The propensity for breast cancer to metastasize to bone is coupled to the most common complaint among breast cancer patients: bone pain. Classically, this type of pain is treated using escalating doses of opioids, which lack long-term efficacy due to analgesic tolerance, opioid-induced hypersensitivity, and have recently been linked to enhanced bone loss. To date, the molecular mechanisms underlying these adverse effects have not been fully explored. Using an immunocompetent murine model of metastatic breast cancer, we demonstrated that sustained morphine infusion induced a significant increase in osteolysis and hypersensitivity within the ipsilateral femur through the activation of toll-like receptor-4 (TLR4). Pharmacological blockade with TAK242 (resatorvid) as well as the use of a TLR4 genetic knockout ameliorated the chronic morphine-induced osteolysis and hypersensitivity. Genetic MOR knockout did not mitigate chronic morphine hypersensitivity or bone loss. In vitro studies using RAW264.7 murine macrophages precursor cells demonstrated morphine-enhanced osteoclastogenesis that was inhibited by the TLR4 antagonist. Together, these data indicate that morphine induces osteolysis and hypersensitivity that are mediated, in part, through a TLR4 receptor mechanism.
Evolving acidic microenvironments during colitis provide selective analgesic targets for a pH-sensitive opioid
Authors: Degro Claudius E. , Jiménez-Vargas Nestor Nivardo , Tsang Quentin , Yu Yang , Guzman-Rodriguez Mabel , Alizadeh Elahe , Hurlbut David , Reed David E. , Lomax Alan E. , Stein Christoph , Bunnett Nigel W. , Vanner Stephen J. 
Published: June 2023

AbstractTargeting the acidified inflammatory microenvironment with pH-sensitive opioids is a novel approach for managing visceral pain while mitigating side effects. The analgesic efficacy of pH-dependent opioids has not been studied during the evolution of inflammation, where fluctuating tissue pH and repeated therapeutic dosing could influence analgesia and side effects. Whether pH-dependent opioids can inhibit human nociceptors during extracellular acidification is unexplored. We studied the analgesic efficacy and side-effect profile of a pH-sensitive fentanyl analog, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), during the evolution of colitis induced in mice with dextran sulphate sodium. Colitis was characterized by granulocyte infiltration, histological damage, and acidification of the mucosa and submucosa at sites of immune cell infiltration. Changes in nociception were determined by measuring visceromotor responses to noxious colorectal distension in conscious mice. Repeated doses of NFEPP inhibited nociception throughout the course of disease, with maximal efficacy at the peak of inflammation. Fentanyl was antinociceptive regardless of the stage of inflammation. Fentanyl inhibited gastrointestinal transit, blocked defaecation, and induced hypoxemia, whereas NFEPP had no such side effects. In proof-of-principle experiments, NFEPP inhibited mechanically provoked activation of human colonic nociceptors under acidic conditions mimicking the inflamed state. Thus, NFEPP provides analgesia throughout the evolution of colitis with maximal activity at peak inflammation. The actions of NFEPP are restricted to acidified layers of the colon, without common side effects in normal tissues.N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide could provide safe and effective analgesia during acute colitis, such as flares of ulcerative colitis.