bluuebunny/crossref_metadata_2025_split huggingface dataset:
Affective Responses to Fitness Testing in College-Aged Women
Authors: Abreu Alyssa , Thompson Jessica , Cofield Danielle N. , Faries Mark D. , Jones Eric J. 
Published: October 2022

Physical inactivity is common among women and a quarter of college-aged women are classified as overweight or obese, making this population an important target for obesity prevention. Fitness testing is commonplace, and practitioners can hold an underlying belief that discrepancies will promote positive responses. However, little research has examined the affective responses to fitness testing in adults. The purpose of this study was to assess the affective responses to common fitness testing, while examining relationships to physical self to help elucidate why some respond to such testing and others do not. Forty-eight college-aged women were presented with their discrepancy from a normative standard across six fitness tests. Findings support previous conceptualizations on discrepancies and affective responses, in that greater negative discrepancies from normative standards were associated with greater changes in negative feeling states. In addition, the results suggest that only certain discrepancies pose a threat to perceived satisfaction with one’s physical self (i.e., self-concept)—mainly though subdomains related to body appearance and aerobic fitness. In other words, the greater the perceived satisfaction of self, the greater negative emotional response was experienced to the specific test discrepancy. The notation of “threats” to important domains of self-concept might help explain why fitness testing that alerts individuals where they are discrepant produce behavioral changes in some but not others. Professionals should consider the impact of providing fitness test discrepancies on negative affective responses, with the possible impact on motivation and future behavior choices to reduce the discrepancy.
Prevalence and risk factors for age-related macular degeneration in a population-based cohort study of older adults in Northern Ireland using multimodal imaging: NICOLA Study
Authors: Hogg Ruth E , Wright David M , Quinn Nicola B , Muldrew Katherine Alyson , Hamill Barbra , Smyth Laura , McKnight Amy Jayne , Woodside Jayne , Tully Mark A , Cruise Sharon , McGuinness Bernadette , Young Ian S , Kee Frank , Peto Tunde , Chakravarthy Usha 
Published: October 2022

Purpose
To report prevalence and risk factor associations for age-related macular degeneration (AMD) and AMD features from multimodal retinal grading in a multidisciplinary longitudinal population-based study of aging in Northern Ireland.

Study design
Population-based longitudinal cohort study.

Methods
Retinal imaging at the Norther Ireland Cohort for the Longitudinal Aging Study health assessment included stereo Colour Fundus Photography (CFP) (Canon CX-1, Tokyo, Japan) and Spectral-Domain Optical Coherence Tomography (SD-OCT) ((Heidelberg Retinal Angopgraph (HRA)+OCT; Heidelberg Engineering, Heidelberg, Germany). Medical history and demographic information was obtained during a home interview. Descriptive statistics were used to describe the prevalence of AMD and individual AMD features. Multiple imputation followed by multiple regression modelling was used to explore risk factor associations including relationships with AMD genetic risk score.

Results
Retinal images from 3386 participants were available for analysis. Mean age of the sample was 63.4 (SD 9.01, range: 36–99). Population weighted prevalence of AMD using colour grading in those over 55 years was: no drusen: 6 0.4%; drusen <63 μm: 15.9%; drusen 63–125 µm: 13.7%; drusen >125 µm or pigmentary changes: 8.3%; late AMD: 1.6%. Prevalence of AMD features in those over 55 years was: OCT drusen 27.5%, complete outer retinal pigment epithelium and outer retinal atrophy (cRORA) on OCT was 4.3%, reticular drusen 3.2% and subretinal drusenoid deposits 25.7%. The genetic risk score was significantly associated with drusen and cRORA but less so for SDD alone and non-significant for hyperpigmentation or vitelliform lesions.

Conclusions
Multimodal imaging-based classification has provided evidence of some divergence of genetic risk associations between classical drusen and SDD. Our findings support an urgent review of current AMD severity classification systems.
Respiratory function and CT abnormalities among survivors of COVID-19 pneumonia: a nationwide follow-up study
Authors: Axelsson Gisli Thor , Halldorsson Arnljotur Bjorn , Jonsson Helgi Mar , Eythorsson Elias , Sigurdardottir Sigridur Erla , Hardardottir Hronn , Gudmundsson Gunnar , Hansdottir Sif 
Published: October 2022

IntroductionConsidering the pulmonary burden caused by acute COVID-19, questions remain of respiratory consequences after recovery. The aim of the study was to describe respiratory function of COVID-19 pneumonia survivors at mid-term follow-up (median 68 days) and assess whether impairments were predicted by acute illness severity or residual CT abnormalities.MethodsResidents of Iceland that had COVID-19 and oxygen saturation ≤94% from 28 February 2020 to 30 April 2021 were offered a clinical follow-up visit with an interview, a 6 min walk test (6MWT), spirometry with gas exchange measurement and chest CT. The results of these examinations were described, grouped by the level of care during acute illness. The associations of disease severity and CT abnormalities at follow-up with subjective dyspnoea, 6MWT results and lung function test results were estimated with regression analyses.ResultsOf 190 eligible patients, 164 (86%) participated in the study. Of those, 32 had never been admitted to hospital, 103 were admitted to hospital without intensive care and 29 had required intensive care. At a follow-up, need for intensive care during acute illness was associated with shorter walking distance on 6MWT, lower oxygen saturation and lower DLCO. Imaging abnormalities at follow-up were observed for most participants (74%) and the magnitude of these changes was associated with decrements in 6MWT distance, oxygen saturation, forced vital capacity and DLCO.ConclusionsThe findings show that impaired exercise capacity and lung physiology at follow-up were primarily observed for patients with COVID-19 pneumonia that required intensive care treatment and/or had persistent imaging abnormalities.
Clinical, neuroimaging and molecular characteristics ofPPP2R5D-related neurodevelopmental disorders: an expanded series with functional characterisation and genotype–phenotype analysis
Authors: Oyama Nora , Vaneynde Pieter , Reynhout Sara , Pao Emily M , Timms Andrew , Fan Xiao , Foss Kimberly , Derua Rita , Janssens Veerle , Chung Wendy , Mirzaa Ghayda M 
Published: October 2022

BackgroundVariants inPPP2R5D, affecting the regulatory B56δ subunit of protein phosphatase 2A (PP2A), have been identified in individuals with neurodevelopmental abnormalities. However, the molecular and clinical spectra remain incompletely understood.MethodsIndividuals withPPP2R5Dvariants were enrolled through Simons Variation in Individuals Project/Simons Searchlight. Data were collected from medical history interviews, medical record review, online validated instruments and neuroimaging review. Genetic variants were biochemically characterised.ResultsWe studied 76 individuals withPPP2R5Dvariants, including 68 with pathogenic de novo variants, four with a variant of uncertain significance (VUS) and four siblings with a novel dominantly inherited pathogenic variant. Among 13 pathogenic variants, eight were novel and two (p.Glu198Lys and p.Glu200Lys) were highly recurrent. Functional analysis revealed impaired PP2A A/C-subunit binding, decreased short linear interaction motif-dependent substrate binding or both—with the most severe phenotypes associated with variants that completely retained one of these binding characteristics and lost the other—further supporting a dominant-negative disease mechanism. p.Glu198Lys showed the highest C-binding defect and a more severe clinical phenotype. The inherited p.Glu197Gly variant had a mild substrate binding defect, and three of four VUS had no biochemical impact. Common clinical phenotypes were language, intellectual or learning disabilities (80.6%), hypotonia (75.0%), macrocephaly (66.7%), seizures (45.8%) and autism spectrum disorder (26.4%). The mean composite Vineland score was 59.8, and most participants were in the ‘moderate to low’ and ‘low’ adaptive levels in all domains.ConclusionOur study delineates the most common features ofPPP2R5D-related neurodevelopmental disorders, expands the clinical and molecular spectrum and identifies genotype–phenotype correlations.
Demonstrating quantum properties of triple photons generated by $$\chi ^3$$ processes
Authors: Bencheikh Kamel , Cenni Marina F. B. , Oudot Enky , Boutou Véronique , Félix Corinne , Prades Joel Compte , Vernay Augustin , Bertrand Julien , Bassignot Florent , Chauvet Mathieu , Bussières Félix , Zbinden Hugo , Levenson Ariel , Boulanger Benoît 
Published: October 2022

Abstract
Triple-photon generation (TPG) is based on a third-order nonlinear optical interaction, which is the most direct way to produce pure quantum three-photon states. These states can exhibit three-body quantum correlations, and their statistics cannot be reproduced by any Gaussian statistics of coherent sources or optical parametric twin-photon generator, making them potentially useful for quantum information processing tasks such as quantum state distillation, quantum error-correction and universal quantum computing. Furthermore, the generation of entangled photon pairs heralded by the detection of a third photon can be used in advanced quantum communication protocols. We made the first experimental demonstration of TPG in 2004 using a bi-stimulation scheme in a bulk KTP crystal, followed by the quantum theory. The new challenges are now to achieve a spontaneous TPG and the corresponding quantum experiments and protocols using oriented ridge KTP waveguides, which ensures both birefringence phase-matching and light confinement. The waveguides are cut by a precision dicing saw. We recently performed their characterization using third-harmonic generation measurements, which showed their good quality. A rate of about 5 triplets per second is expected when pumping a 5-cm-long waveguide with a 5-W 532 nm beam in the CW regime. Such a spontaneous TPG exhibits low rate of triple photons, which makes the certification of quantum features hard. In this article, we review our theoretical and experimental work on TPG and the associated quantum modeling. We also develop theoretical tools for the certification of quantum features of spontaneous triple-photon states.

Graphic abstract
MNX1-AS1 Promotes Phase Separation of IGF2BP1 to Drive c-Myc–Mediated Cell-Cycle Progression and Proliferation in Lung Cancer
Authors: Zhu Qingqing , Zhang Chongguo , Qu Tianyu , Lu Xiyi , He Xuezhi , Li Wei , Yin Dandan , Han Liang , Guo Renhua , Zhang Erbao 
Published: October 2022

Abstract

c-Myc and E2F1 play critical roles in many human cancers. As long noncoding RNAs (lncRNA) are known to regulate various tumorigenic processes, elucidation of mechanisms of cross-talk between lncRNAs and c-Myc/E2F1-related signaling pathways could provide important insights into cancer biology. In this study, we used integrated bioinformatic analyses and found that the lncRNA MNX1-AS1 is upregulated in non–small cell lung cancer (NSCLC) via copy-number gain and c-Myc–mediated transcriptional activation. High levels of MNX1-AS1 were associated with poor clinical outcomes in patients with lung cancer. MNX1-AS1 promoted cell proliferation and colony formation in vitro and tumor growth in vivo. MNX1-AS1 bound and drove phase separation of IGF2BP1, which increased the interaction of IGF2BP1 with the 3′-UTR (untranslated region) of c-Myc and E2F1 mRNA to promote their stability. The c-Myc/MNX1-AS1/IGF2BP1 positive feedback loop accelerated cell-cycle progression and promoted continuous proliferation of lung cancer cells. In a lung cancer patient-derived xenograft model, inhibition of MNX1-AS1 suppressed cancer cell proliferation and tumor growth. These findings offer new insights into the regulation and function of c-Myc and E2F1 signaling in NSCLC tumorigenesis and suggest that the MNX1-AS1/IGF2BP1 axis may serve as a potential biomarker and therapeutic target in NSCLC.

Significance:
MNX1-AS1 drives phase separation of IGF2BP1 to increase c-Myc and E2F1 signaling and to activate cell-cycle progression to promote proliferation in NSCLC.
Validation of the Nigerian Breast Cancer Study Model for Predicting Individual Breast Cancer Risk in Cameroon and Uganda
Authors: Ashi Kevin , Ndom Paul , Gakwaya Antony , Makumbi Timothy , Olopade Olufunmilayo I. , Huo Dezheng 
Published: October 2022

Abstract

Background:
The Nigerian Breast Cancer Study (NBCS) model is a new risk assessment tool developed for predicting risk of invasive breast cancer in Nigeria. Its applicability outside of Nigeria remains uncertain as it has not been validated in other sub-Saharan Africa populations.

Methods:
We conducted a case–control study among women with breast cancer and controls ascertained in Cameroon and Uganda from 2011 to 2016. Structured questionnaire interviews were performed to collect risk factor characteristics. The NBCS model, the Gail model, the Gail model for Black population, and the Black Women's Health Study model were applied to the Cameroon and Uganda samples separately. Nigerian as well as local incidence rates were incorporated into the models. Receiver-Operating Characteristic analyses were performed to indicate discriminating capacity.

Results:
The study included 550 cases (mean age 46.8 ± 11.9) and 509 controls (mean age 46.3 ± 11.7). Compared with the other three models, the NBCS model performed best in both countries. The discriminating accuracy of the NBCS model in Cameroon (age-adjusted C-index = 0.602; 95% CI, 0.542–0.661) was better than in Uganda (age-adjusted C-index = 0.531; 95% CI, 0.459–0.603).

Conclusions:
These findings demonstrate the potential clinical utility of the NBCS model for risk assessment in Cameroon. All currently available models performed poorly in Uganda, which suggests that the NBCS model may need further calibration before use in other regions of Africa.

Impact:
Differences in risk profiles across the African diaspora underscores the need for larger studies and may require development of region-specific risk assessment tools for breast cancer.
Fibroblast Activation Protein Triggers Release of Drug Payload from Non-internalizing Small Molecule Drug Conjugates in Solid Tumors
Authors: Zana Aureliano , Galbiati Andrea , Gilardoni Ettore , Bocci Matilde , Millul Jacopo , Sturm Theo , Stucchi Riccardo , Elsayed Abdullah , Nadal Lisa , Cirillo Martina , Roll Wolfgang , Stegger Lars , Asmus Inga , Backhaus Philipp , Schäfers Michael , Neri Dario , Cazzamalli Samuele 
Published: October 2022

Abstract

Purpose:
Small molecule drug conjugates (SMDC) are modular anticancer prodrugs that include a tumor-targeting small organic ligand, a cleavable linker, and a potent cytotoxic agent. Most of the SMDC products that have been developed for clinical applications target internalizing tumor-associated antigens on the surface of tumor cells. We have recently described a novel non-internalizing small organic ligand (named OncoFAP) of fibroblast activation protein (FAP), a tumor-associated antigen highly expressed in the stroma of most solid human malignancies.

Experimental Design:
In this article, we describe a new series of OncoFAP-Drug derivatives based on monomethyl auristatin E (MMAE; a potent cytotoxic tubulin poison) and dipeptide linkers that are selectively cleaved by FAP in the tumor microenvironment.

Results:
The tumor-targeting potential of OncoFAP was confirmed in patients with cancer using nuclear medicine procedures. We used mass spectrometry methodologies to quantify the amount of prodrug delivered to tumors and normal organs, as well as the efficiency of the drug release process. Linkers previously exploited for anticancer drug conjugates were used as benchmark. We identified OncoFAP-Gly-Pro-MMAE as the best performing SMDC, which has now been prioritized for further clinical development. OncoFAP-Gly-Pro-MMAE selectively delivered more than 10% injected dose per gram of MMAE to FAP-positive tumors, with a tumor-to-kidney ratio of 16:1 at 24 hours post-injection.

Conclusions:
The FAP-specific drug conjugates described in this article promise to be efficacious for the targeting of human malignancies. The extracellular release of potent anticancer payloads mediates durable complete remission in difficult-to-treat animal models of cancer.
Mitochondrial Aconitase ACO2 Links Iron Homeostasis with Tumorigenicity in Non–Small Cell Lung Cancer
Authors: Mirhadi Shideh , Zhang Wen , Pham Nhu-An , Karimzadeh Fereshteh , Pintilie Melania , Tong Jiefei , Taylor Paul , Krieger Jonathan , Pitcher Bethany , Sykes Jenna , Wybenga-Groot Leanne , Fladd Christopher , Xu Jing , Wang Tao , Cabanero Michael , Li Ming , Weiss Jessica , Sakashita Shingo , Zaslaver Olga , Yu Man , Caudy Amy A. , St-Pierre Julie , Hawkins Cynthia , Kislinger Thomas , Liu Geoffrey , Shepherd Frances A. , Tsao Ming-Sound , Moran Michael F. 
Published: October 2022

Abstract

The ability of a patient tumor to engraft an immunodeficient mouse is the strongest known independent indicator of poor prognosis in early-stage non–small cell lung cancer (NSCLC). Analysis of primary NSCLC proteomes revealed low-level expression of mitochondrial aconitase (ACO2) in the more aggressive, engrafting tumors. Knockdown of ACO2 protein expression transformed immortalized lung epithelial cells, whereas upregulation of ACO2 in transformed NSCLC cells inhibited cell proliferation in vitro and tumor growth in vivo. High level ACO2 increased iron response element binding protein 1 (IRP1) and the intracellular labile iron pool. Impaired cellular proliferation associated with high level ACO2 was reversed by treatment of cells with an iron chelator, whereas increased cell proliferation associated with low level ACO2 was suppressed by treatment of cells with iron. Expression of CDGSH iron-sulfur (FeS) domain-containing protein 1 [CISD1; also known as mitoNEET (mNT)] was modulated by ACO2 expression level and inhibition of mNT by RNA interference or by treatment of cells with pioglitazone also increased iron and cell death. Hence, ACO2 is identified as a regulator of iron homeostasis and mNT is implicated as a target in aggressive NSCLC.

Implications:
FeS cluster–associated proteins including ACO2, mNT (encoded by CISD1), and IRP1 (encoded by ACO1) are part of an “ACO2–Iron Axis” that regulates iron homeostasis and is a determinant of a particularly aggressive subset of NSCLC.
Influence of Age on the Diagnosis of Myocardial Infarction
Authors: Lowry Matthew T.H. , Doudesis Dimitrios , Wereski Ryan , Kimenai Dorien M. , Tuck Christopher , Ferry Amy V. , Bularga Anda , Taggart Caelan , Lee Kuan K. , Chapman Andrew R. , Shah Anoop S.V. , Newby David E. , Mills Nicholas L. , Anand Atul ,   on behalf of the High-STEACS Investigators
Published: October 2022

Background:
The 99th centile of cardiac troponin, derived from a healthy reference population, is recommended as the diagnostic threshold for myocardial infarction, but troponin concentrations are strongly influenced by age. Our aim was to assess the diagnostic performance of cardiac troponin in older patients presenting with suspected myocardial infarction.

Methods:
In a secondary analysis of a multicenter trial of consecutive patients with suspected myocardial infarction, we assessed the diagnostic accuracy of high-sensitivity cardiac troponin I at presentation for the diagnosis of type 1, type 2, or type 4b myocardial infarction across 3 age groups (<50, 50–74, and ≥75 years) using guideline-recommended sex-specific and age-adjusted 99th centile thresholds.

Results:
In 46 435 consecutive patients aged 18 to 108 years (mean, 61±17 years), 5216 (11%) had a diagnosis of myocardial infarction. In patients <50 (n=12 379), 50 to 74 (n=22 380), and ≥75 (n=11 676) years, the sensitivity of the guideline-recommended threshold was similar at 79.2% (95% CI, 75.5–82.9), 80.6% (95% CI, 79.2–82.1), and 81.6% (95% CI, 79.8–83.2), respectively. The specificity decreased with advancing age from 98.3% (95% CI, 98.1–98.5) to 95.5% (95% CI, 95.2–95.8), and 82.6% (95% CI, 81.9–83.4). The use of age-adjusted 99th centile thresholds improved the specificity (91.3% [90.8%–91.9%] versus 82.6% [95% CI, 81.9%–83.4%]) and positive predictive value (59.3% [57.0%–61.5%] versus 51.5% [49.9%–53.3%]) for myocardial infarction in patients ≥75 years but failed to prevent the decrease in either parameter with increasing age and resulted in a marked reduction in sensitivity compared with the use of the guideline-recommended threshold (55.9% [53.6%–57.9%] versus 81.6% [79.8%–83.3%].

Conclusions:
Age alters the diagnostic performance of cardiac troponin, with reduced specificity and positive predictive value in older patients when applying the guideline-recommended or age-adjusted 99th centiles. Individualized diagnostic approaches rather than the adjustment of binary thresholds are needed in an aging population.
Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury
Authors: Stüdemann Tim , Rössinger Judith , Manthey Christoph , Geertz Birgit , Srikantharajah Rajiven , von Bibra Constantin , Shibamiya Aya , Köhne Maria , Wiehler Antonius , Wiegert J. Simon , Eschenhagen Thomas , Weinberger Florian 
Published: October 2022

Background:
Transplantation of pluripotent stem cell–derived cardiomyocytes represents a promising therapeutic strategy for cardiac regeneration, and the first clinical studies in patients with heart failure have commenced. Yet, little is known about the mechanism of action underlying graft-induced benefits. Here, we explored whether transplanted cardiomyocytes actively contribute to heart function.

Methods:
We injected cardiomyocytes with an optogenetic off-on switch in a guinea pig cardiac injury model.

Results:
Light-induced inhibition of engrafted cardiomyocyte contractility resulted in a rapid decrease of left ventricular function in ≈50% (7/13) animals that was fully reversible with the offset of photostimulation.

Conclusions:
Our optogenetic approach demonstrates that transplanted cardiomyocytes can actively participate in heart function, supporting the hypothesis that the delivery of new force-generating myocardium can serve as a regenerative therapeutic strategy.