bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal photograph-based deep learning predicts biological age, and stratifies morbidity and mortality risk
Authors: Nusinovici Simon , Rim Tyler Hyungtaek , Yu Marco , Lee Geunyoung , Tham Yih-Chung , Cheung Ning , Chong Crystal Chun Yuen , Da Soh Zhi , Thakur Sahil , Lee Chan Joo , Sabanayagam Charumathi , Lee Byoung Kwon , Park Sungha , Kim Sung Soo , Kim Hyeon Chang , Wong Tien-Yin , Cheng Ching-Yu 
Published: March 2022

Abstract

Background
ageing is an important risk factor for a variety of human pathologies. Biological age (BA) may better capture ageing-related physiological changes compared with chronological age (CA).

Objective
we developed a deep learning (DL) algorithm to predict BA based on retinal photographs and evaluated the performance of our new ageing marker in the risk stratification of mortality and major morbidity in general populations.

Methods
we first trained a DL algorithm using 129,236 retinal photographs from 40,480 participants in the Korean Health Screening study to predict the probability of age being ≥65 years (‘RetiAGE’) and then evaluated the ability of RetiAGE to stratify the risk of mortality and major morbidity among 56,301 participants in the UK Biobank. Cox proportional hazards model was used to estimate the hazard ratios (HRs).

Results
in the UK Biobank, over a 10-year follow up, 2,236 (4.0%) died; of them, 636 (28.4%) were due to cardiovascular diseases (CVDs) and 1,276 (57.1%) due to cancers. Compared with the participants in the RetiAGE first quartile, those in the RetiAGE fourth quartile had a 67% higher risk of 10-year all-cause mortality (HR = 1.67 [1.42–1.95]), a 142% higher risk of CVD mortality (HR = 2.42 [1.69–3.48]) and a 60% higher risk of cancer mortality (HR = 1.60 [1.31–1.96]), independent of CA and established ageing phenotypic biomarkers. Likewise, compared with the first quartile group, the risk of CVD and cancer events in the fourth quartile group increased by 39% (HR = 1.39 [1.14–1.69]) and 18% (HR = 1.18 [1.10–1.26]), respectively. The best discrimination ability for RetiAGE alone was found for CVD mortality (c-index = 0.70, sensitivity = 0.76, specificity = 0.55). Furthermore, adding RetiAGE increased the discrimination ability of the model beyond CA and phenotypic biomarkers (increment in c-index between 1 and 2%).

Conclusions
the DL-derived RetiAGE provides a novel, alternative approach to measure ageing.
Probing RNA structures and functions by solvent accessibility: an overview from experimental and computational perspectives
Authors: Solayman Md , Litfin Thomas , Singh Jaswinder , Paliwal Kuldip , Zhou Yaoqi , Zhan Jian 
Published: March 2022

Abstract
Characterizing RNA structures and functions have mostly been focused on 2D, secondary and 3D, tertiary structures. Recent advances in experimental and computational techniques for probing or predicting RNA solvent accessibility make this 1D representation of tertiary structures an increasingly attractive feature to explore. Here, we provide a survey of these recent developments, which indicate the emergence of solvent accessibility as a simple 1D property, adding to secondary and tertiary structures for investigating complex structure–function relations of RNAs.
spatialGE: quantification and visualization of the tumor microenvironment heterogeneity using spatial transcriptomics
Authors: Ospina Oscar E , Wilson Christopher M , Soupir Alex C , Berglund Anders , Smalley Inna , Tsai Kenneth Y , Fridley Brooke L 
Published: March 2022

AbstractSummarySpatially resolved transcriptomics promises to increase our understanding of the tumor microenvironment and improve cancer prognosis and therapies. Nonetheless, analytical methods to explore associations between the spatial heterogeneity of the tumor and clinical data are not available. Hence, we have developed spatialGE, a software that provides visualizations and quantification of the tumor microenvironment heterogeneity through gene expression surfaces, spatial heterogeneity statistics that can be compared against clinical information, spot-level cell deconvolution and spatially informed clustering, all using a new data object to store data and resulting analyses simultaneously.Availability and implementationThe R package and tutorial/vignette are available at https://github.com/FridleyLab/spatialGE. A script to reproduce the analyses in this manuscript is available in Supplementary information. The Thrane study data included in spatialGE was made available from the public available from the website https://www.spatialresearch.org/resources-published-datasets/doi-10-1158-0008-5472-can-18-0747/.Supplementary informationSupplementary data are available at Bioinformatics online.
Tau and the fractionated default mode network in atypical Alzheimer’s disease
Authors: Putcha Deepti , Eckbo Ryan , Katsumi Yuta , Dickerson Bradford C. , Touroutoglou Alexandra , Collins Jessica A. 
Published: March 2022

Abstract
Alzheimer’s disease-related atrophy in the posterior cingulate cortex, a key node of the default mode network, is present in the early stages of disease progression across clinical phenotypic variants of the disease. In the typical amnestic variant, posterior cingulate cortex neuropathology has been linked with disrupted connectivity of the posterior default mode network, but it remains unclear if this relationship is observed across atypical variants of Alzheimer’s disease. In the present study, we first sought to determine if tau pathology is consistently present in the posterior cingulate cortex and other posterior nodes of the default mode network across the atypical Alzheimer’s disease syndromic spectrum. Second, we examined functional connectivity disruptions within the default mode network and sought to determine if tau pathology is related to functional disconnection within this network. We studied a sample of 25 amyloid-positive atypical Alzheimer’s disease participants examined with high-resolution MRI, tau (18F-AV-1451) PET, and resting-state functional MRI. In these patients, high levels of tau pathology in the posteromedial cortex and hypoconnectivity between temporal and parietal nodes of the default mode network were observed relative to healthy older controls. Furthermore, higher tau signal and reduced grey matter density in the posterior cingulate cortex and angular gyrus were associated with reduced parietal functional connectivity across individual patients, related to poorer cognitive scores. Our findings converge with what has been reported in amnestic Alzheimer’s disease, and together these observations offer a unifying mechanistic feature that relates posterior cingulate cortex tau deposition to aberrant default mode network connectivity across heterogeneous clinical phenotypes of Alzheimer’s disease.
Abnormal development of transient fetal zones in mild isolated fetal ventriculomegaly
Authors: Vasung Lana , Rollins Caitlin K , Zhang Jennings , Velasco-Annis Clemente , Yang Edward , Lin Pei-Yi , Sutin Jason , Warfield Simon Keith , Soul Janet , Estroff Judy , Connolly Susan , Barnewolt Carol , Gholipour Ali , Feldman Henry A , Grant Patricia Ellen 
Published: March 2022

AbstractMild isolated fetal ventriculomegaly (iFVM) is the most common abnormality of the fetal central nervous system. It is characterized by enlargement of one or both of the lateral ventricles (defined as ventricular width greater than 10 mm, but less than 12 mm). Despite its high prevalence, the pathophysiology of iFVM during fetal brain development and the neurobiological substrate beyond ventricular enlargement remain unexplored.In this work, we aimed to establish the relationships between the structural development of transient fetal brain zones/compartments and increased cerebrospinal fluid volume.For this purpose, we used in vivo structural T2-weighted magnetic resonance imaging of 89 fetuses (48 controls and 41 cases with iFVM). Our results indicate abnormal development of transient zones/compartments belonging to both hemispheres (i.e. on the side with and also on the contralateral side without a dilated ventricle) in fetuses with iFVM. Specifically, compared to controls, we observed enlargement of proliferative zones and overgrowth of the cortical plate in iFVM with associated reduction of volumes of central structures, subplate, and fetal white matter. These results indicate that enlarged lateral ventricles might be linked to the development of transient fetal zones and that global brain development should be taken into consideration when evaluating iFVM.
Host Finding Behavior of the ParasitoidHadronotus pennsylvanicus(Hymenoptera: Scelionidae) for Egg Masses of the Squash BugsAnasa tristisandAnasa armigera(Hemiptera: Coreidae) in Squash and Cucumber Fields
Authors: Cornelius Mary L , Haber Ariela I , Weber Donald C 
Published: March 2022

AbstractParasitoid foraging behavior is affected by habitat and host plant differences. Egg parasitoids also use a combination of oviposition-induced and host-derived cues to find host eggs. This study compared parasitism by Hadronotus pennsylvanicus (Ashmead) (Hymenoptera: Scelionidae) on two squash bug species, Anasa tristis (DeGeer) and Anasa armigera Say (Hemiptera: Coreidae), by placing sentinel squash and cucumber plants with egg masses of either of the two squash bug species in squash and cucumber fields in a 3-way factorial design. Host density of wild A. tristis egg masses in squash fields may have influenced parasitoid foraging behavior on sentinel plants. In the 3-way factorial design, parasitism was higher on sentinel squash plants and in squash fields overall. However, parasitism on A. armigera egg masses was highest on sentinel cucumber plants in squash fields and parasitism on A. tristis egg masses was higher on sentinel squash plants in either squash or cucumber fields and lowest on sentinel cucumber plants in cucumber fields. Results suggest that parasitoids were able to specifically orient to the combination of host plant and host cues associated with A. tristis egg masses on sentinel squash plants, but that they were more responsive to plant-induced cues associated with cucumber when searching for A. armigera egg masses. Parasitoids appear to utilize different combinations of host plant and host cues when searching for eggs of the two squash bug species.
Socioeconomic variations determine the clinical presentation, aetiology, and outcome of infective endocarditis: a prospective cohort study from the ESC-EORP EURO-ENDO (European Infective Endocarditis) registry
Authors: Sengupta Shantanu P , Prendergast Bernard , Laroche Cécile , Furnaz Shumaila , Ronderos Ricardo , Almaghraby Abdallah , Asch Federico M , Blechova Kamila , Zaky Hosam , Strahilevitz Jacob , Dworakowski Rafal , Miyasaka Yoko , Sebag Igal , Izumi Chisato , Axler Olivier , Jamiel Abdulrahman , Philip Mary , Campos Vieira Marcelo Luiz , Lancellotti Patrizio , Habib Gilbert 
Published: March 2022

Abstract

Aims
Infective endocarditis (IE) is a life-threatening disease associated with high mortality and morbidity worldwide. We sought to determine how socioeconomic factors might influence its epidemiology, clinical presentation, investigation and management, and outcome, in a large international multicentre registry.

Methods and results
The EurObservational Programme (EORP) of the European Society of Cardiology EURO-ENDO (European Infective Endocarditis) registry comprises a prospective cohort of 3113 adult patients admitted for IE in 156 hospitals in 40 countries between January 2016 and March 2018. Patients were separated in three groups, according to World Bank economic stratification [group 1: high income (75.6%); group 2: upper-middle income (15.4%); group 3: lower-middle income (9.1%)]. Group 3 patients were younger [median age (interquartile range, IQR): group 1, 66 (53–75) years; group 2, 57 (41–68) years; group 3, 33 (26–43) years; P &lt; 0.001] with a higher frequency of smokers, intravenous drug use, and human immunodeficiency virus infection (all P &lt; 0.001) and presented later [median (IQR) days since symptom onset: group 1, 12 (3–35); group 2, 19 (6–54); group 3, 31 (12–62); P &lt; 0.001] with a higher likelihood of developing congestive heart failure (13.6%, 11.1%, and 22.6%, respectively; P &lt; 0.001) and persistent fever (9.8%, 14.2%, and 27.9%, respectively; P &lt; 0.001). Among 2157 (69.3%) patients with theoretical indication for cardiac surgery, surgery was performed less frequently in group 3 patients (75.5%, 76.8%, and 51.3%, respectively; P &lt; 0.001), who also demonstrated the highest mortality (15.0%, 23.0%, and 23.7%, respectively; P &lt; 0.001).

Conclusion
Socioeconomic factors influence the clinical profile of patients presenting with IE across the world. Despite younger age, patients from the poorest countries presented with more frequent complications and higher mortality associated with delayed diagnosis and lower use of surgery.
The Conundrum of Clinical Trials for the Uveitides: Appropriate Outcome Measures for One Treatment Used in Several Diseases
Authors: Jabs Douglas A , Berkenstock Meghan K , Altaweel Michael M , Holbrook Janet T , Sugar Elizabeth A ,   for the ADVISE Research Group
Published: March 2022

Abstract
The uveitides consist of &gt;30 diseases characterized by intraocular inflammation. Noninfectious intermediate, posterior, and panuveitides typically are treated with oral corticosteroids and immunosuppression, with a similar treatment approach for most diseases. Because these uveitides collectively are considered a rare disease, single-disease trials are difficult to impractical to recruit for, and most trials have included several different diseases for a given protocol treatment. However, measures of uveitis activity are disease specific, resulting in challenges for trial outcome measures. Several trials of investigational immunosuppressive drugs or biologic drugs have not demonstrated efficacy, but design problems with the outcome measures have limited the ability to interpret the results. Successful trials have included diseases for which a single uveitis activity measure suffices or a composite measure of uveitis activity is used. One potential solution to this problem is the use of a single, clinically relevant outcome, successful corticosteroid sparing, defined as inactive uveitis with a prednisone dose ≤7.5 mg/day coupled with disease-specific guidelines for determining inactive disease. The clinical relevance of this outcome is that active uveitis is associated with increased risks of visual impairment and blindness, and that prednisone doses ≤7.5 mg/day have a minimal risk of corticosteroid side effects. The consequence of this approach is that trial visits require a core set of measures for all participants and a disease-specific set of measures, both clinical and imaging, to assess uveitis activity. This approach is being used in the Adalimumab Versus Conventional Immunosuppression (ADVISE) Trial.
Replication stress induced by the ribonucleotide reductase inhibitor guanazole, triapine and gemcitabine in fission yeast
Authors: Alyahya Mashael Y , Khan Saman , Bhadra Sankhadip , Samuel Rittu E , Xu Yong-jie 
Published: March 2022

Abstract
Schizosaccharomyces pombe is an established yeast model for studying the cellular mechanisms conserved in humans, such as the DNA replication checkpoint. The replication checkpoint deals with replication stress caused by numerous endogenous and exogenous factors that perturb fork movement. If undealt with, perturbed forks collapse, causing chromosomal DNA damage or cell death. Hydroxyurea (HU) is an inhibitor of ribonucleotide reductase (RNR) commonly used in checkpoint studies. It produces replication stress by depleting dNTPs, which slows the movement of ongoing forks and thus activates the replication checkpoint. However, HU also causes side effects such as oxidative stress, particularly under chronic exposure conditions, which complicates the studies. To find a drug that generates replication stress more specifically, we tested three other RNR inhibitors gemcitabine, guanazole and triapine in S. pombe under various experimental conditions. Our results show that guanazole and triapine can produce replication stress more specifically than HU under chronic, not acute drug treatment conditions. Therefore, using the two drugs in spot assay, the method commonly used for testing drug sensitivity in yeasts, should benefit the checkpoint studies in S. pombe and likely the research in other model systems.
Art-based reflections from 12 years of adolescent health and development-related research in South Africa
Authors: Gittings Lesley , Medley Sally , Logie Carmen H , Ralayo Nokubonga , Cluver Lucie , Petersen Nabeel , Chen-Charles Jenny , Toska Elona 
Published: March 2022

SummaryThis paper presents empirical and methodological findings from an art-based, participatory process with a group (n = 16) of adolescent and young advisors in the Western Cape Province of South Africa. In a weekend workshop, participants reflected on their participation in 12 years of health and development-related research through theatre, song, visual methodologies and semi-structured interviews. Empirical findings suggest that participants interpreted the group research encounter as a site of empowerment, social support and as a socio-political endeavour. Through song, theatre and a mural illustration, they demonstrated that they value ‘unity’ in research, with the aim of ameliorating the conditions of adolescents and young people in other parts of South Africa and the continent. Methodological findings document how participants deployed art-based approaches from South Africa’s powerful history of activism, including the struggle against apartheid, the fight for anti-retroviral therapy and more recent social movements towards decolonization.
Exploring the causes of semen quality changes post-bariatric surgery: a focus on endocrine-disrupting chemicals
Authors: Magalhaes Danielly P , Mahalingaiah Shruthi , Perry Melissa J 
Published: March 2022

Abstract
Rapid weight loss promoted by bariatric surgery (BS) can release accumulated lipophilic endocrine-disrupting chemicals (EDCs), making these chemicals systemically available. Men typically have a higher EDC body burden and lose more weight post-BS than women, which may put male BS patients at high risk for testicular toxicity. In this review, we analyze the impacts of BS on semen parameters with a particular focus on the potential effects of EDCs. After BS, serum EDC concentrations progressively increase; and there is evidence that semen parameters deteriorate after BS. Although elevated serum EDC concentrations are associated with inferior sperm parameters, links between semen parameters and EDCs post-BS have not been studied. Understanding these potential associations requires adequately powered studies, particularly within prospective longitudinal cohorts with long-term follow-up for sperm parameters, nutritional status, sex-hormones levels and serum EDC concentrations. Studying BS patients prospectively provides the important opportunity to evaluate dose–response effects of EDC serum concentrations on sperm quality and function. Research is also needed to identify critical chemical exposure periods post-BS to inform reproductive decisions, including consideration of sperm preservation before surgery.
The vitality of trusting relations in multilateral diplomacy: an account of the European Union
Authors: Versloot Larissa 
Published: March 2022

Abstract
Trust is commonly considered a foundation of multilateral diplomacy. Amidst concerns about eroding trust in this realm, due to a ‘crisis’ of multilateralism and ‘hollowing out’ of diplomacy in a socially distanced world, it is surprising that our knowledge of the role trust plays in everyday multilateral diplomacy remains limited at best. In this article, I explore how trusting relations affect multilateral diplomatic practice. I construct a novel theoretical framework that centres on the notion of ‘vitality’—a useful metaphor to capture the lively character of trusting relations and how they differ in what I call intensity, shape and age. I use this framework to analyse the workings of trust in diplomatic practice, based on empirical material gathered over three years (2018–2021) at the Council of the European Union. Contrary to what is often assumed, I find that trusting relations as such do not unequivocally enable smooth decision-making and can also hinder cooperation. We can understand this, I argue, by grasping the social opportunities and constraints that arise from trust ‘climates’ as constituted by configuring trusting relations. Overall, the analysis unpacks complexities in the connection between trust and cooperation in multilateralism. The analytical vocabulary offered in this article allows both scholars and practitioners to comprehend the manifold ways in which trust matters in multilateral diplomacy.
Urban insurgency in the twenty-first century: smaller militaries and increased conflict in cities
Authors: King Anthony 
Published: March 2022

Abstract
In the last two decades, urban insurgencies have become a major concern for scholars and practitioners. It is widely assumed that because half the human population now live in cities in often appalling conditions, it is inevitable that conflict has migrated to cities, not least because urban areas offer would-be insurgents the best opportunity to evade state security forces and their advanced technologies. Demography and asymmetry have been all but universally accepted in the literature as the sole causes of urban insurgency. They are certainly important. Yet, scholars have overlooked a third vital factor: the size of state forces. In the twentieth century, urban insurgencies were common. However, because states commanded very large military forces at that time, insurgents found it very difficult to operate in urban areas. By contrast, as their forces have contracted in the twenty-first century, states have been unable to dominate urban areas, as they typically did in the twentieth century. Consequently, urban enclaves have appeared inside cities from which insurgents have mounted their attacks and contested with state forces.
Lipschitz Functions on Submanifolds of Heisenberg Groups
Authors: Julia Antoine , Nicolussi Golo Sebastiano , Vittone Davide 
Published: March 2022

AbstractWe study the behavior of Lipschitz functions on intrinsic $C^1$ submanifolds of Heisenberg groups: our main result is their almost everywhere tangential Pansu differentiability. We also provide two applications: a Lusin-type approximation of Lipschitz functions on ${\mathbb {H}}$-rectifiable sets and a coarea formula on ${\mathbb {H}}$-rectifiable sets that completes the program started in [18].
NGOs and States: Exploring National Diversity and Global Liberalism
Authors: Stroup Sarah S 
Published: March 2022

AbstractRecent assessments of relations between states and nongovernmental organizations (NGOs) claim a global wave of state crackdowns, raising questions about the continued authority and influence of NGOs. The works reviewed here challenge the idea of a pattern of global conflict, demonstrating a range of ways in which states work with, through, and alongside NGOs. They also demonstrate that the diversity of NGO–state relations can make it difficult to generalize about these interactions across national contexts. One way to reconceptualize these relationships may be to focus on the normative commitments that states and NGOs do or do not share. Conflictual and cooperative NGO–state dynamics emerge from the many and sometimes contradictory liberal values that enabled the rise of NGOs. NGOs can embody three liberal values: visions of civil society can emphasize political freedoms, market-based visions of private action, or universalism. States may embrace some of these values while rejecting others. Thus, while the era of the unimpeded rise of NGOs may have come to an end, the shifting political spaces for NGOs do not spell an end to their influence.