bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving trust and confidence in medical skin lesion diagnosis through explainable deep learning
Authors: Metta Carlo , Beretta Andrea , Guidotti Riccardo , Yin Yuan , Gallinari Patrick , Rinzivillo Salvatore , Giannotti Fosca
Published: June 2023

A key issue in critical contexts such as medical diagnosis is the interpretability of the deep learning models adopted in decision-making systems. Research in eXplainable Artificial Intelligence (XAI) is trying to solve this issue. However, often XAI approaches are only tested on generalist classifier and do not represent realistic problems such as those of medical diagnosis. In this paper, we aim at improving the trust and confidence of users towards automatic AI decision systems in the field of medical skin lesion diagnosis by customizing an existing XAI approach for explaining an AI model able to recognize different types of skin lesions. The explanation is generated through the use of synthetic exemplar and counter-exemplar images of skin lesions and our contribution offers the practitioner a way to highlight the crucial traits responsible for the classification decision. A validation survey with domain experts, beginners, and unskilled people shows that the use of explanations improves trust and confidence in the automatic decision system. Also, an analysis of the latent space adopted by the explainer unveils that some of the most frequent skin lesion classes are distinctly separated. This phenomenon may stem from the intrinsic characteristics of each class and may help resolve common misclassifications made by human experts.
The effects of selection and scaling procedures of earthquake records on the seismic response dispersion of structures and recommendations toward seismic upgrading of codes
Authors: Mansouri Saman , Kontoni Denise-Penelope N. , Pouraminian Majid
Published: June 2023

In this study, the effects of selection and scaling procedures of earthquake records on the dispersion of seismic response of structures are examined. This is according to the Standard No. 2800 seismic code and the ASCE code. So that during two case studies, seven earthquakes have been selected and scaled with the spectral acceleration of the seismic Standard No. 2800. Besides, the seismic response of a reinforced concrete (RC) bridge and a 7-story RC building is evaluated against scaled earthquakes. The results of the studies indicate that structures respond differently to earthquake records. However, in order to avoid designers' different decisions and align their views to choose suitable earthquakes and to evolve the selection and scaling methods of earthquake records for the seismic design of structures, in the end, some recommendations are presented. The results show that in selecting earthquakes, it is crucial to consider PGA, magnitude, and a classified range of intensities and durations of strong ground motion. In addition, to select earthquakes, paying attention to the frequency content of accelerograms and the shape of the response spectrum is also of particular importance. Considering the ranges of the scale of accelerograms depending on the importance of the structures is significant. By applying the mentioned recommendations, the methods of selecting and scaling earthquake records will be improved to some extent. In addition, seismic response dispersion will be prevented.
Mechanical properties and constitutive model of fractured red sandstone under acid corrosion
Authors: Liu Yongsheng , Liu Wang , Wang Cui
Published: June 2023

Red sandstone was selected for the study and specimens were prepared at 0°, 30°, 45° and 60° fracture inclinations and maintained in an acid solution at pH = 2. The specimens were subjected to uniaxial compression tests before and after maintenance to obtain the mechanical parameters and to observe the damage properties of the specimens. Based on the Lemaitre strain equivalence principle, a macroscopic fracture model for single-fissure rock masses and a statistical damage model for the Weibull distribution of micro-fissures were combined to derive macro-and micro-coupled damage variables for the specimens. The damage variables after acid solution corrosion are considered to derive the constitutive model for fractured red sandstone containing fractures after acid corrosion. The theoretical damage constitutive curves were compared with the experimental curves to analyse the applicability of the constitutive equation. The results show that the peak stress, peak strain and elastic modulus of the fractured specimens all vary regularly with the inclination angle, first decreasing and then increasing with the increase in the inclination angle; the peak compressive strength and elastic modulus of the fractured sandstone all tend to decrease and the peak strain tends to increase after corrosion by acid solution; the damage characteristics of the fractured sandstone are more influenced by the inclination angle and less influenced by acid corrosion; by comparing the theoretical curve with the experimental curve, the established damage constitutive model is in good agreement at the elastic deformation and plastic yielding stages. The mechanical properties of rock masses with different inclinations of fracture are quantified on the basis of the test results. The damage characteristics of rock masses with different fracture inclinations under normal and acid corrosion conditions are studied. The macro- and micro-coupled damage variables of fractured rock masses under acid corrosion are derived and validated.
A Novel Similarity Measure Based on Accuracy Score of Conventional Type of Trapezoidal-Valued Intuitionistic Fuzzy Sets and Its Applications in Multi-criteria Decision-Making Problems
Authors: Nayagam V. Lakshmana Gomathi , Suriyapriya K. , Jagadeeswari M.
Published: June 2023

The article aims to investigate the distance measure between any two conventional type trapezoidal-valued intuitionistic fuzzy sets (CTrVIFSs) whose membership and non-membership grades of an element are expressed as conventional trapezoidal intuitionistic fuzzy numbers (CTrIFN). Using the proposed distance measure, the similarity measure of CTrVIFSs is determined and its efficiency is shown by applying it to pattern recognition problems and MCDM problems. The similarity measure propounded in this article can be used to tackle real-world problems involving CTrVIFS as parameters, such as clustering, machine learning, and DNA matching. The application section discusses that this research can help decision-makers to recognize patterns and categorize samples with those patterns. Furthermore, the model of a real-world problem is given which utilizes the suggested similarity measure to solve MCDM problems, demonstrate the usability of the new technique and comprehend its applied intelligence above other methods. Finally, a general conclusion and future scope on this topic are discussed.
Water blister geomorphology and subglacial drainage sediments: an example from the bed of the Fennoscandian Ice Sheet in SW Finland
Authors: Mäkinen Joni , Dow Christine F. , Ahokangas Elina , Ojala Antti , Kajuutti Kari , Kautto Juulia , Palmu Jukka-Pekka
Published: June 2023

This study presents the first light detection and ranging (LiDAR)-based morphometric description of a water blister from a past ice-sheet bed caused by rapid supraglacial drainage. The blister formed during the rapid early Holocene deglaciation of the Fennoscandian Ice Sheet (FIS). It is located in southwest Finland within a subglacial meltwater route interpreted to represent the transition from a distributed to a channelized drainage system. A LiDAR digital elevation model was supplemented with sedimentological and ground-penetrating radar data on blister outflow channels and sedimentology of downflow polymorphous mounds and ridges (PMRs). Unlike the water blisters recorded from the rapid drainage of supraglacial lakes on the Greenland Ice Sheet, the smaller blister size here was either due to crevasse or moulin drainage, or was a supraglacial lake drainage that tapped into a pre-existing, relatively efficient drainage system and related semi-sorted sediments, promoting rapid drainage and reworking of PMRs along the meltwater route. The preservation potential or exposure probability of blister marks is presumably low but they can provide important information about evolution of subglacial drainage systems that is of value to modern interpretations of glacial hydrology.
Transitions between peace and systemic war as bifurcations in a signed network dynamical system
Authors: Morrison Megan , Kutz J. Nathan , Gabbay Michael
Published: June 2023

We investigate structural features and processes associated with the onset of systemic conflict using an approach which integrates complex systems theory with network modeling and analysis. We present a signed network model of cooperation and conflict dynamics in the context of international relations between states. The model evolves ties between nodes under the influence of a structural balance force and a dyad-specific force. Model simulations exhibit a sharp bifurcation from peace to systemic war as structural balance pressures increase, a bistable regime in which both peace and war stable equilibria exist, and a hysteretic reverse bifurcation from war to peace. We show how the analytical expression we derive for the peace-to-war bifurcation condition implies that polarized network structure increases susceptibility to systemic war. We develop a framework for identifying patterns of relationship perturbations that are most destabilizing and apply it to the network of European great powers before World War I. We also show that the model exhibits critical slowing down, in which perturbations to the peace equilibrium take longer to decay as the system draws closer to the bifurcation. We discuss how our results relate to international relations theories on the causes and catalysts of systemic war.
Endoscopic classification system of pars tensa retractions
Authors: Mahajan Nilesh , Vijayendra Vinay Kumar , Redleaf Miriam , Honnurappa Vijayendra
Published: June 2023

Background

Previous classification systems of pars tensa retractions have not consistently incorporated ossicular erosion or the presence of cholesteatoma.

Objective

This study aimed to illustrate our classification of pars tensa retractions, which is more precise than previous systems, with aided use of the endoscope.

Methods

A retrospective study was carried out on 200 ears of 170 patients whose pars tensa retractions had been documented at a tertiary otological referral centre.

Results

A classification system was developed. Pars tensa retractions were divided into the following subcategories: grade 0, grade 1, grade 2a, grade 2b, grade 3a, grade 3b, grade 3c, grade 4a, grade 4b, grade 4c, grade 5a, grade 5b and grade 5c.

Conclusion

This classification system was able to accommodate all pars tensa retractions. The distribution of grades of pars tensa retractions was based on ossicular status and the presence or absence of cholesteatoma. It is therefore a more applicable, and functionally based system than previous alternatives.
Changes in vocal fold gene expression and histology after injection augmentation in a recurrent laryngeal nerve injury model
Authors: Malka Ronit , Isaac Alisa , Gonzales Gabriela , Miar Solaleh , Walters Benjamin , Baker Amelia , Guda Teja , Dion Gregory R
Published: June 2023

Objective

To investigate changes in neuroregenerative pathways with vocal fold denervation in response to vocal fold augmentation.

Methods

Eighteen Yorkshire crossbreed swine underwent left recurrent laryngeal nerve transection, followed by observation or augmentation with carboxymethylcellulose or calcium hydroxyapatite at two weeks. Polymerase chain reaction expression of genes regulating muscle growth (MyoD1, MyoG and FoxO1) and atrophy (FBXO32) were analysed at 4 and 12 weeks post-injection. Thyroarytenoid neuromuscular junction density was quantified using immunohistochemistry.

Results

Denervated vocal folds demonstrated reduced expression of MyoD1, MyoG, FoxO1 and FBXO32, but overexpression after augmentation. Healthy vocal folds showed increased early and late MyoD1, MyoG, FoxO1 and FBXO32 expression in all animals. Neuromuscular junction density had a slower decline in augmented compared to untreated denervated vocal folds, and was significantly reduced in healthy vocal folds contralateral to augmentation.

Conclusion

Injection augmentation may slow neuromuscular degeneration pathways in denervated vocal folds and reduce compensatory remodelling in contralateral healthy vocal folds.
China's Corporate Social Credit System: The Dawn of Surveillance State Capitalism?
Authors: Lin Lauren Yu-Hsin , Milhaupt Curtis J.
Published: June 2023

Chinese state capitalism may be transitioning towards a technology-assisted variant that we call “surveillance state capitalism.” The mechanism driving this development is China's corporate social credit system (CSCS) – a data-driven project to evaluate the “trustworthiness” of all business entities in the country. In this paper, we provide the first empirical analysis of CSCS scores in Zhejiang province, as the Zhejiang provincial government is to date the only local government to publish the scores of locally registered firms. We find that while the CSCS is ostensibly a means of measuring legal compliance, politically connected firms receive higher scores. This result is driven by a “social responsibility” category in the scoring system that valorizes awards from the government and contributions to causes sanctioned by the Chinese Communist Party. Our analysis underscores the potential of the CSCS to nudge corporate fealty to party-state policy and provides an early window into the far-reaching potential implications of the CSCS.
‘Omelette Without Eggs’: Eating Under War and Dictatorship
Authors: Román Ruiz Gloria
Published: June 2023

During the Dutch Hunger Winter (1944–5), a woman sold ration cards on the Noordplein, one of the busiest streets in Rotterdam. She was paid twenty guilders for each ration card. Her buyers, in turn, resold the coupons for sugar, butter or bread separately in order to make a higher profit. They could make up to 150 guilders per ration card. Not far from there, in Amsterdam, people went to the corner of Rozendwarsstraat to fraudulently buy coupons for bread or wheat cake on the black market. Anyone with seven guilders could buy a slice. Considering that some people only earned twenty-two guilders a week, not everyone could afford to go to the black market for extra calories. Both of these stories were told by women who survived the Dutch Hunger Winter, and are included in Ingrid de Zwarte's recent monograph. They illustrate some of the important contributions that have emerged from recent historical works in the related fields of Hunger and Food Studies. They demonstrate the agency of ordinary and marginalised subjects, particularly women, in the face of scarcity. They reveal the importance of the coping strategies people developed, which allows us to think of these individuals beyond their traditional status as passive victims of scarcity. And they show us how, in the context of hunger and famine, ideas of what was normal or acceptable behaviour could be transformed.
“EM Doc On Call:” A Pilot Study to Improve Interhospital Transfers in Rwanda
Authors: Ndebwanimana Vincent , Beeman Aly , Gallaer Alexander , Uwamahoro Chantal , Uwamahoro Doris , Ritz Cody , Lewis Samuel , Hoyt Savanna Dayne , Jean Paul Nzabandora , Gonsalves-Domond Gersandre , Odoom Enyonam , Vital Mutijima , Martin Kyle Denison
Published: June 2023

Introduction:

Treatment of seriously ill patients is often complicated by prolonged or complex transfers between hospitals in sub-Saharan Africa. Difficulties or inefficiency in these transfers can lead to poor outcomes for patients. “On-call” triage systems have been utilized to facilitate communication between facilities and to avoid poor outcomes associated with patient transfer. This study attempts to examine the effects of a pilot study to implement such a system in Rwanda.

Methods:

Data collection occurred prospectively in two stages, pre-intervention and intervention, in the emergency department (ED) at Kigali University Teaching Hospital (CHUK). All patients transferred during the pre-determined timeframe were enrolled. Data were collected by ED research staff via a standardized form. Statistical analysis was performed using STATA version 15.0. Differences in characteristics were assessed using χ2 or Fisher’s exact tests for categorical variables and independent sample t-tests for normally distributed continuous variables.

Results:

During the “on call” physician intervention, the indication for transfer was significantly more likely to be for critical care (P <.001), transfer times were faster (P <.001), patients were more likely to be displaying emergency signs (P <.001), and vital signs were more likely to be collected prior to transport (P <.001) when compared to the pre-interventional phase.

Conclusion:

The “[Emergency Medicine] EM Doc On Call” intervention was associated with improved timely interhospital transfer and clinical documentation in Rwanda. While these data are not definitive due to multiple limitations, it is extremely promising and worthy of further study.
Predicting Exporters with Machine Learning
Authors: Micocci Francesca , Rungi Armando
Published: June 2023

In this contribution, we exploit machine learning techniques to evaluate whether and how close firms are to become successful exporters. First, we train various algorithms using financial information on both exporters and non-exporters in France in 2010–2018. Thus, we show that it is possible to predict the distance non-exporters are from export status. In particular, we find that a Bayesian Additive Regression Tree with Missingness In Attributes (BART-MIA) performs better than other techniques with an accuracy of up to 0.90. Predictions are robust to changes in definitions of exporters and in the presence of discontinuous exporting activity. Eventually, we discuss how our exporting scores can be helpful for trade promotion, trade credit, and assessing aggregate trade potential. For example, back-of-the-envelope estimates show that a representative firm with just below-average exporting scores needs up to 44% more cash resources and up to 2.5 times more capital to get to foreign markets.
An Unlikely Duet: Public-Private Interaction in China's Environmental Public Interest Litigation
Authors: Xia Ying , Wang Yueduan
Published: June 2023

Increasing research has been devoted to examining collaborations between public and private actors in environmental regulation under neoliberal democracies. However, this public-private interaction in authoritarian regimes remains understudied. This article seeks to address this gap in the literature through an empirical examination of the interaction between environmental non-governmental organizations (NGOs) and procuratorates in China's environmental public interest litigation. We find emerging complementarity: NGOs focus on new issues and target high-profile defendants to increase the socio-legal impact of their civil litigation, whereas procuratorates increasingly engage in administrative litigation against government agencies. This complementarity is shaped by the different legal opportunities for Chinese NGOs and procuratorates, as well as their respective institutional objectives and capacities. Their divergent regulatory preferences have also fostered synergy between these two actors, allowing them to collaborate on legal experimentation and innovation.
How Ecuador's Courts Are Giving Form and Force to Rights of Nature Norms
Authors: Kauffman Craig M. , Martin Pamela L.
Published: June 2023

In 2008, Ecuador recognized rights of nature (RoN) in its Constitution. Since then, RoN have been relied upon in judicial decisions 55 times in Ecuador. Following years of ad hoc treatment of RoN by Ecuador's government and courts, its Constitutional Court selected various cases to establish binding jurisprudence in respect of RoN. In doing so, the Constitutional Court and various provincial courts in Ecuador have clarified the content of RoN, including specific criteria for determining RoN violations and the relationship between RoN and other constitutional rights, including community and economic rights related to development. Moreover, the courts are imposing sanctions on RoN violators, including the state and powerful commercial sectors. This article shows how Ecuadorian court decisions are changing RoN from a vague, abstract concept into a set of specific standards for how to balance RoN with various human rights and existing environmental law in order to implement sustainable development in an integrated and holistic manner that does not sacrifice ecosystem functioning. In doing so, the article contributes to the emerging literature on how new environmental law norms are constructed as they are put into practice, as well as the important role that judges play as norm entrepreneurs.
Safety and efficacy of endovenous thermal ablation for treatment of symptomatic varicose veins during summertime
Authors: Uthoff Heiko , Teruzzi Elisa , Boesch Patricia , Hofer Manuel , Spinedi Luca , Bossart Simon , Staub Daniel , Keo Hak Hong
Published: June 2023

Summary: Background: Traditionally, varicose vein treatment is predominately performed during the colder seasons. However, data whether higher outdoor temperatures affect the outcome and/or complication rate of endovenous thermal ablation (ETA) for treatment of symptomatic varicose veins are missing. Patients and methods: In this observational study, the medical records of all patients who had ETA of the great saphenous vein (GSV), accessory saphenous vein (ASV), or small saphenous vein (SSV) between September 2017 and October 2020 were reviewed. Results: In total 846 ETA interventions in 679 patients with 1239 treated truncal veins and an average length of 69 cm phlebectomy were included. The highest temperature recorded on and within the first 14 days after treatment was on average 19.0°C (SD±7.2°C) with a minimum and maximum of −1°C and 35.9°C. Interventions were categorized according to the recorded temperature (<25°C n=584; 25–29.9°C n=191; and ≥30°C n=71). The occlusion rates were excellent (99–100%) across groups. Despite a significantly higher proportion of patients with obesity, personal history of superficial vein thrombosis and length of phlebectomies in the high temperature groups, no significant difference regarding days of work loss, patients’ satisfaction or complications including bleeding or thromboembolic events was observed. Infections were rare (0.8%), but more frequently observed in the 25–29.9°C group (2.6%; p=0.058). No infection was observed in the ≥30°C group and pain 6 weeks after the intervention was even lower (VAS 0.5±1.0 and 0.5±1.2 vs. 0.0±0.1, p=0.008). Conclusions: Given the minimal invasive nature of ETA, our results can reassure clinicians and patients that ETA varicose vein treatment is possible and safe throughout the year, even on hot summer days. A non-significant trend to more infections was observed but was not associated with other adverse outcomes such as prolonged analgetics intake or inability to work.
Material Properties of Sediments Steer Burrowers and Effect Bioturbation
Authors: Dorgan Kelly M. , Arwade Sanjay R.
Published: June 2023

Infaunal organisms mix sediments through burrowing, ingestion and egestion, enhancing fluxes of nutrients and oxygen, yet the mechanisms underlying bioturbation remain unresolved. Burrows are extended through muddy sediments by fracture, and we hypothesize that the cohesive properties of sediments play an important but unexplored role in resisting bioturbation. Specifically, we suggest that crack branching, tortuosity, and microcracking are important in freeing particles from the cohesive matrix, and that the sediment properties that affect these processes are important predictors of bioturbation. We use finite element modeling and simplified, mechanics‐based models to explore the relative importance of sediment mechanical properties and worm behaviors in determining crack propagation paths. Our results show that crack propagation direction depends on variability in fracture toughness, and that applying more force to one side of the burrow wall, simulating “steering” behavior, has surprisingly little effect on crack propagation direction. Burrowers instead steer by choosing among crack branches. Paths created by burrowing worms in natural sediments are mostly straight with some crack branching, consistent with modeling results. Crack branching also requires sufficient stored elastic energy to drive two cracks, and worms can exert larger forces resulting in more stored energy in stiffer sediments. This implies that more crack branching and consequently more particle mixing occurs in heterogeneous sediments with low fracture toughness relative to stiffness. Whether sediments with greater potential for crack branching also experience higher bioturbation remains to be tested, but these results indicate that material properties of sediments may be important in resisting or facilitating bioturbation.
Protecting the Ozone Layer Is Delaying Arctic Melting
Authors: Moutinho Sofia
Published: June 2023

The Montreal Protocol has unintentionally slowed global warming and pushed back the first ice-free Arctic summer by 15 years, according to new research.
Quantifying Antarctic‐Wide Ice‐Shelf Surface Melt Volume Using Microwave and Firn Model Data: 1980 to 2021
Authors: Banwell Alison F. , Wever Nander , Dunmire Devon , Picard Ghislain
Published: June 2023

Antarctic ice‐shelf stability is threatened by surface melt, which has been implicated in several ice‐shelf collapse events over recent decades. Here, we first analyze cumulative days of wet snow/ice status (“melt days”) for melt seasons from 1980 to 2021 over Antarctica's ice shelves using passive and active microwave satellite observations. As these observations do not directly reveal meltwater volumes, we calculate these using the physics‐based multi‐layer snow model SNOWPACK, driven by the global climate‐reanalysis model Modern‐Era Retrospective analysis for Research and Applications Version 2. We find a strong non‐linear relationship between melt days and meltwater production volume. SNOWPACK's calculation of melt days shows agreement with observations of both cumulative days, and spatial and interannual variability. Highest melt rates are found on the Peninsula ice shelves, particularly in the 1992/1993 and 1994/1995 austral summers. Over all ice shelves, SNOWPACK calculates a small, but significant, decreasing trend in both annual melt days and meltwater production volume over the 41 years.
Human pluripotent stem cell (hPSC) and organoid models of autism: opportunities and limitations
Authors: Kilpatrick Savannah , Irwin Courtney , Singh Karun K.
Published: June 2023

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder caused by genetic or environmental perturbations during early development. Diagnoses are dependent on the identification of behavioral abnormalities that likely emerge well after the disorder is established, leaving critical developmental windows uncharacterized. This is further complicated by the incredible clinical and genetic heterogeneity of the disorder that is not captured in most mammalian models. In recent years, advancements in stem cell technology have created the opportunity to model ASD in a human context through the use of pluripotent stem cells (hPSCs), which can be used to generate 2D cellular models as well as 3D unguided- and region-specific neural organoids. These models produce profoundly intricate systems, capable of modeling the developing brain spatiotemporally to reproduce key developmental milestones throughout early development. When complemented with multi-omics, genome editing, and electrophysiology analysis, they can be used as a powerful tool to profile the neurobiological mechanisms underlying this complex disorder. In this review, we will explore the recent advancements in hPSC-based modeling, discuss present and future applications of the model to ASD research, and finally consider the limitations and future directions within the field to make this system more robust and broadly applicable.
Mitochondria-wide association study observed significant interactions of mitochondrial respiratory and the inflammatory in the development of anxiety and depression
Authors: Liu Li , Cheng Shiqiang , Qi Xin , Meng Peilin , Yang Xuena , Pan Chuyu , Chen Yujing , Zhang Huijie , Zhang Zhen , Zhang Jingxi , Li Chune , Wen Yan , Jia Yumeng , Cheng Bolun , Zhang Feng
Published: June 2023

The aim of this study was to investigate the possible interaction of mitochondrial dysfunction and inflammatory cytokines in the risk of anxiety and depression. We utilized the UK Biobank for the sample of this study. A mitochondria-wide association(MiWAS) and interaction analysis was performed to investigate the interaction effects of mitochondrial DNA (mtDNA)×C-reactive protein (CRP) on the risks of self-reported anxiety (N = 72,476), general anxiety disorder (GAD-7) scores (N = 80,853), self-reported depression (N = 80,778), Patient Health Questionnaire (PHQ-9) scores (N = 80,520) in total samples, females and males, respectively, adjusting for sex, age, Townsend deprivation index (TDI), education score, alcohol intake, smoking and 10 principal components. In all, 25 mtSNPs and 10 mtSNPs showed significant level of association with self-reported anxiety and GAD-7 score respectively. A total of seven significant mtDNA × CRP interactions were found for anxiety, such as m.3915G>A(MT-ND1) for self-reported anxiety in total subjects (P = 6.59 × 10−3), m.4561T>C(MT-ND2) (P = 3.04 × 10−3) for GAD-7 score in total subjects. For depression, MiWAS identified 17 significant mtSNPs for self-reported depression and 14 significant mtSNPs for PHQ-9 scores. 17 significant mtDNA associations (2 for self-reported depression and 15 for PHQ-9 score) was identified, such as m.14869G>A(MT-CYB; P = 2.22 × 10−3) associated with self-reported depression and m.4561T>C (MT-ND2; P value = 3.02 × 10−8) associated with PHQ-9 score in all subjects. In addition, 5 common mtDNA shared with anxiety and depression were found in MiWAS, and 4 common mtDNA variants were detected to interact with CRP for anxiety and depression, such as m.9899T>C(MT-CO3). Our study suggests the important interaction effects of mitochondrial function and CRP on the risks of anxiety and depression.
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity
Authors: Vicente Manuel M. , Alves Inês , Fernandes Ângela , Dias Ana M. , Santos-Pereira Beatriz , Pérez-Anton Elena , Santos Sofia , Yang Tao , Correia Alexandra , Münster-Kühnel Anja , Almeida Afonso R. M. , Ravens Sarina , Rabinovich Gabriel A. , Vilanova Manuel , Sousa Ana E. , Pinho Salomé S.
Published: June 2023

T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens. Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to disease. Here, we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes, as well as dynamic alterations. After restricting the N-glycosylation profile of thymocytes to high-mannose structures, using specific glycoengineered mice (Rag1CreMgat1fl/fl), we showed remarkable defects in key developmental checkpoints, including ß-selection, regulatory T-cell generation and γδT-cell development, associated with increased susceptibility to colon and kidney inflammation and infection. We further demonstrated that a single N-glycan antenna (modeled in Rag1CreMgat2fl/fl mice) is the sine-qua-non condition to ensure normal development. In conclusion, we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.
Imaging the field inside nanophotonic accelerators
Authors: Fishman Tal , Haeusler Urs , Dahan Raphael , Yannai Michael , Adiv Yuval , Abudi Tom Lenkiewicz , Shiloh Roy , Eyal Ori , Yousefi Peyman , Eisenstein Gadi , Hommelhoff Peter , Kaminer Ido
Published: June 2023

Controlling optical fields on the subwavelength scale is at the core of nanophotonics. Laser-driven nanophotonic particle accelerators promise a compact alternative to conventional radiofrequency-based accelerators. Efficient electron acceleration in nanophotonic devices critically depends on achieving nanometer control of the internal optical nearfield. However, these nearfields have so far been inaccessible due to the complexity of the devices and their geometrical constraints, hampering the design of future nanophotonic accelerators. Here we image the field distribution inside a nanophotonic accelerator, for which we developed a technique for frequency-tunable deep-subwavelength resolution of nearfields based on photon-induced nearfield electron-microscopy. Our experiments, complemented by 3D simulations, unveil surprising deviations in two leading nanophotonic accelerator designs, showing complex field distributions related to intricate 3D features in the device and its fabrication tolerances. We envision an extension of our method for full 3D field tomography, which is key for the future design of highly efficient nanophotonic devices.
Genome analyses reveal population structure and a purple stigma color gene candidate in finger millet
Authors: Devos Katrien M. , Qi Peng , Bahri Bochra A. , Gimode Davis M. , Jenike Katharine , Manthi Samuel J. , Lule Dagnachew , Lux Thomas , Martinez-Bello Liliam , Pendergast Thomas H. , Plott Chris , Saha Dipnarayan , Sidhu Gurjot S. , Sreedasyam Avinash , Wang Xuewen , Wang Hao , Wright Hallie , Zhao Jianxin , Deshpande Santosh , de Villiers Santie , Dida Mathews M. , Grimwood Jane , Jenkins Jerry , Lovell John , Mayer Klaus F. X. , Mneney Emmarold E. , Ojulong Henry F. , Schatz Michael C. , Schmutz Jeremy , Song Bo , Tesfaye Kassahun , Odeny Damaris A.
Published: June 2023

Finger millet is a key food security crop widely grown in eastern Africa, India and Nepal. Long considered a ‘poor man’s crop’, finger millet has regained attention over the past decade for its climate resilience and the nutritional qualities of its grain. To bring finger millet breeding into the 21st century, here we present the assembly and annotation of a chromosome-scale reference genome. We show that this ~1.3 million years old allotetraploid has a high level of homoeologous gene retention and lacks subgenome dominance. Population structure is mainly driven by the differential presence of large wild segments in the pericentromeric regions of several chromosomes. Trait mapping, followed by variant analysis of gene candidates, reveals that loss of purple coloration of anthers and stigma is associated with loss-of-function mutations in the finger millet orthologs of the maize R1/B1 and Arabidopsis GL3/EGL3 anthocyanin regulatory genes. Proanthocyanidin production in seed is not affected by these gene knockouts.
Selective oxidative protection leads to tissue topological changes orchestrated by macrophage during ulcerative colitis
Authors: Du Juan , Zhang Junlei , Wang Lin , Wang Xun , Zhao Yaxing , Lu Jiaoying , Fan Tingmin , Niu Meng , Zhang Jie , Cheng Fei , Li Jun , Zhu Qi , Zhang Daoqiang , Pei Hao , Li Guang , Liang Xingguang , Huang He , Cao Xiaocang , Liu Xinjuan , Shao Wei , Sheng Jianpeng
Published: June 2023

Ulcerative colitis is a chronic inflammatory bowel disorder with cellular heterogeneity. To understand the composition and spatial changes of the ulcerative colitis ecosystem, here we use imaging mass cytometry and single-cell RNA sequencing to depict the single-cell landscape of the human colon ecosystem. We find tissue topological changes featured with macrophage disappearance reaction in the ulcerative colitis region, occurring only for tissue-resident macrophages. Reactive oxygen species levels are higher in the ulcerative colitis region, but reactive oxygen species scavenging enzyme SOD2 is barely detected in resident macrophages, resulting in distinct reactive oxygen species vulnerability for inflammatory macrophages and resident macrophages. Inflammatory macrophages replace resident macrophages and cause a spatial shift of TNF production during ulcerative colitis via a cytokine production network formed with T and B cells. Our study suggests components of a mechanism for the observed macrophage disappearance reaction of resident macrophages, providing mechanistic hints for macrophage disappearance reaction in other inflammation or infection situations.
Artificial intelligence driven design of catalysts and materials for ring opening polymerization using a domain-specific language
Authors: Park Nathaniel H. , Manica Matteo , Born Jannis , Hedrick James L. , Erdmann Tim , Zubarev Dmitry Yu. , Adell-Mill Nil , Arrechea Pedro L.
Published: June 2023

Advances in machine learning (ML) and automated experimentation are poised to vastly accelerate research in polymer science. Data representation is a critical aspect for enabling ML integration in research workflows, yet many data models impose significant rigidity making it difficult to accommodate a broad array of experiment and data types found in polymer science. This inflexibility presents a significant barrier for researchers to leverage their historical data in ML development. Here we show that a domain specific language, termed Chemical Markdown Language (CMDL), provides flexible, extensible, and consistent representation of disparate experiment types and polymer structures. CMDL enables seamless use of historical experimental data to fine-tune regression transformer (RT) models for generative molecular design tasks. We demonstrate the utility of this approach through the generation and the experimental validation of catalysts and polymers in the context of ring-opening polymerization—although we provide examples of how CMDL can be more broadly applied to other polymer classes. Critically, we show how the CMDL tuned model preserves key functional groups within the polymer structure, allowing for experimental validation. These results reveal the versatility of CMDL and how it facilitates translation of historical data into meaningful predictive and generative models to produce experimentally actionable output.
Photo-produced aromatic compounds stimulate microbial degradation of dissolved organic carbon in thermokarst lakes
Authors: Hu Jie , Kang Luyao , Li Ziliang , Feng Xuehui , Liang Caifan , Wu Zan , Zhou Wei , Liu Xuning , Yang Yuanhe , Chen Leiyi
Published: June 2023

Photochemical and biological degradation of dissolved organic carbon (DOC) and their interactions jointly contribute to the carbon dioxide released from surface waters in permafrost regions. However, the mechanisms that govern the coupled photochemical and biological degradation of DOC are still poorly understood in thermokarst lakes. Here, by combining Fourier transform ion cyclotron resonance mass spectrometry and microbial high-throughput sequencing, we conducted a sunlight and microbial degradation experiment using water samples collected from 10 thermokarst lakes along a 1100-km permafrost transect. We demonstrate that the enhancement of sunlight on DOC biodegradation is not associated with the low molecular weight aliphatics produced by sunlight, but driven by the photo-produced aromatics. This aromatic compound-driven acceleration of biodegradation may be attributed to the potential high abilities of the microbes to decompose complex compounds in thermokarst lakes. These findings highlight the importance of aromatics in regulating the sunlight effects on DOC biodegradation in permafrost-affected lakes.
Gravitational effects on fibroblasts’ function in relation to wound healing
Authors: Radstake Wilhelmina E. , Gautam Kiran , Miranda Silvana , Van Rompay Cynthia , Vermeesen Randy , Tabury Kevin , Verslegers Mieke , Dowson Alan , Gorissen Jeffrey , van Loon Jack J. W. A. , Savage Nigel D. L. , Baatout Sarah , Baselet Bjorn
Published: June 2023

The spaceflight environment imposes risks for maintaining a healthy skin function as the observed delayed wound healing can contribute to increased risks of infection. To counteract delayed wound healing in space, a better understanding of the fibroblasts’ reaction to altered gravity levels is needed. In this paper, we describe experiments that were carried out at the Large Diameter Centrifuge located in ESA-ESTEC as part of the ESA Academy 2021 Spin Your Thesis! Campaign. We exposed dermal fibroblasts to a set of altered gravity levels, including transitions between simulated microgravity and hypergravity. The addition of the stress hormone cortisol to the cell culture medium was done to account for possible interaction effects of gravity and cortisol exposure. Results show a main impact of cortisol on the secretion of pro-inflammatory cytokines as well as extracellular matrix proteins. Altered gravity mostly induced a delay in cellular migration and changes in mechanosensitive cell structures. Furthermore, 20 × ghypergravity transitions induced changes in nuclear morphology. These findings provide insights into the effect of gravity transitions on the fibroblasts’ function related to wound healing, which may be useful for the development of countermeasures.
Proteomic analysis of the effect of hemin in breast cancer
Authors: Coló G. P. , Schweitzer K. , Oresti G. M. , Alonso E. G. , Chávez L. Fernández , Mascaró M. , Giorgi G. , Curino A. C. , Facchinetti M. M.
Published: June 2023

Heme, an iron-containing prosthetic group found in many proteins, carries out diverse biological functions such as electron transfer, oxygen storage and enzymatic reactions. Hemin, the oxidised form of heme, is used to treat porphyria and also to activate heme-oxygenase (HO) which catalyses the rate-limiting step in heme degradation. Our group has previously demonstrated that hemin displays antitumor activity in breast cancer (BC). The aim of this work has been to study the effect of hemin on protein expression modifications in a BC cell line to gain insight into the molecular mechanisms of hemin antitumor activity. For this purpose, we carried out proteome analysis by Mass Spectrometry (MS) which showed that 1309 proteins were significantly increased in hemin-treated cells, including HO-1 and the proteases that regulate HO-1 function, and 921 proteins were significantly decreased. Furthermore, the MS-data analysis showed that hemin regulates the expression of heme- and iron-related proteins, adhesion and cytoskeletal proteins, cancer signal transduction proteins and enzymes involved in lipid metabolism. By biochemical and cellular studies, we further corroborated the most relevant in-silico results. Altogether, these results show the multiple physiological effects that hemin treatment displays in BC and demonstrate its potential as anticancer agent.
Explainable AI via learning to optimize
Authors: Heaton Howard , Fung Samy Wu
Published: June 2023

Indecipherable black boxes are common in machine learning (ML), but applications increasingly require explainable artificial intelligence (XAI). The core of XAI is to establish transparent and interpretable data-driven algorithms. This work provides concrete tools for XAI in situations where prior knowledge must be encoded and untrustworthy inferences flagged. We use the “learn to optimize” (L2O) methodology wherein each inference solves a data-driven optimization problem. Our L2O models are straightforward to implement, directly encode prior knowledge, and yield theoretical guarantees (e.g. satisfaction of constraints). We also propose use of interpretable certificates to verify whether model inferences are trustworthy. Numerical examples are provided in the applications of dictionary-based signal recovery, CT imaging, and arbitrage trading of cryptoassets. Code and additional documentation can be found at https://xai-l2o.research.typal.academy.
Development of CuMnxOy (x = 2, and y = 4)-GO heterostructure for the synthesis of pyranoquinoline derivatives
Authors: Farajollahi Ayda , Noroozi Pesyan Nader , Poursattar Marjani Ahmad , Alamgholiloo Hassan
Published: June 2023

The pyranoquinoline derivatives are synthetically important due to their biological properties. In this research, these derivatives were produced through an environmentally friendly method. This method includes the use of CuMnxOy (x = 2, and y = 4)-GO as a nanocatalyst, which is easy to produce, has excellent performance, cost-effectiveness, and recyclability among its features, and also the use of water as a green solvent. Pyranoquinolines through the one-pot, the multi-component reaction between different derivatives of aryl glyoxal, ethyl cyanoacetate, and 4-hydroxyquinoline-2(1H)-one were synthesized using nanocatalyst, K2CO3, and H2O. Also, the structure of the CuMnxOy-GO nanocatalyst was evaluated and confirmed via different analyses. The distinguishing features of this work compared to previous works are easy workup, recyclability of nanocatalyst, facile synthesis process, and provide high yields of products.
Single-cell Raman microscopy with machine learning highlights distinct biochemical features of neutrophil extracellular traps and necrosis
Authors: Lelliott Patrick Michael , Hobro Alison Jane , Pavillon Nicolas , Nishide Masayuki , Okita Yasutaka , Mizuno Yumiko , Obata Sho , Nameki Shinichiro , Yoshimura Hanako , Kumanogoh Atsushi , Smith Nicholas Isaac
Published: June 2023

The defining biology that distinguishes neutrophil extracellular traps (NETs) from other forms of cell death is unresolved, and techniques which unambiguously identify NETs remain elusive. Raman scattering measurement provides a holistic overview of cell molecular composition based on characteristic bond vibrations in components such as lipids and proteins. We collected Raman spectra from NETs and freeze/thaw necrotic cells using a custom built high-throughput platform which is able to rapidly measure spectra from single cells. Principal component analysis of Raman spectra from NETs clearly distinguished them from necrotic cells despite their similar morphology, demonstrating their fundamental molecular differences. In contrast, classical techniques used for NET analysis, immunofluorescence microscopy, extracellular DNA, and ELISA, could not differentiate these cells. Additionally, machine learning analysis of Raman spectra indicated subtle differences in lipopolysaccharide (LPS)-induced as opposed to phorbol myristate acetate (PMA)-induced NETs, demonstrating the molecular composition of NETs varies depending on the stimulant used. This study demonstrates the benefits of Raman microscopy in discriminating NETs from other types of cell death and by their pathway of induction.