bluuebunny/crossref_metadata_2025 huggingface dataset:
GIS and Virtual Reality
Authors: Chen Min , Zhang Chunxiao , Shu Yucheng
Published: July 2023

The geographic information system (GIS) dates back to the mid-1960s. It is a computer-based hardware and software system capable of capturing, storing, analyzing, and displaying geographically referenced data. GIS manages geographic, spatial, or geospatial data for spatiotemporal applications and geographic research, and employs cognition to comprehend geographical configurations and perceptions through computer mapping, spatial analysis, and geographic problem solving. Over the past decade, GIS technology has made significant contributions to mainstream geographic research and applications and demonstrated its potential benefits in various related disciplines (e.g., earth system science). In addition to its traditional role in geographic studies, the advent of the Internet and the World Wide Web in 1995 resulted in a dramatic shift in how GIS was viewed as a means of information sharing between individuals. Several websites provided visitors with geographic datasets, enabling them to create maps on demand and perform simple GIS services based on user specifications using data supplied by the user or the website. In another field, virtual reality (VR)—characterized by immersion, interaction, and the use of one’s imagination—is the application of computer modeling and simulation that enables a person to interact with artificial three-dimensional (3D) visual or other sensory environments. ‘Extended reality’ (XR) has recently been adopted as an umbrella term for virtual, augmented, and mixed reality (VR, AR, MR), referring to technologies and conceptual propositions of spatial interfaces studied by engineers, computer scientists, and scholars who study human-computer interaction (HCI). With the advancements in computer graphics hardware and algorithms, visualization, and interactive techniques for analysis, it is possible to establish the systems coupling of a truly interactive, multidimensional GIS and VR. Such systems, including Virtual Geographic Environments (VGEs), Digital Earth (DE), Cyberinfrastructure-Based Geographic Information Systems (CyberGIS), and Digital Twin (DT) have been developed and applied in numerous fields and applications, such as urban planning; evaluation of vegetation, soil, and waterways; human behavior and management of recreational areas; and geological fields. With the evolution of GIS from 2D static to 3D (or 4D) dynamic and the simultaneous evolution of VR technology to XR, the integrations of GIS and VR have undergone significant changes. Consequently, many publications on the theory and practice of integrating GIS and VR have been written and published worldwide.
Astronomy under Mongol Rule
Authors: Yang Qiao , Guo Jinsong
Published: July 2023

Astronomy in the premodern world comprised a spectrum of knowledge and practices—cosmology, theoretical astronomy, calendrical computation, systematic observations and surveys, instrument making, astrology (ranging from direct reading of heavenly patterns to horoscopes), and other forms of divination that were more indirectly related to the heavens. Some scholars use the term “astral sciences” to refer to these comprehensive, and interrelated, realms of knowledge of the heavens in premodern times. In the history of science in general, the more “scientific” subfields have been better studied than astrological practices. This also applies to the study of astronomy under Mongol rule. The Mongol Empire, ruling over a great part of Eurasia in the thirteenth to fourteenth centuries, brought about, or coincided with, significant developments in astronomy in many regions. Although diverse astronomical traditions were active within the empire, history of astronomy normally falls into the framework of regional history. Therefore, historians of Chinese astronomy have mainly focused on the Mongol state in East Asia known as the Yuan, while historians of Islamicate (referring to Islam as a culture rather than religion) astronomy, working with Persian and Arabic sources, have focused on the Ilkhanate, the Mongol state in West Asia. Other astronomical traditions, such as those of the Uighur and Tibetan, Nestorian, and other regions—the Chaghadeids in Central Asia, and the Golden Horde in Russia—are yet to be studied. A notable exception is Mongol astronomy. Despite the scattered sources, historians have revealed insights into the traditional Mongol knowledge of the heavens, and the Mongols’ relation to Heaven, which was the driving force of their sponsorship of astronomy in East and West Eurasia.
Impact of Baseline and Week 2 and Week 4 Posttransplant CMV Cell-Mediated Immunity on Risk of CMV Infections and Mortality in Recipients of Allogeneic Hematopoietic Cell Transplant
Authors: Ariza-Heredia Ella J , Winston Drew J , Rowley Scott D , Mullane Kathleen , Chandrasekar Pranatharthi , Hari Parameswaran , Avery Robin K , Peggs Karl S , Kumar Deepali , Nath Rajneesh , Ljungman Per , Mossad Sherif B , El Haddad Lynn , Shah Dimpy P , Jiang Ying , Khawaja Fareed , Dadwal Sanjeet , Blanchard Ted , Chemaly Roy F
Published: July 2023

Background

Cytomegalovirus (CMV) infection is a common opportunistic infection after allogeneic hematopoietic cell transplant (alloHCT). We explored whether a change in CMV cell-mediated immunity during the first month after transplant predicts the risk of development of CMV infection and all-cause mortality.

Methods

This follow-up analysis is based on data from the REACT study, a multicenter prospective observational study of recipients of alloHCT who were CMV-seropositive. Production of interferon γ following ex vivo stimulation with CMV antigens IE1 (immediate early 1) and pp65 (phosphoprotein 65) was assessed by CMV ELISPOT assay at baseline and 2 and 4 weeks after transplant. Clinically significant CMV infection (CS-CMVi) was defined as CMV viremia and/or disease necessitating antiviral therapy. We evaluated the impact of CMV CMI changes on the risk of CS-CMVi and post transplant mortality.

Results

The analysis included 226 recipients of alloHCT with CMV cell-mediated immunity data at baseline and 2 and/or 4 weeks after transplant. CS-CMVi occurred in 64 patients (28%). On Cox regression analyses, independent predictors of CS-CMVi included a negative Δ change from baseline to week 2 of pp65 spot counts (hazard ratio, 3.65 [95% CI, 1.65–8.04]; P = .001) to week 4 of IE1 spot counts (hazard ratio, 2.79 [95% CI, 1.46–5.35]; P = .002), anti-thymocyte globulin conditioning regimen, type of transplant, female sex, and corticosteroid use. Kaplan-Meir analysis showed a significant association of a negative IE1 change from baseline to week 4 and increased all-cause mortality after transplant (log rank test = 0.041).

Conclusions

A decrease in CMV-specific T-cell responses during the first month after transplant may predict CS-CMVi and is associated with all-cause mortality in recipients of alloHCT.
Defeating the Hidden Foe: Antibiotic Therapy and Clinical Outcomes of Cutibacterium acnes Spinal Implant Infections
Authors: Tai Don Bambino Geno , Lahr Brian , Suh Gina A , Berbari Elie F , Huddleston Paul M , Tande Aaron J
Published: July 2023

Background

Cutibacterium acnes can cause spinal implant infections. However, little is known about the optimal medical management and outcomes of C. acnes spinal implant infections (CSII). Our study aims to describe the management of patients with CSII and evaluate the clinical outcomes.

Methods

We performed a retrospective cohort study of patients aged 18 years or older who underwent spinal fusion surgery with instrumentation between January 1, 2011, and December 31, 2020, and whose intraoperative cultures were positive for C. acnes. The primary outcome was treatment failure based on subsequent recurrence, infection with another organism, or unplanned surgery secondary to infection.

Results

There were 55 patients with a median follow-up (interquartile range) of 2 (1.2–2.0) years. Overall, there were 6 treatment failures over 85.8 total person-years, for an annual rate of 7.0% (95% CI, 2.6%–15.2%). Systemic antibiotic treatment was given to 74.5% (n = 41) of patients for a median duration of 352 days. In the subgroup treated with systemic antibiotics, there were 4 treatment failures (annual rate, 6.3%; 95% CI, 1.7%–16.2%), all of which occurred while on antibiotic therapy. Two failures occurred in the subgroup without antibiotic treatment (annual rate, 8.8%; 95% CI, 1.1%–31.8%).

Conclusions

Our study found that the estimated annual treatment failure rate was slightly higher among patients who did not receive antibiotics. Of the 6 failures observed, 4 had recurrence of C. acnes either on initial or subsequent treatment failures. More studies are warranted to determine the optimal duration of therapy for CSII.
La prise en charge de la neutropénie fébrile chez les enfants et les adolescents immunocompétents
Authors: Lirette Marie-Pier , Wright Nicola , Trottier Evelyne D , Beck Carolyn E
Published: July 2023

La neutropénie fébrile est une manifestation clinique fréquente en pédiatrie, qui peut être associée à une infection bactérienne invasive. Cependant, le risque de ce type d’infection est faible chez les enfants et les adolescents autrement en santé qui font de la fièvre et présentent une neutropénie, la plupart des cas étant causés par une infection virale. Les enfants âgés de six mois à 18 ans qui ont l’air bien, ne souffrent pas d’un cancer, sont considérés comme immunocompétents et présentent un premier épisode de neutropénie, sans autres facteurs de risque, n’ont généralement pas besoin d’antibiotiques empiriques. Cependant, une évaluation approfondie est indiquée, y compris une anamnèse et un examen physique complets, de même qu’une hémoculture lorsque la numération absolue des neutrophiles est inférieure à 0,5 × 109/L. Il est recommandé d’assurer un suivi étroit, de reprendre l’hémogramme et de donner des conseils préventifs stricts.
La réduction du risque d’infection périnatale chez les nouveau-nés de mères dont les soins prénatals étaient inappropriés
Authors: Bitnun Ari , Sauvé Laura , Fanella Sergio
Published: July 2023

Le risque que des infections maternelles ne soient ni décelées ni traitées augmente lorsque les soins prénatals sont inappropriés, ce qui met la santé de la mère et de son nouveau-né à risque. Lorsqu’une femme enceinte se présente tardivement pour recevoir des soins, les tests systématiques qui influent sur la prise en charge du nouveau-né devraient inclure l’antigène de surface de l’hépatite B (AgHBs), la sérologie du virus de l’hépatite C (VHC), du virus de l’immunodéficience humaine (VIH) et de la syphilis, de même que le dépistage de la Chlamydia trachomatis et de la Neisseria gonorrhoeae. Si la mère ne s’est pas soumise aux dépistages avant ou après l’accouchement et qu’elle n’est pas disponible pour s’y soumettre, il faudrait procéder au dépistage du VIH, du virus de l’hépatite B (VHB), du VHC et de la syphilis chez le nouveau-né. Le dépistage de la C. trachomatis et de la N. gonorrhoeae est toutefois réservé aux cas où le nouveau-né démontre des manifestations cliniques compatibles avec ces infections. Il est optimal d’obtenir rapidement les résultats du dépistage du VIH, du VHB et de la syphilis, car l’utilisation des traitements préventifs est circonscrite dans le temps. Il existe des interventions préventives précoces et efficaces pour les nouveau-nés à risque de VIH, de VHB, de syphilis ou de gonorrhée. Un suivi clinique étroit et des tests de suivi s’imposent auprès des nouveau-nés de mères dont les soins prénatals étaient inappropriés, car il est impossible d’exclure pleinement toutes les infections pendant la période périnatale.
Neural substrates of behavioral inhibitory control during the two-choice oddball task: functional neuroimaging evidence
Authors: Zhao Shirui , Yuan Ruosong , Gao Wei , Liu Qiang , Yuan Jiajin
Published: July 2023

Background

Behavioral inhibitory control (BIC) depicts a cognitive function of inhibiting inappropriate dominant responses to meet the context requirement. Despite abundant research into neural substrates of BIC during the go/no-go and stop signal tasks, these tasks were consistently shown hard to isolate neural processes of response inhibition, which is of primary interest, from those of response generation. Therefore, it is necessary to explore neural substrates of BIC using the two-choice oddball (TCO) task, whose design of dual responses is thought to produce an inhibition effect free of the confounds of response generation.

Objective

The current study aims at depicting neural substrates of performing behavioral inhibitory control in the two-choice oddball task, which designs dual responses to balance response generation. Also, neural substrates of performing BIC during this task are compared with those in the go/no-go task, which designs a motor response in a single condition.

Methods

The present study integrated go/no-go (GNG) and TCO tasks into a new Three-Choice BIC paradigm, which consists of standard (75%), deviant (12.5%), and no-go (12.5%) conditions simultaneously. Forty-eight college students participated in this experiment, which required them to respond to standard (frequent) and deviant stimuli by pressing different keys, while inhibiting motor response to no-go stimuli. Conjunction analysis and ROI (region of interest) analysis were adopted to identify the unique neural mechanisms that subserve the processes of BIC.

Results

Both tasks are effective in assessing BIC function, reflected by the significantly lower accuracy of no-go compared to standard condition in GNG, and the significantly lower accuracy and longer reaction time of deviant compared to standard condition in TCO. However, there were no significant differences between deviant and no-go conditions in accuracy. Moreover, functional neuroimaging has demonstrated that the anterior cingulate cortex (ACC) activation was observed for no-go vs. standard contrast in the GNG task, but not in deviant vs. standard contrast in the TCO task, suggesting that ACC involvement is not a necessary component of BIC. Second, ROI analysis of areas that were co-activated in TCO and GNG showed co-activations in the right inferior frontal cortex (triangle and orbital), with the signals in the TCO task significantly higher than those in the GNG task.

Conclusions

These findings show that the designed responses to both standard and deviant stimuli in the TCO task, compared to the GNG task, produced a more prominent prefrontal inhibitory processing and extinguished an unnecessary component of ACC activation during BIC. This implies that prefrontal involvement, but not that of ACC, is mandatory for the successful performance of inhibiting prepotent behaviors.
Wealth and the Transition to Motherhood
Authors: Su Jessica Houston , Addo Fenaba R
Published: July 2023

Wealth, a significant dimension of inequality that captures both financial security and social position, shapes patterns of family formation. This study evaluates the role of wealth in the transition to motherhood. We argue that wealth is particularly relevant to when women become mothers, and whether their first birth is desired or undesired. Leveraging longitudinal panel data from the NLSY79 (n=2,382), we find that net worth is linked with a higher risk of a desired first birth and lower risk of an undesired first birth in the subsequent year. These countervailing effects are obscured when desired and undesired births are combined. Our study adds another important dimension to existing research by highlighting the distinct effects of both assets and debts, components of net worth that are typically obscured in aggregate measures. This analysis reveals that having financial assets, such as a savings account, are associated with a lower risk of undesired first birth in the next year, while unsecured consumer debts, such as credit cards, are associated with a lower risk of desired first births in the subsequent year. Our findings have important implications for social stratification in family formation given rising wealth inequality among families with children.
A three-pronged lesson in differential equations in a calculus course: analytical, numerical and experimental
Authors: Chow Amenda N , Harrington Peter D , Leung Fok-Shuen
Published: July 2023

Physical experiments in classrooms have many benefits for student learning, including increased student interest, participation and knowledge retention. While experiments are common in engineering and physics classes, they are seldom used in first-year calculus, where the focus is on solving problems analytically and, occasionally, numerically. In this paper, we detail a three-pronged lesson introducing differential equations using analytical, numerical and experimental approaches in a large first-year differential calculus course. Presenting the three approaches in succession allows students to evaluate advantages and disadvantages. The lesson incorporates software and programming and provides opportunities for active, experiential, team-based learning.
Tolerance against exposure to solution of magnesium perchlorate in microinvertebrates
Authors: Kayastha Pushpalata , Rzymski Piotr , Gołdyn Bartłomiej , Nagwani Amit Kumar , Fiałkowska Edyta , Pajdak-Stós Agnieszka , Sobkowiak Robert , Robotnikowski Gracjan , Kaczmarek Łukasz
Published: July 2023

Perchlorates are present at high concentrations in Martian regolith and pose an additional challenge to the survival of terrestrial life on Mars. Some microinvertebrates can resist extreme conditions (e.g. low temperatures, lack of oxygen and radiation), making them suitable model species for space experiments. Clarification of whether they can tolerate high levels of perchlorates is crucial for understanding the scope of application of small invertebrates in Mars exploration. We assessed the activity of some Crustacea, Nematoda, Rotifera and Tardigrada exposed to 0.25–1.00% magnesium perchlorate. The number of active specimens decreased with exposure time and perchlorate concentration. However, exposure of selected species to 0.25% perchlorate for 24 or 72 h showed activity in some specimens. Only Caenorhabditis elegans, Lecane inermis and Artemia salina exhibited activity after 24 h exposure to 1.00% perchlorate. Lecane inermis was the only species to remain active after 72 h of incubation with 1.00% perchlorate. Transferring specimens to distilled water after perchlorate exposure generally resulted in high recovery rates. The study indicates that all the tested invertebrates resist extremely high concentrations of perchlorates, which has implications for further research on their potential use in development of biological systems with improved performance and utility on Mars.
FISHing for Rickettsia in tardigrades: additional evidence for tardigrade endosymbionts
Authors: Tibbs-Cortes Bienvenido W , Schultz Dylan L , Tibbs-Cortes Laura E , Schmitz-Esser Stephan
Published: July 2023

Many ecdysozoans harbour endosymbiotic bacteria within their microbiota, and these endosymbionts can have a range of positive and negative effects on their hosts. Recent 16S rRNA gene amplicon sequencing studies have provided evidence for endosymbionts within the tardigrade microbiota. In a previous amplicon study, we determined that sequences corresponding to the endosymbiotic genus Rickettsia were significantly more associated with tardigrades than with the substrate from which they were isolated. Here, we performed fluorescence in situ hybridization (FISH) using a Rickettsia-specific probe, RickB1, to determine if Rickettsia could be found in tardigrades. RickB1 and a probe targeting most bacteria, EUB338, colocalized within tardigrade tissues, indicating the presence of Rickettsia. We also performed FISH using RickB1 and a nonsense probe, which allowed us to distinguish between false-positives and true positives. This method revealed RickB1 signals in tardigrades that were not due to erroneous probe binding, providing further evidence that Rickettsia is present in tardigrades. Future research will be necessary to determine the effects, if any, of these endosymbionts on their tardigrade hosts.
Blockade of the mineralocorticoid receptor improves markers of human endothelial cell dysfunction and hematological indices in a mouse model of sickle cell disease
Authors: Rivera Alicia , Vega Christopher , Ramos‐Rivera Arelys , Maldonado Enrique R. , Prado Gregory N. , Karnes Hope E. , Fesko Yuri A. , Snyder L. Michael , Alper Seth L. , Romero Jose R.
Published: July 2023

Increased endothelin‐1 (ET‐1) levels in patients with sickle cell disease (SCD) and transgenic mouse models of SCD contribute to disordered hematological, vascular, and inflammatory responses. Mineralocorticoid receptor (MR) activation by aldosterone, a critical component of the Renin‐Angiotensin‐Aldosterone‐System, modulates inflammation and vascular reactivity, partly through increased ET‐1 expression. However, the role of MR in SCD remains unclear. We hypothesized that MR blockade in transgenic SCD mice would reduce ET‐1 levels, improve hematological parameters, and reduce inflammation. Berkeley SCD (BERK) mice, a model of severe SCD, were randomized to either sickle standard chow or chow containing the MR antagonist (MRA), eplerenone (156 mg/Kg), for 14 days. We found that MRA treatment reduced ET‐1 plasma levels (p = .04), improved red cell density gradient profile (D50; p < .002), and increased mean corpuscular volume in both erythrocytes (p < .02) and reticulocytes (p < .024). MRA treatment also reduced the activity of the erythroid intermediate‐conductance Ca2+‐activated K+ channel – KCa3.1 (Gardos channel, KCNN4), reduced cardiac levels of mRNAs encoding ET‐1, Tumor Necrosis Factor Receptor‐1, and protein disulfide isomerase (PDI) (p < .01), and decreased plasma PDI and myeloperoxidase activity. Aldosterone (10−8 M for 24 h in vitro) also increased PDI mRNA levels (p < .01) and activity (p < .003) in EA.hy926 human endothelial cells, in a manner blocked by pre‐incubation with the MRA canrenoic acid (1 μM; p < .001). Our results suggest a novel role for MR activation in SCD that may exacerbate SCD pathophysiology and clinical complications.
The cellular landscape of the endochondral bone during the transition to extrauterine life
Authors: Rueda Alejandro Díaz , Salvador-Martínez Irepan , Sospedra-Arrufat Ismael , Alcaina-Caro Ana , Fernández-Miñán Ana , Burgos-Ruiz Ana M. , Cases Ildefonso , Mohedano Alberto , Tena Juan J. , Heyn Holger , Lopez-Rios Javier , Nusspaumer Gretel
Published: July 2023

The cellular complexity of the endochondral bone underlies its essential and pleiotropic roles during organismal life. While the adult bone has received significant attention, we still lack a deep understanding of the perinatal bone cellulome. Here, we have profiled the full composition of the murine endochondral bone at the single-cell level during the transition from fetal to newborn life and in comparison to the adult tissue, with particular emphasis on the mesenchymal compartment. The perinatal bone contains different fibroblastic clusters with blastema-like characteristics in organizing and supporting skeletogenesis, angiogenesis, and hematopoiesis. Our data also suggests dynamic inter- and intra-compartment interactions as well as a bone marrow milieu that seems prone to anti-inflammation, which we hypothesize is necessary to ensure the proper program of lymphopoiesis and the establishment of central and peripheral tolerance in early life. Our study provides an integrative roadmap for the future design of genetic and cellular functional assays to validate cellular interactions and lineage relationships within the perinatal bone.
CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel driver of metastasis in prostate cancer
Authors: Rodrigo-Faus Maria , Vincelle-Nieto Africa , Vidal Natalia , Puente Javier , Saiz-Pardo Melchor , Lopez-Garcia Alejandra , Mendiburu-Eliçabe Marina , Palao Nerea , Baquero Cristina , Cuesta Angel M , Qu Hui-Qi , Hakonarson Hakon , Musteanu Monica , Reyes-Palomares Armando , Porras Almudena , Bragado Paloma , Gutierrez-Uzquiza Alvaro
Published: July 2023

Owing to the inefficacy of available treatments, the survival rate of patients with metastatic prostate cancer (mPCa) is severely decreased. Therefore, it is crucial to identify new therapeutic targets to increase their survival. This study aim was to identify the most relevant regulators of mPCa onset by performing two high-throughput CRISPR/Cas9 screenings. Furthermore, some of the top hits were validated using small interfering RNA (siRNA) technology, with protein arginine methyltransferase 7(PRMT7)being the best candidate. Its inhibition or depletion via CRISPR significantly reduced mPCa cell capacitiesin vitro. Moreover,PRMT7ablation reduced mPCa appearance in chicken chorioallantoic membrane and mouse xenograft assays. Molecularly, PRMT7 reprograms the expression of several adhesion molecules through methylation of several transcription factors, such as FoxK1 or NR1H2, which results in primary tumor PCa cell adhesion loss and motility gain. Importantly,PRMT7is upregulated in advanced stages of Spanish PCa tumor samples and PRMT7 pharmacological inhibition reduces the dissemination of mPCa cells. Thus, here is shown thatPRMT7is a potential therapeutic target and biomarker of mPCa.
Sorcin-STAT3-Serpin E1/CCL5 axis can be the trigger of pancreatic cancer-associated new-onset diabetes
Authors: Gong Jiali , Li Xiawei , Feng Zengyu , Lou Jianyao , Pu Kaiyue , Sun Yongji , Hu Sien , Wu Jian , Wu Yulian
Published: July 2023

A rise in blood glucose is the early warning signs of underlying pancreatic cancer (PC), which could be the externalization of genetic events in PC progression. But there is still a vacancy in the field of mechanism research on pancreatic cancer-associated new-onset diabetes (PCAND). Using siRNA-mediated gene knockdown in vitro, we made MIN6 cells incubated with conditioned media from transfected PC cells, and detected its response. Immunological techniques were used to explore the interaction between sorcin and STAT3. Human cytokine array was performed to explore the inflammatory cytokines downstream of sorcin. In the present study, we have identified a PCAND driver gene SRI. In PC cells, sorcin and STAT3 form a positive feedback loop to enhance the transcription of serpin E1 and CCL5, which can impair nearby islet β-cells, likely by activating the p38 pathway. In 88 biopsies, expression of sorcin was elevated in PC tissues, especially so in PCAND patient samples. Furthermore, clinical-SRI gene combination model can better distinguish PCAND from T2DM, and serpin E1 level is higher in the peripheral blood samples from PCAND than T2DM. Thus, Sorcin could be the key driver in PCAND, and figuring out sorcin-STAT3-serpin E1/CCL5 signaling axis can help us better understand the pathogenesis of PCAND and identify potential biomarkers.

Statement of significance

This study mapped out a novel sorcin-STAT3-Serpin E1/CCL5 signaling axis in pancreatic cancer cells, which explains how early pre-symptomatic pancreatic cancer may coincide with new-onset diabetes in some patients.
WITHDRAWN: Genetic complexity alters drug susceptibility of asexual and gametocyte stages ofP. falciparumto antimalarial candidates
Authors: Greyling Nicola , van der Watt Mariëtte , Gwarinda Hazel , van Heerden Ashleigh , Greenhouse Bryan , Leroy Didier , Niemand Jandeli , Birkholtz Lyn-Marié
Published: July 2023

Withdrawal statement

The authors have withdrawn their manuscript owing to internal reviewing and agreement to submission by all parties involved in the work not yet completed on this version of the paper. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
GxE PRS: Genotype-environment interaction in polygenic risk score models for quantitative and binary traits
Authors: Jayasinghe Dovini , Momin Md. Moksedul , Beckmann Kerri , Hypponen Elina , Benyamin Beben , Lee S. Hong
Published: July 2023

The use of polygenic risk score (PRS) models has transformed the field of genetics by enabling the prediction of complex traits and diseases based on an individual’s genetic profile. However, the impact of genotype-environment interaction (GxE) on the performance and applicability of PRS models remains a crucial aspect to be explored. Currently, existing GxE PRS models are often inappropriately used, which can result in inflated type 1 error rates and compromised results. In this study, we propose a novel GxE PRS model that correctly incorporates the GxE component to analyze complex traits and diseases. Through extensive simulations, we demonstrate that our proposed model outperforms existing models in terms of controlling type 1 error rates and enhancing statistical power. Furthermore, we apply the proposed model to real data, and report significant GxE effects. Specifically, we highlight the impact of our model on both quantitative and binary traits. For quantitative traits, we uncover the GxE modulation of genetic effects on body mass index (BMI) by alcohol intake frequency (ALC). In the case of binary traits, we identify the GxE modulation of genetic effects on hypertension (HYP) by waist-to-hip ratio (WHR). These findings underscore the importance of employing a robust model that effectively controls type 1 error rates, thus preventing the occurrence of spurious GxE signals. To facilitate the implementation of our approach, we have developed an innovative R software package called GxE PRS, specifically designed to detect and estimate GxE effects. Overall, our study highlights the importance of accurate GxE modeling and its implications for genetic risk prediction, while providing a practical tool to support further research in this area.
Predicting Gene Spatial Expression and Cancer Prognosis: An Integrated Graph and Image Deep Learning Approach Based on HE Slides
Authors: Gao Ruitian , Yuan Xin , Ma Yanran , Wei Ting , Johnston Luke , Shao Yanfei , Lv Wenwen , Zhu Tengteng , Zhang Yue , Zheng Junke , Chen Guoqiang , Sun Jing , Wang Yu Guang , Yu Zhangsheng
Published: July 2023

Interpreting the tumor microenvironment (TME) heterogeneity within solid tumors presents a cornerstone for precise disease diagnosis and prognosis. However, while spatial transcriptomics offers a wealth of data, ranging from gene expression and spatial location to corresponding Hematoxylin and Eosin (HE) images, to explore the TME of various cancers, its high cost and demanding infrastructural needs significantly limit its clinical application, highlighting the need for more accessible alternatives. To bridge this gap, we introduce the Integrated Graph and Image Deep Learning (IGI-DL) model. This innovation, a fusion of Convolutional Neural Networks and Graph Neural Networks, is designed to predict gene spatial expression using HE images. The IGI-DL model outperforms its predecessors in analyzing colorectal cancer (CRC), breast cancer, and cutaneous squamous cell carcinoma (cSCC) by leveraging both pixel intensity and structural features in images. Significantly, across all cancer types, the IGI-DL model enhances the mean correlation of the top five genes by an average of 0.125 in internal and external test sets, rising from 0.306 to 0.431, surpassing existing state-of-the-art (SOTA) models. We further present a novel risk score derived from a super-patch graph, where gene expression predicted by IGI-DL serves as node features. Demonstrating superior prognostic accuracy, this risk score, with a C-index of 0.713 and 0.741 for CRC and breast cancer, supersedes traditional HE-based risk scores. In summary, the approach augments our understanding of the TME from the aspect of histological images, portending a transformation in cancer prognostics and treatment planning and ushering in a new era of personalized and precision oncology.
Modeling Human Spine-Spinal Cord Organogenesis by hPSC-Derived Neuromesodermal Progenitors
Authors: Li Dairui , Ma Yuanchen , Huang Weijun , Li Xiaoping , Liu Huanyao , Xiong Chuanfeng , Zhao Qi , Wang Bin , Lai Xingqiang , Huang Shanshan , Wei Yili , Chen Junhua , Zhang Xiyu , Wei Lan , Ye Wenjin , Chen Qiumin , Rong Limin , Xiang Andy Peng , Li Weiqiang
Published: July 2023

Human trunk development, including spine and spinal cord organogenesis, is a coordinated, orderly, and interdependent process with spatiotemporal tissue patterning. However, the underlying cellular and molecular mechanisms remain largely unclear due to the lack of an effective model that can simulate the early development of human body axis. Here, we reported the long-term patterning and dynamic morphogenesis of human trunk through the formation of spine-spinal cord organoids (SSCOs) self-organized from three-dimensional culture of human PSC-derived neuromesodermal progenitors (NMPs). The SSCOs resembled the morphogenetic features of spine and spinal cord along the anterior–posterior axis, and showed the chondro-osteogenic and neural trajectories consistent with developmental dynamics of spine and spinal cord in gestational embryo through single-cell RNA sequencing (scRNA-seq). In addition, we identified a new HMMR+ bipotent cell population with self-renewal ability and neural/mesodermal competence but distinct from NMPs, which may be involved in trunk development and represent an invaluable tool for disease modeling of spine- and spinal cord-related disorders.

Graphic Abstract
Structured demographic buffering: A framework to explore the environment drivers and demographic mechanisms underlying demographic buffering
Authors: Gascoigne Samuel J L , Kajin Maja , Tuljapurkar Shripad , Santos Gabriel Silva , Compagnoni Aldo , Steiner Ulrich K , Vinton Anna C , Jaggi Harman , Sepil Irem , Salguero-Gómez Roberto
Published: July 2023

Environmental stochasticity is a key determinant of population viability. Decades of work exploring how environmental stochasticity influences population dynamics have highlighted the ability of some natural populations to limit the negative effects of environmental stochasticity, one of these strategies being demographic buffering. Whilst various methods exist to quantify demographic buffering, we still do not know which environment factors and demographic characteristics are most responsible for the demographic buffering observed in natural populations. Here, we introduce a framework to quantify the relative effects of three key drivers of demographic buffering: environment components (e.g., temporal autocorrelation and variance), population structure, and demographic rates (e.g., progression and fertility). Using Integral Projection Models, we explore how these drivers impact the demographic buffering abilities of three plant species with different life histories and demonstrate how our approach successfully characterises a population’s capacity to demographically buffer against environmental stochasticity in a changing world.
Neuromolecular responses in disrupted mutualistic cleaning interactions under future environmental conditions
Authors: Ramírez-Calero S. , Paula J. R. , Otjacques E. , Ravasi T. , Rosa R. , Schunter C.
Published: July 2023

Mutualistic interactions, which constitute some of the most advantageous interactions among fish species, are highly vulnerable to environmental changes. A key mutualistic interaction is the cleaning service rendered by the cleaner wrasse,Labroides dimidiatus, which involves intricate processes of social behaviour to remove ectoparasites from client fish and can be altered in near-future environmental conditions. Here, we evaluated the neuromolecular mechanisms behind the behavioural disruption of cleaning interactions in response to future environments. We subjected cleaner wrasses and surgeonfish (Acanthurus leucosternon, serving as clients) to elevated temperature (Warming, 32°C), increased levels of CO2(High CO2, 1000 ppm), and a combined condition of elevated CO2and temperature (Warming & High CO2, 32°C & 1000 ppm) for 28 days. Each of these conditions resulted in behavioural disruptions concerning the motivation to interact and the quality of interaction (High CO2-80.7%, Warming – 92.6%, Warming & High CO2-79.5%,p<0.001). Using transcriptomic of the fore-, mid-, and hindbrain, we discovered that most transcriptional reprogramming in both species under warming conditions occurred primarily in the hind- and forebrain. The associated functions under warming were linked to stress, heat shock proteins, hypoxia, and behaviour. In contrast, elevated CO2exposure affected a range of functions associated with GABA, behaviour, visual perception, and circadian rhythm. Interestingly, in the combined Warming & High CO2condition, we did not observe any expression changes of behaviour. However, we did find signs of endoplasmic reticulum stress and apoptosis, suggesting not only an additive effect of the environmental conditions but also a trade-off between physiological performance and behaviour in the cleaner wrasse. We suggest that impending environmental shifts can affect the behaviour and molecular processes that sustain mutualistic interactions betweenL. dimidiatusand its clients, which could have a cascading effect on their adaptation potential and possibly cause large-scale impacts on coral reef ecosystems.
Coevolution-driven method for efficiently simulating conformational changes in proteins reveals molecular details of ligand effects in the β2AR receptor
Authors: Mitrovic Darko , Chen Yue , Marciniak Antoni , Delemotte Lucie
Published: July 2023

With the advent of AI-powered structure prediction, the scientific community is inching ever closer to solving protein folding. An unresolved enigma, however, is to accurately, reliably and deterministically predict alternative conformational states that are crucial for the function of e.g. transporters, receptors or ion channels where conformational cycling is innately coupled to protein function. Accurately discovering and exploring all conformational states of membrane proteins has been challenging due to the need to retain atomistic detail while enhancing the sampling along interesting degrees of freedom. The challenges include but are not limited to finding which degrees of freedom are relevant, how to accelerate the sampling along them, and then quantifying the populations of each micro- and macrostate. In this work, we present a methodology that finds the relevant degrees of freedom by combining evolution and physics through machine learning and apply it to the β2 adrenergic receptor conformational sampling. In addition to predicting new conformations that are beyond the training set, we have computed free energy surfaces associated with the protein’s conformational landscape. We then show that the methodology is able to quantitatively predict the effect of an array of ligands on the β2 adrenergic receptor activation, and that the full conformational landscape, including states related to biased signaling, is discovered using this procedure. Lastly, we also stake out the structural determinants of activation and inactivation pathway signaling through different ligands.
Three-dimensional study of spur morphogenesis in the flower ofStaphisagria picta(Ranunculaceae) – from cellular level to organ scale
Authors: Delpeuch Pauline , Nadot Sophie , Belcram Katia , Plumerault Antoine , Damerval Catherine , Jabbour Florian
Published: July 2023

Floral spurs are invaginations borne by perianth organs (petals and/or sepals) that have evolved repeatedly in various angiosperm clades. They typically store nectar and can limit the access of pollinators to this reward, resulting in pollination specialization that can lead to speciation in both pollinator and plant lineages.

Despite the ecological and evolutionary importance of nectar spurs, the cellular mechanisms involved during spur development have only been described in detail in a handful of species, primarily with respect to epidermal cells. These studies show that the mechanisms involved are taxon-specific.

Using confocal microscopy and automated 3D image analysis, we studied spur morphogenesis inStaphisagria picta(Ranunculaceae) and showed that the process is marked by an early phase of dominant cell proliferation, followed by a phase of anisotropic (directional) cell expansion.

The comparison withAquilegia, another taxon of Ranunculaceae with spurred petals, revealed that the convergence in form between the spurs of both taxa is obtained by partially similar developmental processes. The analytical pipeline designed here is an efficient method to visualize in 3D each cell of a developing organ, paving the way for future comparative studies of organ morphogenesis in multicellular eukaryotes.

Highlight

A new method of 3D analysis of plant tissues at the cellular level revealed that spur morphogenesis inStaphisagria pictais marked by an early phase of dominant cell proliferation, followed by a phase of anisotropic cell expansion. Floral spur development is analysed for the first time quantitatively, taking into account all tissues composing the organ, namely epidermis and parenchyma.
Impact Evaluation of Significant Feature Set in Cross Project for Defect Prediction through Hybrid Feature Selection in Multiclass
Authors: Gul Sana , Faiz Rizwan Bin , Aljaidi Mohammad , Samara Ghassan , Alsarhan Ayoub , al-Qerem Ahmad
Published: July 2023

Abstract

Cross-project defect prediction (CPDP) is a significant way of defect identification in the project. In cross-project defect prediction, we extract knowledge from the source project and apply that learned knowledge to predict labels for the target project. However, the model performance can be affected by features that are insignificant and irrelevant. Hybrid feature selection (HFS) can play a significant role in achieving high prediction accuracy by selecting significant and only relevant features. Our aim is to explore effect of significant feature selection through a hybrid approach upon cross-project (CP) defect prediction for datasets which are multi-class in nature. We leveraged the strengths of Random Forest (RF) and Recursive Feature Elimination Cross Validation (RFECV) which can constructively select few features which are significant. The design of our controlled experiment is 1 Factor 2 Treatments (1F2T). Exploratory Data Analysis (EDA) proves that all versions of PROMISE repository are multi class and have duplicated rows in data, distribution gap among values, and imbalance classes. Hence after removing duplicated rows, reducing the gap present in distribution of data, and balancing classes, we selected significant feature set through Hybrid approach i.e. Random Forest (RF) and Recursive Feature Elimination Cross Validation (RFECV). We used Convolutional Neural Network (CNN) as a classifier to predict Cross project defects along with SoftMax as the last layer. Our experimental setup resulted in the average 78% prediction accuracy measure of all 14 versions in terms of AUC. Our experimental result showed that there is significant impact of HFS on defect prediction accuracy for different datasets in the CP.
Spatial analysis of environmental factors at found locations of orphaned mammals (Didelphis virginiana,Procyon lotor,Sciurus carolinensis, andSylvilagus floridanus) in Champaign County, Illinois, USA
Authors: Heniff Stephanie , Sander William , Elzinga Colleen , Varga Csaba , Brown William Marshall , Sander Samantha J.
Published: July 2023

Interactions between people and wildlife are increasing as developments encroach on nature. Concurrently, neonatal and juvenile mammals are presented to rehabilitation centers as real or perceived “orphans”, believed to be lacking appropriate parental care for survival. Four common orphaned mammals presented to wildlife rehabilitation facilities are the Virginia opossum (Didelphis virginiana,DIVI), common raccoon (Procyon lotor,PRLO), eastern gray squirrel (Sciurus carolinensis,SCCA), and eastern cottontail rabbit (Sylvilagus floridanus,SYFL). As some individuals are unnecessarily taken from their habitat, there is a benefit to characterizing where they are collected. This study utilized Geographic Information System to examine the spatial relationship between the environment and originating locations of orphans presented to the University of Illinois Wildlife Medical Clinic within Champaign County from 2015-2020 (99 Virginia opossums, 80 common raccoons, 441 eastern gray squirrels, and 602 eastern cottontails). Environmental factors evaluated included percent tree canopy, land cover classification, and distance to water. Overall, these species were frequently found in highly developed areas (p < 0.001), near water (p < 0.027), with a low percent canopy (p < 0.001). Our analysis identifies environments associated with greater human-wildlife interactions and opportunities for targeted educational outreach.
LEF1 isoforms regulate cellular senescence and aging
Authors: Jia Minxue , Sayed Khaled , Kapetanaki Maria G. , Dion William , Rosas Lorena , Irfan Saad , Valenzi Eleanor , Mora Ana L. , Lafyatis Robert A. , Rojas Mauricio , Zhu Bokai , Benos Panayiotis V.
Published: July 2023

Background

The study of aging and its mechanisms, such as cellular senescence, has provided valuable insights into age-related pathologies, thus contributing to their prevention and treatment. The current abundance of high throughput data combined with the surge of robust analysis algorithms has facilitated novel ways of identifying underlying pathways that may drive these pathologies.

Methods

With the focus on identifying key regulators of lung aging, we performed comparative analyses of transcriptional profiles of aged versus young human subjects and mice, focusing on the common age-related changes in the transcriptional regulation in lung macrophages, T cells, and B immune cells. Importantly, we validated our findings in cell culture assays and human lung samples.

Results

We identified Lymphoid Enhancer Binding Factor 1 (LEF1) as an important age-associated regulator of gene expression in all three cell types across different tissues and species. Follow-up experiments showed that the differential expression of long and short LEF1 isoforms is a key regulatory mechanism of cellular senescence. Further examination of lung tissue from patients with Idiopathic Pulmonary Fibrosis (IPF), an age-related disease with strong ties to cellular senescence, we demonstrated a stark dysregulation of LEF1.

Conclusions

Collectively, our results suggest that the LEF1 is a key factor of aging, and its differential regulation is associated with human and murine cellular senescence.
Coordination of cell cycle and morphogenesis during organ formation
Authors: Matthew Jeffrey , Vishwakarma Vishakha , Le Thao Phuong , Agsunod Ryan A. , Chung SeYeon
Published: July 2023

Organ formation requires precise regulation of cell cycle and morphogenetic events. Using theDrosophilaembryonic salivary gland (SG) as a model, we uncover the role of the SP1/KLF transcription factor Huckebein (Hkb) in coordinating cell cycle regulation and morphogenesis. Thehkbmutant SG exhibits defects in invagination positioning and organ size due to abnormal death of SG cells. Normal SG development involves distal-to-proximal progression of endoreplication (endocycle), whereashkbmutant SG cells undergo abnormal cell division, leading to cell death. Hkb represses the expression of key cell cycle and pro-apoptotic genes in the SG. Knockdown ofcyclin Eorcyclin-dependent kinase 1,or overexpression offizzy-relatedrescues most of the morphogenetic defects observed in thehkbmutant SG. These results indicate that Hkb plays a critical role in controlling endoreplication by regulating the transcription of key cell cycle effectors to ensure proper organ formation.