bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted design of synthetic enhancers for selected tissues in the Drosophila embryo
Authors: de Almeida Bernardo P. , Schaub Christoph , Pagani Michaela , Secchia Stefano , Furlong Eileen E. M. , Stark Alexander 
Published: December 2023

AbstractEnhancers control gene expression and have crucial roles in development and homeostasis1–3. However, the targeted de novo design of enhancers with tissue-specific activities has remained challenging. Here we combine deep learning and transfer learning to design tissue-specific enhancers for five tissues in the Drosophila melanogaster embryo: the central nervous system, epidermis, gut, muscle and brain. We first train convolutional neural networks using genome-wide single-cell assay for transposase-accessible chromatin with sequencing (ATAC-seq) datasets and then fine-tune the convolutional neural networks with smaller-scale data from in vivo enhancer activity assays, yielding models with 13% to 76% positive predictive value according to cross-validation. We designed and experimentally assessed 40 synthetic enhancers (8 per tissue) in vivo, of which 31 (78%) were active and 27 (68%) functioned in the target tissue (100% for central nervous system and muscle). The strategy of combining genome-wide and small-scale functional datasets by transfer learning is generally applicable and should enable the design of tissue-, cell type- and cell state-specific enhancers in any system.
Construction of a ceRNA regulatory network to explore potential pathogenesis mechanisms involved in human hepatocellular carcinoma
Authors: Liu Yicun , Dong Zhixing , Chen WeiJie , Chen Lin , Ju Linling , Cai Weihua , Luo Xi , Bian Zhaolian 
Published: December 2023

AbstractWorldwide, primary liver cancer is the third leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Recent studies have shown that circular RNAs (circRNAs) that interact with microRNAs (miRNAs) are involved in the occurrence and development of various tumours. Transcriptional profile analysis was used to analyse expression of circRNAs in HCC in this study. The top ten upregulated circRNAs were selected and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in another 34 HCC patients. MiRNAs and mRNAs downstream of these circRNAs were explored through database analysis, and finally, the competitive endogenous RNA (ceRNA) networks were constructed for 5 selected circRNAs. We identified 9658 differentially expressed circRNAs by transcriptional profile analysis. QRT-PCR was performed to validate the top ten upregulated circRNAs, and five circRNAs were selected for further analysis. The miRNAs and mRNAs downstream of these five circRNAs were predicted to construct ceRNA network diagrams. Further analysis revealed five circRNA–miRNA–mRNA axes that correlate negatively with HCC prognosis. Numerous differentially expressed circRNAs exist in HCC, and they can regulate the biological behaviour of HCC through ceRNA networks. Bioinformatics analysis showed that ceRNA regulatory axes involved in HCC have high diagnostic and prognostic value and deserve further exploration.
Using broadband infrastructure as a social sensor to detect inequities in unemployment during the COVID-19 pandemic
Authors: Ritsch Nicola , Armanios Daniel Erian 
Published: December 2023

AbstractThis study explores the potential of using physical infrastructure as a “social sensor” for identifying marginalized communities. Prior work tends to explore biases in infrastructure as a retrospective “social autopsy”. Instead, our study aims to create an introspective “social biopsy”, using existing infrastructure gaps to inform how future policy and investment can address existing inequities more sharply and proactively. Specifically, this work explores the possibility of using U.S. county-level broadband penetration rates as a social sensor to predict rates of unemployment amidst the COVID-19 pandemic. The result is a 2 × 2 typology of where broadband as a social sensor is sharper (or coarser), as well as prone to error (either false positives or false negatives). We further explore combining broadband with other forms of physical infrastructure (i.e., bridges, buildings, and WiFi-enabled libraries) to create a sensor “array” to further enhance detection. Overall, this work proposes an “infrastructure-as-sensor” approach to better detect social vulnerability during times of crises in hopes of enhancing resilience through providing services more quickly and precisely to those who most need it.
Microbial shifts associated to ENSO-derived thermal anomalies reveal coral acclimation at holobiont level
Authors: Montaño-Salazar Sandra , Quintanilla Elena , Sánchez Juan A. 
Published: December 2023

AbstractThe coral microbiome conforms a proxy to study effects of changing environmental conditions. However, scarce information exists regarding microbiome dynamics and host acclimation in response to environmental changes associated to global-scale disturbances. We assessed El Niño Southern Oscillation (ENSO)-derived thermal anomalies shifts in the bacterial microbiome of Pacifigorgia cairnsi (Gorgoniidae: Octocorallia) from the remote island of Malpelo in the Tropical Eastern Pacific. Malpelo is a hot spot of biodiversity and lacks direct coastal anthropogenic impacts. We evaluated the community composition and predicted functional profiles of the microbiome during 2015, 2017 and 2018, including different phases of ENSO cycle. The bacterial community diversity and composition between the warming and cooling phase were similar, but differed from the neutral phase. Relative abundances of different microbiome core members such as Endozoicomonas and Mycoplasma mainly drove these differences. An acclimated coral holobiont is suggested not just to warm but also to cold stress by embracing similar microbiome shifts and functional redundancy that allow maintaining coral’s viability under thermal stress. Responses of the microbiome of unperturbed sea fans such as P. cairnsi in Malpelo could be acting as an extended phenotype facilitating the acclimation at the holobiont level.
Characterizing viral species in mosquitoes (Culicidae) in the Colombian Orinoco: insights from a preliminary metagenomic study
Authors: Gómez Marcela , Martínez David , Páez-Triana Luisa , Luna Nicolás , De las salas Jorge Luis , Hernández Carolina , Flórez Alexander Zamora , Muñoz Marina , Ramírez Juan David 
Published: December 2023

AbstractMosquitoes (Diptera: Culicidae) are primary vectors of arthropod-borne viruses (arboviruses) that pose significant public health threats. Recent advances in sequencing technology emphasize the importance of understanding the arboviruses and insect-specific viruses (ISVs) hosted by mosquitoes, collectively called the “virome”. Colombia, a tropical country with favorable conditions for the development and adaptation of multiple species of Culicidae, offers a favorable scenario for the transmission of epidemiologically important arboviruses. However, entomovirological surveillance studies are scarce in rural areas of the country, where humans, mosquitoes, and animals (both domestic and wild) coexist, leading to a higher risk of transmission of zoonotic diseases to humans. Thus, our study aimed to perform a preliminary metagenomic analysis of the mosquitoes of special relevance to public health belonging to the genera Ochlerotatus, Culex, Limatus, Mansonia, Psorophora, and Sabethes, within a rural savanna ecosystem in the Colombian Orinoco. We employed third-generation sequencing technology (Oxford Nanopore Technologies; ONT) to describe the virome of mosquitoes samples. Our results revealed that the virome was primarily shaped by insect-specific viruses (ISVs), with the Iflaviridae family being the most prevalent across all mosquito samples. Furthermore, we identified a group of ISVs that were common in all mosquito species tested, displaying the highest relative abundance concerning other groups of viruses. Notably, Hanko iflavirus-1 was especially prevalent in Culex eknomios (88.4%) and Ochlerotatus serratus (88.0%). Additionally, other ISVs, such as Guadalupe mosquito virus (GMV), Hubei mosquito virus1 (HMV1), Uxmal virus, Tanay virus, Cordoba virus, and Castlerea virus (all belonging to the Negevirus genus), were found as common viral species among the mosquitoes, although in lower proportions. These initial findings contribute to our understanding of ISVs within mosquito vectors of the Culicidae family in the Eastern Plains of Colombia. We recommend that future research explore deeper into ISV species shared among diverse vector species, and their potential interactions with arboviruses. In addition, we also showed the need for a thorough exploration of the influence of local rural habitat conditions on the shape of the virome in mosquito vectors.
Fine-grained interplanetary dust input during the Turonian (Late Cretaceous): evidence from osmium isotope and platinum group elements
Authors: Matsumoto Hironao , Ishikawa Akira , Coccioni Rodolfo , Frontalini Fabrizio , Suzuki Katsuhiko 
Published: December 2023

AbstractThe Turonian age (~ 90–94 Ma) was the hottest geological interval in the Cretaceous and also marked by the K3 event, a pronounced enrichment of 3He in pelagic sediments (i.e., massive input of extraterrestrial materials). Here, we present Os isotopic (187Os/188Os) and platinum group element (PGE) data from Turonian sedimentary records. After a sharp unradiogenic shift during the end-Cenomanian oceanic anoxic event 2, the 187Os/188Os ratios declined continuously throughout the Turonian, which could be ascribed to the formations of several large igneous provinces (LIPs). Because the interval with the most unradiogenic 187Os/188Os ratios (i.e., enhanced LIP volcanism) does not correspond to the warmest interval during the mid-Cretaceous, additional sources of CO2, such as subduction zone volcanism or the kimberlite formation, may explain the Cretaceous Thermal Maximum. As Os isotope ratios do not show any sharp unradiogenic shifts and PGE concentrations do not exhibit a pronounced enrichment, an influx of fine-grained cosmic dust to the Earth’s surface, possibly from the long-period comet showers, can be inferred at the time of the 3He enrichment during the mid-Turonian K3 event. Our findings highlight the different behaviors of 3He and PGE information in the sedimentary rocks during the input of fined-grained extraterrestrial materials.
Accuracy of physician and nurse predictions for 28-day prognosis in ICU: a single center prospective study
Authors: Huang Yanxia , Zhang Renjing , Deng Yunxin , Meng Mei 
Published: December 2023

AbstractThe proportion of correctly predicted prognoses and factors associated with prediction accuracy are unknown. The objective of this study was to explore the accuracy of physician and nurse predictions of 28-day mortality in the ICU. This was a prospective observational single-center study. All medical staff in the ICU have access to patient data, can communicate with patients or clients, and can independently predict the prognosis of patients within 24 h of patient admission. The only question of the questionnaire survey was: What is the patient’s outcome on day 28 (alive or death)? There were 2155 questionnaires completed by 18 physicians and 1916 submitted by 15 nurses. In the 312 patients included, the 28-day mortality rates were predicted by physicians and nurses. The overall proportion of correct prognosis prediction was 90.1% for physicians and 64.4% for nurses (P = 0.000). There was no significant difference in the overall correct proportion and average correct proportion among physicians with different seniority levels. The overall correct proportion and average correct proportion increased among nurses with seniority. Physicians in the ICU can moderately predict 28-day mortality in critically ill patients. Nurses with a seniority of less than 10 years in ICU cannot accurately predict 28-day mortality in critically ill patients. However, the accuracy of nurses’ prediction of patients’ 28-day prognosis increased with their seniority in the ICU.
Diagnosing callous-unemotional personality traits by heart rate orienting responses to images inducing threat and distress
Authors: Schulter Günter , Milek Beatrice , Lackner Helmut Karl , Weber Bernhard , Fink Andreas , Rominger Christian , Perchtold-Stefan Corinna , Papousek Ilona 
Published: December 2023

AbstractThe present study aimed at developing a rather easily applicable method of testing physiological reactions to images of threats and misery. To this end, rapid-changing, transient heart rate orienting responses were used for gaining physiologically based, objective responses to the images. Additionally, subjective ratings were obtained. A significant insensitivity to other's welfare and well-being was already demonstrated as a core feature of callous-unemotional personalities. Thus, physiologically based methods may supplement and possibly improve existing assessments and, in particular, may contribute to a multimodal assessment of psychopathic traits. Out of a non-forensic community sample of 122 men, we selected two extreme groups of 30 participants with the lowest and highest callous-unemotional traits respectively, ascertained by questionnaires. As expected, participants with higher scores of callous-unemotional traits showed smaller responses to distress cues in both heart rate responses and subjective ratings. Moreover, within the group with high callous-unemotional traits heart rate responses to threatening as well as distress cues did not significantly differ from responses to neutral pictures. The study provides further evidence for the idea that a lack of responsiveness to distress cues may be seen as a central feature of callous-unemotional personalities.
Heavy-chain antibody targeting of CD38 NAD+ hydrolase ectoenzyme to prevent fibrosis in multiple organs
Authors: Shi Bo , Amin Asif , Dalvi Pranjali , Wang Wenxia , Lukacs Nicholas , Kai Li , Cheresh Paul , Peclat Thais R. , Chini Claudia C. , Chini Eduardo N. , van Schooten Wim , Varga John 
Published: December 2023

AbstractThe functionally pleiotropic ectoenzyme CD38 is a glycohydrolase widely expressed on immune and non-hematopoietic cells. By converting NAD+ to ADP-ribose and nicotinamide, CD38 governs organismal NAD+ homeostasis and the activity of NAD+-dependent cellular enzymes. CD38 has emerged as a major driver of age-related NAD+ decline underlying adverse metabolic states, frailty and reduced health span. CD38 is upregulated in systemic sclerosis (SSc), a chronic disease characterized by fibrosis in multiple organs. We sought to test the hypothesis that inhibition of the CD38 ecto-enzymatic activity using a heavy-chain monoclonal antibody Ab68 will, via augmenting organismal NAD+, prevent fibrosis in a mouse model of SSc characterized by NAD+ depletion. Here we show that treatment of mice with a non-cytotoxic heavy-chain antibody that selectively inhibits CD38 ectoenzyme resulted in NAD+ boosting that was associated with significant protection from fibrosis in multiple organs. These findings suggest that targeted inhibition of CD38 ecto-enzymatic activity could be a potential pharmacological approach for SSc fibrosis treatment.
Multiple sclerosis susceptibility may be associated with the coding rs20541 (R130Q) IL-13 gene polymorphism in the Polish population
Authors: Grunwald Cezary , Adamska-Patruno Edyta , Wawrusiewicz-Kurylonek Natalia , Czarnowska Agata , Snarska Katarzyna , Dardzińska-Głębocka Agnieszka , Kapica-Topczewska Katarzyna , Mirończuk Anna , Bazylewicz Marcin , Kochanowicz Jan , Krętowski Adam , Kułakowska Alina , Chorąży Monika 
Published: December 2023

AbstractSome of the multiple autoimmune diseases have been already associated with IL-13 single-nucleotide polymorphisms (SNPs). However, there are only few studies regarding multiple sclerosis (MS) risk and IL-13 rs20541 (R130Q) polymorphism, and their results are conflicting. Therefore, the aim of our study was to investigate the frequency of the IL-13 gene rs20541 (R130Q) polymorphism in MS participants and its association with MS clinical subsets in the Polish population. We conducted a case‒control study including 94 relapsing remitting MS patients and 160 healthy volunteers. We genotyped the rs20541 polymorphism in the IL-13 gene and analysed the genotype frequency, age of MS onset and clinical condition (EDSS values) of the MS participants. Fisher’s exact test was used for statistical analysis, and the log-linear model was applied to test for associations. Allele A, as well as the AA and AG genotypes, was observed to be significantly more common in the MS subjects. The OR (odds ratio) for the A compared to the G allele was 1.71 (1.14–2.56), whereas OR 2.33 (0.86–6.26) and OR 1.92 (1.11–3.30) were obtained for the AA and AG genotypes, respectively. We did not identify any significant associations of the studied IL-13 SNP with the investigated clinical parameters of the MS participants. Our results suggest that the rs20541 polymorphism in the IL-13 gene may play an important role in MS predisposition but not in investigated clinical parameters in MS subjects of the Polish population.
Prediction of atrial fibrillation from at-home single-lead ECG signals without arrhythmias
Authors: Gadaleta Matteo , Harrington Patrick , Barnhill Eric , Hytopoulos Evangelos , Turakhia Mintu P. , Steinhubl Steven R. , Quer Giorgio 
Published: December 2023

AbstractEarly identification of atrial fibrillation (AF) can reduce the risk of stroke, heart failure, and other serious cardiovascular outcomes. However, paroxysmal AF may not be detected even after a two-week continuous monitoring period. We developed a model to quantify the risk of near-term AF in a two-week period, based on AF-free ECG intervals of up to 24 h from 459,889 patch-based ambulatory single-lead ECG (modified lead II) recordings of up to 14 days. A deep learning model was used to integrate ECG morphology data with demographic and heart rhythm features toward AF prediction. Observing a 1-day AF-free ECG recording, the model with deep learning features produced the most accurate prediction of near-term AF with an area under the curve AUC = 0.80 (95% confidence interval, CI = 0.79–0.81), significantly improving discrimination compared to demographic metrics alone (AUC 0.67; CI = 0.66–0.68). Our model was able to predict incident AF over a two-week time frame with high discrimination, based on AF-free single-lead ECG recordings of various lengths. Application of the model may enable a digital strategy for improving diagnostic capture of AF by risk stratifying individuals with AF-negative ambulatory monitoring for prolonged or recurrent monitoring, potentially leading to more rapid initiation of treatment.
Network-based restoration strategies maximize ecosystem recovery
Authors: Bhatia Udit , Dubey Sarth , Gouhier Tarik C. , Ganguly Auroop R. 
Published: December 2023

AbstractRedressing global patterns of biodiversity loss requires quantitative frameworks that can predict ecosystem collapse and inform restoration strategies. By applying a network-based dynamical approach to synthetic and real-world mutualistic ecosystems, we show that biodiversity recovery following collapse is maximized when extirpated species are reintroduced based solely on their total number of connections in the original interaction network. More complex network-based strategies that prioritize the reintroduction of species that improve ‘higher order’ topological features such as compartmentalization do not provide meaningful performance improvements. These results suggest that it is possible to design nearly optimal restoration strategies that maximize biodiversity recovery for data-poor ecosystems in order to ensure the delivery of critical natural services that fuel economic development, food security, and human health around the globe.
Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes
Authors: Baumann Claudia , Zhang Xiangyu , Kandasamy Muthugapatti K. , Mei Xiaohan , Chen Shiyou , Tehrani Kayvan F. , Mortensen Luke J. , Watford Wendy , Lall Ashley , De La Fuente Rabindranath 
Published: December 2023

AbstractThe mechanisms leading to changes in mesoscale chromatin organization during cellular aging are unknown. Here, we used transcriptional activator-like effectors, RNA-seq and superresolution analysis to determine the effects of genotoxic stress on oocyte chromatin structure. Major satellites are organized into tightly packed globular structures that coalesce into chromocenters and dynamically associate with the nucleolus. Acute irradiation significantly enhanced chromocenter mobility in transcriptionally inactive oocytes. In transcriptionally active oocytes, irradiation induced a striking unfolding of satellite chromatin fibers and enhanced the expression of transcripts required for protection from oxidative stress (Fermt1, Smg1), recovery from DNA damage (Tlk2, Rad54l) and regulation of heterochromatin assembly (Zfp296, Ski-oncogene). Non-irradiated, senescent oocytes exhibit not only high chromocenter mobility and satellite distension but also a high frequency of extra chromosomal satellite DNA. Notably, analysis of biological aging using an oocyte-specific RNA clock revealed cellular communication, posttranslational protein modifications, chromatin and histone dynamics as the top cellular processes that are dysregulated in both senescent and irradiated oocytes. Our results indicate that unfolding of heterochromatin fibers following acute genotoxic stress or cellular aging induced the formation of distended satellites and that abnormal chromatin structure together with increased chromocenter mobility leads to chromosome instability in senescent oocytes.
Parkin-mediated ubiquitination inhibits BAK apoptotic activity by blocking its canonical hydrophobic groove
Authors: Cheng Peng , Hou Yuzhu , Bian Mingxing , Fang Xueru , Liu Yan , Rao Yuanfang , Cao Shuo , Liu Yanjun , Zhang Shuai , Chen Yanke , Dong Xu , Liu Zhu 
Published: December 2023

AbstractBAK permeabilizes the mitochondrial outer membrane, causing apoptosis. This apoptotic activity of BAK is stimulated by binding prodeath activators within its canonical hydrophobic groove. Parkin, an E3 ubiquitin (Ub) ligase, can ubiquitinate BAK, which inhibits BAK apoptotic activity. However, the molecular mechanism underlying the inhibition of ubiquitination remains structurally uncharacterized. Here, we utilize truncated and soluble BAK to construct a mimetic of K113-ubiquitinated BAK (disulfide-linked UbG76C ~ BAKK113C) and further present its NMR-derived structure model. The classical L8-I44-H68-V70 hydrophobic patch of the conjugated Ub subunit binds within the canonical hydrophobic groove of BAK. This Ub occludes the binding of prodeath BID activators in the groove and impairs BID-triggered BAK activation and membrane permeabilization. Reduced interaction between Ub and BAK subunits allows BID to activate K113-ubiquitinated BAK. These mechanistic insights suggest a nonsignaling function of Ub in that it directly antagonizes stimuli targeting Ub-modified proteins rather than by recruiting downstream partners for cellular messaging.