bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and genetic analysis of a wellbeing factor score in the UK Biobank and the impact of childhood maltreatment and psychiatric illness
Authors: Jamshidi Javad , Schofield Peter R. , Gatt Justine M. , Fullerton Janice M. 
Published: March 2022

AbstractWellbeing is an important aspect of mental health that is moderately heritable. Specific wellbeing-related variants have been identified via GWAS meta-analysis of individual questionnaire items. However, a multi-item within-subject index score has potential to capture greater heritability, enabling improved delineation of genetic and phenotypic relationships across traits and exposures that are not possible on aggregate-data. This research employed data from the UK Biobank resource, and a wellbeing index score was derived from indices of happiness and satisfaction with family/friendship/finances/health, using principal component analysis. GWAS was performed in Caucasian participants (N = 129,237) using the derived wellbeing index, followed by polygenic profiling (independent sample; N = 23,703). The wellbeing index, its subcomponents, and negative indicators of mental health were compared via phenotypic and genetic correlations, and relationships with psychiatric disorders examined. Lastly, the impact of childhood maltreatment on wellbeing was investigated. Five independent genome-wide significant loci for wellbeing were identified. The wellbeing index had SNP-heritability of ~8.6%, and stronger phenotypic and genetic correlations with its subcomponents (0.55–0.77) than mental health phenotypes (−0.21 to −0.39). The wellbeing score was lower in participants reporting various psychiatric disorders compared to the total sample. Childhood maltreatment exposure was also associated with reduced wellbeing, and a moderate genetic correlation (rg = ~−0.56) suggests an overlap in heritability of maltreatment with wellbeing. Thus, wellbeing is negatively associated with both psychiatric disorders and childhood maltreatment. Although notable limitations, biases and assumptions are discussed, this within-cohort study aids the delineation of relationships between a quantitative wellbeing index and indices of mental health and early maltreatment.
Genetic alteration of human MYH6 is mimicked by SARS-CoV-2 polyprotein: mapping viral variants of cardiac interest
Authors: Anand Praveen , Lenehan Patrick J. , Niesen Michiel , Yoo Unice , Patwardhan Dhruti , Montorzi Marcelo , Venkatakrishnan A. J. , Soundararajan Venky 
Published: March 2022

AbstractAcute cardiac injury has been observed in a subset of COVID-19 patients, but the molecular basis for this clinical phenotype is unknown. It has been hypothesized that molecular mimicry may play a role in triggering an autoimmune inflammatory reaction in some individuals after SARS-CoV-2 infection. Here we investigate if linear peptides contained in proteins that are primarily expressed in the heart also occur in the SARS-CoV-2 proteome. Specifically, we compared the library of 136,704 8-mer peptides from 144 human proteins (including splicing variants) to 9926 8-mers from all the viral proteins in the reference SARS-CoV-2 proteome. No 8-mers were exactly identical between the reference human proteome and the reference SARS-CoV-2 proteome. However, there were 45 8-mers that differed by only one amino acid when compared to the reference SARS-CoV-2 proteome. Interestingly, analysis of protein-coding mutations from 141,456 individuals showed that one of these 8-mers from the SARS-CoV-2 Replicase polyprotein 1a/1ab (KIALKGGK) is identical to anMYH6peptide encoded by the c.5410 C > A (Q1804K) genetic variation, which has been observed at low prevalence in Africans/African Americans (0.08%), East Asians (0.3%), South Asians (0.06%), and Latino/Admixed Americans (0.003%). Furthermore, analysis of 4.85 million SARS-CoV-2 genomes from over 200 countries shows that viral evolution has already resulted in 20 additional 8-mer peptides that are identical to human heart-enriched proteins encoded by reference sequences or genetic variants. Whether such mimicry contributes to cardiac inflammation during or after COVID-19 illness warrants further experimental evaluation. We suggest that SARS-CoV-2 variants harboring peptides identical to human cardiac proteins should be investigated as “viral variants of cardiac interest”.
UBAP2L promotes gastric cancer metastasis by activating NF-κB through PI3K/AKT pathway
Authors: Li Ou , Zhao Cheng , Zhang Jian , Li Feng-Nan , Yang Zi-Yi , Liu Shi-Lei , Cai Chen , Jia Zi-Yao , Gong Wei , Shu Yi-Jun , Dong Ping 
Published: March 2022

AbstractUbiquitin-associated protein 2-like (UBAP2L) is highly expressed in various types of tumors and has been shown to participate in tumor growth and metastasis; however, its role in gastric cancer (GC) remains unknown. In this study, we observed that UBAP2L expression was markedly elevated in GC tissues and five GC cell lines. Higher expression of UBAP2L was associated with poor prognosis as revealed by bioinformatics analysis on online websites and laboratory experiments. Knockdown of UBAP2L impeded the migration and invasion abilities of GC cell lines. In contrast, its overexpression enhanced the migration and invasion abilities of GC cell lines. Overexpression of UBAP2L also increased the number and size of lung metastatic nodules in vivo. According to the results of mass spectrometry and pathway annotation of the identified proteins, the PI3K/AKT pathway was found to be related to UBAP2L regulation. Further exploration and rescue experiments revealed that UBAP2L stimulates the expression and nuclear aggregation of p65 and promotes the expression of SP1 by activating the PI3K/AKT pathway. In summary, our findings indicate that UBAP2L regulates GC metastasis through the PI3K/AKT/SP1/NF-κB axis. Thus, targeting UBAP2L may be a potential therapeutic strategy for GC.
Rapid age-grading and species identification of natural mosquitoes for malaria surveillance
Authors: Siria Doreen J. , Sanou Roger , Mitton Joshua , Mwanga Emmanuel P. , Niang Abdoulaye , Sare Issiaka , Johnson Paul C. D. , Foster Geraldine M. , Belem Adrien M. G. , Wynne Klaas , Murray-Smith Roderick , Ferguson Heather M. , González-Jiménez Mario , Babayan Simon A. , Diabaté Abdoulaye , Okumu Fredros O. , Baldini Francesco 
Published: March 2022

AbstractThe malaria parasite, which is transmitted by several Anopheles mosquito species, requires more time to reach its human-transmissible stage than the average lifespan of mosquito vectors. Monitoring the species-specific age structure of mosquito populations is critical to evaluating the impact of vector control interventions on malaria risk. We present a rapid, cost-effective surveillance method based on deep learning of mid-infrared spectra of mosquito cuticle that simultaneously identifies the species and age class of three main malaria vectors in natural populations. Using spectra from over 40, 000 ecologically and genetically diverse An. gambiae, An. arabiensis, and An. coluzzii females, we develop a deep transfer learning model that learns and predicts the age of new wild populations in Tanzania and Burkina Faso with minimal sampling effort. Additionally, the model is able to detect the impact of simulated control interventions on mosquito populations, measured as a shift in their age structures. In the future, we anticipate our method can be applied to other arthropod vector-borne diseases.
ADARs act as potent regulators of circular transcriptome in cancer
Authors: Shen Haoqing , An Omer , Ren Xi , Song Yangyang , Tang Sze Jing , Ke Xin-Yu , Han Jian , Tay Daryl Jin Tai , Ng Vanessa Hui En , Molias Fernando Bellido , Pitcheshwar Priyankaa , Leong Ka Wai , Tan Ker-Kan , Yang Henry , Chen Leilei 
Published: March 2022

AbstractCircular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function. We find that editing can stabilize or destabilize secondary structures formed between RCMs via correcting A:C mismatches to I(G)-C pairs or creating I(G).U wobble pairs, respectively. We provide experimental evidence that editing also favors the binding of RNA-binding proteins such as PTBP1 to regulate back-splicing. These ADARs-regulated circRNAs which are ubiquitously expressed in multiple types of cancers, demonstrate high functional relevance to cancer. Our findings support a hitherto unappreciated bidirectional regulation of circular transcriptome by ADARs and highlight the complexity of cross-talk in RNA processing and its contributions to tumorigenesis.
Microbiomes in the Challenger Deep slope and bottom-axis sediments
Authors: Zhou Ying-Li , Mara Paraskevi , Cui Guo-Jie , Edgcomb Virginia P. , Wang Yong 
Published: March 2022

AbstractHadal trenches are the deepest and most remote regions of the ocean. The 11-kilometer deep Challenger Deep is the least explored due to the technical challenges of sampling hadal depths. It receives organic matter and heavy metals from the overlying water column that accumulate differently across its V-shaped topography. Here, we collected sediments across the slope and bottom-axis of the Challenger Deep that enable insights into its in situ microbial communities. Analyses of 586 metagenome-assembled genomes retrieved from 37 metagenomes show distinct diversity and metabolic capacities between bottom-axis and slope sites. 26% of prokaryotic 16S rDNA reads in metagenomes were novel, with novelty increasing with water and sediment depths. These predominantly heterotrophic microbes can recycle macromolecules and utilize simple and complex hydrocarbons as carbon sources. Metagenome and metatranscriptome data support reduction and biotransformation of arsenate for energy gain in sediments that present a two-fold greater accumulation of arsenic compared to non-hadal sites. Complete pathways for anaerobic ammonia oxidation are predominantly identified in genomes recovered from bottom-axis sediments compared to slope sites. Our results expand knowledge of microbially-mediated elemental cycling in hadal sediments, and reveal differences in distribution of processes involved in nitrogen loss across the trench.
Comparative effectiveness of the BNT162b2 and ChAdOx1 vaccines against Covid-19 in people over 50
Authors: Xie Junqing , Feng Shuo , Li Xintong , Gea-Mallorquí Ester , Prats-Uribe Albert , Prieto-Alhambra Dani 
Published: March 2022

AbstractAlthough pivotal trials with varying populations and study methods suggest higher efficacy for mRNA than adenoviral Covid-19 vaccines, not many studies have directly compared vaccine effectiveness in the population. Here, we conduct a head-to-head comparison of BNT162b2 versus ChAdOx1 against Covid-19. We analyse 235,181 UK Biobank participants aged 50 years or older and vaccinated with one or two doses of BNT162b2 or ChAdOx1. People are followed from the vaccination date until 18/10/2021. Inverse probability weighting is used to minimise confounding and the Cox models to derive hazard ratio. We find that, compared with one dose of ChAdOx1, vaccination with BNT162b2 is associated with a 28% (95% CI, 12-42) decreased risk of SARS-CoV-2 infection. Also, two doses of BNT162b2 vs ChAdOx1 confers 30% (95% CI, 25-35) and 29% (95% CI, 10-45) lower risks of both infection and hospitalisation during the study period when the Delta variant is dominant. Furthermore, the comparative protection against the infection persists for at least six months among the fully vaccinated, suggesting no differential waning between the two vaccines. These findings can inform evidence-based Covid-19 vaccination campaigns and booster strategies.
A pharmacogenetic interaction analysis of bevacizumab with paclitaxel in advanced breast cancer patients
Authors: Coltelli Luigi , Allegrini Giacomo , Orlandi Paola , Finale Chiara , Fontana Andrea , Masini Luna Chiara , Scalese Marco , Arrighi Giada , Barletta Maria Teresa , De Maio Ermelinda , Banchi Marta , Fini Elisabetta , Guidi Patrizia , Frenzilli Giada , Donati Sara , Giovannelli Simona , Tanganelli Lucia , Salvadori Barbara , Livi Lorenzo , Meattini Icro , Pazzagli Ilaria , Di Lieto Marco , Pistelli Mirco , Casadei Virginia , Ferro Antonella , Cupini Samanta , Orlandi Francesca , Francesca Damiana , Lorenzini Giulia , Barellini Leonardo , Falcone Alfredo , Cosimi Alessandro , Bocci Guido 
Published: March 2022

AbstractTo investigate pharmacogenetic interactions among VEGF-A, VEGFR-2, IL-8, HIF-1α, EPAS-1, and TSP-1 SNPs and their role on progression-free survival (PFS) in metastatic breast cancer (MBC) patients treated with bevacizumab plus first-line paclitaxel or with paclitaxel alone. Analyses were performed on germline DNA, and SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction (MDR) methodology was applied to investigate the interaction between SNPs. The present study was an explorative, ambidirectional cohort study: 307 patients from 11 Oncology Units were evaluated retrospectively from 2009 to 2016, then followed prospectively (NCT01935102). Two hundred and fifteen patients were treated with paclitaxel and bevacizumab, whereas 92 patients with paclitaxel alone. In the bevacizumab plus paclitaxel group, the MDR software provided two pharmacogenetic interaction profiles consisting of the combination between specific VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes. Median PFS for favorable genetic profile was 16.8 vs. the 10.6 months of unfavorable genetic profile (p = 0.0011). Cox proportional hazards model showed an adjusted hazard ratio of 0.64 (95% CI, 0.5–0.9; p = 0.004). Median OS for the favorable genetic profile was 39.6 vs. 28 months of unfavorable genetic profile (p = 0.0103). Cox proportional hazards model revealed an adjusted hazard ratio of 0.71 (95% CI, 0.5–1.01; p = 0.058). In the 92 patients treated with paclitaxel alone, the results showed no effect of the favorable genetic profile, as compared to the unfavorable genetic profile, either on the PFS (p = 0.509) and on the OS (p = 0.732). The pharmacogenetic statistical interaction between VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes may identify a population of bevacizumab-treated patients with a better PFS.
Synthesis of new series of quinoline derivatives with insecticidal effects on larval vectors of malaria and dengue diseases
Authors: Murugan Kadarkarai , Panneerselvam Chellasamy , Subramaniam Jayapal , Paulpandi Manickam , Rajaganesh Rajapandian , Vasanthakumaran Murugan , Madhavan Jagannathan , Shafi S. Syed , Roni Mathath , Portilla-Pulido Johan S. , Mendez Stelia C. , Duque Jonny E. , Wang Lan , Aziz Al Thabiani , Chandramohan Balamurugan , Dinesh Devakumar , Piramanayagam Shanmughavel , Hwang Jiang-Shiou 
Published: March 2022

AbstractMosquito borne diseases are on the rise because of their fast spread worldwide and the lack of effective treatments. Here we are focusing on the development of a novel anti-malarial and virucidal agent with biocidal effects also on its vectors. We have synthesized a new quinoline (4,7-dichloroquinoline) derivative which showed significant larvicidal and pupicidal properties against a malarial and a dengue vector and a lethal toxicity ranging from 4.408 µM/mL (first instar larvae) to 7.958 µM/mL (pupal populations) for Anopheles stephensi and 5.016 µM/mL (larva 1) to 10.669 µM/mL (pupae) for Aedes aegypti. In-vitro antiplasmodial efficacy of 4,7-dichloroquinoline revealed a significant growth inhibition of both sensitive strains of Plasmodium falciparum with IC50 values of 6.7 nM (CQ-s) and 8.5 nM (CQ-r). Chloroquine IC50 values, as control, were 23 nM (CQ-s), and 27.5 nM (CQ-r). In vivo antiplasmodial studies with P. falciparum infected mice showed an effect of 4,7-dichloroquinoline compared to chloroquine. The quinoline compound showed significant activity against the viral pathogen serotype 2 (DENV-2). In vitro conditions and the purified quinoline exhibited insignificant toxicity on the host system up to 100 µM/mL. Overall, 4,7-dichloroquinoline could provide a good anti-vectorial and anti-malarial agent.
Smartphone app reveals that lynx avoid human recreationists on local scale, but not home range scale
Authors: Thorsen Neri H. , Bischof Richard , Mattisson Jenny , Hofmeester Tim R. , Linnell John D. C. , Odden John 
Published: March 2022

AbstractOutdoor recreation is increasing and affects habitat use and selection by wildlife. These effects are challenging to study, especially for elusive species with large spatial requirements, as it is hard to obtain reliable proxies of recreational intensity over extensive areas. Commonly used proxies, such as the density of, or distance to, hiking paths, ignore outdoor recreation occurring on other linear feature types. Here we utilized crowdsourced data from the Strava training app to obtain a large-scale proxy for pedestrian outdoor recreation intensity in southeast Norway. We used the proxy and GPS-tracking data from collared Eurasian lynx (Lynx lynx) to investigate how recreation affects habitat selection at the home range scale and local scale by lynx during summer. We fitted resource selection functions at the two scales using conditional logistic regression. Our analysis revealed that lynx avoided areas of recreational activity at the local scale, but not at home range scale. Nonetheless, lynx frequently used areas associated with recreation, and to a greater degree at night than during the day. Our results suggest that local-scale avoidance of recreation and temporal adjustments of habitat use by lynx mitigate the need for a home range-scale response towards recreation. Scale-dependent responses and temporal adjustments in habitat use may facilitate coexistence between humans and large carnivores.
Beta-blocker/ACE inhibitor therapy differentially impacts the steady state signaling landscape of failing and non-failing hearts
Authors: Sorrentino Andrea , Bagwan Navratan , Linscheid Nora , Poulsen Pi C. , Kahnert Konstantin , Thomsen Morten B. , Delmar Mario , Lundby Alicia 
Published: March 2022

AbstractHeart failure is a multifactorial disease that affects an estimated 38 million people worldwide. Current pharmacotherapy of heart failure with reduced ejection fraction (HFrEF) includes combination therapy with angiotensin-converting enzyme inhibitors (ACEi) and β-adrenergic receptor blockers (β-AR blockers), a therapy also used as treatment for non-cardiac conditions. Our knowledge of the molecular changes accompanying treatment with ACEi and β-AR blockers is limited. Here, we applied proteomics and phosphoproteomics approaches to profile the global changes in protein abundance and phosphorylation state in cardiac left ventricles consequent to combination therapy of β-AR blocker and ACE inhibitor in HFrEF and control hearts. The phosphorylation changes induced by treatment were profoundly different for failing than for non-failing hearts. HFrEF was characterized by profound downregulation of mitochondrial proteins coupled with derangement of β-adrenergic and pyruvate dehydrogenase signaling. Upon treatment, phosphorylation changes consequent to HFrEF were reversed. In control hearts, treatment mainly led to downregulation of canonical PKA signaling. The observation of divergent signaling outcomes depending on disease state underscores the importance of evaluating drug effects within the context of the specific conditions present in the recipient heart.
Relevance of cortisol and copeptin blood concentration changes in an experimental pain model
Authors: Blum Claudine A. , Velly Laëtitia , Brochet Christine , Ziegler Frédéric , Tavolacci Marie-Pierre , Hausfater Pierre , Lvovschi Virginie Eve 
Published: March 2022

AbstractThe effect of pain and analgesics on stress biomarkers is not well studied. We evaluated the effect of acute pain and analgesics on serum cortisol and copeptin in an experimental pain model in healthy volunteers. Healthy volunteers presented at 8 a.m. for an experimental pain stimulation. Cortisol and copeptin levels were measured before, during and after electrophysiological stimulation, first before and then during opioid delivery. Difference in biomarker levels compared to baseline levels was calculated, and potential influencing factors were evaluated by linear regression analysis. Cortisol decreased by 13% during the 10 min of rest at baseline, but copeptin did not change significantly. Cortisol had a median decrease of −24% or −83 nmol/l (−44 to −124 nmol/l, p = 0.0002) during the electrophysiological stimulation training session, while the median difference for copeptin was −22% or −1.01 pmol/l (−2.35 to 0.08 pmol/l, p = 0.0003). After administration of opioids, cortisol did not decrease but increased by 3% (p = 0.043), indicating an increasing opioids effect on cortisol. This effect was not visible for copeptin (median change −0.003 pmol/l (−0.50 to 0.24), p = 0.45). In this experimental pain model performed in the morning, moderate pain did not have a relevant effect on cortisol or copeptin levels, whereas opioids led to a discrete peak of cortisol.Clinicaltrials.gov identifier: NCT01975753 (registered on November 5, 2013, before start of recruitment).
Gossip promotes cooperation only when it is pro-socially motivated
Authors: Testori Martina , Hemelrijk Charlotte K. , Beersma Bianca 
Published: March 2022

AbstractHumans are often shown to cooperate with one another. Most of the mechanisms that foster cooperation among humans rely on reputation, which itself relies on the acquisition of information about other people’s behaviors. Gossip has been proposed as a cheap yet efficient tool to acquire information, and it has largely been proved to be an effective means to foster and maintain cooperation. However, empirical studies supporting this claim have ignored two aspects: (1) they often compared gossip to treatments in which no reputation was available, impeding a direct assessment of whether it is gossip that promotes cooperation or rather the introduction of a reputation system; and (2) they focused on pro-social gossip (e.g., gossip aimed at helping the receiver), neglecting the impact of other types of gossip. We show here that, in contrast with the widespread notion that gossip promotes cooperation, gossip mostly depletes cooperation compared to first-hand information. If lying is fruitful for individuals or if a group’s behavior is largely uncooperative, gossip leads to negative reputational information and decreased cooperation.