bluuebunny/crossref_metadata_2025_split huggingface dataset:
cardiovascular safety of COVID-19 vaccines in real-world studies: a systematic review and meta-analysis
Authors: Chang Yafei , Lv Guoli , Liu Chao , Luo Bin , Huang Erwen 
Published: August 2022

AbstractAimsTo assess the association between COVID-19 vaccines and the risk of major adverse cardiovascular events (MACE) in the real world and to provide a reliable evidence-based basis for the cardiovascular safety of COVID-19 vaccines.MethodsWe conducted a comprehensive search in databases from January 1, 2020 to June 15, 2022 for observational studies, that included reporting of MACE and COVID-19 vaccines were included. Random-effects or fixed-effects models were used to estimate the pooled incidence rate and risk ratio of MACE after vaccination. Meta-regression, subgroup analyses, publication bias, sensitivity analyses were performed to evaluate the process and quality of meta-analysis.ResultsThe analyses included data from 43 studies reporting of 16,978 cases, 28,451 cases, and 96,269 cases of myocarditis, myocardial infarction, and cardiac arrhythmia, respectively. The overall incidence rate was 14.8 events per million persons of myocarditis, and 1.73 and 9.6 events per 10,000 persons of myocardial infarction and cardiac arrhythmia after COVID-19 vaccination, respectively. Overall and subgroup analyses showed the increased risks of myocarditis associated with second dose (RR, 2.09; 95%CI: 1.59-2.58), third dose (RR, 2.02; 95%CI: 1.40-2.91), mRNA-1273 (RR, 3.13; 95%CI: 2.11-4.14), or BNT162b2 (RR, 1.57; 95%CI: 1.30-1.85) vaccination. The risk ratios of myocarditis events were more frequently in males than in females (3.44, 2.61-4.54), in younger than in older (2.20, 1.06-4.55). No significant increase risk of myocardial infarction (RR, 0.96; 95%CI: 0.84-1.08) or cardiac arrhythmia (RR, 0.98; 95%CI: 0.84-1.12) events was observed following vaccination. The risk of cardiovascular events (myocarditis, RR, 8.53; myocardial infarction, RR, 2.59; cardiac arrhythmia, RR, 4.47) after SARS-CoV-2 infection was much higher than after vaccination.ConclusionAlthough there is a risk of cardiovascular events following vaccination, the risk was much lower than that following SARS-CoV-2 infection. The benefits of COVID-19 vaccination to the population outweigh the risks in terms of cardiovascular safety assessment.
Combination Venetoclax and Selinexor Effective in Relapsed Refractory Multiple Myeloma with Translocation t(11;14)
Authors: Nguyen Nina , Chaudhry Sana , Totiger Tulasigeri M. , Diaz Robert , Roberts Evan , Montoya Skye , Pardo Gabriel , Pardo Alejandro , Afaghani Jumana , Affer Maurizio , Jahn Jacob , Bradley Terrence , Maura Francesco , Kazandjian Dickran , Bilbao Daniel , Chapman Jennifer , Landgren Ola , Hoffman James , Taylor Justin 
Published: August 2022

AbstractPatients with multiple myeloma bearing translocation t(11;14) have recently been shown to benefit from the apoptosis-inducing drug venetoclax; however, the drug lacks FDA approval in multiple myeloma thus far due to a potential safety signal in the overall patient population. Selinexor is an inhibitor of nuclear export that is FDA-approved for patients with multiple myeloma refractory multiple lines of therapy. Here, we report that in four patients with multiple myeloma with t(11;14), the concomitant administration of venetoclax and selinexor was safe and associated with disease response. Moreover, the combination was synergistic in t(11;14) multiple myeloma cell lines and caused decreased levels of Cyclin D1 (which is overexpressed due to the CCND1-IGH fusion) when given in combination as compared to single agents. These data suggest that the combination of venetoclax and selinexor is effective and t(11;14) may serve as a therapeutic marker for response and target for future clinical trials.
Gene expression levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence and risk of death in cervical cancer
Authors: Bolaños-Suárez Verónica , Alfaro Ana , Espinosa Ana María , Medina-Martínez Ingrid , Juárez Eligia , Villegas-Sepúlveda Nicolás , Gudiño-Zayas Marco , Gutiérrez-Castro América , Román-Bassaure Edgar , Salinas-Nieves María Eugenia , Bruno-Muñoz Sergio , Flores-Herrera Oscar , Berumen Jaime 
Published: August 2022

AbstractBackgroundUp to 74% of patients with cervical cancer (CC) may experience recurrence after their treatment, and most of them are identified late when only the clinical parameters are used, which decreases their chances of recovery. Molecular markers can improve the prediction of clinical outcome and identify therapeutic targets in CC. Glycolysis is altered in 70% of CCs, so it could be a metabolic pathway in which molecular markers associated with the aggressiveness of CC can be identified.MethodsThe expression of 14 glycolytic genes was analyzed in 118 CC samples by microarrays, and only LDHA and PFKP were validated by qRT–PCR (n=58) and in second and third replicates by Western blotting (n=69) and immunohistochemistry (n=18).ResultsLDHA and PFKP were associated with poor overall survival [OS: LDHA HR=3.0 (95% CI= 1.1-8.2);p=2.9 × 10-2; PFKP HR=3.4 (95% CI= 1.1-10.5);p= 3.5 × 10-2] and disease-free survival [DFS: LDHA HR=2.7 (95% CI= 1.6-6.3);p=2.6 × 10-2] independent of FIGO clinical stage. The risk of death was greater when both biomarkers were overexpressed than when using only FIGO stage [HR =7 (95% CI 1.6-31.1,p=1.0 × 10-2) versus HR=8.1 (95% CI=2.6-26.1;p=4.3 × 10-4)] and increased exponentially as the expression of LDHA and PFKP increased.ConclusionsLDHA and PFKP at the mRNA and protein levels were associated with poor overall survival, disease-free survival and increased risk of death of patients with CC regardless of FIGO stage. The measurement of expression of these two markers could be very useful to evaluate the clinical evolution and the risk of death from CC and to make better therapeutic decisions at the beginning of treatment.
The Parasite Intraerythrocytic Cycle and Human Circadian Cycle are Coupled During Malaria Infection
Authors: Motta Francis C. , McGoff Kevin , Moseley Robert C. , Cho Chun-Yi , Kelliher Christina M. , Smith Lauren M. , Ortiz Michael S. , Leman Adam R. , Campione Sophia A. , Devos Nicolas , Chaorattanakawee Suwanna , Uthaimongkol Nichaphat , Kuntawunginn Worachet , Thongpiam Chadin , Thamnurak Chatchadaporn , Arsanok Montri , Wojnarski Mariusz , Vanchayangkul Pattaraporn , Boonyalai Nonlawat , Smith Philip L. , Spring Michele , Jongsakul Krisada , Chuang Ilin , Harer John , Haase Steven B. 
Published: August 2022

SummaryDuring infections with malaria parasitesP. vivax, patients exhibit rhythmic fevers every 48 hours. These fever cycles correspond with the time parasites take to traverse the Intraerythrocytic Cycle (IEC) and may be guided by a parasite-intrinsic clock. Different species ofPlasmodiahave cycle times that are multiples of 24 hours, suggesting they may be coordinated with the host circadian clock. We utilized anex vivoculture of whole blood from patients infected withP. vivaxto examine the dynamics of the host circadian transcriptome and the parasite IEC transcriptome. Transcriptome dynamics revealed that the phases of the host circadian cycle and the parasite IEC were correlated across multiple patients, suggesting that the cycles are coupled. In mouse model systems, host-parasite cycle coupling appears to provide a selective advantage for the parasite. Thus, understanding how host and parasite cycles are coupled in humans could enable anti-malarial therapies that disrupt this coupling.
Multifunctional requirements for ERK1/2 signaling in the development of ganglionic eminence derived glia and cortical inhibitory neurons
Authors: Knowles Sara J. , Holter Michael C. , Li Guohui , Bjorklund George R. , Rees Katherina P. , Martinez-Fuentes Johan S. , Nishimura Kenji J. , Afshari Ariana E. , Fry Noah , Stafford April M , Vogt Daniel , Mangone Marco , Anderson Trent , Newbern Jason M. 
Published: August 2022

AbstractThe RAS/RAF/MEK/ERK1/2 intracellular signaling pathway is activated by numerous cues during brain development and dysregulated in neurodevelopmental syndromes, particularly the RASopathies and certain forms of autism. Cortical excitatory/inhibitory imbalance is thought to be critical in the neuropathogenesis of these conditions. However, the developmental functions of ERK1/2 signaling in cortical inhibitory neurons (CINs) and other medial ganglionic eminence (MGE)-derived non-neuronal cells are poorly understood. Here, we genetically modulated ERK1/2 signaling in mouse MGE neural progenitors or GABAergic neurons in vivo. We find that MEK-ERK1/2 signaling is essential for regulating MGE-derived oligodendrocyte number in the anterior commissure. WhileErk1/2inactivation does not alter CIN number, we discovered a significant and persistent reduction in somatostatin, but not parvalbumin, expression in a subset of CINs. ERK1/2 signaling is also necessary for chemogenetic activity-dependent FOSB expression in CINs in vivo. Interestingly, one week of chronic chemogenetic stimulation in juvenile or adult animals partially rescues the decrease in somatostatin expression inErk1/2mutant CINs. Our data demonstrate ERK1/2 signaling is required for the establishment of MGE-derived glia, whereas in CINs, ERK1/2 drives activity dependent-responses and the expression of somatostatin in a subset of neurons.
Seasonal eDNA-based monitoring ofBatrachochytrium dendrobatidisand amphibian species in Norway
Authors: Ahmed Omneya , Andersson Johan , Martin-Sanchez Pedro M. , Eiler Alexander 
Published: August 2022

AbstractFreshwaters represent the most threatened environments with regard to biodiversity loss and therefore there is a need for national monitoring programs to effectively document species distribution and evaluate potential risks for vulnerable species. The monitoring of species for effective management practices is, however, challenged by insufficient data acquisition when using traditional methods. Here we present the application of environmental DNA (eDNA) metabarcoding of amphibians in combination with quantitative PCR assays for an invasive pathogenic chytrid species (Batrachochytrium dendrobatidis-Bd), a potential threat to endemic and endangered amphibian species. Statistical comparison of amphibian species detection using either traditional or eDNA-based approaches showed weak correspondence. By tracking the distribution ofBdover three years, we concluded that the risk for amphibian extinction is low sinceBdwas only detected at five sites where multiple amphibians were present over the sampled years. Our results show that eDNA-based detection can be used for simultaneous monitoring of amphibian diversity and the presence of amphibian pathogens at the national level in order to assess potential species extinction risks and establish effective management practices. As such our study represents suggestions for a national monitoring program based on eDNA.
Representing experience over time: sustained sensory patterns and transient frontroparietal patterns
Authors: Vishne Gal , Gerber Edden M. , Knight Robert T. , Deouell Leon Y. 
Published: August 2022

SummaryInstances of sustained stationary sensory input are ubiquitous. However, previous work focused almost exclusively on the transient onset responses. This presents a critical challenge for neural theories of consciousness, which should account for the full temporal extent of experience. Here we use intracranial recordings from human patients viewing diverse images in multiple durations. In sensory regions, we reveal that despite dramatic changes in activation magnitude, the distributed representation of categories and exemplars remains sustained and stable. In contrast, in frontoparietal regions we find transient content representation at stimulus onset. Our results highlight the connection between the anatomical and temporal correlates of experience. To the extent perception is sustained, it may rely on sensory representations, and to the extent it is discrete, centered on perceptual updating, it may rely on frontoparietal representations.
Nucleation and spreading rejuvenate polycomb domains every cell cycle
Authors: Veronezi Giovana M. B. , Ramachandran Srinivas 
Published: August 2022

AbstractGene repression by the polycomb pathway is essential for proper development in metazoans. Polycomb domains, characterized by trimethylation of histone H3 (H3K27me3), carry the memory of repression through successive cell divisions, and hence, need to be maintained to counter dilution during replication of parental H3K27me3 with unmodified nascent H3. Yet, how locus-specific H3K27me3 is maintained through replication is unknown. To understand H3K27me3 recovery post-replication, we first defined nucleation sites within each polycomb domain in mouse embryonic stem cells. Then, to track H3K27me3 dynamics in unperturbed cells during replication, we developed CUT&Flow, which maps H3K27me3 domains as a function of the cell cycle stage. Using CUT&Flow, we show that post-replication rejuvenation of polycomb domains occurs by nucleation and spreading, using the same nucleation sites used duringde novodomain formation. By using subunit-specific inhibitors of the PRC2 complex, we find that PRC2 need not rely on pre-existing H3K27me3 to target nucleation sites post-replication. The timing of nucleation relative to the cell cycle reflects the combination of replication timing and H3K27me3 deposition kinetics derived fromde novodomain formation. Thus, competition between H3K27me3 deposition and nucleosome turnover drives bothde novodomain formation and maintenance during every cell cycle.
Do Newly Born Orphan Proteins Resemble Never Born Proteins? A Study Using Three Deep Learning Algorithms
Authors: Liu Jing , Yuan Rongqing , Shao Wei , Wang Jitong , Silman Israel , Sussman Joel L. 
Published: August 2022

ABSTRACT‘Newly Born’proteins, devoid of detectable homology to any other proteins, known as orphan proteins, occur in a single species or within a taxonomically restricted gene family. They are generated by expression of novel Open Reading Frames, and appear throughout evolution. We were curious if the three recently developed programs for predicting protein structures, viz., AlphaFold2, RoseTTAFold, and ESMFold, might be of value for comparison of such ‘Newly Born’proteins to random polypeptides with amino acid content similar to that of native proteins, which have been called ‘Never Born’ proteins. The programs were used to compare the structures of two sets of ‘Never Born’proteins that had been expressed – Group 1, which had been shown experimentally to possess substantial secondary structure, and Group 3, which had been shown to be intrinsically disordered. Overall, the models generated were scored as being of low quality but revealed some general principles. Specifically, all four members of Group 1 were predicted to be compact by all three algorithms. The members of Group 3 were predicted to be very extended, as would be expected for intrinsically disordered proteins. The three programs were then used to predict the structures of three orphan proteins whose crystal structures had been solved, two of which display novel folds. Finally, they were used to predict the structures of seven orphan proteins with well-identified biological functions, whose 3D structures are not known. Two proteins, which were predicted to be disordered based on their sequences, are predicted by all three structure algorithms to be extended structures. The other five were predicted to be compact structures with two exceptions in the case of AlphaFold2. All three prediction algorithms make remarkably similar and high-quality predictions for one large protein, HCO_11565, from a nematode. It is conjectured that this is due to many homologs in the taxonomically restricted family of which it is a member and to the fact that theDaliserver revealed several non-related proteins with similar folds. Overall, orphan and taxonomically restricted proteins are often predicted to have compact 3D structures, sometimes with a novel fold that is a consequence of their novel sequences, which are associated with the appearance of new biological functions.
Confirming the Pro-longevity Effects of H3K4me3-deficient set-2 Mutants in Extending Lifespan in C. elegans
Authors: Silva-García Carlos G. , Mair William B. 
Published: August 2022

ABSTRACTThe COMPASS chromatin complex, which trimethylates lysine 4 on histone H3 (H3K4me3), regulates lifespan in Caenorhabditis elegans. Knockdown or partial loss-of-function of SET-2, a member of the COMPASS complex, extends the lifespan of worms. However, recent observations suggested that full loss of SET-2 methyltransferase activity via deletion of its active site reduces lifespan, indicating the degree of COMPASS inhibition may be critical to its effects on aging. To further explore these inconsistencies, we examined set-2 longevity across a range of interventions from weak to full inhibition. Via CRISPR/Cas9 genome-editing, we made two new set-2 mutants, a new genocopy of the most commonly used set-2(ok952) allele for mild set-2 inhibition, and a full set-2 genomic deletion. We found that both new strains (partial and null) and RNAi show a lifespan extension in C. elegans fed HT115 E. coli. However, neither mutant was long-lived in C. elegans fed OP50-1 E. coli. These data confirm that the previous lifespan extension observed in set-2(ok952) mutants was indeed the result of set-2 inhibition (and not a secondary linked mutation generated in the original strain). These data also indicate that a diet-dependent mechanism might contribute to the regulation of lifespan under H3K4me3 deficiency and highlight how COMPASS-mediated longevity involves a complex interaction between chromatin state and environment.
Digital color-coded molecular barcoding reveals dysregulation of common FUS and FMRP targets in soma and neurites of ALS mutant motoneurons
Authors: Garone Maria Giovanna , Salerno Debora , Rosa Alessandro 
Published: August 2022

ABSTRACTMutations in RNA binding proteins (RBPs) have been linked to the motor neuron disease amyotrophic lateral sclerosis (ALS). Extensive auto-regulation, cross-regulation, cooperation and competition mechanisms among RBPs are in place to ensure proper expression levels of common targets, often including other RBPs and their own transcripts. Moreover, several RBPs play a crucial role in the nervous system by localizing target RNAs in specific neuronal compartments. These include the RBPs FUS, FMRP and HuD. ALS mutations in a given RBP are predicted to produce a broad impact on such delicate equilibrium. Here we studied the effects of the severe FUS-P525L mutation on common FUS and FMRP targets. Expression profiling by digital color-coded molecular barcoding in cell bodies and neurites of human iPSC-derived motor neurons revealed altered levels of transcripts involved in cytoskeleton, neural projection and synapses. One of the common targets is HuD, which is upregulated because of the loss of FMRP binding to its 3’UTR due to mutant FUS competition. Notably, many genes are commonly altered upon FUS mutation or HuD overexpression, suggesting that a substantial part of the effects of mutant FUS on the motor neuron transcriptome could be due to HuD gain-of-function. Among altered transcripts we also identified other common FUS and FMRP targets, namely MAP1B, PTEN, and AP2B1, that are upregulated upon loss of FMRP binding on their 3’UTR in FUS-P525L motor neurons. This work demonstrates that the impairment of FMRP function by mutant FUS might alter the expression of several genes, including new possible biomarkers and therapeutic targets for ALS.
Coordinated cadherin functions sculpt respiratory motor circuit connectivity
Authors: Vagnozzi Alicia N. , Moore Matthew T. , Lin Minshan , Brozost Elyse M. , Ritesh KC , Agarwal Aambar , Schwarz Lindsay A. , Duan Xin , Zampieri Niccolò , Landmesser Lynn T. , Philippidou Polyxeni 
Published: August 2022

AbstractBreathing, and the motor circuits that control it, are essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm and pattern of breathing, and phrenic motor neurons (MNs), which provide the final motor output that drives diaphragm muscle contractions during inspiration. Despite their critical function, the principles that dictate how respiratory circuits assemble are unknown. Here we show that coordinated activity of a type I cadherin (N-cadherin) and type II cadherins (Cadherin-6, −9, and −10) is required in both MNs and Dbx1-derived neurons to generate robust respiratory motor output. Both MN- and Dbx1-specific cadherin inactivation during a critical developmental window results in perinatal lethality due to respiratory failure and a striking reduction in phrenic MN bursting activity. This combinatorial cadherin code is required to establish phrenic MN cell body and dendritic topography; surprisingly, however, cell body position appears to be dispensable for the targeting of phrenic MNs by descending respiratory inputs. Our findings demonstrate that type I and type II cadherins function cooperatively throughout the respiratory circuit to generate a robust breathing output and reveal novel strategies that drive the assembly of motor circuits.
Bayesian models for event-related potentials time-series and electrode correlations estimation
Authors: Busch-Moreno Simon , Fu Xiao , Roesch Etienne B. 
Published: August 2022

AbstractRecent developments on Bayesian inference and prediction for effects on event-related potentials (ERPs) stem from a wide variety of methods, including machine learning, multilevel models, and others. However, few of these approaches make use of clear estimates of the ERP voltage across time and across space (scalp). In the present article, via an iterative process, we propose Gaussian random walk (GRW) models that can estimate voltage uncertainty across time and also provide correlation matrices across electrodes. We apply these models to real ERP data from a P3b paradigm as an example. We discuss results in terms of past and current literature of both ERP estimation and electroencephalography analysis in general.
Mouse B2 SINE elements function as IFN-inducible enhancers
Authors: Horton Isabella , Kelly Conor J. , Simpson David M. , Chuong Edward B. 
Published: August 2022

ABSTRACTRegulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance of these elements in facilitating evolutionary diversification of innate immunity remains largely unexplored. Here, we investigated the mouse epigenomic response to type II interferon (IFN) signaling and discovered that elements from a subfamily of B2 SINE (B2_Mm2) contain STAT1 binding sites and function as IFN-inducible enhancers. CRISPR deletion experiments in mouse cells demonstrated that a B2_Mm2 element has been co-opted as an IFN-inducible enhancer of Dicer1 and the nearby Serpina3f and Serpina3g genes. The rodent-specific B2 SINE family is highly abundant in the mouse genome and elements have been previously characterized to exhibit promoter, insulator, and non-coding RNA activity. Our work establishes a new role for B2 elements as inducible enhancer elements that influence mouse immunity and exemplifies how lineage-specific TEs can facilitate evolutionary divergence of innate immune regulatory networks.