bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sirtuin 1 deletion increases inflammation and mortality in sepsis
Authors: Labiner Hanna E. , Sas Kelli M. , Baur Joseph A. , Sims Carrie A. 
Published: July 2022

BACKGROUND
Sepsis is a hyperinflammatory response to infection that can lead to multiorgan failure and eventually death. Often, the onset of multiorgan failure is heralded by renal dysfunction. Sirtuin 1 (SIRT1) promotes cellular stress resilience by inhibiting inflammation and promoting mitochondrial function. We hypothesize that SIRT1 plays an important role in limiting the inflammatory responses that drive organ failure in sepsis, predominantly via expression in myeloid cells.

METHODS
We performed cecal ligation and puncture (CLP) on whole body SIRT1 knockout (S1KO) and myeloid cell–specific S1KO (S1KO-LysMCre) mice on a C57BL/6J background. Serum interleukin (IL)-6 was quantified by enzyme-linked immunosorbent assay. Renal mitochondrial complex activity was measured using Oxygraph-2k (Oroboros Instruments, Innsbruck, Austria). Blood urea nitrogen (BUN) was measured from serum. Survival was monitored for up to 5 days.

RESULTS
Following CLP, S1KO mice had decreased renal mitochondrial complex I–dependent respiratory capacity (241.7 vs. 418.3 mmolO2/mg/min, p = 0.018) and renal mitochondrial complex II–dependent respiratory capacity (932.3 vs. 1,178.4, p = 0.027), as well as reduced rates of fatty acid oxidation (187.3 vs. 250.3, p = 0.022). Sirtuin 1 knockout mice also had increased BUN (48.0 mg/dL vs. 16.0 mg/dL, p = 0.049). Interleukin-6 levels were elevated in S1KO mice (96.5 ng/mL vs. 45.6 ng/mL, p = 0.028) and S1KO-LysMCre mice (35.8 ng/mL vs. 24.5 ng/mL, p = 0.033) compared with controls 12 hours after surgery. Five-day survival in S1KO (33.3% vs. 83.3%, p = 0.025) and S1KO-LysMCre (60% vs. 100%, p = 0.049) mice was decreased compared with controls.

CONCLUSION
Sirtuin 1 deletion increases systemic inflammation in sepsis. Renal mitochondrial dysfunction, kidney injury, and mortality following CLP were all exacerbated by SIRT1 deletion. Similar effects on inflammation and survival were seen following myeloid cell–specific SIRT1 deletion, indicating that SIRT1 activity in myeloid cells may be a significant contributor for the protective effects of SIRT1 in sepsis.
The apparent paradox of phenotypic diversity and shared mechanisms across dystonia syndromes
Authors: Di Fonzo Alessio , Albanese Alberto , Jinnah Hyder A. 
Published: July 2022

Purpose of review
We describe here how such mechanisms shared by different genetic forms can give rise to motor performance dysfunctions with a clinical aspect of dystonia.

Recent findings
The continuing discoveries of genetic causes for dystonia syndromes are transforming our view of these disorders. They share unexpectedly common underlying mechanisms, including dysregulation in neurotransmitter signaling, gene transcription, and quality control machinery. The field has further expanded to include forms recently associated with endolysosomal dysfunction.

Summary
The discovery of biological pathways shared between different monogenic dystonias is an important conceptual advance in the understanding of the underlying mechanisms, with a significant impact on the pathophysiological understanding of clinical phenomenology. The functional relationship between dystonia genes could revolutionize current dystonia classification systems, classifying patients with different monogenic forms based on common pathways. The most promising effect of these advances is on future mechanism-based therapeutic approaches.
Recent advances in noninvasive brain stimulation for schizophrenia
Authors: Brunelin Jérôme , Adam Ondine , Mondino Marine 
Published: July 2022

Purpose of review
Noninvasive brain stimulation has emerged in the last three decades as a promising treatment for patients with antipsychotic-resistant symptoms of schizophrenia. This review updates the latest progress in the use of noninvasive brain stimulation to treat schizophrenia symptoms.

Recent findings
Several recently published randomized-controlled trials support a long-lasting clinical effect of stimulation techniques on schizophrenia symptoms. In addition, efforts have been made in recent months to improve efficacy through several optimization strategies. Studies have tested new parameters of stimulation, such as theta burst stimulation, and alternative cortical or subcortical targets and have reported encouraging results. New forms of electrical stimulations such as alternating and random noise stimulation, have also been studied and have shown clinical and cognitive usefulness for patients. Accelerated stimulation protocols, and prospects could arise with deeper stimulation strategies.

Summary
Using brain stimulation to treat symptoms of schizophrenia seems promising and the great flexibility of the stimulation parameters leaves much room for developing optimization strategies and improving its effectiveness. Further studies need to identify the optimal parameters to maximize response rate.
Genetic determinants associated with response to clozapine in schizophrenia: an umbrella review
Authors: van der Horst Marte Z. , Papadimitriou Georgia , Luykx Jurjen J. 
Published: July 2022

Objective
Clozapine response varies widely from person to person, which may be due to inter-individual genetic variability. This umbrella review aims to summarize the current evidence on associations between pharmacodynamic genes and response to clozapine treatment.

Methods
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology, a systematic literature search was conducted in the PubMed and EMBASE databases from inception to November 2021 to identify systematic reviews and meta-analyses of studies that examined genetic determinants of clozapine response. The quality of the reviews was assessed with the AMSTAR-2 tool.

Results
From a total of 128 records, 10 studies representing nine systematic reviews and one meta-analysis met our inclusion criteria. The overall quality of the included studies was poor. All systematic reviews concluded that the results of primary studies were largely negative or conflicting. Most evidence was found for an association with clozapine response and rs6313 and rs6314 within HTR2A and rs1062613 within HTR3A in the serotonergic system.

Conclusions
Conclusive evidence for associations between genetic variants and clozapine response is still lacking. Hypothesis-generating genetic studies in large, well-characterized study populations are urgently needed to obtain more consistent and clinically informative results. Future studies may also include multi-omics approaches to identify novel genetic determinants associated with clozapine response.
Errors of Interpretation - ‘Correcting the record on the comparative efficacy of surgical masks versus respirators: Historical research findings suggesting their equivalence and used to support downgraded respiratory protection for non-ICU UK healthcare workers, resulted from unrecognised errors of arithmetic’
Authors: Wilkinson Martyn AC , Curran Evonne T , Tomlinson David R 
Published: July 2022

AbstractThe first UK ‘COVID-19 Guidance for Infection Prevention and Control (IPC) in healthcare settings’, March 2020, restricted respiratory protection equipment (RPE) to aerosol generating procedures (AGPs) and the ICU. Supportive data in a linked meta-analysis stated equivalent protection – i.e., 80% - afforded by fluid resistant surgical face masks (FRSMs) and RPE, against SARS-CoV-1 infection.Visual inspection of the meta-analysis data suggested greater healthcare worker (HCW) protection from RPE. Detailed statistical analysis confirmed significantly greater HCW protection from RPE (p<0.0009) compared to FRSMs: sadly, the meta-analysis had been subject to calculation error.Research data supporting the restriction of RPE to AGPs and the ICU were flawed. Consequently, non-ICU HCWs have been inappropriately exposed to SARS-CoV-2 aerosol inhalation transmission.To minimise HCW occupational COVID-19, UK IPC guidance should be changed to require RPE during all confirmed / suspected infectious SARS-CoV-2 patient care.
Somatostatin peptide signaling dampens cortical circuits and promotes exploratory behavior
Authors: Brockway Dakota F. , Griffith Keith R. , Aloimonos Chloe M. , Clarity Thomas T. , Moyer J. Brody , Smith Grace C. , Dao Nigel C. , Hossain Md Shakhawat , Drew Patrick J. , Gordon Joshua A. , Kupferschmidt David A. , Crowley Nicole A. 
Published: July 2022

SUMMARYSomatostatin (SST) neurons in the prelimbic (PL) cortex mediate a variety of behavioral states. However, little is known about the actions of somatostatin peptide signaling in shaping cortical functioning and behavior. Here, we sought to characterize the unique physiological and behavioral roles of the SST peptide in the PL cortex. We employed a combination ofex vivopharmacologic and optogenetic electrophysiology,in vivocalcium monitoring, andin vivopeptide pharmacology to explore the role of SST neuron and peptide signaling in the mouse PL cortex. Whole-cell slice electrophysiology was conducted in pyramidal and GABAergic neurons in the PL cortex of C57BL/6J and SST-IRES-Cre male and female mice to characterize the pharmacological mechanism of SST signaling. Fiber photometry of GCaMP6f fluorescent calcium signals from SST neurons was conducted to characterize the activity profile of SST neurons during exploration of an elevated plus maze (EPM) and open field test (OFT). We further used local delivery of both a broad SST receptor (SSTR) agonist and antagonist into bilateral PL cortex to test causal effects of SST administration and receptor blockade on these same exploratory behaviors. SSTR activation broadly hyperpolarized layer 2/3 pyramidal neurons in the PL cortex in both male and female miceex vivo, an effect that was recapitulated with optogenetic stimulation of SST neurons, through both monosynaptic and polysynaptic GABA neuron-mediated mechanisms of action. This hyperpolarization was blocked by pre-application of the SSTR antagonist cyclo-somatostatin (cyclo-SST) and was non-reversible. SST neurons in PL were activated during EPM and OFT exploration, indicating task-related recruitment of these neurons. Lastly, in line with this exploration-related activity profile, SSTR agonist administration directly into the PL enhanced open arm exploration in the EPM, whilein vivoadministration of an antagonist had no effect. Together, this work describes a broad ability for SST peptide signaling to modulate microcircuits within the prefrontal cortex and related exploratory behaviors.
MATEdb, a data repository of high-quality metazoan transcriptome assemblies to accelerate phylogenomic studies
Authors: Rosa Fernández , Vanina Tonzo , Carolina Simón Guerrero , Jesus Lozano-Fernandez , Gemma I. Martínez-Redondo , Pau Balart-García , Leandro Aristide , Klara Eleftheriadi , Carlos Vargas-Chávez 
Published: July 2022

AbstractWith the advent of high throughput sequencing, the amount of genomic data available for animals (Metazoa) species has bloomed over the last decade, especially from transcriptomes due to lower sequencing costs and easier assembling process compared to genomes. Transcriptomic data sets have proven useful for phylogenomic studies, such as inference of phylogenetic interrelationships (e.g., species tree reconstruction) and comparative genomics analyses (e.g., gene repertoire evolutionary dynamics). However, these data sets are often analyzed following different analytical pipelines, particularly including different software versions, leading to potential methodological biases when analyzed jointly in a comparative framework. Moreover, these analyses are computationally expensive and not affordable for a large part of the scientific community. More importantly, assembled transcriptomes are usually not deposited in public databases. Furthermore, the quality of these data sets is hardly ever taken into consideration, potentially impacting subsequent analyses such as orthology and phylogenetic or gene repertoire evolution inference. To alleviate these issues, we present Metazoan Assemblies from Transcriptomic Ensembles (MATEdb), a curated database of 335 high-quality transcriptome assemblies from different animal phyla analyzed following the same pipeline. The repository is composed, for each species, of (1) a de novo transcriptome assembly, (2) its candidate coding regions within transcripts (both at the level of nucleotide and amino acid sequences), (3) the coding regions filtered using their contamination profile (i.e., only metazoan content), (4) the longest isoform of the amino acid candidate coding regions, (5) the gene content completeness score as assessed against the BUSCO database, and (6) an orthology-based gene annotation. We complement the repository with gene annotations from high-quality genomes, which are often not straightforward to obtain from individual sequencing projects, totalling 423 high-quality genomic and transcriptomic data sets. We invite the community to provide suggestions for new data sets and new annotation features to be included in subsequent versions, that will be analyzed following the same pipeline and be permanently stored in public repositories. We believe that MATEdb will accelerate research on animal phylogenomics while saving thousands of hours of computational work in a plea for open and collaborative science.
Multiset correlation and factor analysis enables exploration of multi-omic data
Authors: Brown Brielin C. , Wang Collin , Kasela Silva , Aguet François , Nachun Daniel C. , Taylor Kent D. , Tracy Russell P. , Durda Peter , Liu Yongmei , Johnson W. Craig , Van Den Berg David , Gupta Namrata , Gabriel Stacy , Smith Joshua D. , Gerzsten Robert , Clish Clary , Wong Quenna , Papanicolau George , Blackwell Thomas W. , Rotter Jerome I. , Rich Stephen S. , Ardlie Kristin G. , Knowles David A. , Lappalainen Tuuli 
Published: July 2022

AbstractMulti-omics datasets are becoming more common, necessitating better integration methods to realize their revolutionary potential. Here, we introduce Multi-set Correlation and Factor Analysis, an unsupervised integration method that enables fast inference of shared and private factors in multi-modal data. Applied to 614 ancestry-diverse participant samples across five ‘omics types, MCFA infers a shared space that captures clinically relevant molecular processes.
Can static optimization detect changes in peak medial knee contact forces induced by gait modifications?
Authors: Kaneda Janelle M. , Seagers Kirsten A. , Uhlrich Scott D. , Kolesar Julie A. , Thomas Kevin A. , Delp Scott L. 
Published: July 2022

AbstractMedial knee contact force (MCF) is related to the pathomechanics of medial knee osteoarthritis. However, MCF cannot be directly measured in the native knee, making it difficult for therapeutic gait modifications to target this metric. Static optimization, a musculoskeletal simulation technique, can estimate MCF, but there has been little work validating its ability to detect changes in MCF induced by gait modifications. In this study, we quantified the error in MCF estimates from static optimization compared to measurements from instrumented knee replacements during normal walking and seven different gait modifications. We then identified minimum magnitudes of simulated MCF changes for which static optimization correctly identified the direction of change at least 70% of the time. A full-body musculoskeletal model with a multi-compartment knee and a custom static optimization implementation was used to estimate MCF. Simulations were evaluated using experimental data from three subjects for a total of 115 steps. Static optimization underpredicted the first peak (mean absolute error = 0.16 bodyweights) and overpredicted the second peak (mean absolute error = 0.31 bodyweights) of MCF. Average root mean square error in MCF over stance phase was 0.32 bodyweights. Static optimization detected the direction of change with at least 70% accuracy for early-stance reductions, late-stance reductions, and early-stance increases in peak MCF of 0.10 bodyweights and greater. These results suggest that a simple static optimization approach accurately detects directional effects on early-stance medial knee loading, potentially making it a valuable tool for evaluating the biomechanical efficacy of gait modifications for knee osteoarthritis.
All-optical observation on activity-dependent nanoscale dynamics of myelinated axons
Authors: Kwon Junhwan , Lee Sungho , Jo Yongjae , Choi Myunghwan 
Published: July 2022

ABSTRACTIn the mammalian brain, rapid conduction of neural information is supported by the myelin, whose functional efficacy shows steep dependence on its nanoscale cytoarchitecture. Although previous in vitro studies suggested that neural activity accompanies nanometer-scale cellular deformations, it has remained unexplored whether neural activity can dynamically remodel the myelinated axon due to the technical challenge in observing its nanostructural dynamics in living tissues. To this end, we introduced a novel all-optical approach combining a nanoscale dynamic readout based on spectral interferometry and optogenetic control of neural excitation on a living brain slice preparation. In response to optogenetically evoked neuronal burst firing, the myelinated axons exhibited progressive and reversible spectral redshifts, corresponding to the transient swelling at a subnanometer scale. We further revealed that the activity-dependent nanostructural dynamics was localized to the paranode. In summary, our novel all-optical studies substantiate that myelinated axon exhibits activity-dependent nanoscale swelling, which potentially serves to dynamically tune the transmission speed of neural information.RESEARCH SUMMARIESAs neural activity involves rapid ion flux across the cell membrane, researchers have long been tried to detect the accompanying nanoscale morphological dynamics. However, measuring the activity-dependent nanostructural dynamics in the living mammalian brain has been an enigma due to the technical limitations. By combining excitatory optogenetics and in situ nanoscale metrology based on spectral interference, we demonstrate the first direct observation that the mammalian axons exhibit transient activity-dependent swelling at subnanometer-scale.
Spindle-dependent memory consolidation in healthy adults: A meta-analysis
Authors: Kumral Deniz , Matzerath Alina , Leonhart Rainer , Schönauer Monika 
Published: July 2022

Accumulating evidence suggests a central role for sleep spindles in the consolidation of new memories. However, no metaanalysis of the association between sleep spindles and memory performance has been conducted so far. Here, we report meta-analytical evidence for spindle-memory associations and investigate how multiple factors, including memory type, spindle type, spindle characteristics, and EEG topography affect this relationship. The literature search yielded 53 studies reporting 1427 effect sizes, resulting in a small to moderate effect for the average association. We further found that spindle-memory associations were significantly stronger for procedural memory than for declarative memory. Neither spindle types nor EEG scalp topography had an impact on the strength of the spindle-memory relation, but we observed a distinct functional role of global and fast sleep spindles, especially for procedural memory. We also found a moderation effect of spindle characteristics, with power showing the largest effect sizes. Collectively, our findings suggest that sleep spindles are involved in learning, thereby representing a general physiological mechanism for memory consolidation.HighlightsSpindle measures showed a small to medium-sized association with memory performance.This relationship was stronger for procedural memory than declarative memory.No moderation effects of spindle type and EEG scalp topography have been observed.Spindle power emerged as the strongest predictors.Naps showed similar spindle-related consolidation mechanisms to whole-night sleep.
Neuromorphic Model of Hippocampus Place cells using an Oscillatory Interference Technique for Hardware Implementation
Authors: Chen Zhaoqi , Nasrallah Alia , Alemohammad Milad , Furuta Masanori , Etienne-Cummings Ralph 
Published: July 2022

AbstractIn this paper, we propose a simplified and robust model for Place cell generation based on the Oscillatory Interference (OI) model concept. Aiming toward hardware implementation in bio-inspired Simultaneous Localization and Mapping (SLAM) systems for mobile robotics, we base our model on logic operations that reduce its computational complexity. The model compensates for parameter variations in the behaviors of the population of constituent Theta cells, and allows the Theta cells to have square-wave oscillation profiles. The robustness of the model, with respect to mismatch in the Theta cell’s base oscillation frequency and gain—as a function of modulatory inputs—is demonstrated. Place cell composed of 48 Theta cells with base frequency variations with a 25% standard deviation from the mean and a gain error with 20% standard deviation from the mean only result in a 20% deformations within the place field and 0.24% outer side lobes, and an overall pattern with 0.0015 mean squared error on average. We also present how the model can be used to achieve the localization and path-tracking functionalities of SLAM.
Cannabidiol prevents spontaneous fear recovery after extinction and ameliorates stress-induced extinction resistance
Authors: Papagianni Eleni P. , Warren William G. , Cassaday Helen J. , Stevenson Carl W. 
Published: July 2022

AbstractCannabidiol, the main non-psychotropic constituent of cannabis, has potential as a treatment for anxiety-related disorders since it reduces learned fear expression and enhances fear extinction. The return of fear over time after successful extinction and stress-induced extinction resistance are potential barriers to the treatment of these disorders with extinction-based psychological therapy. In two experiments using rats subjected to auditory fear conditioning, we determined the effects of systemic cannabidiol treatment on (1) delayed extinction and later spontaneous fear recovery, and (2) extinction resistance caused by immediate extinction (the immediate extinction deficit (IED)). In Experiment 1, cannabidiol was given before delayed extinction occurring 24 hr after conditioning, with extinction recall and spontaneous fear recovery tested drug-free 1 and 21 days after extinction, respectively. We found that cannabidiol had no effect on extinction recall but it prevented spontaneous fear recovery. In Experiment 2, the IED procedure was first validated, with immediate extinction occurring 30 min after conditioning. We confirmed that immediate extinction impaired extinction recall, compared to delayed extinction. Next, cannabidiol was given before immediate or no extinction, with extinction recall tested drug-free the next day. We found that cannabidiol rescued the IED, which did not involve effects on fear memory consolidation. In summary, cannabidiol prevented spontaneous fear recovery after delayed extinction and ameliorated extinction resistance caused by immediate extinction. Although the pharmacological mechanisms underlying these effects remain to be determined, our results add to evidence indicating that cannabidiol might prove useful as an adjunct for potentiating the psychological treatment of anxiety-related disorders.