bluuebunny/crossref_metadata_2025_split huggingface dataset:
Placebo Effect in Randomized Trials of Major Depressive Disorder With Psychotic Features
Authors: Perivolaris Argyrios , Ainsworth Nicholas J. , Alexopoulos George S. , Bingham Kathleen S. , Flint Alastair J. , Marino Patricia , Neufeld Nicholas H. , Rothschild Anthony J. , Voineskos Aristotle N. , Whyte Ellen M. , Mulsant Benoit H. ,   on behalf of the STOP-PD II Study Group
Published: August 2022

Abstract

Background
In the 1980s, the response rate of major depressive disorder with psychotic features (MDD-Psy) to placebo pills was reported to be close to 0%. To our knowledge, this placebo response rate has not been systematically reassessed. We undertook a systematic review of randomized controlled trials (RCTs) that have used a placebo or sham control group for MDD-Psy.

Methods
We searched MEDLINE and identified 9 relevant publications reporting on 10 studies comparing a placebo or sham interventions versus an active intervention. We extracted reported rates of response or of dropout for all causes associated with placebo versus active intervention(s) and aggregated response and dropout rates across trials.

Results
Two sham-controlled electroconvulsive therapy (ECT) trials did not provide response rates. In the 3 pharmacotherapy studies published in the 1980s, 0 of 12 participants (0%) responded to placebo versus 13 of 38 (34.2%) responding to the active interventions. In contrast, 5 RCTs published in the 2000s, 114 of 339 participants (33.6%) randomized to placebo responded versus 149 of 373 participants (39.9%) randomized to active interventions; dropout rates were 71/236 (30.1%) for placebo versus 84/282 (29.8%) for the active interventions.

Conclusions
As expected, response rates to placebo pills in RCTs for MDD-Psy increased markedly from the 1980s to the 2000s. Methodological issues in the design and conduct of more recent RCTs may have contributed to the high placebo response. However, one needs to consider this placebo response rate when interpreting the result of recent trials of MDD-Psy, which typically have not included a “pure” placebo condition.
Outcomes and Predictors of Sustained Remission After Drug Withdrawal in Pediatric Crohn Disease
Authors: Stein Ronen , Daniel Scott G. , Baldassano Robert N. , Feigenbaum Kara , Kachelries Kelly , Sigall‐Boneh Rotem , Weston Sarah , Levine Arie , Bittinger Kyle 
Published: August 2022

Objectives:The primary aim of this study was to determine the proportion of pediatric Crohn disease (CD) subjects in sustained drug‐free remission 52 weeks after stopping pharmacological therapy. We also aimed to explore the effects of the Crohn Disease Exclusion Diet (CDED) and microbiome composition on remission.Methods:We performed a prospective study following 18 CD patients ages 13–21 years in deep clinical remission withdrawing from immunomodulator (n = 7) or anti‐TNFα (n = 11) monotherapy at two tertiary care centers. Stool for calprotectin and microbiome analyses was collected over 52 weeks. Participants followed either the CDED or free diet after drug withdrawal. The primary endpoint was sustained relapse‐free drug‐free remission (calprotectin <250 µg/g) at 52 weeks.Results:Seventeen participants were followed through 52 weeks with 11 (64.7%) in sustained remission. There was no improvement in remission among participants following the CDED (5/9; 55.6%), P = 0.63. By 104 weeks, only 8 (47.1 %) participants remained off immunosuppressive therapies. Analysis of shotgun metagenomic sequence data revealed that taxonomic and gene function abundance in the gut microbiome was relatively stable for participants in remission and relapse. However, a predictive model incorporating gut microbial gene pathway abundance for amino sugar/nucleotide sugar metabolism and galactose metabolism from baseline samples predicted relapse at 52 weeks with 80% accuracy.Conclusions:After withdrawal of immunomodulator or anti‐TNFα monotherapy among a small cohort of pediatric CD subjects in deep remission, nearly 65% sustained remission at 52 weeks. Baseline microbiome alterations predicted relapse. Large prospective studies are needed to better understand outcomes after treatment de‐escalation.
Scalable Bayesian functional GWAS method accounting for multivariate quantitative functional annotations with applications to studying Alzheimer’s disease
Authors: Chen Junyu , Wang Lei , De Jager Philip L. , Bennett David A. , Buchman Aron S. , Yang Jingjing 
Published: August 2022

AbstractExisting methods for integrating functional annotations in GWAS to fine-map and prioritize potential causal variants are either limited to using non-overlapped categorical annotations, or limited by the computation burden of modeling genome-wide variants. To overcome these limitations, we propose a scalable Bayesian functional GWAS method to account for multivariate quantitative functional annotations (BFGWAS_QUANT), accompanied by a scalable computation algorithm enabling joint modeling of genome-wide variants. Simulation studies validated the performance of BFGWAS_QUANT for accurately quantifying annotation enrichment and improving GWAS power. Applying BFGWAS_QUANT to study five Alzheimer’s disease (AD) related phenotypes using individual-level GWAS data (n=∼1K), we found that histone modification annotations have higher enrichment than eQTL annotations for all considered phenotypes, with the highest enrichment in H3K27me3 (polycomb regression). We also found that cis-eQTL in microglia had higher enrichment than eQTL of bulk brain frontal cortex tissue for all considered phenotypes. A similar enrichment pattern was also identified using the IGAP summary-level GWAS data of AD (n=∼54K). The strongest known APOE E4 risk allele was identified for all five phenotypes and the APOE locus was validated using the IGAP data. BFGWAS_QUANT fine-mapped 32 significant variants from 1073 genome-wide significant variants in the IGAP data. We further demonstrated that the polygenic risk scores (PRS) using effect size estimates by BFGWAS_QUANT had similar prediction accuracy as other methods assuming a sparse causal model. Overall, BFGWAS_QUANT provides a useful GWAS tool for quantifying annotation enrichment and prioritizing potential causal variants.
Comparative Analysis of Reported Deaths Cases Associated with the New Coronavirus COVID-19 Pandemic in the South Caucasus Countries (Armenia, Azerbaijan, Georgia) from March 2020 to May 2022
Authors: Amiranashvili Avtandil G. , Khazaradze Ketevan R. , Japaridze Nino D. 
Published: August 2022

AbstractThe results of a statistical analysis of daily, total by days of the week and monthly data on officially reported deaths cases from the new coronavirus COVID-19 in the countries of the South Caucasus (Armenia, Azerbaijan, Georgia) from March 12, 2020 to May 31, 2022 are presented. All data are normalized per 1 million populations (mortality rate, hereinafter, this normalization is assumed everywhere). In particular, the following results were obtained.The daily mortality rate in Armenia averaged 3.591 (range: 0-23.622), in Azerbaijan - 1.184 (range: 0-10.969), in Georgia - 5.596 (range: 0-23.189). The total monthly mortality rate in Armenia averaged 107.9 (variability range: 1.01-415.4), in Azerbaijan - 35.6 (variability range: 0.39-122.9), in Georgia - 168.1 (variability range: 0-547.4).A direct linear correlation was observed between the indicated countries in cases of daily and total monthly mortality.An analysis of the intraweek course of mortality showed that in Armenia, on weekdays, the average daily mortality is 4.319, and on weekends - 3.477 (an increase compared to weekends by about 24%); in Azerbaijan, on weekdays and weekends, the average daily mortality is 1.368 and 1.421, respectively (the difference is insignificant); in Georgia on weekdays, the average daily mortality is 7.558, and on weekends - 6.855 (an increase of about 10% compared to weekends).
Development and implementation of a clinical decision support system tool for the evaluation of suspected monkeypox infection
Authors: Albin John S. , Lazarus Jacob E , Hysell Kristen M. , Rubins David M. , Germaine Lindsay , Dugdale Caitlin M. , Heller Howard M. , Hohmann Elizabeth L. , Baugh Joshua J. , Shenoy Erica S. 
Published: August 2022

ABSTRACTMonkeypox virus was historically rare outside of West and Central Africa until the current 2022 global outbreak, which has required clinicians to be alert to identify individuals with possible monkeypox, institute isolation, and take appropriate next steps in evaluation and management. Clinical decision support systems (CDSS), which have been shown to improve adherence to clinical guidelines, can support frontline clinicians in applying the most current evaluation and management guidance in the setting of an emerging infectious diseases outbreak when those guidelines are evolving over time. Here we describe the rapid development and implementation of a CDSS tool embedded in the electronic health record to guide frontline clinicians in the diagnostic evaluation of monkeypox infection and triage patients with potential monkeypox infection to individualized infectious diseases physician review. We also present data on the initial performance of this tool in a large integrated healthcare system.
Mitochondrial DNA haplogroup variation in hydrocephalus
Authors: Munch Tina N , Hedley Paula L , Hagen Christian M , Elson Joanna , Bækvad-Hansen Marie , Geller Frank , Bybjerg-Grauholm Jonas , Nordentoft Merete , Børglum Anders , Mortensen Preben B , Werge Thomas M , Melbye Mads , Hougaard David M , Christiansen Michael 
Published: August 2022

AbstractHydrocephalus is a genetically and phenotypically heterogenous condition with complex etiology. Ciliary dysfunction has been shown to play a role, either through interference with signaling functions in primary cilia, cerebrospinal fluid flow by motile cilia, or both. Ciliary function is highly energy-dependent, consequently, variation in mitochondrial OXPHOS function might be a susceptibility factor for hydrocephalus. Furthermore, familial hydrocephalus exhibits preferential maternal inheritance. Mitochondrial DNA (mtDNA) haplogroups, have been associated with different characteristics of OXPHOS function as well as susceptibility to autism spectrum disorders, a frequent co-morbidity of hydrocephalus. This nested case-cohort study, a substudy of the iPSYCH study, used mtDNA data from 191 hydrocephalus cases and 24,831 population controls and found no association between hydrocephalus and any mtDNA haplogroup. Likewise, the distribution of European macro-haplogroups, HV, JT, and UK, did not differ between 172 hydrocephalus cases and 21,850 population controls. Thus, mtDNA haplogroups are not susceptibility factors for hydrocephalus.
Increased GDF11 expression associated with increased survival of Grade 3 Gliomas
Authors: Lehrer Steven , Rheinstein Peter H. 
Published: August 2022

AbstractBackgroundInfusing young mouse blood into old mice makes the old mice biologically younger. When an old mouse and a young mouse share a circulatory system, the old mouse’s muscle function is improved, and the production of olfactory neurons is increased. GDF11 seems to be a crucial element of the young blood in both instances.MethodsBecause of GDF11’s potential neuroprotective actions, we used The Cancer Genome Atlas (TCGA) to assess the effect of GDF11 expression in malignant gliomas. We analyzed the GDC TCGA lower grade glioma data set. To access TCGA data we used the Xena platform and cBioportal. Statistical analysis was done with SPSS v26.Resultsincreased GDF11 expression in IDH1 mutant subjects was significant. There was significantly increased survival (p = 0.00065, log rank test) with high GDF11 expression in grade 3 gliomas. The survival effect was less prominent in grade 2 gliomas. GDF11 gene expression was highest in anaplastic oligodendrogliomas and mixed gliomas with 1p 19q co-deletions and few or no TP53 or ATRX mutations. GDF11 gene expression was lowest in anaplastic astrocytomas with no 1p 19q co-deletions and many TP53 and ATRX mutations.ConclusionGDF11 or an analogue might be therapeutic in grade 3 glioma. GDF11 does not cross the blood brain barrier but affects the brain by acting on brain endothelial cells. GDF11 might be delivered to a brain tumor intranasally.
Genome-Wide Association Study Finds Multiple Loci Associated with Intraocular Pressure in HS Rats
Authors: Fowler Samuel , Wang Tengfei , Munro Daniel , Kumar Aman , Chitre Apurva S. , Hollingsworth TJ , Martinez Angel Garcia , St. Pierre Celine L. , Bimschleger Hannah , Gao Jianjun , Cheng Riyan , Mohammadi Pejman , Chen Hao , Palmer Abraham A. , Polesskaya Oksana , Jablonski Monica M. 
Published: August 2022

AbstractElevated intraocular pressure (IOP) is influenced by environmental and genetic factors. Increased IOP is a major risk factor for most types of glaucoma, including primary open angle glaucoma (POAG). Investigating the genetic basis of IOP may lead to a better understanding of the molecular mechanisms of POAG. The goal of this study was to identify genetic loci involved in regulating IOP using outbred heterogeneous stock (HS) rats. HS rats are a multigenerational outbred population derived from eight inbred strains that have been fully sequenced. This population is ideal for genome-wide association studies (GWASs) owing to the accumulated recombinations among well-defined haplotypes, the relatively high allele frequencies, the accessibility to a large collection of tissue samples, and the large allelic effect size compared to human studies. Both male and female HS rats (N=1,812) were used in the study. Genotyping-by-sequencing was used to obtain ~3.5 million single nucleotide polymorphisms (SNP) from each individual. SNP heritability for IOP in HS rats was 0.32, which agrees with other studies. We performed a GWAS for the IOP phenotype using a linear mixed model and used permutation to determine a genome-wide significance threshold. We identified three genome-wide significant loci for IOP on chromosomes 1, 5, and 16. Next, we sequenced the mRNA of 51 whole eye samples to find cis-eQTLs to aid in identification of candidate genes. We report 5 candidate genes within those loci:Tyr,Ctsc,Plekhf2,Ndufaf6 and Angpt2.Tyr,Ndufaf6andAngpt2genes have been previously implicated by human GWAS of IOP-related conditions.CtscandPlekhf2genes represent novel findings that may provide new insight into the molecular basis of IOP. This study highlights the efficacy of HS rats for investigating the genetics of elevated IOP and identifying potential candidate genes for future functional testing.Contribution to the field statementGlaucoma is the leading cause of irreversible blindness worldwide. Intraocular pressure (IOP) is the only known modifiable risk factor. This study describes results of the genome-wide association study (GWAS) performed in outbred rats that identifies known and novel genes involved in IOP regulation. To our knowledge, this is the first GWAS performed for IOP in a rat model. Identifying novel candidate genes in the rat model provides insight into the risk factors for glaucoma in humans and potential pharmacological targets for regulating IOP. The rat model is advantageous for studying natural variations in IOP, controlling environmental exposures, and providing easier access to tissue that can be used in phenotyping and gene expression in future studies.
Genomic health is dependent on long-term population demographic history
Authors: Wootton Eric , Robert Claude , Taillon Joëlle , Côté Steeve , Shafer Aaron B.A. 
Published: August 2022

AbstractCurrent genetic methods of population assessment in conservation biology have been challenged by genome-scale analyses due to their quantitatively novel insights. These analyses include assessments of runs-of-homozygosity (ROH), genomic evolutionary rate profiling (GERP), and mutational load. Here, we aim to elucidate the relationships between these measures using three divergent ungulates: the white-tailed deer, caribou, and mountain goat. The white-tailed deer is currently expanding, while caribou are in the midst of a significant decline. Mountain goats remain stable, having suffered a large historical bottleneck. We assessed genome-wide signatures of inbreeding using the inbreeding coefficientFand %ROH (FROH) and identified evolutionarily constrained regions with GERP. Mutational load was estimated by identifying mutations in highly constrained elements (CEs) and sorting intolerant from tolerant (SIFT) mutations. Our results show thatFandFROHare higher in mountain goats than in caribou and white-tailed deer. Given the extended bottleneck and lowNeof the mountain goat, this supports the idea that the genome-wide effects of demographic change take time to accrue. Similarly, we found that mountain goats possess more highly constrained CEs and the lowest dN/dS values, both of which are indicative of greater purifying selection; this is also reflected by fewer mutations in CEs and deleterious mutations identified by SIFT. In contrast, white-tailed deer presented the highest mutational load with both metrics, in addition to dN/dS, while caribou were intermediate. Our results demonstrate that extended bottlenecks may lead to reduced diversity and increasedFROHin ungulates, but not necessarily the accumulation of deleterious alleles, likely due to the purging of deleterious alleles in small populations.
FSTest: an efficient tool for cross-population fixation index estimation on variant call format files
Authors: Vahedi Seyed Milad , Salek Ardestani Siavash 
Published: August 2022

AbstractFixation index (Fst) statistics provide critical insights into the evolutionary processes affecting the structure of genetic variation within and among populations. The Fst statistics have been widely applied in population and evolutionary genetics to identify genomic regions targeted by selection pressures. The FSTest 1.3 software was developed to estimate four Fst statistics of Hudson, Weir and Cockerham, Nei, and Wright using high-throughput genotyping or sequencing data. Here, we introduced FSTest 1.3 and compared its performance with two widely used software of VCFtools 0.1.16 and PLINK 2.0. Chromosome 1 of 1000 Genomes Phase III variant data belonging to South Asian (N = 211) and African (N = 274) populations were included as an example case in this study. Different Fst estimates were calculated for each single nucleotide polymorphism (SNP) in a pairwise comparison of South Asian against African populations, and the results of FSTest 1.3 were confirmed by VCFtools 0.1.16 and PLINK 2.0. Two different sliding window approaches, one based on a fixed number of SNPs and another based on a fixed number of base pair (bp) were conducted using FSTest 1.3 and VCFtools 0.1.16. Our results showed that regions with low coverage genotypic data could lead to an overestimation of Fst in sliding window analysis using a fixed number of bp. FSTest 1.3 could mitigate this challenge by estimating the average of consecutive SNPs along the chromosome. FSTest 1.3 allows direct analysis of VCF files with a small amount of code and can calculate Fst estimates on a desktop computer for more than a million SNPs in a few minutes. FSTest 1.3 is freely available athttps://github.com/similab/FSTest.
Analysis of the complete genome sequence forHalococcus dombrowskiiATCC BAA-364T
Authors: Lim Sung W. , Maurais Elizabeth G. , Farwell Ashlyn C. , Barber Nicolette , Olsen Abbey J. , Shalygina Kristina F. , Omeragic Medina , Fedorov Eugenia A. , MacLea Kyle S. 
Published: August 2022

ABSTRACTWe describe sequencing and assembly of completeHalococcus dombrowskiiH4T(=ATCC BAA-364T) genome using short- and long-read sequencing technologies. The first closed genome within its genus is composed of a 2,767,537 bp chromosome and five additional plasmids totalling 3,965,466 bp, with GC content of 62.18%. The genome contains 4,029 genes, 3,963 coding sequences and two CRISPR arrays. Unusually, this Euryarchaeote carries multiple rRNA operons with divergent ITS identities across both its chromosome and plasmids.
Centripetal integration of past events by hippocampal astrocytes and its regulation by the locus coeruleus
Authors: Rupprecht Peter , Duss Sian N , Becker Denise , Lewis Christopher M , Bohacek Johannes , Helmchen Fritjof 
Published: August 2022

AbstractAn essential feature of neurons is their ability to centrally integrate information from their dendrites. The activity of astrocytes, in contrast, has been described as mostly uncoordinated across cellular compartments without clear central integration. Here, we describe conditional centripetal integration as a principle of how astrocytes integrate calcium signals from their distal processes to induce somatic activation. We found in mouse hippocampus that global astrocytic activity, as recorded with population calcium imaging, is well explained as a leaky integration of past neuronal and behavioral events on a timescale of seconds. Salient past events, indicated by pupil dilations, facilitated propagation of calcium signals from distal processes to the soma on this slow timescale. Centripetal propagation was reproduced by optogenetic activation of the locus coeruleus, a key regulator of arousal, and reduced by pharmacological inhibition of α1-adrenergic receptors. Together, our results establish astrocytes as computational units of the brain that slowly and conditionally integrate calcium signals to activate their somata upon behaviorally relevant events.
Adverse effects of hunting with hounds on participating animals and human bystanders
Authors: Treves Adrian , Menefee Laura 
Published: August 2022

AbstractHunting mammals with hounds is little studied. We present two datasets consisting of quantitative and qualitative data from self-selected respondents. The first came from hound handlers’ reports of hound injuries with post hoc verifications by government agents. The second came from by-standers reporting eyewitness encounters with hounds or handlers. Self-selected samples cannot be used to extrapolate rates in space or time but do provide nuances of human-animal and human-human interactions. From In the state of Wisconsin, USA, we describe government data on 176 hounds reported to have suffered injury during encounters with wolves. The government did not collect data on wolves or other non-target animals that may have been injured during these encounters. We investigate two wolf-centered hypotheses for wolf-hound interactions, find little support for either, and propose new hound-centered hypotheses. We also describe 105 human bystanders’ reports of experiences with hounds, handlers, and law enforcement agents.
UFCG: database of universal fungal core genes and pipeline for genome-wide phylogenetic analysis of fungi
Authors: Kim Dongwook , Gilchrist Cameron L.M. , Chun Jongsik , Steinegger Martin 
Published: August 2022

ABSTRACTIn phylogenomics the evolutionary relationship of organisms is studied by their genomic information. A common approach to phylogenomics is to extract related genes from each organism, build a multiple sequence alignment and then reconstruct evolution relations through a phylogenetic tree. Often a set of highly conserved genes occurring in single-copy, called core genes, are used for this analysis, as they allow efficient automation within a taxonomic clade. Here we introduce the Universal Fungal Core Genes (UFCG) database and pipeline for genome-wide phylogenetic analysis of fungi. The UFCG database consists of 61 curated fungal marker genes, including a novel set of 41 computationally derived core genes and 20 canonical genes derived from literature, as well as marker gene sequences extracted from publicly available fungal genomes. Furthermore, we provide an easy-to-use, fully automated and open-source pipeline for marker gene extraction, training and phylogenetic tree reconstruction. The UFCG pipeline can identify marker genes from genomic, proteomic and transcriptomic data, while producing phylogenies consistent with those previously reported, and is publicly available together with the UFCG database athttps://ufcg.steineggerlab.com.