bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordinated Cortical Thickness Alterations across Psychiatric Conditions: A Transdiagnostic ENIGMA Study
Authors: Hettwer MD , Larivière S , Park BY , van den Heuvel OA , Schmaal L , Andreassen OA , Ching CRK , Hoogman M , Buitelaar J , Veltman DJ , Stein DJ , Franke B , van Erp TGM ,   ENIGMA ADHD Working Group,   ENIGMA Autism Working Group,   ENIGMA Bipolar Disorder Working Group,   ENIGMA Major Depression Working Group,   ENIGMA OCD Working Group,   ENIGMA Schizophrenia Working Group, Jahanshad N , Thompson PM , Thomopoulos SI , Bethlehem RAI , Bernhardt BC , Eickhoff SB , Valk SL 
Published: February 2022

ABSTRACTIntroductionMental disorders are increasingly conceptualized as overlapping spectra with underlying polygenicity, neurodevelopmental etiology, and clinical comorbidity. They share multi-level neurobiological alterations, including network-like brain structural alterations. However, whether alteration patterns covary across mental disorders in a biologically meaningful way is currently unknown.MethodsWe accessed summary statistics on cortical thickness alterations from 12,024 patients with six mental disorders and 18,969 controls from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. First, we studied cortical thickness co-alteration networks as a form of pathological structural covariance. We identified regions exhibiting high inter-regional covariance across disorders (‘hubs’), and regions that strongly connect to these hubs facilitating network spreading of disease effects (‘epicenters’). Next, we applied manifold learning to reveal organizational gradients guiding transdiagnostic patterns of illness effects. Last, we tested whether these gradients capture differential cortical susceptibility with respect to normative cortical thickness covariance, cytoarchitectonic, transcriptomic, and meta-analytical task-based profiles.ResultsCo-alteration network hubs were linked to normative connectome hubs and anchored to prefrontal and temporal disease epicenters. The principal gradient derived from manifold learning captured maximally different embedding of prefrontal and temporal epicenters within co-alteration networks, followed a normative cortical thickness gradient, and established a transcriptomic link to cortico-cerebello-thalamic circuits. Moreover, gradients segregated functional networks involved in basic sensory, attentional/perceptual, and domain-general cognitive processes, and distinguished between regional cytoarchitectonic profiles.ConclusionTogether, our findings indicate that disease impact occurs in a synchronized fashion and along multiple levels of hierarchical cortical organization. Such axes can help to disentangle the different neurobiological pathways underlying mental illness.
Fading of brain network fingerprint in Parkinson’s disease predicts motor clinical impairment
Authors: Troisi Lopez E , Minino R , Liparoti M , Polverino A , Romano A , De Micco R , Lucidi F , Tessitore A , Amico E , Sorrentino G , Jirsa V , Sorrentino P 
Published: February 2022

AbstractThe clinical connectome fingerprint (CCF) was recently introduced as a way to assess brain dynamics and used to predict the cognitive decline in preclinical Alzheimer’s disease. In this paper we explore the performance of CCF in 47 Parkinson’s disease (PD) patients and 47 healthy controls, under the hypothesis that patients would show reduced identifiability as compared to controls, and that such reduction could be used to predict motor impairment. Using source-reconstructed magnetoencephalography signals, we built functional connectomes and observed reduced identifiability in patients compared to healthy individuals in the beta band. Furthermore, we found that the reduction in identifiability was proportional to the motor impairment, assessed through the Unified Parkinson’s Disease Rating Scale, and, interestingly, able to predict it (at the subject level). Along with previous evidence, this paper shows that CCF captures disrupted dynamics in neurodegenerative diseases and is particularly effective in predicting motor clinical impairment in PD.
Transparency and reporting characteristics of COVID-19 randomized controlled trials
Authors: Kapp Philipp , Esmail Laura , Ghosn Lina , Ravaud Philippe , Boutron Isabelle 
Published: February 2022

AbstractRandomized controlled trials (RCTs) are essential to support clinical decision making. We assessed the transparency, completeness and consistency of reporting of 244 reports (120 peer-reviewed journal publications; 124 preprints) of RCTs assessing pharmacological interventions for the treatment of COVID-19 published the first 17 months of the pandemic (up to May 31, 2021). Transparency was poor. Only 55% of trials were prospectively registered; 39% made their full protocols available and 29% provided access to their statistical analysis plan. Only 6% completely reported the most important information. Primary outcome(s) reported in trial registries and published reports were inconsistent in 47% of trials. Of the 124 RCTs published as preprint, 76 were secondarily published in a peer-reviewed journal. There was no major improvement after the peer-review process.Lack of transparency, completeness and consistency of reporting is an important barrier to trust, interpretation and synthesis in COVID-19 clinical trials.
Increase in coercive measures in psychiatric hospitals in Germany during the COVID-19 Pandemic
Authors: Flammer Erich , Eisele Frank , Hirsch Sophie , Steinert Tilman 
Published: February 2022

AbstractObjectiveTo examine whether the pandemic in 2020 caused changes in psychiatric hospital cases, the percentage of patients exposed to coercive interventions, and aggressive incidents.MethodsWe used the case registry for coercive measures of the State of Baden-Wuerttemberg, comprising case-related data on mechanical restraint, seclusion, physical restraint, and forced medication in each of the State’s 31 licensed hospitals treating adults, to compare data from 2019 and 2020.ResultsThe number of cases in adult psychiatry decreased by 7.6% from 105,782 to 97,761. The percentage of involuntary cases increased from 12.3 to 14.1%, and the absolute number of coercive measures increased by 4.7% from 26,269 to 27,514. The percentage of cases exposed to any kind of coercive measure increased by 24.6% from 6.5 to 8.1%, and the median cumulative duration per affected case increased by 13.1% from 12.2 to 13.8 hrs, where seclusion increased more than mechanical restraint. The percentage of patients with aggressive incidents, collected in 10 hospitals, remained unchanged.ConclusionsWhile voluntary cases decreased considerably during the pandemic, involuntary cases increased slightly. However, the increased percentage of patients exposed to coercion is not only due to a decreased percentage of voluntary patients, as the duration of coercive measures per case also increased. The changes that indicate a deterioration in treatment quality were probably caused by the multitude of measures to manage the pandemic. The focus of attention has shifted from prevention of coercion to prevention of infection.
The accuracy of machine learning models using ultrasound images in prostate cancer diagnosis: A systematic review
Authors: Sihotang Retta C , Agustino Claudio , Huang Ficky , Parikesit Dyandra , Rahman Fakhri , Hamid Agus Rizal AH 
Published: February 2022

ABSTRACTProstate Cancer (PCa) is the third most commonly diagnosed cancer worldwide, and its diagnosis requires many medical examinations, including imaging. Ultrasound offers a practical and cost-effective method for prostate imaging due to its real-time availability at the bedside. Nowadays, various Artificial Intelligence (AI) models, including Machine learning (ML) with neural networks, have been developed to make an accurate diagnosis. In PCa diagnosis, there have been many developed models of ML and the model algorithm using ultrasound images shows good accuracy. This study aims to analyse the accuracy of neural network machine learning models in prostate cancer diagnosis using ultrasound images. The protocol was registered with PROSPERO registration number CRD42021277309. Three reviewers independently conduct a literature search in five online databases (MEDLINE, EBSCO, Proquest, Sciencedirect, and Scopus). We screened a total of 132 titles and abstracts that meet our inclusion and exclusion criteria. We included articles published in English, using human subjects, using neural networks machine learning models, and using prostate biopsy as a standard diagnosis. Non relevant studies and review articles were excluded. After screening, we found six articles relevant to our study. Risk of bias analysis was conducted using QUADAS-2 tool. Of the six articles, four articles used Artificial Neural Network (ANN), one article used Recurrent Neural Network (RNN), and one article used Deep Learning (DL). All articles suggest a positive result of ultrasound in the diagnosis of prostate cancer with a varied ROC curve of 0.76-0.98. Several factors affect AI accuracy, including the model of AI, mode and type of transrectal sonography, Gleason grading, and PSA level. Although there was only limited and low-moderate quality evidence, we managed to analyse the predominant findings comprehensively. In conclusion, machine learning with neural network models is a potential technology in prostate cancer diagnosis that could provide instant information for further workup with relatively high accuracy above 70% of sensitivity/specificity and above 0.5 of ROC-AUC value. Image-based machine learning models would be helpful for doctors to decide whether or not to perform a prostate biopsy.
Vitamin D and acute respiratory infection: secondary analysis of a previous randomised controlled trial and updated meta-analyses
Authors: Bolland Mark J , Avenell Alison , Grey Andrew , Gamble Greg 
Published: February 2022

AbstractBackgroundRecent meta-analyses concluded that vitamin D supplementation can prevent acute respiratory infection (ARI). However, the findings were heavily influenced by results from two arms of a six-arm cluster-randomised trial that were analysed without accounting for the cluster trial design. We have used publicly available data to provide results from the remaining four unpublished trial arms and to reanalyse the meta-analyses, accounting for the cluster trial design.MethodsThe intracluster correlation co-efficient (ICC) and design effect were estimated. We then calculated the risk reduction (RR) of ARI from summary statistics, adjusting for the design effect, individually for the five different vitamin D treatment groups (four previously unpublished) and for all the vitamin D groups pooled. For this trial, individual patient data were used to estimate the effect of vitamin D on ARI risk and number of ARIs, adjusting for the cluster trial design, using random-effects models. Finally, we reanalysed the most recent trial-level meta-analysis, including the trial data generated by the correct analysis of the cluster randomized trial.ResultsThere were 744 trial participants (6 treatment groups, 21 clusters, mean cluster size 35.4). The ICC was 0.08 (95% CI 0.02-0.14) and design effect 3.75. In analyses based on summary statistics, there was no statistically significant effect of vitamin D on ARI risk in any individual treatment group, or when groups were pooled (RR 0.75, 95%CI 0.50-1.13). In individual patient data analyses, there was also no statistically significant effect of vitamin D on the ARI risk or number of ARIs in any treatment group, or when pooled: odds ratio 0.58 (0.26-1.29), rate ratio 0.70 (0.44-1.12), respectively. Update of the previous meta-analysis showed no effect of vitamin D on ARI either when data from the two arms of the trial, or when all trial arms were incorporated (RR 0.98, 0.96-1.00, P=0.10 both analyses).ConclusionsOverall, vitamin D supplementation had no effect on the risk of an ARI or on the number of ARIs in this trial or in a re-analysis of the most recent meta-analysis. The results of the updated meta-analysis do not suggest that vitamin D supplementation would reduce the risk of Covid 19.
Genome-wide identification, characterization, and comparative analysis of NLR resistance genes in Coffea spp
Authors: Santos Mariana de Lima , de Resende Mário Lúcio Vilela , Alves Gabriel Sérgio Costa , Huguet-Tapia Jose Carlos , de Resende Márcio Fernando Ribeiro , Brawner Jeremy Todd 
Published: February 2022

AbstractThe largest family of disease resistance genes in plants are nucleotide-binding site leucine-rich repeat genes (NLRs). The products of these genes are responsible for recognizing avirulence proteins (Avr) of phytopathogens and triggering specific defense responses. Identifying NLRs in plant genomes with standard gene annotation software is challenging due to their multidomain nature, sequence diversity, and clustered genomic distribution. We present the results of a genome-wide scan and comparative analysis of NLR loci in three coffee species (Coffea canephora, Coffea eugenioides and their interspecific hybrid Coffea arabica). A total of 1311 non-redundant NLR loci were identified in C. arabica, 927 in C. canephora, and 1079 in C. eugenioides, of which 809, 562, and 695 are complete loci, respectively. The NLR-annotator tool used in this study showed extremely high sensitivities and specificities (over 99%) and increased the detection of putative NLRs in the reference coffee genomes. The NLRs loci in coffee are distributed among all chromosomes and are organized mostly in clusters. The C. arabica genome presented a smaller number of NLR loci when compared to the sum of the parental genomes (C. canephora, and C. eugenioides). There are orthologous NLRs (orthogroups) shared between coffee, tomato, potato, and reference NLRs and those that are shared only among coffee species, which provides clues about the functionality and evolutionary history of these orthogroups. Phylogenetic analysis demonstrated orthologous NLRs shared between C. arabica and the parental genomes and those that were possibly lost. The NLR family members in coffee are subdivided into two main groups: TIR-NLR (TNL) and non-TNL. The non-TNLs seem to represent a repertoire of resistance genes that are important in coffee. These results will support functional studies and contribute to a more precise use of these genes for breeding disease-resistant coffee cultivars.
Cryomilling Tethered Chromatin Conformation Capture reveal new insights into inter-chromosomal interactions
Authors: Xu Jiang , Kumar Sanjeev , Hua Nan , Kou Yi , Lei Xiao , Rout Michael P. , Aitchison John D. , Alber Frank , Chen Lin 
Published: February 2022

AbstractTraditional methods used to map the three-dimensional organization of chromatin in-situ generally involve chromatin conformation capture by formaldehyde crosslinking, followed by detergent solubilization and enzymatic digestion of DNA. Ligation of proximal DNA fragments followed by next generation sequencing (NGS) generates contact information that enables a global view of the chromatin conformation. Here, we explore the use of cryomilling to physically fragmentize the cells under cryogenic conditions to probe chromatin interactions in the cryomilled cell fragments by the tethered chromatin conformation capture (TCC). Our results show that cryomilling TCC (CTCC) can generate a global contact map similar to that obtained with in-situ Hi-C. This result suggests that summation of chromatin interactions mapped in individual subcellular fragments can reconstitute the global contact map of intact cells in an ensemble manner, paving the way for chromatin conformation analyses of solid tissue by CTCC. Compared with the conventional in-situ methods such as Hi-C, CTCC shows more uniform access to different subcompartments of the folded genome. On the other hand, most inter-chromosomal (trans) contacts are diminished or lost in CTCC except for a group of unique trans contacts that remain intact throughout the cryomilling and in- vitro crosslinking steps. These apparently ultra-stable trans interactions have much enhanced signal in CTCC due to the elimination of signals of most, presumably weak and transient trans interactions. Systematic and comparative analyses between CTCC and in-situ Hi-C provide further insights into the chromatin structure organization and reveal a generally unentangled chromosome interface and the existence of stable inter-chromosomal contacts that may represent intermingled inter-chromosomal interfaces.
Scratching bouts are modeled as Bernoulli trials until successful itch-extinguishing in mice
Authors: Honda Kotaro , Tominaga Mitsutoshi , Takamori Kenji 
Published: February 2022

AbstractItching and subsequent scratching behavior have been observed in many species, including humans. The behavior was evolved to remove skin parasites. Yet, scratching is performed without reliable indicators of whether a parasite is present. We addressed this apparent paradox by studying scratching in mice. Video recordings of ~5000 scratching bouts were collected in free-moving C57BL6/J mice. The statistical properties of their temporal sequence were analyzed. Inter-bout time intervals preceding over 50% of 5000 bouts were <10 s. We hypothesized that episodes of repetitive scratching corresponded to the duration of discrete events of itch sensation and comprised bouts separated by inter-bout intervals of <10 s. The distribution of itch episodes comprising n (n = 1, 2, 3, …) scratching bouts was well-approximated by the geometric distribution with success probability = 0.5 in healthy mice and lower probability in dry skin mice. This suggests that scratching bouts are modeled by probabilistic Bernoulli trials, and their repetitive sequence in each episode continues until the itch is successfully extinguished. Accordingly, we can presume the presence of parasites from the repeat length of scratching bouts determined by the probability of successful itch-extinguishing. This may provide a promising stochastic model to assess itchy phenotypes.
Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration
Authors: Fiedler Sebastian , Devenish Sean R. A. , Morgunov Alexey S. , Ilsley Alison , Ricci Francesco , Emmenegger Marc , Kosmoliaptsis Vasilis , Theel Elitza S. , Mills John R. , Sholukh Anton M. , Aguzzi Adriano , Iwasaki Akiko , Lynn Andrew K. , Knowles Tuomas P. J. 
Published: February 2022

AbstractWe assessed the affinities of the therapeutic monoclonal antibodies (mAbs) cilgavimab, tixagevimab, sotrovimab, casirivimab, and imdevimab to the receptor binding domain (RBD) of wild type, Delta, and Omicron spike. The Omicron RBD affinities of cilgavimab, tixagevimab, casirivimab, and imdevimab decreased by at least two orders of magnitude relative to their wild type equivalents, whereas sotrovimab binding was less severely impacted. These affinity reductions correlate with reduced antiviral activities of these antibodies, suggesting that simple affinity measurements can serve as an indicator for activity before challenging and time-consuming virus neutralization assays are performed. We also compared the properties of these antibodies to serological fingerprints (affinities and concentrations) of wild type RBD specific antibodies in 74 convalescent sera. The affinities of the therapeutic mAbs to wild type and Delta RBD were in the same range as the polyclonal response in the convalescent sera indicative of their high antiviral activities against these variants. However, for Omicron RBD, only sotrovimab retained affinities that were within the range of the polyclonal response, in agreement with its high activity against Omicron. Serological fingerprints thus provide important context to affinities and antiviral activity of mAb drugs and could guide the development of new therapeutics.
Interferon receptor gene dosage determines diverse hallmarks of Down syndrome
Authors: Waugh Katherine A. , Minter Ross , Baxter Jessica , Chi Congwu , Tuttle Kathryn D. , Eduthan Neetha P. , Galbraith Matthew D. , Kinning Kohl T. , Andrysik Zdenek , Araya Paula , Dougherty Hannah , Dunn Lauren N. , Ludwig Michael , Schade Kyndal A. , Tracy Dayna , Smith Keith P. , Granrath Ross E. , Busquet Nicolas , Khanal Santosh , Anderson Ryan D. , Cox Liza L. , Estrada Belinda Enriquez , Rachubinski Angela L. , Lyford Hannah R. , Britton Eleanor C. , Orlicky David J. , Matsuda Jennifer L. , Song Kunhua , Cox Timothy C. , Sullivan Kelly D. , Espinosa Joaquin M. 
Published: February 2022

AbstractTrisomy 21 causes Down syndrome, a condition characterized by cognitive impairments, immune dysregulation, and atypical morphogenesis. Using whole blood transcriptome analysis, we demonstrate that specific overexpression of four interferon receptors encoded on chromosome 21 associates with chronic interferon hyperactivity and systemic inflammation in Down syndrome. To define the contribution of interferon receptor overexpression to Down syndrome phenotypes, we used genome editing to correct interferon receptor gene dosage in mice carrying triplication of a large genomic region orthologous to human chromosome 21. Normalization of interferon receptor copy number attenuated lethal antiviral responses, prevented heart malformations, decreased developmental delays, improved cognition and normalized craniofacial anomalies. Therefore, interferon receptor gene dosage determines major hallmarks of Down syndrome, indicating that trisomy 21 elicits an interferonopathy amenable to therapeutic intervention.One-Sentence SummaryCorrection of interferon receptor gene dosage rescues multiple key phenotypes in a mouse model of trisomy 21.
Beta-cell Cre expression and reduced Ins1 gene dosage protect mice from type 1 diabetes
Authors: Skovsø Søs , Overby Peter , Memar-Zadeh Jasmine , Lee Jason T.C. , Yang Jenny C.C. , Shanina Iryna , Sidarala Vaibhav , Levi-D’Ancona Elena , Zhu Jie , Soleimanpour Scott A. , Horwitz Marc S. , Johnson James D. 
Published: February 2022

AbstractA central goal of physiological research is the understanding of cell-specific roles of disease-associated genes. Cre-mediated recombineering is the tool of choice for cell type-specific analysis of gene function in pre-clinical models. In the type 1 diabetes research field, multiple lines of NOD mice have been engineered to express Cre recombinase in pancreatic β-cells using insulin promoter fragments, but tissue promiscuity remains a concern. Constitutive Ins1tm1.1(cre)Thor (Ins1Cre) mice on the C57/bl6-J background has high β-cell specificity and with no reported off-target effects. We explored if NOD:Ins1Cre mice could be used to investigate β-cell gene deletion in type 1 diabetes disease modeling. We studied wildtype (Ins1WT/WT), Ins1 heterozygous (Ins1Cre/WT or Ins1Neo/WT), and Ins1 null (Ins1Cre/Neo) littermates on a NOD background. Female Ins1Neo/WT mice exhibited significant protection from diabetes, with further near-complete protection in Ins1Cre/WT mice. The effects of combined neomycin and Cre knock-in in Ins1Neo/Cre mice were not additive to the Cre knock-in alone. In Ins1Neo/Cre mice, protection from diabetes was associated with reduced insulitis at 12 weeks of age. Collectively, these data confirm previous reports that loss of Ins1 alleles protects NOD mice from diabetes development and demonstrates, for the first time, that Cre itself may have additional protective effects. This has significant implications for the experimental design and interpretation of pre-clinical type 1 diabetes studies using β-cell-specific Cre in NOD mice.