bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spectrum of EEG Abnormalities in COVID-19 Patients
Authors: Hameed Sajid , Saleem Shafaq , Sajjad Ali , Fahim Quratulain , Wasay Mohammad , Kanwar Dureshahwar 
Published: September 2022

Purpose:
Neurologic involvement is commonly reported in coronavirus disease (COVID-19) patients. The published literature regarding the COVID-19–related neurophysiological findings, including the EEG findings, is still quite limited. The objective of this study was to evaluate the EEG findings in patients with a COVID-19 infection and look for a possible correlations and prognosis.

Methods:
This is an inpatient hospital-based retrospective observational study. All admitted COVID-19 patients undergoing an EEG study between January 1, 2020 and June 30, 2021 were included in this study. EEG was ordered by the primary intensive care physician or a neurologist taking part in the clinical care of patients.

Results:
Sixty-six EEG studies in 57 patients were included. Mean age was 62.2 ± 16.3 years with male predominance (65%). Encephalopathy (70%) was the most common indication for an EEG. Background EEG abnormalities were seen in most of the patients (92.4%) with severe abnormalities correlating with the prognosis of the patient. Epileptiform discharges were only seen in 7.5% of the EEGs, with majority of the discharges arising from the frontal region. Mortality reported was high (47%).

Conclusions:
Nonspecific diffuse background EEG abnormalities are commonly seen in COVID-19 patients. Epileptiform discharges are less common but mostly originate from frontal region. Most of these patients also had an abnormal neuroimaging. The significance of this peculiar finding needs further research.

Significance:
Nonspecific background EEG changes are common in COVID-19 patients. Among epileptiform discharges, focal epileptiform discharges arising from the frontal region were common, usually associated with an abnormal neuroimaging.
Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin-beta receptor signaling
Authors: Feng Xing , Sun Ruifeng , Lee Moonyoung , Chen Xinyue , Guo Shangqin , Geng Huimin , Müschen Markus , Choi Jungmin , Pereira Joao P. 
Published: September 2022

AbstractAcute lymphoblastic and myeloblastic leukemias (ALL and AML) have been known to modify the bone marrow microenvironment and disrupt non-malignant hematopoiesis. However, the molecular mechanisms driving these alterations remain poorly defined. Here we show that leukemic cells turn-off lymphopoiesis and erythropoiesis shortly after colonizing the bone marrow. ALL and AML cells express lymphotoxin-α1β2 and activate LTβR signaling in mesenchymal stem cells (MSCs), which turns off IL7 production and prevents non-malignant lymphopoiesis. We show that the DNA damage response pathway and CXCR4 signaling promote lymphotoxin-α1β2 expression in leukemic cells. Genetic or pharmacologic disruption of LTβR signaling in MSCs restores lymphopoiesis but not erythropoiesis, reduces leukemic cell growth, and significantly extends the survival of transplant recipients. Similarly, CXCR4 blocking also prevents leukemia-induced IL7 downregulation, and inhibits leukemia growth. These studies demonstrate that acute leukemias exploit physiological mechanisms governing hematopoietic output as a strategy for gaining competitive advantage.One Sentence SummaryLeukemias colonize bone marrow niches and disrupt hematopoiesis. However, the cross-talk between leukemia and niche cells remains poorly understood. We show that leukemia activates LTβR in mesenchymal stem cells which suppresses IL7 production and IL7-dependent lymphopoiesis and accelerates leukemia growth.
Device-led versus human-led feedback on chest compressions for cardiopulmonary resuscitation and providers’ experience and preference: a randomised crossover study
Authors: Noor Azhar Muhaimin , Bustam Aida , Poh Khadijah , Chew Keng Sheng , Azman Asraff , Kamarudin Anhar , Zambri Aliyah 
Published: September 2022

AbstractBackgroundHigh cardiopulmonary resuscitation (CPR) quality is associated with better patient survival from cardiac arrest. However, CPR providers may not have an accurate perception of the depth and rate of their chest compressions (CC). Realtime feedback during resuscitation improves CPR quality compared to no feedback. Evidence comparing audio-visual feedback device (AVF) and team leader’s feedback (TLF) in improving CPR performance is limited and conflicting.MethodologyWe performed a randomized crossover study to evaluate CC performance with AVF and TLF. Seventy participants performed CC for 1 minute on a CPR manikin connected to ZOLL R series defibrillator with CPR-sensing capability in a randomised crossover sequence. We interviewed participants to explore their perception and preference with both feedback methods.ResultsMean CC rate was higher with AVF than with TLF (121.8 min-1 ± 17.7 vs. 117.4 min-1 ± 13.5, p = 0.005). There was no significant difference in proportions of participants performing CC within the recommended rate of 100-120 beats per minute between AVF and TLF (48.6% and 51.4%, p = 0.824). Overall, CC depth was below the recommended target regardless of feedback method with mean CC depth of 4.4 cm ± 0.8 in AVF and 4.3 cm ± 0.9 in TLF respectively (p = 0.479). Most participants felt that TLF was easier to follow, more motivating and preferable compared to AVF. Those who preferred TLF performed CC at rates above the recommended range with AVF compared to TLF (124.1 min-1 ± 19.4 versus 118.2 min-1 ± 14.9, p = 0.004).ConclusionA well-trained team leader is as effective as an AVF device in leading high-quality CC. CPR providers’ performance may be influenced by their preferred feedback method.
DISCRIMINATOR: Assigning Cohort-Wide Provisional Pathogenicity Classifications to CNVs
Authors: Wetzel Alyssa S. , Major Heather , Parida Mrutyunjaya , Manak J. Robert , Darbro Benjamin W. 
Published: September 2022

AbstractThe interpretation of clinical chromosomal microarrays (CMAs) has historically relied on the relevance of identified copy number variants (CNVs) to the clinical phenotype. New interpretation guidelines are focused on standardizing pathogenicity classifications based on genomic location, gene content, and previous publications, rather than the immediate clinical relevance. Here we report on DISCRIMINATOR, which was developed to assign provisional pathogenicity classifications based on genomic location by integrating information on putative benign and pathogenic loci in the human genome. However, its application extends beyond that of a simple classifier. The novel utility of DISCRIMINATOR is its ability to operate on a cohort-level and easily integrate updated definitions of benign and pathogenic regions of the human genome. We used DISCRIMINATOR to assign provisional pathogenicity classifications (‘Benign’, ‘Secondary’, ‘Primary’ or ‘Non-Coding’) to 87,808 CNVs in 3,362 cases ascertained through clinical CMA testing. The majority of identified CNVs were provisionally classified as ‘Benign’ or ‘Non-Coding’ and consistent with their prevalence rates, 15q11.2, 16p11.2, and 22q11.2 were the most common ‘Primary’ CNVs detected. Targeted re-analysis led to the identification of several cases where DISCRIMINATOR identified a ‘Primary’ CNV within a case that had a non-Abnormal CMA test result, and several cases where only benign and/or non-coding CNVs were identified in reports with a ‘VUS’ CMA test result. Together these results show the utility of large-scale re-analysis of CMA data and how DISCRIMINATOR addresses this long-standing challenge.
Large scale interrogation of retinal cell functions by 1-photon light-sheet microscopy
Authors: Roy Suva , Wang Depeng , Rudzite Andra M. , Perry Benjamin , Scalabrino Miranda L. , Thapa Mishek , Gong Yiyang , Sher Alexander , Field Greg D. 
Published: September 2022

AbstractVisual processing in the retina depends on the collective activity of large ensembles of neurons organized in different layers. Current techniques for measuring activity of layer-specific neural ensembles rely on expensive pulsed infrared lasers to drive 2-photon activation of calcium-dependent fluorescent reporters. Here, we present a 1-photon light-sheet imaging system that can measure the activity in hundreds of ex vivo retinal neurons over a large field of view while simultaneously presenting visual stimuli. This allowed for a reliable functional classification of different retinal ganglion cell types. We also demonstrate that the system has sufficient resolution to image calcium entry at individual synaptic release sites across the axon terminals of dozens of simultaneously imaged bipolar cells. The simple design, a large field of view, and fast image acquisition, make this a powerful system for high-throughput and high-resolution measurements of retinal processing at a fraction of the cost of alternative approaches.
Profound immunomodulatory effects of 225Ac-NM600 drive enhanced anti-tumor response in prostate cancer
Authors: Ferreira Carolina A. , Potluri Hemanth K. , Massey Christopher , Grudzinski Joseph J. , Carston Amanda , Clemons Nathan , Thickens Anna , Rosenkrans Zachary , Choi Cynthia , Pinchuk Anatoly , Kwon Ohyun , Jeffery Justin J. , Bednarz Bryan , Morris Zachary , Weichert Jamey , McNeel Douglas G. , Hernandez Reinier 
Published: September 2022

AbstractAn immunosuppressive tumor microenvironment has hampered the efficacy of immunotherapy in prostate cancer. However, radiation-induced immunological effects can partly mediate anti-tumor effects by promoting a pro-inflammatory environment potentially responsive to immunotherapy. Herein, we examined the immunomodulatory properties of a radiopharmaceutical therapy (RPT) with NM600 radiolabeled with either a beta or alpha emitter in two prostate cancer models. 225Ac-NM600, but not 177Lu-NM600, promoted significant anti-tumor effects and improved overall survival. Immunomodulatory effects were dose, radionuclide, and tumor type-dependent. 225Ac-NM600 elicited an array of immunomodulatory effects such as increased CD8/Treg ratio, activation of effector and memory T cells, abrogation of infiltrating suppressor cells (e.g., Tregs and MDSCs), and increased levels of Th1 cytokine and pro-inflammatory chemokines. Importantly, we demonstrate the need to carefully characterize the immune responses elicited by RPT both pre-clinically and clinically to maximize tumor control and avoid potential counterproductive immunosuppressive effects.TeaserTargeted alpha therapy can create a pro-inflammatory tumor micro-environment that partly explains stronger anti-tumor responses in prostate cancer
Molecular diagnostics for early detection of invasion of malaria vector Anopheles stephensi
Authors: Singh Om P. , Kaur Taranjeet , Sharma Gunjan , Prasad Kona M. , Kapoor Neera , Mallick Prashant K. 
Published: September 2022

AbstractThere are increasing reports of the expansion of the Asian malaria vector Anopheles stephensi in new geographical areas posing a threat to the elimination of urban malaria. Efficient surveillance of this vector in affected areas and early detection in new geographical areas is key for the containment and control of this species. To overcome the practical difficulties associated with the morphological identification of immature stages and adults of An. stephensi, a species-specific PCR and a Real-Time PCR assay were developed for their identification targeting a unique segment of ITS2 lacking homology to any other organism. Both PCRs can be used to identify An. stephensi individually or in pooled samples of mixed species, including when present in extremely low proportion. This study also reports a method for selective amplification and sequencing of An. stephensi for their confirmation in pooled samples of mixed species.
Model-based whole-brain perturbational landscape of neurodegenerative diseases
Authors: Perl Yonatan Sanz , Fittipaldi Sol , González Campo Cecilia , Moguilner Sebastián , Cruzat Josephine , Herzog Rubén , Kringelbach Morten , Deco Gustavo , Prado Pavel , Ibañez Agustín , Tagliazucchi Enzo 
Published: September 2022

AbstractThe treatment of neurodegenerative diseases is hindered by lack of interventions capable of steering multimodal whole-brain dynamics towards patterns indicative of preserved brain health. To address this problem, we combined deep learning with a model capable of reproducing whole-brain functional connectivity in patients diagnosed with Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD). These models included disease-specific atrophy maps as priors to modulate local parameters, revealing increased stability of hippocampal and insular dynamics as signatures of brain atrophy in AD and bvFTD, respectively. Using variational autoencoders, we visualized different pathologies and their severity as the evolution of trajectories in a low-dimensional latent space. Finally, we perturbed the model to reveal key AD− and bvFTD-specific regions to induce transitions from pathological to healthy brain states. Overall, we obtained novel insights on disease progression and control by means of external stimulation, while identifying dynamical mechanisms that underlie functional alterations in neurodegeneration.
Cerebral Small Vessel Disease Burden is Associated with Decreased Abundance of Gut Barnesiella intestinihominis Bacterium in the Framingham Heart Study
Authors: Fongang Bernard , Satizabal Claudia L. , Kautz Tiffany F. , Ngouongo Yannick W. , SherraeMuhammad Jazmyn A. , Vasquez Erin , Mathews Julia , Goss Monica , Saklad Amy R. , Himali Jayandra , Beiser Alexa , Cavazos Jose E. , Mahaney Michael C. , Maestre Gladys , DeCarli Charles , Shipp Eric L. , Vasan Ramachandran S. , Seshadri Sudha 
Published: September 2022

AbstractA bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer’s disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance ofPseudobutyrivibrioandRuminococcusgenera was associated with lower WMH and PSMD (p-values < 0.001), as well as better executive function (p-values < 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacteriumBarnesiella intestinihominiswas strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses usingPICRUStimplicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and β-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings.
Murine breast cancers disorganize the liver transcriptome in zonated manners
Authors: Vandenbon Alexis , Mizuno Rin , Konishi Riyo , Onishi Masaya , Masuda Kyoko , Kobayashi Yuka , Kawamoto Hiroshi , Suzuki Ayako , Shimizu Masahito , Tanaka Yasuhito , Suzuki Yutaka , Kawaoka Shinpei 
Published: September 2022

AbstractThe spatially organized gene expression program within the liver specifies hepatocyte functions according to their relative distances to the bloodstream (i.e., zonation), contributing to liver homeostasis. Despite the knowledge that solid cancers remotely disrupt liver homeostasis, it remains unexplored whether solid cancers affect liver zonation. Here, using spatial transcriptomics, we thoroughly investigate the abundance and zonation of hepatic genes in cancer-bearing mice. We find that breast cancers affect liver zonation in various distinct manners depending on biological pathways. Aspartate metabolism and triglyceride catabolic processes retain relatively intact zonation patterns, but the zonation of xenobiotic catabolic process genes exhibits a strong disruption. The acute phase response is induced in zonated manners. Furthermore, we demonstrate that breast cancers activate innate immune cells in particular neutrophils in distinct zonated manners, rather than in a uniform fashion within the liver. Collectively, breast cancers disorganize hepatic transcriptomes in zonated manners, thereby disrupting zonated functions of the liver.
Classic and dissociative psychedelics induce similar hyper-synchronous states in the cognitive-limbic cortex-basal ganglia system
Authors: Brys Ivani , Barrientos Sebastian , Ward Jon Ezra , Wallander Jonathan , Petersson Per , Halje Pär 
Published: September 2022

ABSTRACTThe neurophysiological mechanisms behind the profound changes in perception and cognition induced by psychedelic drugs are not well understood. To identify neuronal activity specific to the psychedelic state, we here investigated the effects of classic psychedelics (LSD, DOI) and dissociative psychedelics (ketamine, PCP) on neuronal firing rates and local field potentials in several brain structures involved in cognitive processing in freely moving rats.The classic psychedelics had a net inhibitory effect on firing rates of putative interneurons and principal cells in all recorded regions. The dissociative psychedelics had a similar inhibitory effect on principal cells, but an opposite excitatory effect on interneurons in most regions. However, the inhibitory effect on principal cells was not specific to the psychedelic state, as similar inhibition occurred with a non-psychedelic psychotropic control (amphetamine).In contrast, both types of psychedelics dramatically increased the prevalence of high-frequency oscillations (HFOs) in local field potentials, while the non-psychedelic control did not. Further analysis revealed strong HFO phase locking between structures and very small phase differences corresponding to <1 ms delays. Such standing-wave behavior suggests local generation of HFOs in multiple regions and weak, fast coupling between structures.The observed HFO hypersynchrony is likely to have major effects on processes that rely on integration of information across neuronal systems, and it might be an important mechanism behind the changes in perception and cognition during psychedelic drug use. Potentially, similar mechanisms could induce hallucinations and delusions in psychotic disorders and would constitute promising targets for new antipsychotic treatments.
A Genome Scale Transcriptional Regulatory Model of the Human Placenta
Authors: Paquette Alison , Ahuna Kylia , Hwang Yeon Mi , Pearl Jocelynn , Liao Hanna , Shannon Paul , Kadam Leena , Lapehn Samantha , Bucher Matthew , Roper Ryan , Funk Cory , MacDonald James , Bammler Theo , Baloni Priyanka , Brockway Heather , Mason W. Alex , Bush Nicole , Lewinn Kaja Z , Karr Catherine J , Stamatoyannopoulos John , Muglia Louis J , Jones Helen , Sadovsky Yoel , Myatt Leslie , Sathyanarayana Sheela , Price Nathan D. 
Published: September 2022

ABSTRACTGene regulation is essential to placental function and fetal development. We report a genome-scale transcriptional regulatory network (TRN) of the human placenta built using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)-target gene interactions. In an independent dataset, the TRN model predicted target gene expression with an out of sample R2value greater than 0.25 for 74% of target genes. We performed siRNA knockdowns of 4 TFs and achieved concordance between the predicted gene targets in our TRN and differences in expression of knockdowns with an accuracy of >0.7 for 3 of the 4 TFs. Our final model contained 113,158 interactions across 391 TFs and 7,712 target genes and is publicly available. We identified six TFs which were significantly enriched as regulators for genes previously associated with preterm birth.
Disruption of Tonic Endocannabinoid Signaling Triggers the Generation of a Stress Response
Authors: Petrie Gavin N. , Balsevich Georgia , Füzesi Tamás , Aukema Robert J. , Driever Wouter P. F. , van der Stelt Mario , Bainsand Jaideep S. , Hill Matthew N. 
Published: September 2022

AbstractEndocannabinoid (eCB) signalling gates many aspects of the stress response, including the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is controlled by corticotropin releasing hormone (CRH) producing neurons in the paraventricular nucleus of the hypothalamus (PVN). Disruption of eCB signalling increases drive to the HPA axis, but the mechanisms subserving this process are poorly understood. Using an array of cellular, endocrine and behavioral readouts associated with activation of CRH neurons in the PVN, we evaluated the contributions of tonic eCB signaling to the generation of a stress response. The CB1 receptor antagonist/inverse agonist AM251, neutral antagonist NESS243, and NAPE PLD inhibitor LEI401 all uniformly increased c-fos in the PVN, unmasked stress-linked behaviors, such as grooming, and increased circulating CORT, recapitulating the effects of stress. Similar effects were also seen after direct administration of AM251 into the PVN, while optogenetic inhibition of PVN CRH neurons ameliorated stress-like behavioral changes produced by disruption of eCB signaling. These data indicate that under resting conditions, constitutive eCB signaling restricts activation of the HPA axis through local regulation of CRH neurons in the PVN.
Comprehensive Analysis of Peptide-Coding Genes Identifies an LRR-only Microprotein That Regulates Reproductive Organs in Marchantia polymorpha
Authors: Kobayashi Haruaki , Sugano Shigeo S. , Tamura Kentaro , Oka Yoshito , Matsushita Tomonao , Shimada Tomoo 
Published: September 2022

1AbstractIn the past two decades, many plant peptides have been found to play crucial roles in various biological events by mediating cell-to-cell communications. However, a large number of small open reading frames (sORFs) or short genes capable of encoding peptides remain uncharacterized. In this study, we examined several candidate genes for peptides conserved between two model plants: Arabidopsis thaliana and Marchantia polymorpha. We examined the expression pattern in M. polymorpha and subcellular localization using a transient assay with Nicotiana benthamiana. We found that one candidate, MpSGF10B, was expressed in meristems, gemma cups, and male reproductive organs called antheridiophores. MpSGF10B has an N-terminal signal peptide followed by two leucine-rich repeat (LRR) domains and was secreted to the extracellular region in N. benthamiana and M. polymorpha. Compared with the wild type, two independent knockout mutants had an increased number of antheridiophores, which emerged from meristems. It was revealed in gene ontology enrichment analysis that MpSGF10B was significantly co-expressed with genes related to cell cycle and development. These results suggest that MpSGF10B may regulate the reproductive development in M. polymorpha. Our research should shed light on the unknown role of LRR-only proteins in land plants.