bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of En-Bloc Multiple Monitored Electroconvulsive Therapy in Benzodiazepine Refractory Malignant Catatonia
Authors: Louie Anita Tsen-hui , Anand Ekta , Baldwin Isaac , Smith Joshua Ryan 
Published: July 2024

Abstract
We report a case of an adolescent female experiencing benzodiazepine and single-stimulation electroconvulsive (ECT)–refractory malignant catatonia, who improved with the use multiple monitored ECT (mmECT). Per the 2001 American Psychiatric Association guidelines, mmECT should be considered only in cases of intractable seizures or neuroleptic malignant syndrome. Since 2001, neuroleptic malignant syndrome and malignant catatonia have been described as occurring along the same spectrum of illness. Therefore, given the life-threatening nature of her condition, as well as the brief seizure duration she experienced from single-stimulation ECT, the patient was treated with en-bloc and 2-stimulation mmECT. The patient demonstrated a significant improvement in response to this treatment, with her Bush-Francis Catatonia Rating Scale score decreasing by 89%. At 2-year follow-up in an outpatient neurodevelopmental catatonia clinic, the patient has been able to return to school in her previous advanced placement classes and has not required maintenance ECT.
Importance of Multispecialty Coordination of Care in an Electroconvulsive Therapy Patient With Musculoskeletal, Neurological, and Vascular Injuries
Authors: Lee Hong M. , Kisicki Michael D. , Hong Jennifer , Knight Julia C. 
Published: July 2024

Abstract
Electroconvulsive therapy (ECT) is considered an effective therapy for patients suffering from severe, life-threatening, intractable depression. This treatment modality delivers controlled electrical currents (typically no more than 100 J) under general anesthesia to induce seizure. Although generally considered to have a high safety profile, physiological changes induced during the ictal phase of ECT, such as elevation in blood pressure and intracranial pressure, impose additional risks to patients with concomitant cardiovascular or cerebrovascular conditions. We describe the successful use of ECT in a unique case complicated by a combination of acute vertebral artery dissection, traumatic intracerebral hemorrhage, and cervical spine injury sustained from a suicide attempt by intentional motor vehicle collision. Although ECT can be safely administered in the presence of recent vertebral artery dissection and traumatic intraparenchymal hemorrhage, an emphasis on multispecialty coordination is crucial to monitor and reduce the risk of elevated blood pressure and further cervical spine injury.
Psychosis in Fahr Syndrome
Authors: Sieffien Weam , Sorial Sylvia , Ure Robert , Golts Marina 
Published: July 2024

Abstract
Fahr syndrome is a rare neurological disorder characterized by a combination of neurological and psychiatric symptoms. Despite its complexity, there is a significant scarcity of literature addressing the treatment of the psychiatric symptoms of Fahr syndrome. This case report discusses the complexity of management of psychosis in patients with Fahr syndrome emphasizing the delicate balance required to address both psychiatric and neurological symptoms. It underscores the need for a collaborative treatment approach. Furthermore, this case report explores the potential role for electroconvulsive therapy (ECT) in management of psychosis in Fahr syndrome, a topic for which there is limited existing literature. We aim to contribute to bridging this fap with our report.
Catatonia and Maintenance Electroconvulsive Therapy in a 15-Year-Old Patient With MED13L Haploinsufficiency Syndrome in the Context of Epilepsy Diathesis
Authors: Ince H. Yavuz , Neville Kerri , Geller Jamarie , Palffy Alexander , Beser Can , Ziobro Julie , Ghaziuddin Neera 
Published: July 2024

Abstract
This is the first report of pediatric catatonia syndrome in MED13L haploinsufficiency syndrome. This report describes unique challenges in diagnosis and management of catatonia in rare genetic conditions. The case also illustrates the use of electroconvulsive therapy in patients with epilepsy, epileptic encephalopathy, or other epileptic diathesis and the clinical conundrum in determining the course of maintenance electroconvulsive therapy.
Cryo-EM of AKAP350 reveals fibrillar clusters and a potential association with DNA
Authors: Dai David L. , Keszei Alexander F.A. , Kolobova Elena , St-Germain Jonathan , Hasan S.M. Naimul , Liu Alex C.H. , Zhang Xu , Raught Brian , Goldenring James R. , Mazhab-Jafari Mohammad T. 
Published: July 2024

AbstractProtein kinase A (PKA) is a promiscuous serine/threonine kinase that phosphorylates a broad-spectrum of effectors involved in vital processes such as glucose, glycogen, and lipid metabolism. Its activity is thus tightly controlled by a family of eukaryotic scaffolding proteins known as the A-kinase anchoring proteins (AKAPs) that confine PKA signaling to specific compartments in the cell. AKAP350 (the protein encoded byAKAP9) is a massive scaffolding protein that anchors PKA to the Golgi apparatus and the centrosome where it nucleates macromolecular signaling hubs that control microtubule nucleation and dynamics. Here, we have expressed and purified full-length AKAP350 from HEK293F cells in a functional conformation. Electron cryo-microscopy (cryo-EM) of the purified protein revealed polydisperse particles forming fibrillar clusters around 50 nm in diameter, and long, thin filaments that reconstructed into double-stranded DNA. Tomographic reconstruction of a tilt series of the purified protein by electron cryo-tomography (cryo-ET) further elucidated these fibrillar clusters as 3D bundles of entangled filaments. Mass spectrometry and DNA sequencing confirmed the co-purification of DNA and DNA binding proteins such as nuclear factor 1 B (NFIB) and nucleolin (NCL). Pulldown of NFIB and NCL, but not of CEP290, CDK5RAP2, and CEP170 was diminished in the presence of DNase-I, suggesting that AKAP350 interaction with these two proteins is mediated by DNA. Overall, this study has achieved a quality purification of AKAP350 from which a previously uncharacterized interaction landscape with DNA and DNA binding proteins was discovered.
Spatial gene expression at single-cell resolution from histology using deep learning with GHIST
Authors: Fu Xiaohang , Cao Yue , Bian Beilei , Wang Chuhan , Graham Dinny , Pathmanathan Nirmala , Patrick Ellis , Kim Jinman , Yang Jean YH 
Published: July 2024

AbstractThe increased use of spatially resolved transcriptomics provides new biological insights into disease mechanisms. However, the high cost and complexity of these methods are barriers to broad clinical adoption. Consequently, methods have been created to predict spot-based gene expression from routinely-collected histology images. Recent benchmarking showed that current methodologies have limited accuracy and spatial resolution, constraining translational capacity. Here, we introduce GHIST, a deep learning-based framework that predicts spatial gene expression at single-cell resolution by leveraging subcellular spatial transcriptomics and synergistic relationships between multiple layers of biological information. We validated GHIST using public datasets and The Cancer Genome Atlas data, demonstrating its flexibility across different spatial resolutions and superior performance. Our results underscore the utility ofin silicogeneration of single-cell spatial gene expression measurements and the capacity to enrich existing datasets with a spatially resolved omics modality, paving the way for scalable multi-omics analysis and new biomarker discoveries.
C5aR1 inhibition alleviates cranial radiation-induced cognitive decline
Authors: Krattli Robert P. , Do An H. , El-Khatib Sanad M. , Alikhani Leila , Markarian Mineh , Vagadia Arya R. , Usmani Manal T. , Madan Shreya , Baulch Janet E. , Clark Richard J. , Woodruff Trent M. , Tenner Andrea J. , Acharya Munjal M. 
Published: July 2024

ABSTRACTCranial radiation therapy (RT) for brain cancers leads to an irreversible decline in cognitive function without an available remedy. Radiation-induced cognitive deficits (RICD) are a particularly pressing problem for the survivors of pediatric and low grade glioma (LGG) cancers who often live long post-RT lives. Radiation-induced elevated neuroinflammation and gliosis, triggered by the detrimental CNS complement cascade, lead to excessive synaptic and cognitive loss. Using intact and brain cancer-bearing mouse models, we now show that targeting anaphylatoxin complement C5a receptor (C5aR1) is neuroprotective against RICD. We used a genetic knockout, C5aR1 KO mouse, and a pharmacologic approach, employing the orally active, brain penetrant C5aR1 antagonist PMX205 to reverse RICD. Irradiated C5aR1 KO and WT mice receiving PMX205 showed significant neurocognitive improvements in object recognition memory and memory consolidation tasks. Inhibiting C5a/C5aR1 axis reduced microglial activation, astrogliosis, and synaptic loss in the irradiated brain. Importantly, C5aR1 blockage in two syngeneic, orthotopic glioblastoma-bearing mice protected against RICD without interfering with the therapeutic efficacy of RT to reduce tumor volumein vivo. PMX205 clinical trials with healthy individuals and amyotrophic lateral sclerosis (ALS) patients showed no toxicity, drug-related adverse events, or infections. Thus, C5aR1 inhibition is a translationally feasible approach to address RICD, an unmet medical need.SIGNIFICANCECranial radiotherapy for brain cancers activates CNS complement cascade, leading to cognitive decline. Ablation of the complement C5a/C5aR1 axis alleviates radiation-induced neuroinflammation, synaptic loss, and cognitive dysfunction, providing a novel tractable approach.
Compressive Pangenomics Using Mutation-Annotated Networks
Authors: Walia Sumit , Motwani Harsh , Smith Kyle , Corbett-Detig Russell , Turakhia Yatish 
Published: July 2024

AbstractPangenomics is an emerging field that uses a collection of genomes of a species instead of a single reference genome to overcome reference bias and study the within-species genetic diversity. Future pangenomics applications will require analyzing large and ever-growing collections of genomes. Therefore, the choice of data representation is a key determinant of the scope, as well as the computational and memory performance of pangenomic analyses. Current pangenome formats, while capable of storing genetic variations across multiple genomes, fail to capture the shared evolutionary and mutational histories among them, thereby limiting their applications. They are also inefficient for storage, and therefore face significant scaling challenges. In this manuscript, we propose PanMAN, a novel data structure that is information-wise richer than all existing pangenome formats – in addition to representing the alignment and genetic variation in a collection of genomes, PanMAN represents the shared mutational and evolutionary histories inferred between those genomes. By using “evolutionary compression”, PanMAN achieves 5.2 to 680-fold compression over other variation-preserving pangenomic formats. PanMAN’s relative performance generally improves with larger datasets and it is compatible with any method for inferring phylogenies and ancestral nucleotide states. Using SARS-CoV-2 as a case study, we show that PanMAN offers a detailed and accurate portrayal of the pathogen’s evolutionary and mutational history, facilitating the discovery of new biological insights. We also presentpanmanUtils, a software toolkit that supports common pangenomic analyses and makes PanMANs interoperable with existing tools and formats. PanMANs are poised to enhance the scale, speed, resolution, and overall scope of pangenomic analyses and data sharing.
Facilitating the Virtual Exercise Games for Youth with T1D (ExerT1D) Peer Intervention: Protocol Development and Feasibility
Authors: Ash Garrett , Nam Soohyun , Stults-Kolehmainen Matthew , Haughton Adrian D. , Turek Carolyn , Chmielewski Annette , Shelver Michael , Baker Julien S. , Weinzimer Stuart A. , Nally Laura M. 
Published: July 2024

ABSTRACTBackgroundBarriers to moderate-to-vigorous physical activity (MVPA) for adolescents with type 1 diabetes (T1D) include physiology, transition to autonomy, and diabetes-specific stigma. Opportunities for T1D peer activities with T1D role model support are limited. To address this need, our single-arm pilot study tested Virtual Exercise Games for Youth with T1D (ExerT1D) for feasibility.MethodThe program included an MVPA videogame, physician-led education regarding managing T1D around MVPA, objective habitual MVPA goal-setting, and T1D management skills guided by young adult instructors living with T1D.ResultsFifteen adolescents (median age 15.4 (IQR 14.5 - 16.4) years, 7 non-Hispanic white, 7 male, median HbA1c 7.8% (IQR 7.4%-11.2%) enrolled; 13 attended 83% of sessions. Participants rated the program, comfort, instructors, and group cohesion high/very high (4.2±0.5 to 4.8±0.3 out of 5). They also rated motivation for the videogame high (4.1±0.4 out of 5). Instructor-adolescent interactions related to building T1D management skills were rated as excellent for 78% of sessions by intervention evaluators. Similarly, sharing knowledge and experiences were rated as excellent for 68% of sessions. However, adolescent-adolescent interactions were rated poorly (communication 29% excellent, peer interactions 8% excellent). The most reported barriers to participation were negative mood and oversleeping. No participants experienced diabetic ketoacidosis, severe hypoglycemia, or injuries during the study period. Compared to baseline, glycemic metrics appeared to decrease over time (d= -1.12, 90% CI [- 1.78, -0.48]).ConclusionsOverall, ExerT1D facilitated excellent peer support by engaging diverse youth with T1D in an MVPA program led by role models living with T1D.
Harnessing early multimodal motor training to drive motor recovery and brain-wide structural reorganization after stroke
Authors: Teichert Manuel , Gull Sidra , Herrmann Karl-Heinz , Gaser Christian , Reichenbach Jürgen R. , Urbach Anja , Frahm Christiane , Holthoff Knut , Witte Otto W. , Schmidt Silvio 
Published: July 2024

AbstractStroke survivors often suffer from severe motor impairments, highlighting the critical need for effective rehabilitation strategies. In experimental models, extensive task-specific motor training within the first few weeks post-stroke significantly mitigates motor deficits. However, whether more multimodal motor training approaches after stroke can restore task-specific performance in non-trained motor tasks remains largely unknown. Additionally, while stroke itself triggers structural brain reorganization, the influence of early multimodal motor training on this process remains unclear. Here, we employed T2-weighted MRI to investigate brain region-specific volumetric changes over eight weeks in rats subjected to stroke and subsequent early multimodal motor training. We found that this combination not only facilitated task-specific motor function recovery, but also induced dramatic, multi-region, brain-wide volumetric changes. Specifically, over 80 locations within 50 distinct brain regions across both hemispheres exhibited substantial volumetric alterations in a predominantly bilateral symmetric pattern. In contrast, stroke or training alone resulted in changes in 8-15 locations within 7-13 brain regions, with stroke alone primarily affecting the infarcted hemisphere. Analysis of temporal volume changes revealed two distinct trajectories in post-stroke trained rats: one of initial swelling followed by shrinkage, and another of initial shrinkage followed by swelling, suggesting an early and delayed motor learning period. Overall, our findings demonstrate that multimodal motor training early after stroke effectively restores task-specific motor function and profoundly reshapes brain structure on a brain-wide scale, offering vital insights for developing optimized rehabilitation protocols to maximize recovery in stroke patients.
Inhibition of influenza virus replication by artificial proteins (αReps) targeting its RNA-polymerase
Authors: Bessonne Mélissa , Morel Jessica , Nevers Quentin , Urvoas Agathe , Valerio-Lepiniec Marie , Crépin Thibaut , Minard Philippe , Delmas Bernard 
Published: July 2024

AbstractSeasonal epidemics and pandemics caused by influenza A viruses still represent a main public health burden in the world. Influenza viruses replicate and transcribe their genome in the nucleus of the infected cells, two functions that are supported by the viral RNA-dependent RNA-polymerase (FluPol) through extensive structural rearrangements and differential interactions with host cell factors. To get insights into its functioning, we screened a phage-display library of biosynthetic proteins (named αReps and build on a rigid alpha-helicoidal HEAT-like scaffold) against the structurally invariant FluPol core and several flexibly-linked domains of the FluPol PB2 subunit. Several αReps specific of the cap binding domain [CBD], the 627-domain and the NLS domain of the PB2 FluPol subunit displayed FluPol inhibitory and virus neutralization activities when transiently expressed in the cytosol. Furthermore, intracellular ectopic inducible expression of the αReps C3 and F3 (specific of the CBD and the 627-domain, respectively) in influenza virus permissive cells blocked transcription and multiplication of viruses representative of the H1N1, H3N2 and H7N1 subtypes, even when induced at late times post-infection. A synergic inhibitory effect on FluPol activity and virus multiplication was evidenced when the two αReps were covalently linked. These results suggest that i) interfering with FluPol structural rearrangements that are concomitant to its various activities may represent a promising strategy to block virus multiplication and to design new types of antivirals such as dual binders targeting distant sites on FluPol and ii) the 627-domain could be efficiently targeted to design influenza antivirals.Author SummaryThe influenza virus RNA-polymerase (FluPol) ensures genome transcription and replication in the nucleus of the infected cells. To select ligands able to interfere with FluPol functions, we screened a library of phages encoding biosynthetic proteins (named αReps) for binding to FluPol subunits and domains. When expressed intracellularly, several of them display efficient FluPol blocking and virus neutralizing activities. αReps C3 and F3 assembled through covalent linkages blocked FluPol activity more efficiently than their precursors. These αReps impaired multiplication of H1N1, H3N2 and H7N1 viruses, showing that their binding sites may constitute effective targets for new antiviral development.
BLOOD PROTEOMICS AND PAIN - A TRANSLATIONAL STUDY TO PROGNOSTICATE PAIN PHENOTYPES AND ASSESS NEW BIOMARKERS FOR PREVENTING PAIN IN HUMANS
Authors: Segelcke Daniel , Sondermann Julia R. , Kappert Christin , Pradier Bruno , Görlich Dennis , Fobker Manfred , Vollert Jan , Zahn Peter K. , Schmidt Manuela , Pogatzki-Zahn Esther M. 
Published: July 2024

ABSTRACTPersonalized strategies in pain management and prevention should be based on individual risk factors as early as possible, but the factors most relevant are not yet known. An innovative approach would be to integrate multi-modal risk factors, including blood proteomics, in predicting high pain responders and using them as targets for personalized treatment options. Here, we determined and mapped multi-modal factors to prognosticate a phenotype with high risk of developing pain and hyperalgesia after an experimental incision in humans. We profiled unbiased blood plasma proteome signature of 26 male volunteers, assessed psychophysical and psychological aspects before incision injury. Outcome measures were pain intensity ratings and the extent of the area of hyperalgesia to mechanical stimuli surrounding the incision as a proxy for central sensitization. Phenotype-based stratification resulted in the identification of low- and high-responders for the two different outcome measures. Logistic regression analysis revealed prognostic potential for blood plasma proteins and for psychophysical and psychological parameters. The combination of certain parameters increased the prognostic accuracy for both outcome measures, exceeding 97%. In high-responders, term-term-interaction network analysis showed a proteome signature of a low-grade inflammation reaction. Intriguingly,in silicodrug repurposing indicates a high potential for specific antidiabetic and anti-inflammatory drugs already available. In conclusion, we show an integrated pipeline that provides a valuable resource for patient stratification and the identification of (i) multi-feature prognostic models, (ii) treatment targets, and (iii) mechanistic correlates that may be relevant for individualized management of pain and its long-term consequences.One Sentence SummaryUnbiased identification of blood protein signatures in a translational human postoperative pain model provides new targets for managing pain.
Variability in Radiotherapy Outcomes Across Cancer Types: A Comparative Study of Glioblastoma Multiforme and Low-Grade Gliomas
Authors: Veviorskiy Alexander , Mkrtchyan Garik V , Osipov Andreyan N , Ozerov Ivan V , Aliper Alex , Zhavoronkov Alex , Scheibye-Knudsen Morten 
Published: July 2024

AbstractRadiotherapy is a crucial treatment option for various cancers. However, the results of radiotherapy can vary widely across different cancer types and even among patients with the same type of cancer. This variability presents a major challenge in optimizing treatment strategies and improving patient survival. Here, we collected radiotherapy phenotype and expression data from 32 TCGA cancer datasets and performed overall survival analysis for 32 cancer types. Additionally, we conducted a signalling pathway enrichment analysis to identify key pathways involved in radiotherapy resistance and sensitivity. Our findings show that radiotherapy improves survival outcomes in certain cancer types, such as GBM, while worsening outcomes in others, such as LGG. Next, we focused on exploring the differences in radiotherapy outcomes between GBM and LGG, focusing on the molecular mechanisms contributing to these variations. The differential regulation of pathways related to programmed cell death, DNA repair, telomere maintenance, chromosome condensation, antiviral responses, and interferon signaling between GBM and LGG patients may elucidate the underlying reasons for these observed differences. These insights underscore the importance of personalized treatment approaches and the need for further research to improve radiotherapy outcomes in cancer patients.
Activated RNAi does not rescue piRNA pathway deficiency in testes
Authors: Taborska Eliska , Loubalova Zuzana , Kulmann Marcos Iuri Roos , Malik Radek , Buccheri Valeria , Pasulka Josef , Horvat Filip , Jenickova Irena , Sedlacek Radislav , Svoboda Petr 
Published: July 2024

AbstractRNA interference (RNAi) and PIWI-associated RNAs (piRNA) pathways use small RNAs as sequence-specific guides to repress transposable elements. In mice, the loss ofMili, an essential piRNA pathway factor, causes male sterility associated with mobilization of LINE L1 retrotransposons while female mutants remain fertile. At the same time, mouse oocytes have exceptionally active RNAi thanks to an oocyte-specific variant of RNase III Dicer, which efficiently makes small RNAs from long dsRNA substrates. In oocytes of mice lacking functional MILI and the oocyte-specific Dicer variant, we previously observed that L1 retrotransposons are redundantly targeted by both, RNAi and piRNA pathways. To test whether enhanced RNAi may reduce theMilimutant phenotype in testes, we used transgenic mice ectopically expressing the oocyte-specific Dicer variant during spermatogenesis. We report here that this genetic modification increases siRNA biogenesis and supports RNAi but is not sufficient to reduce spermatogenic defects caused by the loss ofMili.