bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection conferred by Delta and BA.1/BA.2 infection against BA.4/BA.5 infection and hospitalization: A Retrospective Cohort Study
Authors: Winchester Nicole E , Shrestha Nabin K. , Kim Priscilla , Tereshchenko Larisa G. , Rothberg Michael B 
Published: November 2022

AbstractBackgroundSARS-CoV-2 immunity has declined with subsequent waves and accrual of viral mutations. In vitro studies raise concern for immune escape by BA.4/BA.5, and a study in Qatar showed moderate protection, but these findings have yet to be reproduced.MethodsThis retrospective cohort study included individuals tested for COVID-19 by PCR during Delta or BA.1/BA.2 and retested during BA.4/BA.5. The preventable fraction (PF) was calculated as ratio of the infection/hospitalization rate for initially positive patients divided by infection/hospitalization rate for initially negative patients, stratified by age, and adjusted for age, gender, comorbidities, and vaccination using logistic regression.Results20,987 patients met inclusion criteria. Prior Delta infection provided no protection against BA.4/BA.5 infection (Adjusted PF: 11.9% (95% confidence interval [CI], 0.8-21.8); p=0.036) and minimal protection against hospitalization (Adjusted PF: 10.7% (95%CI, 4.9-21.7); p=0.003). In adjusted models, prior BA.1/BA.2 infection provided 45.9% (95%CI, 36.2-54.1) (p <0.001) protection against BA.4/BA.5 reinfection and 18.8% (95% CI, 10.3-28.3) (p<0.0001) protection against hospitalization. Up-to-date vaccination provided modest protection against reinfection with BA.4/BA.5 and hospitalization.ConclusionsPrior infection with BA.1/BA.2 and up-to-date vaccination provided modest protection against infection with BA.4/BA.5 and hospitalization, while prior Delta infection provided minimal protection against hospitalization, and no infection protection.
Volatile Organic Compounds for the Detection of Hepatocellular Carcinoma – a Systematic Review
Authors: Metwaly Sayed , Psica Alicja , Sogaolu Opeyemi , Ahmed Irfan , Mukhopadhya Ashis , Delibegović Mirela , Bekheit Mohamed 
Published: November 2022

AbstractBackgroundHepatocellular carcinoma (HCC) is an increasingly common and one of the leading causes of cancer mortality worldwide. Only a small percentage of HCC patients are eligible to curative treatment. There is a need for a point of care, early diagnostic or screening tool. It is not clear whether exhaled volatile organic compounds (VOCs) could fulfil those needs.HypothesisWe postulate that exhaled VOCs can identify potential biomarkers for non-invasive detection of HCC.AimsThis systematic review aims to critically review the current knowledge regarding the exhaled VOCs linked to HCC detection.MethodsA systematic electronic search was conducted. Search strategy included all studied published until the 24th of March 2021 using a combination of relevant keywords.ResultsThe search yielded 6 publications using the PRISMA pathway. Two of the studies described in vitro experiments, and four clinical studies were conducted on small groups of patients. Overall, 42 headspace gases were analysed in the in vitro studies. Combined, the clinical studies included 164 HCC patients and 260 controls. The studies reported potential role for a combination of VOCs in the diagnosis of HCC. However, only limonene, acetaldehyde and ethanol could be traced back to their biological pathways using KEGG pathway enrichment analysis.ConclusionsAlthough there appears to be promise in VOCs research associated with HCC, there is no single volatile biomarker in exhaled breath attributed to HCC and data from extracted studies indicates a lack of standardization. Large population studies are required to verify the existence of VOCs linked to HCC.
Costs and models used in the economic analysis of Total Knee Replacement (TKR): A Systematic Review
Authors: Gandhi Naline , Qadeer Amatullah Sana , Meher Ananda , Rachel Jennifer , Patra Abhilash , John Jebamalar , Anilkumar Aiswarya , Dutta Ambarish , Nanda Lipika , Rout Sarit Kumar 
Published: November 2022

AbstractObjectivesThe major objective of this review was to summarize the evidence on the core modelling specifications and procedures on the cost-effectiveness of TKR compared to non-surgical management. Another objective of this study was to synthesize evidence of TKR cost and compare it across countries using purchasing power parity (PPP).MethodologyThe electronic databases used were MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), HTAIn repository and Cost effectiveness Analysis (CEA) registry. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) was used to assess the validity of the methods and transparency in reporting the results of the included studies. The cost of TKR surgery from high income and low-or middle-income countries were extracted and converted to single USD ($) using purchasing power parities (PPP) method.Result29 studies were included in this review, out of which eight studies used Markov model, five studies used regression model, one study each reported Marginal structure model and discrete simulation model and decision tree analysis to assess cost-effectiveness of TKR. For PPP, 23 studies were included in the analysis of TKR cost. The average cost of TKR surgery was lowest in developing country like India ($3457) and highest in USA ($19,645).ConclusionThe findings of this review showed that the Markov model was most widely used in the analysis of the cost effectiveness of TKR. Our review also concluded that the cost of TKR was higher in developed countries as compared to developing countries.
Dysfunction of the Visual Sensory Thalamus in Developmental Dyslexia
Authors: Müller-Axt Christa , Kauffmann Louise , Eichner Cornelius , von Kriegstein Katharina 
Published: November 2022

AbstractDevelopmental dyslexia (DD) is a reading disorder with a prevalence of 5-10%. Neuroscientific research has typically focused on explaining DD symptoms based on pathophysiological changes in the cerebral cortex. However, DD might also be associated with alterations in sensory thalami – central subcortical stations of sensory pathways. A post-mortem study on the visual sensory thalamus (lateral geniculate nucleus, LGN) showed histopathological changes in the magnocellular (M-LGN), but not in the parvocellular (P-LGN), subdivisions. M-LGN and P-LGN have different functional properties and belong to two different visual systems. Whether M-LGN alterations also exist in DDin-vivois unclear. Also, the potential relevance of M-LGN alterations to DD symptoms is unknown. This lack of knowledge is partly due to considerable technical challenges in investigating LGN subdivisions non-invasively in humans. Here, we employed recent advances in high-field 7 Tesla functional magnetic resonance imaging (fMRI) to map the M- and P-LGNin-vivoin DD adults (n=26) and matched controls (n=28). We show that (i) M-LGN responses differ between DD and control participants, (ii) these differences are more pronounced in male than in female DD participants, and (iii) M-LGN alterations predict a core symptom of DD in male DD participants only, i.e., rapid naming ability. Our results provide a first functional interpretation of M-LGN changes in DD and support DD theories that propose a direct relevance of sensory thalamus alterations for DD symptoms. In addition, the sex-specific behavioral relevance of M-LGN alterations within DD calls for taking sex differences into account when planning brain-based therapeutic interventions.Significance StatementDevelopmental dyslexia (DD) is one of the most common learning disorders affecting millions of children and adults world-wide. Several decades ago, pioneering research in five DD post-mortem brains suggested that DD is characterized not only by alterations of the cerebral cortex, but also by changes in a subsection of the visual sensory thalamus – the so-called M-LGN. The relevance of these findings for DD remained highly controversial. Using recent developments in high-resolution functional neuroimaging, we now discovered that M-LGN alterations are present also in DDin-vivoand predict a core symptom of DD in males. Our results provide a first functional interpretation of M-LGN alterations in DD and provide a basis for better understanding sex-specific differences in DD.
Chromatin states at homeoprotein loci distinguish axolotl limb segments prior to regeneration
Authors: Kawaguchi Akane , Wang Jingkui , Knapp Dunja , Murawala Prayag , Nowoshilow Sergej , Masselink Wouter , Taniguchi-Sugiura Yuka , Fei Jifeng , Tanaka Elly M. 
Published: November 2022

AbstractThe salamander limb regenerates only the missing portion. Each limb segment can only form segments equivalent to- or more distal to their own identity, relying on a property termed “positional information”. How positional information is encoded in limb cells has been unknown. By cell-type-specific chromatin profiling of upper arm, lower arm, and hand, we found segment-specific levels of histone H3K27me3 at limb homeoprotein gene loci but not their upstream regulators, constituting an intrinsic segment information code. During regeneration, regeneration-specific regulatory elements became active prior to the re-appearance of developmental regulatory elements. This means that, in the hand segment, the permissive chromatin state of the hand homeoprotein geneHoxA13engages with regeneration regulatory elements, bypassing the upper limb program.
Transcription regulates bleb formation and stability independent of nuclear rigidity
Authors: Berg Isabel K. , Currey Marilena L. , Gupta Sarthak , Berrada Yasmin , Viet Bao Nyugen , Pho Mai , Patteson Alison E. , Schwarz J. M. , Banigan Edward J. , Stephens Andrew D. 
Published: November 2022

AbstractChromatin is an essential component of nuclear mechanical response and shape that maintains nuclear compartmentalization and function. The biophysical properties of chromatin alter nuclear shape and stability, but little is known about whether or how major genomic functions can impact the integrity of the nucleus. We hypothesized that transcription might affect cell nuclear shape and rupture through its effects on chromatin structure and dynamics. To test this idea, we inhibited transcription with the RNA polymerase II inhibitor alpha-amanitin in wild type cells and perturbed cells that present increased nuclear blebbing. Transcription inhibition suppresses nuclear blebbing for several cell types, nuclear perturbations, and transcription inhibitors. Furthermore, transcription is necessary for robust nuclear bleb formation, bleb stabilization, and bleb-based nuclear ruptures. These morphological effects appear to occur through a novel biophysical pathway, since transcription does not alter either chromatin histone modification state or nuclear rigidity, which typically control nuclear blebbing. We find that active/phosphorylated RNA pol II Ser5, marking transcription initiation, is enriched in nuclear blebs relative to DNA. Thus, transcription initiation is a hallmark of nuclear blebs. Polymer simulations suggest that motor activity within chromatin, such as that of RNA pol II, can generate active forces that deform the nuclear periphery, and that nuclear deformations depend on motor dynamics. Our data provide evidence that the genomic function of transcription impacts nuclear shape stability, and suggests a novel mechanism, separate and distinct from chromatin rigidity, for regulating large-scale nuclear shape and function.
Discovery, Synthesis, and Optimization of 1,2,4-Triazolyl Pyridines TargetingMycobacterium tuberculosis
Authors: Berida Tomayo , McKee Samuel R. , Chatterjee Shamba , Li Wei , Pandey Pankaj , Tripathi Siddharth Kaushal , Doerksen Robert J. , Jackson Mary , Ducho Christian , Stallings Christina L. , Roy Sudeshna 
Published: November 2022

ABSTRACTTuberculosis (TB) results in 1.5 million deaths every year. The rise in multi-drug resistant TB underscores the urgent need to develop new antibacterials, particularly those with new chemical entities and/or novel mechanisms of action that can be used in combination therapy with existing drugs to prevent the rapid emergence of resistance. Herein, we report the discovery and synthesis of a new series of compounds containing a 3-thio-1,2,4-triazole moiety that show inhibition ofMycobacterium tuberculosis(Mtb) growth and survival. Structure-activity relationship studies led us to identify potent analogs displaying nanomolar inhibitor activity, specifically againstMtb. These potent analogs exhibit a promising ADME/pharmacokinetic profile and no cytotoxicity in mammalian cells at over 100 times the effective dose inMtb. Our preliminary investigations into the mechanism of action suggest this series is not engaging promiscuous targets and, thereby, could be acting on a novel target.Abstract Figure
Ketone ester-enriched diet ameliorates motor and dopamine release deficits in MitoPark mice
Authors: Mahajan Vikrant R. , Nadel Jacob A. , King M. Todd , Pawlosky Robert J. , Davis Margaret I. , Veech Richard L. , Lovinger David M. , Salinas Armando G. 
Published: November 2022

AbstractBackgroundParkinson’s disease is a progressive, neurodegenerative disease characterized by motor dysfunction and dopamine deficits. The MitoPark mouse recapitulates several facets of Parkinson’s disease, including gradual development of motor deficits, which enables the study of potential therapeutic interventions. One therapeutic strategy involves decreasing the mitochondrial metabolic load by inducing ketosis and providing an alternative energy source for neurons, leading to decreased neuronal oxidative stress.ObjectiveWe assessed whether administration of a ketone ester-enriched diet would improve motor and dopamine release deficits in MitoPark mice.MethodsMotor function (rotarod and open field tests), dopamine release (fast-scan cyclic voltammetry), tissue dopamine levels (GC-MS), and dopamine neurons and axons (immunofluorescence) were assessed in MitoPark and control mice fed either the standard or ketone ester-enriched diets.ResultsWhen started on the ketone diet before motor dysfunction onset, MitoPark mice had preserved motor function relative to standard diet MitoPark mice. While the ketone ester enriched diet did not preserve dopamine neurons or striatal dopamine axons, dopamine release in ketone diet MitoPark mice was greater than standard diet MitoPark mice but less than control mice. In a follow up experiment, we began the ketone diet after motor dysfunction onset and observed a modest preservation of motor function in ketone diet MitoPark mice relative to standard diet MitoPark mice.ConclusionThe improvement in motor dysfunction indicates that a ketone ester enriched diet or ketone supplement may represent a promising adjunct treatment for Parkinson’s disease.
Tracking lexical and semantic prediction error underlying the N400 using artificial neural network models of sentence processing
Authors: Lopopolo Alessandro , Rabovsky Milena 
Published: November 2022

AbstractRecent research has shown that the internal dynamics of an artificial neural network model of sentence comprehension displayed a similar pattern to the amplitude of the N400 in several conditions known to modulate this event-related potential. These results led Rabovsky, Hansen, and McClelland (2018) to suggest that the N400 might reflect change in an implicit predictive representation of meaning corresponding to semantic prediction error. This explanation stands as an alternative to the hypothesis that the N400 reflects lexical prediction error as estimated by word surprisal (Frank, Otten, Galli, & Vigliocco, 2015). In the present study, we directly model the amplitude of the N400 elicited during naturalistic sentence processing by using as predictor the update of the distributed representation of sentence meaning generated by a Sentence Gestalt model (McClelland, St. John, & Taraban, 1989) trained on a large-scale text corpus. This enables a quantitative prediction of N400 amplitudes based on a cognitively motivated model, as well as quantitative comparison of this model to alternative models of the N400. Specifically, we compare the update measure from the SG model to surprisal estimated by a comparable language model trained on next word prediction. Our results suggest that both Sentence Gestalt update and surprisal predict aspects of N400 amplitudes. Thus, we argue that N400 amplitudes might reflect two distinct but probably closely related sub-processes that contribute to the processing of a sentence.
Cortical reactivations predict future sensory responses
Authors: Nguyen Nghia D. , Lutas Andrew , Fernando Jesseba , Vergara Josselyn , McMahon Justin , Dimidschstein Jordane , Andermann Mark L. 
Published: November 2022

SummaryPrevailing theories of offline memory consolidation posit that the pattern of neurons activated during a salient sensory experience will be faithfully reactivated, thereby stabilizing the entire pattern1-3. However, sensory-evoked patterns are not stable, but instead drift across repeated experiences4-7. To investigate potential roles of reactivations in the stabilization and/or drift of sensory representations, we imaged calcium activity of thousands of excitatory neurons in mouse lateral visual cortex. Presentation of a stimulus resulted in transient, stimulus-specific reactivations during the following minute. These reactivations depended on local circuit activity, as they were abolished by local silencing during the preceding stimulus. Contrary to prevailing theories, reactivations systemically differed from previous patterns evoked by the stimulus. Instead, they were more similar to future patterns evoked by the stimulus, therebypredictingrepresentational drift. In particular, neurons that participated more or less in early reactivations than in stimulus response patterns subsequently increased or decreased their future stimulus responses, respectively. The rate and content of these reactivations was sufficient to accurately predict future changes in stimulus responses and, surprisingly, the decreasing similarity of responses to distinct stimuli. Thus, activity patterns during sensory cortical reactivations may guide the drift in sensory responses to improve sensory discrimination8.
Lysosomes mediate the mitochondrial UPR via mTORC1-dependent ATF4 phosphorylation
Authors: Li Terytty Yang , Wang Qi , Gao Arwen W. , Li Xiaoxu , Mottis Adrienne , Shong Minho , Auwerx Johan 
Published: November 2022

AbstractLysosomes are central platforms for not only the degradation of macromolecules but also the integration of multiple signaling pathways. However, whether and how lysosomes mediate the mitochondrial stress response (MSR) remain largely unknown. Here, we demonstrate that lysosomal acidification via the vacuolar H+-ATPase (v-ATPase) is essential for the transcriptional activation of the mitochondrial unfolded protein response (UPRmt). Mitochondrial stress stimulates v-ATPase-mediated lysosomal activation of the mechanistic target of rapamycin complex 1 (mTORC1), which then directly phosphorylates the MSR transcription factor, activating transcription factor 4 (ATF4). Disruption of mTORC1-dependent ATF4 phosphorylation blocks the UPRmt, but not other similar stress responses, such as the UPRER. Finally, ATF4 phosphorylation downstream of the v-ATPase/mTORC1 signaling is indispensable for sustaining mitochondrial redox homeostasis and protecting cells from reactive oxygen species (ROS)-associated cell death upon mitochondrial stress. Thus, v-ATPase/mTORC1-mediated ATF4 phosphorylation via lysosomes links mitochondrial stress to UPRmtactivation and mitochondrial function resilience.
Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases
Authors: Talbot Steven R. , Kumstel Simone , Schulz Benjamin , Tang Guanglin , Abdelrahman Ahmed , Seume Nico , Wendt Edgar Heinz Uwe , Eichberg Johanna , Häger Christine , Bleich Andre , Vollmar Brigitte , Zechner Dietmar 
Published: November 2022

AbstractThe fundament of an evidence-based severity assessment in laboratory animal science is reliable distress parameters. Many readouts are used to evaluate and determine animal distress and the severity of experimental procedures. Therefore, we analyzed four distinct parameters like the body weight, burrowing behavior, nesting, and distress score in the four gastrointestinal animal models (pancreatic ductal adenocarcinoma (PDA), pancreatitis, CCl4intoxication, and bile duct ligation (BDL)). Further, we determined the parameters‘ robustness in various experimental subgroups due to slight variations like drug treatment or telemeter implantations. We used non-parametric bootstrapping to get robust estimates and 95 % confidence intervals for the experimental groups. It was found that the performance of the readout parameters is model-dependent and that the distress score is prone to experimental variation. On the other hand, we also found that burrowing and nesting can be more robust than, e.g., the body weight when evaluating PDA. However, the body weight still was highly robust in BDL, pancreatitis, and CCl4intoxication. To address the complex nature of the multi-dimensional severity space, we used the Relative Severity Assessment (RELSA) procedure to combine multiple distress parameters into a score and mapped the subgroups and models against a defined reference set obtained by telemeter implantation. This approach allowed us to compare the severity of individual animals in the experimental subgroups using the maximum achieved severity (RELSAmax). With this, the following order of severity was found for the animal models: CCl4< PDA ≈ Pancreatitis < BDL. Furthermore, the robustness of the RELSA procedure and outcome was externally validated with a reference set from another laboratory also obtained from telemeter implantation. Since the RELSA procedure reflects the multi-dimensional severity information and is highly robust in estimating the quantitative severitywithinandbetweenmodels, it can be deemed a valuable tool for laboratory animal severity assessment.
The nature-nurture transform underlying the emergence of reliable cortical representations
Authors: Trägenap Sigrid , Whitney David E. , Fitzpatrick David , Kaschube Matthias 
Published: November 2022

AbstractThe fundamental structure of cortical networks arises early in development prior to the onset of sensory experience. However, how endogenously generated networks respond to the onset of sensory experience, and how they form mature sensory representations with experience remains unclear. Here we examine this ‘nature-nurture transform’ usingin vivocalcium imaging in ferret visual cortex. At eye-opening, visual stimulation evokes robust patterns of cortical activity that are highly variable within and across trials, severely limiting stimulus discriminability. Initial evoked responses are distinct from spontaneous activity of the endogenous network. Visual experience drives the development of low-dimensional, reliable representations aligned with spontaneous activity. A computational model shows that alignment of novel visual inputs and recurrent cortical networks can account for the emergence of reliable visual representations.One sentence summaryThe reliability of cortical representations emerges from experience-driven reorganization of endogenous networks