bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Experience of Deep Brain Stimulation Surgery in a Developing Southeast Asian Country
Authors: Dy Closas Alfand Marl F. , Tan Ai Huey , Tay Yi Wen , Hor Jia Wei , Toh Tzi Shin , Lim Jia Lun , Lew Choey Yee , Cham Chun Yoong , Yim Carolyn Chue Wai , Chee Kok Yoon , Ng Chong Guan , Lit Lei Cheng , Anuar Anis Nadhirah Khairul , Lange Lara M. , Fang Zih-Hua , Ciga Sara Bandres , Lohmann Katja , Klein Christine , Ahmad-Annuar Azlina , Muthusamy Kalai Arasu , Lim Shen-Yang 
Published: August 2023

ABSTRACTBackgroundThe availability of deep brain stimulation (DBS), a highly efficacious treatment for several movement disorders, remains low in developing countries, with scarce data available on utilization and outcomes.ObjectivesWe characterized the DBS cohort and outcomes at a Malaysian quaternary medical centre.MethodsA retrospective chart review was done on DBS-related surgery at the University of Malaya, including clinico-demographic, genetics, and outcomes data focusing on post-operative medication reduction and complications.Results149 Parkinson’s disease (PD) patients underwent DBS targeting the subthalamic nucleus. Six had globus pallidus internus DBS (primarily for dystonia). Only 16.1% of cases were government-funded. Of the 133 PD patients operated in the past decade (2013-2022), 25 (18.8%) had disease duration <5 years. At 6-12 months post-DBS, median levodopa-equivalent daily dosage (LEDD) reduction was 440.5 [418.9] mg/day, corresponding to a reduction of ≥50% and ≥30% in 42.2% and 69.8% of patients, respectively. LEDD reductions were larger in the early-onset and short-duration subgroups. Three patients (1.9% of 155) had symptomatic intracranial hemorrhage, resulting in stroke in two. Pathogenic monogenic orGBA1variants were detected in 12/61 (19.7%) of patients tested, mostly comprising the “severe”GBA1variant p.L483P (14.8%).ConclusionThis is the largest report on DBS from Southeast Asia. The procedures were effective, and complication rates on par with international norms. Our study found a high frequency ofGBA1-PD; and included a substantial number of patients with short-duration PD, who had good outcomes. It also highlights the inequity of access to device-aided therapy.
Generating realistic neurophysiological time series with denoising diffusion probabilistic models
Authors: Vetter Julius , Macke Jakob H. , Gao Richard 
Published: August 2023

AbstractIn recent years, deep generative models have had a profound impact in engineering and sciences, revolutionizing domains such as image and audio generation, as well as advancing our ability to model scientific data. In particular, Denoising Diffusion Probabilistic Models (DDPMs) have been shown to accurately model time series as complex high-dimensional probability distributions. Experimental and clinical neuroscience also stand to benefit from this progress, since accurate modeling of neurophysiological time series, such as electroencephalography (EEG), electrocorticography (ECoG), and local field potential (LFP) recordings, and their synthetic generation can enable or improve a variety of neuroscientific applications. Here, we present a method for modeling multi-channel and densely sampled neurophysiological recordings using DDPMs, which can be flexibly applied to different recording modalities and experimental configurations. First, we show that DDPMs can generate realistic synthetic data for a variety of datasets including different recording techniques (LFP, ECoG, EEG) and species (rat, macaque, human). DDPM-generated time series accurately capture single- and multi-channel statistics such as frequency spectra and phase-amplitude coupling, as well as fine-grained and dataset-specific features such as sharp wave-ripples. In addition, synthetic time series can be generated based on additional information like experimental conditions or brain states. We demonstrate the utility and flexibility of DDPMs in several neuroscience-specific analyses, such as brain-state classification and imputation of missing channels to improve neural decoding. In summary, DDPMs can serve as accurate generative models of neurophysiological recordings, and have a broad utility in the probabilistic generation of synthetic time series for neuroscientific applications.
Hormonal induction, quality assessments and the influence of seasonality on male reproductive viability in a long-term managedex situbreeding colony of Southern Rocky Mountain Boreal toads,Anaxyrus boreas boreas
Authors: Calatayud N.E. , Jacobs Leah , Togna Gina Della , Langhorne Cecilia J. , Mullen Amanda C. , Upton Rose 
Published: August 2023

ABSTRACTThe Southern Rocky Mountain Boreal Toad (Anaxyrus boreas boreas)is anex situmanaged species which relies heavily on the use of assisted reproductive technologies to augment existingin situpopulations. Despite the use of ARTs to manipulate reproduction of this species, theex situprogram continues to face challenges with annual reproduction. Human chorionic gonadotropin (hCG) at 10 IU/gbw singly or in combination with 0.4 ug/gbw GnRH-A have been successfully reported for this species, however, with a number of other available hormones, it is not clear if these are the most effective protocols for this species. Moreover, there is no information on how exogenous hormone administration is affected by other factors such as seasonality. Therefore, in the first part of this study, we compare the efficacy of the 10 IU/g hCG and 0.4 Lg/g Gonadotropin Releasing Hormone agonist (GnRH-A) administered singly or in combination, as well as GnRH-Apd + Amphiplex (0.4 Lg/g GnRH-A + 10 Lg/g Metoclopramide [MET] - a dopamine antagonist), or 10 Lg/g MET alone. Spermiation responses and sperm viability were compared across treatments with hormonal curves then correlated to seasonality. The results of this study suggest that the optimal hormonal stimulation protocol, across all treatments, in terms of sperm quality was 10 IU/g hCG + 0.4 Lg/g GnRH-A. Further optimization is required, in particular the exploration of higher doses of GnRH-A. Lastly, we observed that the effect of seasonality influenced the hormonal efficacy and magnitude of the spermiation response. As was expected, quality and concentration parameters were affected by the month in which hormone administration occurred.HIGHLIGHTSSpermiation in the Southern Rocky Mountain Boreal toad,Anaxyrus boreas boreas,is elicited most effectively by hCG singly or in combination with GnRH-A.Spermiation responses lasted up to 96 hours post injection (hpi) though quantity and quality parameters were highest in the first 12 hpi.Total motility, forward progressive motility and percentage live cells all indicatedA. b. boreassperm quality was in a good range.Acrosome integrity requires more research as it was comparatively lower than expected.Responses to hormone inductions are seasonally affected in this species but suggest semi-discontinuous cycling.Ex situ breeding should perform better sperm assessments before designing breeding strategies.
Polybacterial intracellular coinfection of epithelial stem cells in periodontitis
Authors: Easter Quinn T. , Matuck Bruno Fernandes , Stark Germán Beldorati , Worth Catherine L. , Predeus Alexander V. , Fremin Brayon , Huynh Khoa , Ranganathan Vaishnavi , Pereira Diana , Weaver Theresa , Miller Kathryn , Perez Paola , Hasuike Akira , Chen Zhaoxu , Bush Mandy , Warner Blake M. , Lee Janice , Wallet Shannon M. , Sequeira Inês , Tyc Katarzyna M. , Liu Jinze , Ko Kang I. , Teichmann Sarah A. , Byrd Kevin M. 
Published: August 2023

ABSTRACTPeriodontitis affects billions of people worldwide. To address interkingdom relationships of microbes and niche on periodontitis, we generated the first sin-gle-cell meta-atlas of human periodontium (34-sample, 105918-cell), harmo-nizing 32 annotations across 4 studies1–4. Highly multiplexed immunofluores-cence (32-antibody; 113910-cell) revealed spatial innate and adaptive immune foci segregation around tooth-adjacent epithelial cells. Sulcular and junctional keratinocytes (SK/JKs) within epithelia skewed toward proinflammatory phe-notypes; diseased JK stem/progenitors displayed altered differentiation states and chemotactic cytokines for innate immune cells. Single-cell metagenomics utilizing unmapped reads revealed 37 bacterial species.16Sand rRNA probes detected polybacterial intracellular pathogenesis (“co-infection”) of 4 species within single cells for the first time in vivo. Challenging coinfected primary human SK/JKs with lipopolysaccharide revealed solitary and synergistic ef-fects. Coinfected single-cell analysis independently displayed proinflammatory phenotypes in situ. Here, we demonstrate the first evidence of polybacterial intracellular pathogenesis in human tissues and cells—potentially influencing chronic diseases at distant sites.
Altered metabolic function induced by amyloid-beta oligomers and PSEN1-mutations in iPSC-derived astrocytes
Authors: Elsworthy R. J. , Finelli M. J. , Aqattan S. , Dunleavy C. , King M. , Ludlam A. , Allen S. L. , Prosser S. , Chen R. , Jarquin S. Martinez , Kim D. H. , Brown J. , Parri H. R. , Aldred S. , Hill E. J. 
Published: August 2023

AbstractAltered energy metabolism in Alzheimer’s disease (AD) is considered a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are increasingly implicated in multiple neurodegenerative diseases. We report that astrocytes differentiated from early onset familial Alzheimer’s disease (fAD) patients or control cells treated with Amyloid β oligomers exhibit significant changes in their metabolism including glucose uptake, glutamate uptake and lactate release, with increases in oxidative and glycolytic metabolism. Furthermore, we demonstrate evidence of gliosis in fAD astrocytes in addition to a change in metabolic pathways including glutamate, purines, arginine, and the citric acid cycle. Homeostatic responses to brain activity and cellular metabolism are central to normal brain function. However, altered brain metabolism and cellular stress present significant risk factors for the onset and progression of neurodegenerative disease. This study demonstrates that fAD derived astrocytes present multiple metabolic and disease associated phenotypes early in their development suggesting that chronic alterations in fAD patient early in life that present significant risk factors for disease progression in mid-life and suggest key targets for potential diagnostic features and therapeutic agents late onset dementia in midlife.
SQANTI-SIM: a simulator of controlled transcript novelty for lrRNA-seq benchmark
Authors: Mestre-Tomás Jorge , Liu Tianyuan , Pardo-Palacios Francisco , Conesa Ana 
Published: August 2023

AbstractLong-read RNA-seq has emerged as a powerful tool for transcript discovery, even in well-annotated organisms. However, assessing the accuracy of different methods in identifying annotated and novel transcripts remains a challenge. Here, we present SQANTI-SIM, a versatile utility that wraps around popular long-read simulators to allow precise management of transcript novelty based on the structural categories defined by SQANTI3. By selectively excluding specific transcripts from the reference dataset, SQANTI-SIM effectively emulates scenarios involving unannotated transcripts. Furthermore, the tool provides customizable features and supports the simulation of additional types of data, representing the first multi-omics simulation tool for the lrRNA-seq field. We demonstrate the effectiveness of SQANTI-SIM by benchmarking five transcriptome reconstruction pipelines using the simulated data.
Cell free expression in proteinosomes prepared from native protein-PNIPAAm conjugates
Authors: Gao Mengfei , Wang Dishi , Leng Weihua , Wilsch-Bräuninger Michaela , Schulte Jonathan , Morgner Nina , Appelhans Dietmar , Tang T-Y. Dora 
Published: August 2023

AbstractTowards the goal of building synthetic cells from the bottom-up, the establishment of micrometer-sized compartments that contain and support cell free transcription and translation that couple cellular structure to function is of critical importance. Proteinosomes, formed from crosslinked cationized protein-polymer conjugates offer a promising solution to membrane-bound compartmentalisation with an open, semi-permeable membrane. Critically, to date, there have been no demonstration of cell free transcription and translation within water-in-water proteinosomes. Herein, we present a novel approach to the fabrication of proteinosomes directly from native protein-polymer (BSA-PNIPAAm) conjugates. We show that these native proteinosomes offer an excellent alternative as artificial cell chassis. Significantly, the native proteinosomes are stable under high salt conditions and can consequently support cell free transcription and translation. The native proteinosomes offer enhanced protein expression compared to proteinosomes prepared from traditional methodologies. Furthermore, we demonstrate the integration of proteinosomes into higher order cellular architectures with membrane free compartments and liposomes. The integration of bioinspired architectural elements with the central dogma is an essential building block for realizing minimal synthetic cells and is key for exploiting artificial cells in real-world applications.
Long-term hematopoietic stem cells trigger quiescence inLeishmaniaparasites
Authors: Dirkx Laura , Acker Sara Van , Nicolaes Yasmine , Cunha João Luís Reis , Ahmad Rokaya , Caljon Ben , Imamura Hideo , Ebo Didier G. , Jeffares Daniel C. , Sterckx Yann G.-J. , Maes Louis , Hendrickx Sarah , Caljon Guy 
Published: August 2023

SUMMARYQuiescence and posttreatment relapse constitute an important therapeutic constraint across the microbiological spectrum. This study unveils thatLeishmania infantumandL. donovaniparasites rapidly enter quiescence after an estimated 4-6 divisions in both mouse and human stem cells of the bone marrow but not in macrophages as primary host cells. Quiescent amastigotes display a reduced size and evidence for a rapid evolutionary adaptation response with genetic alterations. We formally demonstrate that acquisition of a quiescent phenotype endows parasites with a capacity to survive antileishmanial treatment. Transition through quiescence also results in an increased cellular infectivity and high transmission capacity through the sand fly vector. Transcriptional profiling of quiescent and non-quiescent metabolic states identified a limited set of 26 upregulated genes that are of particular interest given their predicted involvement as regulators of cell cycle progression and of gene expression at various levels. The differential gene set constitutes a reliable source for the identification of novel markers and potential drivers of quiescence, a metabolic state bestowing parasites the capacity to escape drug treatment.
Disentangling the neural correlates of semantic and domain-general control: The roles of stimulus domain and task process
Authors: Hodgson Victoria J. , Lambon Ralph Matthew A. , Jackson Rebecca L. 
Published: August 2023

ABSTRACTControl processes are critical for the context-appropriate use of meaningful stimuli. Similar definitions have been adopted in two distinct literatures focusing on identifying the neural correlates of ‘semantic control’ and of executive control across domains (the ‘multiple demand network’). Surprisingly, despite their proposed functions varying only in relation to domain-specificity, these networks appear to differ anatomically. However, prior comparisons are confounded by variations in task design. To what extent might varying task requirements drive differences in activation patterns that are typically attributed to stimulus domain? Here, for the first time, we use functional MRI to disentangle the effects of task process and stimulus domain during cognitively demanding tasks. Participants performed an odd-one-out task requiring rule-switching, inhibition and selection processes, and ann-back working memory task, each with meaningful semantic and non-semantic stimuli, in a factorial design. Both stimulus domain and task process affected the control regions activated, indicating that task process is indeed a key factor confounding prior studies. However, core semantic control regions (left inferior frontal gyrus, left posterior temporal cortex) also showed a preference for semantic stimuli even with matched task processes, while more peripheral semantic control regions, overlapping the multiple demand network (dorsomedial prefrontal cortex, right inferior frontal gyrus), showed little preference across task or stimulus. Conversely, most multiple demand network regions were preferentially engaged for non-semantic stimuli. These results highlight the mutual importance of stimulus domain and task process in driving variation in control region engagement, both across and between semantic control and multiple demand networks.SIGNIFICANCE STATEMENTThe flexible, context-appropriate use of concepts requires the selection, inhibition and manipulation of meaningful information. These control processes are thought to be supported by different areas for conceptual processing compared to other task domains. This proposed ‘special’ character of semantic control has important ramifications for the nature of executive control. However, prior assessments confound the presence of meaningful stimuli with the task operations performed. Here we disentangle the effects of task process and stimulus domain for the first time, finding critical effects of both factors on the pattern of activated control regions. The results enhance our understanding of the semantic control network and how it differs from and interacts with the domain-general multiple demand network, functionally characterising each control region.
Plasmodium falciparumRaf kinase inhibitor is a lipid binding protein that interacts with CDPK1 and regulates its activity in asexual blood stage
Authors: Sharma Manish , Krishnan Deepak , Negi Pooja , Rani Komal , Revikumar Amjesh , Munde Manoj , Bansal Abhisheka 
Published: August 2023

ABSTRACTRaf Kinase Inhibitor Protein (RKIP) is an important regulator of MAPK signaling pathway in multicellular eukaryotes.Plasmodium falciparumRKIP (PfRKIP) is a putative phosphatidylethanolamine binding protein (PEBP) that shares limited similarity withHomo sapiensRKIP (HsRKIP). Interestingly, critical components of MAPK pathway are not expressed in malaria parasite and the physiological function of PfRKIP remains unknown. PfRKIP is expressed throughout the asexual schizogony with maximum expression in late schizonts. Interestingly, PfRKIP and HsRKIP show pH dependent differential interaction profiles with various lipids. At physiological pH, PfRKIP show interaction with PE and lipids containing phosphorylated phosphatidylinositol group; however, HsRKIP show no interaction under the same conditions. Mutation of conserved residues in the PEBP domain of PfRKIP decreases its interaction with PI(3)P. Furthermore, our results suggest that PfRKIP leads to increase in the autophosphorylation of PfCDPK1 that leads to transphosphorylation of substrates by PfCDPK1. Using variousin vitroandin vivoexperiments we have demonstrated the interaction of PfRKIP with PfCDPK1 and have also identified key residues in PfRKIP that play important role in this interaction. Interestingly, locostatin, a specific inhibitor of mammalian RKIP increased the interaction of PfRKIP with PfCDPK1 that perhaps leads to the sequestration of PfCDPK1 in a heterodimeric complex. Importantly, treatment of malaria parasite with locostatin shows dose dependent inhibition of parasite growth. This study suggests that specific inhibitors that modify PfRKIP leading to increase in its interaction with PfCDPK1 may be designed and explored as novel anti-malarial compounds to inhibit malaria parasite growth.
Doubling the resolution of fluorescence-lifetime single-molecule localization microscopy with image scanning microscopy
Authors: Radmacher Niels , Nevskyi Oleksii , Gallea José Ignacio , Thiele Jan Christoph , Gregor Ingo , Rizzoli Silvio O. , Enderlein Jörg 
Published: August 2023

AbstractIn this study, we integrate a single-photon detector array into a Confocal Laser Scanning Microscope (CLSM), enabling the combination of Fluorescence Life-time Single-Molecule Localization Microscopy (FL-SMLM) with Image Scanning Microscopy (ISM). This unique combination delivers a two-fold improvement in lateral localization accuracy for SMLM while maintaining its simplicity. More-over, the addition of lifetime information from our CLSM eliminates chromatic aberration, particularly crucial for achieving few-nanometer resolution in SMLM. Our approach, named Fluorescence Lifetime ISM-SMLM (FL-iSMLM), is demon-strated through direct Stochastic Optical Reconstruction Microscopy (dSTORM) and DNA Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) experiments on fluorescently labelled cells, showcasing both resolution enhancement and fluorescence lifetime multiplexing capabilities.
The effect of gaze on EEG measures of multisensory integration in a cocktail party scenario
Authors: Ahmed Farhin , Nidiffer Aaron R. , Lalor Edmund C. 
Published: August 2023

AbstractSeeing the speaker’s face greatly improves our speech comprehension in noisy environments. This is due to the brain’s ability to combine the auditory and the visual information around us, a process known as multisensory integration. Selective attention also strongly influences what we comprehend in scenarios with multiple speakers – an effect known as the cocktail-party phenomenon. However, the interaction between attention and multisensory integration is not fully understood, especially when it comes to natural, continuous speech. In a recent electroencephalography (EEG) study, we explored this issue and showed that multisensory integration is enhanced when an audiovisual speaker is attended compared to when that speaker is unattended. Here, we extend that work to investigate how this interaction varies depending on a person’s gaze behavior, which affects the quality of the visual information they have access to. To do so, we recorded EEG from 31 healthy adults as they performed selective attention tasks in several paradigms involving two concurrently presented audiovisual speakers. We then modeled how the recorded EEG related to the audio speech (envelope) of the presented speakers. Crucially, we compared two classes of model – one that assumed underlying multisensory integration (AV) versus another that assumed two independent unisensory audio and visual processes (A+V). This comparison revealed evidence of strong attentional effects on multisensory integration when participants were looking directly at the face of an audiovisual speaker. This effect was not apparent when the speaker’s face was in the peripheral vision of the participants. Overall, our findings suggest a strong influence of attention on multisensory integration when high fidelity visual (articulatory) speech information is available. More generally, this suggests that the interplay between attention and multisensory integration during natural audiovisual speech is dynamic and is adaptable based on the specific task and environment.