bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ideonella margarita sp. nov., Ideonella lacteola sp. nov., Pseudaquabacterium inlustre sp. nov. and Pseudaquabacterium rugosum sp. nov., isolated from streams in China and re-examining the taxonomic status of all the genera within the family Sphaerotilaceae
Authors: Lu Huibin , Chen Li 
Published: August 2024

Four Gram-stain-negative, aerobic, rod-shaped and motile strains (LYT19WT, DXS22WT, DXS29WT and BYS139WT) were isolated from streams in China. All four strains showed highest 16S rRNA gene sequence similarities to the species of genus Ideonella. The calculated average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity values among strains LYT19WT, DXS22WT, DXS29WT, BYS139WT and other closely related strains were less than 79.5, 22.5 and 74.0%, respectively, indicating that each of the four strains should represent an independent novel species. The further reconstructed phylogenomic tree showed that strains LYT19WT and DXS29WT clustered closely with Ideonella strains, but strains DXS22WT and BYS139WT formed an independent clade with Aquabacterium terrae and Aquabacterium pictum. Comparing with other Aquabacterium species, A. terrae and A. pictum harboured distinct physiological and genetic characteristics, so it was reasonable to propose a novel genus Pseudaquabacterium to accommodate A. terrae, A. pictum, DXS22WT and BYS139WT. The major fatty acids of the four strains contained C16 : 0, summed feature 3 (C16 : 1
ω6c and/or C16 : 1
ω7c) and summed feature 8 (C18 : 1
ω6c and/or C18 : 1
ω7c). The predominant polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol and one unidentified aminophospholipid. Combining above descriptions, strains LYT19WT and DXS29WT should represent two novel species of the genus Ideonella, for which the names Ideonella margarita sp. nov. (type strain LYT19WT=GDMCC 1.3205T=KCTC 92545T) and Ideonella lacteola sp. nov. (type strain DXS29WT=GDMCC 1.3207T=KCTC 92547T) are proposed, respectively. Strains DXS22WT and BYS139WT should represent two novel species of the new genus Pseudaquabacterium, for which the names Pseudaquabacterium inlustre sp. nov. (type strain DXS22WT=GDMCC 1.3206T=KCTC 92546T) and Pseudaquabacterium rugosum sp. nov. (type strain BYS139WT=GDMCC 1.3208T=KCTC 92548T) are proposed, respectively.
Integration of parallel pathways for flight control in a hawkmoth reflects prevalence and relevance of natural visual cues
Authors: Bigge Ronja , Grittner Rebecca , Stöckl Anna 
Published: August 2024

AbstractAn animal’s behaviour is the result of multiple neural pathways acting in parallel, receiving information across and within sensory modalities at the same time. How these pathways are integrated, particularly when their individual outputs are in conflict, is key to understanding complex natural behaviours. We investigated this question in the visually guided flight of the hummingbird hawkmothMacroglossum stellatarum. These insects were recently shown to partition their visual field, using ventrolateral optic-flow cues to guide their flight like most insects, while the same stimuli in the dorsal visual field evoke a novel directional response. Using behavioural experiments which set the two pathways into conflict, we tested whether and how the ventrolateral and dorsal pathway integrate to guide hawkmoth flight. Combined with environmental imaging we demonstrate that the partitioning of the visual field followed the prevalence of visual cues in the hawkmoths’ natural habitats, while the integration hierarchy of the two pathways matched the relevance of these cues for the animals’ flight safety, rather than their magnitude in the experimental setup or in natural habitats. These results provide new mechanistic insights into the vision-based flight control of insects, and link these to their natural context. We anticipate our findings to be the starting point for comparative investigations into parallel pathways for flight guidance in insects from differently structured natural habitats.
Deep Brain Stimulation restores information processing in parkinsonian cortical networks
Authors: Piette Charlotte , Ng Wing Tin Sophie , De Liège Astrid , Bloch-Queyrat Coralie , Degos Bertrand , Venance Laurent , Touboul Jonathan 
Published: August 2024

AbstractParkinson’s disease (PD) is a neurodegenerative disorder associated with alterations of neural activity and information processing primarily in the basal ganglia and cerebral cortex. Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) is the most effective therapy when patients experience levodopa-induced motor complications. A growing body of evidence points towards a cortical effect of STN-DBS, restoring key electrophysiological markers, such as excessive beta band oscillations, commonly observed in PD. However, the mechanisms of STN-DBS remain elusive. Here, we aim to better characterize the cortical substrates underlying STN-DBS-induced improvement in motor symptoms. We recorded electroencephalograms (EEG) from PD patients and found that, although apparent EEG features were not different with or without therapy, EEG signals could more accurately predict limb movements under STN-DBS. To understand the origins of this enhanced information transmission under STN-DBS in the human EEG data, we investigated the information capacity and dynamics of a variety of computational models of cortical networks. The extent of improvement in decoding accuracy of complex naturalistic inputs under STN-DBS depended on the synaptic parameters of the network as well as its excitability and synchronization levels. Additionally, decoding accuracy could be optimized by adjusting STN-DBS parameters. Altogether, this work draws a comprehensive link between known alterations in cortical activity and the degradation of information processing capacity, as well as its restoration under DBS. These results also offer new perspectives for optimizing STN-DBS parameters based on clinically accessible measures of cortical information processing capacity.Significance statementParkinson’s disease, a neurodegenerative disorder associated with a variety of motor symptoms, is due to the progressive degeneration of dopaminergic neurons. Neuronal networks in turn display abnormal activity associated with high excitability and abnormal synchronization. Treatments based on the electrical stimulations of deep brain nuclei (DBS) provide major symptomatic improvement, but their mechanisms of action remain unknown. Here, using mathematical models of the corticalcircuits involved, we show that DBS restores neuronal ability to encode and transmit information. We further show that movements from human patients can be better predicted from brain signals under treatment. These new theory and metrics open the way to personalized and adaptive DBS allowing to personalize stimulation patterns to each patient.
Trends and Influences in women authorship of randomized controlled trials in rheumatology: a comprehensive analysis of all published RCTs from 2009 to 2023
Authors: Lauper Kim , Buitrago-Garcia Diana , Courvoisier Delphine , Iudici Michele , Mongin Denis 
Published: August 2024

AbstractObjectivesThis study aims to examine the evolution and influencing factors of women’s authorship in randomized controlled trials (RCTs) published in rheumatology.MethodsThis study included all rheumatology RCTs published from 2009 to 2023. The gender of authors was determined using forenames and countries of affiliation via the gender API service. The percentage of women in RCT publications and its association with potential factors was assessed using generalized estimating equations, considering women gender as the main binary outcome and the RCT’s continent, international collaboration status, industrial funding, intervention type, sample size, journal adherence to ICMJE recommendations, impact factor, publication year, author’s non-academic affiliation, and author position as covariates.ResultsAmong the 1,092 RCTs authored by 10,794 persons, women accounted for 34.1% of authors. Woman authorship was more frequent in African-based RCTs compared to North America, when the author had a non-academic affiliation and when the last author was a woman (1.83 [1.46, 2.29], +6.1 percentage points – pp). Woman authorship was less frequent in Asian and European-based RCTs, industry-funded RCTs (OR 0.64 [0.56-0.73]; -10.3pp). Women were less often in the last (0.63 [0.54-0.74]; -10.2 pp) and second to last author position (0.73 [0.62-0.85]; -7.3pp). There were no difference looking at international status or year of publication.ConclusionThe overall presence of women authors was 34.1%. The stagnant year-over-year representation of women in RCTs, and the lower likelihood of a woman having a position as senior author, underscores the need for more effective strategies to bridge the gender gap. RCTs with a woman last author were more likely to have a woman first author, suggesting a potential role-model effect.
Survival Following Diagnosis of HIV-Associated Kaposi Sarcoma Among Adults in East Africa in the “Treat-All” Era
Authors: Byakwaga Helen , Semeere Aggrey , Laker-Oketta Miriam , Busakhala Naftali , Freeman Esther , Rotich Elyne , Wenger Megan , Kadama-Makanga Philippa , Kisuya Job , Semakadde Matthew , Mwine Bronia , Kasozi Charles , Mwebesa Bwana , Maurer Toby , Glidden David V. , Kaloustian Kara Wools- , Kambugu Andrew , Martin Jeffrey 
Published: August 2024

AbstractBackgroundDespite widespread access to antiretroviral therapy (ART) in the “Treat All” era, HIV-associated Kaposi sarcoma (KS) remains among the most common malignancies in sub-Saharan Africa. Survival after KS diagnosis has historically been poor in Africa, but knowledge whether survival has changed at the population level in the contemporary era has been limited by lack of community-representative surveillance and monitoring systems.MethodsWe identified all adult persons living with HIV (PLWH) with a new diagnosis of KS made between 2016 and 2019 during outpatient or inpatient care at prototypical primary care-providing medical facilities in Kenya and Uganda using rapid case ascertainment. Participants were subsequently followed for vital status, including community tracking for those who became lost to follow-up.FindingsAmong 411 participants with newly diagnosed KS, 71% were men, median age was 34 (IQR: 30 to 41) years, and 91% had ACTG T1 tumor extent. Over a median follow-up of 7.8 (IQR: 2.4 to 17.9) months, cumulative incidence of death (95% CI) at months 6, 12 and 18 were 34% (30% to 39%), 41% (36% to 46%) and 45% (40% to 51%), respectively. Having the highest number of anatomic sites (11 to 16) harboring KS lesions (hazard ratio 2.2 (95% CI: 1.3-3.8) compared to 1 to 3 sites) and presence of oral KS lesions (hazard ratio 2.2 (95% CI: 1.4-3.3)) were independently associated with higher mortality. Lower hemoglobin and CD4 count as well as higher plasma HIV RNA were also associated with higher mortality.InterpretationAmong PLWH with newly diagnosed KS in East Africa in the “Treat All” era, survival was poor and related to mucocutaneous extent of KS. The findings emphasize the need for better control of KS in Africa, including novel approaches for earlier detection, better linkage to oncologic care, and more potent therapy.
Multi-omics biomarker selection and outlier detection across WHO glioma classifications via robust sparse multinomial regression
Authors: Carrilho João F. , Coletti Roberta , Costa Bruno M. , Lopes Marta B. 
Published: August 2024

AbstractGliomas are aggressive brain tumors difficult to treat mostly due to their large molecular heterogeneity. This requires continuous improvement in the molecular characterization of the glioma types to identify potential therapeutic targets. Advances in glioma research are rapidly evolving, contributing to the updates of the WHO classification of tumors. Data analysis of multiple omics layers through classification and feature selection methods holds promise in identifying crucial molecular features for distinguishing between glioma types. We developed a robust and sparse classification workflow based on multinomial logistic regression to investigate the molecular landscape of gliomas. We considered transcriptomics and methylomics glioma profiles of patients labeled following the latest WHO glioma classification updates (2016 and 2021). Overall, our results show a notable improvement in glioma types separability for the 2021 WHO updated patient labels at both omics levels. Patients flagged as outliers for the 2016 WHO classification exhibited a molecular profile deviating from the one of the respective classes, which was more aligned with the current associated glioma type according to the 2021 WHO update. The methylomics profiles were particularly promising in the identification of outliers. These contributions will support further revisions of glioma molecular characterization and the development of novel targeted therapies.
Carotid plaques show more unstable characteristics between 2010-2021 after a prior decade of stabilization
Authors: Motsak Tetiana , Mol Barend M. , Hoekstra Joost K.R. , Pasterkamp Gerard , de Borst Gert J. , de Kleijn Dominique P.V. 
Published: August 2024

AbstractBackgroundPreviously we reported a time dependent change in atherosclerotic carotid plaque characteristics, with decreasing destabilising characteristics between 2002 -2011. This observation was considered confirmative with a parallel improved adherence to medication and decrease in overall cardiovascular mortality in Western Europe. In the present study, we investigated if these time dependent changes in plaque characteristics still occurred over the last decade.MethodsUsing the Athero Express biobank, atherosclerotic plaques of 1,277 consecutive carotid endarterectomy patients included between 2010 and 2021 were analysed to examine time dependent changes in histological plaque characteristics in intervals of 2 years. These results were compared with our previous time dependent plaque composition data between 2002-2011.ResultsIn contrast to the period 2002-2011, the period 2010-2021 showed a significant increase in vulnerable plaque characteristics: large lipid cores, intraplaque hemorrhage, macrophages, and calcification. When adjusted for confounders related to these plaque characteristics, such as time to operation and pre-operative type of symptoms, the adjusted odds ratios per 2 years increase in time were 1,177 (95% confidence interval, 1,070-1,293; p<0,001) for calcification, 1,352 (95% confidence interval, 1,229-1,487; p<0,000) for intraplaque hemorrhage, 1,277 (95% confidence interval, 1,159-1,407; p<0,001) for plaques consisting of >40% of fat and 1,388 (95% confidence interval, 1,262-1,528; p<0,001) for macrophages. Use of statins increased in both the 2002-2011 and 2010-2021 period.ConclusionOur study did not support a further increase in plaque stabilizing features in carotid atherosclerotic plaques between 2010-2021. In contrast, plaques even showed features of destabilisation in the present cohort.
Practitioner, patient and public views on the acceptability of Mobile Stroke Units in England and Wales: a mixed methods study
Authors: Moseley L. , McMeekin P. , Price C. , Shaw L. , Allen M. , Ford G.A. , James M. , Laws A. , McCarthy S. , McClelland G , Park L.J. , Pearn K. , Phillips D. , White P. , Wilson D. , Scott J. 
Published: August 2024

AbstractBackgroundEvidence for Mobile Stroke Units (MSUs) demonstrates that onset to treatment times for intravenous thrombolysis can be reduced and access to mechanical thrombectomy might be improved. Despite growing use of MSUs internationally, to date there have been no studies in NHS England and NHS Wales exploring the acceptability of MSUs to clinicians, patient and public representatives and other key stakeholders, which are important when considering potential feasibility and implementation.MethodsThis study used a mixed methods design with a cross-sectional survey and qualitative workshops and interviews between October 2023 to May 2024. Survey data were collected from clinicians involved in emergency stroke care. Qualitative data involved clinical and non-clinical professionals involved in stroke care alongside patient and public representatives with experience of stroke. Survey data were descriptively analysed while content analysis was used on open-ended questions. Qualitative data were thematically analysed, prior to triangulation using a convergent coding matrix.ResultsThe study results, drawn from 25 respondents to the survey and 21 participants in qualitative workshops, found that almost all participants had positive affective attitudes to the concept of MSUs. However, several key areas of concern were identified that need to be addressed prior to implementing MSUs. These concerns included how MSUs would be staffed; whether and how telemedicine could contribute; the types of economic impacts; extent to which triage systems could accurately identify stroke patients for MSUs to attend; where the base location and geographic coverage of MSUs should be, the impact of MSUs on equitable access to stroke care, and how to improve public awareness of MSUs.ConclusionWhilst MSUs are mostly acceptable to key stakeholders, numerous areas of concern need to be addressed prior to MSU implementation. We recommend further research to address these issues prior to implementation in the NHS.
Data-guided direct reprogramming of human fibroblasts into the hematopoietic lineage
Authors: Stansbury Cooper , Cwycyshyn Jillian , Pickard Joshua , Meixner Walter , Rajapakse Indika , Muir Lindsey A. 
Published: August 2024

AbstractDirect reprogramming of human fibroblasts into hematopoietic stem cells (HSCs) shows promise for generating autologous cells for treatment of blood and immune-related diseases. However, low conversion efficiency of existing protocols points to gaps in our understanding and opportunities for identification of optimal transcription factor (TF) combinations, which is a major bottleneck for HSC generation. In this study, we tested a novel algorithmically-predicted TF recipe (GATA2, GFIB1, FOS, REL, and STAT5A) for inducing HSC-like states. Our recipe induced CD34+surface expression and single-cell transcriptomic signatures similar to those of native HSCs. Transcriptional heterogeneity within reprogrammed cells included differences in expression of HSC and endothelial-associated genes and in alternatively spliced transcripts as measured by single-cell long- read RNA-sequencing. Further, we proposed an approach to quantify the relative position of reprogrammed cells within the spectrum of initial and target cell states. This study lays the foundation for efficient optimization of direct reprogramming protocols.
Phospho-proteomics identifies D-group MAP kinases as substrates of the Arabidopsis tyrosine phosphatase RLPH2
Authors: Labandera Anne-Marie , Toth Ryan , Mitchell Sierra , Johnson Jayde J , Puyaubert Juliette , Baudouin Emmanuel , Uhrig R. Glen , Moorhead Greg B 
Published: August 2024

AbstractDespite being one of the few bona fide plant tyrosine phosphatases, RLPH2 has no known substrates. Utilizing phospho-proteomics, we identified the activation loop phospho-tyrosine of several D-group mitogen activated protein kinases (MPKs) as potential RLPH2 substrates. All Arabidopsis D-Group MPKs possess a TDY activation loop phosphorylation motif, whereas other MPKs (Groups A, B and C) contain a TEY motif. Our findings reveal that RLPH2 has a strong preference for aspartate (D) in the TXY motif, providing specificity for RLPH2 to exclusively target and dephosphorylate the D-Group MPKs. Additionally, D-Group MPKs contain a unique activation loop insertion that conforms to a protein phosphatase 1 (PP1) binding motif, with findings presented here confirming Arabidopsis PP1 phosphatases dock at this site. Intriguingly, only D-group MPKs among all identified Arabidopsis protein kinases possess this PP1 recruiting motif. Using multiple RLPH2 deficient plant lines, we demonstrate that RLPH2 represses seed dormancy release. Overall, this work highlights the power of phospho-proteomics in identifying substrates of this novel plant tyrosine phosphatase, while also revealing new complexities in the interactions between MPK activation loops and multiple phospho-mediated cell signaling events.One sentence summaryPhospho-proteomic analysis revealsArabidopsistyrosine phosphatase RLPH2 dephosphorylates the activation loop of D-Group mitogen activated protein kinases.
IMMUNE AND MOLECULAR CORRELATES OF RESPONSE TO IMMUNOTHERAPY REVEALED BY BRAIN-METASTATIC MELANOMA MODELS
Authors: Daugherty-Lopès Amélie , Pérez-Guijarro Eva , Gopalan Vishaka , Rappaport Jessica , Chen Quanyi , Huang April , Lam Khiem C. , Chin Sung , Ebersole Jessica , Wu Emily , Needle Gabriel A. , Church Isabella , Kyriakopoulos George , Xie Shaojun , Zhao Yongmei , Gruen Charli , Sassano Antonella , Araya Romina E. , Thorkelsson Andres , Smith Cari , Lee Maxwell P. , Hannenhalli Sridhar , Day Chi-Ping , Merlino Glenn , Goldszmid Romina S. 
Published: August 2024

SUMMARYDespite the promising results of immune checkpoint blockade (ICB) therapy, outcomes for patients with brain metastasis (BrM) remain poor. Identifying resistance mechanisms has been hindered by limited access to patient samples and relevant preclinical models. Here, we developed two mouse melanoma BrM models that recapitulate the disparate responses to ICB seen in patients. We demonstrate that these models capture the cellular and molecular complexity of human disease and reveal key factors shaping the tumor microenvironment and influencing ICB response. BR1-responsive tumor cells express inflammatory programs that polarize microglia into reactive states, eliciting robust T cell recruitment. In contrast, BR3-resistant melanoma cells are enriched in neurological programs and exploit tolerance mechanisms to maintain microglia homeostasis and limit T cell infiltration. In humans, BR1 and BR3 expression signatures correlate positively or negatively with T cell infiltration and BrM patient outcomes, respectively. Our study provides clinically relevant models and uncovers mechanistic insights into BrM ICB responses, offering potential biomarkers and therapeutic targets to improve therapy efficacy.
Non-guided, Mobile, CBT-I-based Sleep Training in War-torn Ukraine: A Feasibility Study
Authors: Kurapov Anton , Blechert Jens , Hinterberger Alexandra , Topalidis Pavlos , Schabus Manuel 
Published: August 2024

AbstractObjectivesTo study whether a mobile, unguided Cognitive Behavior Therapy-based Intervention for Sleep Disturbance, Sleep2is feasible, acceptable, and reduces mental health/sleep disturbance symptoms among the Ukrainian population during the ongoing war.MethodsA single-arm, open-label, uncontrolled pre-post evaluation study was conducted with 487 registered participants: 283 started, out of which 95 completed without an ambulatory heart rate (HR) sensor and 65 with. Assessments were conducted using online questionnaires and continuous objective measurements via HR sensors. Key outcome measures included sleep disturbance, insomnia, fear of sleep, anxiety, depression, PTSD, perceived stress, and somatic symptoms.ResultsEngagement with the program was robust, achieving an 80.72% compliance rate, alongside high levels of feasibility and acceptance. Participants reported significant pre- post reductions in the severity of sleep disturbance (by 22.60%), insomnia (by 35.08%), fear of sleep (by 32.43%), anxiety (by 27.72%), depression (by 28.67%), PTSD (by 32.41%), somatic symptoms (by 24.52%), and perceived stress (by 17.90%), all with medium to high effect sizes. Objective sleep measurements showed a slight reduction in sleep onset latency.ConclusionThe ‘Sleep2Ukraine’ program demonstrated high feasibility and acceptance, with significant improvements in subjective sleep and mental health measures among participants. These findings demonstrate the potential of scalable mobile-based CBT-I interventions in war-torn regions with or without the instrument, based on the heart rate assessment.