bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic cerebral autoregulation during step-wise increases in blood pressure during anaesthesia
Authors: van den Dool Rokus E.C. , Sperna Weiland Nicolaas H. , Schenk Jimmy , Kho Eline , Veelo Denise P. , van der Ster Björn J.P. , Immink Rogier V. 
Published: January 2023

BACKGROUND
Classically, cerebral autoregulation (CA) entails cerebral blood flow (CBF) remaining constant by cerebrovascular tone adapting to fluctuations in mean arterial pressure (MAP) between ∼60 and ∼150 mmHg. However, this is not an on–off mechanism; previous work has suggested that vasomotor tone is proportionally related to CA function. During propofol-based anaesthesia, there is cerebrovascular vasoconstriction, and static CA remains intact. Sevoflurane-based anaesthesia induces cerebral vasodilation and attenuates CA dose-dependently. It is unclear how this translates to dynamic CA across a range of blood pressures in the autoregulatory range.

OBJECTIVE
The aim of this study was to quantify the effect of step-wise increases in MAP between 60 and 100 mmHg, using phenylephrine, on dynamic CA during propofol- and sevoflurane-based anaesthesia.

DESIGN
A nonrandomised interventional trial.

SETTING
Single centre enrolment started on 11 January 2019 and ended on 23 September 2019.

PATIENTS
We studied American Society of Anesthesiologists (ASA) I/II patients undergoing noncardiothoracic, nonneurosurgical and nonlaparoscopic surgery under general anaesthesia.

INTERVENTION
In this study, cerebrovascular tone was manipulated in the autoregulatory range by increasing MAP step-wise using phenylephrine in patients receiving either propofol- or sevoflurane-based anaesthesia. MAP and mean middle cerebral artery blood velocity (MCAV
mean) were measured in ASA I and II patients, anaesthetised with either propofol (n = 26) or sevoflurane (n = 28), during 10 mmHg step-wise increments of MAP between 60 and 100 mmHg. Static CA was determined by plotting 2-min averaged MCAV
mean versus MAP. Dynamic CA was determined using transfer function analysis and expressed as the phase lead (°) between MAP and MCAV
mean oscillations, created with positive pressure ventilation with a frequency of 6 min−1.

MAIN OUTCOMES
The primary outcome of this study was the response of dynamic CA during step-wise increases in MAP during propofol- and sevoflurane-based anaesthesia.

RESULTS
MAP levels achieved per step-wise increments were comparable between anaesthesia regiment (63 ± 3, 72 ± 2, 80 ± 2, 90 ± 2, 100 ± 3 mmHg, and 61 ± 4, 71 ± 2, 80 ± 2, 89 ± 2, 98 ± 4 mmHg for propofol and sevoflurane, respectively). MCAV
mean increased more during step-wise MAP increments for sevoflurane compared to propofol (P≤0.001). Dynamic CA improved during propofol (0.73° mmHg−1, 95% CI 0.51 to 0.95; P ≤ 0.001)) and less pronounced during sevoflurane-based anaesthesia (0.21° mmHg−1 (95% CI 0.01 to 0.42, P = 0.04).

CONCLUSIONS
During general anaesthesia, dynamic CA is dependent on MAP, also within the autoregulatory range. This phenomenon was more pronounced during propofol anaesthesia than during sevoflurane.

TRIAL REGISTRATION
NCT03816072 (https://clinicaltrials.gov/ct2/show/NCT03816072).
Pathways From Recent Incarceration to Antiretroviral Therapy Adherence: Opportunities for Interventions to Support Women Living With HIV Post Release From Correctional Facilities
Authors: Erickson Margaret , Krüsi Andrea , Shannon Kate , Braschel Melissa , Norris Candice , Buxton Jane , Elwood Martin Ruth , Deering Kathleen ,   on behalf of the SHAWNA Project
Published: January 2023

ABSTRACT
Women living with HIV are increasingly incarcerated and experience suboptimal HIV health outcomes post release from incarceration. Drawing on cohort data with cisgender and trans women living with HIV (Sexual Health and HIV/AIDS: Women's Longitudinal Needs Assessment), we used path analysis to investigate pathways from recent incarceration to optimal antiretroviral therapy (ART) adherence. We tested direct effects between recent incarceration, mediating variables, and ART adherence, along with indirect effects between incarceration and ART adherence through each mediator. We assessed model fit using chi-square, root-mean-square error of approximation (RMSEA), and comparative fit index (CFI). Our hypothesized model fit well to the data (χ2(1)=1.100; p=.2943; CFI = 1.000; RMSEA = 0.007). Recent experiences of homelessness, criminalized substance use, and gender-based violence each fully mediated the pathway between recent incarceration and optimal ART adherence. Findings highlight the need for safe and supportive housing, supports for criminalized substance use, and trauma and violence–informed care and practice post release from incarceration.
Social Network Influence on Syphilis Testing for Black Sexual Minority Men in Baltimore, Maryland: A Cross-sectional Social Network Analysis
Authors: Heidari Omeid , Tobin Karin E. , Pollock Sarah , Li Fang-Ying , Webel Allison R. , Duncan Dustin T. , Latkin Carl 
Published: January 2023

Abstract
Black sexual minority men (BSMM), including those with HIV, have disproportionate rates of syphilis infection. This study examines the associations of social network characteristics on syphilis testing, given that social network approaches are well established as effective methods to establish health-promoting social norms. We analyzed baseline data from a sexual health behavioral intervention. Using multivariable logistic regression, we modeled individual and social network characteristics on syphilis testing. Of the 256 participants, 37% tested for syphilis in the past year. In the adjusted model controlling for individual factors, odds of syphilis testing increased 89% for each increase in network member participants being encouraged to get a syphilis test (95% confidence interval [1.19-3.00]). Feeling comfortable accompanying a friend for HIV/sexually transmitted infection testing was associated with 2.47 increased odds of syphilis testing. Encouraging and training individuals to discuss sexual health topics with their network members may lead to the establishment of testing in social networks of Black sexual minority men.
Label-free quantitative proteomics analyses of mouse astrocytes provides insight into the host response mechanism at different developmental stages ofToxoplasma gondii
Authors: Xie Huanhuan , Xu Chao , Zhao Guihua , Dong Hongjie , Dai Lisha , Xu Haozhi , Zhang Lixin , Sun Hang , Wang Qi , Zhang Junmei , Yin Kun 
Published: January 2023

AbstractToxoplasma gondii(T. gondii) is an opportunistic parasite that can infect the central nervous system (CNS), causing severe toxoplasmosis and behavioral cognitive impairment. Mortality is high in immunocompromised individuals with toxoplasmosis, most commonly due to reactivation of infection in the CNS. There are still no effective vaccines and drugs for the prevention and treatment of toxoplasmosis. There are five developmental stages forT. gondiito complete life cycle, of which the tachyzoite and bradyzoite stages are the key to the acute and chronic infection. In this study, to better understanding of howT. gondiiinteracts with the host CNS at different stages of infection, we constructed acute and chronic infection models ofT. gondiiin astrocytes, and used label-free proteomics to detect the proteome changes before and after infection, respectively. A total of 4676 proteins were identified, among which 163 differentially expressed proteins (DEPs) (fold change≥1.5 or ≤0.67 andp-value≤0.05) including 109 up-regulated proteins and 54 down-regulated proteins in C8-TA vs C8 group, and 719 DEPs including 495 up-regulated proteins and 224 down-regulated proteins in C8-BR vs C8-TA group. AfterT. gondiitachyzoites infected astrocytes, DEPs were enriched in immune-related biological processes to promote the formation of bradyzoites and maintain the balance ofT. gondii, CNS and brain. AfterT. gondiibradyzoites infected astrocytes, the DEPs up-regulated the host’s glucose metabolism, and some up-regulated DEPs were closely related to neurodegenerative diseases. These findings not only provide new insights into the psychiatric pathogenesis ofT. gondii, but also provide potential targets for the treatment of acute and chronic Toxoplasmosis.
Association of Abnormal Cytology and risk factors in Women of Assam, India
Authors: Barmon Debabrata , Sarma Anupam , Baruah Upasana , Kakoti Lopamudra , Barman Debanjana , Sarma Pallavi , Kalita Manoj , Rai Avdhesh Kumar 
Published: January 2023

ABSTRACTThe study was conducted to perform cytological abnormality screening by PAP test among women of Assam, India. Two hundred thirty four women in the age group of 35-60 years were enrolled in screening camps for the study. Smear on the glass slide of the cervical scrap specimen were prepared for PAP test. Statistical analysis for PAP test outcome with risk factors was analyzed by applying Fisher’s exact test. Significance was considered for p<0.05.It was found that women using contraceptive piles have higher risk of abnormal cytology (p-0.0238). Women with irregular menstrual cycle frequency have also higher risk of abnormal cytology (p-0.0002). Women not using commercially available sanitary pads ahe also high risk of abnormal cytology( p-0.0052). Women having urinary tract infection have also high risk of abnormal cytology (p-0.0102). Our study finding suggest that use of contraceptive pills, urinary infection, irregular frequency of menstrual cycle, non-use of sanitary pads may increase the risk of abnormal cytology positivity in women of Assam, India. There are limitations of our studyfindings because of small sample size and univariate statistical analysis.
Caution Regarding the Specificities of Pan-Cancer Microbial Structure
Authors: Gihawi Abraham , Cooper Colin S. , Brewer Daniel S. 
Published: January 2023

AbstractThe results published in Poore and Kopylovaet al. 2020[1] revealed the possibility of being able to almost perfectly differentiate between types of tumour based on their microbial composition using machine learning models. Whilst we believe that there is the potential for microbial composition to be used in this manner, we have concerns with the manuscript that make us question the certainty of the conclusions drawn. We believe there are issues in the areas of the contribution of contamination, handling of batch effects, false positive classifications and limitations in the machine learning approaches used. This makes it difficult to identify whether the authors have identified true biological signal and how robust these models would be in use as clinical biomarkers. We commend Poore and Kopylovaet al. on their approach to open data and reproducibility that has enabled this analysis. We hope that this discourse assists the future development of machine learning models and hypothesis generation in microbiome research.
Unlocking the potential ofmiR-19bin the regulation of temozolomide response in glioblastoma patients via targeting PPP2R5E, a subunit of the protein phosphatase 2A complex
Authors: Kashani Elham , Hlavackova Kristyna , Haemmig Stefan , Sadowski Martin C , Phour Jaison , Baumgartner Ulrich , Mueller-Wirth Nicole , Trefny Carmen , Sharf Den Abu Fakher Bushra , Nydegger Coline , Maragkou Theoni , Schucht Philippe , Perren Aurel , Zinn Pascal , Lüdi Markus , Marti Thomas Michael , Krebs Philippe , Vassella Erik 
Published: January 2023

AbstractDespite the standard of care, glioblastoma IDH wildtype (GBM) inevitably recurs, underscoring the need to develop new treatment strategies. To address the role of microRNAs in temozolomide (TMZ) response, we performed functional microRNA screens and consistently identifiedmiR-19b. Our study reveals a novel axis betweenmiR-19band PPP2R5E subunit of serine/threonine protein phosphatase PP2A and establishes a so far unappreciated contribution ofmiR-19bin TMZ resistance of GBM. Specifically, our results demonstrate that attenuation ofmiR-19bin GBM cell lines and glioblastoma stem cells (GSCs) induces DNA damage, which further enhances the cytotoxic effects of TMZ treatment. We confirmed TMZ resistance induced by knocking down PPP2R5E in orthotopic mouse xenografts of GSCs. Furthermore, our results indicate that treating cells with the PP2A-activating drug FTY720 or knocking down endogenous PP2A-inhibiting proteins potentiates the cytotoxic effects of TMZ.MiR-19battenuation or PPP2R5E activation could potentially be exploited in adjuvant therapy of GBM patients.
Hierarchical Bayesian modeling identifies key considerations in the development of quantitative loop-mediated isothermal amplification assays
Authors: Bradley Jacob R. , Borges Diego , Cavaleiro Mafalda , Mayhew Michael B. 
Published: January 2023

AbstractMotivationLoop-mediated isothermal amplification (LAMP) is a rapidly growing, fast, and cost-effective technique for detection of DNA/RNA in point-of-care biomedical applications. However, it remains unclear what factors affect LAMP’s quantitative resolution, and experimental optimization of primers presents a major bottleneck in assay design. A lack of model-based frameworks to characterize LAMP data and address these questions presents an unmet need for LAMP assay development.ResultsWe present hierarchical Bayesian models of LAMP amplification based on Gompertz functions, and use these models to infer the effect of RNA variation and other factors on LAMP amplification curves derived from 80 blood samples of patients with suspected acute infection. Our analysis uncovers associations between LAMP assay resolution and characteristics such as primer sequence composition and thermodynamic properties. In addition to correlations between RNA input abundance and time shift of the the LAMP amplification curve, we also detect RNA-dependent assocations with amplification rate. We further investigate associations between primer/target properties and quantitative performance of the assay by generating a set of synthetic RNA samples with systematically varied primer sequences and applying our framework. We find evidence that the associations observed are driven by across-target rather than within-target variation, an important observation for study design. Our findings represent important first steps towards guided development of quantitative LAMP assays.Availability and ImplementationAnalysis and modeling code is available upon reasonable request.
Ccn2 deficiency causes smooth muscle cell de-differentiation and severe atherosclerosis in hyperlipidemic mice
Authors: Larsen JH , Stubbe J , Beck HC , Overgaard M , Lindegaard CA , Hansen DR , Goldschmeding R , Rodriguez-Díez RR , Ruiz-Ortega M , Pyke C , Wirka RC , Lindholt JS , Rasmussen LM , Steffensen LB 
Published: January 2023

ABSTRACTCellular communication network factor 2 (CCN2/CTGF) is a matricellular protein with an established role in fibrotic diseases and cancers, and therapies targeting CCN2 is currently in Phase II and III clinical trials for idiopathic pulmonary fibrosis, pancreatic cancer and Duchenne Muscular Dystrophy. Recent studies have highlighed a protective role of CCN2 in aortic aneurysm disease, but its role in atherosclerosis remains to be investigated.We identified arteries as having the highest relative expression ofCCN2across 54 human tissues. In aortas,CCN2was among the highest expressed genes, andin situhybridization of human internal thoracic arteries revealed vascular smooth muscle cells (SMCs) as its principal source.Hypothesizing a role for CCN2 in SMC phenotype maintenance and athero-protection, we investigated inducible Ccn2 knockout (Ccn2Δ/Δ) mice in normo- and hyper-lipidemic settings. Induction of hyperlipidemia by single intravenous injection of 1·1011viral genomes of rAAV8-D377Y-mPcsk9 combined with 24 weeks of western type diet resulted in severe enlargement (3-5-fold increase of relative aorta mass compared to wildtype littermates,p< 0.0001) and whitening ofCcn2Δ/Δaortas. Oil Red O-staining ofen faceprepared thoracic aortas showed a marked increase in atherosclerosis inCcn2Δ/Δmice as compared to wildtype littermates (75% vs. 10% Oil Red O-positive aortic area,p< 0.0001). Transcriptomic profiling of cultivated SMCs derived from aortas of normolipidemic mice showed signatures of dedifferentiation (reduced expression ofe.g. Myocd, Acta2andMyh11) and modulation toward a synthetic, pro-inflammatory phenotype ofCcn2Δ/ΔSMCs. These effects were verifiedin vivoand inCCN2-silenced human aortic SMCs. Taken together, we find that CCN2 plays a critical athero-protective role in artery tissues, likely through maintaining SMCs in a differentiated, contractile phenotype.
Nitrogen niche partitioning between tropical legumes and grasses conditionally weakens under elevated CO2
Authors: Churchill Amber C. , Zhang Haiyang , Kim Gil Won , Catunda Karen L. M. , Anderson Ian C. , Isbell Forest , Moore Ben , Pendall Elise , Plett Jonathan M. , Powell Jeff R. , Power Sally A. 
Published: January 2023

AbstractPlant community biodiversity can be maintained, at least partially, by shifts in species interactions between facilitation and competition for resources as environmental conditions change. These interactions also drive ecosystem functioning, including productivity, and can promote over-yielding-an ecosystem service prioritized in agro-ecosystems, such as pastures, that occurs when multiple species together are more productive than the component species alone. Importantly, species interactions that can result in over-yielding may shift in response to rising CO2concentrations and changes in resource availability, and the consequences these shifts have on production is uncertain especially in the context of tropical mixed-species grasslands.We examined the relative performance of two species pairs of tropical pasture grasses and legumes growing in monoculture and mixtures in a glasshouse experiment manipulating CO2. We investigated how over-yielding can arise from nitrogen (N) niche partitioning and biotic facilitation using stable isotopes to differentiate soil N from biological N fixation (BNF) within N acquisition into aboveground biomass for these two-species mixtures.We found that N niche partitioning in species-level use of soil N vs. BNF drove species interactions in mixtures. Importantly partitioning and overyielding were generally reduced under elevated CO2. However, this finding was mixture-dependent based on biomass of dominant species in mixtures and the strength of selection effects for the dominant species.This study demonstrates that rising atmospheric CO2may alter niche partitioning between co-occurring species, with negative implications for the over-yielding benefits predicted for legume-grass mixtures in working landscapes with tropical species. Furthermore, these changes in inter-species interactions may have consequences for grassland composition that are not yet considered in larger-scale projections for impacts of climate change and species distributions.Graphical abstract(Image by H. Zhang): Among our tropical pasture species we found that grasses (dotted lines) grown in monoculture rely fully on soil nitrogen (N), while legumes (solid lines) grown in monoculture relied approximately equally on soil N and biological nitrogen fixation (BNF) to meet N requirements. When grown with tropical grasses, however, legumes shifted to rely more strongly on BNF, indicative of niche partitioning and decreased competition for soil nutrients with grasses. This separation of niche space was weakened under elevated CO2conditions, ultimately reducing legume production.
Dbx2, an aging-related homeobox gene, inhibits the proliferation of adult neural progenitors
Authors: Giuliani Andrea , Licursi Valerio , Nisi Paola S. , Fiore Mario , Biagioni Stefano , Negri Rodolfo , Rugg-Gunn Peter J. , Cacci Emanuele , Lupo Giuseppe 
Published: January 2023

ABSTRACTThe subventricular zone (SVZ) of the adult mouse brain contains quiescent neural stem cells, which can be activated (aNSCs) to generate transit amplifying progenitors (TAPs), neuroblasts (NBs) and newborn neurons. Neurogenesis declines during aging, as the aged SVZ niche causes transcriptomic changes that promote NSC quiescence and decrease proliferating neural/stem progenitor cells (NSPCs). The transcription factors mediating these changes, however, remain unclear. We previously found that the homeobox geneDbx2is upregulated in aged SVZ NSPCs and inhibits NSPC culture growth. Here, we report thatDbx2is repressed by Epidermal Growth Factor Receptor signaling, which promotes NSPC proliferation and decreases in the aged SVZ. We show thatDbx2inhibits NSPC proliferation by hindering the G2/M transition and elucidate the transcriptomic networks modulated byDbx2, highlighting its role in the downregulation of the cell cycle molecular pathways. Accordingly,Dbx2function is negatively correlated with the transcriptional signatures of proliferative NSPCs (aNSCs, TAPs and early NBs). These results point toDbx2as a molecular node relaying the anti-neurogenic input of the aged niche to the NSPC transcriptome.
Astrocyte and neuronal Panx1 support long-term reference memory in mice
Authors: Obot Price , Subah Galadu , Schonwald Antonia , Pan Jian , Velíšek Libor , Velíšková Jana , Stanton Patric K. , Scemes Eliana 
Published: January 2023

ABSTRACTPannexin 1 (Panx1) are ubiquitously expressed proteins that form plasma membrane channels permeable to anions and moderate sized signaling molecules (e.g., ATP, glutamate). In the nervous system, activation of Panx1 channels have been extensively shown to contribute to distinct neurological disorders (epilepsy, chronic pain, migraine, neuroAIDS, etc.) but knowledge of extent to which these channels have a physiological role remains restricted to three studies supporting their involvement in hippocampus dependent learning. Given that Panx1 channels may provide an important mechanism for activity-dependent neuron-glia interaction, we used Panx1 transgenic mice with global and cell-type specific deletions of Panx1 to interrogate their participation in working and reference memory. Using the 8-arm radial maze, we show that long-term spatial reference memory, but not spatial working memory, is deficient in Panx1-null mice and that both astrocyte and neuronal Panx1 contribute to the consolidation of long-term spatial memory. Field potential recordings in hippocampal slices of Panx1-null mice revealed an attenuation of both long-term potentiation (LTP) of synaptic strength and long-term depression (LTD) at Schaffer collateral – CA1 synapses without alterations basal synaptic transmission or pre-synaptic paired-pulse facilitation. Our results implicate both neuronal and astrocyte Panx1 channels as critical players for the development and maintenance of long-term spatial reference memory in mice.
Ankh ☥: Optimized Protein Language Model Unlocks General-Purpose Modelling
Authors: Elnaggar Ahmed , Essam Hazem , Salah-Eldin Wafaa , Moustafa Walid , Elkerdawy Mohamed , Rochereau Charlotte , Rost Burkhard 
Published: January 2023

AbstractAs opposed to scaling-up protein language models (PLMs), we seek improving performance via protein-specific optimization. Although the proportionality between the language model size and the richness of its learned representations is validated, we prioritize accessibility and pursue a path of data-efficient, cost-reduced, and knowledge-guided optimization. Through over twenty experiments ranging from masking, architecture, and pre-training data, we derive insights from protein-specific experimentation into building a model that interprets the language of life, optimally. We present Ankh, the first general-purpose PLM trained on Google’s TPU-v4 surpassing the state-of-the-art performance with fewer parameters (<10% for pre-training, <7% for inference, and <30% for the embedding dimension). We provide a representative range of structure and function benchmarks where Ankh excels. We further provide a protein variant generation analysis on High-N and One-N input data scales where Ankh succeeds in learning protein evolutionary conservation-mutation trends and introducing functional diversity while retaining key structural-functional characteristics. We dedicate our work to promoting accessibility to research innovation via attainable resources.