bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ambisome shows potent anti-Candida auris in vitro and in vivo activity
Authors: Ghannoum Mahmoud , Herrada Janet , Gamal Ahmed , Long Lisa , McCormick Thomas 
Published: December 2021

Candida auris is an emerging multidrug resistant Candida species that has been reported in many parts of the world for causing severe illness in hospitalized patients especially bloodstream infections. The challenge with this type of yeast is its resistance to commonly used antifungal drugs, thus identifying antifungals that are effective against this species is critical.
In this study, we determined the in vitro activity of Ambisome against 35 clinical isolates of C. auris using minimum inhibitory concentration (MIC) assay as well as the efficacy of Ambisome compared to Amphotericin B and fluconazole using a C. auris murine disseminated model.
Antifungal activity of C. auris against Ambisome and comparators was assessed using amicrodilution method performed according to the Clinical and Laboratory Standard Institute (CLSI) M27-A4 methodology. Mice were immunocompromised and challenged with 3 x 107
C. auris blastopores in 0.1 ml of normal saline (via the tail vein). Treatment efficacy was assessed by determining reductions in mortality as well as decrease in tissue fungal burden (CFUs).
Ambisome showed lower MIC50 and MIC90 values (1 and 2 μg/mL, respectively) than the comparators tested. Significant efficacy was observed in the Ambisome 7.5 mg/kg -treated group (100% and 90% survival by day 7- and 14-days post inoculation, respectively). Additionally, Ambisome and fluconazole treated groups showed significant reduction in CFUs in the kidneys (P- values of 0.028 and 0.022, respectively) compared to the untreated group.
Our data shows that Ambisome shows significant antifungal activity against C. auris in vitro as well as in vivo.
Arthrobacter cheniae and Arthrobacter frigidicola sp. nov., isolated from a glacier
Authors: Yang Lei-Lei , Liu Hong-Can , Liu Qing , Xin Yu-Hua 
Published: December 2021

Two Gram-stain-positive, aerobic, rod-shaped, pink and light pink colony-forming bacteria, designated as Hz2T and MDT2-14T, respectively, were isolated from glacier cryoconite samples. Comparisons based on 16S rRNA gene sequences showed that strains Hz2T and MDT2-14T take

Arthrobacter bussei

KR32T and

Arthrobacter zhaoguopingii

J391T as their closest neighbours, respectively. The average nucleotide identity values between the two novel strains and their closest relatives were 83.56 and 93.06 %, respectively. The two strains contain MK-9(H2) as their predominant menaquinone. The polar lipids of both strains were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol and an unidentified glycolipid. The major fatty acids of strain Hz2T were anteiso-C15 : 0, summed feature 3 (comprising C16 : 1
ω7c and/or C16 : 1
ω6c) and iso-C15 : 0, while the major fatty acids of strain MDT2-14T were anteiso-C15 : 0 and anteiso-C17 : 0. Based on these data, we propose two novel species, Arthrobacter cheniae sp. nov. (Hz2T = CGMCC 1.9262T=NBRC 113086T) and Arthrobacter frigidicola sp. nov. (MDT2-14T=CGMCC 1.9882T=NBRC 113089T).
A reusable benchmark of brain-age prediction from M/EEG resting-state signals
Authors: Engemann Denis A. , Mellot Apolline , Höchenberger Richard , Banville Hubert , Sabbagh David , Gemein Lukas , Ball Tonio , Gramfort Alexandre 
Published: December 2021

AbstractPopulation-level modeling can define quantitative measures of individual aging by applying machine learning to large volumes of brain images. These measures of brain age, obtained from the general population, helped characterize disease severity in neurological populations, improving estimates of diagnosis or prognosis. Magnetoencephalography (MEG) and Electroencephalography (EEG) have the potential to further generalize this approach towards prevention and public health by enabling assessments of brain health at large scales in socioeconomically diverse environments. However, more research is needed to define methods that can handle the complexity and diversity of M/EEG signals across diverse real-world contexts. To catalyse this effort, here we propose reusable benchmarks of competing machine learning approaches for brain age modeling. We benchmarked popular classical machine learning pipelines and deep learning architectures previously used for pathology decoding or brain age estimation in 4 international M/EEG cohorts from diverse countries and cultural contexts, including recordings from more than 2500 participants. Our benchmarks were built on top of the M/EEG adaptations of the BIDS standard, providing tools that can be applied with minimal modification on any M/EEG dataset provided in the BIDS format. Our results suggest that, regardless of whether classical machine learning or deep learning was used, the highest performance was reached by pipelines and architectures involving spatially aware representations of the M/EEG signals, leading to R^2 scores between 0.60-0.71. Hand-crafted features paired with random forest regression provided robust benchmarks even in situations in which other approaches failed. Taken together, this set of benchmarks, accompanied by open-source software and high-level Python scripts, can serve as a starting point and quantitative reference for future efforts at developing M/EEG-based measures of brain aging. The generality of the approach renders this benchmark reusable for other related objectives such as modeling specific cognitive variables or clinical endpoints.Highlights- We provide systematic reusable benchmarks for brain age from M/EEG signals- The benchmarks were carried out on M/EEG from four countries > 2500 recordings- We compared machine learning pipelines capable of handling the non-linear regression task of relating biomedical outcomes to M/EEG dynamics, based on classical machine learning and deep learning- Next to data-driven methods we benchmarked template-based source localization as a practical tool for generating features less affected by electromagnetic field spread- The benchmarks are built on top of the MNE ecosystem and the braindecode package and can be applied on any M/EEG dataset presented in the BIDS format
Opposing regulation of short-term memory by basal ganglia direct and indirect pathways that are coactive during behavior
Authors: Tang Yingjun , Yang Hongjiang , Chen Xia , Zhang Zhouzhou , Yao Xiao , Yin Xinxin , Guo Zengcai V. 
Published: December 2021

AbstractThe basal ganglia direct and indirect pathways are viewed to mediate opposing functions in movement. However, this classic model is challenged by recent findings that both pathways are coactive during behavior. We examined the roles of direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons in a decision-making task with a short-term memory (STM) component. Optogenetic stimulation of cortical-input-defined dSPNs and iSPNs during STM oppositely biased upcoming licking choice, without affecting licking execution. Optogenetically identified dSPNs and iSPNs showed similar response patterns, although with quantitative difference in spatiotemporal organization. To understand how coactive dSPNs and iSPNs play opposing roles, we recorded population activity in frontal cortex and the basal ganglia output nucleus SNr. Stimulation of dSPNs and iSPNs bidirectionally regulated cortical decision variable through the differential modulation of SNr ramping activity. These results reconcile different views by demonstrating that coactive dSPNs and iSPNs precisely shape cortical activity in a push-pull balance.
Age determination through DNA methylation patterns of fingernails and toenails
Authors: Fokias Kristina , Dierckx Lotte , Van de Voorde Wim , Bekaert Bram 
Published: December 2021

ABSTRACTOver the past decade, age prediction based on DNA methylation has become a vastly investigated topic; many age prediction models have been developed based on different DNAm markers and using various tissues. However, the potential of using nails to this end has not yet been explored. Their inherent resistance to decay and ease of sampling would offer an advantage in cases where post-mortem degradation poses challenges concerning sample collection and DNA-extraction. In the current study, clippings from both fingernails and toenails were collected from 108 living test subjects (age range: 0 – 96 years). The methylation status of 15 CpGs located in 4 previously established age-related markers (ASPA, EDARADD, PDE4C, ELOVL2) was investigated through pyrosequencing of bisulphite converted DNA. Significant dissimilarities in methylation levels were observed between all four limbs, hence limb-specific age prediction models were developed using ordinary least squares, weighted least squares and quantile regression analysis. When applied to their respective test sets, these models yielded a mean absolute deviation between predicted and chronological age ranging from 6.71 to 8.48 years. In addition, the assay was tested on methylation data derived from 5 nail samples collected from deceased individuals, demonstrating its feasibility for application in post-mortem cases. In conclusion, this study provides the first proof that chronological age can be assessed through DNA methylation patterns in nails.
Dynamic in situ confinement triggers ligand-free neuropeptide receptor signaling
Authors: Sánchez M. Florencia , Dietz Marina S. , Müller Ulrike , Weghuber Julian , Gatterdam Karl , Wieneke Ralph , Heilemann Mike , Lanzerstorfer Peter , Tampé Robert 
Published: December 2021

AbstractMembrane receptors are central to cell-cell communication. Receptor clustering at the plasma membrane modulates physiological responses, and mesoscale receptor organization is critical for downstream signaling. Spatially restricted cluster formation of the neuropeptide Y2 hormone receptor (Y2R) was observed in vivo; however, the relevance of this confinement is not fully understood. Here, we controlled Y2R clustering in situ by a chelator nanotool. Due to the multivalent interaction, we observed a dynamic exchange in the microscale confined regions. Fast Y2R enrichment in clustered areas triggered a ligand-independent downstream signaling determined by an increase in cytosolic calcium, cell spreading, and migration. We revealed that the cell response to ligand-induced activation was amplified when cells were pre-clustered by the nanotool. Ligand-independent signaling by clustering differed from ligand-induced activation in the binding of arrestin-3 as downstream effector, which was recruited to the confined regions only in the presence of the ligand. This approach enables in situ clustering of membrane receptors and raises the possibility to explore different modalities of receptor activation.Abstract Figure
Macrogenetics reveals multifaceted influences of environmental variation on vertebrate population genetic diversity across the Americas
Authors: Lawrence Elizabeth R. , Fraser Dylan J. 
Published: December 2021

AbstractRelative to species diversity gradients, the broad scale distribution of population-specific genetic diversity (PGD) across taxa remains understudied. We used nuclear DNA data collected from 6285 vertebrate populations across the Americas to assess the role environmental variables play in structuring the spatial/latitudinal distribution of PGD, a key component of adaptive potential in the face of environmental change. Our results provide key evidence for taxa-specific responses and that temperature variability in addition to mean temperature may be a primary driver of PGD. Additionally, we found some positive influence of precipitation, productivity, and elevation on PGD; identified trends were dependent on the metric of PGD. In contrast to the classic negative relationship between species diversity and latitude, we report either a positive or taxa-dependent relationship between PGD and latitude, depending on the metric of PGD. The inconsistent latitudinal gradient in different metrics of PGD may be due to opposing processes diminishing patterns across latitudes that operate on different timescales, as well as the flattening of large-scale genetic gradients when assessing across species versus within species. Our study highlights the nuance required to assess broad patterns in genetic diversity, and the need for developing balanced conservation strategies that ensure population, species, and community persistence.
Matchtigs: minimum plain text representation of kmer sets
Authors: Schmidt Sebastian , Khan Shahbaz , Alanko Jarno , Pibiri Giulio E. , Tomescu Alexandru I. 
Published: December 2021

AbstractWe propose a polynomial algorithm computing aminimumplain-text representation of kmer sets, as well as an efficient near-minimum greedy heuristic. When compressing read sets of large model organisms or bacterial pangenomes, with only a minor runtime increase, we shrink the representation by up to 60% over unitigs and 27% over previous work. Additionally, the number of strings is decreased by up to 97% over unitigs and 91% over previous work. Finally, a small representation has advantages in downstream applications, as it speeds up SSHash-Lite queries by up to 4.26× over unitigs and 2.10× over previous work.Availabilitymatchtigs:https://github.com/algbio/matchtigsSSHash-Lite:https://github.com/jermp/sshash-lite
Comparative evaluation of rapid isothermal amplification and antigen assays for screening testing of SARS-CoV-2
Authors: Salcedo Nol , Sena Brena F. , Qu Xiying , Herrera Bobby Brooke 
Published: December 2021

ABSTRACTHuman transmission of SARS-CoV-2 and emergent variants of concern has continued to occur globally, despite mass vaccination campaigns. Public health strategies to reduce virus spread should therefore rely, in part, on frequent screening with rapid, inexpensive, and sensitive tests. We evaluated two digitally integrated rapid tests and assessed their performance using stored nasal swab specimens collected from individuals with or without COVID-19. An isothermal amplification assay combined with a lateral flow test had a limit of detection of 10 RNA copies per reaction, and a positive percent agreement (PPA)/negative percent agreement (NPA) during the asymptomatic and symptomatic phases of 100%/100% and 95.83/100%, respectively. Comparatively, an antigen-based lateral flow test, had a limit of detection of 30,000 copies, and a PPA/NPA during the asymptomatic and symptomatic phases of 82.86%/98.68% and 91.67/100%, respectively. Both the isothermal amplification and antigen-based lateral flow tests had optimized detection of SARS-CoV-2 during the peak period of transmission; however, the antigen-based test had reduced sensitivity in clinical samples with qPCR Ct values greater than 29.8. Low-cost, high-throughput screening enabled by isothermal amplification or antigen-based techniques have value for outbreak control.
A Competing Risk Analysis of Early COVID-19 Treatments
Authors: Gonzalez-Arroyo Gilberto , Rodriguez-Moran Mario F. , Garcia-Arreola Maricela , Lopez-Lopez Karla Guadalupe , Ortiz-Castillo Tonatihu , Gomez-Garcia Salvador , Alvarez-Aguilar Cleto , Gomez-Garcia Anel , Lopez-Pineda Arturo 
Published: December 2021

AbstractIntroductionThe advent of the SARS-CoV-2 virus posed formidable challenges on a global scale. In the year 2020, existing treatments were not tailored specifically to combat this novel virus, and the absence of a developed vaccine added to the complexity. Clinical guidelines underwent rapid evolution during the initial months of the pandemic, leaving uncertainty about the efficacy of various drug combinations in treating the disease. This study delves into an analysis of outcomes during the early stages of the pandemic within the Mexican Institute of Social Security (IMSS), the largest healthcare system in Mexico.Material and MethodsIn this retrospective observational study, we examined the medical records of 130,216 COVID-19 patients treated in two Mexican states throughout the year 2020. We conducted a competing risk analysis, considering death and recovery as potential outcomes. This was further complemented by a Cox-regression and Kaplan-Meier analysis. To enhance predictive insights, machine learning models were constructed to forecast outcomes at 10, 20, and 30 days.ResultsOur analysis revealed a heightened prevalence of comorbidities, including obesity, diabetes, and heart disease, aligning with Mexico’s established epidemiological profile. Mortality patterns indicated occurrences approximately 15-20 days from the onset of symptoms. Notably, patients undergoing treatment with cephalosporin in conjunction with neuraminidase inhibitors (NAIs) exhibited the poorest survival rates, whereas those receiving adamantane, fluoroquinolone, or penicillin demonstrated the most favorable survival outcomes.ConclusionsThe identified associations caution against the utilization of specific treatment combinations, providing crucial insights for refining the country’s clinical guidelines and optimizing patient care strategies.
Individualized exercise in chronic non-specific low back pain: a systematic review with meta-analysis on the effects of exercise alone or in combination with psychological interventions on pain and disability
Authors: Fleckenstein Johannes , Flössel Philipp , Engel Tilman , Klewinghaus Laura , Stoll Josefine , Behrens Martin , Niederer Daniel 
Published: December 2021

ABSTRACTThis systematic review with meta-analysis and meta-regression investigated the effects of individualized exercise interventions consisting with or without combined psychological intervention on pain intensity and disability in patients with chronic non-specific low-back-pain. Databases were searched up to 31 January 2022 and we selected randomized controlled trials involving adults with chronic non-specific low-back-pain being treated with individualized/personalized/stratified exercise interventions with or without psychological treatment compared to any control.Fifty-eight studies (n = 10084) were included.At short-term follow-up (12 weeks), low-certainty evidence for pain intensity (SMD -0.28 [95%CI -0.42 to -0.14]) and very low-certainty evidence for disability (−0.17 [-0.31 to -0.02]) indicates effects of individualized versus active exercises, and very low-certainty evidence for pain intensity (−0.40; [-0.58 to -0.22])), but not (low-certainty evidence) for disability (−0.18; [-0.22 to 0.01]) compared to passive controls.At long-term follow-up (1 year), moderate-certainty evidence for pain intensity (−0.14 [-0.22 to -0.07]) and disability (−0.20 [-0.30 to -0.10]) indicates effects versus passive controls.Sensitivity analyses indicates that the effects on pain, but not on disability (always short-term and versus active treatments) were robust. Pain reduction caused by individualized exercise treatments in combination with psychological interventions (in particular behavioural-cognitive therapies) (−0.28 [-0.42 to -0.14], low certainty) is of clinical importance.Certainty of evidence was downgraded mainly due to evidence of risk of bias, publication bias and inconsistency that could not be explained.Individualized exercise can be recommended from a clinical point of view to treat pain and disability in chronic non-specific low-back-pain. Sub-group analysis suggests a combination of individualized exercise (especially motor-control based treatments) with behavioural therapy interventions to booster effects. Certainty of evidence was moderate for long-term follow-up.PROSPERO registrationCRD42021247331
Social mixing patterns relevant to infectious diseases spread by close contact in urban Blantyre, Malawi
Authors: Thindwa Deus , Jambo Kondwani C , Ojal John , MacPherson Peter , Phiri Mphatso Dennis , Khundi McEwen , Chiume Lingstone , Gallagher Katherine E , Heyderman Robert S , Corbett Elizabeth L , French Neil , Flasche Stefan 
Published: December 2021

AbstractIntroductionUnderstanding human mixing patterns relevant to infectious diseases spread through close contact is vital for modelling transmission dynamics and optimisation of disease control strategies. Mixing patterns in low-income countries like Malawi are not well understood.MethodologyWe conducted a social mixing survey in urban Blantyre, Malawi between April and July 2021 (between the 2nd and 3rd wave of COVID-19 infections). Participants living in densely-populated neighbourhoods were randomly sampled and, if they consented, reported their physical and non-physical contacts within and outside homes lasting at least 5 minutes during the previous day. Age-specific mixing rates were calculated, and a negative binomial mixed effects model was used to estimate determinants of contact behaviour.ResultsOf 1,201 individuals enrolled, 702 (58.5%) were female, the median age was 15 years (interquartile range [IQR] 5-32) and 127 (10.6%) were HIV-positive. On average, participants reported 10.3 contacts per day (range: 1-25). Mixing patterns were highly age-assortative, particularly those within the community and with skin-to-skin contact. Adults aged 20-49y reported the most contacts (median:11, IQR: 8-15) of all age groups; 38% (95%CI: 16-63) more than infants (median: 8, IQR: 5-10), who had the least contacts. Household contact frequency increased by 3% (95%CI 2-5) per additional household member. Unemployed participants had 15% (95%CI: 9-21) fewer contacts than other adults. Among long range (>30 meters away from home) contacts, secondary school children had the largest median contact distance from home (257m, IQR 78-761). HIV-positive status in adults >18 years-old was not associated with increased contact patterns (1%, 95%CI -9-12). During this period of relatively low COVID-19 incidence in Malawi, 301 (25.1%) individuals stated that they had limited their contact with others due to COVID-19 precautions; however, their reported contacts were not fewer (8%, 95%CI 1-13).ConclusionIn urban Malawi, contact rates, are high and age-assortative, with little behavioural change due to either HIV-status or COVID-19 circulation. This highlights the limits of contact-restriction-based mitigation strategies in such settings and the need for pandemic preparedness to better understand how contact reductions can be enabled and motivated.