Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison and Evaluation of Neutralization of Clinically Frequently Used Antimicrobial Agents Using Three Different Culture Media in Simulated Blood Cultures

The performance of BACT/ALERT FA/FN Plu (France) blood culture containing a novel resin, DL (China) blood culture containing common resin, and adsorbent-free Thermo (USA) blood culture relying on dilution for antimicrobial neutralization at %peak serum concentration was evaluated by measuring the recovery of organisms and time to detection (TTD) in nine simulated microorganism-antimicrobial combination blood cultures.There was a significant difference in recovery rates between the aerobic media: 35/40 (87.5%) for BACT/ALERT media, 15/35 (42.9%) for DL media, and 5/40 (12.5%) for Thermo media; whereas, there was no statistical difference in TTD between FA Plus media and DL aerobic media. The recovery rates of the anaerobic media were 32/35 (91.4%) for BACT/ALERT media, 1/35 (2.9%) for DL media, and 5/35 (14.3%) for Thermo media, with significant differences only between BACT/ALERT FN Plus media and the others. Among the seven main antimicrobial categories, only BACT/ALERT FA/FN Plus culture media showed high recovery of microorganisms, except for carbapenems. The DL culture media exhibited a relatively high recovery rate of piperacillin/tazobactam, levofloxacin, and gentamicin only in aerobic media, and Thermo media only displayed the recovery of gentamicin.BACT/ALERT FA/FN Plus culture media with novel resin showed absolute advantages over DL and Thermo culture media and, thus, can be selectively applied clinically with prior use of antimicrobials before pathogen detection. DL culture media containing common resin outperformed adsorbent-free dilution-based Thermo culture media, which can be a backup option. We should focus on improving the neutralization of carbapenems with low efficiency in all three media.
Simultaneous, cortex-wide and cellular-resolution neuronal population dynamics reveal an unbounded scaling of dimensionality with neuron number

The brain’s remarkable properties arise from collective activity of millions of neurons. Widespread application of dimensionality reduction to multi-neuron recordings implies that neural dynamics can be approximated by low-dimensional “latent” signals reflecting neural computations. However, what would be the biological utility of such a redundant and metabolically costly encoding scheme and what is the appropriate resolution and scale of neural recording to understand brain function? Imaging the activity of one million neurons at cellular resolution and near-simultaneously across mouse cortex, we demonstrate an unbounded scaling of dimensionality with neuron number. While half of the neural variance lies within sixteen behavior-related dimensions, we find this unbounded scaling of dimensionality to correspond to an ever-increasing number of internal variables without immediate behavioral correlates. The activity patterns underlying these higher dimensions are fine-grained and cortex-wide, highlighting that large-scale recording is required to uncover the full neural substrates of internal and potentially cognitive processes.
Gene editing of pigs to control influenza A virus infections

Proteolytic activation of the hemagglutinin (HA) glycoprotein by host cellular proteases is pivotal for influenza A virus (IAV) infectivity. Highly pathogenic avian influenza viruses possess the multibasic cleavage site of the HA which is cleaved by ubiquitous proteases, such as furin; in contrast, the monobasic HA motif is recognized and activated by trypsin-like proteases, such as the transmembrane serine protease 2 (TMPRSS2). Here, we aimed to determine the effects of TMPRSS2 on the replication of pandemic H1N1 and H3N2 subtype IAVs in the natural host, the pig. The use of the CRISPR/Cas 9 system led to the establishment of homozygous gene edited (GE) TMPRSS2 knockout (KO) pigs. Delayed IAV replication was demonstrated in primary respiratory cells of KO pigs in vitro. IAV infection in vivo resulted in significant reduction of virus shedding in the upper respiratory tract, and lower virus titers and pathological lesions in the lower respiratory tract of TMPRSS2 KO pigs as compared to WT pigs. Our findings could support the commercial use of GE pigs to minimize (i) the economic losses caused by IAV infection in pigs, and (ii) the emergence of novel IAVs with pandemic potential through genetic reassortment in the “mixing vessel”, the pig.
Single Cell Ca2+ profiling for the discrimination of cancer cell lines

Calcium (Ca2+) is an essential and ubiquitous second messenger controlling numerous cellular functions. Ca2+ signaling relied on the finely tuned oscillations of the cytosolic Ca2+ concentrations induced by components of Ca2+ signaling toolkit (ion channels, pumps and ion exchangers). The regulation of these Ca2+ oscillations define a Ca2+ signature that is representative of the cellular identity and phenotype of a cell. In cancers, molecular actors of the Ca2+ signaling toolkit are aberrantly expressed. We hypothesized that Ca2+ signature of cancer cells are representative of their cellular identity, their tissue of origins (TOO) as well as their isolation site (IS). We defined the Ca2+ signature of prostate and colon cancer cell lines by collecting the profile of cytosolic Ca 2+ responses evoked by a panel of agonists in 22904 individual cells. We then highlighted the heterogeneity of those Ca2+ profiles and successfully developed a classifier predicting the tissue of origins (TOO), the isolation site (IS) or the cellular identity of individual cancer cells using a supervised neural network. Unsupervised clustering revealed that Ca2+ profiles of single cancer cells derived from 3 main classes of Ca2+ responses sub-divided into 50 different clusters. Thus, we highlighted that supervised machine learning applied on top of single cell Ca2+ profiling is an effective method to discriminate cancer cells at single cell level and that the cancer cell Ca 2+ signature can be summarized into 3 main profiles of Ca2+ responses.
Sox9 links biliary maturation to branching morphogenesis

Branching morphogenesis couples cellular differentiation with development of tissue architecture. Intrahepatic bile duct (IHBD) morphogenesis is initiated with biliary epithelial cell (BEC) specification and eventually forms a heterogeneous network of large ducts and small ductules. Here, we show that Sox9 is required for developmental establishment of small ductules. IHBDs emerge as a webbed structure by E15.5 and undergo morphological maturation through 2 weeks of age. Developmental knockout of Sox9 leads to decreased postnatal branching morphogenesis, manifesting as loss of ductules in adult livers. In the absence of Sox9, BECs fail to mature and exhibit elevated TGF-β signaling and Activin A. Activin A induces developmental gene expression and morphological defects in BEC organoids and represses ductule formation in postnatal livers. Our data demonstrate that adult IHBD morphology and BEC maturation is regulated by the Sox9-dependent formation of precursors to ductules during development, mediated in part by downregulation of Activin A.
GABAB- GluK1 kainate receptor interplay modulates amygdala excitability and behavioral response to chronic stress

Amygdala hyperexcitability is a hallmark for stress-induced anxiety disorders. Stress-associated changes in both principal neurons and interneurons contribute to the increased excitability, but how exactly these mechanisms perturb function of behaviorally relevant circuits in the amygdala remains unclear. Here, we show that GluK1 subunit-containing kainate receptors in parvalbumin (PV) interneurons maintain high GABA release and control excitability of lateral amygdala (LA) principal neurons via tonic GABAB-receptor-mediated inhibition. Downregulation of GluK1 expression in PV interneurons after chronic restraint stress (CRS) releases the tonic inhibition and increases excitability of LA principal neurons. Stress-induced LA hyperexcitability facilitates glutamatergic transmission selectively to central amygdala PKCδ-expressing neurons, implicated in fear generalization. Consistent with significance in anxiogenesis, absence of GluK1- GABAB regulation confers resilience against CRS-induced LA hyperexcitability and anxiety-like behavior. Our data reveal a unique novel mechanism involving an interplay between glutamatergic and GABAergic systems in the regulation of amygdala excitability in response to chronic stress.
The threshold for intracranial self-stimulation does not increase in rats exposed to chronic unpredictable stress - a systematic review and meta–analysis

The chronic unpredictable stress model is a laboratory rodent model of stress-induced anhedonia. The sucrose preference test, often used to validate it, suffers from being unreliable. Intracranial self-stimulation offers an alternative and is often cited as supporting evidence of the validity of the model. Our aim was to assess whether an increased self-stimulation threshold is found after stress and if such a change correlates with decreases in sweet consumption. We searched PubMed, Embase, and Web of Science for studies in rats exposed to chronic unpredictable stress that employed intracranial self-stimulation. Thresholds, for stressed and control animals, in 23 experiments (11 studies) were pooled. Over 50% of the data was contributed by one research group, so a three-level meta-analytical random effects model was fit to account for methodological differences between different networks of researchers. After this adjustment, we did not find that the self-stimulation thresholds were increased in stressed rats. Pioneering experiments with positive results failed to be replicated by others, although no specific factor could be pointed to as a likely explanation. What is more, the available evidence suggests a lack of connection between sweet preference and self-stimulation, although this relationship has been seldom investigated. Methods known to mitigate biases were frequently absent, as was a transparent report of crucial study details. Our findings challenge the claim made in support of the validity of the model. Further efforts would be well-invested in assessing how reliably other tests of anhedonia have found the effects of the chronic unpredictable stress model.
Understanding functional brain reorganisation for naturalistic piano playing in novice pianists

Learning to play the piano is a unique complex task, integrating multiple sensory modalities and higher-order cognitive functions. Longitudinal neuroimaging studies on adult novice musicians show training-related functional changes in music perception tasks. The reorganisation of brain activity while actually playing an instrument was studied only on a very short time-frame of a single fMRI session, and longer interventions have not yet been performed. Thus, our aim was to investigate the dynamic complexity of functional brain reorganisation while playing the piano within the first half year of musical training. We scanned twenty-four novice keyboard learners (female, 18-23yo) using fMRI while they played increasingly complex musical pieces after 1, 6, 13 and 26 weeks of training. Playing music evoked responses bilaterally in the auditory, inferior frontal and supplementary motor areas, and the left sensorimotor cortex. The effect of training over time, however, invoked widespread changes encompassing the right sensorimotor cortex, cerebellum, superior parietal cortex, anterior insula and hippocampus, among others. As the training progressed, the activation of these regions decreased while playing music. Post-hoc analysis revealed region-specific time-courses for independent auditory and motor regions of interest. These results suggest that while the primary sensory, motor and frontal regions are associated with playing music, the training decreases the involvement of higher-order cognitive control and integrative regions, and basal ganglia. Moreover, training might affect distinct brain regions in different ways, providing evidence in favour of the dynamic nature of brain plasticity. Significance statement Mastering the piano is a unique process requiring a collaboration of multiple brain regions. However, associated brain activation changes are not well understood. Using functional MRI, we showed that playing the piano activated brain areas associated with movement and auditory processing. However, as the novice pianists progressed through their training, the activation of other brain regions, involved in memory retrieval, auditory-motor integration, or the processing of musical syntax, was gradually reduced. Our findings suggest that musical training is an optimisation process, with higher-order cognitive networks being activated more strongly at the beginning and their activity decreasing with increased proficiency.
Decline of honeybees and its consequences for beekeepers and crop pollination in western Nepal

Pollination service by insects is globally threatened, yet trends outside of Europe and North America are poorly understood. Therefore, in less-studied regions of the world, beekeeper records can provide valuable insights into changes in pollinator populations. We conducted a questionnaire survey of 116 beekeepers in 10 villages in the Jumla District of western Nepal, where the native honeybee Apis cerana cerana is widely kept as a managed honeybee. We complemented the beekeeper survey with field data on insect-crop visitation, a household income survey, and an interview with a local lead beekeeper. 76% of beekeepers reported declines in the Apis cerana cerana population. 86% experienced declines in honey yield per hive, and 78% reported declines in the number of beehives per beekeeper. Honey yield per hive fell by 50% between 2012 and 2022, whilst the number of occupied hives decreased by 44%. Beekeepers ranked climate change and declining flower abundance as the most-important drivers of the decline. The drastic bee declines raise concerns for the future food and economic security of this region, where honey sales contribute to 16% of total household farming income. Apis cerana cerana plays a major role in crop pollination and contributes more than 50% of all flower visits to apple, cucumber, and pumpkin. To mitigate further declines in this region, we promote the use of pollinator-friendly farming practices including more wild flowers and maintenance of native habitat areas, and well-insulated log or top-bar log hives to buffer bees against extreme temperature fluctuations, which are expected to worsen with climate warming.
Impact des processus humides sur les dépressions des latitudes tempérées

Les objectifs de cette these sont d'analyser l'influence des processus humides sur les depressions des moyennes latitudes en s'interessant plus particulierement aux deplacements des depressions et a la formation des vents forts pres de la surface. Ces recherches ont ete effectuees a l'aide de simulations idealisees du modele de meso-echelle Meso-NH. La premiere etude s'est focalisee sur l'effet des processus humides sur le deplacement des depressions dans la direction perpendiculaire a l'axe du courant-jet, c'est a dire principalement le deplacement vers les poles. Le mecanisme expliquant ce deplacement est du a l'advection non-lineaire de la depression de surface par les anomalies cyclonique et anticyclonique d'altitude se trouvant de part et d'autre de la depression de surface. En presence d'humidite, l'anomalie anticyclonique d'altitude se renforce du fait du degagement de chaleur latente dans les zones d'ascendances, et ainsi le deplacement perpendiculairement a l'axe du jet et vers les poles s'accelere. On montre aussi que le deplacement vers l'est des depressions s'accelere en incluant les processus humides. La seconde etude porte sur la formation des vents forts pres de la surface et notamment sur ce qu'on appelle les "sting jets". Les "sting jets" sont des jets dont les masses d'air associees descendent rapidement du milieu de la troposphere au niveau de la tete du nuage jusqu'au sommet de la couche limite et peuvent declencher des vents devastateurs en surface. Ceux-ci se forment lorsque le front chaud se deplace a l'arriere de la depression et qu'une fracture frontale apparait. Les simulations montrent que, lorsqu'une depression traverse l'axe du courant-jet de son cote chaud a son cote froid, le retour en arriere du front chaud se produit tandis qu'une depression naissant cote froid du courant-jet possede un front chaud beaucoup moins actif. Ainsi, la formation d'un " sting jet " n'apparait que dans le premier cas , moyennant une resolution verticale elevee. C'est la presence d'un forcage geostrophique dans un environnement neutre vis-a-vis de l'instabilite symetrique qui facilite la descente des masses d'air et la formation du " sting jet ".
A mechanosensitive channel Pkd2 modulates the assembly of myosin II and actin filaments in the cytokinetic contractile ring

Cytokinesis, the last step in cell division, leads to the separation of daughter cells. This evolutionarily conserved process requires the force generated by an actomyosin contractile ring assembled at the equatorial plane. A newly discovered ion channel Pkd2 localizes to the equatorial plane and its activation by membrane-stretching promotes the cytokinetic calcium spikes in the fission yeast Schizosacchromyces pombe cells. Here, we investigated whether Pkd2 plays a direct role in the assembly and constriction of the contractile ring through quantitative fluorescence microscopy and genetic analyses. The localization of type II myosin Myo2, its regulatory light chain Rlc1 and actin filaments all increased in the contractile ring of a hypomorphic mutant pkd2-81KD, compared to the wild type. This was accompanied by a significant increase of the intracellular concentration of Rlc1 and actin filaments. A strong negative interaction existed between pkd2-81KD and the temperature-sensitive mutant myo2-E1. The pkd2 myo2 double mutant cells failed to assemble a complete contractile ring and separate efficiently, even at the permissive temperature. We conclude that Pkd2 modulates the assembly of myosin and actin in the contractile ring, suggesting that this ion channel mediates a novel pathway to regulate the actin cytoskeletal dynamics during cytokinesis.
A single changing hypernetwork to represent 3 (social-)ecological dynamics

To understand and manage (social-)ecological systems, we need an intuitive and rigorous way 17 to represent them. Recent ecological studies propose to represent interaction networks into 18 modular graphs, multiplexes and higher-order interactions. Along these lines, we argue here 19 that non-pairwise interactions are common in ecology and environmental sciences, 20 necessitating renewed concepts and tools for handling them. In addition, such interaction 21 networks often change sharply, due to appearing and disappearing species and components. 22 We illustrate in a simple example that any ecosystem can be represented by a single 23 hypergraph, here called the ecosystem hypernetwork. Moreover, we highlight that any 24 ecosystem hypernetwork exhibits a changing topology summarizing its long term dynamics 25 (e.g. species extinction/invasion, pollutant or human arrival). Qualitative and discrete-event 26 models developed in computer science appear suitable for modeling hypergraph (topological)
Effective Heuristics for Finding Small Minimal Feedback Arc Set Even for Large Graphs

Given a directed graph 𝐺 = ( 𝑉, 𝐸 ) , we present a heuristic based algorithm to tackle the general Minimum Feedback Arc Problem with the goal of finding good (and often optimal) Feedback Arc Sets which are minimal, i.e. such that none of the arcs can be reintroduced in the graph without disrupting acyclicity. Our algorithm has a good polynomial upper bound which makes it suitable even when dealing with applications on large graphs useful on Big Data problems such as in Social Networks.
First order differential subordination for functions with positive real part

Sharp estimates on $\beta$ are determined so that an analytic function $p$ defined on the open unit disk in the complex plane normalized by $p(0)=1$ is subordinate to some well known starlike functions with positive real part whenever $1+\beta z p'(z), \,\,1+\beta z p'(z)/p(z), \,\,\mbox{or}\,\,1+\beta z p'(z)/p^{2}(z)$ is subordinate to $\sqrt{1+z}$. Our results provide sharp version of previously known results.
Evolving Software: Combining Online Learning with Mutation-Based Stochastic Search

Evolutionary algorithms and related mutation-based methods have been used in software engineering, with recent emphasis on the problem of repairing bugs. In this work, programs are typically not synthesized from a random start. Instead, existing solutions—which may be flawed or inefficient—are taken as starting points, with the evolutionary process searching for useful improvements. This approach, however, introduces a challenge for the search algorithm: what is the optimal number of neutral mutations that should be combined? Too much is likely to introduce errors and break the program while too little hampers the search process, inducing the classic tradeoff between exploration and exploitation. In the context of software improvement, this work considers MWRepair, an algorithm for enhancing mutation-based searches, which uses online learning to optimize the tradeoff between exploration and exploitation. The aggressiveness parameter governs how many individual mutations should be applied simultaneously to an individual between fitness evaluations. MWRepair is evaluated in the context of automated program repair problems, where the goal is repairing software bugs with minimal human involvement. The article analyzes the search space for automated program repair induced by neutral mutations, finding that the greatest probability of finding successful repairs often occurs when many neutral mutations are applied to the original program. Moreover, repair probability follows a characteristic, unimodal distribution. MWRepair uses online learning to leverage this property, finding both rare and multi-edit repairs to defects in the popular Defects4J benchmark set of buggy Java programs.