bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting Regime Shifts: Neurocomputational Substrates for Over- and Underreactions to Change
Authors: Wang Mu-Chen , Wu George , Wu Shih-Wei 
Published: June 2023

AbstractThe world constantly changes, with the underlying state of the world shifting from one regime to another. The ability to detect a regime shift, such as the onset of a pandemic or the end of a recession, significantly impacts individual decisions as well as governmental policies. However, determining whether a regime has changed is usually not obvious, as signals are noisy and reflective of the volatility of the environment. We designed an fMRI paradigm that examines a stylized regime-shift detection task. Human participants showed systematic over- and underreaction: Overreaction was most commonly seen when signals were noisy but when environments were stable and change is possible but unlikely. By contrast, underreaction was observed when signals were precise but when environments were unstable and hence change was more likely. These behavioral signatures are consistent with thesystem-neglectcomputational hypothesis, which posits that sensitivity or lack thereof to system parameters (noise and volatility) is central to these behavioral biases. Guided by this computational framework, we found that individual subjects’ sensitivity to system parameters were represented by two distinct brain networks. Whereas a frontoparietal network selectively represented individuals’ sensitivity to signal noise but not environment volatility, the ventromedial prefrontal cortex (vmPFC) showed the opposite pattern. Further, these two networks were involved in different aspects of regime-shift computations: while vmPFC correlated with subjects’ beliefs about change, the frontoparietal network represented the strength of evidence in favor of regime shifts. Together, these results suggest that regime-shift detection recruits belief-updating and evidence-evaluation networks and that under- and overreactions arise from how sensitive these networks are to the system parameters.Significance statementJudging whether the world has changed, from the onset of a market boom to the end of a pandemic, is ubiquitous. The ability to detect regime shifts not only impacts individual decisions but also governmental policies. However, these judgments are hard to make because the signals we receive are noisy and reflective of the volatility of the environment. We find that people overreact to changes when they receive noisy signals in stable environments, but underreact when facing precise signals in unstable environments. Under- and overreactions can be read out by distinct brain networks according to their sensitivity in responding to different environmental parameters that impact regime changes. This suggests that parameter selectivity at the network level guides regime-shift detection.
Ocular Manifestations in a Cohort of 43 Patients with KBG Syndrome
Authors: Carter Drake C. , Kierzkowska Ola , Sarino Kathleen , Guo Lily , Marchi Elaine , Lyon Gholson J 
Published: June 2023

ABSTRACTOphthalmological conditions are underreported in patients with KBG syndrome, which is classically described as presenting with dental, developmental, intellectual, skeletal, and craniofacial abnormalities. This study analyzed the prevalence of four ophthalmological conditions (strabismus, astigmatism, myopia, hyperopia) in 43 patients with KBG syndrome carrying pathogenic variants inANKRD11or deletions in 16q24.3 and compared it to the literature. 43 patients were recruited via self-referral or a private Facebook group hosted by the KBG Foundation. Virtual interviews were conducted to collect a comprehensive medical history verified by medical records. From these records, data analysis was performed to calculate the prevalence of ophthalmological conditions. Strabismus was reported in 10 (23.3%) participants, while astigmatism, myopia, and hyperopia were reported in 12 (27.9%), 7 (16.3%), and 9 (20.9%) participants, respectively. Other reported conditions include anisometropia, amblyopia, and nystagmus. When compared to the literature, the prevalence of strabismus and refractive errors is higher than other studies. However, more research is needed to determine if mutations inANKRD11play a role in abnormal development of the visual system. In patients with established KBG syndrome, screening for misalignment or refractive errors should be done, as interventions in patients with these conditions can improve functioning and quality of life.
A comprehensive evolutionary scenario for the origin and neofunctionalization of theDrosophilaspeciation geneOdysseus(OdsH)
Authors: Vilas Boas Nunes William , Siqueira de Oliveira Daniel , de Rezende Dias Guilherme , Carvalho Antonio Bernardo , Putinhon Ícaro Caruso , Matos Biselli Joice , Guegen Nathalie , Akkouche Abdou , Burlet Nelly , Vieira Cristina , Carareto Claudia M. A. 
Published: June 2023

AbstractOdysseus(OdsH) was the first gene described inDrosophilarelated to speciation and hybrid sterility. This gene was first described in themelanogastersubgroup and more specifically in the sterile hybrids from crosses betweenD. mauritianaandD. simulans. Its origin is attributed to the duplication of the geneunc-4, which would have occurred in the ancestor of the subgenusSophophora. By using a much larger sample ofDrosophilaspecies, we showed that contrary to what has been previously proposed,OdsHorigin occurred approximately 62 million years ago (Mya). Then,OdsHhave experienced rapid neofunctionalization in male reproductive tracts, evidenced by its evolutionary rates, expression and transcription factor binding sites. Furthermore, the analysis of the OdsH peptide sequence allowed the identification of mutations in the DNA- and protein-binding domains ofD. mauritianathat could result in incompatibility with genomes from other species. We then explored the expression ofOdsHin the spermatocytes ofD. arizonaeandD. mojavensis, a pair of recently diverged sister species with incomplete reproductive isolation and expected to find the involvement ofOdsHin hybrid sterility. Our data indicated thatOdsHexpression is not atypical in male-sterile hybrids from these species. In conclusion, we have demonstrated that the origin ofOdsHoccurred earlier than previously proposed and that its neofunctionalization in male sexual functions occurred rapidly after its origin. Our results also suggested that its role as a speciation gene, as in themelanogastersubgroup of species, may be restricted to this specific taxon.
Distinct neural representations during a brain-machine interface and manual reaching task in motor cortex, prefrontal cortex, and striatum
Authors: Zippi Ellen L. , Shvartsman Gabrielle F. , Vendrell-Llopis Nuria , Wallis Joni D. , Carmena Jose M. 
Published: June 2023

AbstractAlthough brain-machine interfaces (BMIs) are directly controlled by the modulation of a select local population of neurons, distributed networks consisting of cortical and subcortical areas have been implicated in learning and maintaining control. Previous work in rodent BMI has demonstrated the involvement of the striatum in BMI learning. However, the prefrontal cortex has been largely ignored when studying motor BMI control despite its role in action planning, action selection, and learning abstract tasks. Here, we compare local field potentials simultaneously recorded from the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), and the caudate nucleus of the striatum (Cd) while nonhuman primates perform a two-dimensional, self-initiated, center-out task under BMI control and manual control. Our results demonstrate the presence of distinct neural representations for BMI and manual control in M1, DLPFC, and Cd. We find that neural activity from DLPFC and M1 best distinguish between control types at the go cue and target acquisition, respectively. We also found effective connectivity from DLPFC→M1 throughout trials across both control types and Cd→M1 during BMI control. These results suggest distributed network activity between M1, DLPFC, and Cd during BMI control that is similar yet distinct from manual control.
Soil intake modifies the gut microbiota and alleviates ovalbumin-induced mice asthma inflammation
Authors: Li Mengjie , Li Na , Dong Yangyang , Zhang Honglin , Bai Zhimao , Zhang Rui , Fei Zhongjie , Zhu Wenyong , Xiao Pengfeng , Sun Xiao , Zhou Dongrui 
Published: June 2023

AbstractBackgroundLow cleanliness living environment (LCLE) can increase gut microbial diversity and prevent allergic diseases, whereas gut microbial dysbiosis is closely related to the pathogenesis of asthma. Our previous studies suggested that soil in the LCLE is a key factor in shaping intestinal microbiota.ObjectiveWe aimed to explore if sterilized soil intake as prebiotics while being incubated with microbes in the air can attenuate mice asthma symptoms by modifying gut microbiota.Methods16S rRNA gene sequencing was used to analyze the gut microbial composition, in combination with immune parameters measured in the lung and serum samples.Results16S rRNA gene sequencing results showed significant differences in the fecal microbiota composition between the test and control mice, with a higher abundance ofAllobaculum,Alistipes,andLachnospiraceae_UCG-001, which produce short-chain fatty acids and are beneficial for health in the test mice. Soil intake downregulated the concentrations of IL-6, IL-4, IL-17F, TNF-α, and IL-22 in serum and increased the expression of IFN-γ, which regulated the Th1/Th2 balance in lung by polarizing the immune system toward Th1, strongly alleviating ovalbumin-induced asthma inflammation. The effect of sensitization on gut microbiota was greater than that of air microbes and age together, but weaker than that of soil.ConclusionSoil intake had a significant therapeutic effect on mouse asthma, possibly by promoting the growth of multiple beneficial bacteria. The results indicated that the development of soil-based prebiotic products might be used for allergic asthma management and our study provides further evidence for the hygiene hypothesis.ImportanceExposure to a low cleanliness living environment (LCLE), of which soil is an important component, can shape the gut microbiota and support immune tolerance, preventing allergic diseases such as eczema and asthma. However, with the rapid progress of urbanization, it is impossible to return to farm-like living and we are becoming disconnected from the soil. Here, our study found that ingesting sterilized soil and living in an LCLE have the same protective effects on asthma inflammation. Ingestion of sterilized soil significantly altered the gut microbial composition and exerted significant therapeutic effects on asthmatic mice. However, edible sterilized soil possesses more advantages than LCLE exposure, such as the absence of pathogenic bacteria, safer, and convenience. The results indicate that the development of soil-based prebiotic products might be used for allergic asthma management and our study further supports the hygiene hypothesis.NotificationThe article is currently undergoing peer review in the World Allergy Organization Journal.
Audiotactile stimulation can improve syllable discrimination through multisensory integration in the theta frequency band
Authors: Guilleminot Pierre , Graef Cosima , Butters Emilia , Reichenbach Tobias 
Published: June 2023

AbstractSyllables are an essential building block of speech. We recently showed that tactile stimuli linked to the perceptual centers of syllables in continuous speech can improve speech comprehension. The rate of syllables lies in the theta frequency range, between 4 and 8 Hz, and the behavioural effect appears linked to multisensory integration in this frequency band. Because this neural activity may be oscillatory, we hypothesized that a behavioural effect may also occur not only while but also after this activity has been evoked or entrained through vibrotactile pulses. Here we show that audiotactile integration regarding the perception of single syllables, both on the neural and on the behavioural level, is consistent with this hypothesis. We first stimulated subjects with a series of vibrotactile pulses and then presented them with a syllable in background noise. We show that, at a delay of 200 ms after the last vibrotactile pulse, audiotactile integration still occurred in the theta band and syllable discrimination was enhanced. Moreover, the dependence of both the neural multisensory integration as well as of the behavioral discrimination on the delay of the audio signal with respect to the last tactile pulse was consistent with a damped oscillation. In addition, the multisensory gain is correlated with the syllable discrimination score. Our results therefore evidence the role of the theta band in audiotactile integration and provide evidence that these effect may involve oscillatory activity that still persists after the tactile stimulation.
A Novel Amino Acid Deletion and Substitution inamrBGene Associated with Gentamicin Susceptibility inBurkholderia pseudomalleifrom Malaysian Borneo
Authors: Hussin Ainulkhir , Nathan Sheila , Shahidan Muhammad Ashraf , Nor Rahim Mohd Yusof , Zainun Mohamad Yusof , Khairuddinb Nurul Aiman Nafisah , Ibrahim Nazlina 
Published: June 2023

ABSTRACTBurkholderia pseudomalleiis a highly pathogenic saprophyte that is intrinsically resistant to a wide variety of antibiotics. Resistance to gentamicin is considered as an earmark ofB. pseudomallei.However, rare susceptible strains have been isolated in certain regions due to gene mutations. Currently, data on the susceptible strains’ prevalence and the actual causal mutations are still scarce, particularly in Malaysian Borneo. A pool ofB. pseudomalleiisolates (n= 46) were screened for gentamicin susceptibility and phenotypically confirmed using the gradient minimum inhibitory concentration method. Three isolates were gentamicin-susceptible strains and were identified as having originated from Bintulu, Sarawak, Malaysian Borneo. The amrBgene mutation in these mutant strains was analysed, and the effect of amino acid substitution on the stability of the amrB protein was determined by usingin silicoanalysis. The mutagenesis analysis identified a polymorphism-associated mutation, g.1056T>G, and two susceptible-associated mutations identified as novel in-frame amino acid deletion p.Val412del and amino acid substitution p.Thr368Arg that compromised gentamicin resistance.In silicoanalysis using amrB homology-modelled and AlphaFold-solved structures proposed the role of p.Thr368Arg amino acid substitution in conferring GEN susceptibility by other mechanisms than destabilising the structure of amrB protein, which is most probably due to the mutation’s location in the highly conserved region. The findings have shed light on the phenotypic characteristics and mutations involved in theamrBgene of the gentamicin-susceptibleB. pseudomallei.
Heterologous expression ofDictyostelium discoideumNE81 in mouse embryo fibroblasts reveals conserved mechanoprotective roles of lamins
Authors: Odell Jacob , Gräf Ralph , Lammerding Jan 
Published: June 2023

AbstractLamins are nuclear intermediate filament proteins that are ubiquitously found in metazoan cells, where they contribute to nuclear morphology, stability, and gene expression. Lamin-like sequences have recently been identified in distantly related eukaryotes, but it remains unclear if these proteins share conserved functions with the lamins found in metazoans. Here, we investigate conserved features between metazoan and amoebozoan lamins using a genetic complementation system to express theDictyostelium discoideumlamin-like protein NE81 in mammalian cells lacking either specific lamins or all endogenous lamins. We report that NE81 localizes to the nucleus in cells lacking Lamin A/C, and that NE81 expression improves nuclear circularity, reduces nuclear deformability, and prevents nuclear envelope rupture in these cells. However, NE81 did not completely rescue loss of Lamin A/C, and was unable to restore normal distribution of metazoan lamin interactors, such as emerin and nuclear pore complexes, which are frequently displaced in Lamin A/C deficient cells. Collectively, our results indicate that the ability of lamins to modulate the morphology and mechanical properties of nuclei may have been a feature present in the common ancestor ofDictyosteliumand animals, whereas other, more specialized interactions may have evolved more recently in metazoan lineages.
USING MACHINE LEARNING OR DEEP LEARNING MODELS IN A HOSPITAL SETTING TO DETECT INAPPROPRIATE PRESCRIPTIONS: A SYSTEMATIC REVIEW
Authors: Johns E. , Godet J. , Alkanj A. , Beck M. , Mas L. Dal , Gourieux B. , Sauleau E.-A. , Michel B. 
Published: June 2023

ABSTRACTObjectivesThe emergence of artificial intelligence (AI) is catching the interest of hospitals pharmacists. Massive collection of pharmaceutical data is now available to train AI models and hold the promise of disrupting codes and practices. The objective of this systematic review was to examine the state of the art of machine learning or deep learning models that detect inappropriate hospital medication orders.MethodsA systematic review was conducted according to the PRISMA statement. PubMed and Cochrane database were searched from inception to May 2023. Studies were included if they reported and described an AI model intended for use by clinical pharmacists in hospitals.ResultsAfter reviewing, thirteen articles were selected. Eleven studies were published between 2020 and 2023; eight were conducted in North America and Asia. Six analyzed orders and detected inappropriate prescriptions according to patient profiles and medication orders, seven detected specific inappropriate prescriptions. Various AI models were used, mainly supervised learning techniques.ConclusionsThis systematic review points out that, to date, few original research studies report AI tools based on machine or deep learning in the field of hospital clinical pharmacy. However, these original articles, while preliminary, highlighted the potential value of integrating AI into clinical hospital pharmacy practice.What is already known on this topicAI models for pharmacists are at their beginning. Pharmacists need to stay up-to-date and show interest in developing such tools.What this study addsThis systematic review confirms the growing interest of AI in hospital setting. It highlights the challenges faced, and suggests that AI models have a great potential and will help hospital clinical pharmacists in the near future to better manage review of medication orders.How this study might affect research, practice or policyAI models have a gaining interested among hospital clinical pharmacists. This systematic review contributes to understand AI models and the techniques behind the tools.
Nf1Deficiency Increases Mammary Collagen Deposition and Restricts Adipocyte Differentiation Before Tumor Formation
Authors: Arumugam Menusha , Tovar Elizabeth A. , Essenburg Curt J. , Dischinger Patrick S. , Beddows Ian , Wolfrum Emily , Madaj Zach B. , Turner Lisa , Feenstra Kristin , Gallik Kristin L. , Cohen Lorna , Nichols Madison , Sheridan Rachel T.C. , Esquibel Corinne R. , Mouneimne Ghassan , Graveel Carrie R. , Steensma Matthew R. 
Published: June 2023

ABSTRACTBACKGROUNDNeurofibromin, coded by theNF1tumor suppressor gene, is the main negative regulator of the RAS pathway and is frequently mutated in various cancers. Women with Neurofibromatosis Type I (NF1) – a tumor predisposition syndrome caused by a germlineNF1mutation – have an increased risk of developing aggressive breast cancer with poorer prognosis. The mechanism by whichNF1mutations lead to breast cancer tumorigenesis is not well understood. Therefore, the objective of this work was to identify stromal alterations before tumor formation that result in the increased risk and poorer outcome seen among NF1 patients with breast cancer.METHODSTo accurately model the germline monoallelicNF1mutations in NF1 patients, we utilized anNf1-deficient rat model with accelerated mammary development before presenting with highly penetrant breast cancer.RESULTSWe identified increased collagen content inNf1-deficient rat mammary glands before tumor formation that correlated with age of tumor onset. Additionally, gene expression analysis revealed thatNf1-deficient mature adipocytes in the rat mammary gland have increased collagen expression and shifted to a fibroblast and preadipocyte expression profile. This alteration in lineage commitment was also observed within vitrodifferentiation, however, flow cytometry analysis did not show a change in mammary adipose-derived mesenchymal stem cell abundance.CONCLUSIONCollectively, these studies uncovered the previously undescribed role ofNf1in mammary collagen deposition and regulating adipocyte differentiation. In addition to unraveling the mechanism of tumor formation, further investigation of adipocytes and collagen modifications in preneoplastic mammary glands will create a foundation for developing early detection strategies of breast cancer among NF1 patients.GRAPHICAL ABSTRACT
Nuclear MTHFD2 secures mitosis progression by preserving centromere integrity
Authors: Pardo-Lorente Natalia , Gkanogiannis Anestis , Cozzuto Luca , Zapater Antoni Gañez , Espinar Lorena , García-López Laura , Aydin Rabia Gül , Darai Evangelia , Severino Jacqueline , Batlle-Morera Laura , Ponomarenko Julia , Sdelci Sara 
Published: June 2023

AbstractSubcellular compartmentalization of metabolic enzymes may elicit specific cellular functions by establishing a unique metabolic environment. Indeed, the nuclear translocation of certain metabolic enzymes is required for epigenetic regulation and gene expression control. Here, we reveal that, in cancer cells, the mitochondrial enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) localizes in the nucleus during the G2-M phase of the cell cycle to secure mitosis progression. Nuclear MTHFD2 interacts with proteins involved in mitosis regulation and centromere stability, including the methyltransferases KMT5A and DNMT3B. Loss of MTHFD2 induces centromere overexpression and severe methylation defects and impedes correct mitosis completion. As a consequence, MTHFD2 deficient cells accumulate chromosomal aberrations arising from chromosome congression and segregation defects. Blocking the catalytic nuclear function of MTHFD2 recapitulates the phenotype observed in MTHFD2 deficient cells, attributing to nuclear MTHFD2 an enzymatic active role in controlling mitosis. Our discovery uncovers a nuclear moonlighting role for the cancer target MTHFD2, and emphasizes that cancer metabolism rewiring may encompass the relocation of metabolic enzymes to alternative subcellular compartments.
Rim aperture of autophagic membranes balances cargo inclusion with vesicle maturation
Authors: Shatz Oren , Fraiberg Milana , Polyansky Alexandra , Shimoni Eyal , Dadosh Tali , Wolf Sharon , Elazar Zvulun 
Published: June 2023

SummaryAutophagy eliminates cytoplasmic material by engulfment in membranous vesicles targeted for lysosome degradation. Nonselective autophagy coordinates the sequestration of bulk cargo with the growth of the isolation membrane (IM) in a yet-unknown manner. Here we show the yeast IM expands while maintaining a rim sufficiently wide for sequestration of large cargo but tight enough to mature in due time. An obligate complex of Atg24/Snx4 with Atg20 or Snx41 assembles locally at the rim in a spatially-extended manner that specifically depends on autophagic PI(3)P. This assembly stabilizes the open rim to promote autophagic sequestration of large cargo in correlation with vesicle inflation. Moreover, constriction of the rim by the PI(3)P-dependent Atg2-Atg18 complex and clearance of PI(3)P by Ymr1 antagonize the rim opening to promote autophagic maturation and consumption of small cargo. Tight regulation of membrane rim aperture by PI(3)P thus couples the mechanism and physiology of nonselective autophagy.