bluuebunny/crossref_metadata_2025 huggingface dataset:
Same-day discharge after atrial fibrillation ablation under a nurse-coordinated standardized protocol
Authors: Espinosa Teresa , Farrus Anna , Venturas Montserrat , Cano Alba , Vazquez-Calvo Sara , Pujol-Lopez Margarida , Eulogio-Valenzuela Frida , Guichard Jean-Baptiste , Falzone Pasquale V , Graterol Freddy R , Freixa Xavier , Tolosana Jose M , Guasch Eduard , Porta-Sanchez Andreu , Arbelo Elena , Brugada Josep , Sitges Marta , Mont Lluis , Roca-Luque Ivo , Althoff Till F
Published: April 2024

Aims

Same-day discharge (SDD) after atrial fibrillation (AF) ablation is an effective means to spare healthcare resources. However, safety remains a concern, and besides structural adaptations, SDD requires more efficient logistics and coordination. Therefore, in this study, we implement a streamlined, nurse-coordinated SDD programme following a standardized protocol.

Methods and results

As a dedicated SDD coordinator, a nurse specialized in ambulatory cardiac interventions was in charge of the full SDD protocol, including eligibility, patient flow, in-hospital logistics, patient education, and discharge as well as early post-discharge follow-up by smartphone-based virtual visits. Patients planned for AF ablation were considered eligible if they had a left ventricular ejection fraction (LVEF) ≥35%, with basic support at home and accessibility of the hospital within 60 min also forming a part of the eligibility criteria. A total of 420 consecutive patients were screened by the SDD coordinator, of whom 331 were eligible for SDD. The reasons for exclusion were living remotely (29, 6.9%), lack of support at home (19, 4.5%), or LVEF <35% (17, 4.0%). Of the eligible patients, 300 (91%) were successfully discharged the same day. There were no major post-SDD complications. Rates of unplanned medical attention (19, 6.3%) and 30-day readmission (5, 1.6%) were extremely low and driven by femoral access–site complications. These were significantly reduced upon the introduction of compulsory ultrasound-guided punctures after the initial 150 SDD patients (P = 0.0145). Standardized SDD coordination resulted in efficient workflows and reduced the total workload of the medical staff.

Conclusion

Same-day discharge after AF ablation following a nurse-coordinated standardized protocol is safe and efficient. The concept of ambulatory cardiac intervention nurses functioning as dedicated coordinators may be key in the future transition of hospitals to SDD. Ultrasound-guided femoral puncture virtually eliminated relevant femoral access–site complications in our cohort and should therefore be a prerequisite for SDD.
Evolutionary divergence of plasticity in brain morphology between ecologically divergent habitats of Trinidadian guppies
Authors: Axelrod Caleb J , Yang Yusan , Grant Eleanor , Fleming Jorie , Stone Isabel , Carlson Bruce A , Gordon Swanne P
Published: April 2024

Phenotypic plasticity is critical for organismal performance and can evolve in response to natural selection. Brain morphology is often developmentally plastic, affecting animal performance in a variety of contexts. However, the degree to which the plasticity of brain morphology evolves has rarely been explored. Here, we use Trinidadian guppies (Poecilia reticulata), which are known for their repeated adaptation to high-predation (HP) and low-predation (LP) environments, to examine the evolution and plasticity of brain morphology. We exposed second-generation offspring of individuals from HP and LP sites to 2 different treatments: predation cues and conspecific social environment. Results show that LP guppies had greater plasticity in brain morphology compared to their ancestral HP population, suggesting that plasticity can evolve in response to environmentally divergent habitats. We also show sexual dimorphism in the plasticity of brain morphology, highlighting the importance of considering sex-specific variation in adaptive diversification. Overall, these results may suggest the evolution of brain morphology plasticity as an important mechanism that allows for ecological diversification and adaptation to divergent habitats.
Indirect costs of reproduction and the tradeoff between offspring size and number: a framework illustrated by fitness costs and benefits of ovarian fluid
Authors: Johnson Darren W , Chhor James T , Shelley Callyn E , Siegfried Emma J
Published: April 2024

The theory describing the evolution of offspring size often assumes that the production cost per unit volume is the same for small and large offspring. However, this may not be true if indirect costs of reproduction (e.g., material and energetic costs of supporting offspring development) scale disproportionately with offspring size. Here we show how direct and indirect costs of reproduction can be explicitly modeled within the Smith–Fretwell framework and how observations of size-number relationships can thus be used to evaluate indirect costs. We applied this analysis to measures of egg volume and fecundity for over 300 individuals of a coastal fish species and found that the tradeoff was much stronger than the expected inverse (fecundity scaled with volume−1.843). Larger offspring were thus more expensive to produce. For our study species, an important indirect cost was that larger eggs were accompanied by disproportionately more ovarian fluid. Calorimetry and removal experiments were used to further measure both the energetic costs and fitness benefits of ovarian fluid. In addition, we show that indirect costs of reproduction can intensify size-number tradeoffs in a variety of fishes. Indirect costs of reproduction can be large and may therefore play an important role in the evolution of offspring size.
Proteomic insight into arabinogalactan utilization by particle-associated Maribacter sp. MAR_2009_72
Authors: Kalenborn Saskia , Zühlke Daniela , Riedel Katharina , Amann Rudolf I , Harder Jens
Published: April 2024

Arabinose and galactose are major, rapidly metabolized components of marine particulate and dissolved organic matter. In this study, we observed for the first time large microbiomes for the degradation of arabinogalactan and report a detailed investigation of arabinogalactan utilization by the flavobacterium Maribacter sp. MAR_2009_72. Cellular extracts hydrolysed arabinogalactan in vitro. Comparative proteomic analyses of cells grown on arabinogalactan, arabinose, galactose, and glucose revealed the expression of specific proteins in the presence of arabinogalactan, mainly glycoside hydrolases (GH). Extracellular glycan hydrolysis involved five alpha-l-arabinofuranosidases affiliating with glycoside hydrolase families 43 and 51, four unsaturated rhamnogalacturonylhydrolases (GH105) and a protein with a glycoside hydrolase family-like domain. We detected expression of three induced TonB-dependent SusC/D transporter systems, one SusC, and nine glycoside hydrolases with a predicted periplasmatic location. These are affiliated with the families GH3, GH10, GH29, GH31, GH67, GH78, and GH115. The genes are located outside of and within canonical polysaccharide utilization loci classified as specific for arabinogalactan, for galactose-containing glycans, and for arabinose-containing glycans. The breadth of enzymatic functions expressed in Maribacter sp. MAR_2009_72 as response to arabinogalactan from the terrestrial plant larch suggests that Flavobacteriia are main catalysts of the rapid turnover of arabinogalactans in the marine environment.
Colocalization analysis of 3′ UTR alternative polyadenylation quantitative trait loci reveals novel mechanisms underlying associations with lung function
Authors: Saferali Aabida , Kim Wonji , Xu Zhonghui , Chase Robert P , Cho Michael H , Laederach Alain , Castaldi Peter J , Hersh Craig P
Published: April 2024

While many disease-associated single nucleotide polymorphisms (SNPs) are expression quantitative trait loci (eQTLs), a large proportion of genome-wide association study (GWAS) variants are of unknown function. Alternative polyadenylation (APA) plays an important role in posttranscriptional regulation by allowing genes to shorten or extend 3′ untranslated regions (UTRs). We hypothesized that genetic variants that affect APA in lung tissue may lend insight into the function of respiratory associated GWAS loci. We generated alternative polyadenylation (apa) QTLs using RNA sequencing and whole genome sequencing on 1241 subjects from the Lung Tissue Research Consortium (LTRC) as part of the NHLBI TOPMed project. We identified 56 179 APA sites corresponding to 13 582 unique genes after filtering out APA sites with low usage. We found that a total of 8831 APA sites were associated with at least one SNP with q-value < 0.05. The genomic distribution of lead APA SNPs indicated that the majority are intronic variants (33%), followed by downstream gene variants (26%), 3′ UTR variants (17%), and upstream gene variants (within 1 kb region upstream of transcriptional start site, 10%). APA sites in 193 genes colocalized with GWAS data for at least one phenotype. Genes containing the top APA sites associated with GWAS variants include membrane associated ring-CH-type finger 2 (MARCHF2), nectin cell adhesion molecule 2 (NECTIN2), and butyrophilin subfamily 3 member A2 (BTN3A2). Overall, these findings suggest that APA may be an important mechanism for genetic variants in lung function and chronic obstructive pulmonary disease (COPD).
Technical note: utilization of various allotment strategies to evaluate variation and replications required to detect statistical significance in nursery pig research
Authors: Jenkins Abigail K , Bromm Jenna J , Gebhardt Jordan T , Woodworth Jason C , Goodband Robert D , Tokach Mike D , DeRouchey Joel M
Published: April 2024

A total of 720 barrows (line 200 × 400, DNA genetics) were used in two 42-d nursery trials (initially 6.20 ± 0.12 kg and 5.63 ± 0.16 kg, respectively) to evaluate strategies for allotting pigs to pens in randomized controlled trials. At placement, the population was split into three cohorts with similar average weight and standard deviation and randomly assigned to one of the three allotment strategies. Strategy 1 (random) utilized a simple randomization strategy with each pig randomized to pens independent of all other pigs. Strategy 2 (body weight [BW] distribution) sorted each pig within the cohort into one of the five BW groups. One pig from each weight group was then randomly assigned to a pen such that distribution of BW within pen was uniform across pens. Strategy 3 (BW grouping) sorted pigs within the cohort into 3 BW categories: light, medium, and heavy. Within each BW category, pigs were randomized to pen to create pens of pigs from each BW category. Within each experiment, there were 72 pens with five pigs per pen and 24 pens per allotment strategy. For all strategies, once pigs were allotted to pens, pens were allotted to one of the two treatments for a concurrent trial. In experiment 1, environmental enrichment using ropes tied near the pan of the feeder was compared to a control with no enrichment. In experiment 2, treatment diets consisted of basal levels of Zn and Cu from the trace mineral premix for the duration of the study (110 and 17 mg/kg, respectively; control), or diets (supplemented control) with carbadox (50 g/ton; Mecadox, Phibro Animal Health, Teaneck, NJ) fed in phase 1 (days 0 to 22) and 2 (days 22 to 43), pharmacological levels of Zn and Cu (2,414 mg/kg Zn from ZnO; 168 mg/kg Cu from CuSO4) fed in phase 1, and only pharmacological levels of Cu (168 mg/kg Cu from CuSO4) fed in phase 2. These treatment designs were used to determine the impact on coefficient of variation (CV) and to estimate the number of replications required to find significant treatment differences based on allotment strategy. There were no meaningful allotment strategy × treatment interactions for either study. For between-pen CV, pigs allotted using BW distribution and BW grouping strategies had the lowest CV at allotment and final weight in both trials. For overall average daily gain in experiments 1 and 2 in experiment 2, the BW distribution strategy required the fewest replications to detect differences in performance. However, there is no meaningful difference between allotment strategies in replications required to detect significant differences for gain:feed ratio.
Targeting fusion oncoproteins in childhood cancers: challenges and future opportunities for developing therapeutics
Authors: Verma Sharad K , Witkin Keren L , Sharman Anu , Smith Malcolm A
Published: April 2024

Fusion oncoproteins are associated with childhood cancers and have proven challenging to target, aside from those that include kinases. As part of its efforts for targeting childhood cancers, the National Cancer Institute recently conducted a series on Novel Chemical Approaches for Targeting Fusion Oncoproteins. Key learnings on leading platforms and technologies that can be used to advance the development of molecular therapeutics that target fusion oncoproteins in childhood cancers are described. Recent breakthroughs in medicinal chemistry and chemical biology provide new ground and creative strategies to exploit for the development of targeted agents for improving outcomes against these recalcitrant cancers.
Brazilian indigenous nonstarter lactic acid bacteria enhance the diversification of volatile compounds in short-aged cheese
Authors: Barreto Pinilla Cristian Mauricio , da Silva Oliveira Wellington , de Oliveira Garcia Aline , Spadoti Leila Maria , Redruello Begoña , del Rio Beatriz , Alvarez Miguel Angel , Torres Silva e Alves Adriana
Published: April 2024

There is growing interest in using autochthonous lactic acid bacteria (LAB) that provide unique sensory characteristics to dairy products without affecting their safety and quality. This work studied the capacity of three Brazilian indigenous nonstarter LABs (NSLAB) to produce biogenic amines (BAs) and evaluated their effect on the volatile organic compounds (VOCs), microbial LAB communities, and physicochemical profile of short-aged cheese. Initially, the strain's potential for biosynthesis of BAs was assessed by PCR and in vitro assays. Then, a pilot-scale cheese was produced, including the NSLAB, and the microbial and VOC profiles were analyzed after 25 and 45 days of ripening. As a results, the strains did not present genes related to relevant BAs and did not produce them in vitro. During cheese ripening, the Lactococci counts were reduced, probably in the production of alcohols and acid compounds by the NSLAB. Each strain produces a unique VOC profile that changes over the ripening time without the main VOCs related to rancid or old cheese. Particularly, the use of the strain Lacticaseibacillus. paracasei ItalPN16 resulted in production of ester compounds with fruity notes. Thus, indigenous NSLAB could be a valuable tool for the enhancement and diversification of flavor in short-aged cheese.
Advances in isolated phages that affect Ralstonia solanacearum and their application in the biocontrol of bacterial wilt in plants
Authors: Tang You , Zhou Moxi , Yang Chuyun , Liu Rong , Du Hongyi , Ma Ming
Published: April 2024

Bacterial wilt is a widespread and devastating disease that impacts the production of numerous crucial crops worldwide. The main causative agent of the disease is Ralstonia solanacearum. Due to the pathogen's broad host range and prolonged survival in the soil, it is challenging to control the disease with conventional strategies. Therefore, it is of great importance to develop effective alternative disease control strategies. In recent years, phage therapy has emerged as an environmentally friendly and sustainable biocontrol alternative, demonstrating significant potential in controlling this severe disease. This paper summarized basic information about isolated phages that infect R. solanacearum, and presented some examples of their application in the biocontrol of bacterial wilt. The risks of phage application and future prospect in this area were also discussed. Overall, R. solanacearum phages have been isolated from various regions and environments worldwide. These phages belong mainly to the Inoviridae, Autographiviridae, Peduoviridae, and Cystoviridae families, with some being unclassified. Studies on the application of these phages have demonstrated their ability to reduce pathogenicity of R. solanacearum through direct lysis or indirect alteration of the pathogen's physiological properties. These findings suggested bacteriophage is a promising tool for biocontrol of bacterial wilt in plants.
Carbon- and Oxygen-rich stars in MaStar: identification and classification
Authors: Hill Lewis , Maraston Claudia , Thomas Daniel , Yan Renbin , Chen Yanping , Stringfellow Guy S , Lane Richard R , Fernández-Trincado José G
Published: April 2024

Carbon- and Oxygen-rich stars populating the Thermally Pulsing Asymptotic Giant Branch (TP-AGB) phase of stellar evolution are relevant contributors to the spectra of ∼1 Gyr old populations. Atmosphere models for these types are uncertain, due to complex molecules and mass-loss effects. Empirical spectra are then crucial, but samples are small due to the short (∼3 Myr) TP-AGB lifetime. Here we exploit the vastness of the MaNGA Stellar library MaStar (∼60 000 spectra) to identify C and O-rich type stars. We define an optical colour selection with cuts of (g − r) > 2 and (g − i) < 1.55(g − r) − 0.07, calibrated with known C- and O-rich spectra. This identifies C- and O-rich stars along clean, separated sequences. An analogue selection is found in V, R, I  bands. Our equation identifies C-rich and O-rich spectra with predictive performance metric F1-scores of 0.72 and 0.74 (over 1), respectively. We finally identify 41 C- and 87 O-rich type AGB stars in MaStar, 5 and 49 of which do not have a SIMBAD counterpart. We also detect a sample of non-AGB, dwarf C-stars. We further design a fitting procedure to classify the spectra into broad spectral types, by using as fitting templates empirical C- and O-rich spectra. We find remarkably good fits for the majority of candidates and categorize them into C- and O-rich bins following existing classifications, which correlate to effective temperature. Our selection models can be applied to large photometric surveys (e.g. Euclid, Rubin). The classified spectra will facilitate future evolutionary population synthesis models.
Role of ionizing background and galactic feedback in the redshift space clustering of O vi absorbers in hydrodynamical simulations
Authors: Maitra Soumak , Mallik Sukanya , Srianand Raghunathan
Published: April 2024

We explore the effect of ionizing ultraviolet background (UVB) on the redshift space clustering of low-z (z ≤ 0.5) O vi absorbers using the Sherwood simulations incorporating ‘WIND’ (i.e. outflows driven by stellar feedback)-only and ‘WIND + AGN (active galactic nucleus)’ feedback. These simulations show positive clustering signals up to a scale of 3 Mpc. We find that the effect of feedback is restricted to small scales (i.e. ≤2 Mpc or ≈200 km s−1 at z ∼ 0.3) and ‘WIND’-only simulations produce a stronger clustering signal compared to simulations incorporating ‘WIND + AGN’ feedback. How the clustering signal is affected by the assumed UVB depends on the feedback processes assumed. For the simulations considered here, the effect of the UVB is confined to even smaller scales (i.e. <1 Mpc or ≈100 km s−1 at z ∼ 0.3). These scales are also affected by exclusion caused by line blending. Therefore, our study suggests that clustering at intermediate scales (i.e. 1–2 Mpc for simulations considered here) together with the observed column density distribution can be used to constrain the effect of feedback in simulations.
GeV γ-ray emission in the field of young massive star cluster RCW 38
Authors: Ge Ting-Ting , Sun Xiao-Na , Yang Rui-Zhi , Tam Pak-Hin Thomas , Lu Ming-Xuan , Liang En-Wei
Published: April 2024

We report the detection of γ-ray emission by the Fermi Large Area Telescope towards the young massive star cluster RCW 38 in the 1–500 GeV photon energy range. We found spatially extended GeV emission towards the direction of RCW 38, which is best modelled by a Gaussian disc of 0.23° radius with a significance of the extension of ∼11.4σ. Furthermore, the spatial correlation with the ionized and molecular gas content favours the hadronic origin of the γ-ray emission. The γ-ray spectrum of RCW 38 has a relatively hard photon index of 2.44 ± 0.03, which is similar to other young massive star clusters. We argue that the diffuse GeV γ-ray emission in this region likely originates from the interaction of accelerated protons in the stellar cluster with the ambient gas.
Post-AGB candidate IRAS 02143+5852: Cepheid-like variability, three-layer circumstellar dust envelope and spectral features
Authors: Ikonnikova N P , Burlak M A , Dodin A V , Shugarov S Yu , Belinski A A , Fedoteva A A , Tatarnikov A M , Rudy R J , Perry R B , Zheltoukhov S G , Atapin K E
Published: April 2024

We present the results of multicolour UBVRCICJHK photometry, spectroscopic analysis and spectral energy distribution (SED) modelling for the post-AGB candidate IRAS 02143+5852. We detected Cepheid-like light variations with the full peak-to-peak amplitude ΔV ∼ 0.9 mag and the pulsation period of about 24.9 d. The phased light curves appeared typical for the W Vir Cepheids. The period–luminosity relation for the Type II Cepheids yielded the luminosity logL/L⊙ ∼ 2.95. From a low-resolution spectrum, obtained at maximum brightness, the following atmospheric parameters were determined: Teff ∼ 7400 K and logg ∼ 1.38. This spectrum contains the emission lines H α, ${\rm Ba\, {\small II}}$ λ6496.9, ${\rm He\, {\small I}}$λ10830, and Pa β. Spectral monitoring performed in 2019–2021 showed a significant change in the H α profile and appearance of CH and CN molecular bands with pulsation phase. The metal lines are weak. Unlike typical W Vir variables, the star shows a strong excess of infrared radiation associated with the presence of a heavy dust envelope around the star. We modelled the SED using our photometry and archival data from different catalogues and determined the parameters of the circumstellar dust envelope. We conclude that IRAS 02143+5852 is a low-luminosity analogue of dusty RV Tau stars.
C iii] λ1909 emission as an alternative to Ly α in the reionization era: the dependence of C iii] and Ly α at 3 < z < 4 from the VANDELS survey
Authors: Cunningham M H , Saxena A , Ellis R S , Pentericci L
Published: April 2024

The velocity offset of Ly α emission from a galaxy’s systemic redshift is an excellent tracer of conditions that enable the escape of Ly α photons from the galaxy, and potentially the all-important hydrogen ionizing Lyman continuum photons. However at z ≥ 6, Ly α is often heavily attenuated by the neutral intergalactic medium. Here we investigate the utility of C iii] λλ1907, 1909 emission, usually the brightest ultraviolet (UV) line after Ly α, as a proxy estimating the Ly α velocity offset (ΔvLy α). To do so, we use analogues of reionization era galaxies based upon 52 star-forming galaxies with robust C iii] detections drawn from the VANDELS survey. Our sample spans a broad UV magnitude range of −18.5 < MUV < −22.0, with a sample average value of EW(C iii]) = 5.3 Å. We find a slight increase of EW(C iii]) with increasing EW(Ly α), but find a large range of EW(C iii]) ∼ 1–13 Å particularly at EW(Ly α) < 10 Å. Using the C iii] line peak as the systemic redshift, we calculate ΔvLy α and recover the previously reported trend of decreasing ΔvLy α with increasing EW(Ly α). Interestingly, we find an anticorrelation between ΔvLy α and EW(C iii]), which also displays a dependence on the UV absolute magnitude. We derive a multivariate fit to obtain ΔvLy α using both EW(C iii]) and MUV, finding that ΔvLy α is more strongly dependent on EW(C iii]), with a weaker but non-negligible dependence on MUV. We find that for a fixed EW(C iii]), UV-bright Ly α emitting galaxies show smaller values of ΔvLy α,which suggests that such galaxies may be undergoing more bursty star-formation compared to the UV-fainter ones, akin to a population of extremely UV-bright galaxies identified at z > 10.
The heat shock factor 20-HSF4-cellulose synthase A2 module regulates heat stress tolerance in maize
Authors: Li Ze , Li Zerui , Ji Yulong , Wang Chunyu , Wang Shufang , Shi Yiting , Le Jie , Zhang Mei
Published: April 2024

Temperature shapes the geographical distribution and behavior of plants. Understanding the regulatory mechanisms underlying the plant heat stress response is important for developing climate-resilient crops, including maize (Zea mays). To identify transcription factors (TFs) that may contribute to the maize heat stress response, we generated a dataset of short- and long-term transcriptome changes following a heat treatment time course in the inbred line B73. Co-expression network analysis highlighted several TFs, including the class B2a heat shock factor (HSF) ZmHSF20. Zmhsf20 mutant seedlings exhibited enhanced tolerance to heat stress. Furthermore, DNA affinity purification sequencing and Cleavage Under Targets and Tagmentation assays demonstrated that ZmHSF20 binds to the promoters of Cellulose synthase A2 (ZmCesA2) and three class A Hsf genes, including ZmHsf4, repressing their transcription. We showed that ZmCesA2 and ZmHSF4 promote the heat stress response, with ZmHSF4 directly activating ZmCesA2 transcription. In agreement with the transcriptome analysis, ZmHSF20 inhibited cellulose accumulation and repressed the expression of cell wall-related genes. Importantly, the Zmhsf20 Zmhsf4 double mutant exhibited decreased thermotolerance, placing ZmHsf4 downstream of ZmHsf20. We proposed an expanded model of the heat stress response in maize, whereby ZmHSF20 lowers seedling heat tolerance by repressing ZmHsf4 and ZmCesA2, thus balancing seedling growth and defense.
Do Institutional Investors Process and Act on Information? Evidence from M&A Targets
Authors: Kim Kirak , Luu Ellie , Xu Fangming
Published: April 2024

We document important links between targets’ institutional ownership and takeover-bid outcomes. Firms’ institutional ownership increases the likelihood of receiving stock-for-stock bids. The impact becomes stronger when information asymmetries are higher, whereas we find little support for alternative channels, such as bidder misvaluation or target-side adverse selection. The information channel is further buttressed in our analyses of institutions’ share-retention decisions, targets’ demand for top-tier advisors, collar provisions, and targets’ share of expected synergies. Our findings suggest that institutions’ information advantage facilitates rational payment design and targets’ bargaining power gains, alleviating deadweight losses associated with stock-for-stock offers.
Comparison of transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in wild-type and PPARα knockout mouse hepatocytes
Authors: Heintz Melissa M , Klaren William D , East Alexander W , Haws Laurie C , McGreal Steven R , Campbell Rebecca R , Thompson Chad M
Published: April 2024

Recent in vitro transcriptomic analyses for the short-chain polyfluoroalkyl substance, HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate), support conclusions from in vivo data that HFPO-DA-mediated liver effects in mice are part of the early key events of the peroxisome proliferator-activated receptor alpha (PPARα) activator-induced rodent hepatocarcinogenesis mode of action (MOA). Transcriptomic responses in HFPO-DA-treated rodent hepatocytes have high concordance with those treated with a PPARα agonist and lack concordance with those treated with PPARγ agonists or cytotoxic agents. To elucidate whether HFPO-DA-mediated transcriptomic responses in mouse liver are PPARα-dependent, additional transcriptomic analyses were conducted on samples from primary PPARα knockout (KO) and wild-type (WT) mouse hepatocytes exposed for 12, 24, or 72 h with various concentrations of HFPO-DA, or well-established agonists of PPARα (GW7647) and PPARγ (rosiglitazone), or cytotoxic agents (acetaminophen or d-galactosamine). Pathway and predicted upstream regulator-level responses were highly concordant between HFPO-DA and GW7647 in WT hepatocytes. A similar pattern was observed in PPARα KO hepatocytes, albeit with a distinct temporal and concentration-dependent delay potentially mediated by compensatory responses. This delay was not observed in PPARα KO hepatocytes exposed to rosiglitazone, acetaminophen, d-galactosamine. The similarity in transcriptomic signaling between HFPO-DA and GW7647 in both the presence and absence of PPARα in vitro indicates these compounds share a common MOA.
Cadmium inhibits calcium activity in hippocampal CA1 neurons of freely moving mice
Authors: Matsushita Megumi T , Xia Zhengui
Published: April 2024

Cadmium (Cd) is a ubiquitous toxic heavy metal and a potential neurotoxicant due to its wide use in industrial manufacturing processes and commercial products, including fertilizers. The general population is exposed to Cd through food and smoking due to high transfer rates of Cd from contaminated soil. Cd has been shown to mimic calcium ions (Ca2+) and interfere with intracellular Ca2+ levels and Ca2+ signaling in in vitro studies. However, nothing is known about Cd’s effects on Ca2+ activity in neurons in live animals. This study aimed to determine if Cd disrupts Ca2+ transients of neurons in CA1 region of the hippocampus during an associative learning paradigm. We utilized in vivo Ca2+ imaging in awake, freely moving C57BL/6 mice to measure Ca2+ activity in CA1 excitatory neurons expressing genetically encoded Ca2+ sensor GCaMP6 during an associative learning paradigm. We found that a smaller proportion of neurons are activated in Cd-treated groups compared with control during fear conditioning, suggesting that Cd may contribute to learning and memory deficit by reducing the activity of neurons. We observed these effects at Cd exposure levels that result in blood Cd levels comparable with the general U.S. population levels. This provides a possible molecular mechanism for Cd interference of learning and memory at exposure levels relevant to U.S. adults. To our knowledge, our study is the first to describe Cd effects on brain Ca2+ activity in vivo in freely behaving mice.

This study provides evidence for impairment of neuronal calcium activity in hippocampal CA1 excitatory neurons in freely moving mice following cadmium exposure.
Simulation in pediatric anesthesiology: current state and visions for the future
Authors: Daly Guris Rodrigo J. , George Preeta , Gurnaney Harshad G.
Published: April 2024

Purpose of review

Simulation is a well established practice in medicine. This review reflects upon the role of simulation in pediatric anesthesiology in three parts: training anesthesiologists to care for pediatric patients safely and effectively; evaluating and improving systems of care for children; and visions for the future.

Recent findings

Simulation continues to prove a useful modality to educate both novice and experienced clinicians in the perioperative care of infants and children. It is also a powerful tool to help analyze and improve upon how care is provided to infants and children. Advances in technology and computational power now allow for a greater than ever degree of innovation, accessibility, and focused reflection and debriefing, with an exciting outlook for promising advances in the near future.

Simulation plays a key role in developing and achieving peak performance in the perioperative care of infants and children. Although simulation already has a great impact, its full potential is yet to be harnessed.
Post-traumatic Bullous Pilomatrixoma Exploring the Pathogenesis
Authors: Martínez-Ortega Jesús I. , Ortega-Valerio Grisell , Ramirez-Cibrian Arely G.
Published: April 2024

This report demonstrates the rare variant of bullous pilomatrixoma in a 10-year-old boy who presented with a rapidly growing, red-colored, bullous nodule on his neck after trauma. The exact etiology of this subtype of pilomatrixoma is unclear, but previous studies have suggested that mechanical trauma may trigger its development.
Walking on thin endometrium
Authors: Ata Baris , Mathyk Begum , Telek Savci , Kalafat Erkan
Published: April 2024

Purpose of review

Endometrial thickness has been regarded a predictor of success in assisted reproductive technology cycles and it seems a common practice to cancel embryo transfer when it is below a cut-off. However, various cut-offs have been proposed without a causal relationship between endometrial thickness and embryo implantation being established, casting doubt on the current dogma.

Recent findings

Methodological limitations of the available studies on endometrial thickness are increasingly recognized and better designed studies do not demonstrate a cut-off value which requires cancelling an embryo transfer.

Endometrium is important for implantation and a healthy pregnancy; however, ultrasound measured thickness does not seem to be a good marker of endometrial function.
Abnormal Cerebrospinal Fluid Cytology in Functional Movement Disorders
Authors: Serranová Tereza , Slovák Matěj , Forejtová Zuzana , Sieger Tomáš , Dušek Petr , Srpová Barbora , Mrázová Kateřina , Růžička Evžen , Šonka Karel , Espay Alberto J. , Nytrová Petra
Published: April 2024

Objective

The role of inflammation and neuroimmune mechanisms, which have been documented in various neuropsychiatric disorders including the seizure subtype of functional neurological disorder, remains unclear in functional movement disorders (FMD). To explore these mechanisms, we analyzed selected inflammatory markers in cerebrospinal fluid (CSF) in patients with FMD.

Methods

We compared CSF markers in 26 patients with clinically established FMD (20 females; mean [SD] age = 43.3 [10.9], disease duration = 3.9 [3], range = 0.1–11 years; mean follow-up after lumbar puncture = 4.3 [2] years, range = 0.5–7 years) and 26 sex- and age-matched clinical controls with noninflammatory nonneurodegenerative neurological disorders, mostly sleep disorders.

Results

Sixty-five percent of FMD patients versus 15% of controls showed cytological abnormalities (i.e., increased white blood cells [WBC] count, signs of WBC activation, or both; odds ratio [OR] = 9.85, 95% confidence interval = 2.37–52.00, p < .01, corrected), with a significantly higher frequency of an isolated lymphocytic activation, 35% versus 0% (OR = ∞, 95% confidence interval = 2.53–∞, p < .05, corrected). There were no differences in CSF protein and albumin levels, quotient albumin, IgG index, and oligoclonal bands. CSF abnormalities were not associated with more severe motor symptoms or a higher frequency of depression in FMD.

Conclusions

Our results suggest a possible involvement of immune mechanisms in the pathophysiology of (at least a subtype of) FMD that deserves further investigation.
Machine learning-driven COVID-19 early triage and large-scale testing strategies based on the 2021 Costa Rican Actualidades survey
Authors: Pasquier Carlos , Solís Maikol , Vilchez Vivian , Núñez-Corrales Santiago
Published: April 2024

The COVID-19 pandemic underscored the importance of mass testing in mitigating the spread of the virus. This study presents mass testing strategies developed through machine learning models, which predict the risk of COVID-19 contagion based on health determinants. Using the data from the 2021 “Actualidades” survey in Costa Rica, we trained models to classify individuals by contagion risk. After theorize four possible strategies, we evaluated these using Monte Carlo simulations, analyzing the distribution functions for the number of tests, positive cases detected, tests per person, and total costs. Additionally, we introduced the metrics,efficiencyandstock capacity, to assess the performance of different strategies. Our classifier achieved an AUC-ROC of 0.80 and an AUC-PR of 0.59, considering a disease prevalence of 0.26. The fourth strategy, which integrates RT-qPCR, antigen, and RT-LAMP tests, emerged as a cost-effective approach for mass testing, offering insights into scalable and adaptable testing mechanisms for pandemic response.
Combined visualization of genomic and epidemiological data for outbreaks
Authors: Suster Carl J.E. , Watt Anne E. , Wang Qinning , Chen Sharon C.-A. , Kok Jen , Sintchenko Vitali
Published: April 2024

In epidemiological investigations, pathogen genomics can provide insights and test epidemiological hypotheses that would not have been possible through traditional epidemiology. Tools to synthesize genomic analysis with other types of data are a key requirement of genomic epidemiology. We propose a new ‘phylepic’ visualization that combines a phylogenomic tree with an epidemic curve. The combination visually links the molecular time represented in the tree to the calendar time in the epidemic curve, a correspondence that is not easily represented by existing tools. Using an example derived from a foodborne bacterial outbreak, we demonstrated that the phylepic chart communicates that what appeared to be a point-source outbreak was in fact composed of cases associated with two genetically distinct clades of bacteria. We provide an R package implementing the chart. We expect that visualizations that place genomic analyses within the epidemiological context will become increasingly important for outbreak investigations and public health surveillance of infectious diseases.
Nanopore Guided Annotation of Transcriptome Architectures
Authors: Abebe Jonathan S. , Alwie Yasmine , Fuhrmann Erik , Leins Jonas , Mai Julia , Verstraten Ruth , Schreiner Sabrina , Wilson Angus C. , Depledge Daniel P.
Published: April 2024

High-resolution annotations of transcriptomes from all domains of life are essential for many sequencing-based RNA analyses, including Nanopore direct RNA sequencing (DRS), which would otherwise be hindered by misalignments and other analysis artefacts. DRS allows the capture and full-length sequencing of native RNAs, without recoding or amplification bias, and resulting data may be interrogated to define the identity and location of chemically modified ribonucleotides, as well as the length of poly(A) tails on individual RNA molecules. Existing software solutions for generating high-resolution transcriptome annotations are poorly suited to small gene dense organisms such as viruses due to the challenge of identifying distinct transcript isoforms where alternative splicing and overlapping RNAs are prevalent. To resolve this, we identified key characteristics of DRS datasets and developed a novel approach to transcriptome. We demonstrate, using a combination of synthetic and original datasets, that our novel approach yields a high level of precision and recall when reconstructing both gene sparse and gene dense transcriptomes from DRS datasets. We further apply this approach to generate a new high resolution transcriptome annotation of the neglected pathogen human adenovirus type F 41 for which we identify 77 distinct transcripts encoding at least 23 different proteins.
MGPfactXMBD: A Model-Based Factorization Method for scRNA Data Unveils Bifurcating Transcriptional Modules Underlying Cell Fate Determination
Authors: Ren Jun , Zhou Ying , Hu Yudi , Yang Jing , Fang Hongkun , Lyu Xuejing , Guo Jintao , Shi Xiaodong , Li Qiyuan
Published: April 2024

Manifold-learning is particularly useful to resolve the complex cellular state space from single-cell RNA sequences. While current manifold-learning methods provide insights into cell fate by inferring graph-based trajectory at cell level, challenges remain to retrieve interpretable biology underlying the diverse cellular states. Here, we described MGPfactXMBD, a model-based manifold-learning framework and capable to factorize complex development trajectories into independent bifurcation processes of gene sets, and thus enables trajectory inference based on relevant features. MGPfactXMBDoffers more nuanced understanding of the biological processes underlying cellular trajectories with potential determinants. When bench-tested across 239 datasets, MGPfactXMBDshowed advantages in major quantity-control metrics, such as branch division accuracy and trajectory topology, outperforming most established methods. In real datasets, MGPfactXMBDrecovered the critical pathways and cell types in microglia development with experimentally valid regulons and markers. Furthermore, MGPfactXMBDdiscovered evolutionary trajectories of tumor-associated CD8+T cells and yielded new subtypes of CD8+T cells with gene expression signatures significantly predictive of the responses to immune checkpoint inhibitor in independent cohorts. In summary, MGPfactXMBDoffers a manifold-learning framework in scRNA-seq data which enables feature selection for specific biological processes and contributing to advance our understanding of biological determination of cell fate.
Vinegar injections can be used safely to control outbreaks of crown-of-thorns starfish (Acanthaster solaris) during the peak spawning season
Authors: Dumas Pascal , Durbano Amaury , Bourgeois Bertrand , Gossuin Hugues , Peignon Christophe
Published: April 2024

Concerns are mounting over the effects of COTS outbreaks, prompting the need for integrated management strategies. Although direct control methods are short-term and localized, they remain one of the few operational tools that can be easily implemented by local actors. Vinegar injections have recently emerged as highly effective method; however their impact on reproductive behavior remains untested. Here, we investigated the short-term spawning response of mature COTS to double injections of household vinegar. First, COTS abundances and reproductive status were monitored during a massive outbreak affecting New Caledonia’s reefs. In-situ and laboratory experiments were then conducted to determine whether injected COTS would eventually release their eggs and trigger synchronized spawning among mature individuals in close proximity. Our results indicated that injections had no significant effect on spawning behavior, even in densely populated aggregations (>4000 COTS.ha-1). In the field, starfish exhibited ripe gonads with high gamete content (up to 35% of body weight) three days after conspecifics were injected. In the laboratory, mature COTS kept with injected, decaying individuals in a confined volume did not expel their gametes after two days. This suggests that vinegar injections could be used at any time, even during peak spawning, without risking synchronized spawning in the affected areas.
Terroir and rootstock effects on leaf shape in California Central Valley vineyards
Authors: Migicovsky Zoë , Swift Joel F. , Awale Mani , Helget Zachary , Klein Laura L. , Pinkner Leah , Woodhouse Karoline , Cousins Peter , Fennell Anne Y. , Miller Allison J. , Chitwood Daniel H.
Published: April 2024

Embedded in a single leaf shape are the latent signatures of genetic, developmental, and environmental effects. In viticulture, choice of location and rootstock are important decisions that affect the performance and production of the shoot. We hypothesize that these effects influence plant morphology, as reflected in leaf shape.

We sample 1879 leaves arising from scion and rootstock combinations from commercial vineyards in the Central Valley of California. Our design tests 20 pairwise contrasts between Cabernet Sauvignon and Chardonnay scions from San Joaquin, Merced, and Madera counties from vines grafted to Teleki 5C, 1103 Paulsen, and Freedom rootstocks.

Using geometric morphometric approaches, we visualize a morphospace in which, in addition to clear separation of Cabernet Sauvignon and Chardonnay scion leaf shapes, an orthogonal source of shape variation affects both varieties. Comparing the Procrustes distances to within and between group means, the additional source of variance is found to arise from location and rootstock effects.

We describe and visualize a specific shape feature, the angle of the proximal lobe to the midvein that defines the closure of the petiolar sinus, that is attributable to location and rootstock effects and orthogonal to and separate from genetic, developmental, or allometric effects attributable to leaf size.

Societal Impact Statement (EN)

The innumerable effects of terroir—including climate, soil, microbial environment, biotic interactions, and cultivation practice—collectively alter plant performance and production. A more direct agricultural intervention is grafting, in which genetically distinct shoot and root genotypes are surgically combined to create a chimera that alter shoot performance at a distance. Selection of location and rootstock are intentional decisions in viticulture to positively alter production outcomes. Here, we show that terroir and rootstock alter the shapes of grapevine leaves in commercial vineyards throughout the California Central Valley, documenting the profound effects of these agricultural interventions that alter plant morphology.
RELAX-Jr: An Automated Pre-Processing Pipeline for Developmental EEG Recordings
Authors: Hill Aron T. , Enticott Peter G. , Fitzgerald Paul B. , Bailey Neil W.
Published: April 2024

Automated EEG pre-processing pipelines provide several key advantages over traditional manual data cleaning approaches; primarily, they are less time-intensive and remove potential experimenter error/bias. Automated pipelines also require fewer technical expertise as they remove the need for manual artifact identification. We recently developed the fully automated Reduction of Electroencephalographic Artifacts (RELAX) pipeline and demonstrated its performance in cleaning EEG data recorded from adult populations. Here, we introduce the RELAX-Jr pipeline, which was adapted from RELAX to be designed specifically for pre- processing of data collected from children. RELAX-Jr implements multi-channel Wiener filtering (MWF) and/or wavelet-enhanced independent component analysis (wICA) combined with the adjusted-ADJUST automated independent component classification algorithm to identify and reduce all artifacts using algorithms adapted to optimally identify artifacts in EEG recordings taken from children. Using a dataset of resting-state EEG recordings (N = 136) from children spanning early-to-middle childhood (4-12 years), we assessed the cleaning performance of RELAX-Jr using a range of metrics including signal-to-error ratio, artifact-to-residue ratio, ability to reduce blink and muscle contamination, and differences in estimates of alpha power between eyes-open and eyes-closed recordings. We also compared the performance of RELAX- Jr against four publicly available automated cleaning pipelines. We demonstrate that RELAX-Jr provides strong cleaning performance across a range of metrics, supporting its use as an effective and fully automated cleaning pipeline for neurodevelopmental EEG data.
Decoding region-level visual functions from invasive EEG data
Authors: Zhang Xin-Ya , Lin Hang , Deng Zeyu , Siegel Markus , Miller Earl K. , Yan Gang
Published: April 2024

Decoding vision is an ambitious task as it aims to transform scalar brain activity into dynamic images with refined shapes, colors and movements. In familiar environments, the brain may trigger activity that resembles specific pattern, thereby facilitating decoding. Can an artificial neural network (ANN) decipher such latent patterns? Here, we explore this question using invasive electroencephalography data from monkeys. By decoding multiregion brain activity, ANN effectively captures individual regions’ functional roles as a consequence of minimizing visual errors. For example, ANN recognizes that regions V4 and LIP are involved in visual color and shape processing while MT predominantly handles visual motion, aligning with regional visual functions evident in the brain. ANN likely reconstructs vision by seizing hidden spike patterns, representing stimuli distinctly in a two-dimensional plane. Furthermore, during the encoding process of transforming visual stimuli into neuronal activity, optimal performance is achieved in regions closely associated with vision processing.