bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Mixed Methods System for the Assessment of Post Exertional Malaise in Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Stussman Barbara , Calco Brice , Norato Gina , Gavin Angelique , Chigurupati Snigdha , Nath Avindra , Walitt Brian 
Published: April 2023

AbstractBackgroundA central feature of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is post exertional malaise (PEM), which is an acute worsening of symptoms after a physical, emotional and/or mental exertion. PEM is also a feature of Long COVID. Dynamic measures of PEM have historically included scaled questionnaires which have not been validated in ME/CFS. To enhance our understanding of PEM and how best to measure it, we conducted semi-structured qualitative interviews (QIs) at the same intervals as Visual Analog Scale (VAS) measures after a Cardiopulmonary Exercise Test (CPET).MethodsTen ME/CFS and nine healthy volunteers participated in a CPET. For each participant, PEM symptom VAS (7 symptoms) and semi-structured QIs were administered at six timepoints over 72 hours before and after a single CPET. QI data were used to plot the severity of PEM at each time point and identify the self-described most bothersome symptom for each patient. QI data were used to determine the symptom trajectory and peak of PEM. Performance of QI and VAS data were compared to each other using Spearman correlations.ResultsQIs documented that each ME/CFS volunteer had a unique PEM experience, with differences noted in the onset, severity, trajectory over time, and most bothersome symptom. No healthy volunteers experienced PEM. Scaled QI data were able to identify PEM peaks and trajectories, even when VAS scales were unable to do so due to known ceiling and floor effects. QI and VAS fatigue data corresponded well prior to exercise (baseline, r=0.7) but poorly at peak PEM (r=0.28) and with the change from baseline to peak (r=0.20). When the most bothersome symptom identified from QIs was used, these correlations improved (r=.0.77, 0.42. and 0.54 respectively) and reduced the observed VAS scale ceiling and floor effects.ConclusionQIs were able to capture changes in PEM severity and symptom quality over time in all the ME/CFS volunteers, even when VAS scales failed to do so. Information collected from QIs also improved the performance of VAS. Measurement of PEM can be improved by using a quantitative-qualitative mixed model approach.DisclaimerThis research/work/investigator was supported (in part) by the Division of Intramural Research of the National Institutes of Health, NINDS. The content is solely the responsibility of the author(s) and does not necessarily represent the official views of the National Institutes of Health.
WITHDRAWN: Evaluation of Fourier Transform Infrared spectroscopy (IR Biotyper) as a complement to Whole genome sequencing (WGS) to characteriseEnterobacter cloacae,Citrobacter freundiiandKlebsiella pneumoniaeisolates recovered from hospital sinks
Authors: Aranega-Bou P , Cornbill C , Rodger G , Bird M , Moore G , Roohi A , Hopkins KL , Hopkins S , Ribeca P , Stoesser N , Lipworth SI 
Published: April 2023

Withdrawal statementThe authors have withdrawn their manuscript due to becoming aware of methodology issues related to the curation of the training set used to determine cut-off values for Biotyper cluster assignation and lack of replicate measurements on different days for the isolates analysed. It is therefore unclear whether the conclusions of the manuscript are founded and no further work is possible to correct these issues as the instrument is no longer available to the authors. If you have any questions, please contact the corresponding author.
Estimation of Near-kink Reproduction Numbers During the Emergent Variants of the COVID-19 Pandemic: Log-quadratic and Forward-imputation Approach
Authors: Nakamoto Ichiro 
Published: April 2023

AbstractBackgroundSketching the major portraits of the COVID-19 epidemic when variants of the pathogen emerge is critical to inform the dynamics of disease transmission, reproduction (i.e., the average counts of individuals of secondary infections generated by an index individual infected by the virus) strength of the pathogen, and countermeasure strategies. Multiple approaches, including log-linear, EpiEstim (an R package generally utilized to estimate the evolution traits of epidemics), and near-log-linear techniques, have been exploited to evaluate the principal parameters such as basic and effective reproduction numbers of an epidemic outbreak.ObjectiveThis study focuses on the kink corner (i.e., sharp alternation of direction of the transmission curve) presenting differentiated log-quadratic traits where more infectious variants of viruses emerge at the diminishing transmission phase of an infectious disease.MethodsA novel log-quadratic trending framework was proposed to project potentially unidentified cases (i.e., forward imputing approximately one week ahead) of COVID-19 around the kink, where the transmission of the pandemic initially lowered and accelerated subsequently, and exercised with the updated framework of classic EpiEstim and Log-linear model. I first compared the performance near the kink using the proposed technique versus the two traditional models taking into account a variety of levels of transmissibility, data distribution (Weibull, Gamma, and Lognormal distributions), and reporting rates (0.2, 0.4, 0.6, 0.8 and 1.0 respectively). Thereafter I utilized the revised framework on the outbreak data of four settings including Bulgaria, Japan, Poland, and South Korea from June to August 2022.ResultsThe proposed framework reduced the estimation bias versus traditional EpiEstim and log-linear methods near the kink. The coverage estimates of 95% confidence intervals improved. The proposed forward-imputation method implied generally a consistent ascending trend of effective reproduction number estimation applying to a precipitous transition from diminishing to diverging scenarios versus the irregular zigzagging outcomes in classic methods when more contagious variants of the virus were present in the absence of effective vaccines.ConclusionsThe log-quadratic correction accounting for transmissibility, data distribution, reporting rates, sliding windows, and generation intervals improved the basic and effective reproduction numbers estimation at the kink corner versus the classic EpiEstim and log-linear models by refined amendment of curve fitting. This is of concern when essentially the fundamental transmission traits of a pandemic alter expeditiously and countermeasures are needed at the earlier variant phases of the transiting climax with the advancement of the pandemic.
Is Covid-19 Mortality “Like the Flu”? A Cumulative Death Rates Comparison
Authors: Wrigley-Field Elizabeth , Himmelstern Jessie 
Published: April 2023

ABSTRACTIt has been common both to make and to resist comparisons that equate the Covid-19 pandemic to influenza. We take the comparison between Covid-19 and flu seriously by asking how many years of influenza and pneumonia deaths are needed for cumulative deaths to those two causes to equal the cumulative toll of the Covid-19 pandemic between March 2020 and February 2023—that is, three years of pandemic deaths. We find that in one state alone—Hawaii—three years of Covid-19 mortality is equivalent to influenza and pneumonia mortality in the three years preceding the Covid-19 pandemic. For all other states, at least nine years of flu and pneumonia are needed to match Covid-19; for the United States as a whole, seventeen years are needed; and for four states, more than 21 years (the maximum observable) are needed. These results provide an easy-to-understand calibration of flu as a heuristic for Covid-19, and vice versa.
Bifrontal transcranial direct current stimulation normalises learning rate adjustment in low mood
Authors: Sarrazin Verena , Overman Margot , Mezossy-Dona Luca , Browning Michael , O’Shea Jacinta 
Published: April 2023

AbstractBackgroundTranscranial direct current stimulation (tDCS) applied to dorsolateral prefrontal cortex has mild to moderate antidepressant effects. Little is known about the mechanisms of action. Other antidepressant treatments have been shown to act in part by reducing negative biases, which are thought to play a causal role in the maintenance of depression. Negative biases are hypothesized to stem from aberrant reinforcement learning processes, more precisely from overestimation of the informativeness of negative outcomes. The aim of this study was to test whether bifrontal tDCS might normalise such aberrant reinforcement learning processes in depressed mood.Methods85 community volunteers with low mood received tDCS during (or before) the performance of a reinforcement learning task that manipulated the informativeness (volatility) of positive and negative outcomes. In two sessions participants received real or sham tDCS in counter-balanced order. Baseline performance (sham tDCS) was compared to a sample of healthy individuals (n = 40) to identify the effect of low mood on task performance. The impact of tDCS on task performance was assessed by contrasting real and sham tDCS.ResultsLow mood was characterised by decreased adjustment of loss relative to win learning rates in response to changes in informativeness. Bifrontal tDCS applied during task performance normalised this deficit by increasing the adjustment of loss learning rates to informativeness. Bifrontal tDCS applied before task performance had no effect indicating that the stimulation effect is cognitive state dependent.ConclusionsOur study provides preliminary evidence that bifrontal tDCS can normalise aberrant reinforcement learning processes in low mood. Crucially, this was only the case if stimulation was applied during task performance, suggesting that combining tDCS with a concurrent cognitive manipulation might increase the functional impact on cognitive functions and potentially on emotional symptoms. Future studies are needed to test if the effect on learning processes might have a beneficial effect on mood itself.
Assembly and Cation-selectivity Mechanisms of Neuronal Gap Junction Channel Connexin 36 Elucidated by Cryo-EM
Authors: Mao Wenxuan , Chen Shanshuang 
Published: April 2023

AbstractElectrical synapses are essential components of neural circuits. Dysfunction of electrical synapses can lead to obstacles in learning and memory. Neural signal transduction across electrical synapses is primarily mediated by a gap junction channel, Connexin 36 (Cx36), the lack of which causes impaired electrical couplings in cortical interneurons and thalamic reticular nucleus (TRN) neurons. Unique characteristics of Cx36 gap junction channel include its insensitivity in transjunctional membrane potential, as well as its preference for homomeric assembly, prone to exclude other paralogous connexins from co-assembly. However, the structural basis underlying Cx36 function and assembly remains elusive. Here, we report the cryo-EM structure of human Cx36 at 2.67 Å resolution and identified critical residues underpinning its obligatory homomeric assembly. In particular, we found non-canonical electrostatic interactions between protomers from opposing hemichannels and a steric complementary site between adjacent protomers within a hemichannel, which together offer a structural explanation for the assembly specificity in homomeric and heteromeric gap junction channels. Moreover, the narrowest restriction along the channel axis overlaps with an acidic patch, where Glu43, Asp47 and Asp48 may contribute to cation-selectivity. Also, the amino-terminal helix reported to be responsible for sensing membrane potential in other connexins was disordered in our Cx36 structure, in line with its channel activity independent of membrane potential. Together, this work elucidated the assembly mechanisms of the electrical synaptic gap junction channel, and offered possible explanations for sustained Cx36 activity upon membrane depolarization, which allows efficient action potential propagation across electrical synapses.
Multicomponent regulation of actin barbed end assembly by twinfilin, formin and capping protein
Authors: Ulrichs Heidi , Gaska Ignas , Shekhar Shashank 
Published: April 2023

AbstractLiving cells assemble their actin networks by regulating reactions at the barbed end of actin filaments. Formins accelerate elongation, capping protein (CP) arrests growth and twinfilin promotes depolymerization at barbed ends. How cells integrate these disparate activities within a shared cytoplasm to produce diverse actin networks, each with distinct morphologies and finely tuned assembly kinetics, is unclear. We used microfluidics-assisted TIRF microscopy to investigate how formin mDia1, CP and twinfilin influence the elongation of actin filament barbed ends. We discovered that the three proteins can simultaneously bind a barbed end in a multiprotein complex. Three-color single molecule experiments showed that twinfilin cannot bind actin filament ends occupied by formin mDia1 unless CP is present. The trimeric complex is short-lived (∼1s) and results in rapid dissociation of CP by twinfilin causing resumption of rapid formin- based elongation. Thus, the depolymerase twinfilin acts as a pro-formin factor that promotes polymerization when both CP and formin are present. While a single twinfilin binding event is sufficient to displace CP from the trimeric complex, it takes about 30 independent twinfilin binding events to remove capping protein from CP-bound barbed end. Our findings establish a new paradigm in which polymerases, depolymerases and cappers work in concert to tune cellular actin assembly.
B cells from aged mice do not have intrinsic defects in affinity maturation
Authors: Lee Jia Le , Innocentin Silvia , Silva-Cayetano Alyssa , Guillaume Stephane M. , Linterman Michelle A. 
Published: April 2023

AbstractAffinity maturation, the progressive increase in serum antibody affinity after vaccination, is an essential process that contributes to an effective humoral response against vaccines and infections. Germinal centres (GCs) are key for affinity maturation, as they are where B cells undergo somatic hypermutation of their immunoglobulin genes in the dark zone, before going through positive selection in the light zone via interactions with T follicular helper cells and follicular dendritic cells. In aged mice, affinity maturation has been shown to be impaired, but whether B cell-intrinsic factors contribute to this defect remains unclear. In this study, we show that B cells from aged B cell receptor transgenic mice are able to become GC B cells, which are capable of receiving positive selection signals to a similar extent as B cells from young adult mice. Consistent with this, ageing also does not impact the ability of B cells to undergo somatic hypermutation and acquire affinity-enhancing mutations. Together, this shows that there are no B cell-intrinsic defects in affinity maturation with age when the B cell receptor repertoire is constant.
Assessing Genetic Diversity in Critically EndangeredChieniodendron hainanensePopulations within Fragmented Habitats in Hainan
Authors: Zhang Li , Zhang Hai-Li , Chen Yukai , Nizamani Mir Muhammad , Wu Tingtian , Liu Tingting , Zhou Qin 
Published: April 2023

AbstractHabitat fragmentation engenders a reduction in the geographic distribution of species, thereby rendering diminutive populations susceptible to extinction due to environmental, demographic, and genetic factors.Chieniodendron hainanense(henceforthC. hainanense) exemplifies a wild plant with extremely small populations (WPESP) and faces endangerment, necessitating urgent national conservation efforts. Elucidating the genetic diversity ofC. hainanenseis crucial for uncovering underlying mechanisms and devising protective strategies. In the present study, 35 specimens from six distinct cohort groups were genotyped utilizing genotyping-by-sequencing (GBS) and single nucleotide polymorphism (SNP) methodologies. The results indicated thatC. hainanenseexhibits limited genetic diversity. Observed heterozygosity withinC. hainanensepopulations spanned from 10.79% to 14.55%, with an average value of 13.15%. The sixC. hainanensepopulations can be categorized into two distinct groups: (1) Diaoluoshan and Baishaling, and (2) Wuzhishan, Huishan, Bawangling, and Jianfengling. The degree of genetic differentiation amongC. hainanensepopulations is relatively weak. The observed loss of diversity can be attributed to the effects of natural selection.
The vascularised chamber device significantly enhances the survival of transplanted liver organoids
Authors: Shi Denis D. , Makris Evelyn , Gerrand Yi-Wen , Lo Pu-Han , Yeoh George C. , Morrison Wayne A. , Mitchell Geraldine M. , Yap Kiryu K. 
Published: April 2023

ABSTRACTOrganoid transplantation has a promising future in the treatment of liver disease, but a major limitation is the lack of guidance on the most appropriate method for transplantation that maximises organoid survival. Human induced pluripotent stem cell (hiPSC)-derived liver progenitor cell organoids were transplanted into four different transplantation sites in a mouse model of liver disease, using five organoid delivery methods. Organoids were transplanted into the vascularised chamber device established in the groin, or into the liver, spleen, and subcutaneous fat. For organoid transplantations into the liver, organoids were delivered either in Matrigel alone, or in Matrigel and a polyurethane scaffold. At 2 weeks post-transplantation, the vascularised chamber had the highest organoid survival, which was 5.1x higher than the site with second highest survival (p=0.0002), being the intra-hepatic scaffold approach. No organoid survival was observed when delivered into the liver without a scaffold, or when injected into the spleen. Very low survival occurred in transplantations into subcutaneous fat. Animals with the vascularised chamber also had the highest levels of human albumin (0.33 ± 0.09 ng/mL). This study provides strong evidence supporting the use of the vascularised chamber for future liver organoid transplantation studies, including its translation into clinical therapy.
ORFeus: A Computational Method to Detect Programmed Ribosomal Frameshifts and Other Non-Canonical Translation Events
Authors: Richardson Mary O. , Eddy Sean R. 
Published: April 2023

AbstractBackgroundCanonical protein translation requires that ribosomes initiate translation at the correct start codon, maintain a single reading frame throughout elongation, and terminate at the first in-frame stop codon. However, ribosomal behavior can deviate at each of these steps, sometimes in a programmed manner. Certain mRNAs contain sequence and structural elements that cause ribosomes to begin translation at non-canonical start codons, shift reading frame, read through stop codons, or reinitiate on the same mRNA. These processes represent important translational control mechanisms that can allow an mRNA to encode multiple functional protein products or regulate protein expression. The prevalence of these events remains uncertain, due to the difficulty of systematic detection.ResultsWe have developed a computational model to infer non-canonical translation events from ribosome profiling data.ConclusionORFeus identifies known examples of alternative open reading frames and recoding events across different organisms and enables transcriptome-wide searches for novel events.
A unique cell division protein critical for the assembly of the bacterial divisome
Authors: Chu Xiao , Wang Lidong , Zhu Yiheng , Feng Zhengshan , Guan Qingtian , Song Lei , Luo Zhaoqing 
Published: April 2023

AbstractIdentification of unique essential bacterial genes is important for not only the understanding of their cell biology but also the development of new antimicrobials. Here we report a previously unrecognized core component of theAcinetobacter baumanniidivisome. Our results reveal that the protein, termed Aeg1 interacts with multiple cell division proteins, including FtsN, which is required for components of the divisome to localize to the midcell. We demonstrate that the FtsAE202Kand FtsBE65Amutants effectively bypassed the need of Aeg1 byA.baumannii, as did the activation variants FtsWM254Iand FtsWS274G. Our results suggest that Aeg1 is a cell division protein that arrives at the division site to initiate cell division by recruiting FtsN, which activates FtsQLB and FtsA to induce the septal peptidoglycan synthase FtsWI. The discovery of the new essential cell division protein has provided a new target for the development of antibacterial agents.
Building subtraction operators and controllers via molecular sequestration
Authors: Samaniego Christian Cuba , Qian Yili , Carleton Katelyn , Franco Elisa 
Published: April 2023

AbstractWe show how subtraction can be performed via a simple chemical reaction network that includes molecular sequestration. The network computes the difference between the production rate parameters of the two mutually sequestering species. We benefit from introducing a simple change of variables, that facilitates the derivation of an approximate solution for the differential equations modeling the chemical reaction network, under a time scale separation assumption that is valid when the sequestration rate parameter is sufficiently fast. Our main result is that we provide simple expressions confirming that temporal subtraction occurs when the inputs are constant or time varying. Through simulations, we discuss two sequestration-based architectures for feedback control in light of the subtraction operations they perform.
Tension sensing by FAK governs nuclear mechanotransduction, endothelial transcriptome and fate
Authors: Akhter Md Zahid , Yazbeck Pascal , Tauseef Mohammad , Anwar Mumtaz , Hossen Faruk , Datta Sayanti , Vellingiri Vigneshwaran , Joshi Jagdish Chandra , Srivastava Nityanand , Lenzini Stephen , Zhou Guangjin , Lee James , Jain Mukesh K , Shin Jae-Won , Mehta Dolly 
Published: April 2023

AbstractVascular endothelium forms a restrictive barrier to defend the underlying tissue against uncontrolled influx of circulating protein and immune cells. Mechanisms that mediate the transition from restrictive to leaky endothelium, a hallmark of tissue injury exemplified by acute lung injury (ALI), remain elusive. Using endothelial cell(EC)-Fak-/-mice, we show that FAK sensing and transmission of mechanical tension to the EC nucleus governs cell fate. In FAK- deleted EC, increased EC tension induced by Rho kinase caused tyrosine phosphorylation of nuclear envelope protein, emerin at Y74/Y95, and its localization in a nuclear cap. Activated emerin stimulated DNMT3a activity and methylation of theKLF2promoter, impairing the restrictive EC transcriptome, includingS1PR1. Inhibiting emerin phosphorylation or DNMT3a activity enabled KLF2 transcription ofS1PR1, rescuing the restrictive EC phenotype inEC-Fak-/-lungs. Thus, FAK sensing of tension transmission to the nucleus is crucial for maintaining a restrictive EC fate and lung homeostasis.