bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model-based hypothesis framework to define and estimate the diel niche via the ‘Diel.Niche’ R package
Authors: Gerber Brian D. , Devarajan Kadambari , Farris Zach J. , Fidino Mason 
Published: June 2023

AbstractHow animals use the diel period (24-hour light-dark cycle) is of fundamental importance to understand their niche. While ecological and evolutionary literature abound with discussion of diel phenotypes (e.g., diurnal, nocturnal, crepuscular, cathemeral), they lack clear and explicit quantitative definitions. As such, inference can be confounded when evaluating hypotheses of animal diel niche switching or plasticity across studies because researchers may be operating under different definitions of diel phenotypes.We propose quantitative definitions of diel phenotypes using four alternative hypotheses sets (Maximizing, Traditional, General, and Selection) aimed at achieving different objectives. Each hypothesis set is composed of mutually exclusive hypotheses defined based on the activity probabilities in the three fundamental periods of light availability (twilight, daytime, and nighttime).We develop a Bayesian modeling framework that compares diel phenotype hypotheses using Bayes factors and estimates model parameters using a multinomial model with linear inequality constraints. Model comparison, parameter estimation, and visualizing results can be done in the Diel.Niche R package. A simplified R Shiny web application is also available.We provide extensive simulation results to guide researchers on the power to discriminate among hypotheses for a range of sample sizes (10 to 1280). We also work through several examples of using data to make inferences on diel activity, and include online vignettes on how to use the Diel.Niche package. We demonstrate how our modeling framework complements analyses that are commonly used to investigate diel activity, such as circular kernel density estimators.Our aim is to encourage standardization of the language of diel activity and bridge conceptual frameworks and hypotheses in diel research with data and models. Lastly, we hope more research focuses on the ecological and conservation importance of understanding how animals use diel time.
Quantitative analysis of chest computed tomography of COVID-19 pneumonia using a software widely used in Japan
Authors: Suzuki Minako , Fujii Yoshimi , Nishimura Yurie , Yasui Kazuma , Fujisawa Hidefumi 
Published: June 2023

AbstractThis study aimed to determine the optimal conditions to measure the percentage of area considered as pneumonia (pneumonia volume ratio, PVR) and the computed tomography (CT) score due to coronavirus disease 2019 (COVID-19) using the Ziostation2 image analysis software (Z2; Ziosoft, Tokyo, Japan), which is popular in Japan, and to evaluate its usefulness in assessing the clinical severity. We included 53 patients (41 men and 12 women, mean age: 61.3 years) diagnosed with COVID-19 using the polymerase chain reaction who had undergone chest CT and were hospitalized between January 2020 and January 2021. Based on the COVID-19 infection severity, the patients were classified as mild (n=38) or severe (n=15). For 10 randomly selected samples, the PVR and CT scores by Z2 under different conditions and the visual simple PVR and CT scores were compared, and the conditions with the highest statistical agreement were determined. The usefulness of the clinical severity assessment based on PVR and CT scores using Z2 under the determined conditions was statistically evaluated. The best agreement with the visual measurement was achieved by the Z2 measurement condition of ≥ –600 HU. The areas under the receiver operating characteristic curves, the Youden index, and the sensitivity, specificity, and p-values of PVR and CT scores by Z2 were as follows: PVR; 0.881, 18.69, 66.7, 94.7, and <0.001, CT score; 0.77, 7.5, 40, 74, and 0.002, respectively. We determined the optimal condition for assessing the PVR of COVID-19 pneumonia using Z2 and demonstrated that the AUC of PVR was higher than that of the CT score in the assessment of clinical severity. The introduction of new technologies is time-consuming and expensive; our method has high clinical utility and can be promptly used in any facility where Z2 has been introduced.
The influence of the way of regression on the results obtained by the receptorial responsiveness method (RRM), a procedure to estimate a change in the concentration of a pharmacological agonist near the receptor
Authors: Ovari Ignac , Viczjan Gabor , Erdei Tamas , Takacs Barbara , Szekeres Reka , Lampe Nora , Zsuga Judit , Szucs Miklos , Szilvassy Zoltan , Juhasz Bela , Gesztelyi Rudolf 
Published: June 2023

AbstractThe receptorial responsiveness method (RRM) enables the estimation of a change in the concentration of a degradable agonist, near its receptor, by fitting its model to (at least) two concentration-effect (E/c) curves of a stable agonist of this receptor. One curve should be generated before this change in concentration, while the other one after this change, in the same (or in identical) biological system(s). It follows that RRM yields a surrogate parameter (“cx”), the concentration of the stable agonist that is equieffective with the change in the concentration of the degradable agonist. However, the curve fitting can be implemented several ways, which can affect accuracy, precision and convenience of use.This study utilized data of previousex vivoinvestigations. Known concentrations of stable agonists were estimated with RRM by performing individual (local) or global fitting (with one or two model(s)), combined with the use of a logarithmic (logcx) or non-logarithmic parameter (cx), and with ordinary least-squares or robust regression.We found that the individual regression, the most complicated option, was the most accurate, followed closely by the moderately complicated two-model global regression and then by the easy-to-perform one-model global regression. The two-model global fitting was the most precise, followed by the individual fitting (closely) and by the one-model global fitting (from afar). The use of cxand robust regression did not, whereas pairwise fitting (i.e. fitting only two E/c curves at once) did improve the quality of estimation. Thus, the two-model global fitting, performed pairwise, is recommended for RRM, but the individual fitting is a good alternative.
The European Reality Regarding ICU Follow–Up Clinics: A Systematic Review
Authors: Charalampopoulos Marios , Triantafyllaki Panagiota , Sampani Christina-Athanasia , Triantafyllou Christos , Papageorgiou Dimitrios 
Published: June 2023

AbstractIntroductionThe ICU Follow up Clinics support and treat adult patients in the community in order to cover the needs that occur after their discharge from the ICU at the hospital.AimTo study the effectiveness and the way of the ICU Follow up Clinic operation management for adult patients after their discharge from the hospital.MethodsA search was performed on the Greek and international literature, as well as at the online Databases PubMed, Cochrane, EMBASE and Google Scholar. Exclusion and integration criteria were set for the studies found, and a flow chart was created for the studies included.ResultsThrough the search, 30 articles were found matching the subject under study, and after further evaluation, seven articles were included. The majority of the articles highlight the importance of these services at the patients’ follow-up after discharge. More specifically, through these services, the mortality rate, the risk of recurrence, and the readmission risk are decreased as well as the patient’s mental health is improved.ConclusionsThe main aim of these Services is the follow-up of the adult patients after discharge, the consultation, and the application of therapeutic protocols in order to face the primary pathological cause, as well as matters that occurred as a result of the hospitalization. At the same time, they can help to detect the needs of the patients that occurred after the discharge so that finally, improve the care given and the patient’s outcome.
HPC-based genome variant calling workflow (HPC-GVCW)
Authors: Zhou Yong , Kathiresan Nagarajan , Yu Zhichao , Rivera Luis F. , Thimma Manjula , Manickam Keerthana , Chebotarov Dmytro , Mauleon Ramil , Chougule Kapeel , Wei Sharon , Gao Tingting , Green Carl D. , Zuccolo Andrea , Ware Doreen , Zhang Jianwei , McNally Kenneth L. , Wing Rod A. 
Published: June 2023

AbstractA high-performance computing genome variant calling workflow was designed to run GATK on HPC platforms. This workflow efficiently called an average of 27.3 M, 32.6 M, 168.9 M, and 16.2 M SNPs for rice, sorghum, maize, and soybean, respectively, on the most recently released high-quality reference sequences. Analysis of a rice pan-genome reference panel revealed 2.1 M novel SNPs that have yet to be publicly released.
PepFlow: direct conformational sampling from peptide energy landscapes through hypernetwork-conditioned diffusion
Authors: Abdin Osama , Kim Philip M. 
Published: June 2023

AbstractDeep learning approaches have spurred substantial advances in the single-state prediction of biomolecular structures. The function of biomolecules is, however, dependent on the range of conformations they can assume. This is especially true for peptides, a highly flexible class of molecules that are involved in numerous biological processes and are of high interest as therapeutics. Here, we introduce PepFlow, a generalized Boltzmann generator that enables direct all-atom sampling from the allowable conformational space of input peptides. We train the model in a diffusion framework and subsequently use an equivalent flow to perform conformational sampling. To overcome the prohibitive cost of generalized all-atom modelling, we modularize the generation process and integrate a hyper-network to predict sequence-specific network parameters. PepFlow accurately predicts peptide structures and effectively recapitulates experimental peptide ensembles at a fraction of the running time of traditional approaches. PepFlow can additionally be used to sample conformations that satisfy constraints such as macrocyclization.
Isolation of stage-specific spermatogenic cells by dynamic histone incorporation and removal in spermatogenesis
Authors: Fujiwara Yasuhiro , Hada Masashi , Fukuda Yuko , Koga Chizuko , Inoue Erina , Okada Yuki 
Published: June 2023

AbstractDue to the lack of anin vitrospermatogenesis system, studies on mammalian spermatogenesis require the isolation of specific germ cell populations for further analyses. BSA gradient and elutriation have been used for several decades to purify testicular germ cells; more recently, fluorescence-activated cell sorting (FACS) has become popular. Although each method has its advantages and disadvantages and is used depending on the purpose of the experiment, reliance on FACS is expected to be more prevalent because fewer cells can be managed. However, the currently used FACS method for testicular germ cells relies on karyotypic differences via DNA staining. Thus, it remains challenging to separate post-meiotic haploid cells (spermatids) according to their differentiation stage despite significant variations in morphology and chromatin state. In this study, we developed a method for finely separating testicular germ cells using VC mice carrying fluorescently tagged histones. This method enables the separation of spermatogonia, spermatocytes, and spermatids based on the intensity of histone fluorescence and cell size. Combined with a DNA staining dye, this method separates spermatids after elongation according to each spermiogenic stage. Although the necessity for a specific transgenic mouse line is less versatile, this method is expected to be helpful for the isolation of testicular germ cell populations because it is highly reproducible and independent of complex cell sorter settings and staining conditions.
Saliva as an alternative sample type for detection of pneumococcal carriage in young children
Authors: Wyllie Anne L. , Rots Nynke Y. , Wijmenga-Monsuur Alienke J. , van Houten Marlies A. , Sanders Elisabeth A.M. , Trzciński Krzysztof 
Published: June 2023

ABSTRACTIn children, the gold standard for the detection of pneumococcal carriage is conventional culture of a nasopharyngeal swab. Saliva, however, has a history as one of the most sensitive methods for surveillances on pneumococcal colonisation and has recently been shown to improve carriage detection in older age groups. Here, we compared the sensitivity of nasopharyngeal and saliva samples from PCV7-vaccinated 24-month-old children for pneumococcal carriage detection using conventional and molecular diagnostic methods.Nasopharyngeal and saliva samples were collected from 288 24-month-old children during the autumn/winter, 2012/2013. All samples were first processed by conventional diagnostic techniques. Next, DNA extracted from all plate growth was tested by qPCR for the presence of pneumococcal genespiaBandlytAand a subset of serotypes.By culture, 164/288 (57%) nasopharyngeal swabs tested positive for pneumococcus, but detection was not possible from saliva due to abundant polymicrobial growth on culture-plates. Molecular methods increased the number of children pneumococci-positive to 172/288 (60%) when testing culture-enriched saliva and to 212/288 (73%) when testing nasopharyngeal samples. Altogether, by molecular methods 239/288 (83%) infants were positive, with qPCR-based carriage detection of culture-enriched nasopharyngeal swabs significantly detecting more carriers compared to either conventional culture (p<0.001) or qPCR-detection of saliva (p<0.001). However, 27/240 (11%) carriers were positive only in saliva, significantly contributing to the overall number of carriers detected (p<0.01).While testing nasopharyngeal swabs with qPCR proved most sensitive for pneumococcal detection in infants, saliva sampling could be considered as complementary to provide additional information on carriage and serotypes which may not be detected in the nasopharynx and may be particularly useful in longitudinal studies, requiring repeated sampling events.
Complex Patient Perspectives on Evolving Diverticulitis Treatment
Authors: Altman-Merino Annie , Bonnet Kemberlee , Schlundt David , Wrenn Jessie , Self Wesley H. , Gordon Elisa J. , Hawkins Alexander T. 
Published: June 2023

AbstractBackgroundDespite evidence that antibiotics may not be necessary to treat acute uncomplicated diverticulitis, they remain the mainstay of treatment in the United States. A randomized controlled trial evaluating antibiotic effectiveness could accelerate implementation of an antibiotic-free treatment strategy, but patients may be unwilling to participate.ObjectiveThis study aims to assess patients’ attitudes regarding participation in a randomized trial of antibiotics versus placebo for acute diverticulitis, including willingness to participate.DesignThis is a mixed-methods study with qualitative and descriptive methods.SettingsInterviews were conducted in a quaternary care emergency department and surveys were administered virtually through a web-based portal.PatientsPatients with either current or previous acute uncomplicated diverticulitis participated.InterventionsPatients underwent semi-structured interviews or completed a web-based survey.Main Outcome measuresRates of willingness to participate in a randomized controlled trial was measured. Salient factors related to healthcare decision-making were also identified and analyzed.ResultsThirteen patients completed an interview. Reasons to participate included a desire to help others or contribute to scientific knowledge. Doubts about the efficacy of observation as a treatment method were the main barrier to participation. In a survey of 218 subjects, 62% of respondents reported willingness to participate in a randomized clinical trial. “What my doctor thinks,” followed by “What I’ve experienced in the past” were the most important decision-making factors.LimitationsThere is possible selection bias inherent to using a study to evaluate willingness to participate in a study. Also, the population sampled was disproportionately White compared to the population affected by diverticulitis.ConclusionsPatients with acute uncomplicated diverticulitis maintain complex and varying perceptions of the use of antibiotics. Most surveyed patients would be willing to participate in a trial of antibiotics versus placebo. Our findings support a trial’s feasibility and facilitate an informed approach to recruitment and consent.
DNA hypomethylation activates Cdk4/6 and ATR to cause dormant origin firing and cell cycle arrest that restricts liver outgrowth in zebrafish
Authors: Madakashira Bhavani P. , Magnani Elena , Ranjan Shashi , Sadler Kirsten C. 
Published: June 2023

AbstractCoordinating epigenomic inheritance and cell cycle progression is essential for organogenesis. UHRF1 connects these functions by facilitating maintenance of DNA methylation and cell cycle progression. Here, we provide evidence resolving the paradoxical phenotype ofuhrf1mutant zebrafish embryos that have both activation of pro-proliferative E2F target genes and increased number of hepatocytes in S-phase, but the liver fails to grow. We find that Atr inhibition reduces DNA replication and increases liver size inuhrf1mutants, suggesting thatuhrf1mutant hepatocytes have replication stress leading to Atr-mediated cell cycle inhibition and dormant origin firing. We uncover persistent Cdk4/6 activation as the mechanism drivinguhrf1mutant hepatocytes into S-phase, activating Atr and restricting hepatic outgrowth. Palbociclib treatment ofuhrf1mutant embryos prevented aberrant S-phase entry, and the DNA damage response. Palbociclib rescued most cellular and developmental phenotypes inuhrf1mutants, except DNA hypomethylation, transposon activation and the interferon response. Pro-proliferative genes were also activated in a Cdk4/6 dependent fashion in the liver ofdnmt1mutants, suggesting DNA hypomethylation as a mechanism of Cdk4/6 activation. Thus, the developmental defects caused by DNA hypomethylation are attributed to persistent Cdk4/6 activation leading to DNA replication stress, dormant origin firing and cell cycle inhibition, preventing hepatic outgrowth.
Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy
Authors: Sun Weiwei , Rassadkina Yelizaveta , Gao Ce , Collens Sarah Isabel , Lian Xiaodong , Solomon Isaac H. , Mukerji Shibani , Yu Xu G. , Lichterfeld Mathias 
Published: June 2023

AbstractHIV-1 reservoir cells that circulate in peripheral blood during suppressive antiretroviral therapy (ART) have been well characterized, but little is known about the dissemination of HIV-1-infected cells across multiple anatomical tissues, especially the central nervous system (CNS). Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia. Multi-compartment dissemination of clonal intact and defective proviral sequences occurred across multiple anatomical tissues, including the CNS, and evidence for the clonal proliferation of HIV-1-infected cells was found in the basal ganglia, in the frontal lobe, in the thalamus and in periventricular white matter. Deep analysis of HIV-1 reservoirs in distinct tissues will be informative for advancing HIV-1 cure strategies.
Thymidylate synthase disruption to limit cell proliferation in cell therapies
Authors: Sartori-Maldonado Rocio , Montaser Hossam , Soppa Inkeri , Eurola Solja , Balaz Melanie , Puttonen Henri , Otonkoski Timo , Saarimäki-Vire Jonna , Wartiovaara Kirmo 
Published: June 2023

AbstractEngineered cells hold great promise for regenerative medicine and gene therapy. However, living cell products entail a fundamental biological risk of unwanted growth. Here, we describe a novel metabolic safety system to control cell proliferation without added genetic elements. We inactivated a key enzyme for nucleotide metabolism,TYMS, in several cell lines, thus obtaining cells that proliferate only when supplemented with exogenous thymidine but fail to replicate in its absence. Under supplementation,TYMS-/-pluripotent stem cells proliferate normally, produce teratomas and differentiate into potentially therapeutic cell types such as pancreatic beta cells. After differentiation, the postmitotic cells do not require thymidine to function, as seen by prolongedin vivoproduction of human insulin in implanted mice. Hence, this method allows robust cell culture and manufacture while mitigating the risk of uncontrolled growth of transplanted cells.One Sentence Summary:Genetic disruption of DNA synthesis prevents unwanted proliferation in cell therapies without affecting cell function.
USP16 is an ISG15 cross-reactive deubiquitinase targeting a subset of metabolic pathway-related proteins
Authors: Gan Jin , Pinto-Fernández Adán , Flierman Dennis , Akkermans Jimmy J. L. L. , O’Brien Darragh P. , Greenwood Helene , Scott Hannah Claire , Neefjes Jacques , Fritz Günter , Knobeloch Klaus-Peter , van Dam Hans , Kessler Benedikt M. , Ovaa Huib , Geurink Paul P. , Sapmaz Aysegul 
Published: June 2023

ABSTRACTThe ubiquitin-like modifier ISG15 can modulate host and viral proteins to restrict viral and microbial infections, and act as a cytokine. Its expression and conjugation are strongly up-regulated by type I interferons. Here we identify the deubiquitinating enzyme USP16 as an ISG15 cross-reactive protease. Ubiquitin-specific protease 16 (USP16) was found to react with an ISG15 activity-based probe in pull-down experiments using chronic myeloid leukaemia-derived human cells (HAP1). Supporting this finding, recombinant USP16 cleaved pro-ISG15 and ISG15 iso-peptide linked model substratesin vitro, as well as ISGylated substrates present in cell lysates. Moreover, the interferon-induced stimulation of ISGylation in human HAP1 cells was increased by knockdown or knockout of USP16. Depletion of USP16 did not affect interferon signaling, and interferon treatment did not affect USP16 expression or enzymatic activity either. A USP16-dependent ISG15 interactome was established by anti-ISG15 immunoprecipitation mass spectrometry (IP-MS), which indicated that the deISGylating function of USP16 may regulate metabolic pathways involving GOT1, ALDOA, SOD1 and MDH1, all of which were further confirmed to be deISGylated by USP16 in HEK293T cells. Together, our results indicate that USP16 may contribute to regulating the ISGylation status of a subset of proteins related to metabolism during type I interferon responses.