bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison Between Physicians' and Nurse Practitioners' Resource Utilization in the Diagnosis and Management of Bronchiolitis in the Pediatric Emergency Department
Authors: Bouchibti Salma , Maul Timothy , Rivera-Sepulveda Andrea 
Published: December 2021

Objective
This study aimed to describe the resource utilization of nurse practitioners (NPs) in the pediatric emergency department (ED) and compare among physicians.

Methods
A retrospective cross-sectional study of secondary data analysis in a level 1 academic pediatric trauma center was conducted. Patients were aged 1 to 24 months, evaluated in the ED between January 1, 2014, and November 30, 2018, with a diagnosis of bronchiolitis or wheezing. Data included age group, length of stay, disposition, diagnostic tests (chest radiography [CXR], viral testing, respiratory syncytial virus test), treatment (bronchodilator, corticosteroid, antibiotic), and medical provider (physician, NP, combination of both). Resources were evaluated before (early era) and after (late era) the implementation of an institutional clinical practice guideline.
Comparisons between groups were done through χ2, Fisher exact, or Kruskal-Wallis test, as appropriate.

Results
A total of 5311 cases were treated by a physician (65.3%), an NP (30.3%), or a combination of both (4.3%). The was a difference in the use of CXR, respiratory syncytial virus testing, bronchodilators, and corticosteroids among providers (P = 0.001). In the late era, NPs were less likely to order a bronchodilator (odds ratio [OR], 0.390 [95% confidence interval, 0.318–0.478; P < 0.001]), whereas physicians were less likely to order a CXR (OR, 0.772 [0.667–0.894, P = 0.001]), bronchodilator (OR, 0.518 [0.449–0.596, P < 0.001]), or a corticosteroid (OR, 0.630 [0.531–0.749, P < 0.001]).

Conclusions
Nurse practitioners made fewer diagnostic and therapeutic orders. A clinical practice guideline on the diagnosis and management of children with bronchiolitis successfully decreased the use of nonrecommended tests and therapies among NP and physicians.
Towards equitable diagnoses for autism and attention-deficit/hyperactivity disorder across sexes and genders
Authors: Lai Meng-Chuan , Lin Hsiang-Yuan , Ameis Stephanie H. 
Published: December 2021

Purpose of review
Sex/gender-related factors contribute to contextual issues influencing the recognition of autism and attention-deficit/hyperactivity disorder (ADHD), and modulate how neurodevelopmental characteristics are manifested. This review summarizes the empirical literature to provide directions for improving clinical diagnostic practices.

Recent findings
Timing of autism and/or ADHD diagnosis, particularly in girls/women, is related to the individual's developmental characteristics and co-occurring diagnoses, and expectancy, alongside gender stereotype biases, of referral sources and clinicians. This is further compounded by sex and gender modulations of behavioural presentations. The emerging ’female autism phenotype’ concept may serve as a helpful illustration of nuanced autism phenotypes, but should not be viewed as essential features of autism in a particular sex or gender. These nuanced phenotypes that can present across sexes and genders include heightened attention to socially salient stimuli, friendship and social groups, richness in language expression, and more reciprocal behaviours. The nuanced female-predominant ADHD phenotypes are characterized by subtle expressions in hyperactivity-impulsivity (e.g., hyper-verbal behaviours). Optimizing neurodevelopmental diagnoses across sexes and genders also requires an understanding of sex-related and gender-related variations in developmental trajectories, including compensation/masking efforts, and the influences of co-occurring conditions on clinical presentations.

Summary
Equitable diagnoses across sexes and genders for autism and ADHD require understanding of the nuanced presentations and the Gestalt clinical-developmental profiles, and addressing contextual biases that influence diagnostic practices.
Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein
Authors: Boer Elke de , Ockeloen Charlotte W. , Kampen Rosalie A. , Hampstead Juliet E. , Dingemans Alexander J.M. , Rots Dmitrijs , Lütje Lukas , Ashraf Tazeen , Baker Rachel , Barat-Houari Mouna , Angle Brad , Chatron Nicolas ,   The DDD study, Denommé-Pichon Anne-Sophie , Devinsky Orrin , Dubourg Christèle , Elmslie Frances , Elloumi Houda Zghal , Faivre Laurence , Fitzgerald-Butt Sarah , Geneviève David , Goos Jacqueline A.C. , Helm Benjamin M. , van de Kamp Jiddeke M. , Kini Usha , Lasa-Aranzasti Amaia , Lesca Gaetan , Lynch Sally A. , Mathijssen Irene M.J. , McGowan Ruth , Monaghan Kristin G. , Odent Sylvie , Pfundt Rolph , Putoux Audrey , van Reeuwijk Jeroen , Santen Gijs W.E. , Sasaki Erina , Sivanathan Jesitha , Sorlin Arthur , van der Spek Peter J. , Stegmann Alexander P.A. , Swagemakers Sigrid M.A. , Valenzuela Irene , Viora-Dupont Eléonore , Vitobello Antonio , Ware Stephanie M. , Wéber Mathys , Gilissen Christian , Low Karen J. , Fisher Simon E. , Vissers Lisenka E.L.M. , Wong Maggie M.K. , Kleefstra Tjitske 
Published: December 2021

AbstractPurposeAlthough haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized the clinical, molecular and functional spectra of ANKRD11 missense variants.MethodsWe collected clinical information of individuals with ANKRD11 missense variants and evaluated phenotypic fit to KBG syndrome. We assessed pathogenicity of variants by in silico analyses and cell-based experiments.ResultsWe identified 29 individuals with (mostly de novo) ANKRD11 missense variants, who presented with syndromic neurodevelopmental disorders and were phenotypically similar to individuals with KBG syndrome caused by ANKRD11 protein truncating variants or 16q24.3 microdeletions. Missense variants significantly clustered in Repression Domain 2. Cellularly, most variants caused reduced ANKRD11 stability. One variant resulted in decreased proteasome degradation and loss of ANKRD11 transcriptional activity.ConclusionOur study indicates that pathogenic heterozygous missense variants in ANKRD11 cause the clinically recognizable KBG syndrome. Disrupted transrepression capacity and reduced protein stability each independently lead to ANKRD11 loss-of-function, consistent with haploinsufficiency. This highlights the diagnostic relevance of ANKRD11 missense variants, but also poses diagnostic challenges, as the KBG-associated phenotype may be mild and inherited pathogenic ANKRD11 (missense) variants are increasingly observed, warranting stringent variant classification and careful phenotyping.
Paralog editing tunes rice stomatal density to maintain photosynthesis and improve drought tolerance
Authors: Karavolias Nicholas G. , Patel-Tupper Dhruv , Seong Kyungyong , Tjahjadi Michelle , Gueorguieva Gloria-Alexandra , Tanaka Jaclyn , Cruz Ana Gallegos , Liebermann Samantha , Litvak Lillian , Dahlbeck Douglas , Cho Myeong-Je , Niyogi Krishna K. , Staskawicz Brian J. 
Published: December 2021

AbstractRice (Oryza sativa) is of paramount importance for global nutrition, supplying at least 20% of global calories. However, water scarcity and increased drought severity are anticipated to reduce rice yields globally. Rice stomatal developmental genetics were explored as a mechanism to improve drought resilience while maintaining yield under climate stress. CRISPR/Cas9-mediated knockouts of EPFL10 and STOMAGEN yielded lines with c. 80% and 25% of wild-type stomatal density, respectively.epfl10lines with moderate reductions in stomatal densities are able to conserve water to similar extents asstomagenlines, but do not suffer from the concomitant reductions in stomatal conductance, carbon assimilation, or thermoregulation observed instomagenknockouts. Moderate reductions in stomatal densities achieved by editing EPFL10 may be a climate-adaptive approach in rice that can safeguard yield. Editing the paralog of STOMAGEN in other species may provide a means to tune stomatal density in agriculturally important crops beyond rice.
Hydrogen properties and charges in a sub-1.2 Å resolution cryo-EM structure revealed by a cold field emission beam
Authors: Maki-Yonekura Saori , Kawakami Keisuke , Hamaguchi Tasuku , Takaba Kiyofumi , Yonekura Koji 
Published: December 2021

AbstractThe cold field emission (CFE) beam produces the less-attenuated contrast transfer function of electron microscopy, thereby enhancing high-resolution signals and this particularly benefits higher-resolution single particle cryogenic electron microscopy. Here, we present a sub-1.2 Å resolution structure of a standard protein sample, apoferritin. Image data were collected with the CFE beam in a high-throughput scheme while minimizing beam tilt deviations from the coma-free axis. A difference map reveals positive densities for most hydrogen atoms in the core region of the protein complex including those in water molecules, while negative densities around acidic amino-acid side chains likely represent negative charges. The position of the hydrogen densities depends on parent bonded-atom type, which is validated by an estimated level of coordinate errors.
Epi-MEIF, a flexible and efficient method for detection of high order epistatic interactions from complex phenotypic traits
Authors: Saha Saswati , Perrin Laurent , Röder Laurence , Brun Christine , Spinelli Lionel 
Published: December 2021

ABSTRACTUnderstanding the relationship between genetic variations and variations in complex and quantitative phenotypes remains an ongoing challenge. While Genome-wide association studies (GWAS) have become a vital tool for identifying single-locus associations, we lack methods for identifying epistatic interactions. In this article, we propose a novel method for high-order epistasis detection using mixed effect conditional inference forest (epiMEIF). The epiMEIF model is fitted on a group of potential causal SNPs and the tree structure in the forest facilitates the identification of n-way interactions between the SNPs. Additional testing strategies further improve the robustness of the method. We demonstrate its ability to detect true n-way interactions via extensive simulations in both cross-sectional and longitudinal synthetic datasets. This is further illustrated in an application to reveal epistatic interactions from natural variations of cardiac traits in flies (Drosophila). Overall, the method provides a generalized way to identify high order interactions from any GWAS data, thereby greatly improving the detection of the genetic architecture of complex phenotypes.
Visual, delay and oculomotor timing and tuning in macaque dorsal pulvinar during instructed and free choice memory saccades
Authors: Schneider Lukas , Dominguez-Vargas Adan-Ulises , Gibson Lydia , Wilke Melanie , Kagan Igor 
Published: December 2021

AbstractCausal perturbations suggest that the primate dorsal pulvinar (dPul) plays a crucial role in target selection and saccade planning, but its basic visuomotor neuronal properties are unclear. While some functional aspects of dPul and interconnected frontoparietal areas – e.g. ipsilesional choice bias after inactivation – are similar, it is unknown if dPul shares oculomotor properties of the cortical circuitry, in particular the delay and choice-related activity. We investigated such properties in macaque dPul during instructed and free-choice memory saccades. Most recorded units showed visual (16%), visuomotor (29%) or motor-related (35%) responses. Visual responses were mainly contralateral; motor-related responses were predominantly post-saccadic (64%) and showed weak contralateral bias. Pre-saccadic enhancement was infrequent (9-15%) – instead, activity was often suppressed during saccade planning (30%) and execution (19%). Surprisingly, only few units exhibited classical visuomotor patterns combining cue and continuous delay activity until the saccade or pre-saccadic ramping, and most spatially-selective neurons did not encode the upcoming decision during free-choice delay. Thus, in absence of a visible goal, the dorsal pulvinar has a limited role in prospective saccade planning, with patterns partially complementing its frontoparietal partners. Conversely, prevalent cue and post-saccadic responses imply the participation in integrating spatial goals with processing across saccades.
Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells
Authors: Sokal Aurélien , Broketa Matteo , Meola Annalisa , Barba-Spaeth Giovanna , Fernández Ignacio , Fourati Slim , Azzaoui Imane , de La Selle Andrea , Vandenberghe Alexis , Roeser Anais , Bouvier-Alias Magali , Crickx Etienne , Languille Laetitia , Michel Marc , Godeau Bertrand , Gallien Sébastien , Melica Giovanna , Nguyen Yann , Zarrouk Virginie , Canoui-Poitrine Florence , Noizat-Pirenne France , Megret Jérôme , Pawlotsky Jean-Michel , Fillatreau Simon , Simon-Lorière Etienne , Weill Jean-Claude , Reynaud Claude-Agnès , Rey Félix A. , Bruhns Pierre , Chappert Pascal , Mahévas Matthieu 
Published: December 2021

SummaryMemory B cells (MBCs) represent a second layer of immune protection against SARS-CoV-2. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant is of major concern. We used bio-layer interferometry to assess the affinity against the receptor-binding-domain (RBD) of Omicron spike of 313 naturally expressed monoclonal IgG that were previously tested for affinity and neutralization against VOC prior to Omicron. We report here that Omicron evades recognition from a larger fraction of these antibodies than any of the previous VOCs. Additionally, whereas 30% of these antibodies retained high affinity against Omicron-RBD, our analysis suggest that Omicron specifically evades antibodies displaying potent neutralizing activity against the D614G and Beta variant viruses. Further studies are warranted to understand the consequences of a lower memory B cell potency on the overall protection associated with current vaccines.
Antagonism of Saxitoxin and Tetrodotoxin Block by Internal Monovalent Cations in Squid Axon
Authors: Oxford Gerry S. , Forscher Paul , Wagoner P. Kay , Adams David J. 
Published: December 2021

ABSTRACTThe block of voltage-dependent sodium channels by saxitoxin (STX) and tetrodotoxin (TTX) was investigated in voltage-clamped squid giant axons internally perfused with a variety of permeant monovalent cations. Substitution of internal Na+by either NH4+or N2H5+resulted in a reduction of outward current through sodium channels under control conditions. In contrast, anomalous increases in both inward and outward currents were seen for the same ions if some of the channels were blocked by STX or TTX, suggesting a relief of block by these internal cations. External NH4+was without effect on the apparent magnitude of toxin block. Likewise, internal inorganic monovalent cations were without effect, suggesting that proton donation by NH4+might be involved in reducing toxin block. Consistent with this hypothesis, decreases in internal pH mimicked internal perfusion with NH4+in reducing toxin block. The interaction between internally applied protons and externally applied toxin molecules appears to be competitive, as transient increases in sodium channel current were observed during step increases in intracellular pH in the presence of a fixed STX concentration. In addition to these effects on toxin block, low internal pH produced a voltage-dependent block of sodium channels and enhanced steady-state inactivation. Elevation of external buffer capacity only marginally diminished the modulation of STX block by internal NH4+, suggesting that alkalinization of the periaxonal space and a resultant decrease in the cationic STX concentration during NH4+perfusion may play only a minor role in the effect. These observations indicate that internal monovalent cations can exert trans-channel influences on external toxin binding sites on sodium channels.
The origins of placental mesenchymal stromal cells: Full spectrum flow cytometry reveals mesenchymal heterogeneity in first trimester placentae, and phenotypic convergence in culture
Authors: Boss A.L. , Damani T. , Chamley L.W. , James J.L. , Brooks A.E.S. 
Published: December 2021

AbstractSingle-cell technologies (RNA-sequencing, flow cytometry) are critical tools to reveal how cell heterogeneity impacts developmental pathways. The placenta is a fetal exchange organ, containing a heterogeneous mix of mesenchymal cells (fibroblasts, myofibroblasts, perivascular, and progenitor cells). Placental mesenchymal stromal cells (pMSC) are also routinely isolated, for therapeutic and research purposes. However, our understanding of the diverse phenotypes of placental mesenchymal lineages, and their relationships remain unclear. We designed a 23-colour flow cytometry panel to assess mesenchymal heterogeneity in first-trimester human placentae.. Four distinct mesenchymal subsets were identified; CD73+CD90+mesenchymal cells, CD146+CD271+perivascular cells, podoplanin+CD36+stromal cells, and CD26+CD90+myofibroblasts. CD73+CD90+and podoplanin+CD36+ cells expressed markers consistent with cultured pMSCs, and were explored further. Despite their distinct ex-vivo phenotype, in culture CD73+CD90+cells and podoplanin+CD36+cells underwent phenotypic convergence, losing CD271 or CD36 expression respectively, and homogenously exhibiting a basic MSC phenotype (CD73+CD90+CD31-CD144-CD45-). However, some markers (CD26, CD146) were not impacted, or differentially impacted by culture in different populations. Comparisons of cultured phenotypes to pMSCs further suggested cultured pMSCs originate from podoplanin+CD36+cells. This highlights the importance of detailed cell phenotyping to optimise therapeutic capacity, and ensure use of relevant cells in functional assays.
Accumulation of TERT in Mitochondria Shows Two Opposing Effects on Apoptosis
Authors: Ebata Hiroshi , Shima Tomohiro , Iizuka Ryo , Uemura Sotaro 
Published: December 2021

ABSTRACTTelomerase reverse transcriptase (TERT) is a protein that catalyzes the reverse transcription of telomere elongation. TERT is also expected to play a noncanonical role beyond telomere lengthening since it localizes not only in the nucleus but also in mitochondria, where telomeres do not exist. Several studies have reported that mitochondrial TERT regulates apoptosis induced by oxidative stress. However, there remains controversy about whether mitochondrial TERT promotes or inhibits apoptosis, mainly due to the lack of information on changes in the TERT distribution in individual cells over time. Here we simultaneously detected apoptosis and TERT localization after oxidative stress in individual HeLa cells by live-cell tracking. This tracking revealed that the stress-induced accumulation of TERT in mitochondria caused apoptosis but that the accumulation positively correlated with the time until cell death. The results suggest a new model in which mitochondrial TERT has two opposing effects at different stages of apoptosis: it predetermines apoptosis at the first stage of cell-fate determination but also delays apoptosis at the second stage. Because these distinct effects respectively support both sides of the controversy regarding the role of mitochondrial TERT in apoptosis, our model integrates two opposing hypotheses. Furthermore, detailed statistical analysis of TERT mutations, which have been predicted to inhibit TERT transport to mitochondria, revealed that these mutations suppress apoptosis independent of the mitochondrial localization of TERT. Together, these results indicate that the non-canonical functions of TERT affect a wide range of pathways.
Construction of a potent pan-vaccine based on the evolutionary tendency of SARS-CoV-2 spike protein
Authors: Zhao Yongliang , Ni Wenjia , Liang Simeng , Dong Lianghui , Xiang Min , Cai Zeng , Niu Danping , Zhang Qiuhan , Wang Dehe , Zheng Yucheng , Zhang Zhen , Zhou Dan , Guo Wenhua , Pan Yongbing , Wu Xiaoli , Yang Yimin , Jing Zhaofei , Jiang Yongzhong ,   SARS-CoV-2 Vaccine Task Force Group, Chen Yu , Yan Huan , Zhou Yu , Xu Ke , Lan Ke 
Published: December 2021

AbstractSARS-CoV-2 continued to spread globally along with different variants. Here, we systemically analyzed viral infectivity and immune-resistance of SARS-CoV-2 variants to explore the underlying rationale of viral mutagenesis. We found that the Beta variant harbors both high infectivity and strong immune resistance, while the Delta variant is the most infectious with only a mild immune-escape ability. Remarkably, the Omicron variant is even more immune-resistant than the Beta variant, but its infectivity increases only in Vero E6 cells implying a probable preference for the endocytic pathway. A comprehensive analysis revealed that SARS-CoV-2 spike protein evolved into distinct evolutionary paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance, resulting in a narrow spectrum of the current single-strain vaccine. In light of these findings and the phylogenetic analysis of 2674 SARS-CoV-2 S-protein sequences, we generated a consensus antigen (S6) taking the most frequent mutations as a pan-vaccine against heterogeneous variants. As compared to the ancestry SWT vaccine with significantly declined neutralizations to emerging variants, the S6 vaccine elicits broadly neutralizing antibodies and full protections to a wide range of variants. Our work highlights the importance and feasibility of a universal vaccine strategy to fight against antigen drift of SARS-CoV-2.
Scars of hope and forewarn of a bleak future: Post-mortem findings of dugongs (Dugong dugon) belonging to a relict population in the Gulf of Kachchh, India
Authors: Pathan Sameeha , Pande Anant , Johnson J.A. , Sivakumar Kuppusamy 
Published: December 2021

AbstractA relict dugong population resides in the Gulf of Kachchh in Gujarat state of India. Very little is known on this population stemming from lack of focused studies and inadequate examinations of previous strandings. In this study, crucial ecological information is gathered through a systematic necropsy on stranded dugongs in the gulf. As indicated through dorsal tusk-rake scars on both the carcasses, this study presents first records of derivative physical evidence to the presence of a socially interacting population. Progressive healing and differences in width of the scars indicated more than two individuals had participated in a sexual agnostic or courtship event. Conversely, our findings report that both the animals suffered relative effects of asphyxiation after fishing net entanglement. An implication of a prior pathological condition(s) in the form of dermal cysts, swollen mesenteric lymph nodes, and endoparasites are also reported. Stomach content was examined for a qualitative dietary characterization. Other potential threats along with fishing net microfilaments found in the stomach contents of both dugongs are discussed in brief.