bluuebunny/crossref_metadata_2025 huggingface dataset:
The Rapid Reduction of Infection-Related Visits and Antibiotic Use Among People With Cystic Fibrosis After Starting Elexacaftor-Tezacaftor-Ivacaftor
Authors: Miller Aaron C , Harris Logan M , Cavanaugh Joseph E , Abou Alaiwa Mahmoud , Stoltz David A , Hornick Douglas B , Polgreen Philip M
Published: February 2022

Background

People with cystic fibrosis (CF) routinely suffer from recurrent sinopulmonary infections. Such infections require frequent courses of antimicrobials and often involve multidrug-resistant organisms. The goal of this study was to identify real-world evidence for the effectiveness of elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) in decreasing infection-related visits and antimicrobial use in people with CF.

Methods

Using IBM MarketScan data, we identified 389 enrollees with CF who began taking ELX/TEZ/IVA before 1 December 2019 and were enrolled from 1 July 2019 to 14 March 2020. We also identified a comparison population who did not begin ELX/TEZ/IVA during the study period. We compared the following outcomes in the 15 weeks before and after medication initiation: total healthcare visits, inpatient visits, infection-related visits, and antimicrobial prescriptions. We analyzed outcomes using both a case-crossover analysis and a difference-in-differences analysis, to control for underlying trends.

Results

For the case-crossover analysis, ELX/TEZ/IVA initiation was associated with the following changes over a 15-week period: change in overall healthcare visit dates, −2.5 (95% confidence interval, −3.31 to −1.7); change in inpatient admissions, −0.16 (−.22 to −.10); change in infection-related visit dates, −0.62 (−.93 to −.31); and change in antibiotic prescriptions, −0.78 (−1.03 to −.54). Results from the difference-in-differences approach were similar.

Conclusions

We show a rapid reduction in infection-related visits and antimicrobial use among people with CF after starting a therapy that was not explicitly designed to treat infections. Currently, there are >30 000 people living with CF in the United States alone. Given that this therapy is effective for approximately 90% of people with CF, the impact on respiratory infections and antimicrobial use may be substantial.
Trauma-Informed Restorative Justice Practices in Schools: An Opportunity for School Social Workers
Authors: Sedillo-Hamann Dayna
Published: February 2022

Restorative justice (RJ) is both a philosophy and a set of practices meant to repair harm and maintain connection in the face of wrongdoing. While RJ is becoming increasingly popular among K–12 educators and in schools, emphasis is typically on its social justice applications, including its use as an alternative to zero-tolerance discipline policies and its role in dismantling the school-to-prison pipeline. However, RJ can also be understood as a trauma-informed mental health intervention allowing perpetrators, who have frequently been victims of past trauma, to regain a sense of voice and control, and to maintain social connection within their community. Social workers in school settings are in a prime position to explore and advocate for its increased use with vulnerable youth populations. Through review of relevant literature and use of a composite case example, this article outlines the harmful impacts of punitive and exclusionary discipline; describes the potential benefit of schools utilizing RJ as a mental health intervention; and recommends further research to understand RJ's effect on self-efficacy, self-regulation, and healthy attachment.
Norton Scale Score and long-term healthcare services utilization after acute myocardial infarction
Authors: Plakht Ygal , Silber Hagar , Shiyovich Arthur , Arbelle Jonathan Eli , Greenberg Dan , Gilutz Harel
Published: February 2022

Aims

Many patients admitted with acute myocardial infarction (AMI) have considerable multimorbidity, sometimes associated with functional limitations. The Norton Scale Score (NSS) evaluates clinical aspects of well-being and predicts numerous clinical outcomes. We evaluated the association between NSS and long-term healthcare utilization (HU) following a non-fatal AMI.

Methods and results

A retrospective observational study including AMI survivors during 1 January 2004 to 31 December 2015 with a filled NSS report. Data were recouped from the electronic medical records of the hospital and two Health Maintenance Organizations. Norton Scale Score ≤16 or >16 was defined as low or high respectively. The outcome was annual HU, encompassing length of hospital stay (LOS), emergency department (ED) visits, primary care, and other ambulatory service utilization during up to 10 years of follow-up. HU costs were compared between groups. Two-level models were built: unadjusted and adjusted for patients’ baseline characteristics. The study included 4613 patients, 784 (17%) had low NSS. Patients with low NSS compared with patients with high NSS were older, had a higher rate of multimorbidity, and had significantly lower coronary angiography and revascularization rates. In addition, low NSS patients presented higher annual HU costs (4879 vs. 3634 Euro, P <0.001), primarily due to LOS, ED visits, and less frequent ambulatory services usage.

Conclusion

In patients after non-fatal AMI, low NSS is a signal for higher long-term costs reflecting the presence of expensive comorbidities. Management disparity and impaired mobility may offset the real need of these patients. Therefore, the specific proactive nursing intervention in that population is recommended.
Investigation on the indoor thermal comfort in sports settings and an improvement to Fanger model
Authors: Ji Tai , Cai Jingyong , Wang Kun
Published: February 2022

Player in sports is characterized as large metabolic rate and perspiration, small thermal resistance, low coverage rate of clothing and short breath. The heat transfer from the player to environment is generally strong. It is difficult to accurately predict the thermal comfort of the player in strenuous sports based on the traditional Fanger’s model. To overcome this limitation, an improved Fanger’s model is established on the basis of the original predicted mean vote (PMV) model in this paper. Theoretical analysis of PMV based on traditional model and improved model is performed, and a series of experiments involving 798 surveys in 40 experimental sessions under various sport events are conducted. On this basis, the accuracy of traditional Fanger’s model and the improved model is compared. Results show that the improved model is more reasonable and has better agreement with the experiment results. In both simulation and experiment, the PMV predicted by the improved model is lower than that predicted by traditional Fanger’s model, which indicates that the heat dissipation calculated by the new model is higher. The improved model can predict thermal comfort of human in sports under different thermal environment with higher accuracy compared with conventional Fanger’s model. Finally, based on improved Fanger’s model, reasonable ambient temperature under different exercise intensities is recommended, which is significant to prevent occurrence of heat injury in sports and energy saving of heating, ventilation, and air conditioning (HVAC) system in gymnasium.
Adaptation of clinical isolates of Klebsiella pneumoniae to the combination of niclosamide with the efflux pump inhibitor phenyl-arginine-β-naphthylamide (PaβN): co-resistance to antimicrobials
Authors: Pacios Olga , Fernández-García Laura , Bleriot Inés , Blasco Lucia , Ambroa Antón , López María , Ortiz-Cartagena Concha , González de Aledo Manuel , Fernández-Cuenca Felipe , Oteo-Iglesias Jesús , Pascual Álvaro , Martínez-Martínez Luis , Tomás María
Published: February 2022

Objectives

To search for new means of combatting carbapenemase-producing strains of Klebsiella pneumoniae by repurposing the anti-helminth drug niclosamide as an antimicrobial agent and combining it with the efflux pump inhibitor (EPI) phenyl-arginine-β-naphthylamide (PaβN).

Methods

Niclosamide and PaβN MICs were determined for six clinical K. pneumoniae isolates harbouring different carbapenemases by broth microdilution and chequerboard assays. Time–kill curves in the presence of each drug alone and in combination were conducted. The viability of bacterial cells in the presence of repetitive exposures at 8 h to the treatment at the same concentration of niclosamide and/or PaβN (adapted isolates) was determined. The acrAB-tolC genes and their regulators were sequenced and quantitative RT–PCR was performed to assess whether the acrA gene was overexpressed in adapted isolates compared with non-adapted isolates. Finally, the MICs of several antimicrobials were determined for the adapted isolates.

Results

Niclosamide and PaβN had synergistic effects on the six isolates in vitro, but adaptation appeared when the treatment was applied to the medium every 8 h, with an increase of 6- to 12-fold in the MIC of PaβN. Sequencing revealed different mutations in the regulators of the tripartite AcrAB-TolC efflux pump (ramR and acrR) that may be responsible for the overexpression of the efflux pump and the adaptation to this combination. Co-resistance to different antimicrobials confirmed the overexpression of the AcrAB-TolC efflux pump.

Conclusions

Despite the synergistic effect that preliminary in vitro stages may suggest, the combinations of drugs and EPI may generate adapted phenotypes associated with antimicrobial resistance that must be taken into consideration.
Interacting Antagonisms: Parasite Infection Alters Bombus impatiens (Hymenoptera: Apidae) Responses to Herbivory on Tomato Plants
Authors: Aguirre Luis A , Adler Lynn S
Published: February 2022

Little is known about how simultaneous antagonistic interactions on plants and pollinators affect pollination services, even though herbivory can alter floral traits and parasites can change pollinator learning, perception, or behavior. We investigated how a common herbivore and bumble bee (Bombus spp.) parasite impact pollination in tomatoes (Solanum lycopersicum L.) (Solanales: Solanaceae). We exposed half the plants to low-intensity herbivory by the specialist Manduca sexta L. (Lepidoptera: Sphigidae), and observed bumble bee visits and time spent on flowers of damaged and control plants. Following observations, we caught the foraging bees and assessed infection by the common gut parasite, Crithidia bombi Lipa & Triggiani (Trypanosomatida: Trypanosomatidae). Interestingly, we found an interactive effect between herbivory and Crithidia infection; bees with higher parasite loads spent less time foraging on damaged plants compared to control plants. However, bees did not visit higher proportions of flowers on damaged or control plants, regardless of infection status. Our study demonstrates that multiple antagonists can have synergistic negative effects on the duration of pollinator visits, such that the consequences of herbivory may depend on the infection status of pollinators. If pollinator parasites indeed exacerbate the negative effects of herbivory on pollination services, this suggests the importance of incorporating bee health management practices to maximize crop production.
A Risk Tool and Production Log Created using Microsoft Excel to Manage Pests in Peanut (Arachis hypogaea)
Authors: Jordan David L , Buol Greg S , Brandenburg Rick L , Shew Barbara B , Wilkerson Gail G , Lassiter Bridget R , Dunne Jeff , Gorny Adrienne , Washburn Derek , Hoisington David , Rhoads James
Published: February 2022

Peanut (Arachis hypogaea L.) growers and their advisors need to address a wide range of biotic and abiotic stresses to maximize yield and financial return. Mitigating risk to yield and financial investment requires knowledge of interactions among pests and strategies to manage pests, including chemical inputs, crop rotation, cultivar selection, field pest history, planting pattern and population, planting date, and tillage systems. Using Microsoft Excel, a comprehensive peanut risk tool was developed to assist growers and advisors in identifying and selecting production strategies to minimize risk to yield based on empirical data and practical experience while providing cost estimates of production practices. Initially, the risk tool was developed for North Carolina (USA) peanut production. However, the current platform is designed to facilitate the development of similar tools for other USA peanut regions, peanut production systems in other countries, and with the capability to develop risk tools for other crops. This article discusses components of the risk management tool developed for North Carolina peanut production. Benefits of the risk tool to practitioners, extension services, genetics and breeding programs, and formal classroom instruction will be discussed. One goal of this paper is to provide an example of how the Microsoft Excel framework used for peanut in North Carolina can be used for peanut in other regions of the USA and other countries.
Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss
Authors: Wang Xiaobo , Gu Min , Ju Yongjian , Zhou Juying
Published: February 2022

Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable because of old age or the advanced stage of the disease; thus radio- and chemotherapy are believed as the standard treatments for these patients. However, due to the radio-resistance of tumor cells that may develop during radiotherapy, results remain unsatisfactory. In this article, the possible relationship between the expression of lysine demethylase 5B (KDM5B) and ESCC radio-resistance is clarified, and the underlying mechanism is evaluated. Using the GSE75241 microarray, we identified KDM5B as a potential oncogene in ESCC. KDM5B was overexpressed in ESCC patients and cells. Inhibition of KDM5B enhanced the H3K4me3 methylation of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) promoter and induced the expression of PIK3C3. Knockdown of KDM5B or overexpression of PIK3C3 in KYSE-150 and TE-10 cells promoted apoptosis, cell cycle arrest, autophagy, and increased sensitivity to radiotherapy. Silencing of PIK3C3 attenuated the promoting effect of sh-KDM5B on the sensitivity of ESCC cells to radiotherapy. The inhibition of sh-KDM5B in radio-resistance of ESCC cells was also reproduced in vivo. Taken together, our findings provide evidence that reduced expression of KDM5B has a critical role in promoting ESCC radio-sensitivity by upregulating PIK3C3, suggesting KDM5B may function as an oncogene in ESCC.
Actualizing distributed knowledge in bounded groups
Authors: Solaki Anthia
Published: February 2022

The idealizations resulting from the use of Kripke semantics in Epistemic Logic are inherited by formalizations of group epistemic notions. For example, distributed knowledge is often taken to reflect the potential knowledge of a group: what agents would know if they had unbounded means of communication and deductive ability. However, this does not specify whether/how this potential can be actualized, especially since real people are not unbounded reasoners. Inspired by experiments on group reasoning, we identify two dimensions of actualizing distributed knowledge: communication and inference. We build a dynamic framework with effortful actions accounting for both, combining impossible-worlds semantics and action models, and we provide a method for extracting a sound and complete axiomatization.
Epidemiology and outcomes of invasive aspergillosis among pediatric immunocompromised patients: A 12-year single-center experience
Authors: Al Dhaheri Fatima , Lee Rose A , Sharma Tanvi S , Nakamura Mari M , Marty Francisco M
Published: February 2022

Invasive aspergillosis (IA) remains a common cause of mortality in pediatric immunocompromised populations. Much of our knowledge of IA stems from adult literature. We conducted a retrospective evaluation of cases of proven or probable IA, defined according to the 2019 EORTC/MSG criteria, in patients with underlying immunocompromising conditions at Boston Children's Hospital from January 1, 2007 to January 1, 2019. We estimated survival curves over 12 weeks using the Kaplan-Meier method for all-cause mortality, and we used univariate Cox proportional hazards modeling to evaluate for mortality risk factors. We identified 59 cases, 29% with proven and 71% with probable IA. Pulmonary IA was the most common presentation (78%). The median age at diagnosis was 11 years (range, 0.5–28). Hematopoietic cell transplantation (HCT) was the most frequent predisposing underlying condition (41%). Among affected patients, 44.8% were neutropenic and 59.3% were lymphopenic at diagnosis. The 12-week all-cause mortality rate was 25.4%; HCT recipients comprised the majority of deaths (9/15) with a hazard ratio of 2.47 [95% CI, 0.87–6.95]. No patients with congenital immunodeficiencies (n = 8) died within 12 weeks of IA diagnosis. Other risk factors that were significantly associated with mortality included mechanical ventilation at diagnosis, intensive care unit stay, and lymphopenia; treatment with an Aspergillus-active azole was associated with decreased mortality.

In conclusion, our study found that in pediatric immunocompromised hosts, IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the HCT population.

Lay abstract

This study explores the epidemiology, outcomes and predictors of mortality of invasive aspergillosis (IA) at a high-volume pediatric center for immunocompromised hosts. Much of our understanding of pediatric IA is extrapolated from the adult literature. Our study found that IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the hematopoietic cell transplantation study cohort.
Chaotic star formation: error bars for the star formation efficiency and column density PDF
Authors: Jaffa S E , Dale J , Krause M , Clarke S D
Published: February 2022

Simulations are very useful for testing our theoretical understanding of star formation by varying the initial conditions or treatment of various physical mechanisms. However, large well-resolved simulations including complex physics are computationally costly and therefore are normally only performed once. This leads to a crisis in modelling, because star formation is a chaotic system, where a small variation in initial conditions can be magnified to a large change in results. We create a suite of cluster-scale simulations with 30 different random realizations of the turbulent velocity field applied to the same initial conditions of an isolated spherical molecular cloud. We test commonly used metrics of star formation activity and cloud structure and measure the variance cause by this random variation in initial conditions to quantify the error that should be applied to single-realization simulations. We find that after 5 Myr the number of stars varies by 58 per cent of the mean, the star formation efficiency by 60 per cent of the mean, and the shape of the column density PDF by 7 per cent of the mean. We provide a standard deviation at different times that should be applied as an error margin on all single realization simulations to enable robust statistical comparison.
Laser guide star return-flux gain from frequency chirping
Authors: Hellemeier J , Enderlein M , Hager M , Bonaccini Calia D , Johnson R L , Lison F , Byrd M O , Kann L A , Centrone M , Hickson P
Published: February 2022

Spectral hole burning reduces sodium laser guide star efficiency. Due to photon recoil, atoms that are initially resonant with the single-frequency laser get Doppler shifted out of resonance, which reduces the return flux. Frequency-chirped (also known as frequency-swept) continuous-wave lasers have the potential to mitigate the effect of spectral hole burning and even increase the laser guide star efficiency beyond the theoretical limit of a single-frequency laser. We investigate the return flux of frequency-chirped laser guide stars and its dependence on environmental and chirping parameters. On-sky measurements of a frequency-chirped, single-frequency laser guide star are performed at the Roque de los Muchachos Observatory on La Palma. A fast photon-counting receiver system is employed to resolve the return-flux response during laser frequency sweeps gaining insights into the population dynamics of the sodium layer. At a launched laser power of 16.5 W, we find a maximum gain in return flux of 22 per cent compared to a fixed-frequency laser at a chirping amplitude of the order of 150 MHz and a chirping rate of 0.8 MHz µs−1. Time-resolved measurements during the chirping period confirm our understanding of the population dynamics in the sodium layer. These are the first measurements of return-flux enhancement for laser guide stars excited by a single-frequency-chirped continuous-wave laser. For higher laser powers, the effectiveness of chirping is expected to increase, which could be highly beneficial for telescopes equipped with high-power laser guide star adaptive optics systems.
The effect of spin mismodelling on gravitational-wave measurements of the binary neutron star mass distribution
Authors: Biscoveanu Sylvia , Talbot Colm , Vitale Salvatore
Published: February 2022

The binary neutron star (BNS) mass distribution measured with gravitational-wave observations has the potential to reveal information about the dense matter equation of state, supernova physics, the expansion rate of the Universe, and tests of general relativity. As most current gravitational-wave analyses measuring the BNS mass distribution do not simultaneously fit the spin distribution, the implied population-level spin distribution is the same as the spin prior applied when analysing individual sources. In this work, we demonstrate that introducing a mismatch between the implied and true BNS spin distributions can lead to biases in the inferred mass distribution. This is due to the strong correlations between the measurements of the mass ratio and spin components aligned with the orbital angular momentum for individual sources. We find that applying a low-spin prior that excludes the true spin magnitudes of some sources in the population leads to significantly overestimating the maximum neutron star mass and underestimating the minimum neutron star mass at the population level with as few as six BNS detections. The safest choice of spin prior that does not lead to biases in the inferred mass distribution is one that allows for high spin magnitudes and tilts misaligned with the orbital angular momentum.
Joint-Predominant Rheumatic Complications of Immune Checkpoint Inhibitor Therapy in Patients with Thymic Epithelial Tumors
Authors: Mullenix Cristina , Ballman Madison , Chen Haobin , Swift Shannon , McAdams Meredith J , Tsai Yo-Ting , Donahue Renee N , Poretta Trina , Gupta Sarthak , Loehrer Patrick J , Schlom Jeffrey , Gulley James L , Rajan Arun
Published: February 2022

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. However, activation of the immune system can occasionally cause life-threatening toxicity involving critical organs. Induction of immune-mediated toxicity is a significant concern for patients with thymic epithelial tumors (TETs) due to defects in immune tolerance. An increased risk of skeletal and cardiac muscle inflammation following treatment with ICIs is well recognized in patients with advanced TETs. However, uncommon musculoskeletal and rheumatic complications can also occur. The cases presented in this report highlight the spectrum of presentation of immune-mediated, joint-predominant musculoskeletal adverse events in patients with advanced TETs treated with ICIs, including polymyalgia rheumatica-like illness and inflammatory arthritis.
The Ethics of COVID-19 Vaccine Allocation: Don't Forget the Trade-Offs!
Authors: März Julian W , Molnar Anett , Holm Søren , Schlander Michael
Published: February 2022

The issue of COVID-19 vaccine allocation is still highly controversial on the international as well as on the national level (particularly in many low- and middle-income countries), and policy-makers worldwide struggle in striking a fair balance between different ethical principles of vaccine allocation, in particular maximum benefit, reciprocity, social justice and equal respect. Any political decision that implements these principles comes at a cost in terms of loss of lives and of loss of life years that could potentially have been prevented by a different vaccination strategy. This article illustrates these trade-offs using quantitative analysis and shows how this approach can contribute to providing a rational and transparent grounding of political decisions on COVID-19 vaccine allocation.
Dark radiation in spectator axion–gauge models
Authors: Kakizaki Mitsuru , Ogata Masahito , Seto Osamu
Published: February 2022

In the framework of axion–gauge field models, primordial gravitational wave perturbations could be generated during the inflationary epoch from not only the quantum fluctuation of gravitons but also the dynamics of hidden gauge fields coupled with an axion field. We investigate the evolution of the axion and the gauge field of an additional hidden SU(2) gauge group and those energy densities during and after the inflation. We show that the extra radiation component of the hidden gauge bosons produced by the axion decay can be sizable in the cases where the gauge-field-sourced additional gravitational waves is subdominant. We point out that future measurements of the dark radiation energy, such as CMB-S4, can impose significant constraints on this cosmological scenario.
Carreau law for non-newtonian fluid flow through a thin porous media
Authors: Anguiano María , Bonnivard Matthieu , Suárez-Grau Francisco J
Published: February 2022

We consider the flow of generalized Newtonian fluid through a thin porous media. The media under consideration is a bounded perforated three dimensional domain confined between two parallel plates, where the distance between the plates is described by a small parameter $\varepsilon$. The perforation consists in an array of solid cylinders, which connect the plates in perpendicular direction, with diameter of size $\varepsilon$ and distributed periodically with period $\varepsilon$. The flow is described by the three dimensional incompressible stationary Stokes system with a nonlinear viscosity following the Carreau law. We study the limit when the thickness tends to zero and prove that the averaged velocity satisfies a nonlinear two-dimensional homogenized law of Carreau type. We illustrate our homogenization result by numerical simulations showing the influence of the Carreau law on the behavior of the limit system, in the case where the flow is driven by a constant pressure gradient and for different geometries of perforations.
Meta-analytic activation maps can help identify affective processes captured by contrast-based task fMRI: the case of threat-related facial expressions
Authors: Kim M Justin , Knodt Annchen R , Hariri Ahmad R
Published: February 2022

Meta-analysis of functional magnetic resonance imaging (fMRI) data is an effective method for capturing the distributed patterns of brain activity supporting discrete cognitive and affective processes. One opportunity presented by the resulting meta-analysis maps (MAMs) is as a reference for better understanding the nature of individual contrast maps (ICMs) derived from specific task fMRI data. Here, we compared MAMs from 148 neuroimaging studies representing emotion categories of fear, anger, disgust, happiness and sadness with ICMs from fearful > neutral and angry > neutral faces from an independent dataset of task fMRI (n = 1263). Analyses revealed that both fear and anger ICMs exhibited the greatest pattern similarity to fear MAMs. As the number of voxels included for the computation of pattern similarity became more selective, the specificity of MAM–ICM correspondence decreased. Notably, amygdala activity long considered critical for processing threat-related facial expressions was neither sufficient nor necessary for detecting MAM–ICM pattern similarity effects. Our analyses suggest that both fearful and angry facial expressions are best captured by distributed patterns of brain activity, a putative neural correlate of threat. More generally, our analyses demonstrate how MAMs can be leveraged to better understand affective processes captured by ICMs in task fMRI data.
Asymmetric Pericentrosomal CD133 Endosomes Induce the Unequal Autophagic Activity During Cytokinesis in CD133-Positive Human Neuroblastoma Cells
Authors: Izumi Hideki , Li Yuanyuan , Yasunami Michio , Sato Seiji , Mae Takao , Kaneko Yasuhiko , Nakagawara Akira
Published: February 2022

CD133 is a transmembrane protein that mainly localizes to the plasma membrane in hematopoietic/neural stem cells and cancer stem cells. Although CD133 also localizes to the cytoplasm and is degraded through autophagy, the precise mechanisms responsible for the autophagic degradation of endosomal CD133 currently remain unknown. We demonstrated that endosomal CD133 has unique properties for cell homeostasis. Endosomal CD133 is degraded through p62/SQSTM1-mediated selective autophagy. However, in low basal autophagic cells, such as SK-N-DZ and SH-SY5Y cells, endosomal CD133 accumulates at the pericentrosomal region and conversely suppresses autophagy. Endosomal CD133 also asymmetrically distributes to the pericentrosomal region and induces unequal autophagic activity between 2 daughter cells during cytokinesis in SK-N-DZ and TGW cells. In addition, the asymmetric distribution of pericentrosomal CD133 endosomes and nuclear β-catenin cooperatively suppresses autophagic activity against p62 in SK-N-DZ cells. Thus, the present study suggests that the asymmetric distribution of pericentrosomal CD133 endosomes induces the symmetry breaking of autophagic activity during cytokinesis in cooperation with nuclear β-catenin.
The Influence of Host Genotypes on the Endophytes in the Leaf Scar Tissues of Apple Trees and Correlation of the Endophytes with Apple Canker (Neonectria ditissima) Development
Authors: Papp-Rupar Matevz , Karlstrom Amanda , Passey Thomas , Deakin Greg , Xu Xiangming
Published: February 2022

Bacterial and fungal endophytes may help their host in terms of improved tolerance to abiotic and biotic stresses and enhanced growth. European apple canker, caused by Neonectria ditissima, is widespread in apple-growing regions. Infection by N. ditissima occurs through artificial or natural wounds, including leaf scars, picking wounds, and pruning cuts. Using F1progeny trees in an experimental orchard derived from a cross between a canker-susceptible genotype and a canker-tolerant or -resistant genotype, we assessed both bacterial and fungal endophyte communities in apple leaf scars, and determined correlations of endophytes with canker development. All trees were artificially inoculated with an N. ditissima isolate postplanting. Specific components of apple endophytes as well as a number of individual fungal or bacterial groups in leaf scars were partially genetically controlled by host genotypes. Several bacterial groups were significantly correlated with canker-related traits, mostly positively associated with canker tolerance. A few fungal groups may facilitate canker development whereas others may compete with canker. However, most of these microbial groups could not be identified to the species level with confidence; even for those groups which could be assigned to the species level, there is insufficient knowledge about their ecological characteristics in relation to plants. The present results may be used to inform further research using biocontrol to manage N. ditissima and breeding for resistance.
Exposure to nanoparticles and occupational allergy
Authors: Di Gioacchino Mario , Di Giampaolo Luca , Mangifesta Rocco , Gangemi Sebastiano , Petrarca Claudia
Published: February 2022

Purpose of review

To provide an update on the possible role of nanoparticles as sensitizing occupational agents and on the influence of nanoparticles-exposure on the appearance/exacerbation of occupational allergy.

Recent findings

Recent case reports, epidemiological studies, and experimental investigations in cellular and animal models demonstrated the potential for nanomaterials to favor/interfere with occupational allergy. First data are emerging on the sensitizing potential of nanoparticles that can act as haptens linking to proteins, with a formation of a ‘corona’. Nanoparticles with carrier protein become a complete antigen and induce specific immune response. Moreover, they act as adjuvant favoring sensitization to bound molecules. The disruption of the respiratory and skin barrier, the modulation of immune response toward Th1 or Th2 immune reaction and the interaction with immune effector cells (mast cells and eosinophil in particular) can explain the potential for nanoparticles to exacerbate pre-existing allergic conditions.

the exposure to nanoparticles represents a possible risk for occupational allergy both in the respiratory tract and in the skin. A deeper knowledge on the role of nanomaterials in the etiology/development of the allergic disease will allow to implement risk assessment and preventive measures for nanosafety in the contest of technological expansion.
MAP 65-is it enough?
Authors: Hu Yaqi , Lim Aaron
Published: February 2022

Purpose of review

The purpose of this review is to look at the current evidence on the consequences of intraoperative hypotension and discuss improvements that can be implemented for its prevention.

Recent findings

Literature continues to supply convincing evidence that even brief periods of intraoperative hypotension are associated with increased perioperative morbidity and mortality. Recent randomized controlled trial showed intraoperative early use of vasopressor and maintaining blood pressure within tight ranges improves outcomes.

There should be a shift in paradigm in focusing on the prevention of intraoperative hypotension instead treatment. The suggested goals to help maintaining hemodynamic stability during anesthesia include ensure adequate blood pressure and flow; hypotension prevention; and ensure adequate anesthetic depth without overdose.
Clinical Efficacy of Perioperative Intravenous Dexmedetomidine and Lidocaine Combined Infusion for Thyroidectomy
Authors: Guo Hao , Ao Tingting , Wang Jiagao , Zhang Xi , Zheng Junwei , Xiao Yun , Xue Rui , Kalika Prakash , Ran Ran
Published: February 2022

Objectives:

The aim of this study was to evaluate the efficacy of perioperative dexmedetomidine (DEX) combined with lidocaine intravenous infusion on relieving postoperative pain and improving recovery for patients undergoing thyroidectomy.

Materials and Methods:

A total of 138 patients undergoing thyroidectomy with general anesthesia were randomly divided into 4 groups: lidocaine (1.5 mg/kg bolus followed by 2 mg/kg/h infusion) in the group L, DEX (0.5 µg/kg) in the group D, lidocaine (same as the group L) with DEX (0.5 µg/kg) in the group L+D, and placebo as normal saline in the group C. All drugs were infused until the end of the surgery. The visual analog scale (VAS) scores of patients at 1, 4, 8, 12, and 24 hours following surgery, opioid requirement, propofol consumption, incidence of postoperative nausea and vomiting, awaking time, hemodynamic variables, and any adverse effects were assessed.

Results:

Compared with the group C, the VAS scores in the group L+D were significantly lower until 8 hours after surgery (P<0.05), while the VAS scores were significantly decreased just until 4 hours in the group L and 1 hour in the group D after surgery (P<0.05). There was no significant difference in opioid consumption between 4 groups. Propofol consumption in the group L+D was significantly lower than other groups (P<0.05). Compared with the group C, the incidence of postoperative nausea and vomiting in the group L+D was lower (P<0.05), and awaking time in the group L+D and the group L was shorter (P<0.05).

Conclusion:

DEX combined with lidocaine infusion can effectively attenuate the postoperative pain without any serious adverse events, which may improve postoperative recovery in patients undergoing thyroidectomy.
Predicting Mortality Following Traumatic Brain Injury or Subarachnoid Hemorrhage: An Analysis of the Validity of Standardized Mortality Ratios Obtained From the APACHE II and ICNARCH-2018 Models
Authors: Rowe Matt , Brown Jules , Marsh Aidan , Thompson Julian
Published: February 2022

Introduction:

Standardized mortality ratios (SMRs), calculated using the Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) and Intensive Care National Audit and Research Centre H-2018 (ICNARCH-2018) risk prediction models, are widely used in UK intensive care units (ICUs) to measure and compare the quality of critical care delivery. Both models incorporate an assumption of Glasgow Coma Score (GCS) if an actual GCS without sedation is not recordable in the first 24 hours after ICU admission. This study assesses the validity of the APACHE II and ICNARCH-2018 models to predict mortality in ICU patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (aSAH) in whom GCS is related to outcomes.

Methods:

In a retrospective analysis, the SMR calculated by the APACHE II and ICNARCH-2018 models for all UK ICU admissions in a 1-year period was compared with calculated SMRs in TBI/aSAH patients and at 3 GCS groups. Data for patients admitted to a single tertiary neurocritical care unit were similarly analyzed.

Results:

Both models predicted mortality well for the overall TBI/aSAH population; SMR (95% confidence interval) was 1.00 (0.96-1.04) and 0.99 (0.95-1.03) for the APACHE II and ICNARCH-2018 models, respectively. When analyzed by GCS grouping, both models underpredicted mortality in TBI/aSAH patients with GCS ≤8 (SMR, 1.1 [1.05-1.15]) and “unrecordable” GCS (SMR, 1.88 [1.77-1.99]). Similar findings were identified in the local data analysis.

Discussion:

The APACHE II and ICNARCH-2018 models predicted mortality well for the overall TBI/aSAH ICU population but underpredicted mortality when GCS was ≤8 or “unrecordable.” This raises questions about the accuracy of these risk prediction models in TBI/aSAH patients and their use to evaluate treatments and compare outcomes between centers.
Lateral Cuneiform Ossification and Tibialis Anterior Tendon Width in Children Ages 3 to 6: Implications for Interference Screw Fixation of Tibialis Anterior Tendon Transfers in Children
Authors: Meyer Zachery I. , Polk Jordan L. , Zide Jacob R. , Kanaan Yassine , Riccio Anthony I.
Published: February 2022

Background:

While the transfer of the tibialis anterior tendon (TAT) to the lateral cuneiform (LC) following serial casting has been used for nearly 60 years to treat relapsed clubfoot deformity, modern methods of tendon fixation remain largely unstudied. Interference screw fixation represents an alternative strategy that obviates concerns of plantar foot skin pressure-induced necrosis and proper tendon tensioning associated with button suspensory fixation. A better understanding of LC morphology in young children is a necessary first step in assessing the viability of this fixation technique. Therefore, the purpose of this investigation is to define LC morphology and TAT width in children aged 3 to 6 years.

Methods:

A retrospective radiographic review of 40 healthy pediatric feet aged 3 to 6 years who had either magnetic resonance imaging or computed tomography scans was performed at a single pediatric hospital. The length, width, and height of only the ossified portion of the LC were measured digitally using sagittal, coronal, and axial imaging. In addition, the maximal cross-sectional diameter of the TAT was measured at the level of the tibiotalar joint.

Results:

The average ossified LC width ranged from 8.5 mm in the 3-year-old cohort to 10.3 mm in 6-year-old children. Analysis of variance testing revealed no statistically significant difference in width between age groups. Average ossified LC length ranged from 13.5 mm in the 3-year-old cohort to 18.3 mm in 6-year-old children with statistically significant increases in age groups separated by 2 or more years. Significant differences in LC height, volume, and TAT diameter were demonstrated after analysis of variance testing. The TAT to ossified LC width ratio ranged from 44% to 53% across age groups.

Conclusions:

The dimensions of the LC ossification center are large enough to allow interference screw fixation in children 3 to 6 years of age. Further studies are needed to investigate interference screw fixation performance in the pediatric clubfoot population.

Level of Evidence:

Level IV.
Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia
Authors: Zhu Haichuan , Dong Bingjie , Zhang Yingchi , Wang Mei , Rao Jianan , Cui Bowen , Liu Yu , Jiang Qian , Wang Weitao , Yang Lu , Yu Anqi , Li Zongru , Liu Chao , Zhang Leping , Huang Xiaojun , Zhu Xiaofan , Wu Hong
Published: February 2022

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy often associated with poor outcomes. To identify high-risk factors and potential actionable targets for T-ALL, we perform integrated genomic and transcriptomic analyses on samples from 165 Chinese pediatric and adult T-ALL patients, of whom 85% have outcome information. The genomic mutation landscape of this Chinese cohort is very similar to the Western cohort published previously, except that the rate of NOTCH1 mutations is significant lower in the Chinese T-ALL patients. Among 47 recurrently mutated genes in 7 functional categories, we identify RAS pathway and PTEN mutations as poor survival factors for non-TAL and TAL subtypes, respectively. Mutations in the PI3K pathway are mutually exclusive with mutations in the RAS and NOTCH1 pathways as well as transcription factors. Further analysis demonstrates that approximately 43% of the high-risk patients harbor at least one potential actionable alteration identified in this study, and T-ALLs with RAS pathway mutations are hypersensitive to MEKi in vitro and in vivo. Thus, our integrated genomic analyses not only systematically identify high-risk factors but suggest that these high-risk factors are promising targets for T-ALL therapies.
Suicidal Ideation in Adolescents: Understanding Results from Screening with the PHQ-9M and the PSC-17P
Authors: Holcomb Juliana M. , Dutta Anamika , Bergmann Paul , Riobueno-Naylor Alexa , Haile Haregnesh , Benheim Talia S. , Sturner Raymond , Howard Barbara , Jellinek Michael , Murphy J. Michael
Published: February 2022

Objective:

The objective of the study was to help pediatricians understand and respond to suicidal ideation (SI) in adolescents based on data from 2 widely used screening measures that assessed SI and other psychosocial vulnerabilities in a large, national sample.

Methods:

Adolescents (ages 11–17 years) completed the Patient Health Questionnaire Modified for Teenagers (PHQ-9M) using the Comprehensive Health and Decision Information System software before their well-child visits. Question 9 asks about past 2-week SI. Their parents filled out the Pediatric Symptom Checklist (PSC-17P), which screens for a broad range of psychosocial problems. Chi-square analyses and one-way analysis of variances assessed the relationship between SI and psychosocial problems.

Results:

Among 5411 adolescents, 266 (4.9%) reported SI at least several days in the past 2 weeks. Among adolescents with SI, 187 (70.3%) reported moderate to very severe depression on the PHQ-9M (≥10), 68.1% were at risk on at least 1 PSC-17P problem subscale, 59.7% on the PSC-17P internalizing scale, 42.9% on PSC-17P overall, 20.6% on PSC-17P externalizing, and 18.5% on PSC-17P attention. Within the subsample endorsing SI nearly all days, 35.7% had a former suicide attempt.

Conclusion:

The PHQ-9M identifies a clinically heterogeneous subset of approximately 5% of adolescents who report occasional to frequent SI. The PSC-17P corroborates their high degree of overall risk and offers additional information that can help pediatricians assess clinical severity and range of psychosocial problems. Given our limited knowledge of how to predict and prevent an individual adolescent's suicide, the focus of screening should be to identify and help the subset of patients with chronic psychosocial vulnerability of any type.
Recurrence Status, Perineural Invasion, and Hypothyroidism Are Associated With Lymph Node Metastasis in Cutaneous Squamous Cell Carcinoma: A Case–Control Study
Authors: Lobl Marissa , Feinstein Shera , Lauer Scott , Sutton Adam , Wysong Ashley
Published: February 2022

BACKGROUND

Lymph node metastasis is a critical prognostic indicator for mortality in patients with cutaneous squamous cell carcinoma (SCC).

OBJECTIVE

To identify and characterize key risk factors for SCC lymph node metastasis.

METHODS

This was a multi-institutional, case–control study of 65 cutaneous SCCs with known lymph node metastasis matched with 195 cutaneous SCCs without lymph node metastasis (3:1 matching). The cases and controls were matched by anatomic location, age, and sex. Odds ratios (ORs) and their 95% confidence intervals (CIs) were generated to determine the association between specific risk factors and lymph node metastasis in a multivariate analysis.

RESULTS

Recurrent tumors (p < .001), perineural invasion (p < .001), lymphovascular invasion (p = .002), size of 2 cm or greater (p = .008), and hypothyroidism (p = .03) were significantly more common in the lymph node metastasis cohort. Recurrence (OR 6.3, 95% CI 2.6–15.3), perineural invasion (OR 4.5, 95% CI 1.7–11.8), and hypothyroidism (OR 2.7, 95% CI 1.04–7.0) remained significant on performing a multivariate analysis.

CONCLUSION

Lymph node metastasis in SCC is associated with recurrence, perineural invasion, lymphovascular invasion, size of 2 cm or greater, and hypothyroidism. Clinical consideration of these findings within the context of current staging systems may help improve patient outcomes.
¿Qué Está Haciendo Papá? Mexican-Heritage Fathers' Physical Activity Networks After a Father-Focused Health Program
Authors: Prochnow Tyler , Umstattd Meyer M. Renee , Patterson Megan S. , Talbert Tony , Meyer Andrew , Sharkey Joseph
Published: February 2022

Physical activity (PA) is a public health priority due to holistic health benefits; however, many adults do not meet PA guidelines. Few studies have examined Mexican-heritage fathers' social networks, specifically with whom they are physically active. This study examines changes in Mexican-heritage fathers' PA networks after participation in a father-focused, family-centered health program. Families consisting of child (aged 9-11 years), mother, and father were recruited from colonias on the Texas-Mexico border for participation in a 6-week father-focused, family-centered program concentrated on healthy eating and active living. Fathers reported up to 5 people with whom they were active most in the previous month before and after the program as well as how often they were active with the person and what activities they did most often. Multilevel regression models examined changes in networks. Fathers (n = 42; mean age = 39.07 years, SD = 7.45) were significantly more likely to report more frequent PA with others after the program as compared with before. General active play and conditional support were mentioned most frequently. This study provides context to the social networks and PA behaviors of Mexican-heritage fathers and suggests that a father-focused, family-centered health program can increase the PA frequency with social network connections.