bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological Emergency management of Agitation in Children and Young people: protocol for a randomised controlled trial of intraMuscular medication (PEAChY-M)
Authors: Bourke Elyssia M , Borland Meredith L , Kochar Amit , George Shane , Shellshear Deborah , Jani Shefali , Perkins Kent , Tham Doris , Gordon Michael Solomon , Klein Kate , Prakash Chidambaram , Lee Katherine , Davidson Andrew , Knott Jonathan C , Craig Simon , Babl Franz E
Published: March 2023

Introduction

Acute severe behavioural disturbance (ASBD) is a condition seen with increasing frequency in emergency departments (EDs) in adults and young people. Despite the increasing number of presentations and significant associated risks to patients, families and caregivers, there is limited evidence to guide the most effective pharmacological management in children and adolescents. The aim of this study is to determine whether a single dose of intramuscular olanzapine is more effective than intramuscular droperidol at successfully sedating young people with ASBD requiring intramuscular sedation.

Methods and analysis

This study is a multicentre, open-label, superiority randomised controlled trial. Young people aged between 9 and 17 years and 364 days presenting to an ED with ASBD who are deemed to require medication for behavioural containment will be recruited to the study. Participants will be randomised in a 1:1 allocation between a single weight-based dose of intramuscular olanzapine and intramuscular droperidol. The primary outcome is the proportion of participants who achieve successful sedation at 1-hour post randomisation without the need for additional sedation. Secondary outcomes will include assessing for adverse events, additional medications provided in the ED, further episodes of ASBD, length of stay in the ED and hospital and satisfaction with management.

Effectiveness will be determined using an intention-to-treat analysis, with medication efficacy determined as part of the secondary outcomes using a per-protocol analysis. The primary outcome of successful sedation at 1 hour will be presented as a percentage within each treatment group, with comparisons presented as a risk difference with its 95% CIs.

Ethics and dissemination

Ethics approval was received from the Royal Children’s Hospital Human Research Ethics Committee (HREC/69948/RCHM-2021). This incorporated a waiver of informed consent for the study. The findings will be disseminated in a peer-reviewed journal and at academic conferences.

Trial registration number

ACTRN12621001238864.
Potential role of the seed bank in spreading invasive plants in a tundra-edge environment
Authors: Syed Omer A. , Zhang Vicki M. , Kotanen Peter M.
Published: March 2023

Although relatively infrequent, invasions by non-native plants at high latitudes are increasingly recognized as an emerging problem. Churchill, MB, Canada is unusual as over 100 non-native species have been found in human-disturbed areas, making it an outlier amongst subarctic habitats. Although these non-native species have persisted almost exclusively within town, some occur in isolated locations throughout the local road network. Most of these non-native species have been observed in areas with a history of soil movement (e.g., for construction or road repairs), suggesting that they have been moved within the soil, likely either germinating from seeds or growing clonally from root and rhizome fragments. Using a greenhouse experiment, we found evidence that soils from human-disturbed sites can contain a substantial non-native seed bank. In particular, we grew a significantly higher number of non-native seedlings from translocated soils compared with uninvaded soils. These germinated non-native species are native to Europe but have widely invaded temperate regions. This study provides the first direct evidence that movement of seed-contaminated soil is a significant source of local non-native species spread. Future warming in Arctic regions may increase seed production of these species, leading to increased spread and persistence via contaminated soil.
Dark matter effects on hybrid star properties
Authors: Lenzi C. H. , Dutra M. , Lourenço O. , Lopes L. L. , Menezes D. P.
Published: March 2023

In the present work, we investigate the effects of dark matter (DM) on hybrid star properties. We assume that dark matter is mixed with both hadronic and quark matter and interacts with them through the exchange of a Higgs boson. The hybrid star properties are obtained from equations of state calculated with a Maxwell prescription. For the hadronic matter, we use the NL3* parameter set, and for the quark matter, the MIT bag model with a vector interaction. We see that dark matter does not influence the phase transition points (pressure and chemical potential) but shifts the discontinuity on the energy density, which ultimately reduces the minimum mass star that contains a quark core. Moreover, it changes considerably the star family mass-radius diagrams and moves the merger polarizability curves inside the confidence lines. Another interesting feature is the influence of DM in the quark core of the hybrid stars constructed. Our results show an increase of the core radius for higher values of the dark particle Fermi momentum.
A concise proof of the equivalence of the Nernst theorem and the heat capacity statement of the third law of thermodynamics
Authors: Su Shanhe , Chen Jincan
Published: March 2023

It is pointed out that the equivalence of the Nernst theorem and the heat capacity statement of the third law of thermodynamics can be mathematically proved through a simple method.
A SHORT SOLUTION OF THE LOCAL FRACTIONAL (2+1)-DIMENSIONAL DISPERSIVE LONG WATER WAVE SYSTEM
Authors: BENLI FATMA BERNA , BASKONUS HACI MEHMET , GAO WEI
Published: March 2023

In this paper, a local fractional Riccati differential equation method is applied. A new travelling wave solution to the nonlinear local fractional [Formula: see text]-dimensional dispersive long water wave system is investigated. After travelling wave transformation, the governing model studied is converted into nonlinear ordinary differential equation. Some properties with the strain conditions are also reported.
r-Dynamic chromatic number of subdivision-edge neighborhood corona of certain graph families
Authors: Kalaiselvi K. , Mohanapriya N. , Aparna V.
Published: March 2023

Let [Formula: see text] be a simple connected graph consisting of n vertices and m edges. In a proper [Formula: see text]-coloring, an [Formula: see text]-dynamic coloring of a graph [Formula: see text] is one in which each vertex’s neighbors are provided at least min [Formula: see text] different colors. The [Formula: see text]-dynamic chromatic number of graph [Formula: see text], given as [Formula: see text], is the minimal [Formula: see text] such that the graph has [Formula: see text]-dynamic [Formula: see text] coloring of [Formula: see text]. In this study, we combine a few common graphs to provide the [Formula: see text]-dynamic coloring of the subdivision-edge neighborhood corona of path graph [Formula: see text] and star graph [Formula: see text]. These graphs include path graph [Formula: see text], cycle graph [Formula: see text], complete graph [Formula: see text], star graph [Formula: see text], and double star graph [Formula: see text].
LFR-GAN: Local Feature Refinement based Generative Adversarial Network for Text-to-Image Generation
Authors: Deng Zijun , He Xiangteng , Peng Yuxin
Published: March 2023

Text-to-image generation aims to generate images from text descriptions. Its main challenge lies in two aspects: (1) Semantic consistency, i.e., the generated images should be semantically consistent with the input text; and (2) Visual reality, i.e., the generated images should look like real images. To ensure text-image consistency, existing works mainly learn to establish the cross-modal representations via a text encoder and image encoder. However, due to the limited representation capability of the fixed-length embeddings and the flexibility of the free-form text descriptions, the learned text-to-image model is incapable of maintaining the semantic consistency between image local regions and fine-grained descriptions. As a result, the generated images sometimes miss some fine-grained attributes of the generated object, such as the color or shape of a part of the object. To address this issue, this paper proposes a
Local Feature Refinement Based Generative Adversarial Network (LFR-GAN)
, which first divides the text into some independent fine-grained attributes and generates an initial image, then refines the image details based on these attributes. The main contributions are three-fold: (1)
An attribute modeling
approach is proposed to model the fine-grained text descriptions by mapping them into representations of independent attributes, which provides more fine-grained details for image generation. (2)
A local feature refinement
approach is proposed to enable the generated image to form a complete reflection of the fine-grained attributes contained in the text description. (3)
A multi-stage generation
approach is proposed to realize the fine-grained manipulation of complex images progressively, which aims to improve the performance of the refinement and generate photo-realistic images. Extensive experiments on the CUB and Oxford102 datasets show the effectiveness of our LFR-GAN approach in both text-to-image generation and text-guided image manipulation tasks. Our LFR-GAN approach shows superior performance compared to the state-of-the-art methods. The codes will be released at
https://github.com/PKU-ICST-MIPL/LFR-GAN_TOMM2023
.
Factors Influencing Engagement in Hybrid Virtual and Augmented Reality
Authors: Li Yue , Ch’ng Eugene , Cobb Sue
Published: March 2023

Hybridity in immersive technologies has not been studied for factors that are likely to influence engagement. A noticeable factor is the spatial enclosure that defines where users meet. This involves a mutual object of interest, contents that the users may generate around the object, and the proximity between users. This study examines these factors, namely how object interactivity,
user-generated contents (UGC)
and avatar proximity influence engagement. We designed a
Hybrid Virtual and Augmented Reality (HVAR)
environment that supports paired users to experience cultural heritage in both
Virtual Reality (VR)
and
Augmented Reality (AR)
. A user study was conducted with 60 participants, providing assessments of engagement and presence via questionnaires, together with mobile
electroencephalogram (mEEG)
and user activity data that measures VR user engagement in real-time. Our findings provide insights into how engagement between users can occur in HVAR environments for the future hybrid reality with multi-device connectivity.
Improvement on End-to-End Encryption May Lead to Silent Revolution
Authors: Limoncelli Thomas A.
Published: March 2023

Privacy is an increasing concern, whether you are texting with a business associate or transmitting volumes of data over the Internet. Over the past few decades, cryptographic techniques have enabled privacy improvements in chat apps and other electronic forms of communication. Now researchers are on the brink of what could be the next big improvement in communication privacy: E2EEEE (End-to-End Encryption with Endpoint Elimination). This article is based on interviews with researchers who plan on presenting at a symposium on the topic scheduled for April 1, 2023.
Mechanism for Long Photocurrent Time Constants in α-Ga2O3 UV Photodetectors
Authors: Polyakov A. Y. , Almaev A. V. , Nikolaev V. I. , Pechnikov A. I. , Shchemerov V. I. , Vasilev A. A. , Yakimov E. B. , Kochkova A. I. , Kopyev V. V. , Kushnarev B. O , Pearton S. J.
Published: March 2023

Deep centers and their influence on photocurrent spectra and transients were studied for interdigitated photoresistors on α-Ga2O3 undoped semi-insulating films grown by Halide Vapor Phase Epitaxy (HVPE) on sapphire. Characterization involving current-voltage measurements in the dark and with monochromatic illumination with photons with energies from 1.35 eV to 4.9 eV, Thermally Stimulated Current (TSC), Photoinduced Current Transients Spectroscopy (PICTS) showed the Fermi level in the dark was pinned at Ec−0.8 eV, with other prominent centers being deep acceptors with optical thresholds near 2.3 eV and 4.9 eV and deep traps with levels at Ec−0.5 eV, Ec−0.6 eV. Measurements of photocurrent transients produced by illumination with photon energies 2.3 eV and 4.9 eV and Electron Beam Induced Current (EBIC) imaging point to the high sensitivity and external quantum efficiency values being due to hole trapping enhancing the lifetime of electrons and inherently linked with the long photocurrent transients. The photocurrent transients are stretched exponents, indicating the strong contribution of the presence of centers with barriers for electron capture and/or of potential fluctuations.
Regulatory Networks of lncRNAs, miRNAs, and mRNAs in Response to Heat Stress in Wheat (Triticum Aestivum L.): An Integrated Analysis
Authors: Mishra Dwijesh Chandra , Majumdar Sayanti Guha , Kumar Anuj , Bhati Jyotika , Chaturvedi K. K. , Kumar Ranjeet Ranjan , Goswami Suneha , Rai Anil , Budhlakoti Neeraj
Published: March 2023

Climate change has become a major source of concern, particularly in agriculture, because it has a significant impact on the production of economically important crops such as wheat, rice, and maize. In the present study, an attempt has been made to identify differentially expressed heat stress-responsive long non-coding RNAs (lncRNAs) in the wheat genome using publicly available wheat transcriptome data (24 SRAs) representing two conditions, namely, control and heat-stressed. A total of 10,965 lncRNAs have been identified and, among them, 153, 143, and 211 differentially expressed transcripts have been found under 0 DAT, 1 DAT, and 4 DAT heat-stress conditions, respectively. Target prediction analysis revealed that 4098 lncRNAs were targeted by 119 different miRNA responses to a plethora of environmental stresses, including heat stress. A total of 171 hub genes had 204 SSRs (simple sequence repeats), and a set of target sequences had SNP potential as well. Furthermore, gene ontology analysis revealed that the majority of the discovered lncRNAs are engaged in a variety of cellular and biological processes related to heat stress responses. Furthermore, the modeled three-dimensional (3D) structures of hub genes encoding proteins, which had an appropriate range of similarity with solved structures, provided information on their structural roles. The current study reveals many elements of gene expression regulation in wheat under heat stress, paving the way for the development of improved climate-resilient wheat cultivars.
Comparison of Osimertinib versus Almonertinib in T790M+ EGFR Non-Small-Cell Lung Cancer Patients
Authors: Li Yuan , Zhou Kun , Meng Ying
Published: March 2023

What is Known and Objective. Almonertinib was newly approved for treating non-small-cell lung cancer (NSCLC) patients with EGFR T790M mutation, and the therapeutic effect of almonertinib needed to be investigated. This study aims to investigate the efficacy and safety of almonertinib compared with osimertinib in EGFR-T790M+ patients who used earlier-generation EGFR-TKI and experienced disease progression. Methods. Among all 160 patients, 80 received osimertinib, while the other 80 patients took almonertinib once daily. The objective response rate (ORR) and disease control rate (DCR) were analyzed, while overall survival (OS) and progression-free survival (PFS) were estimated. In terms of safety, adverse events (AEs) were compared. Results and Discussions. The ORR and DCR were significantly higher in patients who received almonertinib than those in the osimertinib group (70.0% vs. 47.5%,

P
=
0.004

; 90.0% vs. 77.5%,

P
=
0.032

). The OS was significantly higher in the almonertinib group than in patients who received osimertinib (

P
=
0.031

), while the PFS was similar between the two groups (

P
=
0.226

). Of 28 patients with brain metastasis, the OS was not raised after using almonertinib compared with the osimertinib group (

P
=
0.626

). The number of AEs was similar between the almonertinib and osimertinib groups (all

P
>
0.05

). Treatment-related AEs of grade ≥3 occurred in 20.0% and 15.0% of patients in the osimertinib and almonertinib arms, respectively. What is New and Conclusion. Almonertinib may become an alternative option for EGFR-T790M + NSCLC patients after earlier-generation EGFR-TKI for its promising efficacy and manageable tolerability. However, the treatment option for patients with brain metastasis remains to be explored further.
Industrial Robot Assembly Line Design Using Machine Vision
Authors: Xie Xiang
Published: March 2023

In order to further improve the functional requirements and performance indicators of the industrial robot assembly system and more accurately realize the measurement and recognition of the target position of the assembly line by the vision system, this article constructs a robot assembly line system based on obstacle detection and robot arm obstacle path planning based on machine vision technology and further improves the intelligence and accuracy of the assembly line system through the design and optimization of the system software module. Through the experimental verification of the positioning error based on the eye-to-hand binocular vision system and eye-in-hand monocular vision system, the system proposed in this article meets the design accuracy requirements of less than 0.1 mm in x/y direction and less than 1 mm in depth direction and verifies the feasibility and high accuracy of the system.
A New Ensemble Learning Method for Multiple Fusion Weighted Evidential Reasoning Rule
Authors: Zhang YiZhe , Zhang YunYi , Zhou GuoHui , Zhang Wei , Li KangLe , Mu QuanQi , He Wei , Tang Kai
Published: March 2023

Ensemble learning, as a kind of method to improve the generalization ability of classifiers, is often used to improve the model effect in the field of deep learning. However, the present ensemble learning methods mostly adopt voting fusion in combining strategies. This strategy has difficulty mining effective information from the classifiers and cannot effectively reflect the relationship between different classifiers. Ensemble learning based on the evidential inference rule (ER rule) can effectively excavate the internal relationships among different classifiers and has a certain interpretability. However, the ER rule depends on the weight distribution of different combination strategies, and the setting of the evidence weight will affect the accuracy and stability of the model. Therefore, this paper proposes a new ensemble learning method based on multiple fusion weighted evidential reasoning rules and constructs an ensemble learning framework for data fusion and decision mapping. This framework takes the evidence weight, confidence, and feature data of each classifier as input and the integration results as output. The weight of evidence was determined by multiple fusion weights of the entropy weight method and order relation method. Finally, the integrated learning process is set up by the ER algorithm. The method proposed in this paper is verified by multiple datasets. Experimental results show that the surface construction model has good performance, and the defects of single weighting instability are greatly improved under the premise of improving the integration effect.
Thermal Management Analysis of Proton Exchange Membrane Fuel Cell Filled with Phase Change Material in Cooling Channel
Authors: Wang Wanteng , Li Nan , Zhang Jinhui , Zhang Caihong , Zhang Liang
Published: March 2023

Passive thermal management using a phase-change material (PCM) for proton exchange membrane fuel cells (PEMFCs) has been proposed and widely used in the thermal management of Li-ion batteries. A three-dimensional and nonisothermal numerical model of a PEMFC with a PCM cooling channel (PCC) is established in this study. The PCC is better than an air-cooling channel (ACC) in terms of reactant distribution and water removal. Its temperature at the interface of the gas diffusion layer and catalyst layer is lower, and the uniformity of temperature is better. The peak current and power density of the PCC are 4.60% and 5.14% higher than those of the ACC, respectively. Furthermore, the PCC does not increase parasitic power, unlike the ACC. In addition, owing to the high temperature near the outlet, the cooling effects of filling 1/3 PCM and filling 2/3 PCM near the outlet and filling of all PCM are investigated, which shows that the filling of 2/3 PCM provides a better cooling performance.
Data from Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma
Authors: Dharanipragada Prashanthi , Zhang Xiao , Liu Sixue , Lomeli Shirley H. , Hong Aayoung , Wang Yan , Yang Zhentao , Lo Kara Z. , Vega-Crespo Agustin , Ribas Antoni , Moschos Stergios J. , Moriceau Gatien , Lo Roger S.
Published: March 2023

Abstract
Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients and mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), and homologous recombination repair (HRR) genes via complex genomic rearrangements (CGR) and extrachromosomal DNAs (ecDNA). Almost all sensitive and acquired-resistant genomes harbor pervasive chromothriptic regions with disproportionately high mutational burdens and significant overlaps with ecDNA and CGR spans. Recurrently, somatic mutations within ecDNA and CGR amplicons enrich for HRR signatures, particularly within acquired resistant tumors. Regardless of sensitivity or resistance, breakpoint–junctional sequence analysis suggests NHEJ as critical to double-stranded DNA break repair underlying CGR and ecDNA formation. In human melanoma cell lines and PDXs, NHEJ targeting by a DNA-PKCS inhibitor prevents/delays acquired MAPKi resistance by reducing the size of ecDNAs and CGRs early on combination treatment. Thus, targeting the causes of genomic instability prevents acquired resistance.
Significance:
Acquired resistance often results in heterogeneous, redundant survival mechanisms, which challenge strategies aimed at reversing resistance. Acquired-resistant melanomas recurrently evolve resistance-driving and resistance-specific amplicons via ecDNAs and CGRs, thereby nominating chromothripsis–ecDNA–CGR biogenesis as a resistance-preventive target. Specifically, targeting DNA-PKCS/NHEJ prevents resistance by suppressing ecDNA/CGR rearrangements in MAPKi-treated melanomas.

This article is highlighted in the In This Issue feature, p. 799
Data from Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma
Authors: Dharanipragada Prashanthi , Zhang Xiao , Liu Sixue , Lomeli Shirley H. , Hong Aayoung , Wang Yan , Yang Zhentao , Lo Kara Z. , Vega-Crespo Agustin , Ribas Antoni , Moschos Stergios J. , Moriceau Gatien , Lo Roger S.
Published: March 2023

Abstract
Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients and mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), and homologous recombination repair (HRR) genes via complex genomic rearrangements (CGR) and extrachromosomal DNAs (ecDNA). Almost all sensitive and acquired-resistant genomes harbor pervasive chromothriptic regions with disproportionately high mutational burdens and significant overlaps with ecDNA and CGR spans. Recurrently, somatic mutations within ecDNA and CGR amplicons enrich for HRR signatures, particularly within acquired resistant tumors. Regardless of sensitivity or resistance, breakpoint–junctional sequence analysis suggests NHEJ as critical to double-stranded DNA break repair underlying CGR and ecDNA formation. In human melanoma cell lines and PDXs, NHEJ targeting by a DNA-PKCS inhibitor prevents/delays acquired MAPKi resistance by reducing the size of ecDNAs and CGRs early on combination treatment. Thus, targeting the causes of genomic instability prevents acquired resistance.
Significance:
Acquired resistance often results in heterogeneous, redundant survival mechanisms, which challenge strategies aimed at reversing resistance. Acquired-resistant melanomas recurrently evolve resistance-driving and resistance-specific amplicons via ecDNAs and CGRs, thereby nominating chromothripsis–ecDNA–CGR biogenesis as a resistance-preventive target. Specifically, targeting DNA-PKCS/NHEJ prevents resistance by suppressing ecDNA/CGR rearrangements in MAPKi-treated melanomas.
Supplementary Fig. S8 from The PARP1 Inhibitor AZD5305 Impairs Ovarian Adenocarcinoma Progression and Visceral Metastases in Patient-derived Xenografts Alone and in Combination with Carboplatin
Authors: Dellavedova Giulia , Decio Alessandra , Formenti Laura , Albertella Mark R. , Wilson Joanne , Staniszewska Anna D. , Leo Elisabetta , Giavazzi Raffaella , Ghilardi Carmen , Bani Maria Rosa
Published: March 2023

Fig. S8 shows olaparib pharmacokinetics and target engagement
Supplementary Fig. S4 from The PARP1 Inhibitor AZD5305 Impairs Ovarian Adenocarcinoma Progression and Visceral Metastases in Patient-derived Xenografts Alone and in Combination with Carboplatin
Authors: Dellavedova Giulia , Decio Alessandra , Formenti Laura , Albertella Mark R. , Wilson Joanne , Staniszewska Anna D. , Leo Elisabetta , Giavazzi Raffaella , Ghilardi Carmen , Bani Maria Rosa
Published: March 2023

Figure S4 shows AZD5305 target engagement
CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin A.
Published: March 2023

The interaction between neoplastic and stromal cells within a tumor mass plays an important role in cancer biology. However, it is challenging to distinguish between tumor and stromal cells in mesenchymal tumors because lineage-specific cell surface markers typically used in other cancers do not distinguish between the different cell subpopulations. Desmoid tumors consist of mesenchymal fibroblast-like cells driven by mutations stabilizing beta-catenin. Here we aimed to identify surface markers that can distinguish mutant cells from stromal cells to study tumor–stroma interactions. We analyzed colonies derived from single cells from human desmoid tumors using a high-throughput surface antigen screen, to characterize the mutant and nonmutant cells. We found that CD142 is highly expressed by the mutant cell populations and correlates with beta-catenin activity. CD142-based cell sorting isolated the mutant population from heterogeneous samples, including one where no mutation was previously detected by traditional Sanger sequencing. We then studied the secretome of mutant and nonmutant fibroblastic cells. PTX3 is one stroma-derived secreted factor that increases mutant cell proliferation via STAT6 activation. These data demonstrate a sensitive method to quantify and distinguish neoplastic from stromal cells in mesenchymal tumors. It identifies proteins secreted by nonmutant cells that regulate mutant cell proliferation that could be therapeutically.

Significance:

Distinguishing between neoplastic (tumor) and non-neoplastic (stromal) cells within mesenchymal tumors is particularly challenging, because lineage-specific cell surface markers typically used in other cancers do not differentiate between the different cell subpopulations. Here, we developed a strategy combining clonal expansion with surface proteome profiling to identify markers for quantifying and isolating mutant and nonmutant cell subpopulations in desmoid tumors, and to study their interactions via soluble factors.
Improving the Clinical Interpretation of Transcutaneous Carbon Dioxide and Oxygen Measurements in the Neonatal Intensive Care Unit
Authors: van Essen Tanja , Gangaram-Panday Norani H. , van Weteringen Willem , Goos Tom G. , Reiss Irwin K.M. , de Jonge Rogier C.J.
Published: March 2023

Introduction: Transcutaneous blood gas monitoring allows for continuous non-invasive evaluation of carbon dioxide and oxygen levels. Its use is limited as its accuracy is dependent on several factors. We aimed to identify the most influential factors to increase usability and aid in the interpretation of transcutaneous blood gas monitoring. Methods: In this retrospective cohort study, transcutaneous blood gas measurements were paired to arterial blood gas withdrawals in neonates admitted to the neonatal intensive care unit. The effects of patient-related, microcirculatory, macrocirculatory, respiratory, and sensor-related factors on the difference between transcutaneously and arterially measured carbon dioxide and oxygen values (ΔPCO2 and ΔPO2) were evaluated using marginal models. Results: A total of 1,578 measurement pairs from 204 infants with a median [interquartile range] gestational age of 273/7 [261/7–313/7] weeks were included. ΔPCO2 was significantly associated with the postnatal age, arterial systolic blood pressure, body temperature, arterial partial pressure of oxygen (PaO2), and sensor temperature. ΔPO2 was, with the exception of PaO2, additionally associated with gestational age, birth weight Z-score, heating power, arterial partial pressure of carbon dioxide, and interactions between sepsis and body temperature and sepsis and the fraction of inspired oxygen. Conclusion: The reliability of transcutaneous blood gas measurements is affected by several clinical factors. Caution is recommended when interpreting transcutaneous blood gas values with an increasing postnatal age due to skin maturation, lower arterial systolic blood pressures, and for transcutaneously measured oxygen values in the case of critical illness.
Evaluation of the Clinical Features and Laboratory Data of Patients with Severe Eosinophilic Asthma Classified as Super-Responders, Partial Responders, or Nonresponders to Mepolizumab Treatment: A Real-Life Study
Authors: Cakmak Mehmet Erdem , Öztop Nida , Yeğit Osman Ozan , Özdedeoğlu Özlem
Published: March 2023

Introduction: Mepolizumab is a treatment option in patients with severe eosinophilic asthma, which inhibits interleukin-5. The aim of this study was to evaluate the clinical features and laboratory data of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. Methods: In this retrospective real-life study, the clinical features and laboratory data were compared between groups of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. Results: Evaluation was made of a total of 55 patients, comprising 17 (30.9%) males and 38 (69.1%) females with a mean age of 51.28 ± 14.32 years. All the patients were receiving mepolizumab treatment for severe eosinophilic asthma, with 17 (30.9%) patients evaluated as super-responders, 26 (47.3%) as partial responders, and 12 (21.8%) as nonresponders. After mepolizumab treatment, there was a statistically significant decrease in asthma exacerbations, the number of oral corticosteroids (OCSs) used, the rate of hospitalization due to asthma attacks, and the eosinophil count (cells/µL) (p < 0.001, p < 0.001, p < 0.001, and <0.001, respectively). A statistically significant increase was determined in the forced expiratory volume in 1 s (FEV1) value (p = 0.010) and asthma control test (ACT) score (p < 0.001) after mepolizumab treatment. The baseline eosinophil count, eosinophil/lymphocyte ratio and FEV1 (%) values were significantly higher in the super-responder and partial responder groups (p < 0.001, p = 0.002, and p = 0.002, respectively). The baseline ACT score and the rate of chronic sinusitis with nasal polyps were significantly higher in the partial responder group (p = 0.004, p = 0.015, respectively). The rate of regular OCS use before mepolizumab treatment was significantly higher in the nonresponder group (p = 0.049). As a result of the receiver operating characteristics curve analysis, the blood eosinophil count (area under the curve [AUC]: 0.967, p < 0.001), eosinophil/lymphocyte ratio (AUC: 0.921, p < 0.001), and FEV1 (%) (AUC: 0.828, p = 0.002) were found to have diagnostic value in predicting the response to mepolizumab treatment in patients with severe eosinophilic asthma. Conclusion: Baseline eosinophil count, eosinophil/lymphocyte ratio, and FEV1 (%) were found to be important predictors of response to mepolizumab treatment. Further studies are needed to define the characterization of mepolizumab responders in the real world.
Increased Plasma Homocysteine Levels Are Associated with Left Ventricular Hypertrophy in Hypertensive Patients with Normal Renal Function
Authors: Zhang Lingyu , Wang Tingjun , Shen Yihua , Luo Li , Xu Guoyan , Xie Liangdi
Published: March 2023

Introduction: Renal function has an important bearing on plasma homocysteine levels. Plasma homocysteine is related to left ventricular hypertrophy (LVH). However, it remains unclear whether the association between plasma homocysteine levels and LVH is influenced by renal function. This study aimed to investigate relationships among left ventricular mass index (LVMI), plasma homocysteine levels, and renal function in a population from southern China. Methods: A cross-sectional study was performed in 2,464 patients from June 2016 to July 2021. Patients were divided into three groups based on gender-specific tertiles of homocysteine levels. LVMI ≥115 g/m2 for man or ≥95 g/m2 for woman was defined as LVH. Results: LVMI and the percentage of LVH were increased, while estimated glomerular filtration rate (eGFR) was decreased with the increase in homocysteine levels, both significantly. Multivariate stepwise regression analysis showed that eGFR and homocysteine were independently associated with LVMI in patients with hypertension. No correlation was observed between homocysteine and LVMI in patients without hypertension. Stratified by eGFR, further analysis confirmed homocysteine was independently associated with LVMI (β = 0.126, t = 4.333, p < 0.001) only in hypertensive patients with eGFR ≥90 mL/(min·1.73 m2), not with 60≤ eGFR <90 mL/(min·1.73 m2). Multivariate logistic regression indicated that in hypertensive patients with eGFR ≥90 mL/(min·1.73 m2), the patients in high tertile of homocysteine levels had a nearly twofold increased risk of occurring LVH compared with those in low tertile (high tertile: OR = 2.780, 95% CI: 1.945–3.975, p < 0.001). Conclusion: Plasma homocysteine levels were independently associated with LVMI in hypertensive patients with normal eGFR.
The Influence of Part-Time Occlusion Therapy on Control of Intermittent Exotropia: A Meta-Analysis of Randomized Controlled Trials
Authors: Song Desheng , Yang Mengting , Qian Jing , Chen Zhijun , Zhou Qing , Chen Juan
Published: March 2023

Background: Intermittent exotropia is the most prevalent subtype of exotropia in children. Part-time occlusion (PTO) as an anti-suppression therapy was applied for nonsurgical management of intermittent exotropia. Objective: The aim of the study was to compare the effectiveness of PTO therapy and observation in the treatment of intermittent exotropia. Method: An exhaustive search of the literature from PubMed, Embase, Web of Science, and Cochrane Library databases was carried out until July 2022. No language restrictions were applied. The literature was rigorously screened against eligibility criteria. Weighted mean differences and 95% confidence interval (CI) were calculated. Results: A total of 4 articles with 617 participants were included in this meta-analysis. Our pooled results showed that PTO exhibited superior effects compared to observation, with greater decrease in exotropia control at distance and near (MD = −0.38, 95% CI: −0.57 to −0.20, p < 0.001; MD = −0.36, 95% CI: −0.54 to −0.18, p < 0.001); patients subjected to PTO therapy had greater decrease in distance deviations (MD = −1.95, 95% CI: −3.13 to −0.76, p = 0.001), and there was greater improvement in near stereoacuity among the PTO group in comparison with the observation group (p < 0.001). Conclusions: The present meta-analysis indicated that PTO therapy showed a better effect in improving control and near stereopsis and decreasing distance exodeviation angle of children with intermittent exotropia in comparison with observation.
Prenatal Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Promising Way to Change the Impact of Cystic Fibrosis
Authors: Gómez-Montes Enery , Salcedo Lobato Enrique , Galindo Izquierdo Alberto , García Alcázar Diana , Villalain González Cecilia , Moral-Pumarega Maria Teresa , Bustos Lozano Gerardo , Luna-Paredes Carmen
Published: March 2023

Introduction: Cystic fibrosis (CF) is a potentially severe disease. The development of new therapies with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has been a great advance in the management of this condition because they improve the function of the faulty CFTR protein rather than palliate its consequences. CFTR modulator therapy improves pancreatic and lung function and, therefore, quality of life, with greater benefits the sooner treatment is started. For this reason, the use of these therapies is being approved for increasingly younger patients. Only two cases of pregnant women taking CFTR modulator therapy with CF fetuses have been reported, suggesting that it could resolve meconium ileus (MI) prenatally and delay/prevent other consequences of CF. Case Presentation: We report a case of a healthy pregnant patient who underwent CFTR modulator therapy with elexacaftor-tezacaftor-ivacaftor (ETI) in order to treat her fetus with CF (F508del homozygous CFTR mutation) and MI. Ultrasound findings suggestive of MI were observed at 24 weeks. Both parents were tested for CFTR mutations, and both were carriers of the F508del CFTR mutation. The fetus was diagnosed with CF by amniocentesis at 26+2 weeks. Maternal ETI therapy was initiated at 31+1 weeks, and no dilated bowel was observed at 39 weeks. There were no signs of bowel obstruction after birth. Maternal ETI treatment was continued during breastfeeding, with normal liver function. Immunoreactive trypsinogen in the newborn was 58.1 ng/mL, sweat chloride test was 80 mmol/L, and fecal elastase on the second day of life was 58 μg/g. Conclusion: Prenatal ETI treatment, as well as during breastfeeding, could solve, prevent, and/or delay CF complications.
Associations and Prognostic Significance of Fluctuations in Diabetic Retinopathy Severity in Eyes Treated for Diabetic Macular Edema
Authors: Cicinelli Maria Vittoria , Gregori Giulia , Rabiolo Alessandro , Tombolini Beatrice , Barresi Costanza , Pignatelli Francesco , Lattanzio Rosangela , Bandello Francesco
Published: March 2023

Introduction: The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to explore risk factors for proliferative DR (PDR). Methods: We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study Severity Scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses. Results: We included 111 eyes with a median follow-up of 44 months. Higher DRSS-AUC values (β = +0.03 DRSS DM for unitary DRSS/month increase, p = 0.01) and a higher number of anti-VEGF injections (β = +0.07 DRSS DM for injection, p = 0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR = 1.45 for unitary DRSS/month increase, p = 0.001) and wider DR severity fluctuations (HR = 22.35 4th quartile vs. 1st–3rd quartile of DRSS DM, p = 0.01) were risk factors for PDR. Conclusion: Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early.
Chromosomal Evolution of Suboscines: Karyotype Diversity and Evolutionary Trends in Ovenbirds (Passeriformes, Furnariidae)
Authors: Tura Victoria , Kretschmer Rafael , Sassi Francisco de Menezes Cavalcante , de Moraes Renata Luiza Rosa , Barcellos Suziane Alves , de Rosso Vitor Oliveira , de Souza Marcelo Santos , Cioffi Marcelo de Bello , Gunski Ricardo J. , Garnero Analía del Valle
Published: March 2023

Furnariidae (ovenbirds) is one of the most diversified families in the Passeriformes order and Suboscines suborder. Despite the great diversity of species, cytogenetic research is still in its early stages, restricting our knowledge of their karyotype evolution. We combined traditional and molecular cytogenetic analyses in three representative species, Synallaxis frontalis, Syndactyla rufosuperciliata, and Cranioleuca obsoleta, to examine the chromosomal structure and evolution of ovenbirds. Our findings revealed that all the species studied had the same diploid number (2n = 82). Differences in chromosomal morphology of some macrochromosomes indicate the presence of intrachromosomal rearrangements. Although the three species only had the 18S rDNA on one microchromosome pair, chromosomal mapping of six simple short repeats revealed a varied pattern of chromosome distribution among them, suggesting that each species underwent different repetitive DNA accumulation upon their divergence. The interspecific comparative genomic hybridization experiment revealed that the Furnariidae species investigated carry centromeric regions enriched in similar repetitive sequences, bolstering the Furnariidae family's karyotype conservation. Nonetheless, the outgroup species Turdus rufiventris (Turdidae) demonstrated an advanced stage of sequence divergence with hybridization signals that were almost entirely limited to a few microchromosomes. Overall, the findings imply that Furnariidae species have a high degree of chromosomal conservation, and we could also observe a differentiation of repetitive sequences in both Passeriformes suborders (Suboscines and Oscines).
Primary Effusion Lymphoma in an HIV-Negative Patient with Chronic Myeloid Leukemia Treated with Dasatinib
Authors: SahBandar Ivo N. , Sy Chandler B. , van den Akker Tayler , Kim David , Geyer Julia T. , Chadburn Amy , Cesarman Ethel , Inghirami Giorgio , Allan John N , Siddiqui Momin T. , Ouseph Madhu M.
Published: March 2023

Introduction: Primary effusion lymphoma (PEL) is a malignant lymphomatous effusion, which by definition is Kaposi sarcoma herpesvirus/human herpesvirus 8-positive. PEL typically occurs in HIV-infected patients but can also occur in HIV-negative individuals, including in organ transplant recipients. Tyrosine kinase inhibitors (TKIs) are currently the standard of care for patients with chronic myeloid leukemia (CML), BCR::ABL1-positive. Although TKIs are extremely effective in treating CML, they alter T-cell function by inhibiting peripheral T-cell migration and altering T-cell trafficking and have been associated with the development of pleural effusions. Case Presentation: We report a case of PEL in a young, relatively immunocompetent patient with no history of organ transplant receiving dasatinib for CML, BCR::ABL1-positive. Discussion: We hypothesize that the loss of T-cell function secondary to TKI therapy (dasatinib) may have resulted in the unchecked cellular proliferation of Kaposi sarcoma herpesvirus (KSHV)-infected cells, leading to the emergence of a PEL. We recommend cytologic investigation and KSHV testing in patients being treated with dasatinib for CML who present with persistent or recurrent effusions.
Myeloid Proliferations Associated with Down Syndrome: Clinicopathologic Characteristics of Forty Cases from Five Large Academic Institutions
Authors: van den Akker Tayler A. , Liu Yen-Chun , Liu Huifei , Chapman Jennifer , Levine Jennifer M. , Weinberg Olga K. , Geyer Julia T.
Published: March 2023

Introduction: The incidence of myelodysplastic syndrome and acute myeloid leukemia is significantly increased in children with Down syndrome (DS). Within the revised 2016 WHO edition, these entities are jointly classified as myeloid leukemia associated with DS (ML-DS). Additionally, infants with DS may develop transient abnormal myelopoiesis (TAM) which is histomorphologically similar to ML-DS. While TAM is self-limiting, it is associated with an increased risk of subsequently developing ML-DS. Differentiating TAM and ML-DS is challenging but clinically critical. Methods: We performed a retrospective review of ML-DS and TAM cases collected from five large academic institutions in the USA. We assessed clinical, pathological, immunophenotypical, and molecular features to identify differentiating criteria. Results: Forty cases were identified: 28 ML-DS and 12 TAM. Several features were diagnostically distinct, including younger age in TAM (p < 0.05), as well as presentation with clinically significant anemia and thrombocytopenia in ML-DS (p < 0.001). Dyserythropoiesis was unique to ML-DS, as well as structural cytogenetic abnormalities aside from the constitutional trisomy 21. Immunophenotypic characteristics of TAM and ML-DS were indistinguishable, including the aberrant expression of CD7 and CD56 by the myeloid blasts. Discussion: The findings of the study confirm marked biological similarities between TAM and ML-DS. At the same time, several significant clinical, morphological, and genetic differences were observed between TAM and ML-DS. The clinical approach and the differential diagnosis between these entities are discussed in detail.