bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza presentations and use of neuraminidase inhibitors by Australian general practice registrars: a cross-sectional analysis from the ReCEnT study
Authors: Moller Chris , van Driel Mieke , Davey Andrew , Tapley Amanda , Holliday Elizabeth G , Fielding Alison , Davis Joshua , Ball Jean , Ralston Anna , Turner Alexandria , Mulquiney Katie , Spike Neil , Fitzgerald Kristen , Magin Parker
Published: June 2023

Objective

This study aims to establish prevalence and associations of (1) influenza and influenza-like illness (IILI) presentations to Australian general practice (GP) registrars (trainees) and (2) the use of neuraminidase inhibitors (NAIs) by GP registrars for new presentations of IILI, for the 10 years leading up to the COVID-19 pandemic in Australia (2010–2019).

Design

This was a cross-sectional analysis of the Registrar Clinical Encounters in Training ongoing inception cohort study of the in-consultation experience and clinical behaviours of GP registrars. Data are collected by individual registrars three times (from 60 consecutive consultations each time) at 6 monthly intervals. Data include diagnoses/problems managed and medicines prescribed, along with multiple other variables. Univariate and multivariable logistic regression was used to establish associations of registrars seeing patients with IILI and of prescribing NAIs for IILI.

Setting

Teaching practices within the Australian general practitioner specialist vocational training programme. Practices were located in five of the six Australian states (plus one territory).

Participants

GP registrars in each of their three compulsory 6-month GP training terms.

Results

From 2010 to 2019, 0.2% of diagnoses/problems seen by registrars were IILI. 15.4% of new IILI presentations were prescribed an NAI. IILI diagnoses were less likely in younger (0–14) and older (65+) age groups, and more likely in an area of higher socioeconomic advantage. There was considerable variation in NAI prescribing between regions. There was no significant association of prescribing NAIs with age or Aboriginal and/or Torres Strait Islander patients.

Conclusions

IILI presentations were more likely among working-age adults and not among those groups at higher risk. Similarly, high-risk patient groups who would benefit most were not more likely to receive NAIs. The epidemiology and management of IILI has been distorted by the COVID-19 pandemic, but the burden of influenza in vulnerable populations must not be overlooked. Appropriately targeted antiviral therapy with NAIs influences outcomes for vulnerable patients. General practitioners manage the majority of IILI in Australia, and understanding GP IILI presentation and NAI prescribing patterns is a key first step to enabling sound and rational prescribing decisions for better patient outcomes.
Prevalence and risk factors of suicide and suicidal ideation in veterans who served in the British Armed Forces: a systematic review
Authors: Randles Rebecca , Burroughs H , Green N , Finnegan A
Published: June 2023

Introduction

Research into the factors resulting in suicide in the military veteran population has yet to reach a consensus. Available research is concentrated on a small number of countries, and there is a lack of consistency with contradictory conclusions. The USA has produced a significant amount of research in a country where suicide is identified as a national health crisis, but in the UK, there is little research regarding veterans from the British Armed Forces.

Methods

This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Corresponding literature searches were conducted in PsychINFO, MEDLINE and CINAHL. Articles that discussed suicide, suicidal ideation, prevalence or risk factors among British Armed Forces veterans were eligible for review. A total of 10 articles met the inclusion criteria and were analysed.

Results

Veterans' suicide rates were found to be comparable to those of the general UK population. The method of suicide used was most commonly found to be hanging and strangulation. Firearms was recorded in 2% of suicide cases. Demographic risk factors were often contradictory with some research stating that there was risk in older veterans and some in younger. However, female veterans were found to be at higher risk than female civilians. Those who had deployed on combat operations were at lower risk of suicide, with research finding that veterans who took longer to seek help for mental health (MH) difficulties reported more suicidal ideation.

Conclusions

Peer-reviewed research publications have revealed that UK veteran suicide prevalence is broadly comparable to the general population while highlighting differences across international armed forces. Veteran demographics, service history, transition and MH have all been identified as potential risk factors of suicide and suicidal ideation. Research has also indicated that female veterans are at higher risk than that of their civilian counterparts due to veterans being predominantly male; this could skew results and requires investigation. Current research is limited and further exploration of suicide prevalence and risk factors in the UK veteran population is required.
Concocting of FeO nanoparticles by coalescence of metal oxides for supercapacitor applications
Authors: Kiruthika R. A. , Shanmugapriya B. , Kannagi K. , Sankari P. , Pavithra N. , Mahanim Sarif M. , Asla A. Al-Zaharani
Published: June 2023

Iron oxide (FeO) nanoparticles have gained considerable interest from researchers over the past few decades and have a massive effect on wave absorption materials, magnetic fluid, adsorbent, and a variety of industrial applications. In this study, ferric nitrate, sodium hydroxide, and ammonium hydroxide coalesced to form FeO nanoparticles using the chemical co-precipitation approach. X-ray powder diffraction (XRD), scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), UV-VIS analysis, Photoluminesence (PL) spectrum analysis, and electrochemical measurements were used to characterize FeO nanoparticles. As per XRD, the sample’s crystallite size was 22.63[Formula: see text]nm and 22.64[Formula: see text]nm after it was annealed at 300∘C and 400∘C, respectively. Utilizing XRD, the diffraction patterns were seen. The particles appear to have a fine surface and smooth shape, as seen by SEM photographs. For the detection of FeO nanoparticles, optical and electrochemical examinations were carried out.
Multibiometric Images Encryption Method Based on Fast Fourier Transform and Hyperchaos
Authors: Ding Cong , Xue Ru , Niu Shiming
Published: June 2023

Biometric images are an important means of personal identity verification and identification and are related to personal privacy and property security. To address the problems of poor security and low image reconstruction quality in the encryption and transmission of multibiometric images, a multibiometric images encryption method based on Fast Fourier Transform (FFT) and hyperchaotic system is proposed. First, the FFT is used to transform the multibiometric images from spatial to frequency domain. Then, the initial values of the hyperchaotic Lorenz system are generated using a one-dimensional chaotic logistic system to generate the key stream. Combined with the recoding rules of matrix reconstruction and scrambling without repetition of using multimatrix, the multiple matrices of amplitude and phase in the transform domain are reconstructed to be multiple RGB three-channel color images by using the inverse fast Fourier transform. Then, we combine the two diffusion methods of additive mode and Galois domain diffusion on each color channel to perform confusion and diffusion. Finally, the multiple grayscale images are encrypted to become multiple color images. The experimental results demonstrate that the method can effectively defend against various attacks. In addition, it solves the problem of low reconstruction accuracy that exists in the field of multiple images security.
Spatiotemporal Patterns of a Host-Generalist Parasitoid Reaction–Diffusion Model
Authors: Ma Zhan-Ping , Cheng Zhi-Bo , Liang Wei
Published: June 2023

In this paper, we study a delayed host-generalist parasitoid diffusion model subject to homogeneous Dirichlet boundary conditions, where generalist parasitoids are introduced to control the invasion of the hosts. We construct an explicit expression of positive steady-state solution using the implicit function theorem and prove its linear stability. Moreover, by applying feedback time delay [Formula: see text] as the bifurcation parameter, spatially inhomogeneous Hopf bifurcation near the positive steady-state solution is proved when [Formula: see text] is varied through a sequence of critical values. This finding implies that feedback time delay can induce spatially inhomogeneous periodic oscillatory patterns. The direction of spatially inhomogeneous Hopf bifurcation is forward when parameter [Formula: see text] is sufficiently large. We present numerical simulations and solutions to further illustrate our main theoretical results. Numerical simulations show that the period and amplitude of the inhomogeneous periodic solution increase with increasing feedback time delay. Our theoretical analysis results only hold for parameter [Formula: see text] when it is sufficiently close to 1, whereas numerical simulations suggest that spatially inhomogeneous Hopf bifurcation still occurs when [Formula: see text] is larger than 1 but not sufficiently close to 1.
Moving Towards Sustainable Development: Can Narrowing Income Inequality Facilitate Green Growth in China?
Authors: Zhao Jun , Dong Kangyin , Taghizadeh-Hesary Farhad
Published: June 2023

To test the dynamical linkage between inequality and green growth in China, the green growth index is gauged and the inequality–green growth nexus is detected by employing panel data from 2004 to 2017. The concrete impact channel of urbanisation is further tested in the inequality–growth nexus. The primary findings are presented as follows: (i) China’s green growth is improving, and widening income gap is reversing this active effect; (ii) the inhibiting effect of income inequality on green growth is mainly manifested in the promoting impact of inequality on economic growth and its deteriorative impacts on households’ wellbeing and the ecological environment; and (iii) the intermediary transmission role of urbanisation construction has been strongly proved; in other words, the widening income gap will further optimise the green and clean economy by boosting the construction of urbanisation. Following the above three findings, a series of policy recommendations are presented.
Critical raw materials associated with the lateritic bauxite and red mud in West Kalimantan, Indonesia
Authors: Hakim Andy Yahya Al , Sunjaya Dedi , Hede Arie Naftali Hawu , Indriati Teti , Hidayat Taufiq
Published: June 2023

The Western Indonesia Bauxite Province in Kalimantan is a lateritic bauxite region with a complex history and poorly known sustainable metal contents within the bauxite residue. Bauxite residue produced using the Bayer process contains, notably, scandium. We present new geochemical, mineralogical and geological data from the lateritic bauxite and red mud from the active mine and deposit, which allow us to investigate the behaviour of critical elements during weathering. The geochemical analysis and translated isocon results have shown that the content of scandium in red mud is higher than the average concentration of crustal rocks and is concentrated in the ferrite layer and bauxite residue. A positive correlation between the existence of iron oxyhydroxide mineral in the residual iron-rich layer and red muds with the rare earth elements (REEs) and scandium concentrations may be interpreted as a scavenging effect of mobile REEs. The weathering and leaching processes in bauxite allows the adsorption of the trivalent scandium cation (Sc
3+
) on goethite and are followed by ionic substitution with other trivalent cations in crystals of hematite. The study illustrates the importance of understanding processes during weathering and laterization for geochemical processes and REE exploration in tropical areas.

Supplementary material:
Material A, (A) Mineralogical profile of the bauxite, ferrite, and tonalite in Tayan and Mempawah, (B) Ternary diagram of bauxite and their parent rocks, (C) Trace element ratios in bauxite; Material B, Spearman's correlation rank of bauxite and associated rocks from Tayan mine (
n
 = 35); Material C, (A) XRD patterns of representative samples from the Tayan mine and Mempawah deposit, West Kalimantan, (B) Typical normal (left) and continuum (right) removed reflectance spectral curves of samples are available at
https://doi.org/10.6084/m9.figshare.c.6689139

Thematic collection:
This article is part of the Geochemical processes related to mined, milled, or natural metal deposits collection available at:
https://www.lyellcollection.org/topic/collections/geochemical-processes-related-to-mined-milled-or-natural-metal-deposits
Interactive Murals: New Interactions and Educational Opportunities for Diverse Youth
Authors: Bustos Alyshia , Chacon Nanibah , Buechley Leah
Published: June 2023

Interactive murals integrate electronics into traditional murals to create a new kind of public art as well as a new kind of large-scale and community-situated technology. This article introduces interactive murals along with a set of activities designed to engage young people in technology and the arts. We describe the process and outcome of workshops in which a muralist, two interaction design researchers, and a group of diverse teenagers designed and built a large-scale interactive mural on the exterior wall of a local building.
Testosterone-associated blood pressure dysregulation in women with androgen excess polycystic ovary syndrome
Authors: Stone Tori , Yanes Cardozo Licy L. , Oluwatade Toni N. , Leone Cheryl A. , Burgos Melanie , Okifo Faith , Pal Lubna , Reckelhoff Jane F. , Stachenfeld Nina. S.
Published: June 2023

Here we present evidence for an important role of testosterone in baroreflex control of blood pressure and renal responses to baroreceptor unloading in women with a common, high-risk androgen excess polycystic ovary syndrome (AE-PCOS) phenotype. These data indicate a direct effect of testosterone on the vascular system of women with AE-PCOS independent of body mass index (BMI) and insulin-resistant (IR). Our study indicates that hyperandrogenemia is a central underlining mechanism of heightened cardiovascular risk in women with PCOS.
Application of 4-D ultrasound-derived regional strain and proteomics analysis in Nkx2-5-deficient male mice
Authors: Damen Frederick W. , Gramling Daniel P. , Ahlf Wheatcraft Dorothy , Wilpan Robert Y. , Costa Mauro W. , Goergen Craig J.
Published: June 2023

A multimodal approach using both four-dimensional ultrasound (4DUS) and regional proteomics can help enhance our investigations of murine cardiomyopathy models. We present unique 4DUS-derived strain maps that provide a framework for both cross-sectional and longitudinal analysis of spatiotemporal cardiac function. We further detail and demonstrate an innovative 4DUS-proteomics z-score-based linear regression method, aimed at characterizing relationships between regional cardiac dysfunction and underlying mechanisms of disease.
Physiology of intracellular calcium buffering
Authors: Eisner David , Neher Erwin , Taschenberger Holger , Smith Godfrey
Published: June 2023

Calcium signaling underlies much of physiology. Almost all the Ca2+ in the cytoplasm is bound to buffers, with typically only ∼1% being freely ionized at resting levels in most cells. Physiological Ca2+ buffers include small molecules and proteins, and experimentally Ca2+ indicators will also buffer calcium. The chemistry of interactions between Ca2+ and buffers determines the extent and speed of Ca2+ binding. The physiological effects of Ca2+ buffers are determined by the kinetics with which they bind Ca2+ and their mobility within the cell. The degree of buffering depends on factors such as the affinity for Ca2+, the Ca2+ concentration, and whether Ca2+ ions bind cooperatively. Buffering affects both the amplitude and time course of cytoplasmic Ca2+ signals as well as changes of Ca2+ concentration in organelles. It can also facilitate Ca2+ diffusion inside the cell. Ca2+ buffering affects synaptic transmission, muscle contraction, Ca2+ transport across epithelia, and the killing of bacteria. Saturation of buffers leads to synaptic facilitation and tetanic contraction in skeletal muscle and may play a role in inotropy in the heart. This review focuses on the link between buffer chemistry and function and how Ca2+ buffering affects normal physiology and the consequences of changes in disease. As well as summarizing what is known, we point out the many areas where further work is required.
Noncollinear Equilibrium Points in CRTBP with Yukawa-Like Corrections to Newtonian Potential under an Oblate Primary Model
Authors: Idrisi M. Javed , Haruna Sunusi , Eshetie Teklehaimanot
Published: June 2023

This study is about the effects of Yukawa-like corrections to Newtonian potential on the existence and stability of noncollinear equilibrium points in a circular restricted three-body problem when bigger primary is an oblate spheroid. It is observed that ∂x0/∂λ = 0 = ∂y0/∂λ at λ0 = 1/2, so we have a critical point λ0 = 1/2 at which the maximum and minimum values of x0 and y0 can be obtained, where λ ∈ (0, ∞) is the range of Yukawa force and (x0, y0) are the coordinates of noncollinear equilibrium points. It is found that x0 and y0 are increasing functions in λ in the interval 0 < λ < λ0 and decreasing functions in λ in the interval λ0 < λ < ∞ for all α ∈ α+. On the other hand, x0 and y0 are decreasing functions in λ in the interval 0 < λ < λ0 and increasing functions in λ in the interval λ0 < λ < ∞ for all α ∈ α−, where α ∈ (−1, 1) is the coupling constant of Yukawa force to gravitational force. The noncollinear equilibrium points are found linearly stable for the critical mass parameter β0, and it is noticed that ∂β0/∂λ = 0 at

λ

∗

 = 1/3; thus, we got another critical point which gives the maximum and minimum values of β0. Also, ∂β0/∂λ > 0 if 0 < λ < 

λ

∗

and ∂β0/∂λ < 0 if

λ

∗

 < λ < ∞ for all α ∈ α−, and ∂β0/∂λ < 0 if 0 < λ < 

λ

∗

and ∂β0/∂λ > 0 if

λ

∗

 < λ < ∞ for all α ∈ α+. Thus, the local minima for β0 in the interval 0 < λ < 

λ

∗

can also be obtained.
[Retracted] Parameter Optimization and Performance Analysis of Composite Substance That Can Prevent Burning Based on Machine Learning
Authors: Qiu-yu Zheng , Huahao Yang , Tianming Wang , Lihui Dong , Rui Han
Published: June 2023

In the past 30 years, a substance that can prevent burning has played an important role in reducing the loss of life and property caused by fire. At present, the total amount of antibaking agent is second only to plasticizer and various plastic additives in the world. With an average annual growth rate of 0.5% from 2019 to 2021. The fire protection industry is a regulatory industry and a globally competitive industry. Therefore, the entry into force and gradual improvement of relevant laws and regulations at home and abroad will affect the pattern of the whole fire protection industry. China’s “Twelfth Five‐Year Plan” will bring a substance that can prevent burning into key development industries and form a strategic alliance for technological innovation of green substance that can prevent burning industries. It provides a policy platform for the development of a substance that can prevent burning in industry. Firstly, we introduce several common a substance that can prevent burnings, then we use machine learning method to establish prediction model and to analyze the performance of composite combustibles. And draw the conclusion: composite material is better than the other two composites; among the six machine learning algorithms, the gradient boosting regression (GBR) model has the best prediction ability, followed by the extra tree regressor (ETR) model and the random forest regressor (RFR) model. Compared with the above three integrated algorithms, Ridge, Ada Boost regressor (ABR), and Lasso regression algorithms have relatively poor prediction results.
Realtime Vehicle Tracking Method Based on YOLOv5 + DeepSORT
Authors: Lin Lixiong , He Hongqin , Xu Zhiping , Wu Dongjie
Published: June 2023

In actual traffic scenarios, the environment is complex and constantly changing, with many vehicles that have substantial similarities, posing significant challenges to vehicle tracking research based on deep learning. To address these challenges, this article investigates the application of the DeepSORT (simple online and realtime tracking with a deep association metric) multitarget tracking algorithm in vehicle tracking. Due to the strong dependence of the DeepSORT algorithm on target detection, a YOLOv5s_DSC vehicle detection algorithm based on the YOLOv5s algorithm is proposed, which provides accurate and fast vehicle detection data to the DeepSORT algorithm. Compared to YOLOv5s, YOLOv5s_DSC has no more than a 1% difference in optimal mAP0.5 (mean average precision), precision rate, and recall rate, while reducing the number of parameters by 23.5%, the amount of computation by 32.3%, the size of the weight file by 20%, and increasing the average processing speed of each image by 18.8%. After integrating the DeepSORT algorithm, the processing speed of YOLOv5s_DSC + DeepSORT reaches up to 25 FPS, and the system exhibits better robustness to occlusion.
Clinical Outcomes with Extended Depth of Focus Intraocular Lenses in Cases in Which Multifocal Lenses Are Not Primarily Recommended
Authors: Álvarez-García María Teresa , Fuente-García Carlota , Muñoz-Puyol Cristina , Piñero David P.
Published: June 2023

Purpose. The purpose of the study is to evaluate the visual and patient‐reported outcomes of patients undergoing cataract surgery with implantation of an extended depth of focus (EDOF) intraocular lens (IOL) who were not primarily good candidates for multifocal IOL implantation. Methods. Retrospective analysis of data from 30 eyes (23 patients) undergoing cataract surgery with implantation of one of two EDOF IOLs (follow‐up: 37.9 ± 16.2 months) and prospective observational study including 106 eyes (78 patients) implanted with one of 6 different EDOF models (follow‐up: 8.0 ± 7.7 months). Patients recruited had one of the following conditions: monofocal IOL implanted in the fellow eye, previous corneal refractive surgery, mild and nonprogressive maculopathy or glaucoma, age > 75 years, amblyopia, or previous vitrectomy. Results. In the retrospective phase, significant improvements were found in uncorrected distance (UDVA), corrected distance (CDVA), and corrected near visual acuity (CNVA) (p ≤ 0.013), with a nonsignificant trend to improvement in uncorrected near visual acuity (UNVA). A total of 90% of patients were completely to moderately satisfied with the outcome achieved. In the prospective phase, significant improvements were found in UDVA, CDVA, UNVA, and CNVA (p ≤ 0.032), with a total of 85.5% of patients being completely to moderately satisfied (dissatisfaction 3.3%). In both phases, extreme difficulties were only reported by a limited percentage of patients for performing some near vision activities. Conclusions. EDOF IOLs seem to be a viable option for providing an efficient visual rehabilitation with good levels of patient satisfaction and spectacle independence associated in patients that are not primarily good candidates for multifocal IOL implantation.
N
6-methyladenosine Modification of FZR1 mRNA Promotes Gemcitabine Resistance in Pancreatic Cancer
Authors: Su Jiachun , Li Rui , Chen Ziming , Liu Shaoqiu , Zhao Hongzhe , Deng Shuang , Zeng Lingxing , Xu Zilan , Zhao Sihan , Zhou Yifan , Li Mei , He Xiaowei , Liu Ji , Xue Chunling , Bai Ruihong , Zhuang Lisha , Zhou Quanbo , Zhang Shaoping , Chen Rufu , Huang Xudong , Lin Dongxin , Zheng Jian , Zhang Jialiang
Published: June 2023

The therapeutic options for treating pancreatic ductal adenocarcinoma (PDAC) are limited, and resistance to gemcitabine, a cornerstone of PDAC chemotherapy regimens, remains a major challenge. N6-methyladenosine (m6A) is a prevalent modification in mRNA that has been linked to diverse biological processes in human diseases. Herein, by characterizing the global m6A profile in a panel of gemcitabine-sensitive and gemcitabine-insensitive PDAC cells, we identified a key role for elevated m6A modification of the master G0–G1 regulator FZR1 in regulating gemcitabine sensitivity. Targeting FZR1 m6A modification augmented the response to gemcitabine treatment in gemcitabine-resistant PDAC cells both in vitro and in vivo. Mechanistically, GEMIN5 was identified as a novel m6A mediator that specifically bound to m6A-modified FZR1 and recruited the eIF3 translation initiation complex to accelerate FZR1 translation. FZR1 upregulation maintained the G0–G1 quiescent state and suppressed gemcitabine sensitivity in PDAC cells. Clinical analysis further demonstrated that both high levels of FZR1 m6A modification and FZR1 protein corresponded to poor response to gemcitabine. These findings reveal the critical function of m6A modification in regulating gemcitabine sensitivity in PDAC and identify the FZR1–GEMIN5 axis as a potential target to enhance gemcitabine response.

Significance:

Increased FZR1 translation induced by m6A modification engenders a gemcitabine-resistant phenotype by inducing a quiescent state and confers a targetable vulnerability to improve treatment response in PDAC.
Nanoparticle-Based Combination Therapy Enhances Fulvestrant Efficacy and Overcomes Tumor Resistance in ER-Positive Breast Cancer
Authors: Li Bozhao , Qi Feilong , Zhu Fei , Lu Zefang , Wang Meiqi , Chu Tianjiao , Wu Suying , Wei Jingyan , Song Zhenchuan , Sukumar Saraswati , Zhang Cheng , Xu Jiangfei , Li Suping , Nie Guangjun
Published: June 2023

Nanoparticles (NP) spanning diverse materials and properties have the potential to encapsulate and to protect a wide range of therapeutic cargos to increase bioavailability, to prevent undesired degradation, and to mitigate toxicity. Fulvestrant, a selective estrogen receptor degrader, is commonly used for treating patients with estrogen receptor (ER)–positive breast cancer, but its broad and continual application is limited by poor solubility, invasive muscle administration, and drug resistance. Here, we developed an active targeting motif-modified, intravenously injectable, hydrophilic NP that encapsulates fulvestrant to facilitate its delivery via the bloodstream to tumors, improving bioavailability and systemic tolerability. In addition, the NP was coloaded with abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), to prevent the development of drug resistance associated with long-term fulvestrant treatment. Targeting peptide modifications on the NP surface assisted in the site-specific release of the drugs to ensure specific toxicity in the tumor tissues and to spare normal tissue. The NP formulation (PPFA-cRGD) exhibited efficient tumor cell killing in both in vitro organoid models and in vivo orthotopic ER-positive breast cancer models without apparent adverse effects, as verified in mouse and Bama miniature pig models. This NP-based therapeutic provides an opportunity for continual and extensive clinical application of fulvestrant, thus indicating its promise as a treatment option for patients with ER-positive breast cancer.

Significance:

A smart nanomedicine encapsulating fulvestrant to improve its half-life, bioavailability, and tumor-targeting and coloaded with CDK4/6 inhibitor abemaciclib to block resistance is a safe and effective therapy for ER-positive breast cancer.
Data from Adavosertib Enhances Antitumor Activity of Trastuzumab Deruxtecan in HER2-Expressing Cancers
Authors: DiPeri Timothy P. , Evans Kurt W. , Raso Maria Gabriela , Zhao Ming , Rizvi Yasmeen Q. , Zheng Xiaofeng , Wang Bailiang , Kirby Bryce P. , Kong Kathleen , Kahle Michael , Yap Timothy A. , Dumbrava Ecaterina E. , Ajani Jaffer A. , Fu Siqing , Keyomarsi Khandan , Meric-Bernstam Funda
Published: June 2023

AbstractPurpose:
Cyclin E (CCNE1) has been proposed as a biomarker of sensitivity to adavosertib, a Wee1 kinase inhibitor, and a mechanism of resistance to HER2-targeted therapy.
Experimental Design:
Copy number and genomic sequencing data from The Cancer Genome Atlas and MD Anderson Cancer Center databases were analyzed to assess ERBB2 and CCNE1 expression. Molecular characteristics of tumors and patient-derived xenografts (PDX) were assessed by next-generation sequencing, whole-exome sequencing, fluorescent in situ hybridization, and IHC. In vitro, CCNE1 was overexpressed or knocked down in HER2+ cell lines to evaluate drug combination efficacy. In vivo, NSG mice bearing PDXs were subjected to combinatorial therapy with various treatment regimens, followed by tumor growth assessment. Pharmacodynamic markers in PDXs were characterized by IHC and reverse-phase protein array.
Results:
Among several ERBB2-amplified cancers, CCNE1 co-amplification was identified (gastric 37%, endometroid 43%, and ovarian serous adenocarcinoma 41%). We hypothesized that adavosertib may enhance activity of HER2 antibody–drug conjugate trastuzumab deruxtecan (T-DXd). In vitro, sensitivity to T-DXd was decreased by cyclin E overexpression and increased by knockdown, and adavosertib was synergistic with topoisomerase I inhibitor DXd. In vivo, the T-DXd + adavosertib combination significantly increased γH2AX and antitumor activity in HER2 low, cyclin E amplified gastroesophageal cancer PDX models and prolonged event-free survival (EFS) in a HER2-overexpressing gastroesophageal cancer model. T-DXd + adavosertib treatment also increased EFS in other HER2-expressing tumor types, including a T-DXd–treated colon cancer model.
Conclusions:
We provide rationale for combining T-DXd with adavosertib in HER2-expressing cancers, especially with co-occuring CCNE1 amplifications.
Table S1 from An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression
Authors: Indeglia Alexandra , Leung Jessica C. , Miller Sven A. , Leu Julia I-Ju , Dougherty James F. , Clarke Nicole L. , Kirven Nicole A. , Shao Chunlei , Ke Lei , Lovell Scott , Barnoud Thibaut , Lu David Y. , Lin Cindy , Kannan Toshitha , Battaile Kevin P. , Yang Tyler Hong Loong , Batista Oliva Isabela , Claiborne Daniel T. , Vogel Peter , Liu Lijun , Liu Qin , Nefedova Yulia , Cassel Joel , Auslander Noam , Kossenkov Andrew V. , Karanicolas John , Murphy Maureen E.
Published: June 2023

RNA-seq of top genes identified in Y107H vs WT LCLs, related to Figure 2.
Maternal, Perinatal, and Postnatal Predisposing Factors of Hearing Loss in Full-Term Children: A Matched Case-Control Study
Authors: Tsao Pei-Chen , Lin Hung-Chih , Chiu Hsiao-Yu , Chang Yu-Chia
Published: June 2023

Introduction: Studies on risk factors for childhood hearing loss (HL) are usually based on questionnaires or small sample sizes. We conducted a nationwide population-based case-control study to comprehensively analyze the maternal, perinatal, and postnatal risk factors for HL in full-term children. Methods: We retrieved data from three nationwide databases related to maternal characteristics, perinatal comorbidities, and postnatal characteristics and adverse events. We used 1:5 propensity score matching to include 12,873 full-term children with HL and 64,365 age-, sex-, and enrolled year-matched controls. Conditional logistic regression was used to evaluate the risk factors for HL. Results: Among the various maternal factors, maternal HL (adjusted odds ratio [aOR]: 8.09, 95% confidence interval [95% CI]: 7.16–9.16) and type 1 diabetes (aOR: 3.79, 95% CI: 1.98–7.24) had the highest odds of childhood hearing impairment. The major perinatal risk factors for childhood hearing impairment included ear malformations (aOR: 58.78, 95% CI: 37.5–92.0) and chromosomal anomalies (aOR: 6.70, 95% CI: 5.25–8.55), and the major postnatal risk factors included meningitis (aOR: 2.08, 95% CI: 1.18–3.67) and seizure (aOR: 3.71, 95% CI: 2.88–4.77). Other factors included acute otitis media, postnatal ototoxic drug use, and congenital infections. Conclusions: Many risk factors for childhood HL identified in our study are preventable, such as congenital infection, meningitis, ototoxic drug use, and some maternal comorbidities. Accordingly, more effort is required to prevent and control the severity of maternal comorbidities during pregnancy, initiate genetic diagnostic evaluation for high-risk children, and aggressive screening for neonatal infections.
Estrogen Receptor Beta Mediates the Dipsogenic Effect of Estradiol in Ovariectomized Female Rats
Authors: Santollo Jessica , Edwards Andrea A.
Published: June 2023

Introduction: Although the fluid inhibitory effects of estradiol are well characterized, a dipsogenic role of the hormone was recently identified. In ovariectomized (OVX) rats, unstimulated water intake, in the absence of food, was increased after estradiol treatment. Methods: The goals for these experiments were to further characterize the fluid enhancing effects of estradiol by determining the estrogen receptor subtype mediating the dipsogenic effect, examining saline intake, and testing for a dipsogenic effect of estradiol in male rats. Results: Pharmacological activation of estrogen receptor beta (ERβ) increased water intake, in the absence of food, and was associated with changes in postingestive feedback signals. Surprisingly, activation of ERα reduced water intake even in the absence of food. A follow-up study demonstrated that when food was available, co-activation of ERα and ERβ reduced water intake, but when food was not available water intake was increased. In addition, in OVX rats, estradiol increased saline intake through changes in postingestive and orosensory feedback signals. Finally, although estradiol decreased water intake in male rats with access to food, estradiol had no effect on water intake in the absence of food. Conclusions: These results demonstrate that the dipsogenic effect is mediated by ERβ, the fluid enhancing effects of estradiol generalize to saline, and is limited to females, which implies that a feminized brain is necessary for estradiol to increase water intake. These findings will aid in guiding future studies focused on elucidating the neuronal mechanisms that allow estradiol to both increase and decrease fluid intake.
Comparison of the Intrableb Characteristics of Anterior Segment Optical Coherence Tomography Imaging in Trabeculectomy according to Amniotic Membrane Transplantation
Authors: Moon Sangwoo , Kim Jinmi , Lee Jiwoong
Published: June 2023

Introduction: The purpose of this study was to compare the characteristics of filtering bleb with anterior segment optical coherence tomography (AS-OCT) according to amniotic membrane transplantation (AMT). Methods: One hundred and sixteen eyes of 103 glaucoma patients who underwent trabeculectomy with (AMT group; 85 eyes) or without AMT (control group; 31 eyes) were included. Intrableb parameters were evaluated with AS-OCT. Surgical success was defined as an intraocular pressure (IOP) ≤18 mm Hg and IOP reduction ≥20% without medication at the time of AS-OCT examination. Logistic regression analyses were performed to determine factors associated with IOP control. Results: In the eyes with successful IOP control, the fluid-filled space area, score, and height were greater for the AMT group than the control group (all ps < 0.001), while stripping layer thickness was greater and bleb wall reflectivity was lower for the control group than the AMT group (all ps < 0.001). Surgical success in the AMT group was associated with greater fluid-filled space score, lower bleb wall reflectivity, and microcyst formation (odds ratio [OR] = 8.016, 0.913, and 16.202, respectively, all ps ≤ 0.041). Lower bleb wall reflectivity alone was associated with surgical success in the control group (OR = 0.815, p = 0.019). Conclusion: The extent of the fluid-filled space was associated with successful IOP control after trabeculectomy with AMT. Hyporeflective bleb wall was associated with successful IOP control in AMT and control groups.
Impact of Single Nucleotide Polymorphisms of the Promoter of the TNF Gene on Adalimumab Treatment Responses in Hidradenitis Suppurativa
Authors: Argyropoulou Maria , Trigoni Anastasia , Kaffenberger Jessica , Stergianou Dimitra , Damoraki Georgia , Mingiani Elissavet , Micha Styliani , Krispinsky Andrew , Meltzanidou Parthena , Kanni Theodora , Lazaridou Elizabeth , Giamarellos-Bourboulis Evangelos J.
Published: June 2023

Background: Results of randomized clinical trials show great variation in response to treatment with adalimumab (ADA) in hidradenitis suppurativa (HS). This varied response may be associated with genetic polymorphisms. Objectives: The aim of the study was to study the association between carriage of single nucleotide polymorphisms (SNPs) in the promoter of the tumor necrosis factor (TNF) gene and their response to ADA. Methods: Patients with moderate to severe HS who received ADA treatment for at least 12 weeks were enrolled. SNPs were analyzed with PCR-restriction fragment length polymorphism. Hidradenitis Suppurativa Clinical Response (HiSCR) score, International Hidradenitis Suppurativa Severity Scoring System 4 (IHS4) score, inflammatory lesion (AN) count, and draining tunnel (dT) count were collected at weeks 0, 12, 24, 36, and 48. Results: HiSCR response after 12 weeks of ADA treatment was 71.8% among carriers of the common GGG haplotype and 50.0% among carriers of minor frequency SNP haplotypes (p: 0.031; odds ratio: 0.39). This significant difference persisted until week 36. Carriers of minor frequency SNP haplotypes also had a lower relative decrease of the AN count at weeks 12 and 24; the dT count and IHS4 were not statistically different between the two groups. Conclusions: Carriage of at least one minor frequency SNP haplotype of the promoter of the TNF gene is associated with a decreased response to ADA. This association may have an impact on treatment decision-making.
Trabalho doméstico não remunerado: persistência da divisão sexual e transtornos mentais
Authors: Carneiro Cíntia Maria Moraes , Pinho Paloma de Sousa , Teixeira Jules Ramon Brito , Araújo Tânia Maria de
Published: June 2023

OBJETIVO: Avaliar características do trabalho doméstico não remunerado e sua associação com transtornos mentais, explorando diferenciais de gênero. MÉTODOS: Neste estudo foram analisados dados transversais da segunda onda de uma coorte da população urbana (n = 2.841) com idade a partir dos 15 anos de uma cidade de médio porte da Bahia (BA). A amostra representativa da população foi aleatoriamente selecionada em etapas múltiplas subsequentes. As entrevistas foram realizadas nos domicílios dos participantes do levantamento. O estudo analisou dados sociodemográficos, ocupacionais, do trabalho doméstico não remunerado e adoecimento mental, estratificadas por sexo. Investigou-se associação entre o conflito trabalho-família-tempo para si, o desequilíbrio esforço-recompensa no trabalho doméstico e familiar e a ocorrência de transtornos mentais comuns, de transtorno de ansiedade generalizada e de depressão. Foram estimadas prevalências, razões de prevalência e respectivos intervalos de confiança de 95%. RESULTADOS: Entre os participantes, verificou-se que as atividades domésticas não remuneradas eram realizadas por 71,3% dos homens e 95,2% das mulheres, que se mostraram as principais responsáveis pelas atividades de trabalho investigadas, exceto pequenos consertos. A inserção em trabalho remunerado foi maior entre os homens (68,1% contra 47,2% entre as mulheres). A distribuição dos estressores e experiência de conflitos evidenciou situação inversa entre homens e mulheres: o maior percentual entre os homens foi de baixo conflito trabalho-família-tempo para si (39,0%), já entre as mulheres, maior percentual foi de alto conflito (40,0%); entre os homens, 45,8% referiram baixo desequilíbrio esforço-recompensa no trabalho doméstico e familiar, enquanto apenas 28,8% das mulheres relataram baixo desequilíbrio. Os transtornos mentais investigados foram mais prevalentes entre as mulheres, que apresentaram significativa associação entre o conflito trabalho-família-tempo pessoal e os transtornos mentais comuns e a depressão; entre os homens o conflito teve maior associação com os transtornos mentais comuns. Já o desequilíbrio esforço-recompensa se mostrou fortemente relacionado aos TMC, ao transtorno de ansiedade generalizada e à depressão. Entre os homens, esse desequilíbrio relacionou-se principalmente à depressão. CONCLUSÕES: O trabalho doméstico persiste como atribuição majoritariamente feminina. As situações estressoras do trabalho doméstico não remunerado e o conflito trabalho-família-tempo para si associaram-se mais fortemente aos efeitos adversos na saúde mental das mulheres.
“Remember!”
Authors: Janssen-Wnorowska Arnim
Published: June 2023

By discussing some text-critical findings, this article poses the question of how the concept of emotivity can inform our understanding of the transmission processes which shaped Lam 1. An introduction establishes the theoretical and methodological basis for a comparative analysis of the Masoretic text, the Qumran manuscript of 4QLam, and Targum Lamentations. In various ways, the textual witnesses intensify and emotionalize Lam 1. Moreover, they focus on specific emotion words and make their meaning explicit for readers and listeners. Finally, the textual witnesses use different means to allow recipients to identify with the emotional descriptions.
A new species of pilumnid crab of the genus Vellumnus Ng, 2010 (Brachyura, Pilumnoidea) from the Persian Gulf
Authors: Fahimi Neda , Naderloo Reza
Published: June 2023

A new species of Vellumnus Ng, 2010 (Pilumnidae) is described from coral debris in the Persian Gulf. It differs from its closest congeners by the carapace sculpture, presence of two fissures on the supraorbital margin, the structure of the frontal lobes that are continuous with the inner-orbital angle, and the pattern of the granules on the outer surface of the chela.
Discourse Structure and Argument Realisation in Old Literary Tibetan: From Text Composition to Verb Semantics
Authors: Bialek Joanna
Published: June 2023

The paper discusses disparate language phenomena whose common denominator is their relevance for the study of argument realisation in Old Literary Tibetan. It attempts to outline the boundaries, within which argument realisation should be considered when preparing a verb lexicon, dictionary, or a syntactic annotation of a text. The study focuses on processes and constructions that may have impact on argument realisation of verbs and belong to discourse-forming strategies of the language. In a top-down approach various levels of text composition are examined for their role in presentation of events.
The Structure of the Noun Phrase in Northern and Southern Ewenki Dialects
Authors: Däbritz Chris Lasse
Published: June 2023

The paper investigates the structure of Ewenki noun phrases, dealing with both their semantics and syntax. Whereas semantics are rather uniform cross-dialectally, there is considerable variation in syntax, especially regarding agreement patterns. As a rule, the more northern a dialect is the less agreement it exhibits within the noun phrase; besides that, cardinal numerals greater or equal to ‘2’ call for the modified noun in plural in rather Southern dialects, but for its unmarked form in rather Northern dialects. From a comparative point of view, it can be shown that the areal-typologically unexpected agreement within the noun phrase is probably the inherited pattern in (Northern) Tungusic languages, whereas the relevant Ewenki dialects lost it secondarily due to Turkic (Dolgan and Sakha) influence.
Mitigation Strategies in Colloquial Conversations: A Contrastive Approach in European, Cuban, Mexican, Argentinian and Chilean Spanish
Authors: Marco Marta Albelda
Published: June 2023

This paper compares the pragmatic mitigation strategies used by speakers of five geographic varieties of Spanish: European, Cuban, Mexican, Argentinian and Chilean Spanish. Mitigation can be understood as a pragmatic strategy arising from face-protection needs that seeks to reduce possible adverse effects on the satisfactory progress of communication.

The data are drawn from the Ameresco corpus of colloquial conversations, and the analysis includes four kinds of parameters: linguistic, pragmatic, and socio-situational. The study explores the functions and frequency of use of mitigation, speakers’ and hearers’ exposure to social and relational risks, the degree of their commitment in interaction, and the most productive resources observed in each variety.

The results show convergences and divergences in the use of mitigation in these geographical areas, providing a picture of dialectal and sociolectal patterns here. The study concludes that mitigation varies according to the priorities of face needs in each speech community.
Diagnosis of Antarctic Blowing Snow Properties Using MERRA-2 Reanalysis with a Machine Learning Model
Authors: Yang Yuekui , Kiv Daniel , Bhatta Surendra , Ganeshan Manisha , Lu Xiaomei , Palm Stephen
Published: June 2023

This paper presents work using a machine learning model to diagnose Antarctic blowing snow (BLSN) properties with the Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), data. We adopt the random forest classifier for BLSN identification and the random forest regressor for BLSN optical depth and height diagnosis. BLSN properties observed from the Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) are used as the truth for training the model. Using MERRA-2 fields such as snow age, surface elevation and pressure, temperature, specific humidity, and temperature gradient at the 2-m level, and wind speed at the 10-m level as input, reasonable results are achieved. Hourly blowing snow property diagnostics are generated with the trained model. Using 2010 as an example, it is shown that the Antarctic BLSN frequency is much higher over East than West Antarctica. High-frequency months are from April to September, during which BLSN frequency exceeds 20% over East Antarctica. For May 2010, the BLSN snow frequency in the region is as high as 37%. Due to the suppression by strong surface-based inversions, larger values of BLSN height and optical depth are usually limited to the coastal regions, wherein the strength of surface-based inversions is weaker.