bluuebunny/crossref_metadata_2025 huggingface dataset:
Who to escalate during a pandemic? A retrospective observational study about decision-making during the COVID-19 pandemic in the UK
Authors: Beresford Stephanie , Tandon Aditi , Farina Sofia , Johnston Brian , Crews Maryam , Welters Ingeborg Dorothea
Published: June 2023

Background

Optimal decision-making regarding who to admit to critical care in pandemic situations remains unclear. We compared age, Clinical Frailty Score (CFS), 4C Mortality Score and hospital mortality in two separate COVID-19 surges based on the escalation decision made by the treating physician.

Methods

A retrospective analysis of all referrals to critical care during the first COVID-19 surge (cohort 1, March/April 2020) and a late surge (cohort 2, October/November 2021) was undertaken. Patients with confirmed or high clinical suspicion of COVID-19 infection were included. A senior critical care physician assessed all patients regarding their suitability for potential intensive care unit admission. Demographics, CFS, 4C Mortality Score and hospital mortality were compared depending on the escalation decision made by the attending physician.

Results

203 patients were included in the study, 139 in cohort 1 and 64 in cohort 2. There were no significant differences in age, CFS and 4C scores between the two cohorts. Patients deemed suitable for escalation by clinicians were significantly younger with significantly lower CFS and 4C scores compared with patients who were not deemed to benefit from escalation. This pattern was observed in both cohorts. Mortality in patients not deemed suitable for escalation was 61.8% in cohort 1 and 47.4% in cohort 2 (p<0.001).

Conclusions

Decisions who to escalate to critical care in settings with limited resources pose moral distress on clinicians. 4C score, age and CFS did not change significantly between the two surges but differed significantly between patients deemed suitable for escalation and those deemed unsuitable by clinicians. Risk prediction tools may be useful in a pandemic to supplement clinical decision-making, even though escalation thresholds require adjustments to reflect changes in risk profile and outcomes between different pandemic surges.
Prevalence and risk factors for silicosis among a large cohort of stone benchtop industry workers
Authors: Hoy Ryan F , Dimitriadis Christina , Abramson Michael , Glass Deborah C , Gwini StellaMay , Hore-Lacy Fiona , Jimenez-Martin Javier , Walker-Bone Karen , Sim Malcolm R
Published: June 2023

Objectives

High silica content artificial stone has been found to be associated with silicosis among stone benchtop industry (SBI) workers. The objectives of this study were to determine the prevalence of and risk factors for silicosis among a large cohort of screened SBI workers, and determine the reliability of respiratory function testing (RFT) and chest x-ray (CXR) as screening tests in this industry.

Methods

Subjects were recruited from a health screening programme available to all SBI workers in Victoria, Australia. Workers undertook primary screening, including an International Labour Office (ILO) classified CXR, and subject to prespecified criteria, also underwent secondary screening including high-resolution CT (HRCT) chest and respiratory physician assessment.

Results

Among 544 SBI workers screened, 95% worked with artificial stone and 86.2% were exposed to dry processing of stone. Seventy-six per cent (414) required secondary screening, among whom 117 (28.2%) were diagnosed with silicosis (median age at diagnosis 42.1 years (IQR 34.8–49.7)), and all were male. In secondary screening, silicosis was associated with longer SBI career duration (12 vs 8 years), older age, lower body mass index and smoking. In those with silicosis, forced vital capacity was below the lower limit of normal in only 14% and diffusion capacity for carbon monoxide in 13%. Thirty-six (39.6%) of those with simple silicosis on chest HRCT had an ILO category 0 CXR.

Conclusion

Screening this large cohort of SBI workers identified exposure to dry processing of stone was common and the prevalence of silicosis was high. Compared with HRCT chest, CXR and RFTs had limited value in screening this high-risk population.
Alcohol and the central nervous system
Authors: Wolfe Maytal , Menon Arun , Oto Maria , Fullerton Natasha E , Leach John-Paul
Published: June 2023

Ethanol use is common to most cultures but with varying doses and to varying extents. While research has focused on the effects on the liver, alcohol exerts a range of actions on the function and structure of the nervous system. In the central nervous system (CNS) it can provoke or exacerbate neurological and psychiatric disease; its effects on the peripheral nervous system are not included in this review. Sustained alcohol intake can predispose to acute neurochemical changes which, with continued ingestion and incomplete treatment, can lead to chronic structural changes in the CNS: these include generalised cortical and cerebellar atrophy, amnesic syndromes such as Korsakoff’s syndrome, and specific white matter disorders such as central pontine myelinolysis and Marchiafava–Bignami syndrome. Alcohol in pregnancy commonly and significantly affects fetal health, though this receives less medical and political attention than other causes of fetal harm. This review looks at the range of disorders that can follow acute or chronic alcohol use, and how these should be managed, and we provide a practical overview on how neurologists might diagnose and manage alcohol addiction.
Propagation Effect of Epileptic Seizures in a Coupled Thalamocortical Network
Authors: Yan Luyao , Zhang Honghui , Sun Zhongkui , Cao Zilu , Shen Zhuan , Du Lin
Published: June 2023

Epileptic seizures have spatial features related to the propagation of seizure waves. As the main characteristic of absence seizures, 2–4[Formula: see text]Hz spike-wave discharges (SWDs) originate from the cortices and are maintained by the thalamus. In this study, we explore the onset and propagation effect of absence seizures based on a thalamocortical model. First, we develop a two-compartment model and consider the autapse of the thalamic reticular nucleus as a crucial parameter to investigate transition behaviors. Moreover, we present dynamical mechanisms through bifurcation analysis. Simulation results show that the absence seizures can be induced and advanced as the coupling strength increases. Second, we investigate excitatory and inhibitory coupling functions in a three-compartment model. Our research indicates that the excitatory coupling function can lead to SWDs when all the compartments are initially saturated. In the process of propagation, excitatory coupling also gives rise to SWDs in normal compartments, whereas inhibitory coupling plays a limited role. Finally, we reproduce the above results in a 10-compartment model and verify the robustness against the variation of the number of modules. This work may shed new light on the field of seizure propagation and provide potential dynamical mechanisms.
Bifurcation Analysis of a Wind Turbine Generator Drive System with Stochastic Excitation Under Both Displacement and Velocity Delayed Feedback
Authors: Zhang Jiangang , Nan Mengran , Wei Lixiang , An Xinlei , He Meijuan
Published: June 2023

In this paper, a wind turbine generator drive system with stochastic excitation under both displacement and velocity delayed feedback is considered. Firstly, the center manifold method is used to approximate the delay term of the system, so that the Itô-stochastic differential equation can be obtained by random average method. Through the maximal Lyapunov exponential method, the local stochastic stability and random D-bifurcation conditions of the system are obtained. Secondly, it is verified that the increase of noise intensity and delay value induces the occurrence of random P-bifurcation of the system through Monte Carlo numerical simulations. In addition, the theoretical chaos threshold of the system is derived by the random Melnikov method. The results show that the chaos threshold decreases as the noise intensity increases, and the increase in time delay leads to a delay in the chaotic behavior of the system. Finally, the correctness and effectiveness of the chaos-theoretic analysis are verified based on the one-parameter bifurcation diagrams and the two-parameter bifurcation diagrams.
Estimating the Number of Zeros of Abelian Integrals for the Perturbed Cubic Z4-Equivariant Planar Hamiltonian System
Authors: Chen Aiyong , Huang Wentao , Xia Yonghui , Zhang Huiyang
Published: June 2023

We analyze the dynamics of a class of [Formula: see text]-equivariant Hamiltonian systems of the form [Formula: see text], where [Formula: see text] is complex, the time [Formula: see text] is real, while [Formula: see text] and [Formula: see text] are real parameters. The topological phase portraits with at least one center are given. The finite generators of Abelian integral [Formula: see text] are obtained, where [Formula: see text] is a family of closed ovals defined by [Formula: see text] [Formula: see text], [Formula: see text] is the open interval on which [Formula: see text] is defined, [Formula: see text], [Formula: see text] are real polynomials in [Formula: see text] and [Formula: see text] with degree [Formula: see text]. We give an estimation of the number of isolated zeros of the corresponding Abelian integral by using its algebraic structure. We show that for the given polynomials [Formula: see text] and [Formula: see text] in [Formula: see text] and [Formula: see text] with degree [Formula: see text], the number of the limit cycles of the perturbed [Formula: see text]-equivariant Hamiltonian system does not exceed [Formula: see text] (taking into account the multiplicity).
Synthesis and photophysical properties of subphthalocyanine substituted with tetraphenylethylene moieties
Authors: Furuyama Taniyuki , Shitanda Sho , Fukumura Tomoteru , Kobayashi Nagao
Published: June 2023

Tetraphenylethylene-substituted phthalonitriles and corresponding subphthalocyanines have been synthesized. Mono- and di-substituted phthalonitriles could be prepared by a typical [Formula: see text]Ar reaction. The crystallographic structures of phthalonitriles indicated that intermolecular [Formula: see text]-[Formula: see text] interactions were suppressed by the bulky tetraphenylethylene moieties. Subphthalocyanines substituted with tetraphenylethylenes at peripheral and axial positions were obtained by boron-templated macrocyclization of phthalonitriles. Phthalonitriles showed typical aggregation-induced-emission behavior in THF/water mixed solvents, while fluorescence intensities of subphthalocyanines were decreased with increasing water content.
Permanent displacement characteristics of landslides taking into consideration the frequency and energy behaviour of historical seismic ground motions
Authors: Tang Hua , Fang Yuwei , Cheng Xu , Wu Zhenjun , Qin Yuqiao
Published: June 2023

Landslides often occur along motorways in earthquake-prone areas, leading to casualties and the loss of property. Most previous studies have applied the simplified Newmark method to assess landslide susceptibility at a regional scale, ignoring the characteristics of local ground motions. In this study, we investigated permanent displacement characteristics of three potential landslide areas along the Dayong Expressway using the rigorous Newmark method that considers the frequency and energy characteristics of historical seismic waves. First, the frequency characteristics of historical earthquakes in the study areas were analysed using the fast Fourier transform method and were adopted as input ground motions in calculating the Newmark displacement. Next, the critical accelerations of the three study areas were computed. Parameters such as the elevation, soil layer thickness and soil strength that are required for critical acceleration calculations were obtained using high-precision (
c.
3 cm) unmanned aerial vehicle mapping technology, drilling operations and laboratory tests. Finally, the Newmark displacement was calculated and the landslide susceptibility of the study areas was evaluated. The results showed that the predominant frequency of historical seismic waves in the study areas was 0.38–3.36 Hz, indicating low-frequency characteristics. The results also indicated that the frequency and energy characteristics of the seismic ground motions significantly influenced the Newmark displacement. The maximum Newmark displacement under different waveforms at Damieju ranged from 2 to 18 cm. Under the most dangerous conditions, all three areas showed a potential for landslides. The maximum Newmark displacement positively correlated with the energy of the predominant frequency. The large-energy and low-frequency characteristics of the seismic wave correspond to a large displacement. The simplified Newmark method when used in regional landslide susceptibility analysis did not reflect this effect and may be unsuitable to determine the size of landslides.
The Volterra cliff in the mind of philosophers, savants and geologists (1282–1830)
Authors: Dominici Stefano
Published: June 2023

The Pliocene fossiliferous succession of the Volterra hill, a prominent place in Tuscany, Italy and, since the Renaissance, the site of important archaeological finds of the ancient Etruscan civilization, has formed the object of enquiry over six centuries of research on the inner nature of the Earth system. The works of Restoro d'Arezzo, Leonardo da Vinci, Nicolaus Steno, Giovanni Targioni, Nicolas Desmarest, Giambattista Brocchi, Alexandre Brongniart and Charles Lyell testify to the early recognition through fieldwork that those strata with seashells had formed at the bottom of the sea. This interpretation served different approaches to knowledge. Restoro, Leonardo and Steno, spanning nearly four centuries in the history of science (1282–1669), including the ‘Copernican Revolution’ and the start of the Modern Age, relied also on textual sources and trusted a speculative model of the Earth's interior, so that at Volterra they focused on vertical movements of the earth–water system. The authors of the eighteenth and nineteenth centuries abandoned pre-built young-Earth models and emphasized the geography of ancient Tuscany. Brocchi, Brongniart and Lyell promoted the taxonomic use of seashells to correlate rocks across Europe. This place deserves higher standards of valorization to promote understanding of the history and sociology of ideas.
Climate change impacts on respiratory health: exposure, vulnerability, and risk
Authors: Covert Hannah H. , Abdoel Wahid Firoz , Wenzel Sally E. , Lichtveld Maureen Y.
Published: June 2023

Anthropogenic climate change adversely impacts human health. In this perspective, we examine the impact of climate change on respiratory health risk. We describe five respiratory health threats—heat, wildfires, pollen, extreme weather events, and viruses—and discuss their impact on health outcomes in a warming climate. The risk of experiencing an adverse health outcome occurs at the intersection of exposure and vulnerability, consisting of sensitivity and adaptive capacity. Exposed individuals and communities most at risk are those with high sensitivity and low adaptive capacity, as influenced by the social determinants of health. We call for the implementation of a transdisciplinary strategy for accelerating respiratory health research, practice, and policy in the context of climate change.
Characterization, Expression, and Ligand Binding of LGP2 and MDA5 in Largemouth Black Bass Micropterus salmoides (Lacepède, 1802)
Authors: Pi Xiangyu , Xu Yang , Cao Yiwen , Zhang Qihuan , Wang Zisheng , Qi Zhitao
Published: June 2023

Melanoma differentiation-associated gene 5 (MDA5) and the laboratory of genetics and physiology 2 (LGP2) are family members of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), which play important roles in the immune response against pathogens invasion. In the present study, MDA5 and LGP2 genes were identified in largemouth bass (Micropterus salmoides), a fish species with a great economic value. The two proteins contained similar conserved domains and motifs as their counterparts of other vertebrates, including the DExDc domain (the DEAD/DEAH box helicases domain), HELICc domain (helicases superfamily domain), and regulatory domain (RD). Real-time qPCR revealed that the two genes were constitutively expressed in tissues of healthy fish and could be induced in the spleen by polyinosinic and polycytidylic acid (polyI:C) challenge in vivo. Also, selective pressure analysis revealed that the negative selection had roles in the evolutions of the two genes. Furthermore, the dsRNA binding mechanism of msLGP2 and msMDA5 were analyzed by the molecular docking strategy. The amino acids of msLGP2 involved in dsRNA binding were V604, N663, L682, and L684, which were located in the regulatory domain (RD) of msLGP2. The amino acids of msMDA5 involved in dsRNA binding were G429, H434, L842, and L845, which were located in the DExDc domain and the RD domain of msMDA5. These results indicated that fish LGP2 and MDA5 might share similar functions and ligand binding mechanism as their mammalian counterparts.
Replacement of Artemia franciscana Nauplii by Moina minuta Neonates as Live Food on the Larviculture of Angelfish (Pterophyllum scalare -Schultze, 1823) and Severum (Heros severus - Heckel, 1840)
Authors: Eiras Bruno José Corecha Fernandes , Campelo Daniel Abreu Vasconcelos , de Moura Lorena Batista , de Oliveira Leonnan Carlos Carvalho , de Sousa Liliane Marques , da Costa Rauquírio Marinho
Published: June 2023

The present study aimed to assess the potential substitution of Artemia franciscana nauplii with Moina minuta neonates as the initial feed for angelfish (Pterophyllum scalare) and severum (Heros severus), evaluating the fish growth performance, live food cost, and intestinal histomorphometry. To achieve this goal, two separate experiments were carried out for each species during 20 days, using 200 postlarvae. Both experimental designs consisted of five treatments, namely, 100% A. franciscana nauplii (A100-M0); 75% A. franciscana nauplii and 25% M. minuta neonates (A75-M25); 50% A. franciscana nauplii and 50% M. minuta neonates (A50-M50); 25% A. franciscana nauplii and 75% M. minuta neonates (A25-M75); and 100% M. minuta neonates (A0-M100), with four replications (10 postlarvae per repetition). Angelfish postlarvae fed with A100-M0, A75-M25, A50-M50, and A25-M75 had better values of final length (13.31 mm, 14.15 mm, 13.32 mm, and 13.32 mm), gain in length (7.91 mm, 8.75 mm, 7.92 mm, and 7.92 mm), and length-specific growth rate (4.51% day−1, 4.82% day−1, 4.51% day−1, and 4.51% day−1). In the case of severum postlarvae, the highest length growth performance occurred in those fed with A100-M0 (15.86 mm, 8.90 mm, and 4.12% day−1), A75-M25 (15.45 mm, 8.49 mm, and 3.99% day−1), and A50-M50 (14.78 mm, 7.82 mm, and 3.76% day−1). Both species (angelfish and severum postlarvae) fed with A100-M0 and A75-M25 presented higher values of final weight (28.88 mg and 34.49 mg; 55.84 mg and 53.95 mg), gain in weight (27.56 mg and 33.08 mg; 51.03 mg and 49.14 mg), and weight-specific growth rate (15.42% day−1 and 16.30% day−1; 12.26% day−1 and 12.09% day−1). Live food cost for angelfish and severum postlarvae was higher in A100-M0 (US$ 0.92 and US$ 1.08) and lower for the ones in A0-M100 (US$ 0.36 and US$ 0.35). Severum postlarvae fed with A100-M0 (57.20 µm), A75-M25 (55.66 µm), and A50-M50 (54.27 µm) presented the highest intestinal villi heights. Thus, partial replacement of A. franciscana nauplii by M. minuta neonates in the proportion of A75-M25 or 100A-0M is viable and effective during the first feed of these fish species.
Hsa_circ_0003220 Drives Chemoresistance of Human NSCLC Cells by Modulating miR-489-3p/IGF1
Authors: Xia Shaofeng , Wang Chenliang
Published: June 2023

Circular RNAs (circRNAs) have been shown to have critical roles in developing cancer and treatment resistance in an increasing body of research. The aim was to look into the functions and processes of hsa_circ_0003220 in the non-small cell lung cancer (NSCLC) chemoresistance. The NSCLC cell lines H460 and A549 were employed in present work. hsa_circ_0003220, miR-489-3p, and insulin-like growth factors (IGF1) mRNA levels were assessed with a quantitative real time polymerase chain reaction (qRT-PCR). The cisplatin, docetaxel, and paclitaxel (PTX) resistances were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the enzyme linked immunosorbent assay (ELISA) test measured IGF1 expression. In order to corroborate the miR-489-3p relation with hsa_circ_0003220 or IGF1, a dual-luciferase reporter method was applied. The level of hsa_circ_0003220 was raised in cells and tissues from PTX-resistant (PR) NSCLC. In PR NSCLC cells, hsa_circ_0003220 knockdown reduced chemoresistance. For the purpose of the mechanism study, hsa_circ_0003220 knockdown substantially reduced IGF1 expression via miR-489-3p sponging, reducing chemoresistance in PR NSCLC cells. By controlling the miR-489-3p/IGF1 axis, hsa_circ_0003220 knockdown helped NSCLC overcome chemoresistance, suggesting a potential circRNA-targeted therapy for the disease.
Hypoxia-Responsive lncRNA AC115619 Encodes a Micropeptide That Suppresses m6A Modifications and Hepatocellular Carcinoma Progression
Authors: Zhang Qiangnu , Wei Teng , Yan Lesen , Zhu Siqi , Jin Wen , Bai Yu , Zeng Yuandi , Zhang XiaoFei , Yin Zexin , Yang Jilin , Zhang Wenjian , Wu Meilong , Zhang Yusen , Liu Liping
Published: June 2023

Long noncoding RNAs (lncRNA) regulate a number of aspects of cancer biology. Recent research has shown that lncRNAs can encode micropeptides that mediate their functions in tumors. Here, we revealed that the liver-specific putative lncRNA, AC115619, is expressed at low levels in hepatocellular carcinoma (HCC) and encodes a micropeptide, designated as AC115619–22aa. AC115619 played a crucial role in the regulation of tumor progression and was a prognostic indicator in HCC. The encoded micropeptide AC115619–22aa inhibited the progression of HCC by binding to WTAP and impeding the assembly of the N6-methyladenosine (m6A) methyltransferase complex, which regulates the expression of tumor-associated genes, such as SOCS2 and ATG14. AC115619 was cotranscribed with the adjacent upstream coding gene APOB, and hypoxia induced transcriptional repression of both APOB and AC115619 by controlling HIF1A/HDAC3 and HNF4A signaling. In animal and patient-derived models, AC115619–22aa reduced global m6A levels and suppressed tumor growth. In conclusion, this study establishes AC115619 and its encoded micropeptide as potential prognostic markers and therapeutic targets for patients with HCC.

Significance:

A micropeptide encoded by lncRNA AC115619 impedes formation of the m6A methylation complex to lower m6A levels and reduce the growth of hepatocellular carcinoma.
Supplementary Figure S6 from HLA Class II Loss and JAK1/2 Deficiency Coevolve in Melanoma Leading to CD4 T-cell and IFNγ Cross-Resistance
Authors: Stupia Simone , Heeke Christina , Brüggemann Alicia , Zaremba Anne , Thier Beatrice , Kretz Julia , Sucker Antje , Philip Manuel , Zelinskyy Gennadiy , Ferrone Soldano , Roesch Alexander , Horn Susanne , Hadaschik Eva , Schadendorf Dirk , Trilling Mirko , Dittmer Ulf , Griewank Klaus , Zhao Fang , Paschen Annette
Published: June 2023

JAK inhibition downregulates HLA-II but not HLA-I or PD-L1 expression in melanoma cells
Supplementary Figure S5 from HLA Class II Loss and JAK1/2 Deficiency Coevolve in Melanoma Leading to CD4 T-cell and IFNγ Cross-Resistance
Authors: Stupia Simone , Heeke Christina , Brüggemann Alicia , Zaremba Anne , Thier Beatrice , Kretz Julia , Sucker Antje , Philip Manuel , Zelinskyy Gennadiy , Ferrone Soldano , Roesch Alexander , Horn Susanne , Hadaschik Eva , Schadendorf Dirk , Trilling Mirko , Dittmer Ulf , Griewank Klaus , Zhao Fang , Paschen Annette
Published: June 2023

No chromosomal alterations in the MHC region of HLA-II-loss JAK1/2 mutant melanoma cells
Supplementary Table S1 from Phase II Study of Docetaxel and Trametinib in Patients with KRAS Mutation Positive Recurrent Non–Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042)
Authors: Gadgeel Shirish M. , Miao Jieling , Riess Jonathan W. , Moon James , Mack Philip C. , Gerstner Gregory J. , Burns Timothy F. , Taj Asma , Akerley Wallace L. , Dragnev Konstantin H. , Laudi Noel , Redman Mary W. , Gray Jhanelle E. , Gandara David R. , Kelly Karen
Published: June 2023

Supplementary Table 1. Dose Modifications for Docetaxel and Trametinib
Bavituximab Decreases Immunosuppressive Myeloid-Derived Suppressor Cells in Newly Diagnosed Glioblastoma Patients
Authors: Ly K. Ina , Richardson Leland G. , Liu Mofei , Muzikansky Alona , Cardona Jonathan , Lou Kevin , Beers Andrew L. , Chang Ken , Brown James M. , Ma Xiaoyue , Reardon David A. , Arrillaga-Romany Isabel C. , Forst Deborah A. , Jordan Justin T. , Lee Eudocia Q. , Dietrich Jorg , Nayak Lakshmi , Wen Patrick Y. , Chukwueke Ugonma , Giobbie-Hurder Anita , Choi Bryan D. , Batchelor Tracy T. , Kalpathy-Cramer Jayashree , Curry William T. , Gerstner Elizabeth R.
Published: June 2023

Purpose:

We evaluated the efficacy of bavituximab—a mAb with anti-angiogenic and immunomodulatory properties—in newly diagnosed patients with glioblastoma (GBM) who also received radiotherapy and temozolomide. Perfusion MRI and myeloid-related gene transcription and inflammatory infiltrates in pre-and post-treatment tumor specimens were studied to evaluate on-target effects (NCT03139916).

Patients and Methods:

Thirty-three adults with IDH--wild-type GBM received 6 weeks of concurrent chemoradiotherapy, followed by 6 cycles of temozolomide (C1-C6). Bavituximab was given weekly, starting week 1 of chemoradiotherapy, for at least 18 weeks. The primary endpoint was proportion of patients alive at 12 months (OS-12). The null hypothesis would be rejected if OS-12 was ≥72%. Relative cerebral blood flow (rCBF) and vascular permeability (Ktrans) were calculated from perfusion MRIs. Peripheral blood mononuclear cells and tumor tissue were analyzed pre-treatment and at disease progression using RNA transcriptomics and multispectral immunofluorescence for myeloid-derived suppressor cells (MDSC) and macrophages.

Results:

The study met its primary endpoint with an OS-12 of 73% (95% confidence interval, 59%–90%). Decreased pre-C1 rCBF (HR, 4.63; P = 0.029) and increased pre-C1 Ktrans were associated with improved overall survival (HR, 0.09; P = 0.005). Pre-treatment overexpression of myeloid-related genes in tumor tissue was associated with longer survival. Post-treatment tumor specimens contained fewer immunosuppressive MDSCs (P = 0.01).

Conclusions:

Bavituximab has activity in newly diagnosed GBM and resulted in on-target depletion of intratumoral immunosuppressive MDSCs. Elevated pre-treatment expression of myeloid-related transcripts in GBM may predict response to bavituximab.
Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: June 2023

Purpose:

Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCC), although with mitigated results. We sought to interrogate the cellular and molecular transcriptional reprogramming underlying BCC resistance to immunotherapy.

Experimental Design:

Here, we combined spatial and single-cell transcriptomics to deconvolute the spatial heterogeneity of the tumor microenvironment in regard with response to immunotherapy, in a cohort of both naïve and resistant BCCs.

Results:

We identified subsets of intermingled cancer-associated fibroblasts (CAF) and macrophages contributing the most to CD8 T-cell exclusion and immunosuppression. Within this spatially resolved peritumoral immunosuppressive niche, CAFs and adjacent macrophages were found to display Activin A–mediated transcriptional reprogramming towards extracellular matrix remodeling, suggesting active participation to CD8 T-cell exclusion. In independent datasets of human skin cancers, Activin A–conditioned CAFs and macrophages were associated with resistance to immune checkpoint inhibitors (ICI).

Conclusions:

Altogether, our data identify the cellular and molecular plasticity of tumor microenvironment (TME) and the pivotal role of Activin A in polarizing the TME towards immune suppression and ICI resistance.
Continuous Administration of Anti-VEGFA Antibody Upregulates PAI-1 Secretion from Ovarian Cancer Cells via miR-143-3p Downregulation
Authors: Yagi Taro , Sawada Kenjiro , Miyamoto Mayuko , Shimizu Aasa , Oi Yukako , Toda Aska , Nakamura Koji , Kinose Yasuto , Kodama Michiko , Hashimoto Kae , Kimura Tadashi
Published: June 2023

Although bevacizumab (BEV) plays a key role in ovarian cancer treatment, BEV resistance is often observed in clinical settings. This study aimed to identify the genes responsible for BEV resistance. C57BL/6 mice inoculated with ID-8 murine ovarian cancer cells were treated with anti-VEGFA antibody or IgG (control) twice weekly for 4 weeks. The mice were sacrificed, then, RNA was extracted from the disseminated tumors. qRT-PCR assays were performed to identify angiogenesis-related genes and miRNAs that were altered by anti-VEGFA treatment. SERPINE1/PAI-1 was found to be upregulated during BEV treatment. Therefore, we focused on miRNAs to elucidate the mechanism underlying the upregulation of PAI-1 during BEV treatment. Kaplan–Meier plotter analysis revealed that higher expression levels of SERPINE1/PAI-1 were associated with poor prognoses among BEV-treated patients, suggesting that SERPINE1/PAI may be involved in the acquisition of BEV resistance. miRNA microarray analysis followed by in silico and functional assays revealed that miR-143-3p targeted SERPINE1 and negatively regulated PAI-1 expression. The transfection of miR-143-3p suppressed PAI-1 secretion from ovarian cancer cells and inhibited in vitro angiogenesis in HUVECs. Next, miR-143-3p-overexpressing ES2 cells were intraperitoneally injected into BALB/c nude mice. ES2-miR-143-3p cells downregulated PAI-1 production, attenuated angiogenesis, and significantly inhibited intraperitoneal tumor growth following treatment with anti-VEGFA antibody. Continuous anti-VEGFA treatment downregulated miR-143-3p expression, which upregulated PAI-1 and activated an alternative angiogenic pathway in ovarian cancer. In conclusion, the substitution of this miRNA during BEV treatment may help overcome BEV resistance, and this may be used as a novel treatment strategy in clinical settings.

Implications:

Continuous administration of VEGFA antibody upregulates SERPINE1/PAI-1 expression via the downregulation of miR-143-3p, which contributes to acquiring bevacizumab resistance in ovarian cancer.
Table S5 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

Secondary Validations of top drug hits from HCT116 WT vs Y107H clones.
Table S2 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

Evaluating the association between AA, Y107H variant, and cancer risk.
Data 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

Abstract
TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53–PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors.
Significance:
We analyze the African-centric Y107H hypomorphic variant and show that it confers increased cancer risk; we use Y107H in order to identify PADI4 as a key tumor-suppressive p53 target gene that contributes to an immune modulation signature and that is predictive of cancer survival and the success of immunotherapy.
Increased Ca
2+
Transient Underlies RyR2-Related Left Ventricular Noncompaction
Authors: Ni Mingke , Li Yanhui , Wei Jinhong , Song Zhenpeng , Wang Hui , Yao Jinjing , Chen Yong-Xiang , Belke Darrell , Estillore John Paul , Wang Ruiwu , Vallmitjana Alexander , Benitez Raul , Hove-Madsen Leif , Feng Wei , Chen Ju , Roston Thomas M. , Sanatani Shubhayan , Lehman Anna , Chen S.R. Wayne
Published: June 2023

Background:

A loss-of-function cardiac ryanodine receptor (RyR2) mutation, I4855M
+/–
, has recently been linked to a new cardiac disorder termed RyR2 Ca
2+
release deficiency syndrome (CRDS) as well as left ventricular noncompaction (LVNC). The mechanism by which RyR2 loss-of-function causes CRDS has been extensively studied, but the mechanism underlying RyR2 loss-of-function-associated LVNC is unknown. Here, we determined the impact of a CRDS-LVNC-associated RyR2-I4855M
+/–
loss-of-function mutation on cardiac structure and function.

Methods:

We generated a mouse model expressing the CRDS-LVNC-associated RyR2-I4855M
+/–
mutation. Histological analysis, echocardiography, ECG recording, and intact heart Ca
2+
imaging were performed to characterize the structural and functional consequences of the RyR2-I4855M
+/–
mutation.

Results:

As in humans, RyR2-I4855M
+/–
mice displayed LVNC characterized by cardiac hypertrabeculation and noncompaction. RyR2-I4855M
+/–
mice were highly susceptible to electrical stimulation–induced ventricular arrhythmias but protected from stress-induced ventricular arrhythmias. Unexpectedly, the RyR2-I4855M
+/–
mutation increased the peak Ca
2+
transient but did not alter the L-type Ca
2+
current, suggesting an increase in Ca
2+
-induced Ca
2+
release gain. The RyR2-I4855M
+/–
mutation abolished sarcoplasmic reticulum store overload–induced Ca
2+
release or Ca
2+
leak, elevated sarcoplasmic reticulum Ca
2+
load, prolonged Ca
2+
transient decay, and elevated end-diastolic Ca
2+
level upon rapid pacing. Immunoblotting revealed increased level of phosphorylated CaMKII (Ca
2+
-calmodulin dependent protein kinases II) but unchanged levels of CaMKII, calcineurin, and other Ca
2+
handling proteins in the RyR2-I4855M
+/–
mutant compared with wild type.

Conclusions:

The RyR2-I4855M
+/–
mutant mice represent the first RyR2-associated LVNC animal model that recapitulates the CRDS-LVNC overlapping phenotype in humans. The RyR2-I4855M
+/–
mutation increases the peak Ca
2+
transient by increasing the Ca
2+
-induced Ca
2+
release gain and the end-diastolic Ca
2+
level by prolonging Ca
2+
transient decay. Our data suggest that the increased peak-systolic and end-diastolic Ca
2+
levels may underlie RyR2-associated LVNC.
Picturing the Snakes
Authors: Bhaumik Rahul
Published: June 2023

This paper explores the ways in which Indian snakes were represented through natural history paintings along with textual taxonomic descriptions—a principal means of modern “exploratory experimentation” in early British India. It specifically examines Patrick Russell’s scientific engagement with the subcontinental snakes (a “new” branch of natural history of snakes fashioned by him) and the nature of “local” involvements in his undertaking. While considering the crucial role of colonial natural history in knowing and making visible the “terror” of Indian snakes to manage the snakebite-laden landscape, this paper elucidates how both the Western inferiorisation of non-Western perspective and the non-European indifference towards the European planetary vision disrupted the heterogeneous network of “knowledge making” in late eighteenth-century British India. Thus, this paper questions the recent historiography that projected a seamless “collaboration” or “hybridisation” in the formation of scientific knowledge across the globalised space of empire.
Prevalence of Orthorexic Tendencies and Their Correlates Among Lebanese Patients with Cancer
Authors: Zoghbi Rita , Awad Emmanuelle , Hallit Souheil , Matta Clémence
Published: June 2023

Individuals with cancer face daily challenges regarding diet and healthy lifestyle behaviors that may lead them to better health. This quest for improved health can be exaggerated in unhealthy ways if it is not approached with moderation as occurs with a condition called orthorexia nervosa (ON). Our aim in this study was to determine the prevalence of ON tendencies and their behavioral correlates among Lebanese adults with cancer. This was a monocentric cross-sectional study, conducted between December 2021 and February 2022, involving 366 patients. We collected data via telephone and recorded answers online on a Google form. We used the Düsseldorf Orthorexia Scale (DOS) to assess orthorexic behaviors, and we checked for behavioral correlates of orthorexia through a linear regression model using the DOS score as the dependent variable. On the DOS scale, we found that 9% of these participants showed possible ON tendencies, whereas 22.2% had definite ON tendencies. Factors associated with having more ON tendencies were (a) receipt of hormonotherapy, (b) being female and (c) having breast cancer. Having prostate cancer was significantly associated with fewer ON tendencies. Our results should help improve the management of patients with cancer through programs to increase patient awareness and education.
The Effect of the Benevolent Experienced Sexism and the Sexual Myths on Women’s Health
Authors: Martínez-Marín María Dolores , Martínez Carmen , Ródenas Irene
Published: June 2023

The impact of sexism on health has been widely demonstrated. However, literature affirms sexual myths, as sexual harassment myths, avoid some behaviours being perceived as sexist. This result has been found frequently in studies of simulated situations with students. This research examines the effect of endorsement of sexual myths and of benevolent experienced sexism on women’s health. A first study evaluated the psychometric properties of Spanish’ version of benevolent experienced sexism (EBX-SP). In a second study, a hierarchical multiple regression tested the effect of the two variables on health. Results indicated that benevolent experienced sexism, has more effect in the prediction of health than endorsement of sexual myths. Women who experienced sexual harassment declared fewer myths than those who have not. The women who have suffered sexual harassment also had poorer health and reported more benevolent sexist experiences. Our results suggest that myths do not affect the perception of the benevolent sexist experiences that women undergo, which has an impact on health.
An assessment of the impact of structure and type of microplastics on ultrafiltration technology for microplastic remediation
Authors: Sharma Anuj , Kumari Supriya , Chopade Rushikesh L , Pandit Pritam P , Rai Abhishek R , Nagar Varad , Awasthi Garima , Singh Apoorva , Awasthi Kumud Kant , Sankhla Mahipal Singh
Published: June 2023

Microplastic, which is of size less than 5 mm, is gaining a lot of attention as it has become a new arising contaminant because of its ecophysiology impact on the aquatic environment. These microplastics are found in freshwater or drinking water and are the major carriers of pollutants. Removal of this microplastic can be done through the primary treatment process, secondary treatment process, and tertiary treatment process. One approach for microplastic remediation is ultrafiltration technology, which involves passing water through a membrane with small pores to filter out the microplastics. However, the efficiency of this technology can be affected by the structure and type of microplastics present in the water. New strategies can be created to improve the technology and increase its efficacy in removing microplastics from water by knowing how various types and shapes of microplastics react during ultrafiltration. The filter-based technique, that is, ultrafiltration has achieved the best performance for the removal of microplastic. But with the ultrafiltration, too some microplastic that are of sizes less than of ultrafiltration membrane passes through the filter and enters the food chain. Accumulation of this microplastic on the membrane also leads to membrane fouling. Through this review article, we have assessed the impact of the structure, size, and type of MPs on ultrafiltration technology for microplastic remediation, with that how these factors affect the efficiency of the filtration process and challenges occur during filtration.
Ecosystem responses of shallow thermokarst lakes to climate-driven hydrological change: Insights from long-term monitoring of periphytic diatom community composition at Old Crow Flats (Yukon, Canada)
Authors: Mohammed Wathiq J , MacDonald Lauren A , Thomas Kathryn E , McDonald Ian , Turner Kevin W , Wolfe Brent B , Hall Roland I
Published: June 2023

Shallow waterbodies are abundant in Arctic and subarctic landscapes where they provide productive wildlife habitat and hold cultural and socioeconomic importance for Indigenous communities. Their vulnerability to climate-driven hydrological and limnological changes enhances a need for long-term monitoring data capable of tracking aquatic ecosystem responses. Here, we evaluate biological and inferred physicochemical responses associated with a rise in rainfall-generated runoff and increasingly positive lake water balances in Old Crow Flats (OCF), a 5600 km2 thermokarst landscape in northern Yukon. This is achieved by analyzing periphytic diatom community composition in biofilms accrued on artificial-substrate samplers at 14 lakes collected mostly annually during 2008–2019 CE. Results reveal that diatom communities at 10 of the 14 lakes converged toward a composition typical of lakes with rainfall-dominated input waters. These include six of nine lakes that were not initially dominated by rainfall input. The shifts in diatom community composition infer rise of lake-water pH and ionic content, and they reveal that northern shallow lake ecosystems are responsive to climate-driven increases in rainfall. Based on data generated during the 12 -year-long monitoring period, we conclude that lakes located centrally within OCF are most vulnerable to rapid climate-driven hydroecological change due to flat terrain, larger lake surface area, and sparse terrestrial vegetation, which provide less resistance to lake expansion, shoreline erosion, and sudden drainage. This information assists the local Indigenous community and natural resource stewardship agencies to anticipate changes to traditional food sources and inform adaptation options.
Physical and psychological impact of yoga therapy in improving heart failure
Authors: Prabhu Sridevi , Nayak Krishnananda , Kadiyali Annapoorna , Devasia Tom , Varadaraju Rekha , Moodukudru Manjoosha
Published: June 2023

Effective therapy for patients with chronic cardiac failure (CCF) entails significant lifestyle modifications as well as often complex pharmaceutical regimes to alleviate symptoms, which, however, do not actually cure many patients. The gradual loss of cardiac function is impeded but not halted by such complicated pharmacological therapy, which primarily includes angiotensin-converting enzyme inhibitors, beta-blockers and diuretics, and sometimes digoxin, aspirin, warfarin, and anti-arrhythmic agents. Patients may be advised to track their weight and modify their diuretic prescription accordingly to avoid fluid overload or dehydration as part of the treatment plan. Non-pharmacologic treatment options are routinely integrated to improve the management of somatic complaints. Yoga and specialized breathing exercises seem to help CCF patients improve their cardiorespiratory and autonomic system function, and also their quality of life. We present the evidence.
A study of optical properties of copper sulphate pentahydrate doped IOTA-carrageenan polymer electrolytes
Authors: Saranya P. , Vanitha D. , Sundaramahalingam K. , Nandhinilakshmi M.
Published: June 2023

Biodegradable polymer films composed of Iota-Carrageenan and Copper Sulphate Pentahydrate (CuSO4.5H2O) were prepared by using the Solution Casting process. To investigate the optical property, different wt.% of CuSO4.5H2O were added to I-carrageenan polymer films. X-Ray diffraction analysis was used to study the structural properties of prepared electrolytes. FTIR study revealed the complexation between the polymer and the salt. The increase in the amorphous nature of the film by the addition of the salt was confirmed using an X-Ray Diffraction (XRD) pattern. The functional group and interaction between the different components present in the polymer film are observed from Fourier Transform Infrared (FTIR) analysis, implying that the addition of (CuSO4.5H2O) salt causes microstructural differences in the polymer film. The UV-Visible Spectrometer was used to record the optical properties like the absorption coefficient, extinction coefficient, and optical bandgap energy of the polymer blend electrolytes. From this, it was observed that the absorption value was increased with the addition of salt. The optical band gap was also recorded and it was observed that 20 wt.% of CuSO4.5H2O added film was found to have a higher energy gap (4.3 eV) compared with the other.