bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation and growth of the first supermassive black holes in MOG
Authors: Zhoolideh Haghighi Mohammad H. , Moffat John
Published: March 2024

The emergence of supermassive black holes (SMBHs) in the early universe remains a topic of profound interest and debate. In this paper, we investigate the formation and growth of the first SMBHs within the framework of Modified Gravity (MOG), where gravity exhibits increased strength. We explore how MOG, as an alternative to the standard model, may offer novel insights into the emergence of SMBHs and potentially reconcile the discrepancies observed in the accretion and growth processes. We examine the dynamics of gas and matter in this modified gravitational framework, shedding light on the unique interplay between gravity and the formation of SMBHs.
Geometrical and Numerical Analysis of Predator–Prey System Based on the Allee Effect in Predator
Authors: Gupta M. K. , Sahu Abha , Yadav C. K.
Published: March 2024

This study explores the complex dynamics of the predator–prey interactions, with a specific emphasis on the influence of the Allee effect on the predator population. We examined the fundamental mathematical characteristics of the model under consideration, such as the positivity of the system and the boundedness of the solutions. We investigated the equilibrium points and analyzed their stability using the Jacobi and Lyapunov methods. A comprehensive examination was carried out on the geometric properties of the dynamical system to compute the five invariants of the KCC theory. In particular, the deviation curvature tensor and its eigenvalues are investigated to demonstrate the behavior of the system stability. We have also obtained the necessary and sufficient conditions for the given set of parameters of the system in order to have the Jacobi stability (instability) near the equilibrium point. To visualize the dynamical behavior of the predator–prey model with the Allee effect in the predator density, numerical simulations were conducted. The investigation encompasses an examination of the system’s behavior from both geometric and numerical standpoints, with the objective of attaining a thorough comprehension using few examples.
Existence and Uniqueness of a Canard Cycle with Cyclicity at Most Two in a Singularly Perturbed Leslie–Gower Predator–Prey Model with Prey Harvesting
Authors: Wen Zhenshu , Shi Tianyu
Published: March 2024

Yao and Huzak [2022] proved that the cyclicity of canard cycles in a singularly perturbed Leslie–Gower predator–prey model with prey harvesting is at most two in a region of parameters. In this paper, we further show that there exists only one canard cycle with cyclicity at most two under explicit parameters conditions.
Rings and radicals related to n-primariness
Authors: Chen Hongying , Kim Hong Kee , Kwak Tai Keun , Lee Yang
Published: March 2024

This paper concerns ring properties which are induced from the structure of the powers of prime ideals. An ideal [Formula: see text] of a ring [Formula: see text] is called [Formula: see text]-primary (respectively, [Formula: see text]-primary) provided that [Formula: see text] for ideals [Formula: see text] of [Formula: see text] implies that [Formula: see text] or [Formula: see text] is nil of index [Formula: see text] (respectively, [Formula: see text] or [Formula: see text] is nil) in [Formula: see text], where [Formula: see text]. It is proved that for a proper ideal [Formula: see text] of a principal ideal domain [Formula: see text], [Formula: see text] is [Formula: see text]-primary if and only if [Formula: see text] is of the form [Formula: see text] for some prime element [Formula: see text] and [Formula: see text] if and only if [Formula: see text] is [Formula: see text]-primary, through which we study the structure of matrices over principal ideal domains. We prove that for a [Formula: see text]-primary ideal [Formula: see text] of a ring [Formula: see text], [Formula: see text] is prime when the Wedderburn radical of [Formula: see text] is zero. In addition we provide a method of constructing strictly descending chain of [Formula: see text]-primary radicals from any domain, where the [Formula: see text]-primary radical of a ring [Formula: see text] means the intersection of all the [Formula: see text]-primary ideals of [Formula: see text].
On weakly pullback flat S-posets
Authors: Zhao Tingting , Qiao Husheng , Zhang Xia
Published: March 2024

In 2005, Bulman-Fleming and Laan established an analog of the Lazard–Govorov–Stenström theorem in the convex of [Formula: see text]-posets, which shows that an [Formula: see text]-poset [Formula: see text] is strongly flat if and only if [Formula: see text]-preserves subpullbacks and subequalizers if and only if [Formula: see text] satisfies condition (P) and condition (E). Using subpullback diagrams, the equivalent descriptions of flatness and properties (P), (PWP) and (WP) were presented by Golchin and Rezaei in 2009. In this paper, we first give the definition of weak pullback flatness by using subpullback diagram. We then introduce condition (E[Formula: see text]) and prove that a right [Formula: see text]-poset [Formula: see text] is weakly pullback flat if and only if [Formula: see text] satisfies condition (P) and condition (E[Formula: see text]). At the same time, we correct an error in the paper “Strongly flat and po-flat [Formula: see text]-posets” by Shi, Comm. Algebra 33 (2005) 4515–4531. After that we investigate homological classification problems for cyclic [Formula: see text]-posets and Rees factor [Formula: see text]-posets using weak pullback flatness. Finally, we characterize the pomonoids over which every right [Formula: see text]-poset has a weakly pullback flat cover.
Jump Snatch
Authors: Shasha Dennis
Published: March 2024

Overcoming a checkered pass.
How Generative AI Fits into Knowledge Work
Authors: Sako Mari
Published: March 2024

Seeking to influence how generative artificial intelligence affects various professions.
A cross-disciplinary approach to learning medical physiology and behavioral skills involving drama students performing as simulated patients
Authors: Roe Seán , McGahon Mary K. , Parkinson Sharon , Tansey Etain , Murphy Paul
Published: March 2024

This work details how physiology tutorials for early years medical students are transformed by taking the clinical case off the two-dimensional page and instead having the case scenario acted by drama students. This adds context and authenticity. The benefits are twofold: emphasizing the importance of physiology to the budding clinician and embedding empathy and compassion from the earliest points in a clinician’s career.
Approaches to teaching about mechanisms of obesity in undergraduate pathophysiology courses
Authors: Walton Kristen L. W.
Published: March 2024

This article describes approaches for teaching obesity in an allied health major pathophysiology course, and, additionally, in an upper-division biology major course on the cellular and molecular basis of disease.
Joint angle-specific neuromuscular time course of recovery after isometric resistance exercise at shorter and longer muscle lengths
Authors: McMahon Gerard , Onambele-Pearson Gladys
Published: March 2024

Despite the established long-term benefits of training at longer muscle lengths for muscle size and strength, acutely performing resistance exercise at longer muscle lengths may require a longer time course of neuromuscular recovery compared with performing resistance exercises at shorter muscle lengths. Furthermore, there appear to be different joint angle-specific recovery profiles, depending on the muscle length of the preceding exercise.
Effects of Combining Music Therapy, Light Therapy, and Chromotherapy in the Treatment of Chronic Pain Patients: A Pilot Study
Authors: Suarez Alcira , Delgado Yannick , Servais Alain , Verardi Nicolas , Durand Delphine , Litaneur Severine , Wyart Vincent , Nizard Julien , Nguyen Jean-Paul
Published: March 2024

Background. It is currently considered that around 30% of chronic pain patients are totally refractory to medical treatment. Among patients who remain responsive to medical treatment, it is estimated that between 20% and 50% are likely to discontinue treatment due to severe side effects. Given these therapeutic difficulties, a significant number of patients turn to complementary therapies. Objective. The LineQuartz® is a medical device that combines 3 complementary therapies, namely, music therapy, light therapy, and chromotherapy. We propose to evaluate its effectiveness in chronic pain patients. Methods. Between October 2021 and October 2022, 44 patients aged between 23 and 85 years (mean: 55.4 years) were included in a prospective study. All patients had background pain intensity greater than 4/10 on the Numerical Pain Scale (NS). Treatment consisted of 4 half-hour sessions, divided into one session per week for 3 weeks (21 days). Patients were assessed by the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression scale (HAD) the day before starting treatment (Day 0) and the day after the end of treatment (Day 22). Results. Apart from the BPI item, “relationship with others,” all items improved significantly (p<0.050). Background pain intensity (NS) and frequency of painful attacks improved very significantly (p<0.001). The HAD anxiety subscore was also significantly improved (p<0.001). Discussion. This open pilot study supports the idea that LineQuartz® has a place among complementary therapies dedicated to the treatment of chronic pain. However, these results need to be confirmed by a controlled study.
Real-Time HIL Simulation of Nonlinear Generalized Model Predictive-Based High-Order SMC for Permanent Magnet Synchronous Machine Drive
Authors: Djouadi Hafidh , Ouari Kamel , Belkhier Youcef , Lehouche Hocine
Published: March 2024

The dynamics of the permanent magnet synchronous motor (PMSM) are described by nonlinear equations, which present challenges. Variations in external factors such as unidentified disturbances (loads) and evolving motor properties add complexity to control efforts. To tackle these intricacies and limitations, a nonlinear control approach is essential. Recent attention has turned to employing predictive control techniques for nonlinear multivariable systems, offering an intriguing avenue for research. In this context, this study introduces a novel hybrid control approach that addresses nonlinearity, parametric fluctuations, and external disturbances. The method combines two essential components: first, the outer loop utilizes high-order sliding mode control (HSMC) to optimize torque and trajectory speed, mitigating chattering phenomena while preserving the PMSM’s convergence and robustness traits. The inner loop, known as the current control, employs the newly developed nonlinear robust generalized predictive control (RNGPC) technique. Importantly, this strategy circumvents the need for direct measurement and observation of external disturbances and parameter uncertainties. The proposed strategy follows a two-phase process. Initially, the reference quadratic current is designed using the electromagnetic torque computed via HSMC, subsequently determining the necessary current to achieve the desired torque. The second phase involves computing the controller law through the robust generalized nonlinear predictive control technique. The approach’s strength lies in its ability to maintain stability and convergence in the face of external disturbances and parameter fluctuations, without necessitating precise measurements or knowledge of the disturbances. To validate the proposed control approach, simulation and experimental tests have been conducted across various operational scenarios. The obtained results demonstrate the method’s robustness against external disturbances and parameter changes while ensuring rapid convergence and reliable performance.
Existence, Decay, and Blow-up of Solutions for a Weighted m-Biharmonic Equation with Nonlinear Damping and Source Terms
Authors: Fidan Ayşe , Pişkin Erhan , Çelik Ercan
Published: March 2024

In this paper, we consider the weighted m-biharmonic equation with nonlinear damping and source terms. We proved the global existence of solutions. Later, the decay of the energy is established by using Nakao’s inequality. Finally, we proved the blow-up of solutions in finite time.
Acute Oral Toxicological Profile of Croton membranaceus Mull. Arg. Aqueous Stem Extract, a Herbal Treatment for Benign Prostate Hyperplasia, in Male Sprague–Dawley Rats
Authors: Afriyie Daniel Kwame , Ameyaw Elvis Ofori , Henneh Isaac Tabiri , Asare George , Ofori-Atta Ebenezer , Amponsah Seth Kwabena , Appiah-Opong Regina
Published: March 2024

Croton membranaceus Mull. Arg. is a traditional medicinal plant frequently employed in Ghana for the treatment of benign prostatic hyperplasia and prostate cancer. The objective of this study was to determine the acute oral toxicity of the aqueous stem extract of Croton membranaceus (CMASE) in male Sprague–Dawley (S-D) rats. The acute toxicity of CMASE was evaluated using S-D rats randomly divided into four groups of five animals each. Three groups (low dose, median dose, and high dose) of rats received single oral doses of CMASE (1000, 2500, and 5000 mg/kg body weight, respectively) using an oral gavage. The control group was given distilled water. After 14 days of daily observations, hematological, biochemical, and histopathological analyses were conducted on the rats. From the results obtained, doses of CMASE up to 5000 mg/kg did not cause death or induce any clinical indications of toxicity during the study period. Also, the mean body weight and the hematological indices assessed were not significantly affected by the various doses of CMASE compared to the control group. However, serum uric acid and creatinine levels decreased significantly (p<0.001) 14 days after the extract administration. Serum liver function enzyme levels, including alkaline phosphatase (ALP), alanine aminotransferases (ALT), and aspartate aminotransferases (AST), and serum proteins (total proteins and albumin) exhibited significant (p<0.001) non dose-dependent changes (increases and decreases) in treated groups compared to the controls. Other biochemical indices, however, did not differ significantly between the treated groups and the controls. The gross pathological and histological analysis of the heart, liver, and kidney tissues did not reveal any significant changes in histoarchitecture. The oral LD50 of CMASE in rats was greater than 5000 mg/kg, indicating that the extract was relatively safe. It must, however, be used with care as a substitute for the roots.
A Novel Approach for Conducting a Catchment Area Analysis of Breast Cancer by Age and Stage for a Community Cancer Center
Authors: Siegel Scott D. , Zhang Yuchen , Lynch Shannon M. , Rowland Jennifer , Curriero Frank C.
Published: March 2024

Background:

The U.S. Preventive Services Task Force recently issued an updated draft recommendation statement to initiate breast cancer screening at age 40, reflecting well-documented disparities in breast cancer–related mortality that disproportionately impact younger Black women. This study applied a novel approach to identify hotspots of breast cancer diagnosed before age 50 and/or at an advanced stage to improve breast cancer detection within these communities.

Methods:

Cancer registry data for 3,497 women with invasive breast cancer diagnosed or treated between 2012 and 2020 at the Helen F. Graham Cancer Center and Research Institute (HFGCCRI) and who resided in the HFGCCRI catchment area, defined as New Castle County, Delaware, were geocoded and analyzed with spatial intensity. Standardized incidence ratios stratified by age and race were calculated for each hotspot.

Results:

Four hotspots were identified, two for breast cancer diagnosed before age 50, one for advanced breast cancer, and one for advanced breast cancer diagnosed before age 50. Younger Black women were overrepresented in these hotspots relative to the full-catchment area.

Conclusions:

The novel use of spatial methods to analyze a community cancer center catchment area identified geographic areas with higher rates of breast cancer with poor prognostic factors and evidence that these areas made an outsized contribution to racial disparities in breast cancer.

Impact:

Identifying and prioritizing hotspot breast cancer communities for community outreach and engagement activities designed to improve breast cancer detection have the potential to reduce the overall burden of breast cancer and narrow racial disparities in breast cancer.
Table S4 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: March 2024

Table of mice enrolled in drug study
Table S1 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: March 2024

Gene set enrichment analysis of RAS signatures
Figure S5 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: March 2024

CSF1R Mouse IHC, CSF1R and STK10 Western Blot, CDK6 Human, phospho-Rb (S807/811) Human, and pRSK1 (S380) Human IHC
Figure S3 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: March 2024

Hallmark E2F Targets Enrichment Plot and Top DEGs
Figure S2 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: March 2024

Reactome G1 Phase Heatmap and Top DEGs
Figure S10 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: March 2024

Western Blots
Table S6 from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Table S6: Fish centromere counts.
Table S3 from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Table S3: Antibodies used in the study.
Figure S7 from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Figure S7: Drug-resilient 786-0 cells exhibit 1-2 whole genome duplications with high fidelity
Figure S6 from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Figure S6: Distribution fitting and Cell population identification for cell line 786-0
Figure S5 from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Figure S5: Distribution fitting and Cell population identification for cell line HCT116
Figure S4 from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Figure S4: Distribution fitting and cell population identification for cell line HCC1806.
Figure S10 from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Figure S10: EPAS1 FPKM reads at different timepoints post treatment in HCC1806.
Figure S1 from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Figure S1: Dose response curves for cell lines after 72h cisplatin treatment
FIGURE 1 from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Drug-resilient cells triple in size and mass for up to 10 days posttreatment. A, Our treatment protocol entailed that seeded cells were treated with cisplatin (T = −3 days) for 72 hours (T = 0 days posttreatment; DPT) and, following filtration, studied for 10 DPT. After a subsequent time interval (between 2–12 weeks depending on cell line), surviving cells gave rise to progeny. B, Cells from four cancer cell lines stained with Giemsa when untreated (CTL) and treated at timepoint 0 DPT, 5 DPT, and 10 DPT, and progeny from these cells at 28 DPT (HCC1806, 786-0, and HCT116 cells), and 49 DPT (U1890 cells; n = 3 biological replicates). Scale bar, 20 µm. C, Detailed view of nuclei of untreated HCC1806 cells and when surviving 5 DPT, using TEM. Scale bar, 2 µm. D, Size of untreated (CTL) cells, surviving cells at 0 DPT, 5 DPT, 10 DPT, and progeny at 28 DTP (HCC1806, 786-0), 21 DTP (HCT116), and 49 DTP (U1890). Sizes acquired by imaging of adherent cells and analyzed in ImageJ. Cell size average from biological triplicates (n = 3) and P-value (∗∗, P < 0.01; ∗, P < 0.05; NS, not significant) by ANOVA test as indicated. E, Mass of untreated (CTL) cells, surviving cells at 10 DPT, and progeny at 28 DTP (HCC1806, 786-0), 21 DTP (HCT116), and 49 DTP (U1890). Cell mass average from biological triplicates (n = 3) and P-value (∗∗, P < 0.01; ∗, P < 0.05; NS, not significant) by ANOVA test as indicated. F, Cell diameter distributions and frequency of 10,000 sorted HCC1806 cells in control (CTL) and treated cells at 0 DPT, 5 DPT, and 10 DPT (biological replicates n = 3). G, Representative image of proliferating clones of progeny 28 DTP (HCC1806, 786-0, HCT116, and U1890). Cells are stained with 0.5% crystal violet solution. H, Distribution of surviving cells that died or regained proliferative capacity 2 months after treatment of HCC1806, 786-0, HCT116, and U1890 cells. Treated and filtered cells (n = 96) at 0 DPT were transferred to individual wells. Average of the number of wells with dead cells, large cells, and proliferating progeny cells from biological replicates (n = 3) and P value (∗∗, P < 0.01; ∗, P < 0.05, significant relative to vehicle) by ANOVA test as indicated.
Data from Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation
Authors: Carroll Christopher , Manaprasertsak Auraya , Boffelli Castro Arthur , van den Bos Hilda , Spierings Diana C.J. , Wardenaar René , Bukkuri Anuraag , Engström Niklas , Baratchart Etienne , Yang Minjun , Biloglav Andrea , Cornwallis Charlie K. , Johansson Bertil , Hagerling Catharina , Arsenian-Henriksson Marie , Paulsson Kajsa , Amend Sarah R. , Mohlin Sofie , Foijer Floris , McIntyre Alan , Pienta Kenneth J. , Hammarlund Emma U.
Published: March 2024

Abstract
Therapeutic resistance and recurrence remain core challenges in cancer therapy. How therapy resistance arises is currently not fully understood with tumors surviving via multiple alternative routes. Here, we demonstrate that a subset of cancer cells survives therapeutic stress by entering a transient state characterized by whole-genome doubling. At the onset of the polyploidization program, we identified an upregulation of key transcriptional regulators, including the early stress-response protein AP-1 and normoxic stabilization of HIF2α. We found altered chromatin accessibility, ablated expression of retinoblastoma protein (RB1), and enrichment of AP-1 motif accessibility. We demonstrate that AP-1 and HIF2α regulate a therapy resilient and survivor phenotype in cancer cells. Consistent with this, genetic or pharmacologic targeting of AP-1 and HIF2α reduced the number of surviving cells following chemotherapy treatment. The role of AP-1 and HIF2α in stress response by polyploidy suggests a novel avenue for tackling chemotherapy-induced resistance in cancer.
Significance:
In response to cisplatin treatment, some surviving cancer cells undergo whole-genome duplications without mitosis, which represents a mechanism of drug resistance. This study presents mechanistic data to implicate AP-1 and HIF2α signaling in the formation of this surviving cell phenotype. The results open a new avenue for targeting drug-resistant cells.
Prior Exposure to Experimental Preeclampsia Increases Atherosclerotic Plaque Inflammation in Atherogenic Mice—Brief Report
Authors: Biwer Lauren A. , Man Joshua J. , Camarda Nicholas D. , Carvajal Brigett V. , Karumanchi S. Ananth , Jaffe Iris Z.
Published: March 2024

BACKGROUND:

Women with a history of preeclampsia have evidence of premature atherosclerosis and increased risk of myocardial infarction and stroke compared with women who had a normotensive pregnancy. Whether this is due to common risk factors or a direct impact of prior preeclampsia exposure has never been tested in a mouse atherosclerosis model.

METHODS:

Pregnant LDLR-KO (low-density lipoprotein receptor knockout; n=35) female mice were randomized in midgestation to sFlt1 (soluble fms-like tyrosine kinase 1)-expressing adenovirus or identical control adenovirus. Postpartum, mice were fed high-fat diet for 8 weeks to induce atherogenesis. Comparison between the control and preeclampsia models was made for metabolic parameters, atherosclerosis burden and composition by histology, plaque inflammation by flow cytometry, and aortic cytokines and inflammatory markers using a cytokine array.

RESULTS:

In pregnant LDLR-KO mice, sFlt1 adenovirus significantly induced serum sFlt1, blood pressure, renal endotheliosis, and decreased pup viability. After 8 weeks of postpartum high fat feeding, body weight, fasting glucose, plasma cholesterol, HDL (high-density lipoprotein), and LDL (low-density lipoprotein) were not significantly different between groups with no change in aortic root plaque size, lipid content, or necrotic core area. Flow cytometry demonstrated significantly increased CD45+ aortic arch leukocytes and CD3+T cells and aortic lysate contained more CCL (CC motif chemokine ligand) 22 and fetuin A and decreased expression of IGFBP6 (insulin-like growth factor-binding protein 6) and CCL21 in preeclampsia-exposed mice compared with controls.

CONCLUSIONS:

In atherogenic LDLR-KO mice, exposure to sFlt1-induced preeclampsia during pregnancy increases future atherosclerotic plaque inflammation, supporting the concept that preeclampsia directly exacerbates atherosclerotic inflammation independent of preexisting risk factors. This mechanism may contribute to ischemic vascular disease in women after preeclampsia pregnancy.
The Implicit Association Test
Authors: Ratliff Kate A. , Smith Colin Tucker
Published: March 2024

Among the general public and behavioral scientists alike, the Implicit Association Test (IAT) is the best known and most widely used tool for demonstrating implicit bias: the unintentional impact of social group information on behavior. More than forty million IATs have been completed at the Project Implicit research website. These public datasets are the most comprehensive documentation of IAT and self-reported bias scores in existence. In this essay, we describe the IAT procedure, summarize key findings using the IAT to document the pervasiveness and correlates of implicit bias, and discuss various ways to interpret IAT scores. We also highlight the most common uses of the IAT. Finally, we discuss unanswered questions and future directions for the IAT specifically, and implicit bias research more generally.
Uncovering Implicit Racial Bias in the Brain: The Past, Present & Future
Authors: Kubota Jennifer T.
Published: March 2024

Neuroscience is a fantastic tool for peeking inside our minds and unpacking the component processes that drive social group biases. Brain research is vital for studying racial bias because neuroscientists can investigate these questions without asking people how they think and feel, as some individuals may be unaware or reluctant to report it. For the past twenty-five years, neuroscientists have diligently mapped implicit racial bias's neural foundations. As with any new approach, the emergence of neuroscience in studying implicit racial bias has elicited excitement and skepticism: excitement about connecting social biases to biological machinery, and skepticism that neuroscience may provide little to our understanding of social injustice. In this essay, I dive into what we have learned about implicit racial bias from the brain and the limitations of our current approach. I conclude by discussing what is on the horizon for neuroscience research on racial bias and social injustice.
Thoughts Turned to Jesus (or someone very probably, almost certainly, clearly somewhat like him) on Reading Crossley and Myles, Jesus
Authors: Seesengood Robert Paul
Published: March 2024

This essay is an extended review of, and engagement with, James Crossley and Robert J. Myles’s Jesus: A Life in Class Conflict (2023). The review particularly commends them for a work which addresses the difficult question of whether one is able to recover an ‘historical’ figure from tradition, and notes that effort, in many ways, becomes a compelling form of reception criticism. It notes, as well, some key places for future consideration (e.g., the implications of their work for masculinity studies).
Creating through Copying: Materia Medica, Women Painters, and Late Ming Culture
Authors: Gao Ruiying
Published: March 2024

In the late Ming, illustrated materia medica works became increasingly salient among educated elites in the Jiangnan area. This article analyzes two hand-illustrated treatises, Jinshi kunchong caomu zhuang and Bencao tupu, and the cultural contexts of their production. The interplays between copying and editing and image-text relationships in the two works provide insight into how materia medica was exploited as a pictorial subject for ideas about the human-nature dynamic. I demonstrate that materia medica images represented symbolic possession of the natural world and thus served as a maker of social distinction. I also shed light on the perpetuated tradition of making images of materia medica as an intellectual practice. My examinations of materia medica images by women artists also challenge the correlations between gender and representations of flora and fauna in the historiography of Chinese paintings.
Great Expectation in Shadow: Globalization and Young Chinese Entrepreneurs in Africa
Authors: Jun Yan , Xianju Guo , Liu Yuzhao
Published: March 2024

As China’s economic power continues to globalize, more and more Chinese companies and people are going overseas to explore new opportunities. In contrast to the existing research that focuses on the overseas operations of Chinese companies or general immigration phenomena, this study focuses on an emerging group of young entrepreneurs in Africa. Based on three exemplary case studies, this paper attempts to explore these young people’s reasons for going to Africa, their strategies for coping with difficulties, and their gradually formed new lifestyles and self-awareness. The study finds that this group has a stronger “entrepreneurial spirit” than the domestic mobile population of the same age, which is also in the context of individualization, and thus shows a different process of individualization. The members of this group came to Africa with high expectations, used creative solutions to solve various problems in work and life, and dared to break traditions, building their life trajectories and self-understanding in continuous actions. Different from the previous immigrant groups, young entrepreneurs in Africa represent a new way for Chinese people to go out in the world in the era of globalization.
The first record of the giant pill-millipede genus Prionobelum Verhoeff, 1924 from Thailand, with the integrative description of two species (Diplopoda, Sphaerotheriida, Zephroniidae)
Authors: DONWORTH PATRICK , WESENER THOMAS
Published: March 2024

Thailand hosts a very rich but underexplored giant pill-millipede (Sphaerotheriida) fauna, with 11 of its 13 species described in the last three years. Currently, all known Thai giant pill-millipedes belong to the genera Zephronia Gray, 1832 (nine species) and Sphaerobelum Verhoeff, 1924 (four species). Here we describe the first two species of the genus Prionobelum Verhoeff, 1924 (previously restricted to Vietnam and China), Prionobelum inthanonense n. sp. and P. naevium n. sp. from Thailand. The species occur at Thailand’s highest mountain (2500 m) Doi Inthanon and the lowland rainforests at Bang Lang National Park touching the border with Malaysia. Both species are described integratively, utilizing light microscopy, scanning electron microscopy as well as DNA barcoding. Both new species of Prionobelum differ from other Zephroniidae species, as well as from one another, by more than 20% p-distance in the COI barcoding gene suggesting that potential closer related species are still awaiting discovery.
Inertial Effect and Its Dependency on the Topographic Geometries in Barotropic Channel Models under the Weakly Nonlinear Regime
Authors: Matsuta Takuro , Mitsudera Humio
Published: March 2024

Recent studies have shown that the sensitivity of the circumpolar transport of channels to the westerlies is controlled by wind-driven gyre circulations. Although the form stress associated with the gyres has been shown to be controlled by eddies, bottom friction, and topographic width, the role of inertial effects has not been fully understood. In this study, we conduct a series of sensitivity analyses using the barotropic model with and without the advection term (hereinafter, the model without the advection term is denoted as linear model). Experiments showed that the sensitivity of the circumpolar transport decreased under the westerly winds compared to the linear model, while it increased under the easterly winds. We show that the inertial effect of western boundary currents generates anomalous anticyclonic circulations over the topography, producing the westward topographic form stress anomalies regardless of the wind directions. In addition, we discuss the sensitivity of the inertial effect mechanism to topographic height, width, and geometries. The inertial effect mechanism is robust as long as the gyre circulations dominate while its relative importance changes. We also found that the dynamics of the barotropic channel strongly depend on the geometries of geostrophic contours f/h. Therefore, we conclude that the dynamics of barotropic channel models might be interpreted with caution to understand the dynamics of the Southern Ocean.

Significance Statement

Previous studies have studied baroclinic and barotropic channel models as a benchmark of the Southern Ocean, but the nonlinear dynamics of channels have not been fully understood. In this paper, we show that the inertial effect by the mean flow works to decrease the sensitivity to the westerly winds in the barotropic channel models using numerical experiments. We also show that the inertial effect is robust as long as gyre circulations exist, while its relative importance differs.
Propaganda channels and their comparative effectiveness: The case of Russia’s war in Ukraine
Authors: Oleinik Anton , Paniotto Volodymyr
Published: March 2024

Since Lasswell, propaganda has been considered one of three chief implements of warfare, along with military and economic pressure. Russia’s invasion of Ukraine revives public and scholarly interest in war propaganda. The Russian political leader frames the war as an imperial war. The Ukrainian political leader frames it as a war of national liberation. The discursive battle thus complements the military combat. The outcome of the discursive combat depends on the effectiveness of propaganda deployed by the parties involved. Propaganda effectiveness is the propagation of war-related messages stated by political leaders through various media with no or few distortions. The effectiveness of propaganda is compared (1) across countries, with a particular focus on two belligerents, Russia and Ukraine, (2) in the function of the medium (mass media, digital media), and (iii) using two different methods (content analysis and survey research). Data were collected during the first year of the large-scale invasion (February 2022 to February 2023). Survey data allowed measuring the degree of the target audience’s agreement with key propagated messages.
Utilizing waste manhole covers and fibreboard as reinforcing fillers for thermoplastic composites
Authors: Ayrilmis Nadir , Kanat Gürdal , Yildiz Avsar Esra , Palanisamy Sivasubramanian , Ashori Alireza
Published: March 2024

This study investigated the potential of using recycled manhole cover flour (CMC) and medium density fibreboard (MDF) sawdust as low cost fillers for recycled polypropylene (PP) composites. Various compositions of CMC and MDF flour, up to 40 wt% (20 wt% CMC and 20 wt% MDF), were compounded with recycled PP using maleic anhydride grafted PP. The results showed that increasing the filler content improved the bending strength and modulus, reaching 46.4 MPa and 3399 MPa, respectively, at 40 wt% loading. However, the tensile strength decreased slightly with the addition of 10 wt% filler and showed a slight decrease with the increase in filler content from 20 to 40 wt%. The water absorption of the composites showed only a slight increase from 0% for pure PP to 0.007% for composites with 40 wt% filler. Thermogravimetric analysis confirmed the thermal stability of the composites up to about 400°C. This study demonstrated the potential of using a blend of waste CMC and MDF flour up to 40 wt% to improve the strength and water resistance of recycled PP composites, offering a promising and sustainable approach to cost-effective composite production.
Factors Associated With the Cardiovascular Health of Black and Latino Adults With Type 2 Diabetes
Authors: McCarthy Margaret M. , Fletcher Jason , Wright Fay , Del Giudice Inés , Wong Agnes , Aouizerat Bradley E. , Vaughan Dickson Victoria , Melkus Gail D’Eramo
Published: March 2024

Aims

The purpose of this study was to assess the levels of cardiovascular health (CVH) of Black and Latino adults with type 2 diabetes (T2D) and examine the association of individual and microsystem level factors with their CVH score.

Methods

This was a cross-sectional design in 60 Black and Latino Adults aged 18–40 with T2D. Data were collected on sociodemographic, individual (sociodemographic, diabetes self-management, sleep disturbance, depressive symptoms, quality of life, and the inflammatory biomarkers IL-6 and hs-CRP) and microsystem factors (family functioning), and American Heart Association’s Life’s Simple 7 metrics of CVH. Factors significantly associated with the CVH score in the bivariate analyses were entered into a linear regression model.

Results

The sample had a mean age 34 ± 5 years and was primarily female (75%) with a mean CVH score was 8.6 ± 2.2 (possible range of 0–14). The sample achieved these CVH factors at ideal levels: body mass index <25 kg/m2 (8%); blood pressure <120/80 (42%); hemoglobin A1c < 7% (57%); total cholesterol <200 mg/dL (83%); healthy diet (18%); never or former smoker > one year (95%); and physical activity (150 moderate-to-vigorous minutes/week; 45%). In the multivariable model, two factors were significantly associated with cardiovascular health: hs-CRP (B = −0.11621, p < .0001) and the general health scale (B = 0.45127, p = .0013).

Conclusions

This sample had an intermediate level of CVH, with inflammation and general health associated with overall CVH score.
Commentary on 2022 guidelines on clinical trial design in cluster headache and further suggestions
Authors: Medrea Ioana , Tepper Stewart J. , Wang Donliang , Mathew Paul G. , Burish Mark
Published: March 2024

Background

New guidelines for cluster headache clinical trials were recently published. We welcome these new guidelines and raise additional considerations in trial methodologies.

Main body

We present non-inferiority trials to overcome ethical issues with placebo use, and additionally discuss issues with trial recruitment.

Conclusions

We highlight some possible issues and solutions to be considered with the recently published cluster headache trial guidelines.
Exploring Aeromonas dhakensis in Aldabra giant tortoises: a debut report and genetic characterization
Authors: Zhao Chenxu , Qin Panpan , Li Shuai , Chen Zilu , Wang Tianliang , Liang Qunchao , He Weishi , Peng Zeyu , Yang Yurong , Peng Zhifeng , Li Yongtao
Published: March 2024

Aeromonas dhakensis (A. dhakensis) is becoming an emerging pathogen worldwide, with an increasingly significant role in animals and human health. It is a ubiquitous bacteria found in terrestrial and aquatic milieus. However, there have been few reports of reptile infections. In this study, a bacterial strain isolated from a dead Aldabra giant tortoise was identified as A. dhakensis HN-1 through clinical observation, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF/MS), and gene sequencing analysis. Subsequently, to evaluate its pathogenicity, the detection of virulence genes and mice infection experiments were performed. A. dhakensis HN-1 was found to contain seven virulence genes, including alt, ela, lip, act, aerA, fla, and hlyA. Mice infected with A. dhakensis HN-1 exhibited hemorrhage of varying degrees in multiple organs. The half-maximal lethal dose (LD50) value of A. dhakensis HN-1 for mice was estimated to be 2.05 × 107 colony forming units (CFU)/mL. The antimicrobial susceptibility test revealed that A. dhakensis HN-1 was resistant to amoxicillin, penicillin, ampicillin and erythromycin. This is the first report of A. dhakensis in Aldabra giant tortoises, expanding the currently known host spectrum. Our findings emphasize the need for One Health surveillance and extensive research to reduce the spread of A. dhakensis across the environment, humans, and animals.