bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution and genetic architecture of sex-limited polymorphism in cuckoos
Authors: Merondun Justin , Marques Cristiana I. , Andrade Pedro , Meshcheryagina Swetlana , Galván Ismael , Afonso Sandra , Alves Joel M. , Araújo Pedro M. , Bachurin Gennadiy , Balacco Jennifer , Bán Miklós , Fedrigo Olivier , Formenti Giulio , Fossøy Frode , Fülöp Attila , Golovatin Mikhail , Granja Sofia , Hewson Chris , Honza Marcel , Howe Kerstin , Larson Greger , Marton Attila , Moskát Csaba , Mountcastle Jacquelyn , Procházka Petr , Red’kin Yaroslav , Sims Ying , Šulc Michal , Tracey Alan , Wood Jonathan M. D. , Jarvis Erich D. , Hauber Mark E. , Carneiro Miguel , Wolf Jochen B. W.
Published: April 2024

Sex-limited polymorphism has evolved in many species including our own. Yet, we lack a detailed understanding of the underlying genetic variation and evolutionary processes at work. The brood parasitic common cuckoo (
Cuculus canorus
) is a prime example of female-limited color polymorphism, where adult males are monochromatic gray and females exhibit either gray or rufous plumage. This polymorphism has been hypothesized to be governed by negative frequency-dependent selection whereby the rarer female morph is protected against harassment by males or from mobbing by parasitized host species. Here, we show that female plumage dichromatism maps to the female-restricted genome. We further demonstrate that, consistent with balancing selection, ancestry of the rufous phenotype is shared with the likewise female dichromatic sister species, the oriental cuckoo (
Cuculus optatus
). This study shows that sex-specific polymorphism in trait variation can be resolved by genetic variation residing on a sex-limited chromosome and be maintained across species boundaries.
HIV-1 uncoating requires long double-stranded reverse transcription products
Authors: Burdick Ryan C. , Morse Michael , Rouzina Ioulia , Williams Mark C. , Hu Wei-Shau , Pathak Vinay K.
Published: April 2024

HIV-1 cores, which contain the viral genome and replication machinery, must disassemble (uncoat) during viral replication. However, the viral and host factors that trigger uncoating remain unidentified. Recent studies show that infectious cores enter the nucleus and uncoat near the site of integration. Here, we show that efficient uncoating of nuclear cores requires synthesis of a double-stranded DNA (dsDNA) genome >3.5 kb and that the efficiency of uncoating correlates with genome size. Core disruption by capsid inhibitors releases viral DNA, some of which integrates. However, most of the viral DNA is degraded, indicating that the intact core safeguards viral DNA. Atomic force microscopy and core content estimation reveal that synthesis of full-length genomic dsDNA induces substantial internal strain on the core to promote uncoating. We conclude that HIV-1 cores protect viral DNA from degradation by host factors and that synthesis of long double-stranded reverse transcription products is required to trigger efficient HIV-1 uncoating.
Optoelectronically navigated nano-kirigami microrotors
Authors: Hong Xiaorong , Xu Bingrui , Li Gong , Nan Fan , Wang Xian , Liang Qinghua , Dong Wenbo , Dong Weikang , Sun Haozhe , Zhang Yongyue , Li Chongrui , Fu Rongxin , Wang Zhuoran , Shen Guozhen , Wang Yeliang , Yao Yugui , Zhang Shuailong , Li Jiafang
Published: April 2024

With the rapid development of micro/nanofabrication technologies, the concept of transformable kirigami has been applied for device fabrication in the microscopic world. However, most nano-kirigami structures and devices were typically fabricated or transformed at fixed positions and restricted to limited mechanical motion along a single axis due to their small sizes, which significantly limits their functionalities and applications. Here, we demonstrate the precise shaping and position control of nano-kirigami microrotors. Metallic microrotors with size of ~10 micrometers were deliberately released from the substrates and readily manipulated through the multimode actuation with controllable speed and direction using an advanced optoelectronic tweezers technique. The underlying mechanisms of versatile interactions between the microrotors and electric field are uncovered by theoretical modeling and systematic analysis. This work reports a novel methodology to fabricate and manipulate micro/nanorotors with well-designed and sophisticated kirigami morphologies, providing new solutions for future advanced optoelectronic micro/nanomachinery.
Robot pack mules remain science fiction for now
Authors: Murphy Robin R.
Published: April 2024

The plot of the 2014 science-fiction movie
Young Ones
revolves around a robot pack mule based on the real-world BigDog.
Grasping objects with the aid of haptics
Authors: Matsiko Amos
Published: April 2024

A smart suction cup uses haptics to supplement vision for exploration of objects in a grasping task.
In vitro
activity of gepotidacin and comparator antimicrobials against isolates of nontuberculous mycobacteria (NTM)
Authors: Brown-Elliott Barbara A. , Bush Georgie , Hughes M. Dolores , Rodriguez Eliana , Weikel Chase A. , Min Sharon B. , Wallace Richard J.
Published: April 2024

Novel antimicrobials are needed to treat rising nontuberculous mycobacteria (NTM) infections. Using standard broth microdilution methods, 68 NTM isolates were tested against gepotidacin, a new, first-in-class, oral triazaacenaphthylene bacterial topoisomerase inhibitor. MICs varied (0.25 to >64 µg/mL) with the lowest being
M. fortuitum
complex (0.25–8 µg/mL),
M. mucogenicum
complex (1–2 µg/mL),
M. kansasii
(0.25–8 µg/mL), and
M. marinum
(4–16 µg/mL). Testing greater numbers of some species is suggested to better understand gepotidacin activity against NTM.
Supplemental Material: Long-eccentricity pacing of alluvial stratigraphic architecture in the Eocene Bighorn Basin, Wyoming, USA
Authors: Wang Youwei , Abels Hemmo A , al. et
Published: April 2024

Figure S1 (UAV-based photogrammetric model in the LIME software) and Figure S2 (comparison of channelized sandstone width and depth in Intervals II and III exhibiting varying dominance of river styles).  
Pursuance of a Yoruba name for cervical cancer in Southwest Nigeria: a case study
Authors: Balogun Folusho Mubowale , Omotade Olayemi
Published: April 2024

Objectives

Participants’ comprehension of research process affects the quality of research output, which is the reason why translation of research instruments into local languages is standard practice. Literature has consistently reported that in Africa, knowledge about cervical cancer is low but paradoxically, expressed, and actual uptake of human papillomavirus vaccine for its prevention is high. This study explored the Yoruba names of cervical cancer among Yoruba people in Ibadan, Nigeria to guide the translation of cervical cancer research instruments to Yoruba language.

Design

Exploratory case study design was used and data were obtained with 10 in-depth interviews and four focused group discussions. Data were analysed using content analysis.

Settings

The study took place in Ibadan North local government area, Southwest Nigeria.

Participants

These were 4 traditional healers, 3 Yoruba linguists, 3 public health educators and 38 parents of adolescents.

Measures

These were Yoruba names for cervical cancer and their meanings.

Results

Participants were aware of cervical cancer but only the traditional healers and public health educators had names for it. These names were highly varied. The public health educators gave names that were linked with different parts of the female reproductive system and external genital which were actually different medical conditions. Each traditional healer also had different names for cervical cancer, which either described the female body parts, or symptoms of female genital infections. These various names can lead to unnecessary misconceptions and misinformation about cervical cancer, its prevention, management, and research.

Conclusions

There was no consensus Yoruba name for cervical cancer among the study participants. Efforts to educate the Yoruba speaking populace about cervical cancer, its prevention, management and participation in its research can be frustrated if a generally accepted Yoruba name is not provided for this cancer. Stakeholders’ collaboration is required to get an appropriate Yoruba name for cervical cancer.
Association between onychomycosis and ulcerative complications in patients with diabetes: a longitudinal cohort study in Dutch general practice
Authors: Watjer Roeland M , Heckmans Kim ML , Eekhof Just AH , Gummi Luise , Quint Koen D , Numans Mattijs E , Bonten Tobias N
Published: April 2024

Introduction

Diabetic foot ulcers are feared complications of diabetes mellitus (DM), requiring extensive treatment and hospital admissions, ultimately leading to amputation and increased mortality. Different factors contribute to the development of foot ulcers and related complications. Onychomycosis, being more prevalent in patients with diabetes, could be an important risk factor for developing ulcers and related infections. However, the association between onychomycosis and diabetic complications has not been well studied in primary care.

Research design and methods

To determine the impact of onychomycosis on ulcer development and related complications in patients with diabetes in primary care, a longitudinal cohort study was carried out using routine care data from the Extramural Leiden University Medical Center Academic Network. Survival analyses were performed through Cox proportional hazards models with time-dependent covariates.

Results

Data from 48 212 patients with a mean age of 58 at diagnosis of DM, predominantly type 2 (87.8%), were analysed over a median follow-up of 10.3 years. 5.7% of patients developed an ulcer. Onychomycosis significantly increased the risk of ulcer development (HR 1.37, 95% CI 1.13 to 1.66), not affected by antimycotic treatment, nor after adjusting for confounders (HR 1.23, 95% CI 1.01 to 1.49). The same was found for surgical interventions (HR 1.54, 95% CI 1.35 to 1.75) and skin infections (HR 1.48, CI 95% 1.28 to 1.72), again not affected by treatment and significant after adjusting for confounders (HR 1.32, 95% CI 1.16 to 1.51 and HR 1.27, 95% CI 1.10 to 1.48, respectively).

Conclusions

Onychomycosis significantly increased the risk of ulcer development in patients with DM in primary care, independently of other risk factors. In addition, onychomycosis increased the risk of surgeries and infectious complications. These results underscore the importance of giving sufficient attention to onychomycosis in primary care and corresponding guidelines. Early identification of onychomycosis during screening and routine care provides a good opportunity for timely recognition of increased ulcer risk.
Photobiomodulation in the treatment of palmar–plantar erythrodysesthesia: a randomised controlled clinical study protocol
Authors: Lestido Valentina , Rodríguez Florencia , Rodríguez Agustín , Pombo Valeria , Barrios Romina , Pavani Christiane
Published: April 2024

Introduction

Hand–foot syndrome, also known as palmar–plantar erythrodysesthesia (PPE), is a complication caused by chemotherapy. Clinically, it manifests as erythema and oedema on the palms of the hands and feet, dry and scaly skin, accompanied by a sensation of tightness and pain. Extreme cases have blisters and ulcerations that may require hospitalisation and/or pause in cancer treatment. It can also be accompanied by paraesthesia. Considering the characteristics, photobiomodulation (PBM) may reduce the PPE effects. The objective of this protocol will be to evaluate the efficacy of PBM in reducing PPE induced by capecitabine and 5-fluorouracil chemotherapy.

Methods and analysis

This will be a randomised controlled, double-blind, double-centre clinical trial (Centro Asistencial del Sindicato Médico del Uruguay and Instituto Nacional del Cáncer from Uruguay). The sample population (40 individuals) will be divided into two groups: group 1 will receive moisturising cream plus PBM treatment and group 2 moisturising cream plus PBM sham treatment, at the ratio of 1:1. PBM will be performed at 630 nm two times per week in palmoplantar areas of the hands and feet (4 J/cm2), for 4 weeks. The PPE degree and the data referring to the chemotherapy treatment plan will be measured, prior to the start of treatment in the middle and at the end of it. Quality of life questionnaires will be applied at the beginning of the trial and at the end of treatment. The data will be analysed based on the intention-to-treat analysis and α<0.05 will be considered statistically significant.

Ethics and dissemination

The protocol was approved by the Research Ethics Committee of Universidad Católica del Uruguay (220316b), of Centro Asistencial del Sindicato Médico del Uruguay (221989) and of Instituto Nacional del Cáncer (2023-04). The recruitment has already started (March 2023). Protocol version: V.2, 27 October 2023.

Trial registration number

ClinicalTrials.gov Registry (NCT05337423).
Explore the effect of apparent temperature and air pollutants on the admission rate of acute myocardial infarction in Chongqing, China: a time-series study
Authors: Bai Xiuyuan , Ming Xin , Zhao Mingming , Zhou Li
Published: April 2024

Objective

Limited research has been conducted on the correlation between apparent temperature and acute myocardial infarction (AMI), as well as the potential impact of air pollutants in modifying this relationship. The objective of this study is to investigate the lagged effect of apparent temperature on AMI and assess the effect modification of environmental pollutants on this association.

Design

A time-series study.

Setting and participants

The data for this study were obtained from the Academy of Medical Data Science at Chongqing Medical University, covering daily hospitalisations for AMI between 1 January 2015 and 31 December 2016. Meteorological and air pollutant data were provided by China’s National Meteorological Information Centre.

Outcome measures

We used a combined approach of quasi-Poisson generalised linear model and distributed lag non-linear model to thoroughly analyse the relationships. Additionally, we employed a generalised additive model to investigate the interaction between air pollutants and apparent temperature on the effect of AMI.

Result

A total of 872 patients admitted to hospital with AMI were studied based on the median apparent temperature (20.43°C) in Chongqing. Low apparent temperature (10th, 7.19℃) has obvious lagged effect on acute myocardial infarction, first appearing on the 8th day (risk ratio (RR) 1.081, 95% CI 1.010 to 1.158) and the greatest risk on the 11th day (RR 1.094, 95% CI 1.037 to 1.153). No lagged effect was observed at high apparent temperature. In subgroup analysis, women and individuals aged 75 and above were at high risk. The interaction analysis indicates that there exist significant interactions between PM2.5 and high apparent temperature, as well as nitrogen dioxide (NO2) and low apparent temperature.

Conclusion

The occurrence of decreased apparent temperature levels was discovered to be linked with a heightened relative risk of hospitalisations for AMI. PM2.5and NO2have an effect modification on the association between apparent temperature and admission rate of AMI.
Safety of different concentrations of glycerine enema for meconium evacuation in preterm infants: study protocol for a randomised controlled trial
Authors: Li Xia , Liu Changhong , Zhang Jing , Yu Qingling , Guo Xuemei , Hu Yanling , Shi Jing
Published: April 2024

Introduction

Various approaches are employed to expedite the passage of meconium in preterm infants within the neonatal intensive care unit (NICU), with glycerine enemas being the most frequently used. Due to the potential risk of high osmolality-induced harm to the intestinal mucosa, diluted glycerine enema solutions are commonly used in clinical practice. The challenge lies in the current lack of knowledge regarding the safest and most effective concentration of glycerine enema. This research aims to ascertain the safety of different concentrations of glycerine enema solution in preterm infants.

Methods and analysis

This study protocol is for a single-centre, two-arm, parallel-group, double-blind and non-inferiority randomised controlled trial. Participants will be recruited from a NICU in a teriary class A hospital in China, and eligible infants will be randomly allocated to either the glycerine (mL): saline (mL) group in a 3:7 ratio or the 1:9 ratio group. The enema procedure will adhere to the standardised operational protocols. Primary outcomes encompass necrotising enterocolitis and rectal bleeding, while secondary outcomes encompass feeding parameters, meconium passage outcomes and splanchnic regional oxygen saturation. Analyses will compare the two trial arms based on an intention-to-treat allocation.

Ethics and dissemination

This trial is approved by the ethics committee of the Medical Ethics Committee of West China Second University Hospital of Sichuan University. The results will be published in a peer-reviewed journal.

Trial registration number

ChiCTR2300079199.
Early adopter insights on physical impact mill technology for harvest weed seed control in Canada
Authors: Tidemann Breanne D. , Geddes Charles M. , Sharpe Shaun M.
Published: April 2024

The evolution and spread of herbicide resistance among the weed community has increased interest in alternative weed management strategies such as harvest weed seed control. Western Canadian producers have begun adopting physical impact mills as an additional weed management strategy. A survey of early adopters of physical impact mill technology in Canada was conducted to better understand the motivations behind producers adopting, initial experiences, and research needs. Ten producers responded to the survey, accounting for 18 out of an estimated 30 impact mills in use in Canada, believed to be located primarily in the Canadian Prairies. These producers were mainly from larger farms (>4000 ha), equipped the majority of their combines (75% average) and used the mills in essentially all crops grown. The majority of respondents were located in Saskatchewan, with two mills being used in Alberta. Wild oat ( Avena fatua L.) (60%) and kochia ( Bassia scoparia (L.) A.J. Scott) (50%) were the weeds most frequently mentioned as specific motivators of impact mill adoption. Average increased fuel cost from the mill was estimated at CAD$3.46 ha−1, with average annual maintenance costs of about $1500 per impact mill. Producers relied on information from mill companies and other early-adopting farmers primarily, followed by extension talks and social media. Research needs were also identified by producers that could inform the future direction of harvest weed seed control research in Canada. Future research should focus on confirming efficacy, optimizing combine settings, and looking at integrated systems with precision agriculture technologies.
Mathematical modeling of interactions between colon cancer and immune system with a deep learning algorithm
Authors: Raeisi Elham , Yavuz Mehmet , Khosravifarsani Mohammadreza , Fadaei Yasin
Published: April 2024

Colon cancer is a complex disease with genetically unstable cell lines. In order to better understand the complexity of colon cancer cells and their metastatic mechanisms, we develop a mathematical model in this study. The model is based on a system of fractional-order differential equations and Fractional-Cancer-Informed Neural Networks (FCINN). The model captures a dynamic network of interactions between dendritic cells (DCs), cytotoxic T-cells (CD$$8^+$$8+), helper T-cells (CD$$4^+$$4+), and colon cancer cells through fractional differential equations. By varying the fractional order between 0 and 1, we can classify patients into different groups based on their immune patterns. The goal of this paper is to identify different immune patterns and cancer cell behaviors, as well as the parameters that play an important role in metastasis, control, or elimination of cancer cells in the model. However, several parameters in the model are difficult to estimate in a patient-specific manner. To address this challenge, we use FCINN as an effective deep-learning tool for parameter estimation and numerical simulation of the model. Our findings suggest that the most effective factors in controlling the progression and preventing metastasis of colon cancer are the initial number of cancer cells, the inhibiting rates of tumor cells by DCs, the source of DCs, and the activation of helper T-cells by DCs. These findings suggest that DCs can be used as an immunotherapy tool for the control and treatment of colon cancer.
Eliminating sensing blind spots of field-enhanced Rydberg atomic antenna via an asymmetric parallel-plate resonator
Authors: Wu Bo , Zhou Yan-Li , Ding Zhen-Ke , Mao Rui-Qi , Qian Si-Xian , Wan Zhi-Qian , Liu Yi , An Qiang , Lin Yi , Fu Yun-Qi
Published: April 2024

Due to its large electric dipole moment, the Rydberg atom exhibits a strong response to weak electric fields, hence it is regarded as a highly promising atomic antenna. However, to enhance the reception sensitivity, split-ring resonators are needed normally, which will brings sensing blind spots. Thus it is not conducive to the application of full-coverage space communication. Here we propose that an atomic antenna with an asymmetric parallel-plate resonator, can not only enhance the received signal, but also eliminate sensing blind spots (pattern roundness can reach 7.8 dB while the split-ring resonator can be up to 39 dB). We analyze the influence of structural parameters on the field enhancement factor and directionality, and further discuss the limitation of the sensitivity by using thermal resistor noise theory. This work is expected to pave the way for the development of field-enhanced Rydberg atomic antennas that communicate without a blind spot.
Dark energy stars in the context of black holes — The physical profiles
Authors: Azman Muhamad Ashraf , Yusof Norhasliza , Kassim Hasan Abu , Marcos Juan Carlos Algaba
Published: April 2024

The dark energy star is a hypothetical model proposed as an alternative to address problems related to the structure of black holes (BHs), such as the presence of singularities. While dark energy star models have been previously explored, their application to BHs remains unexplored. This paper aims to investigate the concept of dark energy stars and compare their properties to BHs. The primary objective is to explore the physical profiles of dark energy stars and evaluate their similarity to the physical properties of BHs described by the Schwarzschild solution. To achieve this, specific properties of the dark energy star models need to be satisfied in the context of BHs, and their physical profiles are studied. The metric function [Formula: see text] proposed by M. R. Finch and J. E. F. Skea [Class. Quantum Grav. 6, 467 (1989)], as adopted by A. Banerjee, M. K. Jasim and A. Pradhan [Mod. Phys. Lett. A 35, 2050071 (2020), arXiv:1911.09546 [gr-qc]], is used and parametrized, making it close to BH spacetimes. The findings show that the model exhibits properties similar to BHs in terms of the stellar radius, compactness, surface redshift, and nature of gravity. Specifically, the dark energy star model behaves like BHs with a dark energy parameter [Formula: see text], satisfying all energy conditions. However, it should be noted that the investigation is limited to static spherically symmetric cases and further studies are required to explore the model in rotating cases. Overall, this study sheds light on the potential of dark energy star models in explaining BH properties and presents promising avenues for further research in understanding the nature of BHs and dark energy.
Particle Swarm Optimization-Based Multi-Objective Planning Model for Marketing Strategy Decision
Authors: Li Bohan , Guo Qi
Published: April 2024

Intelligent algorithms have shown promise in supporting marketing strategy decisions through data mining. However, existing methods have primarily relied on expertise, lacking autonomous decision-making abilities. Consequently, a marketing strategy decision model based on particle swarm optimization and multi-objective programming is proposed. This study first explores the potential for integrating particle optimization and multi-objective programming models partially, and then assesses the overall effectiveness of each marketing strategy by defining a fitness function. Subsequently, the particle swarm optimization algorithm is employed to search for and optimize decision variables to identify the optimal combination of marketing strategies. Finally, several simulation experiments are conducted using external real data. The research findings indicate that the algorithm’s error rate in this study was initially 0.23. However, after 500 training sessions, it decreased to 0.08 and maintained a relatively low level. The proportion of marketing strategy revenue increased by 15.2 percentage points between 0 and 100 training sessions, then remained relatively stable at over 30%. Its revenue proportion continued to rise during the training process, significantly surpassing that of other algorithms.
Fairness for Deep Learning Predictions Using Bias Parity Score Based Loss Function Regularization
Authors: Jain Bhanu , Huber Manfred , Elmasri Ramez
Published: April 2024

Rising acceptance of machine learning driven decision support systems underscores the need for ensuring fairness for all stakeholders. This work proposes a novel approach to increase a Neural Network model’s fairness during the training phase. We offer a frame-work to create a family of diverse fairness enhancing regularization components that can be used in tandem with the widely accepted binary-cross-entropy based accuracy loss. We use Bias Parity Score (BPS), a metric that quantifies model bias with a single value, to build loss functions pertaining to different statistical measures — even for those that may not be developed yet. We analyze behavior and impact of the newly minted regularization components on bias. We explore their impact in the realm of recidivism and census-based adult income prediction. The results illustrate that apt fairness loss functions can mitigate bias without forsaking accuracy even for imbalanced datasets.
Stability and Hopf bifurcation of a cytokine-enhanced HIV infection model with antibody immune response delay
Authors: Ye Zhijian , Zhou Yinggao , Zheng Zhoushun , Chen Chong
Published: April 2024

In this paper, the dynamical behaviors of a new cytokine-enhanced HIV infection model with intracellular delay [Formula: see text], virus replication delay [Formula: see text] and immune response delay [Formula: see text] are investigated. The positivity and boundedness of all solutions for the model with non-negative initial values have been proved. Moreover, two important biological parameters, called the virus reproductive number [Formula: see text] and the antibody immune reproductive number [Formula: see text] are established. By constructing suitable Lyapunov functionals and using LaSalle’s invariance principle, the global dynamics of the equilibria is completely determined by [Formula: see text] and [Formula: see text]. On the one hand, the results show that intracellular delay [Formula: see text], viral replication delay [Formula: see text] and immune response delay [Formula: see text] have no effect on the stability of [Formula: see text], [Formula: see text], and if [Formula: see text], [Formula: see text], [Formula: see text], the endemic equilibrium with the presence of antibody response [Formula: see text] is globally asymptotically stable. On the other hand, when [Formula: see text], [Formula: see text], [Formula: see text], numerical analysis confirms the theorems and suggests that time delay play a positive role in virus infection, with the increase of [Formula: see text], the dynamic behavior of the equilibrium [Formula: see text] will change as follows: locally asymptotically stable [Formula: see text] unstable; Hopf bifurcation appears.
How Does the Enhanced Mortality of Wolbachia-Infected Immature Mosquitoes Affect Dengue Transmission?
Authors: Wan Hui , Xu Jiaman
Published: April 2024

One of the promising strategies to reduce dengue transmission is to release Wolbachia-infected mosquitoes, which can reduce the reproductive success of wild female mosquitoes. We develop a dengue transmission model coupled with the Wolbachia infection to consider the impact of the increased mortality of Wolbachia-infected immature mosquitoes on Wolbachia invasion and dengue transmission. To begin with, we analyze the infection model of Wolbachia without dengue transmission dynamics. Next, we establish an optimal control model by introducing a control variable to simulate the continuous (daily) releases of Wolbachia-infected male mosquitoes and find the optimal control by using Pontryagin’s Maximum Principle. We determine the optimal release strategy by minimizing the total cost of releasing infected male mosquitoes. Then, the full dengue transmission model is analyzed. The basic reproduction number of dengue transmission is calculated using the next-generation matrix method. The stability of the dengue-free equilibrium is proved by using the method of monotone dynamical systems. Furthermore, we carry out sensitivity analysis to study the barrier effect of Wolbachia and the impact of the increased mortality of immature mosquitoes on dengue transmission. Our results suggest that the increased mortality of immature Wolbachia-infected mosquitoes is not conducive to Wolbachia establishment and dengue control, which also induces more Wolbachia-infected mosquitoes to be released. In particular, we estimate the threshold mortality rate of infected larvae by using bifurcation analysis, which provides a quantitative basis and theoretical support for rational selection of Wolbachia strains and scientific and effective practice of dengue control.
Oscillatory mechanism in menstrual cycle model regulated by negative feedback loops with two time delays
Authors: Wang Yao , Yu Feng , Yang Ling
Published: April 2024

The menstrual cycle of fertile female is regulated by multiple organs and hormones, controlling the reproductive health and fertility of females. This paper is dedicated to exploring how two negative feedback loops regulate and influence the dynamic behavior of the menstrual cycle. We simplified the regulation circuit of the menstrual cycle into a nonlinear differential equation with two time delays. This simplified mathematical model integrates the hypothalamus–pituitary–ovary primary negative feedback loop and the negative feedback auxiliary loop between the ovary and the pituitary. We investigated the delay-dependent conditions for the stability of the model’s equilibrium points and also demonstrated the presence of Hopf bifurcations. Theoretical analysis suggests that the primary feedback loop is the major factor driving oscillation in the system. Further numerical simulations indicate that the negative feedback auxiliary loop allows the system to adjust its amplitude while maintaining the robustness of the cycle length. Consequently, the results obtained from this model provide new insights into the regulation of oscillations in menstrual cycle irregularities.
Spatial Distribution and Pathogen Profile of Dermacentor reticulatus Ticks in Southeastern Poland: A Genetic and Environmental Analysis
Authors: Zając Zbigniew , Kulisz Joanna , Woźniak Aneta , Obregón Dasiel , Foucault-Simonin Angélique , Bartosik Katarzyna , Moutailler Sara , Cabezas-Cruz Alejandro
Published: April 2024

In recent years, significant changes have been observed in the distribution and abundance of local Dermacentor reticulatus populations. However, changes in D. reticulatus dynamics have not been studied in southeastern Poland. Our objective was to enhance our understanding of the environmental factors influencing the occurrence and density of D. reticulatus in this area. Additionally, we sought to investigate the genetic diversity of the tick population and the prevalence of tick‐borne pathogens (TBPs). To this end, we established 45 study sites in the Subcarpathian province. Ticks were collected during their peak activity in both spring and autumn. A subset of randomly selected specimens underwent molecular analysis for TBPs screening, using high‐throughput microfluidic real‐time PCR. Positive amplicons were then sequenced, and phylogenetic analyses were conducted. Our findings confirmed the presence of D. reticulatus ticks in 24 surveyed sites, primarily concentrated in the northern and eastern parts of the region. The mean density of D. reticulatus ticks in their compact range was 5.8 ± 6.4 specimens/100 m2. Notably, air temperature and altitude emerged as significant factors influencing the species’ activity. We also identified a high prevalence of Rickettsia raoultii infections in adult D. reticulatus, reaching up to 84.21%. Additionally, 9.52% of ticks were found to be infected with R. helvetica and 4.76% with Anaplasma phagocytophilum. Furthermore, our genetic analyses confirmed the identity of D. reticulatus in the Subcarpathian region, aligning with haplotypes found in other regions of Poland, Czechia, Croatia, and Portugal. In conclusion, our study suggests that the surveyed region represents the current boundary of the compact range of D. reticulatus in Poland in which this tick species exhibits low genetic diversity and a narrow spectrum of detected TBPs.
Nucleation‐Controlled Production of Sub‐50 nm Carbon Nanotubes through Electrochemical Conversion of Carbon Dioxide in Carbonate Molten Salt
Authors: Park Min Woo , Lee Chan Woo
Published: April 2024

The increasing emission of carbon dioxide worldwide has emerged as a major global concern in the context of addressing climate change. Converting CO2 to high‐value carbon materials is a promising solution to capture emitted carbon for achieving carbon neutrality. Furthermore, such conversion can provide carbon nanomaterials for key industries, including the lithium battery and fuel cell industries. Here, it is shown that sub‐50 nm tangled carbon nanotubes (CNTs) can be synthesized by adjusting the metaborate concentration and the current density through the electrochemical conversion of carbon dioxide in a molten carbonate salt. The metaborate ion concentration affects the product selectivity and carbon morphology, and the current density is strongly related to the particle size of in situ seed catalysts supplied by the dissolution of an Ni‐Fe‐Cr alloy anode. The optimized process conditions control the nucleation and growth of carbon via a tip‐growth mechanism, thereby promoting the formation of sub‐50 nm CNTs rather than bulky irregular carbon particles. The Raman and Brunauer–Emmett–Teller analyses showed that the properties of the prepared CNTs depended on the synthetic parameters. This study provides deep insights into the mechanism underlying carbon synthesis through the electrochemical reduction of a molten carbonate salt.
Spatial Dissection of the Immune Landscape of Solid Tumors to Advance Precision Medicine
Authors: Di Mauro Francesco , Arbore Giuseppina
Published: April 2024

Chemotherapeutics, radiation, targeted therapeutics, and immunotherapeutics each demonstrate clinical benefits for a small subset of patients with solid malignancies. Immune cells infiltrating the tumor and the surrounding stroma play a critical role in shaping cancer progression and modulating therapy response. They do this by interacting with the other cellular and molecular components of the tumor microenvironment. Spatial multi-omics technologies are rapidly evolving. Currently, such technologies allow high-throughput RNA and protein profiling and retain geographical information about the tumor microenvironment cellular architecture and the functional phenotype of tumor, immune, and stromal cells. An in-depth spatial characterization of the heterogeneous tumor immune landscape can improve not only the prognosis but also the prediction of therapy response, directing cancer patients to more tailored and efficacious treatments. This review highlights recent advancements in spatial transcriptomics and proteomics profiling technologies and the ways these technologies are being applied for the dissection of the immune cell composition in solid malignancies in order to further both basic research in oncology and the implementation of precision treatments in the clinic.
Table S3 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

Supplementary Table 3. DE genes between isotype treated EMT6 and EMT6-B7-H4+ tumors, early timepoint, 7 days post isotype treatment.
Table S1 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

Supplementary Table 1. DE genes between isotype treated and anti-PD-L1 treated EMT6 tumors.
Figure S1 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

Supplemental Figure 1. MMTV-neu epithelial and mesenchymal cells did not undergo EMT or MET. Single cell-derived clones were isolated from parental, heterogeneous MMTV-neu cells by FACS single-cell limiting dilutions. 16 epithelial and 10 mesenchymal single-cell clones were passaged independently for over 20 passages. After 13 passages, conditioned media from the alternate cell line was collected, filtered, and applied to a passage of each single-cell clone. Independent clones or clones treated with conditioned media did not undergo epithelial-to-mesenchymal or mesenchymal-to-epithelial transition in vitro. Two representative clones from each cell line are shown above.
FIGURE 6 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

B7-H4 expression does not correlate with resistance to chemotherapy + immunotherapy in human breast tumors. Patients were from the I-SPY2 clinical trial (paclitaxel control and pembrolizumab arms) or the TBCRC 043 clinical trial (carboplatin control and atezolizumab arms). A, In breast tumors from the I-SPY2 clinical trial (control and pembrolizumab arms), B7-H4 expression is higher in TNBC tumors compared with HR+ tumors. Data were analyzed by unpaired t test. B, In the same patient cohort, B7-H4 expression is not higher in grade III tumors compared with grade I (orange dots) or II. Data analyzed by unpaired t test. C and D, B7-H4 expression is not correlated with pCR in tumors regardless of HR status, treated with either paclitaxel or paclitaxel + pembrolizumab (ICI). Data analyzed by unpaired t test. E, EFS in HR+ (n = 89) and TNBC (n = 62) tumors from the I-SPY2 cohort. Tumors with high B7-H4+ expression (top 33% of patients) have worse EFS when treated with paclitaxel alone and no survival benefit when treated with paclitaxel + ICI. Data were analyzed by log-rank Mantel–Cox test. F, In the metastatic setting, PFS stratified by B7-H4 expression (top and bottom 33% of cohort) from primary breast biopsy or metastatic lesion in patients from the TBCRC 043 trial does not correlate with B7-H4 expression in either control or carboplatin + atezolizumab (ICI) groups. Data were analyzed by log-rank Mantel–Cox test. G and H, We also assessed survival by treatment status. Metastatic tumors (H) from TBCRC 043 with high B7-H4 expression had significantly improved PFS to ICI, and nonmetastatic tumors (I-SPY2) had minimal improvement to ICI (G). Data were analyzed by log-rank Mantel–Cox test. n = 151 patients for A–E and G; n = 91 patients for F and H.
FIGURE 4 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

Overexpression of B7-H4 in the EMT6 murine model induced resistance to anti-PD-L1 ICI. A, EMT6 cells were virally transduced with the pBabe-B7-H4 retroviral vector and overexpress exogenous murine B7-H4. B, EMT6 B7-H4+ tumors maintain high B7-H4 expression in vivo assessed by IHC. C, Animals were orthotopically injected with EMT6 cells ± B7-H4 and treated 1x per week with anti-PD-L1 at 200 µg (first dose) or 100 µg (subsequent doses) for 4 weeks, after tumors reached 100 mm3. D, EMT6-B7-H4+ tumors are significantly resistant to anti-PD-L1 immunotherapy compared with control tumors. Data were analyzed by one-way ANOVA of individual AUC values with Tukey post hoc test for multiple comparisons between EMT6 anti-PD-L1 and EMT6-B7-H4+ anti-PD-L1–treated groups (P = 0.0174, EMT6 Isotype n = 21, EMT6 anti-PD-L1 n = 23, EMT6-B7-H4+ Isotype n = 21, EMT6-B7-H4+ anti-PD-L1 n = 23. Data were collected from a total of three independent experiments). E and F, When tumor response is categorized into three groups, EMT6-B7-H4+ tumors have overall greater intrinsic resistance to treatment and reduced complete response compared with EMT6 control tumors (P = 0.035, χ2 = 6.683, df = 2, n = 23 mice for EMT6 parental tumors and n = 31 mice for B7-H4 tumors). G, EMT6-B7-H4+ tumors were stained by mIF. B7-H4 is expressed on CD45− tumor cells in vivo. Representative image shown. Scale bar 10 µm. H, Quantification of G, n = 3 mice. Data analyzed by unpaired t test. Data were analyzed in GraphPad Prism v10.
FIGURE 1 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

B7-H4 is associated with immune cold tumors and correlated with worse outcomes. A, Representative TNBC samples (residual disease, post-NAC) categorized on the basis of CD8 T-cell infiltration and localization into ID, MR, SR, and FI. B, B7-H4 is heterogeneously expressed in TNBC. C, ID and MR tumors have the highest level of B7-H4 expression (n = 69: ID: 19, MR: 17, SR: 14, FI: 19). MR and SR tumors were analyzed by unpaired t test. D, MR and ID tumors also have worse RFS and OS (n = 69). Data were analyzed by Mantel–Cox test. E, B7-H4 expression directly correlates with worse outcomes in patients (n = 77; >60%: 16, <60%: 51). Data were analyzed by Mantel–Cox test. F, TNBC samples stained with immunofluorescent markers for DAPI, panCK, CD3, and CD8 to identify regions of interest (ROI) for NanoString GeoMX DSP. MR and SR panCK+ ROIs were selected and differential protein expression between tumor samples is shown. G, Within the panCK gated cells, MR tumors had higher EpCAM expression. SR tumors had higher CD44 expression, as well as higher PD-L1. Data shown are log2 fold change of differentially expressed genes (P < 0.05, q < 0.10, data analyzed using R).