bluuebunny/crossref_metadata_2025 huggingface dataset:
An Operations Research–Based Teaching Unit for Grade 11: The ROAR Experience, Part II
Authors: Colajanni Gabriella , Gobbi Alessandro , Picchi Marinella , Raffaele Alice , Taranto Eugenia
Published: August 2023

In this paper, we continue describing the project and the experimentation of Ricerca Operativa Applicazioni Reali (ROAR; in English, Real Applications of Operations Research), a three-year project for higher secondary schools, introduced. ROAR is composed of three teaching units, addressed to Grades 10, 11, and 12, respectively, having the main aim to improve students’ interest, motivation, and skills related to Science, Technology, Engineering, and Mathematics disciplines by integrating mathematics and computer science through operations research. In a previous paper, we reported on the design and implementation of the first unit, started in Spring 2021 at the scientific high school IIS Antonietti in Iseo (Brescia, Italy), in a Grade-10 class. Here, we focus on the second unit, carried out in Winter/Spring 2022 with the same students, now in a Grade-11 class. In particular, we describe objectives, prerequisites, topics and methods, the organization of the lectures, digital technologies used, and a challenging final project. Moreover, we analyze the feedback from students and teachers involved in the experimentation.

Funding: G. Colajanni and E. Taranto were partially supported by the research projects Programma Ricerca di Ateneo UNICT 2020-22 linea 2, EEEP&DLaD, and OMNIA, respectively, of the University of Catania. The research of G. Colajanni was also partially supported by the Italian Ministry of University and Research and the European Union for the PON project on Research and Innovation 2014–2020 [Grant D.M. 1062/2021]. A. Raffaele was partially supported by the Gruppo Nazionale per il Calcolo Scientifico. These supports are gratefully acknowledged.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/ited.2023.0001 .
Dynamic Market Timing in Mutual Funds
Authors: Busse Jeffrey A. , Ding Jing , Jiang Lei , Wu Ke
Published: August 2023

We use the dynamic conditional correlation (DCC) model to estimate daily frequency mutual fund betas. Compared with traditional estimates, daily betas better capture changes in fund risk stemming from daily fund trading activity. Based on these beta estimates and a two-stage estimation procedure, we find significant evidence of market timing ability among actively managed U.S. equity funds that is not apparent via standard approaches. Unlike traditional measures, our timing estimates correlate positively with fund performance. Market timing is especially evident during down markets, with successful timers exhibiting low downside risk. Timing ability persists across time and attracts investor flows.

This paper was accepted by David Sraer, finance.

Funding: This work was supported by the National Natural Science Foundation of China [Grants 72173127 and 72121001] and by the Institute for Industrial Innovation and Finance at Tsinghua University.

Supplemental Material: The data files and online appendix are available at https://doi.org/10.1287/mnsc.2023.4857 .
A Linear-Parameter-Varying Formulation for Model Predictive Perimeter Control in Multi-Region MFD Urban Networks
Authors: Kouvelas Anastasios , Saeedmanesh Mohammadreza , Geroliminis Nikolas
Published: August 2023

An alternative approach for real-time network-wide traffic control in cities that has recently gained attention is perimeter flow control. Many studies have shown that this method is more efficient than state-of-the-art adaptive signal control strategies for heterogeneously congested urban networks. The basic concept of such an approach is to partition heterogeneous cities into a small number of homogeneous regions (zones) and apply perimeter control to the interregional flows along the boundaries between regions. The transferring flows are controlled at the traffic intersections located at the borders between regions so as to distribute the congestion in an optimal way and minimize the total delay of the system. The focus of current work is the mathematical formulation of the original nonlinear problem in a linear parameter-varying (LPV) form so that optimal control can be applied in a (rolling horizon) model predictive concept. This work presents the mathematical analysis of the optimal control problem as well as the approximations and simplifications that are assumed in order to derive the formulation of a linear optimization problem. Numerical simulation results for the case of a macroscopic environment (plant) are presented in order to demonstrate the efficiency of the proposed approach. Results for the closed-loop model predictive control scheme are presented for the nonlinear case, which is used as “benchmark,” as well as the linear case. Furthermore, the developed scheme is applied to a large-scale microsimulation of a European city with more than 500 signalized intersections in order to better investigate its applicability to real-life conditions. The simulation experiments demonstrate the effectiveness of the scheme compared with fixed-time control because all of the performance indicators are significantly improved.

Funding: This work was supported by Dit4Tram “Distributed Intelligence & Technology for Traffic & Mobility Management” project from the European Union’s Horizon 2020 research and innovation programme under [Grant agreement 953783].
Ethics and pharmacists
Authors: Winter George
Published: August 2023

In the current climate, it is understood that many health professionals are suffering from stress-related conditions. In such a context, to what extent can pharmacists be expected to make sound ethical judgments?
Efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate COX regression analysis
Authors: Wang Ding-Ran
Published: August 2023

Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide and the leading contributor to cancer-related deaths. The progression and metastasis of HCC are closely associated with altered mitochondrial metabolism, including mitochondrial stress response. Mitokines, soluble proteins produced and secreted in response to mitochondrial stress, play an essential immunomodulatory role. Immunotherapy has emerged as a crucial treatment option for HCC. However, a positive response to therapy is typically dependent on the interaction of tumor cells with immune regulation within the tumor microenvironment. Therefore, exploring the specific immunomodulatory mechanisms of mitokines in HCC is essential for improving the efficacy of immunotherapy. This study provides a comprehensive overview of the association between HCC and the immune microenvironment and highlights recent progress in understanding the involvement of mitochondrial function in preserving liver function. In addition, a systematic review of mitokines-mediated immunomodulation in HCC is presented. Finally, the potential diagnostic and therapeutic roles of mitokines in HCC are prospected and summarized. Recent progress in mitokine research represents a new prospect for mitochondrial therapy. Considering the potential of mitokines to regulate immune function, investigating them as a relevant molecular target holds great promise for the diagnosis and treatment of HCC.
Anaphylactic shock induced by polyethylene glycol after bowel preparation for the colorectal cancer surgery: A case report
Authors: Park Go Woon , Park Nahyeon , Kuk Jung Cheol , Shin Eung Jin , Lim Dae Ro
Published: August 2023

Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide and the leading contributor to cancer-related deaths. The progression and metastasis of HCC are closely associated with altered mitochondrial metabolism, including mitochondrial stress response. Mitokines, soluble proteins produced and secreted in response to mitochondrial stress, play an essential immunomodulatory role. Immunotherapy has emerged as a crucial treatment option for HCC. However, a positive response to therapy is typically dependent on the interaction of tumor cells with immune regulation within the tumor microenvironment. Therefore, exploring the specific immunomodulatory mechanisms of mitokines in HCC is essential for improving the efficacy of immunotherapy. This study provides a comprehensive overview of the association between HCC and the immune microenvironment and highlights recent progress in understanding the involvement of mitochondrial function in preserving liver function. In addition, a systematic review of mitokines-mediated immunomodulation in HCC is presented. Finally, the potential diagnostic and therapeutic roles of mitokines in HCC are prospected and summarized. Recent progress in mitokine research represents a new prospect for mitochondrial therapy. Considering the potential of mitokines to regulate immune function, investigating them as a relevant molecular target holds great promise for the diagnosis and treatment of HCC.
Pancreatic cavernous hemangioma complicated with chronic intracapsular spontaneous hemorrhage: A case report and review of literature
Authors: Li Ting
Published: August 2023

Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide and the leading contributor to cancer-related deaths. The progression and metastasis of HCC are closely associated with altered mitochondrial metabolism, including mitochondrial stress response. Mitokines, soluble proteins produced and secreted in response to mitochondrial stress, play an essential immunomodulatory role. Immunotherapy has emerged as a crucial treatment option for HCC. However, a positive response to therapy is typically dependent on the interaction of tumor cells with immune regulation within the tumor microenvironment. Therefore, exploring the specific immunomodulatory mechanisms of mitokines in HCC is essential for improving the efficacy of immunotherapy. This study provides a comprehensive overview of the association between HCC and the immune microenvironment and highlights recent progress in understanding the involvement of mitochondrial function in preserving liver function. In addition, a systematic review of mitokines-mediated immunomodulation in HCC is presented. Finally, the potential diagnostic and therapeutic roles of mitokines in HCC are prospected and summarized. Recent progress in mitokine research represents a new prospect for mitochondrial therapy. Considering the potential of mitokines to regulate immune function, investigating them as a relevant molecular target holds great promise for the diagnosis and treatment of HCC.
Trial frame for evaluating eye movements
Authors: Jin Tao , Li Guanglin , Lei Lihua
Published: August 2023

Eye movement research is an established methodology and widely used in fundamental research fields such as psychology or neuroscience. Most research is performed in controlled environments with screen-based eye trackers, but demand for a wearable requirement is on the rise. Yet, a state of the art wearable eye tracking system thus far has not been feasible for subjects with refractive errors; therefore, a trial frame is proposed for researching the eye movement of people with or without refractive errors. Two iris cameras and several infrared radiation LEDs were fixed behind the frame for recording eye images. The images were sent to a host computer using 2.4G wireless, which was also fixed on the frame. The entire electronic system in the trial frame was driven using a battery. Eye position in the images was recognized and segmented by a model that was trained through machine learning. Then the pupil and blinks were detected from the segmented eye area using ellipse fitting and the eye aspect ratio. Experiments showed that the correct rate of pupil and blink detections were 97.24% and 96.14%, respectively.
Photonic crystal concentric dual-microring resonator for refractive index sensing
Authors: Shi Bingyao , Chen Xiao , Cai Yuanyuan , Kang Qi , Wang Yiquan
Published: August 2023

A high-performance photonic crystal (PhC) concentric dual-microring resonator (PhCCDMRR) for refractive index sensing is proposed in this paper. It confines the energy into PhC air holes to enhance the light–matter interaction, and the increased modal area of the concentric rings improves the sensing sensitivity. The slow-light effect near the photonic bandgap results in a PhC waveguide with a maximum group index of 18.2. In the transmission spectrum, a high extinction ratio of 22 dB is achieved. This sensor obtains a refractive index (RI) sensitivity of 265 nm/RIU (RI unit) using sodium chloride solution as samples, which has promising applications in RI sensing.
Ultra-broadband 3-dB coupler based on dual-hollow-core polymer fiber covering E + S + C + L + U band
Authors: Jia Haoqiang , Lou Shuqin , Hou Donglian , Xue Lu , Sheng Xinzhi , Chu Paul K , Wang Xin
Published: August 2023

An ultra-broadband 3-dB coupler based on a polymer dual-hollow-core anti-resonant fiber (DHC-ARF) is designed to work in the E + S + C + L + U communication band. By incorporating two elliptical-like cores and modulating the air gap between the two cores, the wavelength and polarization dependence of the DHC-ARF-based coupler is reduced effectively. The feasibility of using a 1.46 cm long DHC-ARF as the ultra-broadband coupler for the operating bandwidth of 400 nm in the range between 1.33 µm and 1.73 µm is demonstrated theoretically. The coupling ratio of each polarized mode stabilizes at 50 ± 2% and the coupling ratio difference between the two polarized modes changes within ±0.6%. This DHC-ARF coupler which is made of a polymer can be fabricated by high-resolution 3D printing. Compared to a silica-based DHC-ARF coupler, the polymer-based DHC-ARF coupler is easier to manufacture and the total loss of the latter is only 0.041 ± 0.006 dB in the operating bandwidth. The polymer hollow-core fiber coupler boasting an ultra-broadband, short component length, and low loss is very promising in next-generation, high-speed, and large-capacity hollow-core fiber communication systems.
Laser damage properties of LiB3O5 crystal surface under UV laser irradiation
Authors: Liu Hongjie , Wang Fang , Sun Laixi , Zheng Tianran , Wang Fengrui
Published: August 2023

LiB3O5 (LBO) crystal has a very high bulk laser damage threshold. Laser damage often occurs on the surfaces with a large number of processing defects during application. In this paper, the surface laser damage threshold, damage growth threshold, and damage growth curve of LBO crystal and fused silica under the same processing process have been comparatively studied by using a 355 nm pulsed laser. The surface laser damage performance of LBO crystal has been comprehensive evaluated. The results show that the laser damage threshold and damage growth threshold of LBO are about twice that of fused silica, and the damage growth coefficient is about 0.7 times that of fused silica. The detection and analysis of impurity defects and photothermal weak absorption defects show that the subsurface defects of LBO crystal are less than that of fused silica. Laser damage morphologies show that the damage process is related to strongly bonded chemical structure and anisotropic physical characteristics of LBO crystal. These characteristics together determine the high threshold damage performance of LBO crystal. The results of this study are of great guidance for the application of LBO crystal in high-power laser systems.
Polycrystalline silicon 2 × 2 Mach-Zehnder interferometer optical switch
Authors: Xu Xinru , Yin Yuexin , Sun Chunlei , Li Junying , Lin Hongtao , Tang Bo , Zhang Peng , Li Lan , Zhang Daming
Published: August 2023

In this paper, we demonstrate a broadband Mach-Zehnder interferometer optical switch based on polycrystalline silicon (poly-Si), which enables the development of multilayer photonics integrated circuits. The poly-Si is deposited under a low temperature of 620 °C to avoid unexpected thermal stress and influence on optoelectronic performance. By introducing a π/2 phase shifter and a push-pull configuration, the switch achieved low power consumption and loss caused by carrier plasma absorption (CPA). The switch operates effectively in both “Bar” and “Cross” states at voltages of −3.35 V and 3.85 V. The power consumptions are 7.98 mW and 9.39 mW, respectively. The on-chip loss is 5.9 ± 0.4 dB at 1550 nm, and the crosstalk is below −20 dB within the C-band. The switch exhibits a 10%-90% rise time of 7.7 µs and a 90%-10% fall time of 3.4 µs at 1550 nm. As far as we know, it is the first demonstration of a poly-Si switch on an 8-inch wafer pilot-line. The low-temperature deposited poly-Si switch is promising for multilayer active photonic devices and photonic-electronic applications.
Mode mixing and losses in misaligned microcavities
Authors: Hughes William J. , Doherty T. H. , Blackmore J. A. , Horak P. , Goodwin J. F.
Published: August 2023

We present a study on the optical losses of Fabry-Pérot cavities subject to realistic transverse mirror misalignment. We consider mirrors of the two most prevalent surface forms: idealised spherical depressions, and Gaussian profiles generated by laser ablation. We first describe the mode mixing phenomena seen in the spherical mirror case and compare to the frequently-used clipping model, observing close agreement in the predicted diffraction loss, but with the addition of protective mode mixing at transverse degeneracies. We then discuss the Gaussian mirror case, detailing how the varying surface curvature across the mirror leads to complex variations in round trip loss and mode profile. In light of the severe mode distortion and strongly elevated loss predicted for many cavity lengths and transverse alignments when using Gaussian mirrors, we suggest that the consequences of mirror surface profile are carefully considered when designing cavity experiments.
Color image information transmission based on elliptic optical vortex array encoding/decoding
Authors: Liu Xianpeng , Huang Sujuan , Li Chunyu
Published: August 2023

A multichannel high-dimensional data encoding/decoding scheme based on composite elliptic optical vortex (EOV) arrays is proposed. By exploiting the rotation angle of the EOV, a 4 × 4 composite EOV array is used for high-dimensional data encoding. The conjugate symmetric extension Fourier computer-generated holography algorithm with controllable reconstruction focus is used to assign different reconstruction focus to the data of the three channels (R, G, and B) of the color image. Then, the data of the three channels is transmitted simultaneously by a single hologram to further improve the transmission efficiency. At the receiver, the initial information sequence is decoded by directly identifying the captured intensity patterns with a deep learning-based convolutional neural network. In the experiment, a 128 × 128-pixel color image is successfully transmitted, which confirms the feasibility of our proposed encoding/decoding scheme. This method has great potential for future high-capacity optical communications.
Microlens array camera with variable apertures for single-shot high dynamic range (HDR) imaging
Authors: Cha Young-Gil , Na Jiwoong , Kim Hyun-Kyung , Kwon Jae-Myeong , Huh Seok-Haeng , Jo Seung-Un , Kim Chang-Hwan , Kim Min H. , Jeong Ki-Hun
Published: August 2023

We report a microlens array camera with variable apertures (MACVA) for high dynamic range (HDR) imaging by using microlens arrays with various sizes of apertures. The MACVA comprises variable apertures, microlens arrays, gap spacers, and a CMOS image sensor. The microlenses with variable apertures capture low dynamic range (LDR) images with different f-stops under single-shot exposure. The reconstructed HDR images clearly exhibit expanded dynamic ranges surpassing LDR images as well as high resolution without motion artifacts, comparable to the maximum MTF50 value observed among the LDR images. This compact camera provides, what we believe to be, a new perspective for various machine vision or mobile devices applications.
Passive white light cavities with metal coatings
Authors: Wang Jianshan , Xie Xiaohan , Li Na , Dong Jie , Wang Shuailing , Wang Yiqing , Qiu Xingze , Xu Jingping , Yang Yaping
Published: August 2023

White light cavities with broadband resonance are usually filled with negative dispersion medium, which inevitably leads to gain. In this article, pure passive white light cavities are designed, in which negative dispersion medium is no longer necessary. Theoretically, if the reflection phase of the cavity wall can exhibit a negative dispersion slope, then it can also satisfy white light cavities conditions without medium. In practice, the negative dispersion property of the cavity wall can be realized by two metal coatings with different reflection coefficients. Therefore, our white light cavities are composite cavities, in which the main cavity provides resonance while the auxiliary cavity forms the cavity wall, providing negative dispersion reflection phase. Further, atomic gas can be employed to improve the performance of the white light cavities. Atomic gas exploits effects such as Electromagnetic Induced Transparency (EIT), enabling the white light cavities to be controlled by coherent driving field. With the passive characters, our design can be realized and implemented much more easily.
On-chip gain switched frequency comb generation using a two sectioned single cavity laser without additional optical injection
Authors: McCarthy John , Peters Frank H.
Published: August 2023

A tunable comb source is demonstrated on a monolithically integrated photonic integrated circuit (PIC). The PIC is a two section device designed to produce a single mode tunable spectrum, and the comb is generated by gain switching one section of the two sectioned laser. The laser produces a single mode spectra with a tunable range of 1543 - 1565 nm, and combs were generated with a frequency range of 1 - 10 GHz without requiring additional optical injection to maintain the phase coherence.
Turning whispering-gallery-mode responses through Fano interferences in coupled all-dielectric block-disk cavities
Authors: Du Xiao-Jing , Tang Xu-Tao , Xie Bo , Ma Lin , Hu Ma-Long , He Jun , Yang Zhong-Jian
Published: August 2023

Here, we theoretically demonstrate a strategy for efficiently turning whispering-gallery-mode (WGM) responses of a subwavelength dielectric disk through their near-field couplings with common low-order electromagnetic resonances of a dielectric block. Both simulations and an analytical coupled oscillator model show that the couplings are Fano interferences between dark high-quality WGMs and bright modes of the block. The responses of a WGM in the coupled system are highly dependent on the strengths and the relative phases of the block modes, the coupling strength, and the decay rate of the WGM. The WGM responses of coupled systems can exceed that of the individual disk. In addition, such a configuration will also facilitate the excitation of WGMs by a normal incident plane wave in experiments. These results could enable new applications for enhancing light-matter interactions.
Imaging through a square multimode fiber by scanning focused spots with the memory effect
Authors: Mezil Sylvain , Wang Irène , Bossy Emmanuel
Published: August 2023

The existence of a shift–shift memory effect in square waveguides, whereby any translation of the input field induces translations in the output field in four symmetrical directions, has been previously observed by correlation measurements. Here we demonstrate that this memory effect is also observed in real space and can be put to use for imaging purposes. First, a focus is created at the output of a square-core multimode fiber, by wavefront shaping based on feedback from a guide-star. Then, because of the memory effect, four symmetrical spots can be scanned at the fiber output by shifting the wavefront at the fiber input. We demonstrate that this property can be exploited to perform fluorescence imaging through the multimode fiber, without requiring the measurement of a transmission matrix.
Exact envelope solitons in topological Floquet insulators
Authors: Deb Subimal , Singh Dheerendra , Chakraborty Munmun , Panigrahi Prasanta K. , Khare Avinash
Published: August 2023

The existence of new types of four-wave mixing Floquet solitons were recently realized numerically through a resonant phase matching in a photonic lattice of type-I Dirac cones; specifically, a honeycomb lattice of helical array waveguides imprinted on a weakly birefringent medium. We present a wide class of exact solutions in this system for the envelope solitons in dark–bright pairs and a “molecular” form of bright–dark combinations. Some of the solutions, red or blue detuned, are mode-locked in their momenta, while the others offer a spectrum of allowed momenta subject to constraints amongst the system and solution parameters. We show that the characteristically different solutions exist at and away from the band edge, with the exact band edge possessing a periodic pair of sinusoidal excitations akin to that of two-level systems apart from localized solitons. These could have possible applications for designing quantum devices.
Millimeter-wave noise generation based on a monolithically integrated dual-mode chaotic laser
Authors: Chen Tianxiang , Liu Wenjie , Tao Xingyu , Lu Dan , Sun Yuehui , Liu Junbin , Jia Zhiwei , Wang Yuncai
Published: August 2023

A millimeter-wave noise generation scheme is proposed in this paper. The scheme is based on a monolithically integrated dual-mode chaotic laser, which consists of a distributed Bragg feedback (DFB) section, a phase section, and an optical amplification section. The output spectrum state of the dual-mode laser can be controlled by adjusting the injection current in the three regions. The monolithically integrated dual-mode chaotic laser has stable chaotic output and can be used as a light source for integrated millimeter-wave noise source. As a feasibility demonstration, a dual-mode chaotic laser with a mode interval of 2.05 nm was generated in the experiment, the optical mixing on a photodetector produced millimeter-wave noise with a center frequency of 259 GHz and a bandwidth of 44 GHz (237–281 GHz), achieving a typical value of excess noise ratio of 47 dB. It has the advantages of high noise source utilization, small noise source volume, and high integration.
Research on hollow-core Terahertz fiber based on Bragg anti-resonant elements arranged in a hexagonal structure
Authors: Ding Jin long , Ding Li-Sha , Chen Ming-Yang , Dong Zhe-Yan
Published: August 2023

A hollow-core terahertz fiber composed of Bragg anti-resonant elements in a hexagonal structure is proposed. The function of Bragg elements on the transmission losses and bending losses of the hollow-core terahertz fiber is investigated using finite element method. Numerical simulations demonstrate that the introduction of Bragg elements for the anti-resonant cladding can significantly reduce the confinement losses of the fiber. The absorption loss shows low dependence on the number of anti-resonant layers. The introduction of the Bragg elements is also contributed to the reduction of the bending loss. It is found that the reduction of the diameter of the outer cladding can effectively reduce the mode coupling between the core and cladding modes. Compared with the anti-resonant hollow-core terahertz fiber composed of only a single dielectric layer, the bending losses of the hollow-core terahertz fiber with the Bragg elements can be reduced by more than an order of magnitude.
The shape of cancer relapse: Topological data analysis predicts recurrence in paediatric acute lymphoblastic leukaemia
Authors: Chulián Salvador , Stolz Bernadette J. , Martínez-Rubio Álvaro , Blázquez Goñi Cristina , Rodríguez Gutiérrez Juan F. , Caballero Velázquez Teresa , Molinos Quintana Águeda , Ramírez Orellana Manuel , Castillo Robleda Ana , Fuster Soler José Luis , Minguela Puras Alfredo , Martínez Sánchez María V. , Rosa María , Pérez-García Víctor M. , Byrne Helen M.
Published: August 2023

Although children and adolescents with acute lymphoblastic leukaemia (ALL) have high survival rates, approximately 15-20% of patients relapse. Risk of relapse is routinely estimated at diagnosis by biological factors, including flow cytometry data. This high-dimensional data is typically manually assessed by projecting it onto a subset of biomarkers. Cell density and “empty spaces” in 2D projections of the data, i.e. regions devoid of cells, are then used for qualitative assessment. Here, we use topological data analysis (TDA), which quantifies shapes, including empty spaces, in data, to analyse pre-treatment ALL datasets with known patient outcomes. We combine these fully unsupervised analyses with Machine Learning (ML) to identify significant shape characteristics and demonstrate that they accurately predict risk of relapse, particularly for patients previously classified as ‘low risk’. We independently confirm the predictive power of CD10, CD20, CD38, and CD45 as biomarkers for ALL diagnosis. Based on our analyses, we propose three increasingly detailed prognostic pipelines for analysing flow cytometry data from ALL patients depending on technical and technological availability: 1. Visual inspection of specific biological features in biparametric projections of the data; 2. Computation of quantitative topological descriptors of such projections; 3. A combined analysis, using TDA and ML, in the four-parameter space defined by CD10, CD20, CD38 and CD45. Our analyses readily extend to other haematological malignancies.
A stochastic analysis of the interplay between antibiotic dose, mode of action, and bacterial competition in the evolution of antibiotic resistance
Authors: Czuppon Peter , Day Troy , Débarre Florence , Blanquart François
Published: August 2023

The use of an antibiotic may lead to the emergence and spread of bacterial strains resistant to this antibiotic. Experimental and theoretical studies have investigated the drug dose that minimizes the risk of resistance evolution over the course of treatment of an individual, showing that the optimal dose will either be the highest or the lowest drug concentration possible to administer; however, no analytical results exist that help decide between these two extremes. To address this gap, we develop a stochastic mathematical model of bacterial dynamics under antibiotic treatment. We explore various scenarios of density regulation (bacterial density affects cell birth or death rates), and antibiotic modes of action (biostatic or biocidal). We derive analytical results for the survival probability of the resistant subpopulation until the end of treatment, the size of the resistant subpopulation at the end of treatment, the carriage time of the resistant subpopulation until it is replaced by a sensitive one after treatment, and we verify these results with stochastic simulations. We find that the scenario of density regulation and the drug mode of action are important determinants of the survival of a resistant subpopulation. Resistant cells survive best when bacterial competition reduces cell birth and under biocidal antibiotics. Compared to an analogous deterministic model, the population size reached by the resistant type is larger and carriage time is slightly reduced by stochastic loss of resistant cells. Moreover, we obtain an analytical prediction of the antibiotic concentration that maximizes the survival of resistant cells, which may help to decide which drug dosage (not) to administer. Our results are amenable to experimental tests and help link the within and between host scales in epidemiological models.
Prediction of opioid-related outcomes in a medicaid surgical population: Evidence to guide postoperative opiate therapy and monitoring
Authors: El Hajouji Oualid , Sun Ran S. , Zammit Alban , Humphreys Keith , Asch Steven M. , Carroll Ian , Curtin Catherine M. , Hernandez-Boussard Tina
Published: August 2023

Background

Treatment of surgical pain is a common reason for opioid prescriptions. Being able to predict which patients are at risk for opioid abuse, dependence, and overdose (opioid-related adverse outcomes [OR-AE]) could help physicians make safer prescription decisions. We aimed to develop a machine-learning algorithm to predict the risk of OR-AE following surgery using Medicaid data with external validation across states.

Methods

Five machine learning models were developed and validated across seven US states (90–10 data split). The model output was the risk of OR-AE 6-months following surgery. The models were evaluated using standard metrics and area under the receiver operating characteristic curve (AUC) was used for model comparison. We assessed calibration for the top performing model and generated bootstrap estimations for standard deviations. Decision curves were generated for the top-performing model and logistic regression.

Results

We evaluated 96,974 surgical patients aged 15 and 64. During the 6-month period following surgery, 10,464 (10.8%) patients had an OR-AE. Outcome rates were significantly higher for patients with depression (17.5%), diabetes (13.1%) or obesity (11.1%). The random forest model achieved the best predictive performance (AUC: 0.877; F1-score: 0.57; recall: 0.69; precision:0.48). An opioid disorder diagnosis prior to surgery was the most important feature for the model, which was well calibrated and had good discrimination.

Conclusions

A machine learning models to predict risk of OR-AE following surgery performed well in external validation. This work could be used to assist pain management following surgery for Medicaid beneficiaries and supports a precision medicine approach to opioid prescribing.
In-silico and in-vitro morphometric analysis of intestinal organoids
Authors: Montes-Olivas Sandra , Legge Danny , Lund Abbie , Fletcher Alexander G. , Williams Ann C. , Marucci Lucia , Homer Martin
Published: August 2023

Organoids offer a powerful model to study cellular self-organisation, the growth of specific tissue morphologies in-vitro, and to assess potential medical therapies. However, the intrinsic mechanisms of these systems are not entirely understood yet, which can result in variability of organoids due to differences in culture conditions and basement membrane extracts used. Improving the standardisation of organoid cultures is essential for their implementation in clinical protocols. Developing tools to assess and predict the behaviour of these systems may produce a more robust and standardised biological model to perform accurate clinical studies. Here, we developed an algorithm to automate crypt-like structure counting on intestinal organoids in both in-vitro and in-silico images. In addition, we modified an existing two-dimensional agent-based mathematical model of intestinal organoids to better describe the system physiology, and evaluated its ability to replicate budding structures compared to new experimental data we generated. The crypt-counting algorithm proved useful in approximating the average number of budding structures found in our in-vitro intestinal organoid culture images on days 3 and 7 after seeding. Our changes to the in-silico model maintain the potential to produce simulations that replicate the number of budding structures found on days 5 and 7 of in-vitro data. The present study aims to aid in quantifying key morphological structures and provide a method to compare both in-vitro and in-silico experiments. Our results could be extended later to 3D in-silico models.
Non-asymptotic transients away from steady states determine cellular responsiveness to dynamic spatial-temporal signals
Authors: Nandan Akhilesh , Koseska Aneta
Published: August 2023

Majority of the theory on cell polarization and the understanding of cellular sensing and responsiveness to localized chemical cues has been based on the idea that non-polarized and polarized cell states can be represented by stable asymptotic switching between them. The existing model classes that describe the dynamics of signaling networks underlying polarization are formulated within the framework of autonomous systems. However these models do not simultaneously capture both, robust maintenance of polarized state longer than the signal duration, and retained responsiveness to signals with complex spatial-temporal distribution. Based on recent experimental evidence for criticality organization of biochemical networks, we challenge the current concepts and demonstrate that non-asymptotic signaling dynamics arising at criticality uniquely ensures optimal responsiveness to changing chemoattractant fields. We provide a framework to characterize non-asymptotic dynamics of system’s state trajectories through a non-autonomous treatment of the system, further emphasizing the importance of (long) transient dynamics, as well as the necessity to change the mathematical formalism when describing biological systems that operate in changing environments.
Drosophila embryos allocate lipid droplets to specific lineages to ensure punctual development and redox homeostasis
Authors: Kilwein Marcus D. , Dao T. Kim , Welte Michael A.
Published: August 2023

Lipid droplets (LDs) are ubiquitous organelles that facilitate neutral lipid storage in cells, including energy-dense triglycerides. They are found in all investigated metazoan embryos where they are thought to provide energy for development. Intriguingly, early embryos of diverse metazoan species asymmetrically allocate LDs amongst cellular lineages, a process which can involve massive intracellular redistribution of LDs. However, the biological reason for asymmetric lineage allocation is unknown. To address this issue, we utilize the Drosophila embryo where the cytoskeletal mechanisms that drive allocation are well characterized. We disrupt allocation by two different means: Loss of the LD protein Jabba results in LDs adhering inappropriately to glycogen granules; loss of Klar alters the activities of the microtubule motors that move LDs. Both mutants cause the same dramatic change in LD tissue inheritance, shifting allocation of the majority of LDs to the yolk cell instead of the incipient epithelium. Embryos with such mislocalized LDs do not fully consume their LDs and are delayed in hatching. Through use of adPLIN2mutant, which appropriately localizes a smaller pool of LDs, we find that failed LD transport and a smaller LD pool affect embryogenesis in a similar manner. Embryos of all three mutants display overlapping changes in their transcriptome and proteome, suggesting that lipid deprivation results in a shared embryonic response and a widespread change in metabolism. Excitingly, we find abundant changes related to redox homeostasis, with many proteins related to glutathione metabolism upregulated. LD deprived embryos have an increase in peroxidized lipids and rely on increased utilization of glutathione-related proteins for survival. Thus, embryos are apparently able to mount a beneficial response upon lipid stress, rewiring their metabolism to survive. In summary, we demonstrate that early embryos allocate LDs into specific lineages for subsequent optimal utilization, thus protecting against oxidative stress and ensuring punctual development.
Cultural adaption and validation of the Explanatory Model Interview Catalogue–Community Stigma Scale in the assessment of public stigma related to schistosomiasis in lakeshore areas of Mwanza region, Tanzania
Authors: Klinker Laura , Boeckler Anne , Kreibich Saskia , Mazigo Humphrey
Published: August 2023

Background

Previous qualitative studies on attitudes towards schistosomiasis demonstrated inconclusive results on the extent of stigma towards schistosomiasis in endemic communities around the world. The Explanatory Model Interview Catalogue–Community Stigma Scale (EMIC-CSS) has been used and validated for the assessment of public stigma across numerous countries in various health conditions. This study tested the performance of the scale in the context of stigma related to schistosomiasis in twelve communities in the three districts of Magu, Nyamagana and Ilemela in Mwanza region, Tanzania.

Methodology/Principal findings

The 15-item-version of the EMC-CSS was first translated to Kiswahili language. The translation was discussed within the research team to retain the meaning of the items and implement cultural adaptations. Validation of the adapted EMIC-CSS scale was conducted following the framework of Herdman and Fox- Rushby. A pilot study with 41 participants from two communities provided the basis for testing the performance of each item and assessing the semantic and operational equivalence of the scales. In addition, eight qualitative focus group discussions (FGDs) were conducted to evaluate the conceptional equivalence of the EMIC-CSS. Finally, the performance of the adjusted scale was tested on 200 participants with a 50:50 male-female ratio from ten communities. The mean score of the EMIC-CSS M = 8.35 (SD = 6.63) shows clear indications for public stigma towards schistosomiasis. The EMIC-CSS demonstrated a good internal consistency with Cronbach’s alpha α = .857 and no floor and ceiling effects.

Conclusion/Significance

The results demonstrate that the EMIC-CSS is a useful instrument in assessing public stigma towards schistosomiasis and allow a clear recommendation of the EMIC-CSS for schistosomiasis in the Tanzanian culture. However, future studies are additionally recommended to address specific aspects and forms of the disease and how they contribute to the development of stigma towards schistosomiasis.
Multi-channel feature fusion attention Dehazing network
Authors: Zou Changjun , Xu Hangbin , Ye Lintao
Published: August 2023

Haze is a typical weather phenomena that has a significant negative impact on transportation safety, particularly in the port, highways, and airport runway areas. A multi-scale U-shaped dehazing network is proposed in this research, which is based on our multi-channel feature fusion attention structure. With the help of the feature fusion attention techniques, the model can focus on the intriguing locations with higher haze concentration area. In conjunction with UNet, it can achieve multi-scale feature reuse and residual learning, allowing it to fully utilize the feature information of each layer for image restoration. Experimental resulsts show that our technique performs well on a variety of test datasets. On highway data sets, the PSNR / SSIM / L∞ error performance over the novel technique is increased by 0.52% / 0.5% / 30.84%, 4.68% / 0.78% / 26.19% and 13.84% / 9.05% / 55.57% respectively, when compared to DehazeFormer, MIRNetv2, and FSDGN methods. The findings suggest that our proposed method performs better on image dehazing, especially in terms of L∞ error performance.
Adipose derived stromal vascular fraction and fat graft for treating the hands of patients with systemic sclerosis. A randomized clinical trial
Authors: Iglesias Martin , Torre-Villalvazo Iván , Butrón-Gandarillas Patricia , Rodríguez-Reyna Tatiana S. , Torre-Anaya Erik A. , Guevara-Cruz Martha , Flores-Cháirez Miguel A. , López-Contreras Diana B. , López-Sánchez Joana Y. , Ruiz-Betanzos Ángel J. , Méndez López Ana L. , Rubio-Gutierrez Carolina , Téllez-Pallares Fernando , Nario-Chaidez Fabian
Published: August 2023

Background

Systemic Sclerosis in the hand is characteristically evidenced by Raynaud’s phenomenon, fibrosis of the skin, tendons, ligaments, and joints as well as digital ulcers with prolonged healing. Current medical treatment does not always cure these complications. Local adipose-derived stromal vascular fraction administration into the hands has been proposed as an emerging treatment due to its regenerative properties. The objective of this randomized controlled clinical trial was to evaluate the safety and clinical effects of fat micrografts plus adipose derived-stromal vascular fraction administration into the hands of patients with systemic sclerosis.

Methods

This was an open-label, monocentric, randomized controlled study. Twenty patients diagnosed with systemic sclerosis were assigned to the experimental or control group. Fat micrografts plus the adipose derived-stromal vascular fraction were injected into the right hand of experimental group patients. The control group continued to receive only medical treatment. Demographic, serologic data and disease severity were recorded. Digital oximetry, pain, Raynaud phenomenon, digital ulcers number, mobility, thumb opposition, vascular density of the nail bed, skin affection of the hand, serologic antibodies, hand function, and quality of life scores were evaluated in both groups.

Results

The results of the intervention were analyzed with the Wilcoxon rank test, and the differences between the control and experimental groups at 0 days and 168 days were analyzed with the Mann–Whitney U test. Adverse events were not observed in both groups. At the end of the study, statistically significant improvements were observed in pain levels (p<0.05) and number of digital ulcers (p<0.01) in the experimental vs control group.

Conclusion

The injection of adipose derived-stromal vascular fraction plus fat micrografts is a reproducible, and safe technique. Pain and digital ulcers in the hands of patients with systemic sclerosis can be treated with this technique plus conventional medical treatment.
Exploring the potential of approved drugs for triple-negative breast cancer treatment by targeting casein kinase 2: Insights from computational studies
Authors: Shoaib Tagyedeen H. , Ibraheem Walaa , Abdelrahman Mohammed , Osman Wadah , Sherif Asmaa E. , Ashour Ahmed , Ibrahim Sabrin R. M. , Ghazawi Kholoud F. , Miski Samar F. , Almadani Sara A. , ALsiyud Duaa Fahad , Mohamed Gamal A. , Alzain Abdulrahim A.
Published: August 2023

Triple-negative breast cancer (TNBC) is an aggressive malignancy that requires effective targeted drug therapy. In this study, we employedin silicomethods to evaluate the efficacy of seven approved drugs against human ck2 alpha kinase, a significant modulator of TNBC metastasis and invasiveness. Molecular docking revealed that the co-crystallized reference inhibitor 108600 achieved a docking score of (-7.390 kcal/mol). Notably, among the seven approved drugs tested, sunitinib, bazedoxifene, and etravirine exhibited superior docking scores compared to the reference inhibitor. Specifically, their respective docking scores were -10.401, -7.937, and -7.743 kcal/mol. Further analysis using MM/GBSA demonstrated that these three top-ranked drugs possessed better binding energies than the reference ligand. Subsequent molecular dynamics simulations identified etravirine, an FDA-approved antiviral drug, as the only repurposed drug that demonstrated a stable and reliable binding mode with the human ck2 alpha protein, based on various analysis measures including RMSD, RMSF, and radius of gyration. Principal component analysis indicated that etravirine exhibited comparable stability of motion as a complex with human ck2 alpha protein, similar to the co-crystallized inhibitor. Additionally, Density functional theory (DFT) calculations were performed on a complex of etravirine and a representative gold atom positioned at different sites relative to the heteroatoms of etravirine. The results of the DFT calculations revealed low-energy complexes that could potentially serve as guides for experimental trials involving gold nanocarriers of etravirine, enhancing its delivery to malignant cells and introducing a new drug delivery route. Based on the results obtained in this research study, etravirine shows promise as a potential antitumor agent targeting TNBC, warranting further investigation through experimental and clinical assessments.