bluuebunny/crossref_metadata_2025 huggingface dataset:
Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model
Authors: Ranoa Diana Rose E , Sharma Preeti , Schane Claire P , Lewis Amber N , Valdez Edward , Marada Venkata V V R , Hager Marlies V , Montgomery Will , Wolf Steven P , Schreiber Karin , Schreiber Hans , Bailey Keith , Fan Timothy M , Hergenrother Paul J , Roy Edward J , Kranz David M
Published: May 2023

Background

Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve.

Methods

To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperoneCosmc. The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study.

Results

In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmcknock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. The most effective CARs exhibited the highest affinity for antigen. Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10.

Conclusion

The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system.
Interprofessional palliative and end-of-life education: short-term and long-term outcomes – mixed-methods analysis
Authors: Shaulov Adir , Finkelstein Adi , Vashdi Inon , DeKeyser Ganz Freda , Kienski Woloski-Wruble Anna , Rubinstein Estelle , Marcus Esther-Lee , Lesser Lior , Shaham Dorith
Published: May 2023

Objective

Interprofessional care is integral to end-of-life (EOL) and palliative care (PC) and may be suited for EOL and PC education.

We evaluate the impact of an interprofessional EOL care curriculum on participants, during the course, on completion and 4 years later

using quantitative (questionnaires) and qualitative (open-ended questions and interviews) methods.

The course included 14 fifth and sixth-year medical students, 9 social work students and 7 nursing students enrolled in master’s degree programmes. Seventeen participants completed questionnaires 4 years later and eight participated in interviews.

On postcourse questionnaires, participants attributed high value to interprofessional education (IPE) (4.77/5±0.50 on a Likert scale). Four years later, participants reported that IPE impacted their professional (3.65/5±1.11) and personal lives (3.94/5±1.09) and found PC IPE important (4.88/5±0.33).

Conventional content analysis showed that the course enabled discussion of death and dying and provided an opportunity for a personal-emotional journey. It offered an approach to EOL care and an opportunity to experience interprofessional teamwork at the EOL resulting in behavioural change.

Interprofessional EOL education resulted in meaningful and lasting self-reported personal and professional behavioural outcomes.
Developing a machine learning-based approach for predicting road surface friction using dash camera images—a City of Edmonton, Canada, case study
Authors: Xie Qian , Kwon Tae J.
Published: May 2023

Although road surface friction is considered the most effective performance measure for maintenance operations, it is not commonly used due to the high cost of collection. As a result, most jurisdictions use subjective visual indicators that qualitatively describe the state of the road surface, even though they create measurement inconsistencies and offer less detailed maintenance tracking. For maintenance personnel to transition into using friction, the collection cost must be reduced. This paper attempts to do so by proposing a low-cost, machine learning-based method for predicting road surface friction using dash camera imagery and demonstrates its feasibility through a case study. The dataset used for this project was collected in the City of Edmonton, AB, Canada during its 2021/2022 winter season. Three models were developed using tree-based algorithms, where all three displayed high performance with an average root mean squared error of 0.0796 or 79.3% accuracy based on RMSPE.
Decoy state semi-quantum key distribution
Authors: Dong Shuang , Mi Shang , Hou Qingcheng , Huang Yutao , Wang Jindong , Yu Yafei , Wei Zhengjun , Zhang Zhiming , Fang Junbin
Published: May 2023

Semi-quantum key distribution describes a system in which a fully quantum user and classical user perform key distribution. The main advantage of key distribution is its security. Owing to the bottlenecks of existing technology, highly attenuated lasers and threshold detectors are required for semi-quantum key distribution; however, these components make semi-quantum key distribution susceptible to eavesdroppers. Our previous study presented the first semi-quantum key distribution experiment and verified the feasibility of the mirror protocol in 2021. Herein, we first build a semi-quantum key distribution channel model and use Gottesman-Lo-Lütkenhaus-Preskill theory to evaluate its safety performance in the case of a quasi-single photon source. Moreover, we determine that an eavesdropper can steal all information through the photon-number-splitting attack without being detected. Therefore, we add decoy states to the semi-quantum key distribution to estimate the furthest transmission distance and secure bit rate under asymptotic conditions. Semi-quantum key distribution can still be achieved safely with highly attenuated lasers and threshold detectors in 150 km.
Noncommutative gauge and gravity theories and geometric Seiberg–Witten map
Authors: Aschieri Paolo , Castellani Leonardo
Published: June 2023

We give a pedagogical account of noncommutative gauge and gravity theories, where the exterior product between forms is deformed into a $$\star$$
⋆
-product via an abelian twist (e.g. the Groenewold–Moyal twist). The Seiberg–Witten map between commutative and noncommutative gauge theories is introduced. It allows to express the action of noncommutative Einstein gravity coupled to spinor fields in terms of the usual commutative action with commutative fields plus extra interaction terms dependent on the noncommutativity parameter.
Modelling pyroclastic density currents of the April 2021 La Soufrière, St Vincent eruption: from rapid invasion maps to field-constrained numerical simulations
Authors: Gueugneau Valentin , Charbonnier Sylvain , Miller Victoria L. , Cole Paul , Grandin Raphaël , Dualeh Edna W.
Published: June 2023

The April 2021 La Soufrière of St Vincent eruption generated several pyroclastic density currents (PDCs) during the 2 weeks of the crisis, from 9 to 22 April. To support the hazard assessment team during this eruption, numerical simulations were performed in real time and generated rapid scenario-based PDC invasion maps with the two-phase version of the code VolcFlow, which was able to simulate both the concentrated and dilute regime of PDCs. To generate the maps, only the source properties (shape and location) and the initial volume used to generate the PDCs were varied, all other input parameters were kept constant and estimated from previous simulations. New simulations were then performed based on the field-based deposit map to assess the code's ability to simulate such PDCs. Results show that the syn-crisis invasion maps satisfactorily mimic the observed valley-confined PDCs, while unconfined dilute PDCs were overestimated. The results also highlight that simulation results are greatly improved with additional field-based data, which help constrain the PDC sequence. Numerous lessons were learned, including (1) how to choose the most critical input parameters, (2) the importance of syn-eruptive radar imagery and (3) the potential of this two-phase model for rapid hazard assessment purposes.
Pangaea's breakup: the roles of mantle plumes, orogens and subduction retreat
Authors: Dang Zhuo , Zhang Nan , Li Zheng-Xiang , Yan Peilong
Published: June 2023

What drives the breakup of a supercontinent remains contentious. Previously proposed mechanisms include mantle plumes, subduction retreat and basal traction from mantle convection. Here we review the geological record of plumes, orogens and subduction zones during the breakup of Pangaea and investigate the potential roles played by these factors through 4D spherical geodynamic modelling. We found that mantle plumes provided the dominant force that drove the breakup of Pangaea, particularly in triggering the initial breakup. Young orogens as continental lithospheric weak zones generally guided the development of continental rifts, consistent with the geological record that rifting within Pangaea commonly developed along pre-existing orogens. However, the marginal drag force produced by subduction retreat, and basal traction associated with subduction-related mantle flow, likely also played a role in the breakup of Pangaea. In addition, the weakening effect of plume-induced melts can sometimes help to break the continental lithosphere away from orogens, as exemplified by the breakup between Antarctica and Australia. Furthermore, geodynamic modelling suggests that subduction is responsible for generating mantle plumes. A particular such example is the formation of the Kerguelen plume, triggered by subduction along the northern margin of Australia, which facilitated the breakup between East Antarctica and Australia.
Optimal Checkpointing Strategy for Real-time Systems with Both Logical and Timing Correctness
Authors: Zhang Lin , Wang Zifan , Kong Fanxin
Published: June 2023

Real-time systems are susceptible to adversarial factors such as faults and attacks, leading to severe consequences. This paper presents an optimal checkpoint scheme to bolster fault resilience in real-time systems, addressing both logical consistency and timing correctness. First, we partition message-passing processes into a
directed acyclic graph (DAG)
based on their dependencies, ensuring checkpoint logical consistency. Then, we identify the DAG’s critical path, representing the longest sequential path, and analyze the optimal checkpoint strategy along this path to minimize overall execution time, including checkpointing overhead. Upon fault detection, the system rolls back to the nearest valid checkpoints for recovery. Our algorithm derives the optimal checkpoint count and intervals, and we evaluate its performance through extensive simulations and a case study. Results show a 99.97% and 67.86% reduction in execution time compared to checkpoint-free systems in simulations and the case study, respectively. Moreover, our proposed strategy outperforms prior work and baseline methods, increasing deadline achievement rates by 31.41% and 2.92% for small-scale tasks and 78.53% and 4.15% for large-scale tasks.
Critical University Studies
Authors: Singh Vineeta , Vora Neha
Published: June 2023

In this article, we explore critical university studies (CUS), an interdisciplinary body of scholarship that interrogates structures of higher education and their entanglements with national and global institutions and political movements. Favoring an expansive definition of CUS, we draw from scholars who trace the origins of the American university to the slave trade, racial science, and Native American ethnic cleansing projects, as well as scholars who bring abolitionist and decolonial stances to highlight how the university continues to perpetuate state interests, carceral and settler logics, empire, and antiblackness. We then bring the lens of CUS to bear on critical work by anthropologists on higher education and on the discipline more broadly. We explore the challenges of advocating for antiracist and anti-imperial anthropology without attending to the structures of Western/white superiority that have enabled its institutionalization. We conclude by considering interventions by the emerging field of abolitionist anthropology.
Acknowledging Inspirations in a Lifetime of Shifting and Pivoting Standpoints to Construct the Past
Authors: Tringham Ruth
Published: June 2023

In this Perspective article, I am able to draw the various strands of my intellectual thinking and practice in archaeology and European prehistory into a complex narrative of changing themes. In this narrative, I draw attention to the inspirational triggers of these transformations to be found in works and words of colleagues and events within and outside my immediate discipline. A group of events between 1988 and 1993 disrupted (in a good way) the trajectory of my professional life and provided a convenient anchor around which my themes pivoted and regrouped with very different standpoints. But some trends in my way of working remained constant and contributed, I hope, to a career of cumulative knowledge. Along the way, I show the significance, in terms of my personal intellectual context as well as archaeological practice in general, of my published works as well as more obscure and some unpublished works that are cited here for the first time.
The Rock-Hosted Biosphere
Authors: Templeton Alexis S. , Caro Tristan A.
Published: May 2023

Our understanding of Earth's rock-hosted subsurface biosphere has advanced over the past two decades through the collection and analysis of fluids and rocks from aquifers within the continental and oceanic crust. Improvements in cell extraction, cell sorting, DNA sequencing, and techniques for detecting cell distributions and activity have revealed how the combination of lithology, permeability, and fluid mixing processes controls the diversity and heterogeneous distribution of microbial communities in fractured rock systems. However, the functions of most organisms, and the rates of their activity and growth, remain largely unknown. To mechanistically understand what physiochemical and hydrological factors control the rock-hosted biosphere, future studies are needed to characterize the physiology of microorganisms adapted to mineral-associated growth under energy- and nutrient-limited conditions. Experiments should be designed to detect synergistic interactions between microorganisms, and between microorganisms and minerals, at highly variable turnover rates.▪The heterogeneous distribution of the rock-hosted biosphere is controlled by variations in porosity, permeability, and chemical disequilibrium.▪Several imaging and chemical techniques can sensitively detect microbial activity within the rock-hosted biosphere.▪The physiology and turnover rates of the subsurface rock-hosted biosphere remain poorly known.
Electrodeposition of Copper Thin Films on Screen Printed Carbon Electrodes towards Electrochemical Sensing of Nitrate
Authors: Sethupathi M. , Thulasinathan Boobalan , Jayaraman Mathiyarasu , Manickam Pandiaraj , Rajasekaran N.
Published: May 2023

Accurate and frequent monitoring of NO3
− levels in water bodies is crucial for human health and environment. In this work, copper (Cu) thin films electrodeposited on screen-printed carbon electrodes (SPCEs) were explored as an electrochemical sensing platform for the detection of NO3
− in water. Scanning electron microscopy (SEM) with energy-dispersive X-ray analysis (EDX), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) was employed to characterize the morphology and composition of the thin film modified electrode. The electrochemical response of Cu thin film deposited SPCE under different pH conditions (4 to 10) and various temperature (20 °C–60 °C) was assessed using linear sweep voltammetry (LSV). The developed electrochemical sensor allowed the measurement of NO3
− levels ranging from 50 to 750 μM with a sensitivity of 0.1042 μA mM−1. The sensor exhibited good detection limit in fish culture water (120 nM), reverse osmosis processed water (91 nM) and borewell water (98 nM). The sensor response was found to be stable in the presence of other interfering analytes (NO2
−, K+, Na+, SO4
2−, Mg2+, Cl-, Fe3+, Fe2+, Mn2+, Cu2+, Zn2+). The performance of the sensor was demonstrated in water samples collected from various sources and the sensor showed an acceptable performance rates for practical applications.
Fast Response-Recovery and High Selectivity Chemicapacitive Detection of a Nerve Agent Simulant Vapor
Authors: Kang Miae , Park Jin Hyun , Kim Ayeong , Lee Seongwoo , Lee Chang Young , Kim Joo-Hyung , Song Changsik , Bae Han Yong , Kim Jihyun
Published: May 2023

Early detection of chemical warfare agents (CWAs) is critical in minimizing the exposure to chemical threats. This study presents a fast response-recovery chemicapacitive sensor (chemicapacitor) for a nerve agent simulant, dimethyl methylphosphonate (DMMP), with high selectivity and sensitivity. Chemicapacitors with interdigitated electrodes were fabricated on a SiO2/Si wafer by aligning single-walled carbon nanotubes (SW-CNTs) coated with polyhedral oligomeric silsesquioxane-supported 1,1,1,3,3,3-hexafluoro-2-propanol (POSS-HFIP) receptors. The stable, nano-sized three-dimensional structure with multiple terminal alcohol groups played a crucial role as a high-performance receptor via efficient hydrogen-bonding interaction with the CWA simulant. The response and recovery times of the fabricated chemicapacitors were estimated to be 13 and 88 s, respectively, outperforming chemiresistive sensors in terms of response-recovery dynamics. The capacitive responses were obtained at varying DMMP vapor concentrations, ranging from 25 to 150 ppm, and they exhibited superior sensitivity compared to receptor-free sensor devices. The concentration-dependent sensitivity was well-fitted with the Langmuir isotherm model, indicating that the sensing mechanism is based on the adsorption/desorption process. In addition, excellent selectivity was realized by introducing different toxic molecules (sulfur dioxide, ammonia, and ethylene oxide) and a blood agent (cyanogen chloride), where the fabricated POSS-HFIP/SW-CNTs chemicapacitor selectively responded to the DMMP vapor. The limit-of-detection was calculated to be 0.70 ppm. The proposed POSS-HFIP/SW-CNTs chemicapacitor demonstrated rapid response-recovery characteristics (with improved selectivity towards DMMP), suggesting its potential in reducing casualties or injuries by early identification of CWAs.
Use of a short, in-class drawing activity to assess student understanding of core concepts of the cell membrane in an undergraduate physiology course
Authors: Walton Kristen L. W.
Published: June 2023

Student-constructed drawings can give insight into student understanding, and misunderstandings, of core concepts about the cell membrane.
Computed cardiopulmonography and the idealized lung clearance index, iLCI2.5, in early-stage cystic fibrosis
Authors: Sandhu Dominic , Redmond Jennifer L. , Smith Nicholas M. J. , Short Christopher , Saunders Clare J. , Couper John H. , Fullerton Christopher J. , Richmond Graham , Talbot Nick P. , Davies Jane C. , Ritchie Grant A. D. , Robbins Peter A.
Published: June 2023

Computed cardiopulmonography is a new technique comprising a highly accurate sensor for measuring respiratory gas exchange coupled with a cardiopulmonary model that is used to identify a set of patient-specific characteristics of the lung. Here, we show that this technique can improve on a standard clinical approach for lung function testing in cystic fibrosis. Most particularly, an approach incorporating multiple model parameters can potentially separate different aspects of pathological change in this disease.
Use-dependent facilitation of electrical transmission involves changes to postsynaptic K+ current
Authors: Gu Yueling , Lee Kelly H. , Prosserman Alex B. , Magoski Neil S.
Published: June 2023

The understanding of how activity can facilitate electrical transmission is incomplete. We found that electrotonic potentials between electrically coupled neuroendocrine bag cell neurons facilitated in a use-dependent fashion. Rather than changes to the junctional current, facilitation was associated with cumulative inactivation of postsynaptic K+ current, presumably augmenting responsiveness. When made to burst, neurons synchronized their spiking, in part by use-dependent facilitation bringing quiescent cells to the threshold. Facilitation may foster en masse firing and neurosecretion.
Do Mechatronic Poles Change the Gait Technique of Nordic Walking in Patients with Ischemic Heart Disease?
Authors: Szpala Agnieszka , Winiarski Sławomir , Kołodziej Małgorzata , Pietraszewski Bogdan , Jasiński Ryszard , Niebudek Tadeusz , Lejczak Andrzej , Kałka Dariusz , Lorek Karolina , Bałchanowski Krzysztof , Wudarczyk Sławomir , Woźniewski Marek
Published: June 2023

The study aimed to compare the technique of normal gait with the Nordic walking (NW) gait with classical and mechatronic poles in patients with ischemic heart disease. It was assumed that equipping classical NW poles with sensors enabling biomechanical gait analysis would not cause a change in the gait pattern. The study involved 12 men suffering from ischemic heart disease (age: 66.2 ± 5.2 years, body height: 173.8 ± 6.74 cm; body mass: 87.3 ± 10.89 kg; disease duration: 12.2 ± 7.5 years). The MyoMOTION 3D inertial motion capture system (Noraxon Inc., Scottsdale, AZ, USA) was used to collect biomechanical variables of gait (spatiotemporal and kinematic parameters). The subject’s task was to cover the 100 m distance with three types of gait-walking without poles (normal gait), walking with classical poles to NW, and walking with mechatronic poles from the so-called preferred velocity. Parameters were measured on the right and left sides of the body. The data were analyzed using two-way repeated measures analysis of variance with the between-subject factor “body side.” Friedman’s test was used when necessary. For most kinematic parameters, with the exception of knee flexion–extension (

p
=
0.474

) and shoulder flexion–extension (

p
=
0.094

), significant differences were found between normal and walking with poles for both the left and right side of the body and no differences due to the type of pole. Differences between the left and right movement ranges were identified only for the ankle inversion–eversion parameter (gait without poles

p
=
0.047

; gait with classical poles

p
=
0.013

). In the case of spatiotemporal parameters, a reduction in the cadence step value using mechatronic poles and the stance phase using classical poles compared to normal walking was observed. There was also an increase in the values for step length and step time regardless of the type of poles, stride length, and swing phase when using classical poles and stride time when using mechatronic poles. The differences between the right and left sides of the measurement occurred when walking with both types of poles for single support (gait with classical poles

p
=
0.003

; gait with mechatronic poles

p
=
0.030

), stance phase (gait with classical poles

p
=
0.028

; gait with mechatronic poles

p
=
0.017

) and swing phase (gait with classical poles

p
=
0.028

; gait with mechatronic poles

p
=
0.017

). Mechatronic poles can be used in the study of the biomechanics of gait in real-time with feedback on its regularity because no statistically significant differences were found between the NW gait with classical and mechatronic poles in the studied men with ischemic heart disease.
Machine Learning Model for Computer‐Aided Depression Screening among Young Adults Using Wireless EEG Headset
Authors: Sakib Nazmus , Islam Md Kafiul , Faruk Tasnuva
Published: June 2023

Depression is a disorder that if not treated can hamper the quality of life. EEG has shown great promise in detecting depressed individuals from depression control individuals. It overcomes the limitations of traditional questionnaire‐based methods. In this study, a machine learning‐based method for detecting depression among young adults using EEG data recorded by the wireless headset is proposed. For this reason, EEG data has been recorded using an Emotiv Epoc+ headset. A total of 32 young adults participated and the PHQ9 screening tool was used to identify depressed participants. Features such as skewness, kurtosis, variance, Hjorth parameters, Shannon entropy, and Log energy entropy from 1 to 5 sec data filtered at different band frequencies were applied to KNN and SVM classifiers with different kernels. At AB band (8–30 Hz) frequency, 98.43 ± 0.15% accuracy was achieved by extracting Hjorth parameters, Shannon entropy, and Log energy entropy from 5 sec samples with a 5‐fold CV using a KNN classifier. And with the same features and classifier overall accuracy = 98.10 ± 0.11, NPV = 0.977, precision = 0.984, sensitivity = 0.984, specificity = 0.976, and F1 score = 0.984 was achieved after splitting the data to 70/30 ratio for training and testing with 5‐fold CV. From the findings, it can be concluded that EEG data from an Emotiv headset can be used to detect depression with the proposed method.
Prevalence of Zoonotic Gastrointestinal Helminth Parasite among Dogs in Suryabinayak, Nepal
Authors: Sukupayo Punya Ram , Tamang Semsal
Published: May 2023

Dogs are popular pets around the world and have always had a very close relationship with humans. Zoonotic gastrointestinal helminth parasites are a great threat to both stray and pet dogs. This study was carried out to determine the prevalence of zoonotic gastrointestinal helminths in dogs. 400 samples were collected, including 200 from pet dogs and 200 from stray dogs. The samples from pet dogs were collected from the ground immediately after voiding with the help of the owner, whereas stray dogs were caught by using a dog catcher, and the samples were collected directly from the rectum by using a gloved index finger. All collected samples were examined under a microscope using sedimentation and flotation techniques. The overall prevalence of infection was found to be 59.50%, with a significantly higher prevalence in stray dogs (70%) than that in pet dogs (49%). Ancylostoma spp., Toxocara spp., Trichuris spp., Capillaria spp., Dipylidium caninum, and Taenia/Echinococcus spp. were six different species found in the current study. The study showed the highest prevalence of Ancylostoma spp. (49.16%) and the least prevalence of Capillaria spp. (0.84%). In the age‐wise study, puppies had a significantly high infection rate (86.96%). Similarly, we recorded a significantly higher prevalence of intestinal helminths among nondewormed pet dogs (78.65%) than among dewormed pet dogs (25.23%). This study highlights the severe environmental contamination shed by dogs, causing a higher risk of zoonotic transmission. It indicates the urgent need to manage these parasites in dogs and educate the public on how to care for their pets and the parasites they shed.
Development and Validation of the Promising PPAR Signaling Pathway-Based Prognostic Prediction Model in Uterine Cervical Cancer
Authors: Zhang Yan , Li Xing , Zhang Jun , Mao Lin , Wen Zou , Cao Mingliang , Mu Xuefeng
Published: May 2023

A ligand-activated transcription factor, peroxisome proliferator-activated receptor (PPAR) regulates fatty acid uptake and transport. In several studies, upregulation of PPAR expression/activity by cancer cells has been associated with cancer progression. Worldwide, cancer of the cervix ranks fourth among women’s cancers. Angiogenesis inhibitors have improved treatment for recurrent and advanced cervical cancer since their introduction 5 years ago. In spite of that, the median overall survival rate for advanced cervical cancer is 16.8 months, indicating that treatment effectiveness is still lacking. Thus, it is imperative that new therapeutic methods be developed. In this work, we first downloaded the PPAR signaling pathway-related genes from the previous study. In addition, the single-sample gene set enrichment analysis (ssGSEA) algorithm was applied to calculate the PPAR score of patients with cervical cancer. Furthermore, cervical cancer patients with different PPAR scores show different sensitivity to immune checkpoint therapy. In order to screen the genes to serve as the best biomarker for cervical cancer patients, we then construct the PPAR-based prognostic prediction model. The results revealed that PCK1, MT1A, AL096855.1, AC096711.2, FAR2P2, and AC099568.2 not only play a key role in the PPAR signaling pathway but also show good predictive value in cervical cancer patients. The gene set variation analysis (GSVA) enrichment analysis also proved that the PPAR signaling pathway is one of the most enriched pathways in the prognostic prediction model. Finally, further analysis revealed that AC099568.2 may be the most promising biomarker for the diagnosis, treatment, and prognosis in cervical cancer patients. Both the survival analysis and Receiver Operating Characteristic curve demonstrated that AC099568.2 plays a key role in cervical cancer patients. However, to our knowledge, this is the first time a study focused on the role of AC099568.2 in cervical cancer patients. Our work successfully revealed a new biomarker for cervical cancer patients, which also provides a new direction for future research.
Solid Oxide Fuel Cells for Marine Applications
Authors: van Veldhuizen Berend , van Biert Lindert , Aravind Purushothaman Vellayani , Visser Klaas
Published: May 2023

The marine industry must reduce emissions to comply with recent and future regulations. Solid oxide fuel cells (SOFCs) are seen as a promising option for efficient power generation on ships with reduced emissions. However, it is unclear how the devices can be integrated and how this affects the operation of the ship economically and environmentally. This paper reviews studies that consider SOFC for marine applications. First, this article discusses noteworthy developments in SOFC systems, including power plant options and fuel possibilities. Next, it presents the design drivers for a marine power plant and explores how an SOFC system performs. Hereafter, the possibilities for integrating the SOFC system with the ship are examined, also considering economic and environmental impact. The review shows unexplored potential to successfully integrate SOFC with thermal and electrical systems in marine vessels. Additionally, it is identified that there are still possibilities to improve marine SOFC systems, for which a holistic approach is needed for design at cell, stack, module, and system level. Nevertheless, it is expected that hybridisation is needed for a technically and economically feasible ship. Despite its high cost, SOFC systems could significantly reduce GHG, NOX, SOX, PM, and noise emissions in shipping.
Impact of Consumer Strategic Behavior on the Supplier Channel Selection in a Retailing Platform
Authors: Liu Kaijun , Jiang Jingli
Published: May 2023

Flourishing online retailing has spawned the agency selling channel, which motivates suppliers to choose among traditional reselling (R), agency selling (A), and hybrid channel strategies (H). In this paper, considering a supplier and a retail platform facing strategic consumers, we develop a Stackelberg game to examine the equilibrium pricing under three channel strategies and further analyze the impact of consumer strategic behavior on the supplier’s channel selection. Results indicate that consumer strategic behaviors induce the intertemporal competition, by reducing the price difference between the two periods. Meanwhile, channel competition can mitigate the effect of strategic behaviors. Furthermore, supply chain members also employ different pricing policies in accordance with channel strategies to respond to more strategic consumers. Specifically, prices would be raised to acquire high-valued consumers in Strategy H, while “small profits but quick turnover” would be taken in the pure channel strategies. Moreover, the supplier optimal channel strategy is a threshold strategies of commission rate, below which Strategy H is preferred, and Strategy R is preferred otherwise, noticing that Strategy A is never be selected. Interestingly, we find that the supplier, retail platform, and consumers could be better off at the same time only when the hybrid channel strategy is selected.
Exact Solutions of an Extended Jimbo-Miwa Equation by Three Distinct Methods
Authors: He Yinghui
Published: May 2023

In this article, we focus on exact traveling wave solutions to an extended Jimbo-Miwa equation, which is an extension of the Jimbo-Miwa equation. First, an improved

G

′

/
G

-expansion method, extended

G

′

/
G

-expansion method, and improved two variable (

φ

′

/
φ

,

1

/

φ

) expansion method are introduced. Second, with these introduced methods, many new exact traveling wave solutions of EJM equation are constructed, including hyperbolic function solutions, trigonometric function solutions, and rational function solutions which contain many different parameters. Finally, we depict the physical explanation of the extracted solutions with the free choice of the different parameters by plotting some 3D and 2D illustrations. To the best of our knowledge, the received results have not been reported in other studies on the new extended JM equations. We hope that our results can help enrich the study of this new equation.
Clinical Decision Support System for Diabetic Patients by Predicting Type 2 Diabetes Using Machine Learning Algorithms
Authors: Islam Rakibul , Sultana Azrin , Tuhin Md. Nuruzzaman , Saikat Md. Sazzad Hossain , Islam Mohammad Rashedul
Published: May 2023

Diabetes is one of the most serious chronic diseases that result in high blood sugar levels. Early prediction can significantly diminish the potential jeopardy and severity of diabetes. In this study, different machine learning (ML) algorithms were applied to predict whether an unknown sample had diabetes or not. However, the main significance of this research was to provide a clinical decision support system (CDSS) by predicting type 2 diabetes using different ML algorithms. For the research purpose, the publicly available Pima Indian Diabetes (PID) dataset was used. Data preprocessing, K‐fold cross‐validation, hyperparameter tuning, and various ML classifiers such as K‐nearest neighbor (KNN), decision tree (DT), random forest (RF), Naïve Bayes (NB), support vector machine (SVM), and histogram‐based gradient boosting (HBGB) were used. Several scaling methods were also used to improve the accuracy of the result. For further research, a rule‐based approach was used to escalate the effectiveness of the system. After that, the accuracy of DT and HBGB was above 90%. Based on this result, the CDSS was implemented where users can give the required input parameters through a web‐based user interface to get decision support with some analytical results for the individual patient. The CDSS, which was implemented, will be beneficial for physicians and patients to make decisions about diabetes diagnosis and offer real‐time analysis‐based suggestions to improve medical quality. For future work, if daily data of a diabetic patient can be put together, then a better clinical support system can be implemented for daily decision support for patients worldwide.
The Effect of Different Storage Conditions on the Levels of Bisphenol A in Bottled Drinking Water in Jeddah City, Saudi Arabia
Authors: Baz Lina , Alharbi Asmaa , Al-Zahrani Maryam , Alkhabbaz Sedra , Alsousou Rasha , Aljawadri Hanan
Published: May 2023

Bisphenol A (BPA) in drinking water sources is a significant concern in society because BPA is one of the endocrine disruption compounds (EDCs) that can cause hazards to human health even at extremely low concentration levels. This study investigated the leaching potential of BPA from drinking water bottles in five brands of bottled drinking water in Jeddah, Saudi Arabia, using high-performance liquid chromatography with a diode array detector (HPLC-DAD). To the best of our knowledge, this is the first study to evaluate the level of BPA in bottled water in the city of Jeddah. The separation was carried out under isocratic elution, and the detector was set to UV mode. Low levels of BPA were detected in all samples from polyethylene terephthalate (PET) containers. The mean concentration of BPA in water bottles stored at room temperature for 30 days was 9.46 ng·L−1, while the concentration of BPA in water bottles exposed to sunlight and boiling water bath was 16.13 ng·L−1 and 14.7 ng·L−1, respectively. Although the results show that the daily consumed concentration of BPA for an adult with 60 kg of body weight is 32.26 ng, which is lower than the total tolerable daily intake limit of BPA, health risks from the consumption of bottled water may increase after UV exposure for an extended time.
Characteristics of Bulletproof Vests Made from COPEFB Fiber: Implications on Mechanical, Electrical, and Physical Resistance
Authors: Nikmatin Siti , Irmansyah Irmansyah , Palupi Endah Kinarya , Umam Rofiqul
Published: June 2023

This research aims to examine the characteristics of bulletproof vests from corncob oil palm empty fruit bunch (COPEFB) biocomposite, where mechanical, electrical, and physical resistance tests have been successfully conducted. The variations in the diameter of the twisted thread used to make the basic material for bulletproof vests include 1 mm, 3 mm, 6 mm, and 10 mm, which were tested for their mechanical, electrical, and physical properties. To identify which biocomposite is good at damping bullets, an impact and a firing test were carried out to determine the kinetic energy and the depth of the bullet, respectively. The results showed that the impact value improved with an increase in the diameter of the twisted yarn used. The largest and the lowest impact values were 1.157 kJ and 0.277 kJ on the epoxy sample with a twisted thread diameter of 10 mm and 1 mm, respectively. It was also discovered that the biocomposite samples made from 6 mm to 10 mm twisted threads were the best samples, impermeable to bullets. This was due to the excess natural fiber content which improved the flexibility and absorption of kinetic energy from the high rate of projectile bullets. According to the results of the firing test, some samples are translucent, while others cannot be penetrated by bullet projectiles. The projectile went inside, and the composite was damaged. All the high filler loading samples were translucent to bullets, while some of the low loading samples were translucent and impermeable to bullets. Based on these results, biocomposite samples made of 6 mm and 10 mm twisted yarn are the best samples that are impermeable to bullets.
An Open-label Phase I Study of GDC-0927 in Postmenopausal Women with Locally Advanced or Metastatic Estrogen Receptor–Positive Breast Cancer
Authors: Chandarlapaty Sarat , Dickler Maura N. , Perez Fidalgo Jose Alejandro , Villanueva-Vázquez Rafael , Giltnane Jennifer , Gates Mary , Chang Ching-Wei , Cheeti Sravanthi , Fredrickson Jill , Wang Xiaojing , Collier Ann , Moore Heather M. , Metcalfe Ciara , Lauchle Jennifer , Humke Eric W. , Bardia Aditya
Published: June 2023

Purpose:

GDC-0927 is a novel, potent, nonsteroidal, orally bioavailable, selective estrogen receptor (ER) degrader that induces tumor regression in ER+ breast cancer xenograft models.

Patients and Methods:

This phase I dose-escalation multicenter study enrolled postmenopausal women with ER+/HER2− metastatic breast cancer to determine the safety, pharmacokinetics, and recommended phase II dose of GDC-0927. Pharmacodynamics was assessed with [18F]-fluoroestradiol (FES) PET scans.

Results:

Forty-two patients received GDC-0927 once daily. The MTD was not reached. The most common adverse events (AE) regardless of causality were nausea, constipation, diarrhea, arthralgia, fatigue, hot flush, back pain, and vomiting. There were no deaths, grade 4/5 AEs, or treatment-related serious AEs. Two patients experienced grade 2 AEs of special interest of deep vein thrombosis and jugular vein thrombosis, both considered unrelated to GDC-0927. Following dosing, approximately 1.6-fold accumulation was observed, consistent with the observed half-life and dosing frequency. There were no complete or partial responses. Pharmacodynamics was supported by >90% reduction in FES uptake and an approximately 40% reduction in ER expression, suggesting ER degradation is not the mechanistic driver of ER antagonism. Twelve patients (29%) achieved clinical benefit; 17 patients (41%) showed a confirmed best overall response of stable disease. Baseline levels of ER and progesterone receptor protein and mutant ESR1 circulating tumor DNA did not correlate with clinical benefit.

Conclusions:

GDC-0927 appeared to be well tolerated with pharmacokinetics supporting once-daily dosing. There was evidence of target engagement and preliminary evidence of antitumor activity in heavily pretreated patients with advanced/metastatic ER+/HER2− breast cancer with and without ESR1 mutations.
Additional Oncogenic Alterations inRAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes
Authors: Bikas Athanasios , Ahmadi Sara , Pappa Theodora , Marqusee Ellen , Wong Kristine , Nehs Matthew A. , Cho Nancy L. , Haase Jacob , Doherty Gerard M. , Sehgal Kartik , Barletta Justine A. , Alexander Erik K. , Landa Iñigo
Published: June 2023

Purpose:

RAS mutations occur across the spectrum of thyroid neoplasms, and more tools are needed for better prognostication. The objective of this study was to evaluate how additional genetic events affecting key genes modify prognosis in patients with RAS-mutant thyroid cancers, and specifically differentiated thyroid cancers (DTC).

Experimental Design:

We performed a clinical–genomic analysis of consecutive patients with DTC, poorly differentiated (PDTC), or anaplastic thyroid cancer (ATC) between January 2014 and December 2021, in whom a custom-targeted next-generation sequencing assay was performed. Patients harboring RAS mutations were included, and we compared their clinical features and outcomes based upon the presence of additional oncogenic alterations.

Results:

Seventy-eight patients were identified, with 22% (17/78) harboring a driver RAS mutation plus an additional oncogenic alteration. All six (100%) ATCs had an additional mutation. Compared with DTCs harboring a solitary RAS mutation, patients with DTC with RAS and additional mutation(s) were more likely to be classified as American Thyroid Association high-risk of recurrence (77% vs. 12%; P < 0.001) and to have larger primary tumors (4.7 vs. 2.5 cm; P = 0.002) and advanced stage (III or IV) at presentation (67% vs. 3%; P < 0.001). Importantly, over an average 65-month follow-up, DTC-specific-mortality was more than 10-fold higher (20% vs. 1.8%; P = 0.011) when additional mutations were identified.

Conclusions:

Identification of key additional mutations in patients with RAS-mutant thyroid cancers confers a more aggressive phenotype, increases mortality risk in DTC, and can explain the diversity of RAS-mutated thyroid neoplasia. These data support genomic profiling of DTCs to inform prognosis and clinical decision-making.
Data from Activating an Adaptive Immune Response with a Telomerase-Mediated Telomere Targeting Therapeutic in Hepatocellular Carcinoma
Authors: Mender Ilgen , Siteni Silvia , Barron Summer , Flusche Ann Marie , Kubota Naoto , Yu Chunhua , Cornelius Crystal , Tedone Enzo , Maziveyi Mazvita , Grichuk Anthony , Venkateswaran Niranjan , Conacci-Sorrell Maralice , Hoshida Yujin , Kang Rui , Tang Daolin , Gryaznov Sergei , Shay Jerry W.
Published: June 2023

Abstract
A select group of patients with hepatocellular carcinomas (HCC) benefit from surgical, radiologic, and systemic therapies that include a combination of anti-angiogenic and immune-checkpoint inhibitors. However, because HCC is generally asymptomatic in its early stages, this not only leads to late diagnosis, but also to therapy resistance. The nucleoside analogue 6-thio-dG (THIO) is a first-in-class telomerase-mediated telomere-targeting anticancer agent. In telomerase expressing cancer cells, THIO is converted into the corresponding 5′-triphosphate, which is efficiently incorporated into telomeres by telomerase, activating telomere damage responses and apoptotic pathways. Here, we show how THIO is effective in controlling tumor growth and, when combined with immune checkpoint inhibitors, is even more effective in a T-cell-dependent manner. We also show telomere stress induced by THIO increases both innate sensing and adaptive antitumor immunity in HCC. Importantly, the extracellular high-mobility group box 1 protein acts as a prototypical endogenous DAMP (Damage Associated Molecular Pattern) in eliciting adaptive immunity by THIO. These results provide a strong rationale for combining telomere-targeted therapy with immunotherapy.