bluuebunny/crossref_metadata_2025 huggingface dataset:
A Clash of Powers: Church and State
Authors: Colyer Corey J. , Stein Rachel E. , Corcoran Katie E.
Published: June 2023

Sociologists define power as one party's capacity to influence another's action. Thus, power is a relational property of interpersonal interaction. However, its dynamics embed within institutions such as the church and the state. This paper explores power dynamics using a case study of the conflict between an Old Order Amish church and the civil law of Ohio. The church excommunicated a member for violating community rules. The member countered by suing the church in state court. We trace power within and across these spheres of influence, showing how each party defined the situation according to institutional vectors of power. While one might expect the state to possess greater power in this situation, we demonstrate that ultimately neither party had total power, and both lost to some extent. This case study identifies the importance of viewing power as interactional, dynamic, and contextual.
The molecular chaperone mtHSC70‐1 interacts with DjA30 to regulate female gametophyte development and fertility in Arabidopsis
Authors: Zhai Xiaoting , Bai Jiaoteng , Xu Wenyan , Yang Xiujuan , Jia Zichao , Xia Wenxuan , Wu Xiaoqing , Liang Qi , Li Bing , Jia Ning
Published: June 2023

Arabidopsis mitochondria‐targeted heat shock protein 70 (mtHSC70‐1) plays important roles in the establishment of cytochrome c oxidase‐dependent respiration and redox homeostasis during the vegetative growth of plants. Here, we report that knocking out the mtHSC70‐1 gene led to a decrease in plant fertility; the fertility defect of the mutant was completely rescued by introducing the mtHSC70‐1 gene. mtHSC70‐1 mutants also showed defects in female gametophyte (FG) development, including delayed mitosis, abnormal nuclear position, and ectopic gene expression in the embryo sacs. In addition, we found that an Arabidopsis mitochondrial J‐protein gene (DjA30) mutant, j30+/−, had defects in FG development and fertility similar to those of mtHSC70‐1 mutant. mtHSC70‐1 and DjA30 had similar expression patterns in FGs and interacted in vivo, suggesting that these two proteins might cooperate during female gametogenesis. Further, respiratory chain complex IV activity in mtHSC70‐1 and DjA30 mutant embryo sacs was markedly downregulated; this led to the accumulation of mitochondrial reactive oxygen species (ROS). Scavenging excess ROS by introducing Mn‐superoxide dismutase 1 or catalase 1 gene into the mtHSC70‐1 mutant rescued FG development and fertility. Altogether, our results suggest that mtHSC70‐1 and DjA30 are essential for the maintenance of ROS homeostasis in the embryo sacs and provide direct evidence for the roles of ROS homeostasis in embryo sac maturation and nuclear patterning, which might determine the fate of gametic and accessory cells.
Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch
Authors: Kondo Takumi , Fujii Keiko , Fujii Nobuharu , Sumii Yuichi , Urata Tomohiro , Kimura Maiko , Matsuda Masayuki , Ikegawa Shuntaro , Washio Kana , Fujiwara Hideaki , Asada Noboru , Ennishi Daisuke , Nishimori Hisakazu , Matsuoka Ken‐ichi , Otsuka Fumio , Maeda Yoshinobu
Published: June 2023

Background

Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES.

Study Design and Methods

We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods.

Results

The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation.

Conclusion

Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection.
The Impact of Dyslexia on the Effectiveness of Online Learning: A Systematic Literature Review
Authors: Liu Tinglei , Costa Feroz De , Yasin Megat Al Imran
Published: June 2023

Dyslexia can have an impact on online learning outcomes. However, few studies have examined the association between dyslexia and online learning effectiveness. This systematic review focused on the effects of dyslexia on online learning effectiveness to conduct research in three major categories: analysis of impact, analysis of dyslexia on online learning, and analysis of interventions. A screening of two bibliographic databases identified 37 articles that met the inclusion criteria. The study determined that dyslexic learners are uncomforted with online learning and suffer from frustrated self-confidence and decreased academic performance in the learning process. It even affects the learners' evaluation of themselves and causes a decrease in self-efficacy. Among these, research on influencing factors can be divided into two dimensions: internal and external factors. Dyslexic learners are influenced by both the type of dyslexia and their psychological characteristics, as well as by teachers, teaching strategies, online educational environments, and educational media. These influences provide intervention strategies, such as developing customized online learning systems for dyslexic learners and exploring interventions in telerehabilitation medicine. However, no intervention strategies involve adjustments to the internal psychology of dyslexic learners and external support systems. Therefore, more research is needed to explore the differential impact of dyslexia on online learning and to understand the factors that produce this impact to provide a theoretical basis and direction for the generation of instructional strategies for dyslexics and the adaptation of online learning for dyslexics.
Effect of Aerobic/Strength Training on RANKL Gene DNA Methylation Levels
Authors: Chelly Ameni , Bouzid Amal , Neifar Fadoua , Kammoun Ines , Tekari Adel , Masmoudi Saber , Chtourou Hamdi , Rebai Ahmed
Published: June 2023

Background: The osteoclastogenesis RANKL gene plays a key role in bone remodeling. The hypomethylation of its promoter region may cause osteoporosis. The present study aimed to elucidate the influence of physical activity on DNA methylation changes of RANKL promoter cytosine-phosphate-guanine (CpG)-rich region in active and sedentary adults and to assess the effect of aerobic and strength training on RANKL DNA methylation changes among Tunisian-North African adults. Methods: A total of 104 participants including 52 adults (58% males and 42% females) and 52 adults (31% males and 69% females) were recruited for the observational and interventional part of the study, respectively. The intervention consisted of 12 weeks of aerobic training (30 min/session) followed by 10 minutes of strengthening exercises. All participants completed the International Physical Activity Questionnaire and provided blood samples for quantitative methylation-specific polymerase chain reaction (PCR) analysis. Results: The study revealed a significant difference (P = 6 × 10−10) in the methylation level of the RANKL promoter region between active and sedentary adults, with a 6.68-fold increase observed in the active group. After the intervention, both the trained (P = 41 × 10−5) and untrained (P = .002) groups displayed high methylation levels in the RANKL promoter region. In addition, the trained group exhibited significant improvements in heart rate (P = 2.2 × 10−16), blood pressure (P = 39 × 10−3), maximal oxygen uptake (P = 1.5 × 10−7), and fat mass (P = 7 × 10−4). Conclusion: Exploring epigenetic modifications in the RANKL promoter region may contribute to a more comprehensive understanding of the complexity of osteoporosis. This suggests that aerobic/strength training could potentially improve the bone system, reducing its vulnerability to osteoporosis by increasing RANKL DNA methylation.
Airborne fine particles drive H1N1 viruses deep into the lower respiratory tract and distant organs
Authors: Dong Zheng , Ma Juan , Qiu Jiahuang , Ren Quanzhong , Shan Qing’e , Duan Xuefeng , Li Guangle , Zuo Yi Y. , Qi Yu , Liu Yajun , Liu Guoliang , Lynch Iseult , Fang Min , Liu Sijin
Published: June 2023

Mounting data suggest that environmental pollution due to airborne fine particles (AFPs) increases the occurrence and severity of respiratory virus infection in humans. However, it is unclear whether and how interactions with AFPs alter viral infection and distribution. We report synergetic effects between various AFPs and the H1N1 virus, regulated by physicochemical properties of the AFPs. Unlike infection caused by virus alone, AFPs facilitated the internalization of virus through a receptor-independent pathway. Moreover, AFPs promoted the budding and dispersal of progeny virions, likely mediated by lipid rafts in the host plasma membrane. Infected animal models demonstrated that AFPs favored penetration of the H1N1 virus into the distal lung, and its translocation into extrapulmonary organs including the liver, spleen, and kidney, thus causing severe local and systemic disorders. Our findings revealed a key role of AFPs in driving viral infection throughout the respiratory tract and beyond. These insights entail stronger air quality management and air pollution reduction policies.
Natural flavonoids disrupt bacterial iron homeostasis to potentiate colistin efficacy
Authors: Zhong Zi-xing , Zhou Shuang , Liang Yu-jiao , Wei Yi-yang , Li Yan , Long Teng-fei , He Qian , Li Meng-yuan , Zhou Yu-feng , Yu Yang , Fang Liang-xing , Liao Xiao-ping , Kreiswirth Barry N. , Chen Liang , Ren Hao , Liu Ya-hong , Sun Jian
Published: June 2023

In the face of the alarming rise in global antimicrobial resistance, only a handful of novel antibiotics have been developed in recent decades, necessitating innovations in therapeutic strategies to fill the void of antibiotic discovery. Here, we established a screening platform mimicking the host milieu to select antibiotic adjuvants and found three catechol-type flavonoids—7,8-dihydroxyflavone, myricetin, and luteolin—prominently potentiating the efficacy of colistin. Further mechanistic analysis demonstrated that these flavonoids are able to disrupt bacterial iron homeostasis through converting ferric iron to ferrous form. The excessive intracellular ferrous iron modulated the membrane charge of bacteria via interfering the two-component system
pmrA
/
pmrB
, thereby promoting the colistin binding and subsequent membrane damage. The potentiation of these flavonoids was further confirmed in an in vivo infection model. Collectively, the current study provided three flavonoids as colistin adjuvant to replenish our arsenals for combating bacterial infections and shed the light on the bacterial iron signaling as a promising target for antibacterial therapies.
Ultrawide-bandwidth high-resolution all-optical intravascular ultrasound using miniaturized photoacoustic transducer
Authors: Wang Lei , Zhao Yongwen , Zheng Bo , Huo Yong , Fan Yubo , Ma Dinglong , Gu Ying , Wang Pu
Published: June 2023

Conventional intravascular ultrasound (IVUS) uses piezoelectric transducers to electrically generate and receive ultrasound. However, it remains a challenge to achieve large bandwidth for high resolution without compromising imaging depth. We report an all-optical IVUS (AO-IVUS) imaging system using picosecond laser pulse–pumped carbon composite for ultrasound excitation and π-phase–shifted fiber Bragg gratings for ultrasound detection. Using this all-optical technique, we achieved ultrawide-bandwidth (147%) and high-resolution (18.6 micrometers) IVUS imaging, which is unattainable by conventional technique. Imaging performance has been characterized in phantoms, presenting 18.6-micrometer axial resolution, 124-micrometer lateral resolution, and 7-millimeter imaging depth. Rotational pullback imaging scans are performed in rabbit iliac artery, porcine coronary artery, and rabbit arteries with drug-eluting metal stents, in parallel with commercial intravenous ultrasound scans as reference. Results demonstrated the advantages of high-resolution AO-IVUS in delineating details in vascular structures, showing great potential in clinical applications.
Successful bailout stenting for critical aortic coarctation in a premature baby weighing 590 g
Authors: Matsuo Kumiyo , Asada Dai , Aoki Hisaaki , Kayatani Futoshi
Published: June 2023

Severe aortic coarctation (CoA) is a critical congenital heart disease that requires surgery as the first-line treatment in neonates. However, in very small premature infants, aortic arch repair has a relatively high mortality and morbidity rate. Bailout stenting is an alternative method that can be performed safely and effectively with low morbidity.

We present a case of severe CoA in a premature baby, a monochorionic twin with selective intrauterine growth restriction. The patient was born at 31 weeks of gestation with a birth weight of 570 g. Seven days following her birth, she experienced anuria due to critical neonatal isthmic CoA. She underwent a stent implantation procedure at term neonatal, weighing 590 g. She had good dilatation of the coarcted segment with no complications. Follow-up at infancy showed no CoA recurrence. This is the world’s smallest case of stenting for CoA.
Multiple cutaneous and mucocutaneous lesions as manifestations of pseudo-Behçet’s disease
Authors: Choudhary Sanjiv , Srivastava Ankita , Varadharajan Ariharasudhan , Choudhary Rijavi
Published: June 2023

Pseudo-Behçet’s disease (PBD) is a close clinical mimicker of Behçet’s disease (BD) which can present with orogenital ulceration and uveitis. However, these manifestations in PBD are associated with occult tuberculosis. Sometimes, diagnosis of PBD is established retrospectively when the lesions respond to anti-tubercular therapy (ATT). We here describe a case who presented with a penile ulcer, initially suspected to be a sexually transmitted infection, but was later diagnosed as PBD and resulted in complete healing with ATT. Knowledge about this condition is essential to prevent misdiagnosis as BD and unnecessary treatment with systemic corticosteroids, which can lead to worsening of tuberculosis.
Length of employment in workplaces handling hazardous chemicals and risk of cancer among Japanese men
Authors: Fukai Kota , Furuya Yuko , Nakazawa Shoko , Kojimahara Noriko , Hoshi Keika , Toyota Akihiro , Tatemichi Masayuki
Published: June 2023

Objectives

In Japan, the risk of developing cancer among workers employed in workplaces where chemical substances are handled is unclear. This study aimed to assess the association between cancer risk and employment in workplaces handling hazardous chemicals.

Methods

The Inpatient Clinico-Occupational Survey of the Rosai Hospital Group data of 120 278 male patients with incident cancer and 217 605 hospital controls matched for 5-year age group, hospital (34 hospitals) and year of admission (2005–2019) were analysed. Cancer risk in relation to lifetime employment in workplaces using regulated chemicals was assessed while controlling for age, region and year of diagnosis, smoking, alcohol consumption and occupation. Further analysis stratified by smoking history was performed to examine interaction effects.

Results

In the longest group of employment in tertiles, ORs were increased for all cancers (OR=1.13; 95% CI: 1.07 to 1.19) and lung (OR=1.82; 95% CI: 1.56 to 2.13), oesophageal (OR=1.73; 95% CI: 1.18 to 2.55), pancreatic (OR=2.03; 95% CI: 1.40 to 2.94) and bladder (OR=1.40; 95% CI: 1.12 to 1.74) cancers. Employment of 1+ years was associated with risk for lung cancer; 11+ years for pancreatic and bladder cancers; and 21+ years for all cancers and oesophageal cancer. These positive relationships were particularly obvious among patients with a history of smoking; however, no significant interaction between smoking and length of employment was observed.

Conclusions

There is a high risk of cancer among workers, especially smokers, employed in workplaces handling regulated chemicals in Japan. Thus, future measures for chemical management in workplaces are needed to prevent avoidable cancers.
Short-term exposure to near-future CO2has limited influence on the energetics and behaviour of young-of-year salmonids
Authors: Traynor Emma M. , DePasquale Simon W. , Hasler Caleb T.
Published: June 2023

In many freshwater ecosystems, carbon dioxide (CO2) is increasing. Unknown are the risks that high CO2poses for freshwater organisms, especially fish. The objective of this study was to determine how CO2may influence the growth rate, metabolic rate, feeding rate, and volitional behaviour of young-of-year Arctic charr ( Salvelinus alpinus (Linnaeus, 1758)), brook charr ( Salvelinus fontinalis (Mitchill, 1814)), and rainbow trout ( Oncorhynchus mykiss (Walbaum, 1792)). For this study, fish stayed in control (1100 microatmospheres (µatm)) or elevated (5236 µatm) CO2levels for 15 days. During this time, metabolic rate and behavioural tests were conducted on alternating days for each treatment. Weight and length of each fish were taken on days 0, 7, and 15. There was no evidence that elevated CO2affected the growth rate, feeding rate, or behaviour in any of these species. The standard metabolic rate in Arctic charr differed based on CO2exposure. Therefore, salmonids can withstand short periods of elevated CO2under these conditions. By comparing closely related species, the implications of this work are more ecologically relevant and will also help industry quantify the effects of high CO2on young salmonids.
A new look at the Dirac quantization condition
Authors: Dunia Michael , Hung P. Q. , Singleton Douglas
Published: June 2023

The angular momentum of any quantum system should be unambiguously quantized. We show that such a quantization fails for a pure Dirac monopole due to a previously overlooked field angular momentum from the monopole-electric charge system coming from the magnetic field of the Dirac string and the electric field of the charge. Applying the point-splitting method to the monopole-charge system yields a total angular momentum which obeys the standard angular momentum algebra, but which is gauge variant. In contrast it is possible to properly quantize the angular momentum of a topological ’t Hooft–Polyakov monopole plus charge. This implies that pure Dirac monopoles are not viable – only ’t Hooft–Polyakov monopoles are theoretically consistent with angular momentum quantization and gauge invariance.
Influence of Low Pressures on the Performance of Lithium Ion Batteries for Airplane Applications
Authors: Hoenicke P. , Khatri R. , Bauer C. , Osama M. , Kallo J. , Willich C.
Published: June 2023

The electrification of aircrafts is a recent trend in aviation and with it the use of batteries as energy carriers at high altitudes. These batteries can be exposed to low pressures and it is crucial to understand the influence of low pressures on the battery behavior. In this study, commercially available lithium ion batteries were examined experimentally at low pressures down to 25 kPa. Discharge curves and impedance measurements were performed at 23 °C for each pressure level. Cylindrical Lithium Nickel-Cobalt-Aluminum Oxide (NCA) and Iron-Phosphate (LFP) cells did not show any pressure influence, while Lithium Nickel-Manganese-Cobalt Oxide (NMC) pouch cells showed some performance variation with reduced pressure. The ohmic resistance increased by around 0.1 mΩ per 25 kPa and at 25 kPa the charge transfer impedance increased for low SOCs. The results show that no strong change in performance is to be expected for low pressure applications in airplanes, however further research is needed with respect to long term effects, thermal management and safety.
Slurry Based Lithium-Ion Flow Battery with a Flow Field Design
Authors: Xiong Ningxin , Luo Wenqiang , Lan Quan , Wu Qixing
Published: June 2023

Slurry based lithium-ion flow battery has been regarded as an emerging electrochemical system to obtain a high energy density and design flexibility for energy storage. The coupling nature of electrode thickness and flow resistance in previous slurry flow cell designs, demands a nuanced balance between power output and auxiliary pumping. To address this issue, a slurry based lithium-ion flow battery featuring a serpentine flow field and a stationary porous carbon felt current collector is proposed in this work. The carbon felt serves to provide a stable and efficient pathway for electron transport, while the flow field helps distribute active slurry onto the felt for electrochemical reactions. With such a design, the LiFePO4 (LFP) slurry based flow battery shows a low flow resistance and good flow stability without forming severe filter cakes on the felt surface, similar to cross-flow filtration. A maximum power density of 84.5 mW cm−2 and a stable coulombic efficiency of ∼98% under intermittent flow, and a specific capacity of 164.87 mAh g−1 (based on the total LFP in the tank) in continuous flow are successfully demonstrated. These preliminary yet encouraging results may put forward new avenues for future structural design and optimization of slurry based flow batteries.
Single Crystal Li1+x[Ni0.6Mn0.4]1−xO2 Made by All-Dry Synthesis
Authors: Garayt Matthew D. L. , Zhang Ning , Yu Svena , Abraham Jeffin James , Murphy Aidan , Omessi Roee , Ye Ziwei , Azam Saad , Johnson Michel B. , Yang Chongyin , Dahn J. R.
Published: June 2023

Cobalt-free, single crystal layered-oxide positive electrode materials like Li1+x[Ni0.6Mn0.4]1−xO2 (NM64) have received recent interest because of their low cost, high-voltage stability, and good cycle life. In this work, single crystal NM64 is successfully produced with a simple all-dry synthesis process that requires no water, no intermediate chemicals, and produces little waste. The all-dry synthesized NM64 has ≤ 4% nickel in the lithium layer based on Rietveld refinement of powder XRD patterns, has a median particle size of 2–5 μm based on SEM and particle size analysis, and has excellent high-voltage stability at C/5 up to 4.4 V vs Li+/Li compared to a commercial material. Additionally, tungsten coating is shown to decrease the median particle size and improve the cycling stability in half cells from 91% retained capacity after 100 cycles to 93% retained capacity when 0.3% tungsten is added. It is believed that this incredibly simple process could be adopted relatively easily into current commercial positive electrode manufacturing facilities to reduce the complexity, cost, and time of manufacture.
Scanning Ion Conductance Microscopy of Nafion-Modified Nanopores
Authors: Alanis Kristen , Siwy Zuzanna S. , Baker Lane A.
Published: June 2023

Single nanopores in silicon nitride membranes are asymmetrically modified with Nafion and investigated with scanning ion conductance microscopy, where Nafion alters local ion concentrations at the nanopore. Effects of applied transmembrane potentials on local ion concentrations are examined, with the Nafion film providing a reservoir of cations in close proximity to the nanopore. Fluidic diodes based on ion concentration polarization are observed in the current-voltage response of the nanopore and in approach curves of SICM nanopipette in the vicinity of the nanopore. Experimental results are supported with finite element method simulations that detail ion depletion and enrichment of the nanopore/Nafion/nanopipette environment.
Increased Iron Levels and Oxidative Stress Mediate Age-Related Impairments in Male and Female Drosophila melanogaster
Authors: Gomes Karen Kich , dos Santos Ana Beatriz , dos Anjos Jaciana Sousa , Leandro Luana Paganotto , Mariano Maria Takemura , Pinheiro Felipe Lima , Farina Marcelo , Franco Jeferson Luis , Posser Thais
Published: June 2023

Aging is characterized by a functional decline in the physiological functions and organic systems, causing frailty, illness, and death. Ferroptosis is an iron- (Fe-) dependent regulated cell death, which has been implicated in the pathogenesis of several disorders, such as cardiovascular and neurological diseases. The present study investigated behavioral and oxidative stress parameters over the aging of Drosophila melanogaster that, together with augmented Fe levels, indicate the occurrence of ferroptosis. Our work demonstrated that older flies (30-day-old) of both sexes presented impaired locomotion and balance when compared with younger flies (5-day-old). Older flies also produced higher reactive oxygen species (ROS) levels, decreased glutathione levels (GSH), and increased lipid peroxidation. In parallel, Fe levels were augmented in the fly’s hemolymph. The GSH depletion with diethyl maleate potentiated the behavioral damage associated with age. Our data demonstrated biochemical effects that characterize the occurrence of ferroptosis over the age of D. melanogaster and reports the involvement of GSH in the age-associated damages, which could be in part attributed to the augmented levels of Fe.
The Role of Annealing Treatment on Crystallographic, Optical, and Electrical Features of Bi2O3 Thin Films Prepared Using Reactive Plasma Sputtering Technology
Authors: Beden Sabeeha A. J. , Dumboos Hassan A. , Ismael Mustafa K. , Kadhim Mejbel Mohanad
Published: June 2023

Bismuth oxide (Bi2O3) has attracted considerable research interest in test thin films made utilizing the reactive plasma sputtering (RPS) technology-assisted annealing treatment, allowing the development of diverse BixOx thin films. SEM, phase X-ray diffraction patterns, UV-Vis spectrometers, and D.C. two-probes are used to identify the crystallographic structure and assess the films’ optical-electrical properties. The XRD examination showed that forming Bi2O3 films with an amorphous to multiphase crystalline structure for sputtering time of 40 min was due to soda glass substrate temperature at a range of 30–35°C. Thin films of Bi2O3 crystal structures improved with annealing heat treatment at 200, 300, 400, and 500°C. Yet the formation of crystalline phase (β-Bi2O3 with δ-Bi2O3) Bi2O3 nanostructures occurred at higher temperatures. SEM images showed transparent particles highly affected by annealing temperatures. The nanostructures were about 102–510 nm long, and the diameter was 50–100 nm. The Bi2O3 film optical band gaps and nanostructures ranged from 2.75 to 3.05 eV. The annealing temperature differences affected the crystallite sizes, optical band gaps, and surface roughness. The findings showed that these differences caused the phase transition in Bi2O3 structures. The electrical calculation revealed that the electrical conductivity improved with annealing temperatures of 150–250°C while declining with temperature (300–500)°C with typical semiconductor films.
Table S5 from RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non–Small Cell Lung Cancer
Authors: Nakagawa Kazuhiko , Nadal Ernest , Garon Edward B. , Nishio Makoto , Seto Takashi , Yamamoto Nobuyuki , Park Keunchil , Shih Jin-Yuan , Paz-Ares Luis , Frimodt-Moller Bente , Zimmermann Annamaria H. , Wijayawardana Sameera , Visseren-Grul Carla , Reck Martin
Published: June 2023

RELAY contributing investigators
Table S3 from RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non–Small Cell Lung Cancer
Authors: Nakagawa Kazuhiko , Nadal Ernest , Garon Edward B. , Nishio Makoto , Seto Takashi , Yamamoto Nobuyuki , Park Keunchil , Shih Jin-Yuan , Paz-Ares Luis , Frimodt-Moller Bente , Zimmermann Annamaria H. , Wijayawardana Sameera , Visseren-Grul Carla , Reck Martin
Published: June 2023

Post-study discontinuation therapies by subsequent lines of treatment (first through third) of the baseline EGFR-activating mutation subgroups.
Table S1 from RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non–Small Cell Lung Cancer
Authors: Nakagawa Kazuhiko , Nadal Ernest , Garon Edward B. , Nishio Makoto , Seto Takashi , Yamamoto Nobuyuki , Park Keunchil , Shih Jin-Yuan , Paz-Ares Luis , Frimodt-Moller Bente , Zimmermann Annamaria H. , Wijayawardana Sameera , Visseren-Grul Carla , Reck Martin
Published: June 2023

Overview of adverse events by baseline activating mutation subgroup (safety population).
Figure S1 from RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non–Small Cell Lung Cancer
Authors: Nakagawa Kazuhiko , Nadal Ernest , Garon Edward B. , Nishio Makoto , Seto Takashi , Yamamoto Nobuyuki , Park Keunchil , Shih Jin-Yuan , Paz-Ares Luis , Frimodt-Moller Bente , Zimmermann Annamaria H. , Wijayawardana Sameera , Visseren-Grul Carla , Reck Martin
Published: June 2023

CONSORT diagram of RELAY patients by baseline activating EGFR mutation subgroup. One patient was enrolled with an exon 21 mutation other than L858R and was reported as an important protocol deviation. The patient continued to receive study treatment due to continued treatment benefit and was subsequently discontinued from study prior to Cycle 30. One patient did not have documented evidence of ex21L858R substitution mutation at enrollment and was reported as an important protocol deviation. This patient was subsequently discontinued from study prior to Cycle 3. Progressive disease is defined as the time from the date of randomization until the date of radiographic documentation of progression (as defined by RECIST v1.1) or the date of death due to any cause, whichever is earlier. The translational research population for baseline NGS analyses (TR-BL) included patients who had any detectable NGS alteration at baseline. Treatment-emergent NGS analyses (TR-TE) included patients who had any detectable NGS alteration at baseline and at the poststudy treatment discontinuation visit upon confirmed disease progression.
Data from Identification of 2′,4′,6′-Trihydroxyacetophenone as Promising Cysteine Conjugate Beta-Lyase Inhibitor for Preventing Cisplatin-Induced Nephrotoxicity
Authors: Sukeda Nao , Fujigaki Hidetsugu , Ando Tatsuya , Ando Honomi , Yamamoto Yasuko , Saito Kuniaki
Published: June 2023

Abstract
Cisplatin is a chemotherapeutic agent used to treat many types of malignant tumors. However, irrespective of its potent anticancer properties and efficacy, nephrotoxicity is the dose-limiting factor of cisplatin treatment. Cisplatin infiltrates renal tubular cells in the kidneys and is metabolized by cysteine conjugate-beta lyase 1 (CCBL1) to form highly reactive thiol-cisplatin; this may mediate cisplatin's nephrotoxicity. Therefore, CCBL1 inhibition may prevent cisplatin-induced nephrotoxicity. Using a high-throughput screening assay, we identified 2′,4′,6′-trihydroxyacetophenone (THA) as an inhibitor of CCBL1. THA inhibited human CCBL1 β-elimination activity in a concentration-dependent manner. We further investigated the preventive effect of THA on cisplatin-induced nephrotoxicity. THA attenuated the effect of cisplatin on the viability of confluent renal tubular cells (LLC-PK1 cells) but had no effect on cisplatin-induced reduction of proliferation in the tumor cell lines (LLC and MDA-MB-231). THA pretreatment significantly attenuated cisplatin-induced increases in blood urea nitrogen, creatinine, cell damage score, and apoptosis of renal tubular cells in mice in a dose-dependent manner. Furthermore, THA pretreatment attenuated cisplatin-induced nephrotoxicity without compromising its antitumor activities in mice bearing subcutaneous syngeneic LLC tumors. THA could help prevent cisplatin-induced nephrotoxicity and may provide a new strategy for cisplatin-inclusive cancer treatments.
Abstract 1: Mouse models of cancer available from The Jackson Laboratory
Authors: Beckwith Jason , Merriam Jen , Valenzuela Alicia , Pomerleau Darcy , Davis Crystal
Published: June 2023

Genetically defined mice are a cornerstone of cancer research. The Jackson Laboratory (JAX) offers more than 13,500 unique mouse lines to the scientific community, many useful in advancing cancer research. Available are mouse models for specific cancers, xenograft recipients, immunodeficient platforms for PDX studies and multi-purpose tool strains having CRISPR/Cas9 expression, conditional/inducible expression (Cre-lox, FLP-frt, Tet-On/-Off), optogenetic function and calcium-sensing technologies. This poster will highlight some recently added models, more than 150 of which have cancer research applications. The portfolio of strains useful for transplantation/engraftment and “humanized” mouse research continues to expand and complement the NSG (NOD scid IL2rγc-/-) model as ideal tools for engraftment with a wide range of malignant or non-malignant human or mouse tissues. Fluorescent protein-expressing strains include the Traffic Light Reporter models for tracking of DNA repair pathways and the Gene Editing Reporter models for detection of homology directed repair (HDR) or non-homologous end joining (NHEJ) repair events. As a tool for gene targeting, the RosaBxb-GT/GA mice are designed to allow insertion of ~40kb of desired DNA sequence into the Gt(ROSA)26Sor locus. In addition to safeguarding each strain by cryopreservation, JAX has a comprehensive genetic quality control program that confirms mutation identity and genetic background, and screens for unwanted alleles (such as stray GFP, Cre, neo, etc.). Search the comprehensive collection of innovative mouse models using our improved JAX Mouse Search site (mice.jax.org). This resource includes models created by many generous donating institutions. Researchers are encouraged to donate their mouse lines via a very short Strain Submission form (jax.org/donate-a-mouse). Please also visit the JAX Oncology webpage for cancer research related strains and resources (jax.org/jax-mice-and-services/solutions-by-therapeutic-area/oncology). JAX is supported by the NIH, The Howard Hughes Medical Institute and other private charitable foundations.

Citation Format: Jason Beckwith, Jen Merriam, Alicia Valenzuela, Darcy Pomerleau, Crystal Davis. Mouse models of cancer available from The Jackson Laboratory [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1.
Abstract 1006: Assessment of expression of microRNA-23b as a prognostic marker in cancer
Authors: Wadaaallah Ahmed Mahmoud , Sultan Ahmed Samir
Published: June 2023

Cancer is the major cause of death around the world. MiRNA-23b has been proposed to be expressed in various types of cancer. However, it’s prognostic role in several types of cancer has not been well identified. We conducted this meta-analysis to assess the associations between miRNA-23b expression and overall survival (OS) in various carcinoma. The current study presented the baseline characteristics and pooled survival results using a pooled hazard ratio (HR) with 95% confidence intervals (95% CI). Both Random and fixed effect models were conducted according to the heterogeneity of the analyzed. Then subgroup and publication bias analyses were executed. We identified a total sample size of 1589 in various carcinomas, including gastric (370), breast (203), ovarian (166), colorectal (206), renal (411), bladder (20), prostate (151) and lung cancer (62). The pooled HR of nine studies suggested that low miRNA-23b expression was obviously associated with worse OS (HR 3.2, 95% CI 2.26 to 4.53, P<0.001) with a low statistical heterogeneity index (I2=53%, P=0.03) in most of cancer types. On the other hand, the other three remaining studies (gastric and breast cancer) showed that miRNA-23b high expression was associated with reduced OS (HR 1.59, 95%CI 1.07 to 2.37, P<0.02) with no heterogeneity between the studies (I2=0%, P=0.38). All in all, our data showed that miRNA-23b was highly expressed in the plasma of breast and gastric cancer but was low expressed in most types of cancer. In addition, miRNA -23b expression is significantly associated with poor overall survival in several cancer types and might be considered as a potential prognostic marker.

Citation Format: Ahmed Mahmoud Wadaaallah, Ahmed Samir Sultan. Assessment of expression of microRNA-23b as a prognostic marker in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1006.
Abstract 1061: Digital phenotyping in pediatric oncology: the development of a mobile application for outpatients follow up
Authors: Elmoneim Abeer Abd , Aly Marwan
Published: June 2023

Introduction and aim: Outpatients follow up usually depends on recall of data. This recall is subjective to patients' or gaurdians' memory. Smart phones can capture a lot of data either through inbuilt sensors and connected devices or through the engagement of users. These mobile digital devices brought forth innovative methods of acquiring personal healthcare data. In pediatric oncology, the need for accurate record of serious symptoms while patients are at home is a challenge in outpatients' care. In a step towards collecting real-time events that happened during the outpatient follow up, we develop a smart phone application that can record data actively by patients or their guardians in situ and on time of its occurrence, which can improve the follow up process and facilitate a decision making by the physician that based on objective data more than subjective ones. We aim in this research to generate an easy-to-use mobile application for home follow up of pediatric oncology patients.

Methods: Predictive characteristics of digital features either extracted from studies or generated by field experts were reported to map the associations between digital feature and the disease. Identified digital features were aggregated into categories that represent interpretable serious signs. A smart phone application with the identified digital features is developed with the help of Valid Solutions, LLC (Health Technology Limited Liability Company, USA).

Expected Results: Early and accurate detection of serious symptoms through in situ and on real-time can help to better delivery of required health care.

Conclusion: This research will provide a high level vision on relationships between digital phenotyping and pediatric oncology illnesses and will help to identify gaps requiring further research. It will highlight the digital features with higher value of prediction of serious signs.

Citation Format: Abeer Abd Elmoneim, Marwan Aly. Digital phenotyping in pediatric oncology: the development of a mobile application for outpatients follow up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1061.
Abstract 1073: PRMT5 inhibition synergizes with a natural small molecule compound to kill MTAP-deleted cells and suppress tumor growth
Authors: Barekatain Yasaman , LaBella Kyle , Sugimoto Hikaru , Harris Kristen , Khadka Sunada , Muller Florian , Kalluri Raghu
Published: June 2023

Homozygous deletion of MTAP occurs in about 15% of all human cancers, such as glioblastoma, pancreatic cancer, mesothelioma, urothelial bladder carcinoma, and lung squamous cell carcinoma. PRMT5 inhibitors show activity against MTAP-deleted cancer cells in culture and xenografts with a mechanism that relies on the significant elevation of the MTAP substrate, methylthioadenosine (MTA). Previously, we have shown that unlike cells in culture, MTA levels in MTAP-deleted primary human GBM tumors are not significantly higher than in MTAP-intact tumors. Therefore, combining the PRMT5 inhibitor with another drug may be required to increase the therapeutic window and clinical efficacy of a PRMT5 inhibitor in MTAP-deleted patients. Here, we identified a natural small molecular chemical compound with a good safety profile that synergizes with a PRMT5-MTA complex inhibitor, which boosts the efficacy of MTAP-deleted selective cell killing in the presence of MTA sequestering cells. This combination therapy significantly increases the potency of PRMT5 inhibitor treatment in MTAP-deleted cells across various tumor cell lines and lowers the IC50 of PRMT5 inhibitor treatment. In vivo, PRMT5 inhibitor combination treatment leads to smaller tumor volumes in MTAP-deleted CDX tumors (U87, glioma cell line) compared to PRMT5 inhibitor monotherapy. In summary, our proposed combination therapy of PRMT5 inhibition with a natural compound may increase the therapeutic window and clinical efficacy of PRMT5 inhibitors leading to better treatment options for patients harboring MTAP-deleted cancer.

Citation Format: Yasaman Barekatain, Kyle LaBella, Hikaru Sugimoto, Kristen Harris, Sunada Khadka, Florian Muller, Raghu Kalluri. PRMT5 inhibition synergizes with a natural small molecule compound to kill MTAP-deleted cells and suppress tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1073.
Abstract 111: Characterizing subpopulation response to doxorubicin in a barcode-labeled triple negative breast carcinoma cell line
Authors: Morgan Daylin , Brock Amy
Published: June 2023

Despite recent advances in diagnosis and late-stage treatment, progression-free survival is not achieved for many cancer patients. Triple negative breast cancer (TNBC) poses a particular challenge as an aggressive and heterogeneous disease lacking the benefit of hormonal therapies. We have utilized a novel genetic lineage-tracking system, ClonMapper in TNBC cells to elucidate the pre-existent and de novo cell states that arise from chemotherapeutic intervention.

ClonMapper genetic tags were stably integrated into MDA-MB-231 cells using lentiviral transduction and positively labeled cells were isolated with fluorescence-activated cell sorting to generate a starting library of ~500 uniquely barcoded cells. Barcode-labeled MDA-MB-231 were selected with doxorubicin at 250, 400 and 550 nM for 48 hours and allowed to recover. To determine the contribution of transcriptomic state to cellular drug response we carried out single cell RNA-sequencing (scRNA-seq) on 4 populations: a pretreatment cell library, an intermediary taken 30 h into drug selection, and two recovered populations from the 250 nM group. Importantly, we are able to capture and deconvolve ClonMapper lineage tags from scRNA-seq results and overlay them with transcriptomic state.

Following treatment with doxorubicin we found a dose-dependent reduction in the number of unique lineages, with all replicates showing >6-fold decrease. Post-treatment replicates were each significantly comprised (90%) by fewer than three individual lineages. Lineage-resolved transcriptomics revealed two distinct lineage-specific subpopulations within the pretreatment cell library. These subpopulations demonstrated unique survivorship trajectories, beginning 30 h into selection and remaining well-separated following recovery from treatment. Comparing these subpopulations directly we observe enrichment for several pathways with markers genes remaining highly expressed post-treatment. Crucially, both subpopulations harbor a unique set of lineages which are found to survive treatment. However, in the absence of treatment we find that one subpopulation displays a faster growth rate and is likely to outcompete the other in culture conditions. The more proliferative subpopulation is marked by enrichment of Myc targets, compared with enrichment of glycolysis and KRAS signaling in the less proliferative subpopulation. This data demonstrates that subclonal heterogeneity inherent within this TNBC cell model, drives differential cell responses to chemotherapy.

Citation Format: Daylin Morgan, Amy Brock. Characterizing subpopulation response to doxorubicin in a barcode-labeled triple negative breast carcinoma cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 111.
Abstract 1121: Patient-centric Discovery by Active Learning (PeDAL) platform to predict drug response in a heterogeneous patient population
Authors: Montgomery Robert J. , Gilkey Aaron W. , Kangas Joshua D. , Murphy Robert F. , Uihlein Arlette H.
Published: June 2023

Even after thorough preclinical testing, only 5% of oncology drug candidates entering clinical trials ultimately get approved for use in patients. To find one drug that will be effective in the clinic, drug developers have to test 20 agents, 19 of which will ultimately prove ineffective. Such high attrition rates drive up the cost of treatment and delay getting effective drugs to the market. Here we describe the Patient-centric Discovery by Active Learning (PeDAL) platform and present results of a study that shows it can predict the effectiveness of a drug or a set of drugs in a patient population with 92% accuracy in only 11 weeks while only performing in vitro assays on a fraction of the drug-patient combinations. The power of PeDAL is derived from a combination of AI technology, an extensive drug response and biomarker database, and a biobank of 150,000 tumor samples from 137 tumor types. The study consists of two phases, the first demonstrates that PeDAL’s predictive model efficiently reveals drug-response patterns that provide insight into the treatment of ovarian cancers. The second phase focuses on the in vitro validation of the accuracy of the predictions. The experimental space was 175 FDA-approved drugs and 130 primary ovarian tumor samples. PeDAL’s active machine learning algorithm iteratively optimizes predictive models by learning from in vitro experiments which take into account tumor-stromal interactions and cellular heterogeneity. Importantly, the ability to model patient-drug combinations across a diverse population of primary samples adds a patient heterogeneity dimension to the generated drug response predictions. After performing 720 high throughput experiments, PeDAL was able to make drug-response predictions for an additional 4,600 drug/tumor predictions. Additional in vitro validation experiments confirm the reproducibility and accuracy of the high-confidence predictions generated by PeDAL with area under the curve (AUC) values >0.95. These results have strong implications not only for the new drug discovery process, but also for identifying opportunities for drug repurposing. We demonstrate that the PeDAL platform is a highly efficient tool to make confident predictions about drug-tumor pairings allowing the discovery of many more drug-tumor responses than are practical to test in vitro.

Citation Format: Robert J. Montgomery, Aaron W. Gilkey, Joshua D. Kangas, Robert F. Murphy, Arlette H. Uihlein. Patient-centric Discovery by Active Learning (PeDAL) platform to predict drug response in a heterogeneous patient population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1121.