bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating low birth weight and preterm birth as potential mediators in the relationship between prenatal infections and early child development: a linked administrative health data analysis
Authors: Hardie Iain , Murray Aja , King Josiah , Hall Hildigunnar Anna , Okelo Kenneth , Luedecke Emily , Marryat Louise , Thompson Lucy , Minnis Helen , Lombardo Michael , Wilson Philip , Auyeung Bonnie
Published: June 2024

Background

Prenatal infections are associated with childhood developmental outcomes such as reduced cognitive abilities, emotional problems and other developmental vulnerabilities. However, there is currently a lack of research examining whether this arises due to potential intermediary variables like low birth weight or preterm birth, or due to some other mechanisms of maternal immune activation arising from prenatal infections.

Methods

Administrative data from the National Health Service health board of Greater Glasgow & Clyde, Scotland, were used, linking birth records to hospital records and universal child health review records for 55 534 children born from 2011 to 2015, and their mothers. Causal mediation analysis was conducted to examine the extent to which low birth weight and preterm birth mediate the relationship between hospital-diagnosed prenatal infections and having developmental concern(s) identified by a health visitor during 6–8 weeks or 27–30 months child health reviews.

Results

Model estimates suggest that 5.18% (95% CI 3.77% to 7.65%) of the positive association observed between hospital-diagnosed prenatal infections and developmental concern(s) was mediated by low birth weight, while 7.37% (95% CI 5.36 to 10.88%) was mediated by preterm birth.

Conclusion

Low birth weight and preterm birth appear to mediate the relationship between prenatal infections and childhood development, but only to a small extent. Maternal immune activation mechanisms unrelated to low birth weight and preterm birth remain the most likely explanation for associations observed between prenatal infections and child developmental outcomes, although other factors (for example, genetic factors) may also be involved.
Guidelines for NGS procedures applied to prenatal diagnosis by the Spanish Society of Gynecology and Obstetrics and the Spanish Association of Prenatal Diagnosis
Authors: Abulí Anna , Antolín Eugenia , Borrell Antoni , Garcia-Hoyos Maria , García Santiago Fe , Gómez Manjón Irene , Maíz Nerea , González González Cristina , Rodríguez-Revenga Laia , Valenzuena Palafoll Irene , Suela Javier
Published: June 2024

Objective

This document addresses the clinical application of next-generation sequencing (NGS) technologies for prenatal genetic diagnosis and aims to establish clinical practice recommendations in Spain to ensure uniformity in implementing these technologies into prenatal care.

Methods

A joint committee of expert obstetricians and geneticists was created to review the existing literature on fetal NGS for genetic diagnosis and to make recommendations for Spanish healthcare professionals.

Results

This guideline summarises technical aspects of NGS technologies, clinical indications in prenatal setting, considerations regarding findings to be reported, genetic counselling considerations as well as data storage and protection policies.

Conclusions

This document provides updated recommendations for the use of NGS diagnostic tests in prenatal diagnosis. These recommendations should be periodically reviewed as our knowledge of the clinical utility of NGS technologies, applied during pregnancy, may advance.
Validation of the BOADICEA model in a prospective cohort ofBRCA1/2pathogenic variant carriers
Authors: Yang Xin , Mooij Thea M , Leslie Goska , Ficorella Lorenzo , Andrieu Nadine , Kast Karin , Singer Christian F. , Jakubowska Anna , van Gils Carla H , Tan Yen Y , Engel Christoph , Adank Muriel A , van Asperen Christi J , Ausems Margreet G E M , Berthet Pascaline ,   EMBRACE collaborators, Collee Margriet J , Cook Jackie A , Eason Jacqueline , Spaendonck-Zwarts Karin Y van , Evans D. Gareth , Gómez García Encarna B , Hanson Helen , Izatt Louise , Kemp Zoe , Lalloo Fiona , Lasset Christine , Lesueur Fabienne , Musgrave Hannah , Nambot Sophie , Noguès Catherine , Oosterwijk Jan C , Stoppa-lyonnet Dominique , Tischkowitz Marc , Tripathi Vishakha , Wevers Marijke R , Zhao Emily , van Leeuwen Flora E , Schmidt Marjanka K , Easton Douglas F , Rookus Matti A , Antoniou Antonis C
Published: June 2024

Background

No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically inBRCA1/2pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort ofBRCA1/2PV carriers ascertained through clinical genetic centres.

Methods

We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614BRCA1and 1365BRCA2PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information.

Results

The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell’s C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately inBRCA1orBRCA2PV carriers. The full model identified 5.8%, 12.9% and 24.0% ofBRCA1/2PV carriers with 5-year breast cancer risks of <1.65%, <3% and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options.

Conclusion

BOADICEA may be used to aid personalised cancer risk management and decision-making forBRCA1andBRCA2PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/).
Place of care and death preferences among recently bereaved family members: a cross-sectional survey
Authors: O'Sullivan Anna , Larsdotter Cecilia , Sawatzky Richard , Alvariza Anette , Imberg Henrik , Cohen Joachim , Öhlén Joakim
Published: June 2024

Objectives

The aim was: (1) to investigate preferred place for end-of-life care and death for bereaved family members who had recently lost a person with advanced illness and (2) to investigate associations between bereaved family members’ preferences and individual characteristics, health-related quality of life, as well as associations with their perception of the quality of care that the ill person had received, the ill person’s preferred place of death and involvement in decision-making about care.

Methods

A cross-sectional survey with bereaved family members, employing descriptive statistics and multinominal logistic regression analyses.

Results

Of the 485 participants, 70.7% were women, 36.1% were ≥70 years old, 34.5% were partners and 51.8% were children of the deceased. Of the bereaved family members, 52% preferred home for place of end-of-life care and 43% for place of death. A higher likelihood of preferring inpatient palliative care was associated with being female and having higher education, whereas a lower likelihood of preferring a nursing home for the place of care and death was associated with higher secondary or higher education. Partners were more likely to prefer hospital for place of care and nursing home for place of death.

Conclusions

Home was the most preferred place for end-of-life care and death. Bereaved people’s experiences of end-of-life care may impact their preferences, especially if they had a close relationship, such as a partner who had a higher preference for nursing home and hospital care. Conversations about preferences for the place of care and death considering previous experience are encouraged.
Psychological distress and physical symptoms in advanced cancer: cross-sectional study
Authors: Podbury Bridget , Gurgenci Taylan , Huggett Georgie , Greer Ristan , Hardy Janet , Good Phillip
Published: June 2024

Objectives

Patients with advanced cancer experience varying physical and psychological symptoms throughout the course of their illness. Depression, anxiety and stress affect overall well-being. This study investigates the correlation between emotional distress and physical symptoms in a cohort of patients with advanced cancer.

Methods

There were 238 patients included in this study. Data from participants in two medicinal cannabis randomised controlled trials were analysed. Patients were aged over 18 years and had advanced cancer. Edmonton Symptom Assessment System, and Depression, Anxiety and Stress Scale (DASS-21) were assessed for all patients at baseline.

Results

Moderate-severe depression was reported in 29.8% and moderate-severe anxiety was reported in 47.9% of patients. The emotional subscales of DASS-21 (depression, anxiety, stress) correlated with total symptom distress score (p<0.001) and overall well-being (p<0.001). Depression was correlated with physical symptoms of fatigue, nausea, poor appetite and dyspnoea. Anxiety was correlated with fatigue and dyspnoea. Stress was correlated with fatigue, nausea and dyspnoea.

Conclusions

Depression, anxiety and stress were common in this population. The relationship between physical and psychological well-being is complex. A holistic approach to symptom management is required to improve quality of life in patients with advanced cancer.
Single-arm clinical trials: design, ethics, principles
Authors: Wang Minyan , Ma Huan , Shi Yun , Ni Haojie , Qin Chu , Ji Conghua
Published: June 2024

Although randomised controlled trials are considered the gold standard in clinical research, they are not always feasible due to limitations in the study population, challenges in obtaining evidence, high costs and ethical considerations. As a result, single-arm trial designs have emerged as one of the methods to address these issues. Single-arm trials are commonly applied to study advanced-stage cancer, rare diseases, emerging infectious diseases, new treatment methods and medical devices. Single-arm trials have certain ethical advantages over randomised controlled trials, such as providing equitable treatment, respecting patient preferences, addressing rare diseases and timely management of adverse events. While single-arm trials do not adhere to the principles of randomisation and blinding in terms of scientific rigour, they still incorporate principles of control, balance and replication, making the design scientifically reasonable. Compared with randomised controlled trials, single-arm trials require fewer sample sizes and have shorter trial durations, which can help save costs. Compared with cohort studies, single-arm trials involve intervention measures and reduce external interference, resulting in higher levels of evidence. However, single-arm trials also have limitations. Without a parallel control group, there may be biases in interpreting the results. In addition, single-arm trials cannot meet the requirements of randomisation and blinding, thereby limiting their evidence capacity compared with randomised controlled trials. Therefore, researchers consider using single-arm trials as a trial design method only when randomised controlled trials are not feasible.
An energy-saving loading strategy: cyclic vacuum preloading treatment of soft ground
Authors: Wang Jiahao , Shi Li , Sun Honglei , Cai Yuanqiang , Yu Yanming
Published: June 2024

Vacuum preloading is a commonly adopted method for improving soft ground. During the preloading period, the applied vacuum pressure is constant or multistaged, implying that the vacuum pump must work continuously with constant or increasing operating power. To reduce the energy consumption of the vacuum pump, a new loading strategy of cyclic vacuum loading was proposed in this study, whereby the pump is periodically switched on and off, and hence the vacuum pressure ascends and descends accordingly. To guide the design of cyclic vacuum preloading, a large-strain radial consolidation theory incorporating the shifting of the consolidation status of ground soil from normally consolidated to overconsolidated (and vice versa) was established in the present study. Based on the established theory, the treatment effects of cyclic vacuum loading can be quantitatively determined, including the ground settlement and the degree of consolidation, while the energy consumption can be simply determined by multiplying the power by the operating time of the vacuum pump, which works only during the ascending stage of cyclic vacuum pressure. Two cases of the cyclic vacuum preloading strategy were evaluated herein, that is, the complete cyclic vacuum loading and combined cyclic/constant vacuum loading cases. Finally, experimental tests were conducted to demonstrate the energy-saving effect of cyclic vacuum preloading. Compared to the conventional vacuum preloading strategy (i.e., constant vacuum pressure), the energy consumption of the cyclic vacuum loading strategy can be drastically reduced (80% reduction), while the treatment effects remain basically unaffected.
Modified holographic Ricci interacting dark energy models: dynamical system analysis and Bayesian comparison
Authors: Cid Antonella , Obreque Israel
Published: June 2024

We perform a dynamical system analysis and a Bayesian model selection for a new set of interacting scenarios in the framework of modified holographic Ricci dark energy (MHR-IDE) models. The dynamical analysis shows a modified radiation epoch and a late-time attractor corresponding to an accelerated phase of holographic dark energy. In the Bayesian comparison, we use a combination of background data including type Ia supernovae, cosmic chronometers, the local value of the Hubble constant, baryon acoustic oscillations, and cosmic microwave background data. We find evidence against all the MHR-IDE scenarios studied in comparison with the $$\varLambda $$
Λ
CDM when the full joint analysis is considered.
Hint of a new scalar interaction in LHCb data?
Authors: Datta Alakabha , Marfatia Danny , Mukherjee Lopamudra
Published: June 2024

We explain recent LHCb measurements of the lepton universality ratios, $$R_{D^{(*)}}^{\tau /\ell }\equiv \frac{\mathcal {B}(\bar{B} \rightarrow D^{(*)+} \tau ^- \bar{\nu }_\tau )}{\mathcal {B}(\bar{B} \rightarrow D^{(*)+}\ell ^- \bar{\nu }_\ell )}$$

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decays are significantly affected by the scalar interaction. We construct a simple two Higgs doublet model as a realization of our scenario and consider lepton universality in semileptonic charm and top decays, radiative B decay, B-mixing, and $$Z \rightarrow b \bar{b}$$

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Black bounces in conformal Killing gravity
Authors: Junior José Tarciso S. S. , Lobo Francisco S. N. , Rodrigues Manuel E.
Published: June 2024

In this work, we analyse black bounce solutions in the recently proposed “Conformal Killing gravity” (CKG), by coupling the theory to nonlinear electrodynamics (NLED) and scalar fields. The original motivation of the theory was essentially to fulfill specific criteria that are absent in existing gravitational theories, namely, to obtain the cosmological constant as an integration constant, derive the energy–momentum conservation law as a consequence of the gravitational field equations, rather than assuming it, and not necessarily considering conformally flat metrics as vacuum solutions. In this work, we extend the static and spherically symmetric solutions obtained in the literature, and explore the possibility of black bounces in CKG, coupled to NLED and scalar fields. We find novel NLED Lagrangian densities and scalar potentials, and extend the class of black bounce solutions found in the literature. Furthermore, within black bounce geometries, we find generalizations of the Bardeen-type and Simpson–Visser geometries and explore the regularity conditions of the solutions.
BEYOND THE NUMBERS: THE INTERVENTION OF INNOVATION ORIENTATION BETWEEN THE USE OF THE BUDGET AND PERFORMANCE IN BRAZILIAN ICT COMPANIES
Authors: MARTINS ANDRELA DULCE , LAVARDA CARLOS EDUARDO FACIN
Published: June 2024

This study examined the effect of diagnostic and interactive use of budget on organizational performance mediated by innovation orientation. This was a quantitative and descriptive research in which a survey was carried out with managers of Information and Communication Technology companies. According to the results, the use of the budget does not seem to have a direct relationship with organizational performance, as the relationship was no non-significant. Furthermore, the results suggest that innovation orientation has a positive impact on organizational performance and intervenes positively in the relationship between the interactive use of the budget and organizational performance. The work contributes to budgetary research and innovation, fostering an organizational culture that values both efficiency and the capacity for adaptation and renewal, in addition to guiding managers in the search for best management practices to deal with the dynamism present in the innovative environment.
Tumor Stiffness Measurement at Multifrequency MR Elastography to Predict Lymphovascular Space Invasion in Endometrial Cancer
Authors: Long Ling , Liu Meiling , Deng Xijia , Jin Junjie , Cao Meimei , Zhang Jing , Tao Junli , Shen Hesong , Wang Xiaoxia , Liu Daihong , Zhang Jiuquan
Published: June 2024

A diagnostic model combining tumor stiffness measured at MR elastography with clinical-radiologic variables showed the best performance for predicting lymphovascular space invasion in participants with endometrial cancer.
Electrochemical Nicarbazin Analysis: Rapid Determination on Bucky Paper Disks Constructed from MWCNT
Authors: Lema C. , Álvarez-Lueje A. , Moscoso R. , Squella J. A.
Published: June 2024

Nicarbazin, an anticoccidial drug, is a molecular complex comprising 4,4’-dinitrocarbanilide (DNC) and 2-hydroxy-4,6-dimethylpyrimidine (HDP) in a 1:1 molar ratio. The low solubility of DNC in water (below 0.02 mg L−1) necessitates the use of extraction methods for analysis. Traditional DNC determination methods are time consuming, and involve prolonged sample preparation, extraction procedures, and high costs,. This study presents the results of electrochemical analysis of DNC using an innovative electrode platform composed of bucky paper disks made from a blend of multi-walled carbon nanotubes (MWCNT) and polystyrene (MWCNT/PS/BP). The electroanalytical approach includes an initial adsorption stage of DNC on the electrode platform, followed by its subsequent reduction, capitalizing on the reducibility of the nitro groups within DNC. The analytical parameters of this method are favorable, featuring an average recovery value of 100.22 ± 7.87, a linear range of 2.011–15.112 mg·l−1, a sensitivity of 1.58 μA·mg−1 l−1, LOQ (limit of quantification) of 1.33 mg L−1, and LOD (limit of detection) of 0.40 mg·l−1.
Nano-Structured CuO Grown with Aqueous NH3 for Salivary Glucose Detection
Authors: Bharti Deepak , Sharma Atul Kumar , Mudgal Trapti , Tiwari Manas
Published: June 2024

CuO nanostructures grown on flexible Cu foil by a simple chemical bath deposition in a solution of aqueous ammonia have been explored for non-invasive and nonenzymatic detection of salivary glucose. The nanostructured electrode developed with 100 μl of aqueous ammonia achieves a high sensitivity of 3243 μA mM−1 cm−2, linear range up to 3 mM, and limit of detection of 0.77 μM. The electrode also demonstrates good anti-interference properties, high reproducibility, repeatability, and long-term stability up to 30 days. In addition, the electrode exhibits remarkable sensitivity of 2865 μA mM−1 cm−2 for salivary glucose detection. To explore its potential for non-invasive detection of actual salivary glucose, pre-prandial and post-prandial salivary glucose of different human volunteers were measured using the electrode and were found to be correlated with corresponding blood glucose levels. Development and investigation of similar sensors for non-invasive detection via untraditional methods would certainly pave the way towards next generation glucose monitoring devices and systems.
Effect of Graphene Oxide Incorporation on the Strength of Denture Repair Resin
Authors: Basmaci Fulya , Avukat Esra Nur , Akay Canan , Aykent Filiz
Published: June 2024

To evaluate the effect of incorporating graphene oxide nanoparticles (GO NPs) and graphene sheets on the flexural strength of an auto-polymerized (AP) acrylic resin-repaired denture. 60 heat-activated (HA) resin specimens were fabricated and randomly divided into 6 groups (n = 10). The specimens in Group I were kept intact. 50 specimens were cut into two parts with a 45-degree bevel. Group II specimens were repaired with AP resin and Group III specimens were repaired with HA resin. In the repair of Group IV, Group V, and Group VI specimens, 1%, 2% GO NPs, and graphene sheets were added to AP resin, respectively. A 3-point bending test with a universal test device measured the flexural strength. Statistical analyses of the results were performed with the Kruskal Wallis H-test. (α = 0.05) The flexural strength of Group I (130.05 ± 20.20 MPa) was the highest among all groups. The flexural strength of Group IV (67.49 ± 12.70 MPa) was significantly higher than Group V (50.87 ± 15.02 MPa) and Group VI (44.77 ± 10.70 MPa). The lowest strength value was obtained in Group VI. Adding 1% GO NPs to AP acrylic resins increases flexural strength. However, the increase in nanoparticle concentration and the addition of graphene sheets negatively affect strength.
Supplementary Fig. S6 from Whole-Genome DNA Methylation Profiling of Intrahepatic Cholangiocarcinoma Reveals Prognostic Subtypes with Distinct Biological Drivers
Authors: Liao Haotian , Chen Xing , Wang Haichuan , Lin Youpei , Chen Lu , Yuan Kefei , Liao Mingheng , Jiang Hanyu , Peng Jiajie , Wu Zhenru , Huang Jiwei , Li Jiaxin , Zeng Yong
Published: June 2024

Supplementary Fig. S6
Data from Serotonin Receptor HTR2B Facilitates Colorectal Cancer Metastasis via CREB1–ZEB1 Axis–Mediated Epithelial–Mesenchymal Transition
Authors: Li Tao , Wei Lei , Zhang Xin , Fu Bin , Zhou Yunjiang , Yang Mengdi , Cao Mengran , Chen Yaxin , Tan Yingying , Shi Yongwei , Wu Leyin , Xuan Chenyuan , Du Qianming , Hu Rong
Published: June 2024

Abstract
A number of neurotransmitters have been detected in tumor microenvironment and proved to modulate cancer oncogenesis and progression. We previously found that biosynthesis and secretion of neurotransmitter 5-hydroxytryptamine (5-HT) was elevated in colorectal cancer cells. In this study, we discovered that the HTR2B receptor of 5-HT was highly expressed in colorectal cancer tumor tissues, which was further identified as a strong risk factor for colorectal cancer prognostic outcomes. Both pharmacological blocking and genetic knocking down HTR2B impaired migration of colorectal cancer cell, as well as the epithelial–mesenchymal transition (EMT) process. Mechanistically, HTR2B signaling induced ribosomal protein S6 kinase B1 (S6K1) activation via the Akt/mTOR pathway, which triggered cAMP-responsive element-binding protein 1 (CREB1) phosphorylation (Ser 133) and translocation into the nucleus, then the phosphorylated CREB1 acts as an activator for ZEB1 transcription after binding to CREB1 half-site (GTCA) at ZEB1 promoter. As a key regulator of EMT, ZEB1, therefore, enhances migration and EMT process in colorectal cancer cells. We also found that HTR2B-specific antagonist (RS127445) treatment significantly ameliorated metastasis and reversed EMT process in both HCT116 cell tail-vein–injected pulmonary metastasis and CT26 cell intrasplenic-injected hepatic metastasis mouse models.
Implications:
These findings uncover a novel regulatory role of HTR2B signaling on colorectal cancer metastasis, which provide experimental evidences for potential HTR2B-targeted anti-colorectal cancer metastasis therapy.
Supplementary Table S5 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers
Authors: Jiang Jingjing , Jiang Lingyan , Maldonato Benjamin J. , Wang Yingyun , Holderfield Matthew , Aronchik Ida , Winters Ian P. , Salman Zeena , Blaj Cristina , Menard Marie , Brodbeck Jens , Chen Zhe , Wei Xing , Rosen Michael J. , Gindin Yevgeniy , Lee Bianca J. , Evans James W. , Chang Stephanie , Wang Zhican , Seamon Kyle J. , Parsons Dylan , Cregg James , Marquez Abby , Tomlinson Aidan C.A. , Yano Jason K. , Knox John E. , Quintana Elsa , Aguirre Andrew J. , Arbour Kathryn C. , Reed Abby , Gustafson W. Clay , Gill Adrian L. , Koltun Elena S. , Wildes David , Smith Jacqueline A.M. , Wang Zhengping , Singh Mallika
Published: June 2024

Supplementary Table S5 shows time to tumor doubling of individual animals in RMC-6236 mouse clinical trial.
Supplementary Figure S1-S6 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers
Authors: Jiang Jingjing , Jiang Lingyan , Maldonato Benjamin J. , Wang Yingyun , Holderfield Matthew , Aronchik Ida , Winters Ian P. , Salman Zeena , Blaj Cristina , Menard Marie , Brodbeck Jens , Chen Zhe , Wei Xing , Rosen Michael J. , Gindin Yevgeniy , Lee Bianca J. , Evans James W. , Chang Stephanie , Wang Zhican , Seamon Kyle J. , Parsons Dylan , Cregg James , Marquez Abby , Tomlinson Aidan C.A. , Yano Jason K. , Knox John E. , Quintana Elsa , Aguirre Andrew J. , Arbour Kathryn C. , Reed Abby , Gustafson W. Clay , Gill Adrian L. , Koltun Elena S. , Wildes David , Smith Jacqueline A.M. , Wang Zhengping , Singh Mallika
Published: June 2024

Supplementary Figure 1 shows RMC-6236 crystal structure in tri-complex, as well as biophysical and cellular potencies of RMC-6236 by genotype.
Supplementary Figure 2 shows RMC-6236 demonstrates dose-dependent anti-tumor activities at tolerable doses; and pharmacodynamic effects on RAS signaling in NCI-H441 xenograft tumors as assessed by IHC, and in relatively refractory KP-4 and NCI-H2122 xenograft tumors as assessed by human DUSP6 mRNA expression in vivo.
Supplementary Figure 3 shows genotype dependent response of RMC-6236 across NSCLC, PDAC and CRC; and potential modifiers to the durability of response of KRASG12C NSCLC models upon RMC-6236 treatment assessed by Kaplan-Meier analyses.
Supplementary Figure 4 shows Efficacy of RMC-6236 on KrasG12C–driven autochthonous lung tumors harboring cis second-site mutations within KrasG12C (KrasG12C,H95D or KrasG12C,Y96C) and eCT26 (KrasG12D/G12D) syngeneic model in immunocompetent mice; anti-tumor immunity of RMC-6236; and in intracranially implanted NCI-H1373-Luc xenograft model on nude mice.
Supplementary Figure 5 shows effects of RMC-6236 mediated pharmacological modulation in KP-4 xenograft tumors and normal colon tissues isolated from xenograft tumor bearing mice.
Supplementary Figure 6 shows a graphical representation of the combined mouse PK-Efficacy and PK/PD model.
Table S1 from Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer
Authors: Mikami Hirofumi , Feng Shu , Matsuda Yutaka , Ishii Shinya , Naoi Sotaro , Azuma Yumiko , Nagano Hiroaki , Asanuma Kentaro , Kayukawa Yoko , Tsunenari Toshiaki , Kamikawaji Shogo , Iwabuchi Ryutaro , Shinozuka Junko , Yamazaki Masaki , Kuroi Haruka , Ho Samantha Shu Wen , Gan Siok Wan , Chichili Priyanka , Pang Chai Ling , Yeo Chiew Ying , Shimizu Shun , Hironiwa Naoka , Kinoshita Yasuko , Shimizu Yuichiro , Sakamoto Akihisa , Muraoka Masaru , Takahashi Noriyuki , Kawa Tatsuya , Shiraiwa Hirotake , Mimoto Futa , Kashima Kenji , Kamata-Sakurai Mika , Ishikawa Shumpei , Aburatani Hiroyuki , Kitazawa Takehisa , Igawa Tomoyuki
Published: June 2024

pharmacokinetic parameters of DLL3 trispecific in cynomolgus monkeys
Overexpression of an Engineered SERPINB9 Enhances Allogeneic T-cell Persistence and Efficacy
Authors: Teo Pei Y. , Jung Youngrock , Quach David H. , Koh Joanna , Ong Richard W. , Goh Angeline , Tan Alrina , Ng Chee H. , Seh Cheah C. , Tan Kar W. , Horak Ivan D. , Low Lionel
Published: June 2024

Allogeneic chimeric antigen receptor (CAR)–expressing T cells offer many advantages over autologous therapies, but their benefits are curtailed by graft-versus-host disease and elimination by recipient immune cells. Moreover, just as with autologous therapies, allogeneic CAR T cells are susceptible to activation-induced cell death (AICD) caused by chronic antigen exposure (CAE). Granzyme B– and Fas/Fas ligand–initiated caspase-mediated apoptoses are key mechanisms of T-cell death caused by T/NK cell–mediated allorejection or CAE. We explored a protective strategy of engineering CAR T cells to overexpress variants of the Granzyme B–specific serine protease inhibitor SERPINB9 (SB9) to improve allogeneic T-cell persistence and antitumor efficacy. We showed that the overexpression of an SB9 variant with broadened caspase specificity, SB9(CAS), not only significantly reduced rejection of allogeneic CAR T cells but also increased their resistance to AICD and enabled them to thrive better under CAE, thus improving allogeneic T-cell persistence and antitumor activity in vitro and in vivo. In addition, although SB9(CAS) overexpression improved the efficacy of allogeneic CAR T-cell therapy by conferring protection to cell death, we did not observe any autonomous growth, and the engineered CAR T cells were still susceptible to an inducible suicide switch. Hence, SB9(CAS) overexpression is a promising strategy that can strengthen current development of cell therapies, broadening their applications to address unmet medical needs.
FIGURE 5 from B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors
Authors: Yeo Siok Ping , Kua Lindsay , Tan Jin Wei , Lim Joanna Kristyn , Wong Fiona HS , Santos May Delos , Poh Chek Meng , Goh Angeline XH , Koh Xin Yu , Zhou Xiaohua , Rajarethinam Ravisankar , Chen Qingfeng , Her Zhisheng , Horak Ivan D. , Low Lionel , Tan Kar Wai
Published: June 2024

B7-H3.mCAR T cells exhibit little on-tumor off target toxicity in a syngeneic mouse model. A, Body weight (left), tumor volume measurements (middle), and fold change in tumor volumes (right) of B16F10-hB7H3 tumors after treatment. B, Endpoint murine immune cell counts in blood, bone marrow, spleen, and liver quantified by flow cytometry. Each point on the graph represents a mouse. C, Pathologic evaluation of organs from two B16F10WT-hB7H3 tumor-bearing C57BL/6J mice receiving UT or B7H3.mCAR T cells or left untreated. For A and B, data comprise of 6 mice in each treatment arm. For A, groups were compared using two-way ANOVA with Tukey test for multiple comparisons test. Comparison and P values between untreated versus UT T, untreated versus B7H3.CAR EBVSTs, and UT T versus B7H3.CAR EBVSTs groups is represented in black, blue, and red, respectively. For B, groups were compared using Student unpaired t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Error bars denote means ± SD where applicable.
Data from B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors
Authors: Yeo Siok Ping , Kua Lindsay , Tan Jin Wei , Lim Joanna Kristyn , Wong Fiona HS , Santos May Delos , Poh Chek Meng , Goh Angeline XH , Koh Xin Yu , Zhou Xiaohua , Rajarethinam Ravisankar , Chen Qingfeng , Her Zhisheng , Horak Ivan D. , Low Lionel , Tan Kar Wai
Published: June 2024

Abstract
Encouraged by the observations of significant B7-H3 protein overexpression in many human solid tumors compared to healthy tissues, we directed our focus towards targeting B7-H3 using chimeric antigen receptor (CAR) T cells. We utilized a nanobody as the B7-H3–targeting domain in our CAR construct to circumvent the stability issues associated with single-chain variable fragment–based domains. In efforts to expand patient access to CAR T-cell therapy, we engineered our nanobody-based CAR into human Epstein-Barr virus–specific T cells (EBVST), offering a readily available off-the-shelf treatment. B7H3.CAR-armored EBVSTs demonstrated potent in vitro and in vivo activities against multiple B7-H3–positive human tumor cell lines and patient-derived xenograft models. Murine T cells expressing a murine equivalent of our B7H3.CAR exhibited no life-threatening toxicities in immunocompetent mice bearing syngeneic tumors. Further in vitro evaluation revealed that while human T, B, and natural killer cells were unaffected by B7H3.CAR EBVSTs, monocytes were targeted because of upregulation of B7-H3. Such targeting of myeloid cells, which are key mediators of cytokine release syndrome (CRS), contributed to a low incidence of CRS in humanized mice after B7H3.CAR EBVST treatment. Notably, we showed that B7H3.CAR EBVSTs can target B7-H3–expressing myeloid-derived suppressor cells (MDSC), thereby mitigating MDSC-driven immune suppression. In summary, our data demonstrate that our nanobody-based B7H3.CAR EBVSTs are effective as an off-the-shelf therapy for B7-H3–positive solid tumors. These cells also offer an avenue to modulate the immunosuppressive tumor microenvironment, highlighting their promising clinical potential in targeting solid tumors.
Significance:
Clinical application of EBVSTs armored with B7-H3–targeting CARs offer an attractive solution to translate off-the-shelf CAR T cells as therapy for solid tumors.
Phenomenology of Somatization in Immigrants: An Idealtypical Approach
Authors: Aragona Massimiliano , Ferrari Federica , Cavallo Marcella , Pierconti Silvia , Pajno Chiara , Coletta Paola , Barbarossa Giulia , Nicolella Gianluca , Laurendi Giovanna
Published: June 2024

Introduction: Somatization in immigrants is frequent but standard studies do not differentiate between various forms of somatization. In this qualitative study, we used an idealtypical approach with the aim of phenomenologically differentiating between different forms of somatization in immigrants. Methods: The clinical description of the ideal types was based on seven levels: medical examination; description of somatization symptoms; the patients’ own interpretation of their somatic experience; concomitant psychopathological phenomena; genetic understanding; clinician’s interpretation; and course and treatment. Results: Five different ideal typologies of patients emerged: anxious hypochondriasis, somatization with cultural features playing a pathogenetic role, culturally shaped somatization (through pathoplastic effects), somatization as part of adjustment reactions due to migratory living difficulties, and somatization as post-traumatic reaction. Conclusion: These differences are useful to highlight the complex interrelationship between socioeconomic, migratory, cultural, and value factors in the construction of somatization among immigrants. Implications for research methodology, nosology, clinical management, and organization of medical facilities are also discussed.
Laryngeal Mask Airway in Neonatal Resuscitation: A Survey of the Union of European Neonatal and Perinatal Societies
Authors: Trevisanuto Daniele , Gizzi Camilla , Cavallin Francesco , Beke Artur , Buonocore Giuseppe , Charitou Antonia , Cucerea Manuela , Filipović-Grčić Boris , Jekova Nelly Georgieva , Koç Esin , Saldanha Joana , Stoniene Dalia , Varendi Heili , De Bernardo Giuseppe , Madar John , Hogeveen Marije , Orfeo Luigi , Mosca Fabio , Vertecchi Giulia , Moretti Corrado
Published: June 2024

Introduction: Laryngeal mask airway (LMA) use in neonatal resuscitation is limited despite existing evidence and recommendations. This survey investigated the knowledge and experience of healthcare providers on the use of the LMA and explored barriers and solutions for implementation. Methods: This online, cross-sectional survey on LMA in neonatal resuscitation involved healthcare professionals of the Union of European Neonatal and Perinatal Societies (UENPS). Results: A total of 858 healthcare professionals from 42 countries participated in the survey. Only 6% took part in an LMA-specific course. Some delivery rooms were not equipped with LMA (26.1%). LMA was mainly considered after the failure of a face mask (FM) or endotracheal tube (ET), while the first choice was limited to neonates with upper airway malformations. LMA and FM were considered easier to position but less effective than ET, while LMA was considered less invasive than ET but more invasive than FM. Participants felt less competent and experienced with LMA than FM and ET. The lack of confidence in LMA was perceived as the main barrier to its implementation in neonatal resuscitation. More training, supervision, and device availability in delivery wards were suggested as possible actions to overcome those barriers. Conclusion: Our survey confirms previous findings on limited knowledge, experience, and confidence with LMA, which is usually considered an option after the failure of FM/ET. Our findings highlight the need for increasing the availability of LMA in delivery wards. Moreover, increasing LMA training and having an LMA expert supervisor during clinical practice may improve the implementation of LMA use in neonatal clinical practice.
Multi-objective optimal reconfiguration of distribution networks using a novel meta-heuristic algorithm
Authors: Dehghany Negar , Asghari Rasool
Published: June 2024

Reconfiguration strategies are used to reduce power losses and increase the reliability of the distribution systems. Since the optimal reconfiguration problem is a multi-objective optimization problem with non-convex functions and constraints, meta-heuristic algorithms are the most suitable choice for the problem-solving approach. One of the new meta-heuristic algorithms that exhibits excellent performance in solving multi-objective problems is the wild mice colony (WMC) algorithm, which is implemented based on aggressive and mating strategies of wild mice. In this paper, the distribution network reconfiguration problem is solved to reduce power losses, improve reliability, and increase the voltage profile of network buses using the WMC algorithm. In addition, the obtained results are compared with conventional multi-objective algorithms. The optimal reconfiguration problem is applied to the IEEE 33-bus and 69-bus test systems. The comparative study confirms the superior performance of the proposed algorithm in terms of convergence speed, execution time, and the final solution.
A fuzzy-PID controller for load frequency control of a two-area power system using a hybrid algorithm
Authors: Bouaddi Abdessamade , Rabeh Reda , Ferfra Mohammed
Published: June 2024

This paper presents the use of a new hybrid optimization approach known as particle swarm optimization and grey wolf optimizer (PSO-GWO) for improving frequency stability load frequency control (LFC) in tow-area power systems. The approach consists in optimizing the fuzzy proportional-integral-derivative (fuzzy-PID) controller parameters with meta-heuristic hybrid algorithm: PSO-GWO. This technique allows to have dynamic responses with the least possible frequency deviation in very short response times. The approach proposes to controls the tie-line power and the frequency deviation in the considered two-area power systems under variable perturbation in load and changing of system parameters in order to evaluate its effectiveness. The suggested hybrid algorithm-based fuzzy-PID controller is compared with various widely used control methods in the literature such as PID controller and algorithms such as PSO and GWO in order to evaluate its effectiveness and its robustness. Through the simulations carried out on MATLAB/Simulink, the proposed PSO-GWO fuzzy-PID and the objective function exhibit improved performance, achieving minimal objective values. The proposed technique proved to be quite powerful tool in the resolution of problems related to electrical power systems, particularly in load frequency control.
Design of a perturb and observe and neural network algorithms-based maximum power point tracking for a grid-connected photovoltaic system
Authors: Salem Ahmed Ali , Ismail Mohamed Mahmoud , Zedan Honey Ahmed , Elnaghi Basem Elhady
Published: June 2024

Integrating photovoltaic systems (PV) into the grid has garnered significant attention due to increasing interest in renewable energy sources. Maximizing the PV systems output power is crucial for improving energy efficiency and reducing operating costs. This paper presents a comparative analysis of two different techniques of maximum power point tracking (MPPT): perturb and observe (P&O) and artificial neural network (ANN) MPPT, focusing on their application in grid-connected PV systems. The paper evaluates their performance under various operating conditions, including changes in irradiance and temperature, that are discussed in three cases. The comparative analysis includes metrics such as voltage regulation and powerloss. MATLAB Simulink is utilized to implement P&O and ANN MPPT methods, which include a PV cell connected to an MPPT-controlled boost converter. The simulation demonstrates the power loss of the PV model as well as the voltage regulation in the three cases for the two methods. The results obtained in simulation and implementations show that the ANN method outperforms the P&O in the three cases discussed in terms of powerloss, voltage regulation, and efficiency. The results also show that the change in output power from PV is noticeable when compared to changes in radiation, while the change is slight when temperatures change.
Robust parameter determination approach based on red-tailed hawk optimization used for lithium-ion battery
Authors: Z. Almutair Sulaiman , Rezk Hegazy , Hassan Yahia Bahaa
Published: June 2024

Lithium-ion electrochemical batteries are being used more in a large number of applications, such as electric vehicles. However, increasing their efficiency lies in the accuracy of their model. For this, extracting the best values of parameters of the battery model is needed. A recent metaheuristic optimizer named the red-tail hawk (RTH) is used in the current research to extract the battery parameters. The idea of this algorithm is extracted from hunting techniques of red-tail hawks. The RTH algorithm is more likely to avoid entangled local optimums because of its high diversity, fast convergence rate, and appropriate exploitation-exploration balance. The RTH optimizer is compared with other algorithms to check and approve its performance. Using the proposed method, the root mean squared error (RMSE) between the model outputs and the measured voltage dataset was decreased to 8.12E-03, much better than all the other considered algorithms.
Transient response of a megawatt-scale solar photovoltaic in an electric distribution utility
Authors: Judith Paolo Justine , Dellosa Jeffrey T.
Published: June 2024

There is an increasing trend among customers of an electrical distribution utility to adopt grid-tied solar photovoltaic systems. This shift offers multiple benefits to consumers, including lower monthly electricity bills and a contribution to the development of green energy. For the electrical distribution utility, various impacts may arise due to varying levels of solar energy penetration. This study investigates the effects of integrating varying levels of solar photovoltaic penetration into the commercial consumer network of Cagayan de Oro Electric Power and Light Company (CEPALCO) in the Philippines. Utilizing PowerWorld simulator, the research evaluates 11 different scenarios with solar penetration levels adjusted according to the percentage of load demand. Key findings include alterations in solar megavolt ampere of reactive power output, bus voltage levels, transformer power loading, and transmission line ampacity, with frequency levels remaining stable across scenarios. The optimal solar penetration level was identified at 70%, balancing the benefits of solar energy integration with the need to maintain grid stability and operational limits. This optimal level ensures the effective utilization of renewable energy sources without compromising the performance of CEPALCO’s electrical infrastructure. The research concludes with recommendations for maintaining grid stability and operational limits at the optimal solar penetration limits.
Exploring distance-based wireless transceiver placements for wireless network-on-chip architecture with deterministic routing algorithms
Authors: Lit Asrani , Suhaili Shamsiah , Kipli Kuryati , Sapawi Rohana , Mahyan Fariza
Published: June 2024

Network-on-chip (NoC) technology is crucial for integrating multiple embed-ded computing cores onto a single chip. Consequently, this has led to the de-velopment of the wireless network-on-chip (WiNoC) concept, seen as a promis-ing strategy to overcome scalability issues in communication systems withinchips for future many-core architectures. This research analyses the impactof wireless transceiver subnet clustering on the hundred-core mesh-structuredWiNoC architecture. The study aims to examine the effects of distance-basedwireless transceiver placements on the transmission delay, network throughput,and energy consumption within a mesh wireless NoC architecture featuring ahundred cores, under specific routing strategies: X-Y, west-first, negative-first,and north-last. This research investigates the impact of positioning radio sub-nets at the farthest, farther, nearest, and closest positions within an architectureequipped with four wireless transceivers. The Noxim simulator was utilised tosimulate the analysed wireless transceiver placements within the hundred-coremesh-structured WiNoC designs, with the objective of validating the results.The architecture with the wireless transceivers positioned at midway proxim-ity (nearer and further) demonstrated the best performance, as evidenced by thelowest latencies for all evaluated deterministic routing algorithms, according tothe simulation outcomes.
Automated gas-controlled cooker system design and implementation
Authors: Amuta Elizabeth , Orovwode Hope , Airoboman Abel Ehimen , Mene Joseph Anirejuoritse , Sobola Gabriel Oluwatobi , Matthew Simeon , Onyema Daniel
Published: June 2024

Cooking from ancient times has evolved from using open fires to wood, gas cookers, using liquefied petroleum gas (LPG). This has also come with various adverse effects ranging from gas leakages to burnt food due to absent-mindedness, thereby creating a significant disaster that could lead to loss of life and property damage. The study aimed to reduce the rate of liquefied petroleum gas related accidents in domestic usage and improve the safety of domestic gas users. An automated method to enforce safety was proposed to avoid unwanted cooking gas flow consequences, especially in homes. The paper presents a control system using an Arduino Uno with a control design interfaced with a utensil sensor, solenoid valve, and a timer circuit to allow gas flow to commence and ignite a flame automatically. The automatic ignition apparatus, which has a high-voltage electric circuit, begins to function once the utensil detector comes in contact with silverware. The system is designed to function in different modes to ensure safety and prevent gas flow. The prototype serves as a means of curbing gas wastage and increasing the safety of people who use LPG as a source of fuel for cooking.