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Yu-Ming Wang,1– 4,* Yang-Wei Hsieh,1,2,* Bing-Shen Huang,1,2,5 Kuo-Chiang Sung,1,2 Kuo-Jung Juan,1,2 Steve P Lee,6 Shen-Hao Lee,1,2,5 Eng-Yen Huang1,2 1Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Proton and Radiation Therapy Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3School of Traditional Chinese, Chang Gung University, Taoyuan, Taiwan; 4Institute of Physiology, National Yang-Ming University, Taipei, Taiwan; 5Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan; 6Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA*These authors contributed equally to this workCorrespondence: Shen-Hao Lee Email r12233@cgmh.org.twEng-Yen HuangDepartment of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanEmail hey1200@cgmh.org.twBackground: The coronavirus disease 2019 (COVID-19) pandemic has caused extreme challenges for the healthcare system. Medical masks have been proven to effectively block disease transmission. Radiotherapeutic departments are at unique risk for disease exposure with the repeated daily treatment schedule. A protocol of mask wearing during daily treatment was established, and the effect of wearing medical masks on dosimetry during proton beam therapy (PBT) was validated.Methods: A department protocol of medical mask wearing was initiated after the COVID-19 pandemic. Medical masks that were made under standardized specification and regulation were obtained for analyses. The physical and dosimetric characteristics of these medical masks were measured by different proton energies using commercialized measurement tools.Results: Patients and staff were able to adopt the protocol on a weekly basis, and no adverse events were reported. The average physical thickness of a single piece of medical mask was 0.5 mm with a water equivalent thickness (WET) of 0.1 mm.Conclusion: Our study revealed that mask wearing for patients undergoing daily radiotherapy is feasible and can provide basic protection for patients and staff. The impact of mask wearing on dosimetry was only 0.1 mm in WET, which has no impact on clinical PBT treatment. A medical mask-wearing policy can be applied safely without dosimetric concerns and should be considered as a standard practice for PBT centers during the COVID-19 pandemic.Keywords: COVID-19, mask-wearing, radiotherapy, dosimetry, proton beam therapy

Shu Ping Lee,1 Feng Yu Kuo,1,2 Juei-Tang Cheng,3,4 Ming Chang Wu11Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan; 2Cardiovascular Center, Veterans General Hospital, Kaohsiung City 81362, Taiwan; 3Department of Medical Research, Chi-Mei Medical Center, Tainan City 71003, Taiwan; 4Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan City 71101, TaiwanBackground: Thymoquinone (TQ) is a safe nutrient isolated from the seeds or volatile oil extract of Nigella sativa. In addition to its benefits in glucose regulation, TQ improves feeding disorders in diabetic animals. Glucagon-like peptide-1 (GLP-1) analogs improve glycemic control and ameliorate obesity or hyperphagia. Therefore, the present study aimed to investigate the role of GLP-1 in TQ-induced anorexia.Method: Type 2 diabetes was induced in rats by nicotinamide and streptozotocin injection. TQ was orally administered to diabetic rats at different doses for 45 days. Following TQ treatment, changes in serum glucose levels, GLP-1 concentration, body weight, food intake, and water intake were determined. To further explore the interaction between GLP-1 and TQ, the inhibitor of dipeptidyl peptidase 4, sitagliptin and the GLP-1 receptor antagonist exendin 9–39 (Ex 9–39) were separately administered to TQ- or vehicle-treated diabetic rats.Results: TQ treatment attenuated hyperglycemia and reduced hyperphagy and water intake in streptozotocin-induced diabetic rats in a dose-dependent manner. Moreover, TQ treatment elevated plasma GLP-1 levels compared to those in control rats. The effects of TQ were enhanced by treatment with sitagliptin and reduced by the injection of Ex 9–39 into the brain. In contrast, similar treatment with another antioxidant (either ascorbic acid or N-acetylcysteine) produced the same anorexic effect as TQ without changing the plasma GLP-1 levels in diabetic rats. Therefore, TQ attenuated hyperphagy while increasing plasma GLP-1 levels and had antioxidant-like effects.Conclusion: TQ increased endogenous GLP-1 levels to reduce hyperphagy in diabetic rats.Keywords: thymoquinone, GLP-1, sitagliptin, body weight, food intake

Purpose: To determine the utility of ureteral stents in interstitial gynecological brachytherapy. Methods and Materials: We reviewed 289 patients with cervix cancer treated with high-dose-rate interstitial brachytherapy who did not have pretreatment hydronephrosis to determine the relative incidence of benign ureteral strictures after treatment. We also did comparative dosimetry analysis in five cases of high-dose-rate brachytherapy. Bilateral ureteral stents were placed during the procedure. Three dosimetry plans were created to determine the impact of modifying clinical target volume (CTV) and applying ureteral dose constraints. In Plan 1, the ureters were contoured and excluded from the CTV and 120% dose constraints were applied. In Plan 2, the ureters were contoured and excluded, but no dose constraints were applied to the ureter. In Plan 3, the CTV was created as if the location of the ureters was unknown and then ureteral dose was determined. Results: There were 11 ureteral strictures observed in 255 nonstented cases and 0 ureteral strictures in 34 stented cases. Plan 1 reduced the ureter dose (D0.1cc) by a median 22% (7.0-53.8%) compared with Plan 2 and by a median of 30.9% (12.3-65%). compared with Plan3. Conclusions: Placement of stents and ureteral dose constraints facilitates dosimetry and reduces the dose to ureters. Temporary ureteral stents prevent obstruction during interstitial gynecologic brachytherapy and allows the ureters to be addressed as an organ at risk.

A series of 2,3-dihalo-1,1,1,4,4,4-hexafluorobutanes and 2-halo-1,1,1,4,4,4-hexafluorobut-2-enes were prepared from commercially available hydrofluoroolefins 1,1,1,4,4,4-hexafluorobut-2-enes and their 1H, 19F and 13C chemical shifts measured. Some reactions of synthesized 2-halo-1,1,1,4,4,4-hexafluorobut-2-enes have been investigated. A simple, one-pot procedure for the preparation of a new allene (1,1,4,4,4-pentafluorobuta-1,2-diene) and some of its transformations is presented.

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as “Deltacron.” We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.

With the declaration of the COVID-19 pandemic by the World Health Organization on March 11, 2020, the University of Tennessee College of Veterinary Medicine (UTCVM), like other institutions, restructured their services to reduce the potential spread of the COVID-19 virus while simultaneously providing critical and essential veterinary services. A mathematical model was developed to predict the change in the level of possible COVID-19 infections due to the increased number of potential contacts within the UTCVM hospital. A system of ordinary differential equations with different compartments for UTCVM individuals and the Knox county population was formulated to show the dynamics of transmission and the number of confirmed cases. Key transmission rates in the model were estimated using COVID-19 case data from the surrounding county and UTCVM personnel. Simulations from this model show the increasing number of COVID-19 cases among UTCVM personnel as the number of daily clients and the number of veterinary staff in the clinic are increased. We also investigate how changes within the Knox county community impact the UTCVM hospital. These scenarios show the importance of understanding the effects of re-opening scenarios in veterinary teaching hospitals.

The COVID-19 pandemic provides an opportunity to explore the impact of government mandates on movement restrictions and non-pharmaceutical interventions on a novel infection, and we investigate these strategies in early-stage outbreak dynamics. The rate of disease spread in South Africa varied over time as individuals changed behavior in response to the ongoing pandemic and to changing government policies. Using a system of ordinary differential equations, we model the outbreak in the province of Gauteng, assuming that several parameters vary over time. Analyzing data from the time period before vaccination gives the approximate dates of parameter changes, and those dates are linked to government policies. Unknown parameters are then estimated from available case data and used to assess the impact of each policy. Looking forward in time, possible scenarios give projections involving the implementation of two different vaccines at varying times. Our results quantify the impact of different government policies and demonstrate how vaccinations can alter infection spread.

We investigate the galaxy properties of ∼400 low-mass (

We present a multiple emission line study of ∼1300 H α emitters (HAEs) at z ∼ 2.3 in the ZFOURGE survey. In contrast to the traditional spectroscopic method, our sample is selected based on the flux excess in the ZFOURGE K _s broadband data relative to the best-fit stellar continuum. Using the same method, we also extract the strong diagnostic emission lines for these individual HAEs: [O iii ] λ λ 4959, 5007 and [O ii ] λ λ 3726, 3729. Our measurements demonstrate good consistency with those obtained from spectroscopic surveys. We investigate the relationship between the equivalent widths (EWs) of these emission lines and various galaxy properties, including stellar mass, stellar age, star formation rate, specific star formation rate, and ionization state (O32). We have identified a discrepancy between HAEs at z ∼ 2.3 and typical local star-forming galaxies observed in the Sloan Digital Sky Survey, suggesting the evolution of lower gas-phase metallicity ( Z ) and higher ionization parameters ( U ) with redshift. Notably, we have observed a significant number of low-mass HAEs exhibiting exceptionally high EW _[O _iii _] . Their galaxy properties are comparable to those of extreme objects, such as extreme O3 emitters and Ly α emitters at z ≃ 2–3. Considering that these characteristics may indicate potential strong Lyman continuum leakage, higher-redshift analogs of the low-mass HAEs could be significant contributors to the cosmic reionization. Further investigations of this particular population are required to gain a clearer understanding of galaxy evolution and cosmic reionization.

Abstract Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and aggressive malignant cancer caused by a chromosomal translocation t(11;22)(p13;q12) that produces an oncogenic transcription factor, EWSR1-WT1. EWSR1-WT1 is essential for the initiation and progression of DSRCT. However, the precise mechanism by which EWSR1-WT1 drives DSRCT oncogenesis remains unresolved. Through our integrative gene expression analysis, we identified Salt Inducible Kinase 1 (SIK1) as a direct target of EWSR1-WT1. SIK1 as a member of the AMPK related kinase is involved in many biological processes. We showed that depletion of SIK1 causes inhibition of tumor cell growth, similar to the growth inhibition observed when EWSR1-WT1 is depleted. We further showed that silencing SIK1 leads to cessation of DNA replication in DSRCT cells and inhibition of tumor growth in vivo. Lastly, combined inhibition of SIK1 and CHEK1with small molecule inhibitors, YKL-05-099 and prexasertib, respectively, showed enhanced cytotoxicity in DSRCT cells compared to inhibition of either kinases alone. This work identified SIK1 as a new potential therapeutic target in DSRCT and the efficacy of SIK1 inhibition may be improved when combined with other intervention strategies.

Desmoplastic small round cell tumor (DSRCT) is characterized by the t(11;22)(p13;q12) translocation, which fuses the transcriptional regulatory domain of EWSR1 with the DNA-binding domain of WT1, resulting in the oncogenic EWSR1-WT1 fusion protein. The paucity of DSRCT disease models has hampered preclinical therapeutic studies on this aggressive cancer. Here, we developed preclinical disease models and mined DSRCT expression profiles to identify genetic vulnerabilities that could be leveraged for new therapies. We describe four DSRCT cell lines and one patient-derived xenograft model. Transcriptomic, proteomic and biochemical profiling showed evidence of activation of the ERBB pathway. Ectopic expression of EWSR1-WT1 resulted in upregulation of ERRB family ligands. Treatment of DSRCT cell lines with ERBB ligands resulted in activation of EGFR, ERBB2, ERK1/2 and AKT, and stimulation of cell growth. Antagonizing EGFR function with shRNAs, small-molecule inhibitors (afatinib, neratinib) or an anti-EGFR antibody (cetuximab) inhibited proliferation of DSRCT cells. Finally, treatment of mice bearing DSRCT xenografts with a combination of cetuximab and afatinib significantly reduced tumor growth. These data provide a rationale for evaluating EGFR antagonists in patients with DSRCT. This article has an associated First Person interview with the joint first authors of the paper.

Recent work on hybrid quantum-classical machine learning systems has demonstrated success in utilizing parameterized quantum circuits (PQCs) to solve the challenging reinforcement learning (RL) tasks, with provable learning advantages over classical systems, e.g., deep neural networks. While existing work demonstrates and exploits the strength of PQC-based models, the design choices of PQC architectures and the interactions between different quantum circuits on learning tasks are generally underexplored. In this work, we introduce a Multi-objective Evolutionary Architecture Search framework for parameterized quantum circuits (MEAS-PQC), which uses a multi-objective genetic algorithm with quantum-specific configurations to perform efficient searching of optimal PQC architectures. Experimental results show that our method can find architectures that have superior learning performance on three benchmark RL tasks, and are also optimized for additional objectives including reductions in quantum noise and model size. Further analysis of patterns and probability distributions of quantum operations helps identify performance-critical design choices of hybrid quantum-classical learning systems.

Objective: To evaluate whether the addition of cilostazol to dual antiplatelet therapy (DAT, aspirin plus clopidogrel) can attenuate clopidogrel on-treatment platelet reactivity (OPR) in patients with the CYP2C19 loss-of-function (LOF) allele.Methods: In the CILON-T randomised trial, patients were randomly assigned to either DAT or triple antiplatelet therapy (TAT, DAT plus cilostazol). Genotyping of cytochrome P450 CYP2C19 *2, *3 and *17 was performed and OPR was measured using the VerifyNow P2Y12 assay. Carriers were those with at least one CYP2C19 LOF allele.Results: 474 patients were enrolled; 236 received DAT, 238 TAT. Mean OPR was significantly lower in the TAT compared with the DAT group (207 ± 5 vs 236 ± 5, p<0.001, P2Y12 reaction units, PRU). When grouped according to the presence of the CYP2C19 LOF allele, mean OPR was significantly lower in the TAT compared with the DAT group in only carriers of the LOF allele and not non-carriers (213 ± 6 vs 256 ± 7 PRU, p<0.001 in carriers, 196 ± 9 vs 211 ± 8 PRU, p=0.242 in non-carriers for TAT vs DAT, respectively). The proportion of patients with high OPR was highest in carriers receiving DAT (60.8%) compared with the other three groups. On multivariate analysis, carriers on DAT was an independent predictor of high OPR (OR 2.93, 95% CI 1.64 to 5.21) along with female gender and increasing age.Conclusion: TAT significantly reduced OPR compared with DAT in carriers of the CYP2C19 LOF allele, but not in non-carriers. These data suggest that the addition of cilostazol to DAT may be a good strategy to attenuate CYP2C19 LOF-related high OPR. [ABSTRACT FROM AUTHOR]