bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zoledronic acid and thymosin α1 elicit antitumor immunity against prostate cancer by enhancing tumor inflammation and cytotoxic T cells
Authors: Wang Sheng , Huang Maohua , Chen Minfeng , Sun Zhiting , Jiao Yubo , Ye Geni , Pan Jinghua , Ye Wencai , Zhao Jianfu , Zhang Dongmei 
Published: June 2023

BackgroundAdvanced or metastatic prostate cancer (PCa) is still an incurable malignancy with high lethality and a poor prognosis. Despite the remarkable success of immunotherapy against many types of cancer, most patients with PCa receive minimal benefit from current immunotherapeutic strategies, because PCa is an immune cold tumor with scarce T-cell infiltration in the tumor microenvironment. The aim of this study was to develop an effective immunotherapeutic approach for immune cold PCa tumors.MethodsThe therapeutic efficacy of androgen deprivation therapy (ADT) and zoledronic acid (ZA) plus thymosin α1 (Tα1) therapy was analyzed retrospectively in patients with advanced or metastatic PCa. The effects and mechanisms by which ZA and Tα1 regulated the immune functions of PCa cells and immune cells were evaluated by a PCa allograft mouse model, flow cytometric analysis, immunohistochemical and immunofluorescence staining assays, and PCR, ELISA, and Western blot analyses.ResultsIn this study, clinical retrospective analysis revealed that ADT combined with ZA plus Tα1 improved the therapeutic outcomes of patients with PCa, which might be associated with an enhanced frequency of T cells. ZA and Tα1 treatment synergistically inhibited the growth of androgen-independent PCa allograft tumors, with increased infiltration of tumor-specific cytotoxic CD8+T cells and enhanced tumor inflammation. Functionally, ZA and Tα1 treatment relieved immunosuppression in PCa cells, stimulated pro-inflammatory macrophages, and enhanced the cytotoxic function of T cells. Mechanistically, ZA plus Tα1 therapy blocked the MyD88/NF-κB pathway in PCa cells but activated this signaling in macrophages and T cells, altering the tumor immune landscape to suppress PCa progression.ConclusionsThese findings uncover a previously undefined role for ZA and Tα1 in inhibiting the disease progression of immune cold PCa tumors by enhancing antitumor immunity and pave the way for the application of ZA plus Tα1 therapy as an immunotherapeutic strategy for treating patients with immunologically unresponsive PCa.
Gait-combined closed-loop brain stimulation can improve walking dynamics in Parkinsonian gait disturbances: a randomised-control trial
Authors: Nojima Ippei , Horiba Mitsuya , Sahashi Kento , Koganemaru Satoko , Murakami Satona , Aoyama Kiminori , Matsukawa Noriyuki , Ono Yumie , Mima Tatsuya , Ueki Yoshino 
Published: June 2023

ObjectiveGait disturbance lowers activities of daily living in patients with Parkinson’s disease (PD) and related disorders. However, the effectiveness of pharmacological, surgical and rehabilitative treatments is limited. We recently developed a novel neuromodulation approach using gait-combined closed-loop transcranial electrical stimulation (tES) for healthy volunteers and patients who are post-stroke, and achieved significant entrainment of gait rhythm and an increase in gait speed. Here, we tested the efficacy of this intervention in patients with Parkinsonian gait disturbances.MethodsTwenty-three patients were randomly assigned to a real intervention group using gait-combined closed-loop oscillatory tES over the cerebellum at the frequency of individualised comfortable gait rhythm, and to a sham control group.ResultsTen intervention sessions were completed for all patients and showed that the gait speed (F(1, 21)=13.0, p=0.002) and stride length (F(1, 21)=8.9, p=0.007) were significantly increased after tES, but not after sham stimulation. Moreover, gait symmetry measured by swing phase time (F(1, 21)=11.9, p=0.002) and subjective feelings about freezing (F(1, 21)=14.9, p=0.001) were significantly improved during gait.ConclusionsThese findings showed that gait-combined closed-loop tES over the cerebellum improved Parkinsonian gait disturbances, possibly through the modulation of brain networks generating gait rhythms. This new non-pharmacological and non-invasive intervention could be a breakthrough in restoring gait function in patients with PD and related disorders.
Pipeline Embolization Device for intracranial aneurysms presenting with mass effect: a large Chinese cohort
Authors: Zhao Yang , Lu Junlin , Zhang Hongqi , LI Tianxiao , Song Donglei , Guan Sheng , Maimaitili Aisha , Wang Yunyan , Feng Wenfeng , Wang Yang , Wan Jieqing , Mao Guohua , Shi Huaizhang , Yang Xinjian , Liu Jianmin , Zhao Yuanli 
Published: June 2023

BackgroundUnruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding, relieves symptoms and improve the quality of life for patients. This study aimed to assess the safety and efficacy of Pipeline Embolization Device (PED, Covidien/Medtronic, Irvine, CA) treatment for intracranial aneurysms presenting with mass effect in real-world settings.MethodsWe selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation. The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up (3–36 months). We conducted multivariate analysis to identify factors associated with mass effect relief. Subgroup analyses by aneurysm location, size and form were also performed.ResultsThis study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0% (162/218). The postoperative mass effect deterioration rate was 9.6% (21/218). During a median follow-up period of 8.4 months, the mass effect relief rate was 71.6% (156/218). Notably, immediate aneurysm occlusion following treatment was significantly associated with mass effect relief (OR 0.392, 95% CI, 0.170 to 0.907, p=0.029). Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms, while dense embolism impeded symptom relief in aneurysms<10 mm and saccular aneurysms.ConclusionsOur data confirmed the efficacy of PED in relieving mass effect. The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms.Trial registration numberNCT03831672.
Quantum version of transport coefficients in Nambu–Jona-Lasinio model at finite temperature and strong magnetic field
Authors: Bandyopadhyay Aritra , Ghosh Snigdha , Farias Ricardo L. S. , Ghosh Sabyasachi 
Published: June 2023

AbstractWe have estimated parallel and perpendicular components of electrical conductivity and shear viscosity of quark matter at finite magnetic field and temperature by using their one-loop Kubo expressions in the framework of Nambu–Jona-Lasinio (NJL) model. At finite magnetic field, a non-trivial medium dependence of those quantities can be found. Previously these NJL-profiles have been addressed in relaxation time approximation, where cyclotron motion of quarks with medium dependent mass plays the key role. With respect to the earlier estimations, the present work provides further enriched profiles via Kubo framework, where field theoretical descriptions of quark transport with medium dependent mass and (Landau) quantized energy have been identified as the key ingredients. Hence the present study can be considered as the complete quantum field theoretical description of the transport coefficients in the framework of NJL model at finite temperature and magnetic field.
U–Pb zircon ages from tuffaceous beds in the Terreneuvian to Cambrian Series 2 sections of Avalonian southern New Brunswick, Canada: new constraints on chronostratigraphic correlations and the Cambrian time scale
Authors: Hamilton Michael A. , Álvaro J. Javier , Barr Sandra M. , Jensen Sören , Johnson Susan C. , Palacios Teodoro , van Rooyen Deanne , White Chris E. 
Published: June 2023

Abstract

Avalonian sections in the Saint John area, southern New Brunswick, have long contributed to global understanding of Cambrian chronostratigraphy. A tuffaceous bed in the Ratcliffe Brook Formation (RBF) in the Somerset Street section dated at
c.
531 Ma has traditionally been considered to post-date small shelly fossils attributed to the
Watsonella crosbyi
Zone in the Hanford Brook section. A fine-grained tuffaceous bed approximately 8 m stratigraphically lower in the Somerset Street section yields a chemical abrasion isotope dilution–thermal ionization mass spectrometry zircon age of 532.3 ± 0.3 Ma; a tuffaceous carbonate unit in the lower RBF in Hanford Brook gives an age of 531.5 ± 0.3 Ma. Crystal and crystal-lithic tuff beds near the top of the RBF yield ages of 520.3 ± 0.3 Ma (in Hanford Brook) and 519.1 ± 0.3 Ma (in Ratcliffe Brook). The new ages confirm the correlation between the Somerset Street and Hanford Brook sections based on acritarchs and make the association of small shelly fossils in the Hanford Brook section younger than 531 Ma. This result is relevant to ongoing discussions on the age of the base of undefined Cambrian Stage 2. The radiometric ages also support a young age for the upper part of the RBF, perhaps extending into Epoch 2.
Diabetes and Prostate Cancer Outcomes in Men with Nonmetastatic Castration-Resistant Prostate Cancer: Results from the SEARCH Cohort
Authors: Sergeyev Andrei , Gu Lin , De Hoedt Amanda M. , Amling Christopher L. , Aronson William J. , Cooperberg Matthew R. , Kane Christopher J. , Klaassen Zachary , Terris Martha K. , Guerrios-Rivera Lourdes , Freedland Stephen J. , Csizmadi Ilona 
Published: June 2023

AbstractBackground:The prognosis of diabetic men with advanced prostate cancer is poorly understood and understudied. Hence, we studied associations between diabetes and progression to metastases, prostate cancer–specific mortality (PCSM) and all-cause mortality (ACM) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC).Methods:Data from men diagnosed with nmCRPC between 2000 and 2017 at 8 Veterans Affairs Health Care Centers were analyzed using Cox regression to determine HRs and 95% confidence intervals (CI) for associations between diabetes and outcomes. Men with diabetes were classified according to: (i) ICD-9/10 codes only, (ii) two HbA1c values &gt; 6.4% (missing ICD-9/10 codes), and (iii) all diabetic men [(i) and (ii) combined].Results:Of 976 men (median age: 76 years), 304 (31%) had diabetes at nmCRPC diagnosis, of whom 51% had ICD-9/10 codes. During a median follow-up of 6.5 years, 613 men were diagnosed with metastases, and 482 PCSM and 741 ACM events occurred. In multivariable-adjusted models, ICD-9/10 code-identified diabetes was inversely associated with PCSM (HR, 0.67; 95% CI, 0.48–0.92) while diabetes identified by high HbA1c values (no ICD-9/10 codes) was associated with an increase in ACM (HR, 1.41; 95% CI, 1.16–1.72). Duration of diabetes, prior to CRPC diagnosis was inversely associated with PCSM among men identified by ICD-9/10 codes and/or HbA1c values (HR, 0.93; 95% CI, 0.88–0.98).Conclusions:In men with late-stage prostate cancer, ICD-9/10 ‘code-identified’ diabetes is associated with better overall survival than ‘undiagnosed’ diabetes identified by high HbA1c values only.Impact:Our data suggest that better diabetes detection and management may improve survival in late-stage prostate cancer.
Abstract 1051: Liquid biopsy in the detection of genetic biomarkers in gastrointestinal cancer
Authors: Gomes-Fernandes Bianca , Carneiro Juliana Garcia , da Silva Rodrigo Gomes , de Marco Luiz , Bastos-Rodrigues Luciana 
Published: June 2023

Abstract
Colorectal cancer (CRC) is one of the leading causes of morbidity and mortality worldwide. Detection prior to metastasis and appropriate therapeutic application lead to greater patient survival and quality of life. However, the diagnosis and postoperative surveillance are surrounded by limitations. Genetic biomarkers are influential factors that contribute to favorable clinical outcomes. To better understand the molecular basis associated with CRC, we investigated KRAS, NRAS, BRAF, EGFR and TP53 genes in the DNA of tumor and healthy cells using Sanger sequencing. The most frequent alteration, present only in the tumor DNA (somatic), was used to investigate, by Digital PCR (ddPCR), the detection and analysis of circulating tumor DNA (ctDNA) in the plasma. Altogether, 42 subjects made up the study, most of them male (59.5%), with a mean age of 63 years and tumors located in the right colon (21.4%). transversal (2.4%), left (4.8%), sigmoid (33.3%) and straight (38.1%). Germline and somatic allelic variants were found in the KRAS, EGFR and TP53 genes. The most frequent somatic alteration in the study was rs121913529, which showed an association with alcohol consumption (p = 0.002). Patients with a somatic mutation in TP53 are ten times more likely to die, compared with the chance of those without a mutation in this gene (OR 11.2; 95% CI 1.25 - 245). The applicability of these somatic changes in the liquid biopsy technique was demonstrated by ddPCR. Therefore, the results obtained expand the understanding of the molecular basis of CRC and present an optimization of the liquid biopsy, timely for clinical practice.
Citation Format: Bianca Gomes-Fernandes, Juliana Garcia Carneiro, Rodrigo Gomes da Silva, Luiz de Marco, Luciana Bastos-Rodrigues. Liquid biopsy in the detection of genetic biomarkers in gastrointestinal 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 1051.
Abstract 1081: Co-targeting CK1epsilon and PIK3CB/p110beta to treat glioblastoma
Authors: Xu Eileen 
Published: June 2023

Abstract
The purpose of this study is to determine whether co-inhibition of CK1epsilon and PIK3CB/p110β is an effective therapeutic treatment for Glioblastoma (GBM). GBM is the most common and malignant primary brain cancer in adults. GBM has a dismal prognosis of death within 6 months if left untreated, thus there is a clinically unmet need for new and effective treatments. CK1epsilon has been identified as a GBM survival kinase gene. CK1epsilon promotes growth of GBM cells by inhibiting β-catenin. However, blocking CK1epsilon alone fails to completely block tumor growth perhaps because β-catenin can be regulated by other kinases. PIK3CB/p110β is another GBM survival kinase gene which also acts upstream of β-catenin. As seen with CK1epsilon, blocking PIK3CB/p110β alone also fails to completely block tumor growth. It is possible that blocking either CK1epsilon or PIK3CB/p110β alone does not substantially activate β-catenin to induce massive GBM cell death, thus limiting their therapeutic efficacy as a single agent. It is therefore imperative to investigate if co-targeting CK1epsilon and PIK3CB/p110β yields a synergistic inhibitory effect on GBM cell growth.
GBM cells were treated with either DMSO (control), IC261 (chemical inhibitor of CK1epsilon), AZD6482 (chemical inhibitor of PIK3CB/p110β), or both IC261 and AZD6482. Cell viability was measured using the MTS viability assay. Cell viability for the treatment groups were as follows: AZD6482 (88.81%), IC261 (66.78%), and combination of AZD6482+IC261 (42.59%). Statistical analysis of drug synergy using the Bliss independence model yielded an Excess Over Bliss score greater than 0%, indicating a synergistic effect. To further elucidate the mechanism of GBM cell death, immunoblotting will also be performed to detect β-catenin activity after inhibition of CK1epsilon and PIK3CB/p110β. Overall, preliminary results show that co-inhibition of CK1epsilon and PIK3CB/p110β with chemical inhibitors yields synergistic GBM cell death.
Citation Format: Eileen Xu. Co-targeting CK1epsilon and PIK3CB/p110beta to treat glioblastoma [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 1081.
Abstract 1090: Dominant-negative TP53 variants confer radiation resistance in endometrial cancer
Authors: Petty Aaron , Durmaz Arda , Yard Brian , Scott Jacob , Vargas Roberto 
Published: June 2023

Abstract
Introduction: High-grade endometrial cancers (EC) belonging to the “serous-like” cluster are known to portend a worse clinical outcome. The direct contribution of commonly identified TP53 variants on radiotherapy (RT) response has not been demonstrated in EC.
Methods: To assess the impact of TP53 variants, allelic frequency, and p53/p21 signaling on radio-resistance in vitro, we utilized a high-throughput radiation assay and intron targeting CRISPR-Cas9 knockout approach in two low copy-number/TP53 wild-type EC cell lines (JHUEM1/JHUEM2). This approach facilitated TP53 cDNA complementation in a TP53-null background without significant impact from copy-number burden. The effect on radiation response was determined using high-throughput methodology and area under the curve (AUC) calculation along 5 dose-points. All experiments were carried out using 2 monoclonal isolates for each guide RNA (4 total replicates) and 2 non-targeting controls.
Results: Knockout (KO) of wild-type TP53 resulted in loss of downstream p21 signaling and increased radio-resistance, demonstrating the role of p53 signaling on RT response. Complementation with five common TP53 missense variants (Y220C, R273C, R273H, R248Q, R248W) into the KO cell lines led to increased p53 accumulation without an effect on p21 signaling or RT response. Complementation into the WT cell lines, mimicking tumors with low allelic frequency/heterozygous mutations, led to abrogation of p21 signaling and increased radio-resistance, establishing their gain-of-function/dominant-negative impact.
Conclusions: Our findings directly implicate TP53 status on radiotherapy response in EC, providing biologic rationale for the clinical observation that these patients may benefit from chemotherapy. Additionally, our findings demonstrate that dominant-negative variant alleles similarly impact RT response by abrogating p21 signaling.
Citation Format: Aaron Petty, Arda Durmaz, Brian Yard, Jacob Scott, Roberto Vargas. Dominant-negative TP53 variants confer radiation resistance in endometrial 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 1090.
Abstract 1098: Combination of a DNA vaccine-induced immune checkpoint blockade and radiation therapy induces anti-tumor immunity
Authors: Lan Keng-Hsueh , Sheng Ying-Chun , Lan Keng-Li , Kim KyungMann , Kuo Sung-Hsin , Morris Zachary 
Published: June 2023

Abstract
Background: Immune checkpoint blockade (ICB) immunotherapy improves survival for many cancer patients, but those with immunologically ‘cold’ tumors do not derive benefit. Radiation therapy (RT) has been demonstrated to augment antitumor immunity in preclinical and clinical studies and may enhance response to ICB in immunologically cold tumors. We have developed DNA-based, cost-effective, and versatile ICB immunotherapies. Here, we test the use of these alone and in combination with RT as a novel treatment approach in syngeneic murine melanoma models.
Materials and methods: We constructed ICB DNA vaccines targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1), CTLA-4 Vax and PD-1 Vax, respectively. These were delivered to mice by intramuscular or intratumoral electroporation. The effects of combinations of ICB DNA vaccines and RT were monitored for generation of endogenous anti-CTLA-4 and anti-PD-1 antibodies, modification of tumor microenvironment (TME), and tumor response in mice bearing syngeneic B78 or B16 melanoma.
Results: Intramuscular vaccination with CTLA-4 Vax and PD-1 Vax induced endogenous anti-CTLA-4 and anti-PD-1 antibodies, respectively, and the titers increased with additional vaccinations. Vaccination with CTLA-4 Vax and PD-1 Vax alone or in combination (Dual Vax) did not inhibit the murine B16 melanoma model; however, the combination of CTLA-4 Vax and RT (CTLA-4 Vax + RT) led to enhanced infiltration of the TME with effector T cells. Dual Vax combined with RT enabled systemic anti-tumor immunity in mice bearing two B16 melanoma tumors in which only one was radiated. With intra-tumoral route of vaccination, the Dual Vax + RT treatment induced a trend toward systemic anti-tumor response in the immunologically cold B78 tumor model.
Conclusions: DNA vaccines that stimulate endogenous production of antibodies against immune checkpoints may serve as an alternative form of ICB. The combination of ICB DNA vaccine and RT enabled anti-tumor immunity and tumor response in preclinical models of melanoma.
Citation Format: Keng-Hsueh Lan, Ying-Chun Sheng, Keng-Li Lan, KyungMann Kim, Sung-Hsin Kuo, Zachary Morris. Combination of a DNA vaccine-induced immune checkpoint blockade and radiation therapy induces anti-tumor immunity [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 1098.
Abstract 1109: Effects of radiation therapy on the hardness of enamel and dentin
Authors: Kulchar Rachel , Eggmann Florin , Mina Celine , Szewczyk Steven , Yusuke Kakiuchi , Deng Jie , Mante Francis 
Published: June 2023

Abstract
Introduction: Radiation therapy is often used as the main or adjunctive treatment for cancer in the oral cavity. Unfortunately, prolonged exposure to radiation has adverse effects on tissues of the oral cavity, including a decrease in the hardness of dentin. Consequently, patients who receive radiation therapy are susceptible to tooth sensitivity and caries. Fluoride treatments have proven to be effective in restoring the hardness of dentin as it remineralizes the tooth. The aim of this study was to determine the optimal fluoride treatment for restoring the hardness of irradiated teeth.
Methods: 100 teeth were extracted, cleaned, and mounted in acrylic resin. The teeth were ground and polished to expose the dentin and enamel. The initial Knoop hardness of the teeth was measured and split equally among five groups and treated as follows: (1) sodium fluoride varnish (SF), (2) MI varnish (MI), (3) silver diamine fluoride and potassium iodide (SDFKI), (4) silver diamine fluoride (SDF), and (5) no treatment (NT). All groups were subjected to 2 grays of daily radiation treatment for 6 weeks. The hardness of the dentin was measured immediately following radiation. Afterwards, the 5 treatments were applied weekly for 6 weeks. Hardness was measured 1 week after each treatment. Kruskal-Wallis one way analysis of variance on ranks was used to compare the different groups.
Results: After 6 weeks of fluoride treatment, there was a significant difference (p = 0.013) between the hardness of the irradiated enamel, with Group 4 resulting in the largest median measurement (263.4). Similarly, 5 weeks of fluoride application resulted in a mean hardness of dentin that was 15.8%, 13.6%, 16.2%, and 19.4% higher than the control for groups 1, 2, 3, and 4, respectively. Again, Group 4 had the highest hardness measurement.
Conclusions: Radiation therapy decreases the hardness of enamel and dentin. SDF treatment resulted in the highest hardness for both irradiated dentin and enamel, suggesting that SDF is promising as a fluoride treatment for those undergoing radiation therapy for oral cancer.
Citation Format: Rachel Kulchar, Florin Eggmann, Celine Mina, Steven Szewczyk, Kakiuchi Yusuke, Jie Deng, Francis Mante. Effects of radiation therapy on the hardness of enamel and dentin [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 1109.