bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predrawn prehospital medications are microbiologically safe for up to 48 hours
Authors: Soeyland Torgrim , Garner Alan , Vidler Sam , Gutierrez Cristian Humberto , Foster Arnold , Kitcher Jane 
Published: April 2023

BackgroundPrehospital medical teams are commonly required to administer a range of medications for urgent stabilisation and treatment. The safe preparation of medications during resuscitation requires attention, time and resources, and can be a source of medication error. In our two road and HEMS (Helicopter Emergency Medical Service) prehospital services, medication errors are mitigated by predrawing commonly used medications to set concentrations daily (Hunter Retrieval Service, HRS) or second-daily (CareFlight Sydney, CFS). However, there are no published data confirming that such practice is microbiologically safe.MethodsA convenience sample of 299 predrawn medication syringes with syringe dwell times up to 48 hours were collected at the end of their operational deployment. Predrawn medication syringes collected for culture were ketamine, midazolam, fentanyl, thiopentone, rocuronium, suxamethonium, metaraminol and normal saline. The samples were incubated and cultured at a tertiary hospital pathology laboratory using best-practice methodology for non-tissue samples. The samples were collected from June 2017 to February 2018.ResultsThe mean dwell times ranged from 30.7 hours (fentanyl at HRS) to 48.5 hours (rocuronium at CFS). None of the 299 cultured samples yielded significant micro-organisms. One sample of suxamethonium with a syringe dwell time of 34 hours grewBacillus cereusbut was likely a contaminant introduced during sample collection.ConclusionPredrawing of the eight studied medications for urgent prehospital procedures appears to be a microbiologically safe practice with syringe dwell times up to 48 hours.
Ventricular function and biomarkers in relation to repair and pulmonary valve replacement for tetralogy of Fallot
Authors: van der Ven Jelle P G , Günthel Marie , van den Bosch Eva , Kamphuis Vivian P , Blom Nicolaas A , Breur Johannes , Berger Rolf M F , Bogers Ad J J C , Koopman Laurens , Ten Harkel Arend D J , Christoffels Vincent , Helbing Willem A 
Published: April 2023

ObjectiveCardiac surgery may cause temporarily impaired ventricular performance and myocardial injury. We aim to characterise the response to perioperative injury for patients undergoing repair or pulmonary valve replacement (PVR) for tetralogy of Fallot (ToF).MethodsWe enrolled children undergoing ToF repair or PVR from four tertiary centres in a prospective observational study. Assessment—including blood sampling and speckle tracking echocardiography—occurred before surgery (T1), at the first follow-up (T2) and 1 year after the procedures (T3). Ninety-two serum biomarkers were expressed as principal components to reduce multiple statistical testing. RNA Sequencing was performed on right ventricular (RV) outflow tract samples.ResultsWe included 45 patients with ToF repair aged 4.3 (3.4 – 6.5) months and 16 patients with PVR aged 10.4 (7.8 – 12.7) years. Ventricular function following ToF repair showed a fall-and-rise pattern for left ventricular global longitudinal strain (GLS) (−18±4 to −13±4 to −20±2, p < 0.001 for each comparison) and RV GLS (−19±5 to −14±4 to 20±4, p < 0.002 for each comparison). This pattern was not seen for patients undergoing PVR. Serum biomarkers were expressed as three principal components. These phenotypes are related to: (1) surgery type, (2) uncorrected ToF and (3) early postoperative status. Principal component 3 scores were increased at T2. This increase was higher for ToF repair than PVR. The transcriptomes of RV outflow tract tissue are related to patients’ sex, rather than ToF-related phenotypes in a subset of the study population.ConclusionsThe response to perioperative injury following ToF repair and PVR is characterised by specific functional and immunological responses. However, we did not identify factors relating to (dis)advantageous recovery from perioperative injury.Trial registration numberNetherlands Trial Register: NL5129.
Observation of time-dependent internal charge amplification in a planar germanium detector at cryogenic temperature
Authors: Acharya P. , Fritts M. , Mei D.-M. , Mandic V. , Wang C.-J. , Mahapatra R. , Platt M. 
Published: April 2023

AbstractFor the first time, time-dependent internal charge amplification through impact ionization has been observed in a planar germanium (Ge) detector operated at cryogenic temperature. In a time period of 30 and 45 min after applying a bias voltage, the charge energy corresponding to a baseline of the 59.54 keV $$\gamma $$
γ
rays from a $$^{241}$$

241

Am source is amplified for a short period of time and then decreases back to the baseline. The amplification of charge energy depends strongly on the applied positive bias voltage with drifting holes across the detector. No such phenomenon is visible with drifting electrons across the detector. We find that the observed charge amplification is dictated by the impact ionization of charged states, which has a strong correlation with impurity level and applied electric field. We analyze the dominant physics mechanisms that are responsible for the creation and the impact ionization of charged states. Our analysis suggests that the appropriate level of impurity in a Ge detector can enhance charge yield through the impact ionization of charged states to achieve extremely low-energy detection threshold (< 10 meV) for MeV-scale dark matter searches if the charge amplification can be stabilized.
Prevalence and Factors Associated with Drooling in Parkinson’s Disease: Results from a Longitudinal Prospective Cohort and Comparison with a Control Group
Authors: Santos-García Diego , de Deus Fonticoba Teresa , Cores Bartolomé Carlos , Feal Painceiras Maria J. , Íñiguez-Alvarado Maria Cristina , Jesús Silvia , Buongiorno Maria Teresa , Planellas Lluís , Cosgaya Marina , García Caldentey Juan , Caballol Nuria , Legarda Ines , Hernández Vara Jorge , Cabo Iria , López Manzanares Lydia , González Aramburu Isabel , Ávila Rivera Maria A. , Gómez Mayordomo Víctor , Nogueira Víctor , Puente Víctor , Dotor García-Soto Julio , Borrué Carmen , Solano Vila Berta , Álvarez Sauco María , Vela Lydia , Escalante Sonia , Cubo Esther , Carrillo Padilla Francisco , Martínez Castrillo Juan C. , Sánchez Alonso Pilar , Alonso Losada Maria G. , López Ariztegui Nuria , Gastón Itziar , Kulisevsky Jaime , Blázquez Estrada Marta , Seijo Manuel , Rúiz Martínez Javier , Valero Caridad , Kurtis Mónica , de Fábregues Oriol , González Ardura Jessica , Alonso Redondo Ruben , Ordás Carlos , López Díaz Luis M. L. , McAfee Darrian , Martinez-Martin Pablo , Mir Pablo , COPPADIS Study Group 
Published: April 2023

Introduction. Drooling in Parkinson’s disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results. The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls;

p

< 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls;

p

< 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032;

p

= 0.012), being male (OR = 2.333;

p

< 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020;

p

< 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012;

p

< 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121;

p

= 0.007) as a predictor of drooling at V2. Conclusion. Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden.
Study on the Hyperglycemic Effect of GLP-1 in Spinibarbus denticulatus by Oral Administration and Intraperitoneal Injection Methods
Authors: Luo Wei , Li Luojia , Zhang Yue , Xu Zhou , Xiong Yinlin , Guo Zhonggang , Zhang Ning , Zhang Yibo , Chen Pengyu , Wang Yan , Du Zongjun 
Published: April 2023

Glucagon-like peptide-1 (GLP-1), one of the expression products of the proglucagon (pg) gene, is an incretin mainly secreted by the gastrointestinal system. In mammals, GLP-1 has hypoglycemic and food-inhibiting effects; while in some fish species, it has been confirmed to increase blood glucose by promoting gluconeogenesis and stimulating glycogenolysis. In order to more deeply understand the role of GLP-1 in the process of glycometabolism in herbivorous fish, the pg gene was cloned from Spinibarbus denticulatus to obtain its sequence characteristics, and the changes in blood glucose level and pg gene expression in S. denticulatus were further explored by feeding with three kinds of carbohydrates and intraperitoneal injection of GLP-1. Basal and temporal blood glucose levels and pg gene expression of S. denticulatus (

91.68
±
10.79

g

) were measured at 0, 1, 3, 5, 7, and 12 h after oral administration (

n
=
4

). Then, the changes of blood glucose levels and pg and glucokinase (gk) gene expressions of S. denticulatus (

94.29
±
10.82

g

) were determined at 0, 30, 60, and 120 min after intraperitoneal injection (

n
=
4

). It was shown that polysaccharides could induce the upregulation of pg gene expression faster than monosaccharides and stimulate the secretion of GLP-1 in the intestine. Intraperitoneal injection of GLP-1 peptide rapidly raised blood glucose levels, and pg gene expression in the anterior intestine, whole brain, and hepatopancreas decreased continuously after 30 minutes. These results showed that S. denticulatus might inhibit the excessive accumulation of blood glucose by reducing the expression of the pg gene and increasing the expression of gk gene in a short time. It was speculated that GLP-1 of S. denticulatus might have a “gut-brain-liver” pathway similar to mammals in glycemia regulation. Therefore, this study provided a novel perspective for explaining the functional differences of GLP-1 in herbivorous fish and mammals.
Abstract 1129: Targeting tissue-resident macrophage progenitors restores anti-tumor immunity and suppresses tumor growth
Authors: Chen Hui , Paradise Marc , Shepard Ryan , Wang Guangfang , Onaitis Mark , Varner Judith 
Published: April 2023

Abstract
Macrophages are innate immune cells that accumulate rapidly in tumors, where they promote immune suppression, tumor growth and resistance to checkpoint inhibitor therapy. As these cells play critical roles in tumor progression, they are the focus of efforts to develop novel cancer therapeutics. Strategies to inhibit macrophage accumulation to suppress tumor growth by blocking their recruitment from circulation have been only partially effective. In this project, we examined the origins of tumor associated macrophages using lineage tracing, flow cytometry, and single cell sequencing. We found that large proportions of macrophages in subcutaneous and genetically engineered mouse tumors do not derive from Ly6C+ or Ly6C- or CCR2+ monocytes. Instead, a large population of CCR2-Ly6C-F4/80hi macrophages that are CD206+MerTK+ are profoundly immune suppressive resident macrophages that arise from a transcriptionally related proliferative progenitor subpopulation rather than by trafficking from the circulation. By comparing gene expression profiles of resident and recruited macrophages in subcutaneous, alveolar, central nervous and renal normal and tumor tissues, we identified generic tissue resident macrophage and recruited signatures that reveal that resident macrophages are more immune suppressive than recruited macrophages and are associated with worse outcomes in cancer patients. Tissue resident macrophages express signatures of Myc-driven proliferation, cholesterol metabolism and profound immune suppression while bone marrow derived macrophages express mixed signatures of inflammation and immune suppression. Genetic and pharmacological inhibition of c-Kit/mCsf1R, cMyc and cyclin-dependent kinases suppressed the expansion of these macrophages, thereby limiting their accumulation in tumors, promoting anti-tumor adaptive immunity and inhibiting tumor progression in mouse models of cancer. We identified a novel cKit/Csf1r/Cdk19 inhibitor that suppressed tissue resident macrophage accumulation and potently inhibited tumor growth.
These results identify tissue resident macrophage progenitor cells as key targets for the development of therapeutic strategies to stimulate anti-cancer immunity.
Citation Format: Hui Chen, Marc Paradise, Ryan Shepard, Guangfang Wang, Mark Onaitis, Judith Varner. Targeting tissue-resident macrophage progenitors restores anti-tumor immunity and suppresses 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 1129.
Abstract 1237: Zeb1-mediated autophagy enhances resistance of breast cancer cells to genotoxic drugs
Authors: Barlev Nick A. , Fedorova Olga , Daks Alexandra , Tulchinsky Eugene M. 
Published: April 2023

Abstract
This report presents novel results on the involvement of epithelial to mesenchymal transition (EMT) in the process of autophagy. Autophagy is a highly conserved process of cellular self-digestion that involves the formation of autophagosomes for the delivery of intracellular components and dysfunctional organelles to lysosomes. This process is induced by different signals including starvation, mitochondrial dysfunction, and DNA damage. The molecular link between autophagy and DNA damage is not well understood yet. Importantly, tumor cells utilize the mechanism of autophagy to cope with genotoxic anti-cancer drug therapy. Another mechanism of drug resistance is provided to cancer cells via the execution of the EMT program. One of the critical transcription factors of EMT is Zeb1. Here we demonstrate that Zeb1 is involved in the regulation of autophagy in several breast cancer cell models. On the molecular level, forced expression of Zeb1 in otherwise epithelial cells likely facilitates autophagy through the regulation of several autophagic genes, resulting in increased LC3-II levels, augmented staining with Lysotracker, and increased resistance to genotoxic drugs. On the contrary, the attenuation of Zeb1 expression in TNBC cells led to the opposite effect. Consequently, we propose that Zeb1 augments the resistance of breast cancer cells to genotoxic drugs, at least partially, by promoting autophagy. Collectively, we have uncovered a novel function of Zeb1 in the regulation of autophagy in breast cancer cells.
Citation Format: Nick A. Barlev, Olga Fedorova, Alexandra Daks, Eugene M. Tulchinsky. Zeb1-mediated autophagy enhances resistance of breast cancer cells to genotoxic drugs [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 1237.
Abstract 1290: PTEN loss-mediated cell surface translocation of Annexin A2 promotes prostate cancer metastasis
Authors: Chaudhary Pankaj , Howard-Smith Christianna 
Published: April 2023

Abstract
Introduction: Metastasis is a major cause of morbidity in prostate cancer patients. Despite substantial efforts to understand prostate cancer metastasis, the mechanisms involved in preparing the metastatic niche for colonizing the prostate cancer cells are still unknown.
Methods/Materials: The normal prostate epithelial and cancer cells were purchased from American Type Culture Collection (Manassas, VA). Immunoblotting, immunofluorescence, flow cytometry, and plasmin generation assay were performed.
Results: Our results demonstrated that Pten deletion or mutation caused significantly high phosphorylation of Annexin A2 (AnxA2) at tyrosine-23 in human and murine prostate cancer cell lines compared to the normal prostate epithelial cell lines. However, we did not observe any change in total AnxA2 protein level after Pten deletion/mutation in human and murine prostate cancer cells compared to normal prostate epithelial cells. Our flow cytometry data, immunofluorescence, and membrane wash fraction analysis suggest that AnxA2 expression was higher at the cell surface of Pten null/mutated prostate cancer cell lines compared to the normal prostate epithelial cells. Confocal microscopy and immunoprecipitation analysis revealed that AnxA2 interacts with Pten in normal prostate epithelial cells and inhibits AnxA2 phosphorylation at tyrosine 23. Pten deletion/mutation-mediated translocation of AnxA2 is dependent on the phosphorylation of tyrosine 23, and mutation of tyrosine 23 to a non-phosphomimetic variant inhibits the cell surface translocation process. The cell surface-translocated AnxA2 promotes the plasmin generation in prostate cancer cells, and an AnxA2 inhibitory hexapeptide can neutralize this activity.
Conclusions: PTEN loss is the primary driving force for the translocation of AnxA2 to the cell surface and promotes plasmin generation.
Citation Format: Pankaj Chaudhary, Christianna Howard-Smith. PTEN loss-mediated cell surface translocation of Annexin A2 promotes prostate cancer metastasis [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 1290.
Abstract 1312: Oncogenic mutant p53 proteins are selectively shuttled by cancer extracellular vesicles toeducate the tumor microenvironment
Authors: Bhatta Bibek , Luz Ishai , Krueger Christian , Teo Fanny Xueting , Lane David P. , Sabapathy Kanaga , Cooks Tomer 
Published: April 2023

Abstract
IntroductionMost cancers harbor mutations in the TP53 gene (encoding for the p53 tumor suppressor protein). Furthermore, gain-of-function (GOF) mutation in p53 imparts an aggressive traits to the cells when compared to the cancer cells harboring inactivating mutations or wild-type (WT)-p53. Notably, multiple studies have delineated the presence of GOF-mutant p53 protein in untransformed cells or in stromal compartments of tumor microenvironment (TME). In recent years, the involvement of extracellular vesicles (EVs) in cell-to-cell communication has emerged as a major route by which cancer cells can interact and educate immune, and non-immune cells in TME to become tumor supportive. To this end, we hypothesize that mutant p53 protein can be shuttled via EVs to TME cells thus shedding light on a novel non-cell autonomous role of mutant p53 cancers.MethodsEVs were isolated from various cancer cell lines (pancreas, lung, colon) differing by their p53 status and the effect on neighboring cancer cells and TME cells was studied in vitro and in-vivo. We also utilized the human colorectal Colo-320DM cancer cell xenograft model, which expresses the R248W p53 mutant. FFPE sections of subcutaneous tumors derived from the Colo-320DM xenografts were stained for p53 using the DO-1 antibody that specifically recognizes human p53.ResultsOur data demonstrated that mutant p53 protein can be selectively sorted into EVs; that mutant p53 in EVs can be taken up by neighboring cancer cells and macrophages that do not harbor mutant p53 protein. Evident of macrophage education was seen with the increased expression and secretion of pro-inflammatory cytokines. Notably, mutant p53 expression was also found in non-tumor cells in both human cancers, and in non-human tissues in human xenografts.SummaryCancer cells harboring GOF p53 mutants, can package mutant p53 proteins in EVs, and deliver them to neighboring cancer cells and to the TME.
Citation Format: Bibek Bhatta, Ishai Luz, Christian Krueger, Fanny Xueting Teo, David P. Lane, Kanaga Sabapathy, Tomer Cooks. Oncogenic mutant p53 proteins are selectively shuttled by cancer extracellular vesicles toeducate the tumor microenvironment [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 1312.
Abstract 1315: NETs act as immunosuppressive agents within lymph nodes during cancer
Authors: Brassard Ariane , Su Xin , Dhoparee-Doomah Iqraa , Leo Sabrina , Feng Lixuan , Bourdeau France , Giannias Betty , Larson Corissa , Qiu Qian , Spicer Jonathan , Ferri Lorenzo , Cools-Lartigue Jonathan 
Published: April 2023

Abstract
Metastasis is responsible for 90% of all cancer-related deaths, making it the most significant challenge in cancer treatment for clinicians worldwide. Metastasis is thought to occur in a stepwise process, in which local lymph nodes (LNs) are first colonized by tumour cells before proceeding to distal organs. However, the mechanism by which LN metastasis facilitates distal metastasis is poorly understood. LNs undergo environmental changes to accommodate tumour cell growth within, notably by shifting the environment towards immunosuppression to shut down anti-tumour immune cells. This immunosuppressive environment is critical for the establishment of LN metastases, as cytotoxic CD8 T cells will otherwise neutralize incoming circulating tumour cells. Neutrophils are among the first cells recruited to tumour-draining LNs to mediate the environmental shift, and yet their method of action has not been fully elucidated. They have recently been found to secrete NETs within LNs during cancer, which are pro-inflammatory web-like formations of DNA decorated with antimicrobial peptides. While NETs have been shown to exert pro-tumour effects in the tumour microenvironment and to facilitate metastasis as a whole, their role in LNs has never been explored. Using a NETs deficient mouse model (PAD4-/-), we report that NETs deposition within the tumour-draining LNs of mice upregulates the Treg population while simultaneously downregulating anti-tumour CD8 T cell proliferation and activation. Following these findings, we performed an in vitro suppression assay and found that NETs-educated Tregs hinder the expansion of CD8 T cells more than non-NETs-educated Tregs. Finally, through an induced metastasis mouse model, we have observed that tumour-draining LN resection as well as the absence of NETs protects against the development of distal metastasis, and decreases body-wide inflammation as seen by a lowered Neutrophil-to-Lymphocyte ratio in the circulation. Taken together, these findings highlight the role of NETs deposition in LNs as a key player in disease progression and bring forward a potential target for anti-metastatic drug development.
Citation Format: Ariane Brassard, Xin Su, Iqraa Dhoparee-Doomah, Sabrina Leo, Lixuan Feng, France Bourdeau, Betty Giannias, Corissa Larson, Qian Qiu, Jonathan Spicer, Lorenzo Ferri, Jonathan Cools-Lartigue. NETs act as immunosuppressive agents within lymph nodes during 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 1315.