bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous versus subcutaneous tocilizumab in Takayasu arteritis: multicentre retrospective study
Authors: Mekinian Arsène , Biard Lucie , Lorenzo Dagna , Novikov Pavel I , Salvarani Carlo , Espitia Olivier , Sciascia Savino , Michaud Martin , Lambert Marc , Hernández-Rodríguez José , Schleinitz Nicolas , Awisat Abid , Puechal Xavier , Aouba Achille , Munoz Pons Helene , Smitienko Ilya , Gaultier Jean Baptiste , Edwige Le Mouel , Benhamou Ygal , Perlat Antoinette , Jego Patrick , Goulenok Tiphaine , Sacre Karim , Lioger Bertrand , Hassold Nolan , Broner Jonathan , Dufrost Virginie , Sené Thomas , Seguier Julie , Maurier Francois , Berthier Sabine , Belot Alexandre , Frikha Faten , Denis Guillaume , Audemard-Verger Alexandra , Koné-Paut Isabelle , Humbert Sebastien , Woaye-Hune Pascal , Tomelleri Alessandro , Baldissera Elena Marina , Kuwana Masataka , Lo Gullo Alberto , Mukuchyan Vahan , Dellal Azeddine , Gaches Francis , Zeminsky Pierre , Galli Elena , Alvarado Moya , Boiardi Luigi , Muratore Francesco , Vautier Mathieu , Campochiaro Corrado , Moiseev Sergey , Vieira Matheus , Cacoub Patrice , Fain Olivier , Saadoun David
Published: June 2023

Objectives

In this large multicentre study, we compared the effectiveness and safety of tocilizumab intravenous versus subcutaneous (SC) in 109 Takayasu arteritis (TAK) patients.

Methods

We conducted a retrospective multicentre study in referral centres from France, Italy, Spain, Armenia, Israel, Japan, Tunisia and Russia regarding biological-targeted therapies in TAK, since January 2017 to September 2019.

Results

A total of 109 TAK patients received at least 3 months tocilizumab therapy and were included in this study. Among them, 91 and 18 patients received intravenous and SC tocilizumab, respectively. A complete response (NIH <2 with less than 7.5 mg/day of prednisone) at 6 months was evidenced in 69% of TAK patients, of whom 57 (70%) and 11 (69%) patients were on intravenous and SC tocilizumab, respectively (p=0.95). The factors associated with complete response to tocilizumab at 6 months in multivariate analysis, only age <30 years (OR 2.85, 95% CI 1.14 to 7.12; p=0.027) and time between TAK diagnosis and tocilizumab initiation (OR 1.18, 95% CI 1.02 to 1.36; p=0.034). During the median follow-up of 30.1 months (0.4; 105.8) and 10.8 (0.1; 46.4) (p<0.0001) in patients who received tocilizumab in intravenous and SC forms, respectively, the risk of relapse was significantly higher in TAK patients on SC tocilizumab (HR=2.55, 95% CI 1.08 to 6.02; p=0.033). The overall cumulative incidence of relapse at 12 months in TAK patients was at 13.7% (95% CI 7.6% to 21.5%), with 10.3% (95% CI 4.8% to 18.4%) for those on intravenous tocilizumab vs 30.9% (95% CI 10.5% to 54.2%) for patients receiving SC tocilizumab. Adverse events occurred in 14 (15%) patients on intravenous route and in 2 (11%) on SC tocilizumab.

Conclusion

In this study, we confirm that tocilizumab is effective in TAK, with complete remission being achieving by 70% of disease-modifying antirheumatic drugs-refractory TAK patients at 6 months.
Mechanical model for the FCC-ee interaction region
Authors: Boscolo Manuela , Palla Fabrizio , Bosi Filippo , Fransesini Francesco , Lauciani Stefano
Published: June 2023

The Future Circular Collider FCC-ee aims at unprecedented luminosities to be obtained with the crab-waist collision scheme. In this paper we describe the mechanical model of the interaction region layout including its assembly procedure. After a discussion on the requirements and constraints, we present the engineered design of the vacuum chamber with the cooling system, the bellows, the vertex and outer tracker detectors and their integration in a carbon-fibre lightweight support structure that will support also the luminosity calorimeter.
Derivations characterized by monomials x2n in prime rings
Authors: Chang Chung-Wei , Liu Cheng-Kai
Published: June 2023

Let [Formula: see text] be a prime ring of [Formula: see text] or [Formula: see text] and let [Formula: see text] be an additive map such that [Formula: see text] for all [Formula: see text], where [Formula: see text] is a positive integer and [Formula: see text] is the maximal symmetric ring of quotients of [Formula: see text]. It is shown that there exist a derivation [Formula: see text] and an additive map [Formula: see text] with [Formula: see text] for all [Formula: see text], such that [Formula: see text]. This result is a natural generalization of the classic theorem of Herstein for Jordan derivations on prime rings. Moreover, it gives a purely algebraic version of the theorem recently obtained by Kosi-Ulbl, Rodriguez and Vukman for standard operator algebras on Banach spaces.
Wi-CL: Low-Cost WiFi-Based Detection System for Nonmotorized Traffic Travel Mode Classification
Authors: Xu Runnan , Huang Zilin , Chen Sikai , Li Jinlong , Wu Pan , Lin Yongjie
Published: June 2023

Traffic travel mode identification and classification are crucial for the development of intelligent transportation systems (ITSs). At present, scholars have investigated the classification of motorized and nonmotorized traffic travel in various road environments; however, the classification of walking and bicycle modes in nonmotorized travel has been largely ignored. Therefore, in this paper, we investigate nonmotorized traffic travel and propose a new low-cost nonmotorized traffic travel mode classification system, known as the Wi-Fi classification (Wi-CL) system that uses Wi-Fi signal detectors and the refined characteristics of nonmotorized travel modes. The Wi-CL system includes four modules: data acquisition module, data processing module, feature extraction module, and mode classification module. In the data acquisition module, the proposed system detects the Wi-Fi signals of traffic participants in road environments. In addition, we propose a received signal strength indicator (RSSI) filtering algorithm for hybrid traffic networks that effectively addresses surrounding obstacles and environmental noise. In the feature extraction module, we extract relevant traffic features to construct a mode classification model. Finally, a recurrent neural network (RNN) framework based on the long short-term memory (LSTM) algorithm is successfully implemented in the mode classification module for traffic travel mode identification. To validate the effectiveness of the Wi-CL system, extensive experiments were conducted using field data collected by Wi-Fi detectors installed at the South China University of Technology (SCUT). The experimental results show that the proposed RSSI filtering algorithm achieves excellent signal filtering results in real road traffic environments. In addition, the constructed travel speed estimation algorithm outperforms other baseline models in four different scenarios (flat-peak walking, midday peak walking, flat-peak cycling, and midday peak cycling), achieving an overall classification accuracy of 97.92%. In summary, our Wi-CL system is a feasible approach for nonmotorized traffic travel mode classification.
Efficacy for Bone Deterioration in Mice with Osteoporosis and Pharmaceutical Properties of a Novel Compound Calcium Carbonate Granule
Authors: Ma Kun , He Jialuo , Yuan Huimin , He Jiayu , Xiang Ming
Published: June 2023

Osteoporosis (OP) has been a global health concern, and calcium supplements are still an effective method to relieve the disease. In this study, we investigated the pharmaceutical properties, antiosteoporosis, and adverse effects of a novel calcium supplement named compound calcium carbonate granule (CCCG). The dissolution rate, stability of vitamin D3, and drug permeability of the calcium supplements were explored. And the osteoporosis was constructed in mice with retinoic acid (100 mg/kg/d) for 21 days, and orally treated with CCCG (0.34, 0.68, and 1.36 g/kg/d) for 36 days to evaluate the efficacy against osteoporosis and the occurrence of kidney stones. The results showed that CCCG exhibited higher dissolution rate and better vitamin D3 stability than the standard calcium carbonate granule. CCCG also displayed more absorption in Caco-2 cell model. On the other hand, CCCG alleviated the deterioration in femur microstructure and oxidative stress in the liver and kidney, and increased the expression of bone metabolic markers. CCCG also exhibited lower risk of nephrolithiasis than the commercial calcium carbonate granule. In summary, from the perspectives of both pharmaceutics and efficacy, we illustrated the profiles of an intriguing calcium supplement, which could possibly be an alternative of commonly used ones. Practical Application. Calcium carbonate is widely used to supplement calcium, primarily because of its high calcium load, low cost, and good efficacy. Now, we provided a new calcium supplement named CCCG, which was prepared by inclusion and complexation techniques. Vitamin D3 in CCCG was made into vitamin D-β-cyclodextrin inclusion complex by inclusion technology, which improved the stability of vitamin D3. And calcium carbonate was converted to a water-soluble calcium citrate complex via complexation techniques to accelerate the release of calcium ions and minimize the risk of kidney stone formation. From the perspective of both pharmaceutics and efficacy, we illustrated the profiles of an intriguing calcium supplement, which could possibly be an alternative for the supplemental and preventive treatment of osteoporosis.
Nutritional Quality and Popability of Popcorn (Zea mays L. var. everta) in Response to Compost and NPK 20-7-3 Application under Dryland Condition of South Africa
Authors: Dada Oyeyemi A. , Mavengahama Sydney , Kutu Funso R.
Published: June 2023

The dietary value of popcorn, an important snack, depends on its proximate and nutritional constituents, while the economic worth is based on popability and expansion traits of the kernels. There is paucity of information on how soil fertility influences or relates with popping potentials as well as quality of popcorn kernel in semi-arid region. Therefore, the proximate composition and popping parameters of popcorn in response to organic and inorganic fertilizers were investigated. The field trial was conducted in 2017-2019, and it comprised five amendment rates including 90 and 180 kg ha-1 NPK fertilizer and 4 and 8 t ha-1 compost and unamended treatment as the control. The trial was arranged in randomized complete block design in triplicate. Data on kernel yield, biomass, and harvest index were evaluated. Kernels were analysed for proximate composition and popping indices using standard procedures. Across the two seasons, mean protein (8.1%) and fibre (10.2%) contents were highest in kernels from plots fertilized with NPK at 180 kg ha-1, while grains from plots fertilized with 8 t ha-1 compost had the highest moisture (19.3%) and starch (50.1%) contents. The highest kernel expansion of 54.18 cm3 g-1 and 77.6% popped kernels were obtained in plots fertilized with 4 t ha-1 compost. Most of the kernels (61%) were small-sized caryopsis. Popability is significantly associated with volume expansion (

r
=
0.696

). Proximate components and popability improved greatly in compost-augmented field relative to the unfertilized plots. Application of 4 or 8 t ha-1 sorted municipal solid waste compost to Luvisol enhanced growth and nutritional quality of popcorn. In view of promoting nutrient cycling towards improving soil fertility without compromising environmental health, compost is comparable and a good alternative to fossil-based mineral fertilizers.
Gum and Resin Production and Marketing: Implications for Pastoral Livelihood in Adadle District, Somali Region, Ethiopia
Authors: Yussuf Bishar Ahmed , Lelamo Latamo Lameso , Abdi Mahamud Mahamed
Published: June 2023

Both locally and nationally, Ethiopia’s gum resin sector has a substantial economic impact. Even though collecting and selling gum and resin is one of the main livelihood activities in Ethiopia’s remote pastoral areas, there are few case studies that adequately reflect national realities. Therefore, the goal of this study is to pinpoint and evaluate gum and resin production and sale, as well as any implications for pastoral livelihood, in the Adadle district of the Somali Region. Both purposive and random sampling techniques were employed. The primary data gathering technique used were household surveys, key informant interviews, focus groups, market surveys, direct observation, and surveys of community-based organizations. Multiple response tests, one-way ANOVA, and descriptive statistics were used in SPSS Version 26 to statistically analyze the collected data. The study discovered many Acacia, Boswellia, and Commiphora tree species that are employed in the production of gum and resin. It was also found that natural oozing and artificial tapping were the methods used for collecting and harvesting gum and resin. The average amount of gum and resin/frankincense harvested annually by each family was 219.82 kg and 58.27 kg, respectively, with gum harvesting being substantially higher (

p
 
0.05

) than resin harvesting. The recurrent drought, season, and awareness level of harvesters on taping were the factors affecting the quantity and quality of production. The average annual household income from gum and resin/frankincense was 18,684 Ethiopian Birr and 43,704 Ethiopian Birr, respectively. The mean annual income from resin was substantially larger (

p
 
0.05

) than that of gum. The gum and resin market chain in the area comprises eight actors with five market channels. The research also demonstrates that the income made by selling gum and resin was used to pay for basic necessities for the family, save money for health care and medications, and pay for social concerns and educational expenses. Recurrent drought, lack of market access and market expertise, lack of institutional cooperatives, and lack of infrastructure and facilities were all determined to be obstacles to the production and sale of gum and resin. Generally, resources should be conserved and interventions should be done to ensure the sustainability of the resource base and improve production potential. Proper tapping techniques should be introduced to enhance production potential, and access to market information should be ensured to maximize primary producers’ income share insured for maximizing the income share of primary producers.
Prediction of Reservoir Bank Collapse Based on the Limit Equilibrium Theory
Authors: Ma Xuetong , Li Qipeng , Zhang Hao , Gao Debin , Long Jiao , Li Zhengzheng
Published: June 2023

The prediction of reservoir bank collapse width is a unique problem encountered in the construction of hydropower projects. Existing empirical graphic methods are based on the final state of bank collapse and can be used to predict only bank collapse width, and they thus do not adequately reflect the characteristics of the bank collapse process. To solve this problem, a prediction model for bank collapse width based on the limit equilibrium theory was established, and the key parameters and bank collapse process of the model were analyzed. The results reveal the necessity of selecting a reasonable underwater accumulation rate when predicting the bank collapse width using the limit equilibrium theory. At a constant ratio of water depth to bank slope height, the underwater accumulation rate increases with increasing bank slope height, with a linear relationship between them. In contrast, the bank slope angle has little impact on bank collapse width. Specifically, it mainly affects the width of the first bank collapse but has little effect on the width of subsequent bank collapses. With an increase in the bank slope angle, the bank collapse width fluctuates and rises. The prediction model of bank collapse width based on the limit equilibrium theory can better explain the time-dependent behavior of bank collapse. The research results are of high significance for the prediction of loess bank collapse.
A Model for Qur’anic Sign Language Recognition Based on Deep Learning Algorithms
Authors: AbdElghfar Hany A. , Ahmed Abdelmoty M. , Alani Ali A. , AbdElaal Hammam M. , Bouallegue Belgacem , Khattab Mahmoud M. , Tharwat Gamal , Youness Hassan A.
Published: June 2023

Deaf and dumb Muslims cannot reach advanced levels of education due to the impact of obstruction on their educational attainment. This leads to their inability to learn, recite, and understand the meanings and interpretations of the Holy Qur’an as easily as ordinary people, which also prevents them from applying Islamic rituals such as prayer that require learning and reading the Holy Qur’an. In this paper, we propose a new model for Qur’anic sign language recognition based on convolutional neural networks through data preparation, preprocessing, feature extraction, and classification stages. The proposed model is aimed at recognizing the movements of the Arabic sign language by recognizing the hand gestures that refer to the dashed Qur’anic letters in order to help the deaf and dumb learn their Islamic rituals. The experiments have been conducted on a part of a large Arabic sign language dataset called ArSL2018, which represents the 14 dashed letters in the Holy Qur’an, so that this part contains only 24,137 images. The experimental results demonstrate that the proposed model performs better than the other existing models.
Data from An In Vivo CRISPR Screen Identifies That SNRPC Promotes Triple-Negative Breast Cancer Progression
Authors: Lu Xun-Xi , Yang Wen-Xiao , Pei Yu-Chen , Luo Hong , Li Xiao-Guang , Wang Yun-Jin , Zhang Guo-Liang , Ling Hong , Shao Zhi-Ming , Hu Xin
Published: June 2023

Abstract
Dysregulation of RNA-binding proteins (RBP) is one of the characteristics of cancer. Investigating the biological functions and molecular mechanisms of abnormal RBPs can help uncover new cancer biomarkers and treatment strategies. To identify oncogenic RBPs in triple-negative breast cancer (TNBC), we employed an in vivo CRISPR screen and a TNBC progression model, which revealed small nuclear ribonucleoprotein polypeptide C (SNRPC), a subunit of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), as a key modulator of TNBC progression. SNRPC was frequently upregulated, which corresponded to poor prognosis in patients with TNBC. SNRPC ablation significantly impaired the proliferation, migration, and invasion of TNBC cells in vitro and in vivo. In addition, SNRPC was essential for the stability of U1 snRNP and contributed to the RNA Pol II–controlled transcriptional program. Knockdown of SNRPC decreased RNA Pol II enrichment on a subset of oncogenes (TNFAIP2, E2F2, and CDK4) and reduced their expression levels. Furthermore, SNRPC deletion was confirmed to inhibit TNBC progression partially through regulation of the TNFAIP2-Rac1–β-catenin signaling pathway. Taken together, this data suggests that SNRPC plays an oncogenic role in TNBC, is a marker of poor prognosis, and may be a valuable therapeutic target for patients with intractable TNBC.
Significance:
A functional CRISPR screen identifies SNRPC as an RNA-binding protein that promotes the aggressiveness of breast cancer by facilitating Pol II–controlled transcription of oncogenes.
Molekulare Klassifizierung und Therapien des diffusen großzelligen B-Zell-Lymphoms
Authors: Shimkus Gaelen , Nonaka Taichiro
Published: June 2023

Das diffuse großzellige B-Zell-Lymphom (DLBCL) umfasst eine Vielzahl von Krankheitsbildern, die bisher auf der Basis immunhistochemischer Methoden in Untergruppen eingeteilt und charakterisiert wurden, was den Ärzten nur eine eingeschränkte Prognose und keine Änderung des Behandlungsschemas ermöglicht. Die Hinzufügung von Rituximab zur CHOP-Therapie war der letzte Fortschritt in der Behandlung, derzeit folgen die Therapien jedoch einem standardisierten Ablauf, wenn die Krankheit refraktär wird, ohne dass eine Individualisierung auf der Grundlage des Genotyps erfolgt. Forschungsgruppen schlagen neue Strategien zur Kategorisierung von DLBCL auf der Grundlage oft gemeinsam vorgefundener genetischer Anomalien vor, um den Krankheitsverlauf infolge der Dysregulation bestimmter Signalwege besser vorhersagen und gezielter behandeln zu können. Neue Algorithmen in Kombination mit Sequenzierungstechniken der nächsten Generation haben je nach Forschungsteam zwischen 4 und 7 Untergruppen von DLBCL mit potenziell signifikanten und nutzbaren genetischen Veränderungen identifiziert. Verschiedene Medikamente, die auf Signalwege wie nach B-Zell-Rezeptor-Aktivierung, auf die NF-κB-Dysfunktion und auf die epigenetische Regulation abzielen, haben sich in ihren jeweiligen Gruppen als vielversprechend erwiesen und könnten als Zweit- oder Drittlinientherapie für Patienten mit rezidiviertem DLBCL von Nutzen sein. Durch die Einführung von Untergruppen können die erforderlichen Daten gesammelt werden, um festzustellen, welche dieser Gruppen signifikant sind und welche Behandlungen angezeigt sein könnten, und um Ärzten und Patienten ein besseres Verständnis des spezifischen Krankheitsverlaufs zu vermitteln.
AML: Therapie älterer Patient*innen mit rezidivierter oder refraktärer Erkrankung bleibt schwierig
Authors: Neuendorff Nina Rosa
Published: June 2023

This open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 (isocitrate dehydrogenase 2) inhibitor, with conventional care regimens (CCRs) in patients aged ≥60 years with late-stage, mutant-IDH2 acute myeloid leukemia (AML) relapsed/refractory (R/R) to 2 or 3 prior AML-directed therapies. Patients were first preselected to a CCR (azacitidine, intermediate-dose cytarabine, low-dose cytarabine, or supportive care) and then randomized (1:1) to enasidenib 100 mg per day or CCR. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), time to treatment failure (TTF), overall response rate (ORR), hematologic improvement (HI), and transfusion independence (TI). Overall, 319 patients were randomized to enasidenib (n = 158) or CCR (n = 161). The median age was 71 years, median (range) enasidenib exposure was 142 days (3 to 1270), and CCR was 36 days (1 to 1166). One enasidenib (0.6%) and 20 CCR (12%) patients received no randomized treatment, and 30% and 43%, respectively, received subsequent AML-directed therapies during follow-up. The median OS with enasidenib vs CCR was 6.5 vs 6.2 months (HR [hazard ratio], 0.86; P = .23); 1-year survival was 37.5% vs 26.1%. Enasidenib meaningfully improved EFS (median, 4.9 vs 2.6 months with CCR; HR, 0.68; P = .008), TTF (median, 4.9 vs 1.9 months; HR, 0.53; P < .001), ORR (40.5% vs 9.9%; P <.001), HI (42.4% vs 11.2%), and red blood cell (RBC)-TI (31.7% vs 9.3%). Enasidenib safety was consistent with prior reports. The primary study endpoint was not met, but OS was confounded by early dropout and subsequent AML-directed therapies. Enasidenib provided meaningful benefits in EFS, TTF, ORR, HI, and RBC-TI in this heavily pretreated older mutant-IDH2 R/R AML population.
DLBCL: Geriatric Prognostic Index verbessert die prognostische Einschätzung bei älteren Patienten
Authors: Wedding Ulrich
Published: June 2023

International prognostic Index (IPI) is the most widely used clinical prediction model for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but may be suboptimal in older patients. We aimed to develop and externally validate a clinical prediction model for older, R-CHOP treated DLBCL patients by examining geriatric assessment and lymphoma-related parameters in real-world cohorts. A population-based training set of 365 R-CHOP treated DLBCL patients ≥70 years was identified through the Cancer Registry of Norway. The external test set consisted of a population-based cohort of 193 patients. Data on candidate predictors was retrieved from the Cancer Registry and through review of clinical records. Cox regression models for 2-year overall survival (OS) were used for model selection. Activities of daily living (ADL), Charlson Comorbidity index (CCI), age, sex, albumin, stage, ECOG and LDH were identified as independent predictors and combined into a Geriatric prognostic index (GPI). The GPI demonstrated good discrimination (optimism-corrected C-index 0.752), and identified a low-, intermediate- and high-risk group with significantly different survival (2-year OS 94%, 65%, 25%). At external validation, the continuous and grouped GPI demonstrated good discrimination (C-index 0.727, 0.710) and the GPI groups had significantly different survival (2- year OS 95%, 65%, 44%). Both the continuous and grouped GPI showed better discrimination than IPI, R-IPI and NCCN-IPI (C-index 0.621, 0.583, 0.670) We have developed and externally validated the GPI for older DLBCL patients treated with RCHOP that outperformed IPI, R-IPI and NCCN-IPI. A web-based calculator is available at https://wide.shinyapps.io/GPIcalculator/.
Clinical and Proteomic-Based Molecular Characterizations of Invasive and Noninvasive Somatotroph PitNETs
Authors: Chen Meiping , Duan Lian , Sun Wei , Guo Zhengguang , Miao Hui , Yu Na , Yang Shengmin , Wang Linjie , Gong Fengying , Yao Yong , Zhu Huijuan
Published: June 2023

Introduction: Somatotroph pituitary neuroendocrine tumours (PitNETs) are characterized by complex and variable biological behaviours with unpredictable patterns of growth and invasiveness. The molecular mechanisms and reliable predictors of biological markers of invasiveness remain unknown. Methods: Seventy-two acromegaly patients were consecutively enrolled. Data-independent acquisition-based proteomics and ingenuity pathway analysis were conducted between invasive and noninvasive somatotroph PitNETs. The expression of selected biomarkers was verified in PitNET tissue, and its correlation with various clinical indicators and outcomes of these tumours was assessed. The invasive phenotypes of GH3 cells were validated in vitro. Results: Patients with invasive somatotroph PitNETs were significantly younger at onset and diagnosis, with significantly higher secretion and faster growth and a lower long-term biochemical response rate than patients with noninvasive somatotroph PitNETs. Proteomic data were evaluated in a consecutively collected sample of 19 (10 invasive and 9 noninvasive somatotroph PitNETs) tumours and indicated a distinct proteomic pattern. The enriched and important pathways included IL-4, PDGF, PTEN, VEGF, PI3K/AKT, FAK, and other pathways that were significantly associated with tumour proliferation, migration, and invasion. High cathepsin Z (CTSZ) expression was found in invasive somatotroph PitNETs and significantly positively correlated with parameters of tumour invasion and growth. In Ctsz-overexpressing GH3 cells, cell proliferation, invasion, and migration were consequently increased. Conclusion: It is more difficult for patients with invasive somatotroph PitNETs to achieve remission than those with noninvasive somatotroph PitNETs, and proteomic data analysis has revealed the high expression of CTSZ as a contributing factor to invasive transformation and poor prognosis in somatotroph PitNETs for the first time.
Isoflurane Rapidly Modifies Synaptic and Cytoskeletal Phosphoproteomes of the Supraoptic Nucleus of the Hypothalamus and the Cortex
Authors: Bárez-López Soledad , Gadd George J. , Pauža Audrys G. , Murphy David , Greenwood Michael P.
Published: June 2023

Introduction: Despite the widespread use of general anaesthetics, the mechanisms mediating their effects are still not understood. Although suppressed in most parts of the brain, neuronal activity, as measured by FOS activation, is increased in the hypothalamic supraoptic nucleus (SON) by numerous general anaesthetics, and evidence points to this brain region being involved in the induction of general anaesthesia (GA) and natural sleep. Posttranslational modifications of proteins, including changes in phosphorylation, enable fast modulation of protein function which could be underlying the rapid effects of GA. In order to identify potential phosphorylation events in the brain-mediating GA effects, we have explored the phosphoproteome responses in the rat SON and compared these to cingulate cortex (CC) which displays no FOS activation in response to general anaesthetics. Methods: Adult Sprague-Dawley rats were treated with isoflurane for 15 min. Proteins from the CC and SON were extracted and processed for nano-LC mass spectrometry (LC-MS/MS). Phosphoproteomic determinations were performed by LC-MS/MS. Results: We found many changes in the phosphoproteomes of both the CC and SON in response to 15 min of isoflurane exposure. Pathway analysis indicated that proteins undergoing phosphorylation adaptations are involved in cytoskeleton remodelling and synaptic signalling events. Importantly, changes in protein phosphorylation appeared to be brain region specific suggesting that differential phosphorylation adaptations might underlie the different neuronal activity responses to GA between the CC and SON. Conclusion: In summary, these data suggest that rapid posttranslational modifications in proteins involved in cytoskeleton remodelling and synaptic signalling events might mediate the central mechanisms mediating GA.
Oncogeriatric Developments
Authors: Extermann Martine , Al-Jumayli Mohammed , Sam Christine , Kish Julie A.
Published: June 2023

Cancer is a disease of aging and is rapidly becoming the number one cause of mortality in older people. Over their lifetime, one in two men and one in three women will develop a cancer, with half of the risk being beyond the age of seventy. Therefore, cancer is a problem frequently encountered by geriatricians. In this article, we review a few recent progresses that will be of interest to the geriatric community. First, we now have robust evidence that a comprehensive geriatric assessment and management change outcomes in older cancer patients, notably allowing decreased treatment toxicity, better treatment completion, and increased functional outcomes. In gastrointestinal cancers and breast cancer, several recent studies have addressed when treatment intensity can be decreased, and when it cannot. New treatments for acute myeloid leukemia are finally beginning to improve outcomes for older patients and such patients should be referred to oncologists for management. In prostate cancer, new imaging techniques (e.g., PSMA scan) and treatment options can allow better treatment targeting and spare some hormonal and chemotherapy toxicity. Finally, we review recent public policy efforts to address the epidemiologic wave of cancer in older patients on a global scale.
Olinda quer cantar: expressões carnavalescas de uma cidade sem carnaval
Authors: Mello Fernanda de Carvalho Azevedo
Published: June 2023

Em Olinda (PE), durante o mês de momo, as foliãs tomam as ruas com muito glitter, brilho e corpos à mostra. Não há um centímetro sequer de distância entre ninguém e é muito comum observarmos, de alguma forma, como os apaixonados beijos rápidos que são trocados entre desconhecidas conseguem diminuir ainda mais a lonjura. A montagem desse trabalho tem como duplo objetivo mostrar as ruas do trajeto imaginado para o carnaval de Olinda no ano de 2022; e, a partir da ausência de corpos e da fanfarra, cancelada pelo segundo ano consecutivo pela prefeitura da cidade, refletir sobre os sentidos da festa para a cidade. Em outras palavras, o presente trabalho expõe os registros, através de fotografias, do não-carnaval, do não-beijo, da não-multidão, assim como as resistências e insistências em manter acesa a chama da folia, por meio de fotografias do percurso evocado pela memória de carnavais passados.
Abstract 03: Early Post-Cardiac Arrest Blood Pressure Thresholds Associated with Outcomes: A Secondary Analysis of the ICU-Resuscitation Trial
Authors: Gardner Monique M , Hehir David , Reeder Ron , Berg Robert A , Fink Ericka L , Friess Stuart , Graham Kathryn , Harding Monica L , Morgan Ryan W , Nadkarni Vinay M , Wolfe Heather A , Sutton Robert M , Topjian Alexis A
Published: June 2023

Introduction:
Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that maintaining BPs greater than the newly identified post-arrest systolic and diastolic BP thresholds early after IHCA are associated with higher rates of survival to hospital discharge.

Methods:
We performed a secondary analysis of prospectively collected BP data from the first six hours following index IHCA events enrolled in the
ICU-Resuscitation
trial. The lowest documented systolic BP (SBP) and diastolic BP (DBP) 0-6 hours post-arrest were categorized by age-based percentiles. After controlling for illness category and presence of pre-arrest hypotension (systolic or mean arterial blood pressure <5
th
percentile-for-age or vasoactive/inotropic requirement), cubic spline analyses were generated exploring the association of lowest post-arrest SBP and DBP with survival to hospital discharge and survival with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1-3 or no change from baseline). Clinical judgement and visual assessment of the spline curves were used to identify BP thresholds. Logistic regression models accounting for illness category and pre-arrest hypotension examined the associations of these thresholds with outcomes.

Results:
Among 693 index events with 0-6 hour post-arrest BP data, identified thresholds were: SBP >10
th
percentile and DBP >50
th
percentile for age. Fifty-one percent (n=352) of subjects had lowest SBP above threshold, 50% (n=346) had DBP above threshold. SBP and DBP above thresholds were each associated with survival to hospital discharge (SBP aRR 1.21; 95% CI 1.10, 1.33; DBP aRR 1.23; 1.12, 1.34) and favorable neurologic outcome (SBP aRR 1.22; 1.10, 1.35; DBP aRR 1.27; 1.15, 1.40) (all p<0.001).

Conclusions:
These data establish that SBP >10
th
percentile-for-age and DBP >50
th
percentile-for-age during the first 6 hours post-arrest were associated with higher rates of survival to hospital discharge and favorable neurologic outcome.
Abstract 07: Percutaneous Ventricular Assist Devices In Refractory Cardiac Arrest: The Role Of Chest Compressions
Authors: Gottula Adam L , McCracken Brendan , Nakashima Takahiro , Greer Nicholas , Cramer Traci , Sutton Nadia R , Ward Kevin R , Neumar Robert H , Hsu Cindy H , Tiba Mohamad H
Published: June 2023

Background:
Recent studies describe an emerging role for percutaneous ventricular assist devices (pVADs, Impella CP®, Abiomed) as rescue therapy for refractory cardiac arrest (CA). We hypothesized that continuing mechanical chest compressions (mCPR) after initiation of pVAD would improve hemodynamics by decompressing the right ventricle and augmenting pulmonary blood flow and left ventricular filling. We performed a pilot study to test this hypothesis using a swine model of prolonged cardiac arrest.

Methods:
Eight Yorkshire swine, anesthetized, intubated and instrumented for hemodynamic monitoring, were subjected to untreated ventricular fibrillation for 5.75 (SD 2.90) minutes followed by mCPR for a mean of 20.00 (SD 5.0) minutes before initiation of pVAD (Table 1). After pVAD initiation mCPR was stopped (n=4) or continued (n=4). Defibrillation was attempted 4, 8 and 12 minutes after initiating pVAD circulatory support, except for the first pilot animal where it was attempted at 2 minutes. The animals that achieved return of spontaneous heartbeat (ROSHB) were maintained on pVAD support for four additional hours.

Results:
There was no difference in the rate of ROSHB between groups (Table 1). The pVAD + mCPR group had significantly higher pVAD flow prior to ROSHB at four- and twelve-minutes after pVAD initiation, and significantly higher end tidal CO
2
(PetCO
2
) at four- and eight-minutes after pVAD initiation, when compared with the pVAD alone group (Table 1). There was a trend toward higher carotid artery flow prior to ROSHB in the pVAD + mCPR group compared with the pVAD alone group after pVAD initiation, but the difference was not statistically significant (Table 1).

Conclusion:
The addition of mCPR to pVAD support during cardiac arrest may generate higher pVAD flow and cardiac output prior to ROSHB compared to pVAD alone. Further studies are needed to determine if this approach improves other hemodynamic parameters or outcomes after prolonged cardiac arrest.
Abstract 10022: Marijuana Smoke or Vaporizer Aerosol Impairs Endothelial Function Regardless of Drying Regimen or Cannabinoid Profile
Authors: Rao Poonam , Goyal Natasha , Derakhshandeh Ronak , Havel Christopher , Jacob III Peyton , Springer Matthew L
Published: June 2023

Introduction:
Marijuana smoke and vaporizer aerosol adversely affect the cardiovascular system. Most US marijuana research has used research marijuana from the University of Mississippi supplied through the National Institute on Drug Abuse (NIDA). NIDA marijuana is dried at high temperature with maximum of 10% THC, but real-world material is gently dried and is ~20% THC. Because NIDA marijuana differs from what is currently used by the public in terms of THC content and drying regimen, skepticism regarding relevance to the real world is limiting the impact of results obtained from this material. Here, we validated the use of NIDA research marijuana in the study of vascular effects of cannabis.

Hypothesis:
Exposure to marijuana smoke or vaporizer aerosol, regardless of the cannabinoid profile or drying regimen, impairs endothelial function.

Methods:
We exposed groups of rats (n=8) to smoke or Volcano vaporizer aerosol from materials obtained from U Miss (Placebo (<0.01% THC hot), 4.2% THC hot and gentle dried pair, 10% THC hot), from Biopharmaceutical Research Company (Castroville, CA) (20% THC gentle dried), commercial hemp with negligible THC content, and clean air. Exposure was pulsatile, 5s/min over 5 mins. Endothelial function was measured as flow-mediated dilation (FMD) and pre- vs. post-exposure FMD (10 and 30 mins after end of exposure) differences were analyzed.

Results:
We observed significant impairment of FMD after exposure to pulsatile smoke from marijuana with varied cannabinoid profiles and drying regimens (p≤.006), with no effect from clean air (p=.13). No significant recovery of FMD was observed in any group 30 mins after marijuana smoke exposure (p≥.32). Pulsatile exposure to aerosol generated from the same materials impaired FMD in all groups (p≤.001) except clean air (p=.23).

Conclusions:
Acute exposure to marijuana smoke/aerosol impairs endothelial function regardless of the drying regimens or the cannabinoid profile of the marijuana product.
Abstract 10042: Mental Health Conditions In Congenital Heart Disease: A Danish Population Based Cohort Study
Authors: Miles Kimberley , Kasparian Nadine A , Farkas Dora , Laugesen Kristina , Sorensen Henrik Toft , Madsen Nicolas
Published: June 2023

Introduction:
We aimed to investigate mental health condition development by 18 years of age among children with congenital heart disease (CHD).

Methods:
Using Danish health registry data, all children with CHD (n=17,153) were identified from 1996-2017. Mental health conditions were identified using hospital-based diagnoses, medication prescription, and treatment codes during the study period (1996-2019). Children with mental health conditions diagnosed prior to CHD were excluded (n=670, 3.9%). Comparison cohorts included the general population (matched 10:1 for age and sex), siblings of children with CHD, and children with non-CHD major congenital anomalies (MCAs) identified via EUROCAT codes and matched 3:1 for age and sex. Incidence rates per 1,000 person-years, cumulative incidence per 100 persons, and adjusted hazard ratios (aHR [95% CI]) were calculated and stratified by age-based follow-up periods, CHD severity, and sex.

Results:
The CHD cohort had higher overall rates of mental health conditions than their siblings (aHR 1.41 [1.30-1.52]) and the general population (aHR 1.66 [1.60-1.72]), and when stratified by age periods, CHD severity, and sex (Table 1). The cumulative incidence in the CHD cohort was 35.7% compared with 25.6%, 26.6%, and 35.1% for the general population, sibling, and MCA cohorts, respectively (Figure 1).

Conclusions:
This population-based cohort study shows that children with CHD are more likely to be diagnosed with mental health conditions by age 18 years than their siblings and the general population, but not children with non-CHD MCAs. Investigation to determine relevant clinical, sociodemographic, and family risk factors is ongoing.
Abstract 10043: Plasma Metabolite Dimethylguanidino Valeric Acid and Risk of Incident Coronary Heart Disease Among Women
Authors: Heianza Yoriko , Wang Xuan , Tiwari Saumya , Watrous Jeramie , Rexrode Kathryn M , Sun Qi , Jain Mohit , Manson Joann E , Qi Lu
Published: June 2023

Introduction:
Circulating dimethylguanidino valeric acid (DMGV) has been related to visceral adiposity and unhealthy obesogenic lifestyle factors, and recently emerged as an early marker of cardiovascular disease.

Hypothesis:
We tested whether circulating DMGV was associated with the risk of coronary heart disease (CHD) among women. We also investigated obesogenic diet/lifestyle factors and biomarkers associated with higher DMGV levels.

Methods:
This prospective nested case-control study included 1518 women (759 incident cases of fatal CHD and nonfatal myocardial infarction and 759 controls) from the Nurses’ Health Study (NHS). Incident cases of CHD were identified over 10-14 years of follow-up time. Obesogenic lifestyle factors (such as physical inactivity and dietary intakes), adiposity, and cardiometabolic abnormalities (hypertension, dyslipidemia, and diabetes) were assessed in the NHS and the Women's Lifestyle Validation Study (WLVS; n=723).

Results:
In the NHS, higher plasma DMGV levels were related to greater risk of CHD (P for linear relation=0.007) after controlling for demographic factors, family history of myocardial infarction, and postmenopausal hormone. Compared with women in the lowest quartile of DMGV levels, those in the highest quartile had a relative risk (RR) of 1.70 (95% CI: 1.25, 2.31) for CHD. The RR in the highest quartile was attenuated after controlling for obesogenic factors and adiposity. Obesogenic diet/lifestyle factors, adiposity, altered adipokine levels, and cardiometabolic abnormalities were significant factors related to higher plasma DMGV levels in the NHS and WLVS.

Conclusions:
Circulating DMGV may be a significant metabolite related to obesogenic diet quality, lifestyles, and cardiometabolic abnormalities among women. High DMGV levels were associated with an increased risk of incident CHD among women.
Abstract 10045: Higher Renal Vascular Resistance is Associated With Greater Body Mass Index in Children
Authors: Harada Kenji , Harada Yukiko
Published: June 2023

Background:
Obesity is associated with increased risk for cardiovascular and renal diseases, however, there has been little focus on renal vascular function. The purpose of this study is to assess renal vascular flow regulation and investigate their relation to cardiovascular risk factors in obese children.

Methods:
Noninvasive ultrasonographic measurements were made in 108 overweight/obese children aged 7 to 13 years (body mass index 18 to 33kg/m
2
). Using color Doppler sonography, peak systolic (PSV), end-diastolic (EDV), and average peak flow (APV) velocities of renal artery were measured. Pulsatility index as a parameter of vascular resistance was calculated. Pulsatility index was defined as (PSV-EDV)/APV. Quantitative B-mode ultrasound scans were used to measure intima-media thickness and diameters of the common carotid artery. Plasma lipid concentrations, uric acid, homeostasis model assessment of insulin resistance, and high sensitivity C-reactive protein were assessed in the obese children.

Results:
Compared with overweight children with body mass index <25 kg/m
2
, pulsatility index in obese children with body mass index≥25 kg/m
2
was significantly higher (1.24 ±0.13 vs. 1.13 ±0.14 cm/sec, p < 0.01), because APV and EDV were significantly lower (35 ±3 vs. 38 ±7 cm/sec and 21± 3 vs. 25 ±5 cm/sec, p <0.05, respectively), although PSV was not significantly different. Pulsatility index correlated significantly with body mass index (r =0.58, p < 0.01), insulin (r = 0.24, p < 0.05), homeostasis model assessment of insulin resistance (r =0.25, p < 0.01), triglycerides (r = 0.26, p < 0.01), uric acid (r = 0.22, p < 0.05), systolic blood pressure (r = 0.31, p < 0.01), and carotid intima-media thickness (r = 0.36, p<0.01). Renal blood flow velocities did not correlate with high sensitivity C-reactive protein.

Conclusions:
The present study indicates that obesity can adversely affect renal vascular flow and resistance in children. Obesity-related insulin resistance may be a main risk factor for renal vascular flow changes. Obesity not only is a risk factor for later cardiovascular disease, but also is associated with significant impairment of renal arterial flow dynamics.
Abstract 10046: Type I Kounis Syndrome Induced by Echocardiography Contrast Agent Sulfur Hexafluoride
Authors: Nomigolzar Soroush , Khederzadeh Sara , Baggett Alisha , Vallabhaneni Meghana , Younes Ahmed
Published: June 2023

Background:
Acute coronary syndrome (ACS) and anaphylaxis are both medical emergencies that require prompt intervention. ACS occurring in the setting of hypersensitivity reaction, presumably secondary to inflammatory mediator release, is called Kounis Syndrome (KS). There are three subtypes of KS: Type I (clean coronary arteries), type II (pre-existing CAD), and type III (in-stent restenosis). Allergens such as medications, insect bites, foods, and contrast media have been found to result in KS. However, to our knowledge, there is only one reported case of KS induced by sulfur hexafluoride (echocardiography enhancing agent), which was categorized as KS type III. Here, we report a case of allergic reaction to this agent causing KS type I.

Case Presentation:
A 74-year-old woman with a history of anaphylaxis (to penicillin and cephalosporins), provoked pulmonary embolism (PE), hypertension, and hypothyroidism presented with dyspnea and was found to have bilateral subacute PE on CTA chest. She was started on a heparin drip and subsequently underwent echocardiography which showed normal RV size, systolic function, and LVEF with no wall motion abnormalities. However, shortly after receiving the sulfur hexafluoride agent, the patient was noted to be somnolent, hypotensive, and diaphoretic. Allergic reaction to the contrast was suspected and she received methylprednisolone, diphenhydramine, and famotidine. STAT EKG revealed ST elevation in inferior leads and the patient subsequently underwent cardiac catheterization which showed no evidence of significant obstructive disease. The patient remained hemodynamically stable throughout the remainder of her admission and was transitioned from heparin drip to apixaban prior to discharge.

Discussion:
In conclusion, allergic reactions could lead to an acute coronary syndrome with non-obstructive coronaries. As a result, it is crucial to consider KS as a differential.

Figure 1 - ST elevations in the inferior leads