bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study EV-104: Phase 1 study of intravesical enfortumab vedotin for treatment of patients with non-muscle invasive bladder cancer (NMIBC)—Trial in progress.
Authors: Kamat Ashish M. , Steinberg Gary D. , Inman Brant Allen , Kates Max R. , Uchio Edward M. , Porten Sima P. , Roupret Morgan , Redorta Joan , Catto James W.F. , Kulkarni Girish S. , Powles Thomas , Tyson Mark , Haas Gabriel P. , Yu Yao , Birrenkott Matthew , Lotan Yair 
Published: March 2023

TPS582 Background: The majority of patients with bladder cancer present with non-muscle invasive disease (Chang 2016; Woldu 2017; Kates 2020; Li 2020). The standard of care for treatment of high risk NMIBC involves transurethral resection of the bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guerin (BCG) or chemotherapy. Although the response rate to BCG therapy is high, many patients recur within 1–5 years (Matulay JU 2021). For patients who have BCG unresponsive disease after adequate course of BCG, there are limited options. While radical cystectomy (RC) is still considered the standard of care, most patients are reluctant to undergo RC and their options are limited to intravesical chemotherapy or pembrolizumab. Enfortumab vedotin (EV) is an antibody-drug conjugate directed to Nectin-4, which is highly expressed in bladder tumors. In EV-301, a phase 3 study, EV showed an OS benefit vs chemotherapy in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who had previously received platinum-based therapy and a PD-1 or PD-L1 inhibitor (Powles NEJM 2021). Based on its demonstrated benefit in la/mUC, EV is currently being evaluated in earlier UC settings. The purpose of this study is to investigate the intravesical administration of EV for patients with NMIBC. Methods: EV-104 (NCT05014139) is a phase 1, open-label, multicenter, dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, PK, and antitumor activity of intravesical EV in adults with high-risk BCG-unresponsive NMIBC (carcinoma in situ with or without papillary disease) who are ineligible for or refuse RC. The dose escalation part of the trial aims to identify the maximum tolerated dose (MTD) and/or recommended dose of intravesical EV. The dose expansion part will evaluate patients at the MTD or recommended dose and further characterize safety and antitumor activity of intravesical EV. The study treatment regimen will include an induction phase, where patients will receive intravesical EV weekly for 6 weeks followed by monthly maintenance for a total of 9 additional EV doses. Patients will be assessed for response every 3 months by cystoscopy and urine cytology, while on study. Safety and antitumor activity endpoints will be summarized using descriptive statistics. The study is currently enrolling in the US with additional sites planned in Canada and the EU. Clinical trial information: NCT05014139 .
TROPHU-U-01 cohort 5: Evaluation of maintenance sacituzumab govitecan (SG) plus zimberelimab (ZIM), ZIM, or avelumab in cisplatin-eligible patients (pts) with unresectable or metastatic urothelial cancer (mUC).
Authors: Powles Thomas , Necchi Andrea , Duran Ignacio , Loriot Yohann , Ramamurthy Chethan , Recio-Boiles Alejandro , Sweis Randy F. , Bedke Jens , Tonelli Julia , Sierecki Mitch , Grivas Petros , Barthelemy Philippe 
Published: March 2023

TPS598 Background: SG is an antibody-drug conjugate composed of an anti-trophoblast cell-surface antigen-2 (Trop-2) antibody coupled to a topoisomerase-I inhibitor, SN-38, via a hydrolyzable linker. In Cohort 1 of the phase 2 TROPHY-U-01 trial, SG monotherapy resulted in a 27% objective response rate (ORR) and median overall survival (OS) of 10.9 months with an overall manageable toxicity profile in pts with locally advanced or mUC who previously received platinum-based therapy and a checkpoint inhibitor (CPI; Tagawa S, et al. J Clin Oncol. 2021). These results led to accelerated FDA approval of SG in this population. The CPI ZIM is a fully human IgG4 monoclonal antibody targeting PD-1. CPIs are active in mUC, including avelumab that is FDA-approved as switch maintenance therapy for locally advanced or mUC that has not progressed with first-line platinum-based chemotherapy. Cohort 5 of the TROPHY-U-01 trial will evaluate the safety, tolerability, and efficacy of SG + ZIM vs ZIM alone vs avelumab as switch maintenance in pts with mUC who have received gemcitabine (GEM)/cisplatin without progressive disease (PD). Methods: TROPHY-U-01 (NCT03547973) is a multicohort, open-label, global, phase 2 trial. Cohort 5 includes pts who have not progressed after completion of 4-6 cycles of GEM/cisplatin. Key eligibility requirements include ≥18 y; ECOG PS 0-1; available tissue for biomarker testing; adequate blood counts without transfusion or growth factor within 2 weeks of study drug initiation; creatinine clearance ≥30 mL/min. A safety lead-in of 6-8 pts will be conducted, where pts will be treated with SG 10 mg/kg IV on D1 and D8 of a 21-D cycle plus ZIM 360 mg IV q3wk on a 21-D cycle. On safety lead-in, if SG + ZIM is deemed safe, pts will be randomized 1:1:1. Those in Arm 1 will receive SG 10 mg/kg IV on D1 and D8 of a 21-D cycle followed by ZIM 360 mg IV, q3wk (D1 of a 21-D cycle). Pts in Arm 2 will receive avelumab 800 mg IV q2wk (D1 of a 14-D cycle). Pts in Arm 3 will receive ZIM 360 mg IV q3wk. All pts will continue treatment until PD, unacceptable toxicity, or loss of clinical benefit. The primary endpoint is progression-free survival based on central review by RECIST 1.1 criteria. Secondary endpoints include OS (all arms), safety/tolerability of SG in combination with ZIM (Arm 1). Cohort 5 aims to enroll an estimated 158 pts. A sample size of 50 pts per randomized arm is determined based on clinical consideration for exploring the activity of anticancer agents. Clinical trial information: NCT03547973 .
Phase 3 LITESPARK-022: Pembrolizumab (pembro) plus hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan as adjuvant treatment for clear cell renal cell carcinoma (ccRCC).
Authors: Choueiri Toni K. , Bedke Jens , Karam Jose A. , McKay Rana R. , Motzer Robert J. , Pal Sumanta Monty , Suárez Cristina , Uzzo Robert , Liu Hong , Burgents Joseph E. , Sharma Manish , Powles Thomas 
Published: March 2023

TPS748 Background: Treatment with the PD-1 inhibitor pembro produced significant improvement in disease-free survival after surgery for patients (pts) with ccRCC in the phase 3 KEYNOTE-564 trial. Based on these results, pembro was approved by the US Food and Drug Administration and the European Medicines Agency for adjuvant treatment of pts with RCC at increased risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. Despite advances in the treatment landscape for RCC, more effective adjuvant treatment strategies are needed for pts at risk of recurrence after surgery. HIF-2α is an established oncogenic driver in ccRCC, and promising antitumor activity in advanced ccRCC and von Hippel-Lindau disease–associated RCC has been demonstrated with the HIF-2α inhibitor belzutifan. The multicenter, double-blind, randomized, phase 3 LITESPARK-022 study (NCT05239728) will evaluate the efficacy and safety of pembro plus belzutifan compared with placebo plus pembro as adjuvant treatment following nephrectomy in pts with ccRCC. Methods: Key eligibility criteria include adults with histologically or cytologically confirmed intermediate-high risk, high risk, or M1 with no evidence of disease (NED) RCC with a clear cell component; pts with no prior systemic therapy, nephrectomy, and/or metastasectomy ≤12 weeks before randomization; and pts who are tumor free per computed tomography/magnetic resonance imaging. Approximately 1600 pts will be randomly assigned to receive belzutifan 120 mg orally once daily plus pembro 400 mg intravenously (IV) every 6 weeks (Q6W) for ≤9 administrations (~54 weeks) or oral placebo plus pembro 400 mg IV Q6W for ≤9 administrations (~54 weeks) or until verified disease recurrence by blinded independent central review, start of new anticancer treatment, unacceptable toxicity, or decision to withdraw. Stratification factors are tumor grade (1 or 2 vs 3 or 4) and risk type (intermediate-high risk versus high risk versus M1 NED). Pts will be radiologically evaluated Q12W from randomization through year 2, Q16W in years 3 to 5, and Q24W in years 6 and beyond. Adverse events will be monitored throughout the study and for 30 days following cessation of study treatment (90 days for serious adverse events). The primary end point is disease-free survival. Secondary end points include overall survival, safety, disease recurrence–specific survival, and patient-reported outcomes. Recruitment is underway in Asia, Australia, Europe, North America, and South America. © 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved. Clinical trial information: NCT05239728 .
Adipose-derived Mesenchymal Stem Cells Therapy as a new Treatment Option for Diabetes Mellitus
Authors: Mikłosz Agnieszka , Chabowski Adrian 
Published: March 2023

AbstractThe worldwide increase in the prevalence of diabetes mellitus has raised the demand for new therapeutic strategies targeting diabetic symptoms and its chronic complications. Among different treatment options for diabetes, adipose-derived mesenchymal stem cells (ADMSCs) therapy attract the most attention. The therapeutic effects of ADMSCs are based primarily on their paracrine release of immunomodulatory, anti-inflammatory, and trophic factors. Animal models of diabetes as well as human clinical trials have shown that ADMSCs can effectively facilitate endogenous β cell regeneration, preserve residual β cell mass, reduce islet graft rejection, regulate the immune system, and ultimately improve insulin sensitivity or ameliorate insulin resistance in peripheral tissues. Nevertheless, transplantation of mesenchymal stem cells is associated with certain risks; therefore recently much attention has been devoted to ADMSCs derivatives, such as exosomes or conditioned media, as therapeutic agents for the treatment of diabetes. Compared to ADMSCs, cell-free therapy has even better therapeutic potential. This narrative review summarizes recent outcomes and molecular mechanisms of ADMSCs action in the treatment for both type 1 DM and type 2 DM, as well as shows their feasibility, benefits, and current limitations.
Expression of Neurotensin and Its Receptors Along the Intestinal Tract in Type 2 Diabetes Patients and Healthy Controls
Authors: Gilliam-Vigh Hannah , Jorsal Tina , Nielsen Sophie W , Forman Julie L , Pedersen Jens , Poulsen Steen S , Vilsbøll Tina , Knop Filip K 
Published: March 2023

Abstract

Context
Enteroendocrine N cells secrete neurotensin (NTS). NTS reduces food intake in rodents and may increase insulin release. In humans, postprandial NTS responses increase following Roux-en-Y gastric bypass, associating the hormone with the glucose- and body weight-lowering effects of these procedures.

Objective
We looked at N cell density and mucosal messenger RNA (mRNA) expression profiles of NTS and NTS receptors in type 2 diabetes (T2D) patients and healthy controls.

Methods
Using double-balloon enteroscopy, 12 patients with T2D and 12 sex-, age-, and body mass index–matched healthy controls had mucosa biopsies taken from the entire length of the small intestine (at 30-cm intervals) and from 7 anatomically well-defined locations in the large intestine. Biopsies were analyzed using immunohistochemistry and mRNA sequencing.

Results
N cell density and NTS mRNA expression gradually increased from the duodenum to the ileum, while negligible NTS-positive cells and NTS mRNA expression were observed in the large intestine. NTS receptor 1 and 2 mRNA expression were not detected, but sortilin, a single-pass transmembrane neuropeptide receptor of which NTS also is a ligand, was uniformly expressed in the intestines. Patients with T2D exhibited lower levels of NTS-positive cells and mRNA expression than healthy controls, but this was not statistically significant after adjusting for multiple testing.

Conclusion
This unique intestinal mapping of N cell density and NTS expression shows increasing levels from the small intestine's proximal to distal end (without differences between patients with T2D and healthy controls), while negligible N-cells and NTS mRNA expression were observed in the large intestine. Sortilin was expressed throughout the intestines in both groups; no NTS receptor 1 or 2 mRNA expression were detected.
An Eightfold Taxonomy of Harmonic Progressions, and Its Application to Triads Related by Major Third and Their Significance in Recent Screen Music
Authors: Murphy Scott 
Published: March 2023

Abstract
A hybridization of two recent innovations in music theory—a focus on the progression of two triads as a unitary analytical object, and a component-wise formation of a set of equivalence classes—brings together under one conceptual and labeling system eight different approaches to the classification of harmonic progression. A holistic adoption of these eight approaches, each already preexisting within music scholarship in some partial or complete form, affords precise and gradated statements regarding the styles, associative meanings, and hermeneutics of music for recent multimedia. To that end, this article pays particular attention to progressions of like-moded triads a major third apart, as demonstrated through analyses of music for the television series Bridgerton and the movie Ex Machina.
Synthesis of 11C-Radiolabeled Eribulin as a Companion Diagnostics PET Tracer for Brain Glioblastoma
Authors: Niwa Takashi , Tahara Tsuyoshi , Chase Charles E , Fang Francis G , Nakaoka Takayoshi , Irie Satsuki , Hayashinaka Emi , Wada Yasuhiro , Mukai Hidefumi , Masutomi Kenkichi , Watanabe Yasuyoshi , Cui Yilong , Hosoya Takamitsu 
Published: March 2023

Abstract
The successful 11C-radiolabeling of eribulin, an analog of the marine natural product halichondrin B, and an approved anticancer drug for the treatment of breast cancer and liposarcoma, is reported. A rapid sequence involving a nitroaldol reaction with [11C]nitromethane and subsequent reduction of the nitro group enabled the introduction of a carbon-11 atom at the C35-position of eribulin. Optimization of the reaction and purification conditions led to a reproducible synthetic method for [35-11C]eribulin with 248 ± 104 MBq of radioactivity, 88.2 ± 5.8% radiochemical purity, and 132 ± 32 MBq/nmol molar activity. The total synthetic time was 38.0 ± 1.3 min (n = 12). PET imaging using mice bearing brain tumors revealed a specific accumulation of [35-11C]eribulin in tumors without any significant metabolic changes. These results indicate the applicability of [35-11C]eribulin for the quantitative measurement of eribulin migration into tumor tissue, which would be beneficial for exploring the application of eribulin for glioblastoma treatment and estimating the appropriate dosage for each patient.
After-Sales Services During an Asset’s Lifetime: Collaborative Planning of System Upgrades
Authors: Sloothaak Fiona , Akçay Alp , van Houtum Geert-Jan , van der Heijden Matthieu 
Published: March 2023

We consider a physical asset consisting of complex systems, where the systems may require upgrades during the lifetime of the asset. In practice, the asset owner and system supplier can make the upgrade decisions together, requiring a decision-support model that can be jointly used to optimize the total benefit for both parties. Motivated by a real-life use case including an asset owner and a system supplier, we build a continuous-time model to optimize the upgrade decisions of a system during the fixed lifetime of the asset. In our model, we capture the key critical factors that drive the upgrade decisions: increasing functionality requirements due to evolving technology, age-dependent maintenance costs, a predetermined overhaul plan of the asset, and the lifetime of the asset. A system upgrade is less costly if it is executed jointly with an asset overhaul. We first analyze the case with no additional cost of upgrading outside an overhaul. We analytically characterize the structure of the optimal upgrade policy under various realistic assumptions that lead to different types of cost functions. We then use these results as a building block to characterize the optimal policy for a generalized cost function. When there is a penalty for upgrading outside an overhaul moment, we propose a dynamic programming approach that efficiently determines the optimal upgrade policy by using our analytical results. We also prove that as this penalty increases, the optimal policy can only change to one where the number of upgrades not jointly executed with overhauls is reduced. However, the optimal number of upgrades is a nonincreasing function of this penalty. Also, surprisingly, more overhauls may lead to a smaller number of upgrades under the optimal policy. Funding: This publication is part of the project “Maritime Remote Control Tower for Service Logistics Innovation (MARCONI)” (project 439.18.309) of the research program “Integrator-Logistics as Enabler for Enhancing Society,” which is (partly) financed by the Dutch Research Council (NWO).
Associated factors with adherence to preventive behaviors related to COVID-19 among medical students in the university of Monastir, Tunisia
Authors: Zemni Imen , Zemni Kaouthar , Gara Amal , Maatouk Amani , Ben Fredj Manel , Abroug Hela , Kacem Meriem , Benasrallah Cyrine , Dhouib Wafa , Bouanene Ines , Belguith Sriha Asma 
Published: March 2023

Introduction
Medical students should act as a model for the community in terms of compliance with preventive practices toward COVID-19. The aim of this study was to assess adherence to preventive behaviors related to COVID-19 among medical students and to identify its associated factors.

Population and methods
We conducted a cross-sectional survey in October 2020 in the faculty of medicine of Monastir. We included a representative sample of medical students during registration days for the 2020–2021 academic year. The data were collected through a self-administered anonymous questionnaire. Eleven items related to preventive practices against COVID-19 were assessed (respiratory hygiene practices (Six Item), hand hygiene practices (Three Items) and social distancing (two items)). Items were evaluated using a Likert scale of five points (from 0: (Never) to 4: (Always)). The score obtained from the sum of these items allowed to classify students into two categories: “Good compliance” if the score was ≥ 80% and “Poor compliance” if the score was less than 80%. Scores were compared according to the study population characteristics. Multivariate analysis was used to identify associated factors with good practices. The threshold of statistical significance was set at p < 0.05.

Results
We included 678 medical students. The average age was 21.76 (SD = 1.89 years) with a sex ratio of 0.40. The protection measures most respected by the participants were related to the respiratory hygiene: correct coverage of the nose and mouth with the mask (80%), wearing masks regardless of the presence of symptoms (73.3%) and coverage of the mouth during coughing or sneezing (76.6%). Adherence to hand hygiene measures ranged from 51.4% to 66.3%. The least respected measures were related to social distancing: distancing of at least one meter from others (31.2%) and avoiding crowded places (42.5%). An overall score ≥ 80% was obtained among 61.5% of students. Referring to multivariate analysis, variables that positively affected the overall score of preventive measures related to COVID-19 were the female sex and living alone, with Beta coefficients of 3.82 and 1.37 respectively. The perceived level of stress, E-cigarette and Chicha consumption negatively affected the score with Beta coefficients of (-0.13), (-5.11) and (-2.33) respectively.

Conclusion
The level of adherence to good practice among medical students was overall moderate. Awareness programs would be needed in this population, especially for men and those who smoke and vape.
Naringin promotes positive inotropism in atrial tissue through β-AR/PKA-dependent pathway
Authors: Santos Leonardo Rodrigues dos , Souza Diego Santos , Mesquita Thássio Ricardo Ribeiro , Dantas Cácia Oliveira , Araujo Andreza Melo , Cerqueira Sandra Valéria Santos de , Santos Vinicius Cisneiros de Oliveira , Mota Karina Oliveira , Vasconcelos Carla Maria Lins de 
Published: March 2023

Naringin is a flavonoid glycoside found in citrus fruits and grapes with a wide range of therapeutic actions. We aimed to study the inotropic effect of naringin on rat-isolated atria, dissecting intracellular mechanisms involved in this response. Concentration-response curves of naringin (0.003-6 mM) were obtained before and after pre-incubation with selective antagonists. Our results showed that naringin presented a biphasic inotropic response, with a positive inotropic effect at low and middle concentrations (0.003-2.0 mM), and a negative inotropic effect at high concentrations (above 3 mM). Pre-incubation with propranolol or atenolol (β-adrenergic receptors antagonists, β-AR), H89 (protein kinase-A inhibitor, PKA), nifedipine (L-type Ca2+ channel blocker), or ryanodine (ryanodine receptor inhibitor) fully abolished the positive inotropic effect induced by naringin. Pre-treatment of animals with reserpine, catecholamine-depleting drug, also prevented the increase of atrial contractility evoked by naringin. Altogether, we show that naringin causes a positive inotropic effect in isolated atria through β-AR/PKA-dependent pathway.
Comparative study between supported bimetallic catalysts for nitrate remediation in water
Authors: Rachini Mouhamad , Jaafar Mira , Tabaja Nabil , Tlais Sami , Hamdan Rasha , Al Ali Fatima , Haidar Ola , Lancelot Christine , Kassem Mohammad , Bychkov Eugene , Tidahy Lucette , Cousin Renaud , Dewaele Dorothée , Hamieh Tayssir , Toufaily Joumana 
Published: March 2023

Abstract
As the population grows and the demand for water rises, the development of efficient and sustainable water purification techniques is becoming increasingly important to ensure access to clean and safe water in the future. The pollution of surface and groundwater by nitrate (

NO

3

−

{\text{NO}}_{3}^{-}

) is a growing global concern due to the rise in nitrogen-rich waste released from agriculture and industry. The removal of nitrate ions from aqueous media using bimetallic catalysts loaded on several supports was studied. Multiwalled carbon nanotubes, activated carbon, titanium dioxide, titanium dioxide/multiwalled carbon nanotubes, and Santa Barbara Amorphous-15 were used as supports to synthesize these bimetallic catalysts. The effects of the support type, supported metal, and catalyst reduction method on the nitrate reduction activity in water were investigated. The catalysts were characterized by X-ray diffraction, fourier-transform infrared spectroscopy, Brunauer-Emmett-Teller isotherm, inductively coupled plasma spectroscopy, and field emission gun scanning transmission electron microscope. In terms of nitrate conversion, high-temperature hydrogen reduction of the catalysts was a more effective method of catalyst preparation than NaBH4 reduction. Except for the carbon nanotube-TiO2 composite, pH fixation using CO2 flow improved the efficiency of supported catalysts. The catalysts 1Pd–1Cu/TiO2 and 1Pd–Cu/SBA-15 presented the highest catalytic activity, but the latter was the most selective to nitrogen.