Evaluation Period Research Articles

The impact and user experience of a student-led clinic providing preventative services.

Preventative services are required to address the risk factors for chronic conditions such as cardiovascular disease. The National Health Service Health Checks in England were introduced to provide such services. One School of Pharmacy established a student-led clinic to provide this service to the local community. The clinic was provided by undergraduate pharmacy students and delivered free of charge within a central city locality. The aim was to explore the impact of the clinic on user thoughts and motivations around healthy living and investigate user experience. A sequential explanatory mixed methods approach was used consisting of a survey that measured users' thoughts about their health and well-being and experience of the clinic. Qualitative interviews explored the user experience and barriers and facilitators to making healthier lifestyle choices. One hundred and fifty-four members of the public accessed the clinic over the evaluative period. Ninety-six (60%) completed the pre-post survey and 12 participated in follow-up interviews. Users reported statistically significant improvements in how informed, competent and motivated they felt towards making healthier lifestyle choices after the clinic consultation. Interview findings highlighted the positive user experience, reported appreciation for clinic accessibility, availability of healthy lifestyle education, and a desire for more preventative services being as readily available. The student-led clinic has demonstrated positive impacts on user experience, knowledge, competence, and motivation to make healthier lifestyle choices. The clinic provides proof-of-concept for pharmacy students to deliver preventative community services that aim to improve population health at a time when primary care is experiencing unprecedented challenges.

Analyzing the impact of digitized-education toward the future of education: A comparative study based on students’ evaluation of teaching data

This study investigates the key factors that impact the digitalized-education, and what those mean for the new and emerging educational models of learning. The research is based on state-of-the-art education and assessment models for learning such as Descriptive decision theory, Futures Literacy (FLF), and 8-Affordances framework that theoretically addresses both the need to use multidisciplinary components in identifying the several challenges and opportunities to the use of digital technologies in education (digitized-education) and improvement of the student's learning outcomes. Through a quasi-experimental study design and comparative analysis of the students’ evaluation of teaching (SET) dataset (n = 3178) collected in a higher education setting; the study applies a multivariate analysis of covariance (MANCOVA) and multiple comparisons (post-hoc) tests to determine the impact or association that the evaluation period (between 2019–2021) and type of school or discipline have on the students’ learning performance and evaluation. The results show that students’ satisfaction and experiences with digitized-education have exponentially grown in recent times, and mainly varied across the years, and marginally by discipline or school. In addition, the study empirically sheds light on the importance of the key findings and results by considering their pedagogical, technological, economic infrastructure, and ethical implications for the future of education and sustainable educational practice.

Evaluation of Gastric pH and Gastrin Concentrations in Horses Subjected to General Inhalation Anesthesia in Dorsal Recumbency.

The prevalence of gastric disorders in high-performance horses, especially gastric ulceration, ranges from 50 to 90%. These pathological conditions have negative impacts on athletic performance and health. This study was designed to evaluate changes in gastric pH during a 24 h period and to compare gastrin concentrations at different time points in horses undergoing general inhalation anesthesia and dorsal recumbency. Twenty-two mixed-breed mares weighing 400 ± 50 kg and aged 8 ± 2 years were used. Of these, eight were fasted for 8 h and submitted to 90 min of general inhalation anesthesia in dorsal recumbency. Gastric juice samples were collected prior to anesthesia (T0), and then at 15 min intervals during anesthesia (T15-T90). After recovery from anesthesia (45 ± 1 min), samples were collected every hour for 24 h (T1 to T24) for gastric juice pH measurement. During this period, mares had free access to Bermuda grass hay and water and were fed a commercial concentrate twice (T4 and T16). In a second group (control), four non-anesthetized mares were submitted to 8 h of fasting followed by nasogastric intubation. Gastric juice samples were then collected at T0, T15, T30, T45, T60, T75, and T90. During this period, mares did not receive food or water. After 45 min, mares had free access to Bermuda grass hay and water, and gastric juice samples were collected every hour for four hours (T1 to T4). In a third group comprising ten non-fasted, non-anesthetized mares with free access to Bermuda grass hay and water, gastric juice samples were collected 30 min after concentrate intake (T0). In anesthetized mares, blood gastrin levels were measured prior to anesthesia (8 h fasting; baseline), during recovery from anesthesia, and 4 months after the anesthetic procedure, 90 min after the morning meal. Mean values of gastric juice pH remained acidic during general anesthesia. Mean pH values were within the physiological range (4.52 ± 1.69) and did not differ significantly between time points (T15-T90; p > 0.05). After recovery from anesthesia, mean gastric pH values increased and remained in the alkaline range throughout the 24 h period of evaluation. Significant differences were observed between T0 (4.88 ± 2.38), T5 (7.08 ± 0.89), T8 (7.43 ± 0.22), T9 (7.28 ± 0.36), T11 (7.26 ± 0.71), T13 (6.74 ± 0.90), and T17 (6.94 ± 1.04) (p < 0.05). The mean gastric juice pH ranged from weakly acidic to neutral or weakly alkaline in all groups, regardless of food and water intake (i.e., in the fasted, non-fasted, and fed states). Mean gastric pH measured in the control group did not differ from values measured during the 24 h post-anesthesia period or in the non-fasted group. Gastrin concentrations increased significantly during the post-anesthetic period compared to baseline (20.15 ± 7.65 pg/mL and 15.15 ± 3.82 pg/mL respectively; p < 0.05). General inhalation anesthesia and dorsal recumbency did not affect gastric juice pH, which remained acidic and within the physiological range. Gastric juice pH was weakly alkaline after recovery from anesthesia and in the fasted and fed states. Serum gastrin levels increased in response to general inhalation anesthesia in dorsal recumbency and were not influenced by fasting. Preventive pharmacological measures are not required in horses submitted to general anesthesia and dorsal recumbency.

Marginal Leakage in Interfaces Formed by Bovine Dentin and Adhesive Cements Applied with Different Bonding Techniques

Objectives: The aim of this in vitro study was to evaluate the marginal microleakage in interfaces formed by bovine dentin and adhesive cements applied with different bonding techniques. Materials and Methods: Thirty bovine teeth dentin blocks measuring 5 mm x 5 mm x 1 mm were made with one side completely in dentin substract (20 mm2). The dentin blocks were randomly divided into three groups according to the cementation technique used: CTS+RX (conventional 3-step adhesive + dual-activation resin cement), SBS+RX (single-bottle self-etching adhesive + dual-activation resin cement), and SAC (self-adhesive cement). A photopolymerizable composite resin block with the same dimensions was fixed on the dentin block according to the instructions for each adhesive technique. The dentin-composite resin blocks made with each adhesive technique were separated into subgroups (n = 5) for 7 days (control) and for 6 months of water storage. After each period, the blocks were individually immersed in test tubes containing neutral methylene blue dye for 2 hours. The samples were washed, dried, and evaluated with a stereoscopic magnifying glass, and the amount of infiltrated pigment was analyzed using spectrophotometry (Beckman DU 65). The data were submitted to two-way ANOVA and Tukey’s test (5%). Results: Microleakage level for the conventional 3-step or self-etching technique remained similar for 7 days (18 ± 25 and 43 ± 45 μm, respectively) or 6 months (42 ± 55 and 52 ± 87 μm, respectively). The self-adhesive technique showed higher microleakage levels for 7-day (263 ± 98 μm) and 6-month periods (441 ± 226 μm) compared to other adhesive techniques. There was a statistically significant difference between evaluation times only for the self-adhesive technique. Conclusions: Higher microleakage levels by storage in water occurred with the self-adhesive technique in both evaluation periods. Clinical Relevance: The different microleakage levels promoted at the dentin-composite resin interface should be considered in adhesive clinical procedures in relation to long-term use.

Impact of doula's continuous support on serotonin release in parturients: a pilot randomized clinical trial.

To evaluate whether the continuous support provided by doulas influences the endogenous release of serotonin in parturients. This pilot study included 24 primigravidae at term. Of these, 12 women received continuous doula support (Experimental Group), whereas the other 12 received the usual assistance without doula support (Control Group). Blood samples were collected from all the women at the active and expulsion stages of labor and at the fourth period of labor (Greenberg period) for evaluation of their serotonin levels using high-performance liquid chromatography. The average serotonin concentrations in the control and experimental groups were respectively 159.33 and 150.02 ng/mL at the active stage, 179.13 and 162.65 ng/mL at the expulsion stage, and 198.94 and 221.21 ng/mL at the Greenberg period. There were no statistically significant differences in serotonin concentrations between the two groups at the active and expulsion stages of labor. By contrast, within the experimental group, a significant increase in serotonin concentration was observed in the Greenberg period compared with the levels in the active and expulsion stages (p < 0.05). The novelty of this study relies on the ability to correlate the influence of the continuous support offered by doulas with the release of serotonin in parturients, with the results suggesting that the assistance received during labor can modulate the levels of hormone release in the Greenberg period. RBR-4zjjm4h.

Treating Tobacco Dependency in National Health Service Workers in Greater Manchester: An Evaluation of a Bespoke Digital Service

IntroductionTreating tobacco dependency in National Health Service (NHS) workers delivers substantial benefits at an individual, population, and health care system level. We report the outcomes from the Greater Manchester Integrated Care Partnership’s tobacco dependency treatment program for NHS workers which includes 6-months’ access to behavioral support and 12 weeks of treatment through a digital application. MethodsAggregate results for all participants across the program from January 1, 2022, to September 1, 2023, are reported including a deep-dive evaluation of 300 participants recruited to provide chemically validated outcomes. ResultsA total of 1567 NHS workers participated in the program within the evaluation period, completing 24,048 sessions with specialist advisors within the application, ordering 18,710 nicotine vape liquids, 6927 nicotine patches, and 297 short-acting nicotine products. Users reported achieving 89,464 smoke-free days, 1,258,069 less cigarettes smoked, and a financial saving of £622,231. The deep-dive evaluation revealed a CO-verified 12-week abstinence rate of 37% (111 of 300). ConclusionThis evaluation provides assurance of clinical effectiveness within a bespoke digital tobacco dependency treatment program for NHS workers across an Integrated Care Partnership.

Characterization of Antibiotic Resistance in Select Tertiary Hospitals in Uganda: An Evaluation of 2020 to 2023 Routine Surveillance Data.

Antimicrobial resistance (AMR) is a public health concern in Uganda. We sought to conduct an extended profiling of AMR burden at selected Ugandan tertiary hospitals. We analyzed routine surveillance data collected between October 2020 and March 2023 from 10 tertiary hospitals. The analysis was stratified according to the hospital unit, age, gender, specimen type, and time. Up to 2754 isolates were recovered, primarily from pus: 1443 (52.4%); urine: 1035 (37.6%); and blood: 245 (8.9%). Most pathogens were Staphylococcus aureus, 1020 (37%), Escherichia coli, 808 (29.3%), and Klebsiella spp., 200 (7.3%). Only 28% of Escherichia coli and 42% of the other Enterobacterales were susceptible to ceftriaxone, while only 44% of Staphylococcus aureus were susceptible to methicillin (56% were MRSA). Enterococcus spp. susceptibility to vancomycin was 72%. The 5-24-year-old had 8% lower ampicillin susceptibility than the >65-year-old, while the 25-44-year-old had 8% lower ciprofloxacin susceptibility than the >65-year-old. The 0-4-year-old had 8% higher ciprofloxacin susceptibility. Only erythromycin susceptibility varied by sex, being higher in males. Escherichia coli ciprofloxacin susceptibility in blood (57%) was higher than in urine (39%) or pus (28%), as was ceftriaxone susceptibility in blood (44%) versus urine (34%) or pus (14%). Klebsiella spp. susceptibility to ciprofloxacin and meropenem decreased by 55% and 47%, respectively, during the evaluation period. During the same period, Escherichia coli ciprofloxacin susceptibility decreased by 40%, while Staphylococcus aureus gentamicin susceptibility decreased by 37%. Resistance was high across the Access and Watch antibiotic categories, varying with time, age, sex, specimen type, and hospital unit. Effective antimicrobial stewardship targeted at the critical AMR drivers is urgently needed.

Abstract CT090: DAREON™-7: A phase 1, open-label, dose escalation and expansion cohort trial of the delta-like ligand (DLL3)-targeting T-cell engager BI 764532, plus first-line platinum-based chemotherapy in patients with DLL3-positive (+) neuroendocrine carcinomas

Abstract Background Neuroendocrine carcinomas (NECs) have limited treatment options. DLL3 is highly expressed in NECs and is a promising treatment target. In an ongoing phase 1 trial (NCT04429087), BI 764532, a DLL3/CD3 IgG-like T-cell engager, was tolerable with clinical activity in patients with DLL3-positive (+) tumors, including those with small cell lung cancer and other NECs. Purpose DAREON™-7 (NCT06132113), a phase 1, open-label, dose-escalation (Part A) and dose-expansion (Part B) trial, aims to determine the maximum tolerated dose (MTD), recommended dose for expansion (RDE)/recommended phase 2 dose (RP2D), and the safety and efficacy of BI 764532 + platinum and etoposide in patients with DLL3+ NEC. Experimental design Part A: ~25 patients will receive intravenous BI 764532 (target dose after step-in dosing) plus carboplatin/etoposide (CE) until intolerable toxicity, or progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or for a maximum of 36 months. BI 764532 dose escalation will be guided by a Bayesian logistic regression model with overdose control. Part B: 2 cohorts (~15 patients each) will receive BI 764532 at the RDE/RP2D + CE or cisplatin/etoposide (carboplatin/etoposide or cisplatin/etoposide are the most-used standard of care [SOC] regimens). Key inclusion criteria: patients must have no prior systemic treatment for DLL3+ locally advanced or metastatic NEC (extrapulmonary or unknown primary) or large cell NEC of the lung except for 1 cycle of standard platinum/etoposide regimen as first-line treatment prior to entering the treatment period of the trial; patients with localized NEC or resectable disease who received prior adjuvant therapy can participate in the trial if they experienced a treatment-free interval of &amp;gt;6 months prior to the diagnosis of metastatic disease; and patients must have at least 1 measurable lesion as defined per RECIST v1.1. Patients must be adequate candidates to receive platinum/etoposide as the SOC treatment. Primary endpoints: occurrence of dose-limiting toxicities (DLTs) in the MTD evaluation (Part A) and on-treatment (Part B) periods. Secondary endpoints: occurrence of DLTs and adverse events during the on-treatment period (Part B), and efficacy measured by objective response and duration of response (Part B). Enrollment is ongoing. Citation Format: Jaume Capdevila, Timon Vandamme, Patricia Niccoli, Saori Mishima, Ken Kato, Yiyuan Ma, Ping Sun, Lijiang Geng, Ulrich M. Lauer. DAREON™-7: A phase 1, open-label, dose escalation and expansion cohort trial of the delta-like ligand (DLL3)-targeting T-cell engager BI 764532, plus first-line platinum-based chemotherapy in patients with DLL3-positive (+) neuroendocrine carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT090.

Frequency of office blood pressure measurements and the seasonal variability of blood pressure: results of the Hungarian Hypertension Registry

Purpose Hypertension is a major public health problem, thus, its timely and appropriate diagnosis and management are crucial for reducing cardiovascular morbidity and mortality. The aim of the new Hungarian Hypertension Registry is to evaluate the blood pressure measurement practices of general practitioners (GPs), internists and cardiologists in outpatient clinics, as well as to assess the seasonal variability of blood pressure. Materials and methods Omron M3 IT devices were used during four-month periods between October 2018 and April 2023 in GP practices and in hypertension clinics. The blood pressure data were then transmitted online from the monitors’ cuffs to a central database using the Medistance system of Omron. Results Family physicians (n = 2491), and internists/cardiologists (n = 477) participated in the study. A total of 4804 821 blood pressure measurements were taken during 10 four-month evaluation periods. In the ten periods, the daily average number of measurements was between 3.0 and 5.6. Following ESH diagnostic criteria, the proportion of subjects in optimal, normal and high-normal blood pressure categories were 14, 13.4 and 16.7%, respectively. Altogether 56% of the measurements belonged to stage 1, stage 2 or stage 3 hypertension categories (31.6, 17.1 and 7.4%, respectively). On average, a difference of 5/2 mmHg was observed between winter and summer data in systolic and diastolic blood pressures, respectively. The average systolic blood pressure values were higher in GP practices with more than 2000 patients than in the ones with less than 1500 patients (141.86 mmHg versus 140.02 mmHg, p < 0.05). Conclusion In conclusion, the low daily average number of blood pressure measurements indicates a limited blood pressure screening awareness/capacity in the case of Hungarian family physicians. In GP practices with more patients, blood pressure is usually less well-controlled. These results suggest that the further promotion of home blood pressure monitoring is necessary.

Potencial Simbiótico de Microrganismos do Solo na Promoção do Crescimento de Espécies Arbóreas da Mata Atlântica

The objective of this study was to evaluate the potential of topsoil obtained from a natural forest fragment in the Brazilian Atlantic Forest to serve as a source of symbiotic microorganisms capable of promoting the growth of native tree species in ecological restoration projects. In greenhouse conditions, 14 experiments in a completely randomized design were conducted in 1,700 cm³ pots filled with sterilized substrate. The effect of adding 80 g of topsoil, either in natura or sterilized, to the substrate was tested on the growth of 14 tree species. Plant height, stem diameter, mycorrhizal colonization and dry masses of shoot, roots, and nodules of tree species were measured. Applying the topsoil to the pots generally resulted in significant increases in height and stem diameter of seedlings compared to the control group during the four to six-month evaluation period. This effect was particularly greater in the nodulating species Plathymenia reticulata, Dalbergia nigra and Mimosa bimucronata, with increases in height and stem diameter of up to 328% and 484%, respectively. Forest topsoil also had a positive impact on the growth of shoot, roots, and nodules of the plants, significantly differing from the control groups. Only the plants that received the topsoil in natura exhibited mycorrhizal colonization and the formation of nodules in nitrogen-fixing species. These plants that established mycorrhizas and nodules presented higher concentrations of phosphorous and nitrogen in their biomass, respectively. Under controlled conditions, the use of forest topsoil proved to be a promising strategy for the introduction of microorganisms that can enhance the growth of tree species, thereby holding potential for implementation in nurseries and field settings.&#x0D; &#x0D;

Abstract CT084: A phase 1 study of LY4101174 (ETx-22), an antibody-drug conjugate targeting nectin-4, in patients with advanced or metastatic urothelial cancer and other solid tumors (trial in progress)

Abstract Background: Nectin-4 is a cell adhesion molecule expressed in multiple tumor types.1 Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) comprising a fully humanized nectin-4 antibody conjugated to the microtubule inhibitor, monomethyl auristatin E (MMAE), is approved for the treatment of advanced urothelial cancer (UC). However, skin toxicity, peripheral neuropathy, and hyperglycemia are clinically significant toxicities with EV. LY4101174 (ETx-22) is a next-generation nectin-4 targeting ADC comprising a humanized IgG1 Fc-silent monoclonal antibody linked to the topoisomerase I inhibitor, exatecan, via a maleimide-ß-glucuronide poly-sarcosine linker with improved stability and a homogeneous drug-antibody ratio (DAR) of 8. Preclinically, LY4101174 has demonstrated robust in vivo efficacy in tumor models across a range of nectin-4 expression levels and in the nectin-4-MMAE ADC treated resistant tumor model.2 Methods: LOXO-ENC-23001 is a global, open-label, multi-center, first-in-human phase 1 study of LY4101174 in patients (pts) with advanced or metastatic solid tumors known to express nectin-4. LY4101174 will be administered intravenously and evaluated initially on either every 2 weeks or 3 weeks schedule. Eligible pts (≥18 years) must have good performance status (ECOG PS 0-1) with metastatic UC, head and neck squamous cell carcinoma, esophageal, pancreatic, prostate, non-small cell lung, cervical, ovarian, or triple-negative breast cancer, and must have received or not be a candidate for available standard therapies. The study will be conducted in 2 phases: phase 1a dose escalation/dose optimization and phase 1b dose expansion. Dose escalation will utilize a Bayesian optimal interval design. Additional pts will be allowed to backfill to previously cleared dose levels that demonstrate therapeutically relevant exposures or direct evidence of clinical activity. The dose-limiting toxicity evaluation period will be 21 or 28 days based on dosing schedules. Phase 1b dose expansion cohorts will enroll pts with selected tumor types: mUC with no prior EV treatment (cohort B1), mUC with prior EV treatment (cohort B2), and other selected non-UC tumors (cohort C). Primary objectives are to determine the recommended phase 2 dose (RP2D) and assess the safety of LY4101174. Key secondary objectives are to evaluate the pharmacokinetic profile, immunogenicity, and antitumor activity of LY4101174 per RECIST v1.1. Nectin-4 expression and other biomarker data will be generated and correlated with clinical activity. 1Challita-Eid PM et al. 2016 Cancer Res 76(10):3003-13. 2Azim H et al. 2023 Mol Cancer Ther 22(12_Suppl):B128. Citation Format: Jonathan Rosenberg, Renaud Sabatier, Armelle Viceneux, Thibault de La Motte Rouge, Stephane Champiat, Loic Lebellec, Philippe Barthélémy, Guru Sonpavde, Xin Gao, Scot Niglio, Tian Zhang, Craig Gedye, Matthew Galsky, Matthew Milowsky, Melissa Reimers, Andrew Weickhardt, Enrique Grande, Daniel E. Castellano, Mehmet Bilen, Amita Patnaik, Robert Zerbib, Minna Balbas, Xiaojian Xu, Kaitlyn Aptaker, Arjun V. Balar, Ahmad H. Awada. A phase 1 study of LY4101174 (ETx-22), an antibody-drug conjugate targeting nectin-4, in patients with advanced or metastatic urothelial cancer and other solid tumors (trial in progress) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT084.

Abstract CT100: Safety and efficacy of AZD8853, an anti-growth and differentiation factor 15 (GDF15) antibody, in patients (pts) with advanced/metastatic solid tumors: First-in-human study

Abstract Background: GDF15 is overexpressed in solid tumors, with immunosuppressive effects on dendritic cells (DCs), T cells and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. AZD8853 is an IgG1 monoclonal antibody that neutralizes GDF15. This Phase 1/2a, open-label study assessed AZD8853 monotherapy in previously treated advanced/metastatic non-small-cell lung cancer, microsatellite-stable colorectal cancer (MSS-CRC) and urothelial carcinoma (UC) (NCT05397171). Methods: Eligible pts were ≥18 years old with ≥1 measurable lesion per RECIST v1.1 and ECOG PS 0/1. AZD8853 was given IV Q3W until disease progression, unacceptable toxicity or consent withdrawal. The primary objective was safety including dose-limiting toxicities (DLTs). Secondary objectives included efficacy, pharmacokinetics (PK) and pharmacodynamics (PD [free serum GDF15]). Exploratory objectives included peripheral immune PD. Results: During dose escalation, 16 pts (15 MSS-CRC, 1 UC) received AZD8853 (300 mg, n=3; 1000 mg, n=6; 3000 mg, n=7). By June 6, 2023, all pts discontinued treatment and the study. Thirteen pts (81.3%) had treatment-emergent adverse events (TEAEs; Table); the most common were diarrhea (31.3%), abdominal pain (31.3%) and decreased appetite (25%). Eight pts (50%) had Grade ≥3 TEAEs and 6 (37.5%) had serious TEAEs; none treatment-related. There were no DLTs. No pts had responses by RECIST; 5 (31.3%) had stable disease and 11 (68.8%) had disease progression as best response. AZD8853 PK was linear with a half-life of 5-10 days, supporting Q3W dosing. GDF15 suppression was transient. There was no evidence of ctDNA clearance or a dose-dependent change in peripheral immune cells including CD8+ and CD4+ T cells, DCs and MDSCs. Conclusions: AZD8853 was well tolerated. No objective responses or PD effects were seen and GDF15 suppression was not sustained, therefore no further development is planned. TABLE 1. NAND Table. AZD8853 safety AZD8853 300 mg 1000 mg 3000 mg Total Safety, n (%) N=3 N=6 N=7 N=16 TEAEs 3 (100) 4 (66.7) 6 (85.7) 13 (81.3) Grade ≥3 TEAEs 1 (33.3) 3 (50.0) 4 (57.1) 8 (50.0) TRAEs 1 (33.3) 0 2 (28.6) 3 (18.8) Grade ≥3 TRAEs 0 0 0 0 Serious TEAEs 1 (33.3) 3 (50.0) 2 (28.6) 6 (37.5) TEAEs leading to discontinuation of AZD8853 0 1 (16.7)* 0 1 (6.3) TEAEs leading to death 0 1 (16.7)* 0 1 (6.3) DLTs, n (%) N=3 N=6 N=6 † N=15 DLTs 0 0 0 0 *Death due to serious AE of cardiac arrest, unrelated to AZD8853; pt had a history of coronary artery disease, coronary stenting, and pulmonary embolism.†One pt discontinued due to clinical progression prior to completing the DLT evaluation period and was not included in the DLT-evaluable set. DLTs, dose-limiting toxicities; TEAEs, treatment-emergent adverse events, TRAEs, treatment-related adverse events Citation Format: Benedito A. Carneiro, Olumide Gbolahan, Albiruni Abdul Razak, John F. Hilton, Arthur Lambert, John Hood, Michael Pluta, Veronique Bragulat, Elhan Sanai, Rakesh Kumar, Duncan Jodrell, Patricia LoRusso. Safety and efficacy of AZD8853, an anti-growth and differentiation factor 15 (GDF15) antibody, in patients (pts) with advanced/metastatic solid tumors: First-in-human study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT100.

One-time definitive attachment connection versus healing abutment placement for an implant-retained mandibular overdenture: Peri-implant metabolic activity

Statement of problemUnscrewing the healing abutment can affect the soft tissue integration and apical migration of the biological width, which may compromise the integrity of peri-implant soft tissue. PurposeThe purpose of this clinical study was to determine the level of glycosaminoglycan (GAG) detected in the peri-implant crevicular fluid (PICF) between the test group (1-time abutment) and control group (healing abutment) for implant-retained mandibular overdentures. Material and methodsTwo dental implants were installed in the canine regions of the mandibular ridge of 18 healthy completely edentulous participants using 2-stage surgery and a delayed loading protocol. At the second stage surgery, the implant on the right side was exposed, and a healing abutment was screwed onto the implant (control group), while on the left side the definitive ball abutment was screwed onto the implant (test group). After 10 days, the healing abutment in the control group was unscrewed and replaced with the definitive ball abutment. For both groups, the ball attachment was directly picked up to incorporate the attachment house to the mandibular denture. PICF samples were collected from the participants at 7 days, 3 months, and 6 months after overdenture use. Statistical analysis was done with an independent samples t test (α=.05). ResultsA significant difference was found in the volume of PICF and the level of GAG between the test and control groups at the 7-day evaluation period (P=.008, P=.002, respectively), while the volumes of PICF and the levels of GAG were not significantly different (P>.05) at the other evaluation periods. ConclusionsThe 1-time abutment protocol offers biochemical and economic advantages compared with the conventional method of using the healing abutment before placement of the definitive attachment for an implant-retained overdenture with single attachments.

Efficacy of photobiomodulation using diode laser 650 nm combined with nano-cellulose and nano-amorphous calcium phosphate in bone healing of rabbit tibial defects assessed by H&E staining and computed tomography.

The purpose of the current study was to evaluate the effect of Diode LLLT 650 nm, TEMPO oxidized Nano-fibrillated cellulose mixed with Nano-Amorphous calcium phosphate, and their combination on bone healing in rabbit tibia using H&E staining and computed tomography. Eighteen adult male New Zealand rabbits were selected, two circular bone defects were created in each tibia, resulting in four bony defects in each rabbit, representing the four tested groups; group A (negative control), group B (filled with mineralized nano-cellulose), group C (combination), group D (laser). Animals were euthanized after two weeks and one month, defects were assessed by CT for bone density, then histological samples were examined by H&E stain. In both evaluation periods, group D recorded the greatest mean area percent of new bone formation and bone density, followed by group A, while group C recorded the lowest value. Groups A and D showed full closure of the defects, while groups B and C showed partial defect closure with retained bone graft material. H&E and CT showed that Laser group had the best results of defects healing, bone density and new bone formation, followed by the negative control group. Diode laser 650nm photobiomodulation significantly improved bone defects healing. Mineralized nano-cellulose experimental bone substitute material showed a delayed effect in bone healing and graft material resorption. The combination of LLLT with the graft material had no positive outcome on bone defect healing.

How the Assessment of Scientific Performance Impacts the Research Freedom of Scientists

Introduction. Poorly constructed assessment systems can disrupt the logic of scientific development and contribute to a narrow scientific principles. This is particularly facilitated by the predetermination of priority research topics and methods, limitation of funding, and access to scientific communication tools. Understanding the mechanisms of how evaluations influence allows for the improvement of evaluation tools and minimises the likelihood of negative evaluation consequences. Methods. A review of the global document flow reflecting the impact of scientific performance assessments has clarified information about the mechanisms of how assessments impact research freedom. The majority of foreign publications included in the review are from 2008—2023. Results and Discussion. Qualitative research is the main source of information on the impact of evaluation. Strong quantitative evidence of the impact of peer and hybrid assessment on the choice of topics, research areas, and approaches pertains to social sciences and humanities. The mechanism of influence varies depending on the assessment method. The influence of peer review is evident in that researchers take into account expert opinions when planning a study. The impact of quantitative assessment is that researchers consider publication prospects. Therefore, due to risk avoidance, evaluation can stimulate self-limitation, which can ultimately lead to increased uniformity in research. Scientists are required to make additional efforts to find ways to maintain research freedom. Many instances of its manifestation are due to the factors in the environment that counteract evaluation and the adaptation of scientists to the evaluation system. Conclusion. Evaluation is one of the key factors in implementing science policies. It signals which studies are prioritised, which rules they must comply with, and which ones they should not. The impact of evaluation on research freedom is most pronounced for scientifically weak subjects, when evaluation periods are insufficient for obtaining a scientific result, and when formal criteria are used without considering disciplinary specifics. During the implementation of evaluation activities, measures must be taken to preserve research freedom.

Comprehensive beam delivery latency evaluation for gated proton therapy system using customized multi-channel signal acquisition platform.

Beam delivery latency in respiratory-gated particle therapy systems is a crucial issue to dose delivery accuracy. The aim of this study is to develop a multi-channel signal acquisition platform for investigating gating latencies occurring within RPM respiratory gating system (Varian, USA) and ProBeam proton treatment system (Varian, USA) individually. The multi-channel signal acquisition platform consisted of several electronic components, including a string position sensor for target motion detection, a photodiode for proton beam sensing, an interfacing board for accessing the trigger signal between the respiratory gating system and the proton treatment system, a signal acquisition device for sampling and synchronizing signals from the aforementioned components, and a laptop for controlling the signal acquisition device and data storage. RPM system latencies were determined by comparing the expected gating phases extracted from the motion signal with the trigger signal's state turning points. ProBeam system latencies were assessed by comparing the state turning points of the trigger signal with the beam signal. The total beam delivery latencies were calculated as the sum of delays in the respiratory gating system and the cyclotron proton treatment system. During latency measurements, simulated sinusoidal motion were applied at different amplitudes and periods for complete beam delivery latency evaluation under different breathing patterns. Each breathing pattern was repeated 30 times for statistical analysis. The measured gating ON/OFF latencies in the RPM system were found to be 104.20±13.64ms and 113.60±14.98ms, respectively. The measured gating ON/OFF delays in the ProBeam system were 108.29±0.85ms and 1.20±0.04ms, respectively. The total beam ON/OFF latencies were determined to be 212.50±13.64ms and 114.80±14.98ms. With the developed multi-channel signal acquisition platform, it was able to investigate the gating lags happened in both the respiratory gating system and the proton treatment system. The resolution of the platform is enough to distinguish the delays at the millisecond time level. Both the respiratory gating system and the proton treatment system made contributions to gating latency. Both systems contributed nearly equally to the total beam ON latency, with approximately 100ms. In contrast, the respiratory gating system was the dominant contributor to the total beam OFF latency.

Growth performance and carcass characteristics of rabbits fed concentrate diets containing graded levels of Brassica oleracea outer leaves and Musa paradisiaca leaves

Ninety-six (96) 8-wk-old “mixed breed” of New Zealand white, California white and chinchilla rabbits were used to determine the growth performance, carcass and organ percentages of rabbits fed concentrate diets containing graded levels of Brassica oleracea outer leaves and Musa paradisiaca leaves. The rabbits were assigned to two groups of 48. Those in group 1 were allotted to four dietary treatments with concentrate diets containing 0, 10, 20 and 30% inclusion levels of B. oleracea outer leaves for one week and 12-wk adaptation and testing periods, respectively, for growth performance evaluation. Similar treatment and design were adopted for group 2 rabbits using graded levels of M. paradisiaca leaves. Six rabbits were randomly selected from each treatment group for slaughter at the end of the testing period for carcass and internal organ characteristics evaluation. There were no dietary effects on the parameters of rabbits fed graded levels of B. oleracea outer leaves except for M. paradisiaca, where the control diet had the lowest feed intake and the least (P&lt;0.05) feed conversion ratio comparable to 30% inclusion level and final body weight, which was the highest (P&lt;0.05) for rabbits fed diets containing 10 and 20% inclusion levels of M. paradisiaca leaves. The cost of feed was highest for the control diets, and reduced with increasing inclusion levels of the leaves in the diets. None of the rabbits died during the experimental period. The findings suggest that rabbits can be fed concentrate diets containing B. oleracea outer leaves and M. paradisiaca leaves up to 30% inclusion level for good growth performance and high carcass characteristics at a lower production cost than concentrate diets, while maintaining good health.

Utilization of marketing automation tools for delivery of a faculty development curriculum

Background Physician clinical educators play important roles in teaching, providing feedback, and evaluating trainees, but they often have variable preparation and competing demands on their time that make universal participation in workshops, seminars, or short courses designed to foster these skillsets inefficient or impossible. Methods We designed and implemented a 52-week synchronous curriculum designed to address faculty opportunities to improve teaching skills, feedback for residents and medical students, and evaluation skills, which were delivered using marketing automation tools, including text messaging and email. We evaluated the programmatic impact and feasibility of using the implementation science framework. Results Over a 104-week evaluation period, there were at least 10,499 total content impressions and 4558 unique recipients, indicating the significant reach of this program to approximately 120 faculty members. Faculty engagement with continuing education materials remained stable or increased over the 2-year evaluation period, indicating that programs like ours can have sustainable impacts. Resident evaluations of faculty across the six key domains also improved after the implementation of the program. Conclusions Our experience with digital marketing tools reflects that they can be used to deliver impactful curricular content to faculty for continuing educational purposes and that faculty can use these resources in a sustainable way. However, because of the incomplete reach with any single communication, this type of content delivery is not appropriate for isolation as a material of critical importance. More research is needed to identify the best practices and additional education-related uses of this technology.

A hybrid deep learning approach for streamflow prediction utilizing watershed memory and process-based modeling

Abstract Accurate streamflow prediction is essential for optimal water management and disaster preparedness. While data-driven methods’ performance often surpasses process-based models, concerns regarding their ‘black-box’ nature persist. Hybrid models, integrating domain knowledge and process modeling into a data-driven framework, offer enhanced streamflow prediction capabilities. This study investigated watershed memory and process modeling-based hybridizing approaches across diverse hydrological regimes – Korean and Ethiopian watersheds. Following watershed memory analysis, the Soil and Water Assessment Tool (SWAT) was calibrated using the recession constant and other relevant parameters. Three hybrid models, incorporating watershed memory and residual error, were developed and evaluated against standalone long short-term memory (LSTM) models. Hybrids outperformed the standalone LSTM across all watersheds. The memory-based approach exhibited superior and consistent performance across training, evaluation periods, and regions, achieving 17–66% Nash–Sutcliffe efficiency coefficient improvement. The residual error-based technique showed varying performance across regions. While hybrids improved extreme event predictions, particularly peak flows, all models struggled at low flow. Korean watersheds’ significant prediction improvements highlight the hybrid models’ effectiveness in regions with pronounced temporal hydrological variability. This study underscores the importance of selecting a specific hybrid approach based on the desired objectives rather than solely relying on statistical metrics that often reflect average performance.

Abstract 3636: Myeloid cell rebound associated with GD2-CAR-T cell therapy in solid tumor patients

Abstract GD2 is a validated cancer immunotherapy target with highly restricted normal tissue expression. Promising activity of GD2-CAR-T cell therapy in diffuse midline glioma and neuroblastoma has promoted interest in this therapy. We initiated three phase 1 clinical trials of escalating doses of intravenously administered autologous GD2-CAR-T cells in patients with advanced GD2-positive solid tumors. Emerging evidence suggests that CAR-T cells may increase circulating myeloid derived suppressor cells (MDSCs) and that this event may be mediated and/or triggered by CAR-T cell-derived cytokines and chemokines. These findings may help to explain the limited persistence of CAR-T cell therapy in solid tumor patients. Hence, we sought evidence of MDSC generation and secretion of relevant cytokines and chemokines in our clinical trial patients. The CARPETS trial (www.anzctr.org.au: ACTRN12620000622909) recently closed to recruitment after enrolling 12 patients (7 melanoma, 4 colorectal cancer, and 1 sarcoma). No significant adverse events were attributable to CAR-T cell therapy. We opened two other GD2-CAR-T cell therapy trials in 2023: LEVI’S-CATCH (ACTRN12622000675729) in patients with diffuse midline glioma at Sydney Children’s Hospital and KARPOS (ACTRN12622001514796) in adult patients with recurrent glioblastoma at Royal Adelaide Hospital. To date, 3 patients have enrolled to LEVI’S-CATCH with the first patient clearing the dose limiting (DLT) evaluation period. Three patients completed enrolment to the first dose cohort of KARPOS without DLTs. In all CARPETS patients, CAR-T cell expansion, which was measured by by DNA quantitative PCR and flow cytometry, peaked during the 6-week post-CAR-T infusion DLT evaluation period. In 6 CARPETS patients for whom peripheral blood samples were available, we found by flow cytometry, newly formed or increased size of pre-existing subpopulations of non-classical monocytes and/or MDSCs of mononuclear and/or polymorphonuclear class, which peaked at or after the time of peak CAR-T cell expansion. Typically, serum levels of inflammatory cytokines and chemokines such as TNF, IL-6, IL-8, CCL2, GM-CSF, and CXCL10, were detected only after the CAR-T cell infusion with variable patterns of the timing and concentration of analyte observed among the 12 patients. At the time of writing, blood samples from the first KARPOS patient showed CAR-T cell expansion and the subsequent increases in circulating myeloid derived suppressor cells and inflammatory cytokines. We expect that full data sets for these parameters will be presented for current and future enrolled patients to both studies. To improve CAR-T cell persistence in solid tumor patients, these data indicate the need for new therapeutic strategies to mitigate effects of CAR-T cell induced myeloid cells with antitumor activity. Citation Format: Michael P. Brown, Tessa Gargett, Nga T. Truong, Orazio Vittorio, David S. Ziegler. Myeloid cell rebound associated with GD2-CAR-T cell therapy in solid tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3636.