bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 2 basket study of tucatinib and trastuzumab in previously treated solid tumors with HER2 alterations: Urothelial cancer cohort (SGNTUC-019).
Authors: Yu Evan Y. , Jin Fan , Ramos Jorge , Tan Qianwen , Galsky Matt D. 
Published: March 2023

TPS587 Background: Tucatinib, a highly selective human epidermal growth factor receptor 2 (HER2)-directed tyrosine kinase inhibitor approved in multiple regions for HER2-positive (HER2+) metastatic breast cancer, is being investigated as a novel therapy for metastatic colorectal cancer, gastric cancer, and other solid tumors. In xenograft models of HER2+ and HER2-mutated tumors, dual targeting of HER2 with tucatinib plus trastuzumab showed superior activity to either alone (Kulukian 2020; Peterson 2020). Despite development of several new therapies for metastatic urothelial cancer (UC), most patients are refractory to subsequent therapies and die from the disease, highlighting the need for additional therapeutic approaches. Given that 20%–30% of metastatic UCs have molecular alterations of the ErbB family, tucatinib plus trastuzumab warrants further evaluation. SGNTUC-019 (NCT04579380) is a multi-cohort, open-label, phase 2 study evaluating tucatinib plus trastuzumab in patients with previously treated solid tumors displaying HER2+ or HER2-mutated solid tumors, including a cohort with locally advanced or metastatic UC. Methods: Eligible patients in the UC cohort must have HER2+ locally advanced or metastatic disease, with progression during or after, or intolerance of, the most recent line of systemic therapy. Patients must have an ECOG PS ≤1; adequate hepatic, hematologic, renal, and cardiac function; and no prior exposure to HER2-directed therapy. HER2 alterations can be demonstrated by HER2 overexpression/amplification in tumor tissue by prior IHC/ISH or by HER2 amplification in prior or prescreening NGS assay of ctDNA or prior tissue NGS assay. The HER2 overexpression/amplification UC cohort will enroll 12 response-evaluable patients per RECIST 1.1. If ≥2 responses are observed, the cohort will be expanded to 30. The primary objective is antitumor activity, with confirmed ORR as the primary endpoint and DCR, duration of response, PFS, and OS as secondary efficacy endpoints. Confidence intervals (CIs) will be calculated for confirmed ORR and DCR. For time-to-event endpoints, median survival time will be estimated by the Kaplan-Meier method, and the associated 95% CI will be calculated using complementary log-log transformation. Safety endpoints will be assessed using descriptive statistics. Patients will receive tucatinib 300 mg orally twice daily and trastuzumab 8 mg/kg intravenously on Cycle 1 Day 1 and 6 mg/kg every 21 days from Cycle 2 Day 1. Disease assessments per RECIST 1.1 will occur every 6 weeks for 24 weeks, then every 12 weeks. Trough concentrations of tucatinib will be evaluated in Cycles 2–6, with peak concentration sampled in Cycle 3. Quality of life will be evaluated every second cycle using the EQ-5D-5L. Sites are currently enrolling within the US, EU, and Asia Pacific. Clinical trial information: NCT04579380 .
CaboCombo: A prospective international non-interventional study of first-line cabozantinib plus nivolumab for the treatment of patients with advanced renal cell carcinoma.
Authors: Barthelemy Philippe , Dutailly Pascale , Qvick Bryan , Perrot Valérie , Verzoni Elena 
Published: March 2023

TPS740 Background: The combination of cabozantinib plus nivolumab (Cabo + Nivo) was approved in Europe in 2021 for the first-line (1L) treatment of patients with advanced renal cell carcinoma (aRCC) based on evidence from the phase 3 CheckMate 9ER trial. In the CheckMate 9ER trial (N = 651), Cabo + Nivo improved overall survival (hazard ratio [HR] 0.70 [95% confidence interval: 0.55–0.90]; p = 0.0043) and progression-free survival (HR 0.56 [95% CI: 0.46–0.68]; p ≤ 0.0001) versus sunitinib. There is clinical interest in the effectiveness and tolerability of Cabo + Nivo as used in routine cancer care. Methods: CaboCombo is a prospective, international, real-world non-interventional study to evaluate the effectiveness and tolerability of 1L Cabo + Nivo in adults (aged ≥ 18 years) with aRCC with a clear-cell component. In total 311 patients will be enrolled across 70 centers in countries where 1L Cabo + Nivo has marketing authorization and reimbursement. The decision to prescribe Cabo + Nivo will be made prior to, and independently from, the decision to enroll patients. The primary endpoint is real-world landmark overall survival assessed 18 months after Cabo + Nivo initiation. Secondary endpoints include: real-world treatment patterns; median progression-free survival; objective response rate; duration of response; disease control rate; time to response; treatment-emergent adverse events, and changes in disease-related symptoms and pain during the treatment period (assessed by the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index – Disease Related Symptoms questionnaire, and the Numerical Pain Rating Scale). Patients will be enrolled over 24 months and followed for up to 42 months. The nature and timing of study visits and assessments will be as per usual care at each participating center; no additional diagnostic or monitoring procedures will be conducted. Treatment will continue until disease progression, unacceptable toxicity or withdrawal of participant consent. Two interim analyses will be conducted, the first a description of baseline characteristics when at least 50% of participants have been recruited. No changes in study design or conduct will be made based on the results of these analyses. Clinical trial information: NCT05361434 .
Correlation of the immune tumor microenvironment (I-TME) with gene expression profiles as prognostic and predictive factors in patients (pts) with metastatic renal carcinoma (mRCC) treated with immunotherapy (Meet-URO 18 I-TME study).
Authors: Catalano Fabio , Murianni Veronica , Rebuzzi Sara Elena , Galuppini Francesca , Buti Sebastiano , Brunelli Matteo , Maruzzo Marco , Dei Tos Angelo Paolo , Basso Umberto , Banna Giuseppe Lugi , Signori Alessio , Sbaraglia Marta , Damassi Alessandra , Cremante Malvina , Puglisi Silvia , Gandini Annalice , Rebuzzi Marta , Mosca Alessandra , Fornarini Giuseppe , Rescigno Pasquale 
Published: March 2023

TPS753 Background: Several studies suggested that response to immunotherapy may be influenced by many factors, including peripheral blood biomarkers, the composition of I-TME and different molecular expression pathways. In mRCC patients, immunotherapy has become part of clinical practice, but the identification of patients most likely to respond to checkpoint inhibitors is still an unmet clinical need. Moreover, there are no validated and clinically applicable gene expression panels as prognostic and/or predictive response biomarkers. To date, three major groups of immune-related gene expression were identified in mRCC: the angiogenesis pathway, the T-effector pathway and the mixed pathway (doi: 10.1038/s41598-020-58804-y). Each group of gene expression seems to be responsible for a different type of immune response in the I-TME. However, a significant association with treatment response to immunotherapy has not yet been demonstrated. Methods: The Meet-URO 18 is a multicentric retrospective translational study aimed at identifying distinctive molecular patterns of the I-TME with a prognostic and predictive role in mRCC (primary objective). Pretreated mRCC patients receiving ≥2nd line nivolumab have been divided according to clinical benefit in responders (PFS ≥ 12 months) versus non-responders (PFS ≤ 3 months). Secondary objectives include the correlation between primary tumor and metastases to identify a potential inter-tumor heterogeneity and the correlation with survival and response outcomes. Histological samples of primary tumors and/or metastases have been collected for the transcriptomic analyses together with clinical data of patients from medical records. The transcriptomic characterization of the I-TME of the primary tumor and/or metastases will be performed using the analytical platform "nCounter" of NanoString®, which analyzes the expression of 71 genes involved in angiogenesis, immunomodulation mediated by T-effector response, mechanisms of tumor invasion and mechanisms of calcium channel flows. The gene-panel include a group of 66 genes previously demonstrated to be related in the immune-response in mRCC (doi: 10.1038/s41598-020-58804-y) and 5 housekeeping genes (RPS13, PPIA, RPL27, RP2, B-ACT).
Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study
Authors: Lazzeroni Matteo , Puntoni Matteo , Guerrieri-Gonzaga Aliana , Serrano Davide , Boni Luca , Buttiron Webber Tania , Fava Marianna , Briata Irene M. , Giordano Livia , Digennaro Maria , Cortesi Laura , Falcini Fabio , Serra Patrizia , Avino Franca , Millo Francesco , Cagossi Katia , Gallerani Elisa , De Simone Alessia , Cariello Anna , Aprile Giuseppe , Renne Maria , Bonanni Bernardo , DeCensi Andrea 
Published: March 2023

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results. METHODS We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS. RESULTS The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period. CONCLUSION Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.
The Perioperative Frontal Relative Ratio of the Alpha Power of Electroencephalography for Predicting Postoperative Delirium After Highly Invasive Surgery: A Prospective Observational Study
Authors: Kinoshita Hirotaka , Saito Junichi , Kushikata Tetsuya , Oyama Tasuku , Takekawa Daiki , Hashiba Eiji , Sawa Teiji , Hirota Kazuyoshi 
Published: March 2023

BACKGROUND:
We investigated the associations between postoperative delirium (POD) and both the relative ratio of the alpha (α)-power of electroencephalography (EEG) and inflammatory markers in a prospective, single-center observational study.

METHODS:
We enrolled 84 patients who underwent radical cancer surgeries with reconstruction for esophageal cancer, oral floor cancer, or pharyngeal cancer under total intravenous anesthesia. We collected the perioperative EEG data and the perioperative data of the inflammatory markers, including neutrophil gelatinase-associated lipocalin, presepsin, procalcitonin, C-reactive protein, and the neutrophil-lymphocyte ratio (NLR). The existence of POD was evaluated based on the Intensive Care Delirium Screening Checklist. We compared the time-dependent changes in the relative ratio of the EEG α-power and inflammatory markers between the patients with and without POD.

RESULTS:
Four of the 84 patients were excluded from the analysis. Of the remaining 80 patients, 25 developed POD and the other 55 did not. The relative ratio of the α-power at baseline was significantly lower in the POD group than the non-POD group (0.18 ± 0.08 vs 0.28 ± 0.11, P < .001). A time-dependent decline in the relative ratio of α-power in the EEG during surgery was observed in both groups. There were significant differences between the POD and non-POD groups in the baseline, 3-h, 6-h, and 9-h values of the relative ratio of α-power. The preoperative NLR of the POD group was significantly higher than that of the non-POD group (2.88 ± 1.04 vs 2.22 ± 1.00, P < .001), but other intraoperative inflammatory markers were comparable between the groups. Two multivariable logistic regression models demonstrated that the relative ratio of the α-power at baseline was significantly associated with POD.

CONCLUSIONS:
Intraoperative frontal relative ratios of the α-power of EEG were associated with POD in patients who underwent radical cancer surgery. Intraoperative EEG monitoring could be a simple and more useful tool for predicting the development of postoperative delirium than measuring perioperative acute inflammatory markers. A lower relative ratio of α-power might be an effective marker for vulnerability of brain and ultimately for the development of POD.
Feinting Repeats, Repeating Feints: The Developmental “Double Return” in Brahms and Sonata Theory Typology
Authors: Taylor Benedict 
Published: March 2023

AbstractOne of the most prominent characteristics of Johannes Brahms's approach to sonata form is the return to the tonic at the start of the second section (or “rotation”) for a restatement of the exposition's primary theme. Well-known examples include the finales of the First and Third Symphonies, the opening movements of the G-minor Piano Quartet and Fourth Symphony, and the Tragic Overture. This common basic principle can nevertheless underpin a variety of formal typologies. Ostensibly a three-part sonata form with developmental double return would be most likely labeled a sonata rondo (type 4 in Hepokoski and Darcy's sonata theory), while a two-part design is so typical of Brahms's practice that it has become known as a “Brahmsian deformation” (expanded type 1). Yet numerous cases exist in which neither reading above is permitted—most notably, three-part sonata forms with developmental double return used as opening movements. In these cases sonata theory is left classifying these designs as a conventional type 3 sonata with an expositional repeat feint. There are some serious problems, however, with this interpretation. First is the sheer number of pieces in which this double return occurs; in fact, after 1878 Brahms is more likely to “feign” a repeat than to provide one. Second, how the primary theme returns is hardly ever identical to its opening appearance and can rarely be confused with an exposition repeat (the op. 25 Quartet and Fourth Symphony are exceptions in this sense). Exploring these works, the author proposes a new subtype of the type 3 sonata to classify Brahms's mature practice, called “type 34.” Ultimately, though, these findings may lead to questions regarding the efficacy of a classically oriented typology confronted with late nineteenth-century practice.
Performance Spaces for Improvised and Notated Music
Authors: Andersen Drake 
Published: March 2023

Abstract
Abstract compositional spaces have long been used to illustrate structural relationships within and between musical works. However, despite robust scholarship employing spaces to depict the possibilities available to composers, space-based analytical methods have rarely been used to study the performance of music. Through case studies drawn from improvised and notated music, this article introduces the questions and methodologies by which analogous spaces for performance, which the author terms performance spaces, may be generated and analyzed. The author also considers the unique properties of hybrid spaces that combine the tools of discrete mathematics, such as graphs, with distance-based metrics.
POST HOC ANALYSIS ON THE INCIDENCE OF CONGENITAL HEART DISEASE IN BAKU-AZERBAIJAN CALCULATED BY A PROSPECTIVE EPIDEMIOLOGY STUDY
Authors: Petropoulos Andreas 
Published: March 2023

Background: The incidence of Congenital Heart Disease (CHD)in Azerbaijan was firstly published following a prospective study, using Echo-2D as a study method, in 2019.
Aim: Of this post hoc analysis of the first ever prospective epidemiology study that calculated incidence and types of CHD in Baku, Azerbaijan, is to verify the forms of diseases that will have and early clinical impact on the patients and the health system of the country.
Population-method: From June 2016 to August 2018, 2570, term neonates were screened in 2 major state maternity hospitals in Baku. Their screening was randomized to equal females/males with not known previous obstetric alert regarding CHD. Scanning was done by two teams of pediatric cardiologists by using echo-2D. Each team was ‘blinded’ to the findings of each other. All scans were recorded, and a third senior physician reevaluated them.
Results: From 2570 term neonates of the general population, they detected 47 CHD’s. From them, 17 were critical and severe-CHD and 7/47(14.9%) were of moderate complex. 17/47 (36.2%) were cyanotic and 30/47(63.8%) were non-cyanotic. The incidence of simple CHD was 25/47(53.2%). Analysis of the specific anatomy is presented in table1. The estimated incidence was 1.83%. As this incidence has been among the highest reported a post hoc analysis has clarified and presented an important clinical rate of 1.48% after redacting minimal defects without any clinical significance, as minor PDA’s, ASD II, VSD’s. A post hoc calculation of BAov, revealed an anatomical BAov incidence of 1.65% and a functional BAov incidence of 1.4%.
Conclusions: This first-ever prospective epidemiology study in Azerbaijan involving a cohort equal to 1.65% of the annual living births of the country, estimated a high incidence of CHD. This is among the highest reported globally. The amount of critical and severe CHD after the post hoc analysis increased from 46.8% to 55.3%. The incidence of cyanotic CHD after the post hoc analysis increased from 36.2% to 42.1%. These high numbers are possibly related to an isolated population and conjugated marriage customs of the country. As this represented a state population health burden a post hoc analysis based on clinical important CHD minimized the calculated index nearby 20%.
General versus spinal anesthesia in percutaneous nephrolithotomy: A systematic review and meta-analysis
Authors: Indra Rachman Rinaldo , Birowo Ponco , Nurullah Ghifari , Cho Prof. Sung Yong , Atmoko Widi , Widyahening Indah Suci , Rasyid Nur 
Published: March 2023

Background: Percutaneous nephrolithotomy (PCNL) is the preferred treatment for the removal of large kidney stones, sized >20 mm. However, there is still an ongoing debate concerning the best anesthesia for PCNL. This study aimed to compare the efficacy and safety between general and spinal anesthesia for PCNL. Methods: A systematic review and meta-analysis study. A systematic, electronic literature search was performed in several databases, including PubMed, Scopus, and Google Scholar until July 1st, 2022. The quality of the articles was examined using Crombie's Items (for non-randomized controlled trials (RCTs)) and Jadad Scale (for RCTs). The outcomes assessed were operation time, fluoroscopy time, length of stay, stone-free rate, overall complication rate, specific postoperative complications, cost, pain score, and postoperative analgesic requirement. The article selection was reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We assessed four RCTs and eight retrospective studies. Meta-analysis of selected studies was performed using the Review Manager 5.3. Results: General anesthesia resulted in fewer Clavien–Dindo grade II (OR: 0.68; 95% CI: 0.49 – 0.94; p=0.02), major complications (OR: 0.65; 95% CI: 0.45 – 0.94; p=0.02, and lower transfusion rates (OR: 0.70; 95% CI: 0.53 – 0.94; p=0.02). Whereas spinal anesthesia resulted in faster operation time (Mean Difference: -12.98; 95% CI: -20.56 – -5.41; p<0.001, fluoroscopy time (MD: -26.15; 95% CI: -42.79 – -9.50; p=0.002), reduced length of stay (MD: -0.47; 95% CI: -0.75 – 0.20; p<0.001), and lower postoperative analgesic requirement and cost. No significant difference in stone-free rate (OR: 1.08; 95% CI: 0.92 – 1.26; p=0.37). PCNL performed using either general anesthesia or spinal anesthesia is equally safe and effective. Conclusions: Each method of anesthesia has its own advantages and disadvantages. The final choice between general and spinal anesthesia should be based on the patient's condition and surgical team preference.
Knowledge and Practice of Herbal Medicine on Oral Health among Dental Personnel in Malaysia
Authors: Tabnjh Abedelmalek , W Ahmad Wan Muhamad Amir , Hasan Ruhaya , bin Sinor Mohd Zulkarnain , de Abreu Mauro Henrique Nogueira Guimarães , Wong Ling Shing , Djearamane Sinouvassane , Selvaraj Siddharthan 
Published: March 2023

Objective: To investigate the association between knowledge and practice of medical herbs related to oral heath among staffs at School of Dental Sciences, Universiti Sains Malaysia, Malaysia. Methods: A cross-sectional study was conducted at the School of Dental Sciences, USM, on 100 lecturers, dental surgery assistants, nurses, administrative workers, and dental technicians. A set of knowledge and practice questionnaire was used in this study. Descriptive statistics, chi-square and correlation were used to analyze the data. Results: The results showed that the dental staff's knowledge of oral herbal medicines was 32.8%. This indicates that they had a moderate level of knowledge. Almost three-quarters of the employees (73%) practiced at a low level (0-25%), while only 13.85% practiced at a moderate level. The findings revealed that there was no significant relationship between knowledge and practice scores and age or gender. The results, from the other hand, revealed a significant association between practice scores and the type of occupations among staff (P=0.04). The Correlation analyses shows a moderately positive relationship between knowledge and practice. Conclusions: Dental staff had a moderate level of knowledge and a poor level of practice with regard to herbal medicines for oral health. There was a significant association between age and knowledge and there was a significant association between the knowledge and practice among the dental personnel