bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I/II, open label, single arm study on safety, tolerability and anti-tumour effiacy of orellanine treatment in patients with metastatic clear-cell or papillary renal cell carcinoma.
Authors: Lundstam Sven , Haraldsson Boerje , Nystrom Jenny , Yachnin Jeffrey 
Published: January 2024

TPS486 Background: Poisoning by the mushroom ”deadly webcap”( Cortinarius sp.) causes irreversible kidney damage but there are no known effects on other organs. The fungal toxin, orellanine, selectively targets proximal tubular cells in rats and in humans by disturbing the cell metabolism causing decreased protein synthesis and apoptosis. Clear cell and papillary renal cell carcinoma (RCC) originate from proximal tubule cells. Orellanine induced concentration-dependent decline in viability in RCC cell lines and in primary cultures from human clear cell and papillary RCC. Orellanine induced apoptosis and tumour shrinkage in RCC(SKRC-17) transplanted to rats on peritoneal dialysis and the tumours become necrotic with almost no viable tissue. Based on these data a drug has been developed based on chemically synthesized orellanine ( www.oncorena.com ). Methods: The primary objectives of this study are to evaluate the safety and tolerability and to determine the maximum tolerable dose (MTD) of orellanine in patients with metastatic clear cell or papillary RCC and end stage renal disease who are on chronic haemodialysis and who have failed standard of care treatment. The secondary objectives are to study the pharmacokinetic (PK)profile of orellanine and to assess the efficacy of orellanine in treating these patients with respect to objective response (OR). Exploratory objectives are to access progression free and overall survival (PFS and OS) and to conduct analysis of circulating tumour specific DNA in the blood. Serum will be collected for unspecific future research which may include sequencing or genomic analyses. Orellanine will be given intravenously once monthly. A total of 6 to 20 patients will be enrolled in a dose escalation phase to determine MTD or a dose causing complete response (CR). An independent Data Review Committee (DRC) will access cumulative data and provide recommendations and decisions for every change in dose level. Once MTD has been determined up to 20 patients will be treated in a dose expansion phase to better characterize safety, tolerability and primary efficacy. CT/MRI will occur every 4 weeks (Q4W) during dose escalation phase and Q8W during the dose expansion phase. Enrollment has started and since the occurrence of end stage renal disease in patients with metastatic RCC is uncommon, patients in this first in man study are recruited both from western Europe and north America. The study is performed in the Centre for Clinical Cancer Studies (CKC) at Karolinska University Hospital, Stockholm, Sweden Reference: Lisa Buvall et. al. Orellanine specifically targets renal cell carcinoma.Oncotarget. 2017; 8:91085-91098. https://doi.org/10.18632/oncotarget.19555 . Clinical trial information: NCT05287945 .
ABLE-41: Nadofaragene firadenovec-vncg early use and outcomes in a real-world setting in the United States.
Authors: Daneshmand Siamak , Shore Neal D. , Scholz Kristen , Guo Amy , Juul Kristian , Guedes Sandra , Delattre Diane Dalila , Lotan Yair 
Published: January 2024

TPS705 Background: Approximately one-third of patients with non–muscle-invasive bladder cancer (NMIBC) initially responding to Bacillus Calmette-Guérin (BCG) experience recurrence and/or progression in the first year after treatment.1 Local, effective, bladder-preserving options are needed for patients with BCG-unresponsive NMIBC. Nadofaragene firadenovec-vncg is the first FDA-approved intravesical gene therapy for treatment of high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) ± papillary tumors. In a single-arm, multicenter, open-label, repeat-dose, phase 3 study, 53.4% of patients (55/103) with CIS ± high-grade Ta/T1 BCG-unresponsive NMIBC achieved complete response (CR) 3 months after the first instillation of nadofaragene firadenovec.2 The safety profile of nadofaragene firadenovec was manageable, with 103 (66%) patients reporting mild (grade 1/2) study drug-related adverse events (AEs). Six (3.8%) patients had grade 3/4/5 study drug-related AEs. ABLE-41 (NCT06026332) is an observational study evaluating the effectiveness, overall experiences, patterns of use, and safety in patients treated with nadofaragene firadenovec in a US real-world setting. Methods: This noninterventional study includes approximately 50 urology sites in the U.S. with anticipated enrollment of 800 patients. Adults ≥18 years with prescribed and scheduled treatment with nadofaragene firadenovec per physician discretion or those who received their first instillation of nadofaragene firadenovec per physician discretion after September 5, 2023, but before site activation are eligible to enroll. The primary objective is to assess the effectiveness of nadofaragene firadenovec measured as the CR rate as determined by investigator. Secondary outcomes include: nadofaragene firadenovec patterns of use; duration of CR, recurrence-free survival, cystectomy-free survival, progression-free survival, overall survival, and bladder cancer–specific mortality; patient, caregiver and physician experiences; adjunctive use of molecular markers; and safety. Patient and caregiver experiences will be assessed using the respective EuroQol 5 Dimension 5 Level questionnaire and Work Productivity and Activity Impairment questionnaire, adapted for caregiving. Patients and caregivers will be surveyed before all nadofaragene firadenovec administrations. Physicians will be surveyed 1, 12, and 24 months after first patient first instillation. All AE data will be collected starting from index date. The estimated follow-up period is 24 months, until study discontinuation, or withdrawal. Final results from this large, prospective, multi-institutional, real-world registry providing early use and outcomes of nadofaragene firadenovec are expected December 2026. References: 1. Sylvester RJ et al. Eur Urol. 2010;57:766-73; 2. Boorjian SA et al. Lancet Oncol. 2021;22:107-17. Clinical trial information: NCT06026332 .
Intravesical recombinant BCG followed by perioperative chemo-immunotherapy for patients with muscle-invasive bladder cancer (MIBC): A multicenter, single arm phase 2 trial (SAKK 06/19).
Authors: Cathomas Richard , Spahn Martin , Hayoz Stefanie , Chiquet Sabrina , Schneider Martina , Rentsch Cyrill A. , Rothschild Sacha , Petrausch Ulf 
Published: January 2024

TPS707 Background: The integration of immune checkpoint inhibitors (ICI) in the perioperative setting of localized muscle-invasive bladder cancer (MIBC) is extensively investigated and several results from phase 2 trials have been published. While promising, the pathological complete remission rate (pCR, ypT0 ypN0) achieved with ICI-containing regimens appears similar to cisplatin-based chemotherapy alone. Further improvement is needed. Intravesical BCG has successfully been used for decades for non-muscle invasive bladder cancer (NMIBC) in patients (pts) with carcinoma in situ (CIS) and as adjuvant treatment for high-risk papillary tumors. Intravesical BCG induces a local inflammation leading to induction of the innate immune system, probably followed by a tumor-specific adaptive immune response. Recently, a novel recombinant BCG vaccine (VPM1002BC) has been developed and a clinical study in BCG-refractory NMIBC (SAKK 06/14, Eur Urol Oncol. 2022 Apr;5(2):195-202.) has demonstrated good safety with low local toxicity and promising efficacy. We hypothesize that induction therapy with intravesical VPM1002BC improves the efficacy of systemic perioperative chemo-immunotherapy in pts with operable MIBC. Methods: SAKK 06/19 is an open-label single arm phase II trial for pts with operable pT2 or cT2-T4a cN0-1 MIBC without contraindication for cisplatin. Prior intravesical BCG is excluded as are pts unable to keep BCG instillation for less than 1 hour. Intravesical VPM1002BC is administered weekly for 3 instillations. Atezolizumab (atezo) 1200mg is given on day 1 and then every 3 weeks (q3w) for four times. Chemotherapy with cisplatin (70mg/m2 day 1) and gemcitabine (1000mg/m2 day 1 & 8) q3w is started on day 22 and given for four cycles followed by radical cystectomy and lymphadenctomy. Atezo is continued after surgery for 13 cycles in case of residual muscle invasive disease (≥ypT2) or positive lymph nodes (ypN+) only. pCR at cystectomy is the primary endpoint. A total of 46 pts is needed (including 15% dropout rate) using Simon’s minimax two-stage design with type I error 5%, power 80%, a null hypothesis of ≤35% pCR and an alternative hypothesis of ≥55% pCR. Secondary endpoints include pathological response rate (<ypT2N0), event-free survival, recurrence-free survival, overall survival, feasibility and toxicity. An interim safety analysis will be performed after the first 12 pts have completed neoadjuvant treatment specifically assessing toxicity possibly associated with intravesical BCG application. An interim efficacy analysis will be performed after the first 21 pts have undergone surgery. Accrual to the study is currently ongoing (NCT04630730). Clinical trial information: NCT04630730 .
Phase I/II study of ipilimumab plus nivolumab (IPI-NIVO) combined with sacituzumab govitecan in patients with metastatic cisplatin-ineligible urothelial carcinoma.
Authors: Jain Rohit K. , Yang Yuanquan (Aaron) , Chadha Juskaran , Zhang Jingsong , Raymond Sarah , Oschmann Erika , Poehlman Trey , Fan Wenyi , Kim Youngchul , Dhillon Jasreman , Chahoud Jad , Chatwal Monica Sheila , Sonpavde Guru P. 
Published: January 2024

TPS713 Background: Treatment options are suboptimal and limited for cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. Sacituzumab govitecan (SG) is a Trop-2 directed antibody-drug conjugate (ADC) coupled with SN-38 through a hydrolysable linker. In the phase II TROPHY-U-01 study, SG demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.5 months in mUC patients who progressed after platinum-based chemotherapy and immune checkpoint inhibitors (ICI), receiving accelerated approval by the US FDA. In CheckMate 032 study, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1+I3) every 3 weeks (Q3W) x 4 cycles followed by nivolumab monotherapy 3mg/kg Q2W showed promising activity post-platinum that led to the ongoing phase III trial in the first-line setting (NCT03036098). Given potential synergism between immunogenic cell death induced by ADC and ICI, we hypothesized that the combination of SG and IPI-NIVO would benefit patients with manageable toxicities. We designed this study to assess the safety and clinical activity of IPI-NIVO with SG as first-line therapy for cisplatin-ineligible mUC patients. Methods: This is an ongoing phase I/II, single arm, multicenter study for cisplatin-ineligible mUC. The Phase I portion enrolled 9 patients using a 3+3 design with safety and RP2D as primary endpoints. In this part, patients received fixed doses of IPI-NIVO (N1+I3) IV Q3Wx 4 cycles combined with SG (DL1 8 mg/kg or DL2 10mg/kg) IV on days 1, 8 Q3W x 4 cycles. This was followed by maintenance nivolumab 360 mg IV Q3W with SG on days 1, 8 Q3W. The RP2D of SG was determined as 8 mg/kg and combination was deemed safe and tolerable. ORR is the primary endpoint in the ongoing phase II portion of the study using Simon 2 stage design (n=34) with a futility interim analysis after 13 patients. The null hypothesis of ORR ≤ 38% will be tested with a desirable ORR of >60% under a statistical power of 80% and a one-sided type I error rate of 5%. Thirteen of the 34 patients have been enrolled and the study has passed the predefined interim analysis for futility. We aim to continue accrual. Exploratory biomarker analyses will be conducted using tumor and blood samples collected during screening and at progression. Clinical trial (NCT04863885). Clinical trial information: NCT04863885 .
Pembrolizumab with favezelimab or vibostolimab for patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Phase 2 KEYNOTE-057 cohort C.
Authors: Kulkarni Girish S. , Gupta Shilpa , Necchi Andrea , Shore Neal D. , Dave Hema Kishore , Kapadia Ekta , Zhao Qing , Kamat Ashish M. 
Published: January 2024

TPS719 Background: In cohort A of the phase 2 KEYNOTE-057 study (NCT02625961), the PD-1 inhibitor pembrolizumab demonstrated antitumor activity (3-month complete response rate, 41%) in patients with BCG-unresponsive HR NMIBC with carcinoma in situ (CIS) ± papillary tumors who are ineligible for or declined radical cystectomy (RC). However, treatment combinations that improve outcomes and durability of response with pembrolizumab monotherapy are needed. Coinhibitory receptors LAG-3 and TIGIT contribute to immune tolerance in the tumor microenvironment, and co-blockade of PD-1 with LAG-3 or TIGIT has demonstrated antitumor activity in clinical studies. In cohort C of KEYNOTE-057, efficacy and safety of coformulations of pembrolizumab and the LAG-3 inhibitor favezelimab or the TIGIT inhibitor vibostolimab are being evaluated in patients with BCG-unresponsive HR NMIBC with CIS ± papillary tumors. Methods: Key eligibility criteria include adults with histologically confirmed HR NMIBC (CIS ± high-grade Ta or T1 at baseline) that is BCG-unresponsive (persistent or recurrent CIS ± Ta/T1 ≤12 month of completing adequate BCG therapy) who are ineligible for or declined RC and have an ECOG PS of 0-2. Enrollment is planned for 60 patients. Patients will be randomly assigned 1:1 to receive the coformulation of pembrolizumab 200 mg and vibostolimab 200 mg or the coformulation of pembrolizumab 200 mg and favezelimab 800 mg intravenously every 3 weeks for ≤35 cycles or until central pathology–confirmed ≥T1 at any time point, persistent or recurrent CIS or high-grade Ta at 24-week efficacy review or thereafter, unacceptable toxicity, patient or physician decision to withdraw, or administrative reasons to discontinue. Tumor assessment will be performed every 12 weeks for 2 years and every 24 weeks thereafter for up to 5 years. Primary end point is 12-month complete response rate of HR NMIBC by cystoscopy, cytology, biopsy, and radiologic imaging by central pathology and radiology review. Secondary end points include duration of response of HR NMIBC; overall complete response rate and complete response rates at 3 and 6 months; progression-free survival (PFS) to worsening of grade, stage, or death; PFS to muscle-invasive or metastatic disease or death; and overall survival. Efficacy will be evaluated in patients who receive ≥1 dose of treatment and have a baseline evaluation consisting of pre-enrollment cystoscopy, TURBT/biopsy, urine cytology, and baseline CTU imaging. Safety and tolerability will be evaluated in patients who receive ≥1 dose of treatment. Enrollment is ongoing in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT02625961 .
A 15-Year Analysis of Supply and Demand for Hematology and Oncology Training in the United States
Authors: Silvestre Jason , Aakhus Erin , Weldeslase Terhas A. , DeLisser Horace M. 
Published: January 2024

PURPOSE
There is a paucity of research on the supply of the hematology and oncology workforce despite projected shortages in the United States Over the past 15 years of the hematology and oncology match (HOM), we hypothesized that there would be more growth in the number of training positions relative to applicants, higher match rates for US allopathic graduates relative to non-US allopathic graduates, and fewer applicants matching at their top fellowship choices.

METHODS
This was a national, retrospective cohort study of all applicants in the HOM (2009-2023). Match rates and applicant-to-training position ratios were calculated and compared over time with Pearson tests.

RESULTS

Growth in the number of annual training positions (426-708; 66% increase) exceeded growth in the number of interested applicants (706-945; 34% increase;
P
< .001). Annual applicant-to-training position ratios decreased from 1.7 to 1.3 (
r
= –0.813;
P
< .001). Match rates increased over the study period for both US allopathic graduates (79%-88%;
r
= 0.761;
P
= .001) and non-US allopathic graduates (45%-63%;
r
= 0.801;
P
< .001). During each year, match rates for US allopathic graduates exceeded those for non-US allopathic graduates (
P
< .001). From 2018 to 2023, US allopathic graduates (83%) had higher match rates than US osteopathic graduates (60%) and international medical graduates (50%;
P
< .001). The percentage of applicants that matched at one of their top three fellowship choices increased from 53% to 60% (
r
= 0.480;
P
= .070). Fewer available annual training positions went unfilled over the study period (3%-0.3%;
r
= – 0.870;
P
< .001).

CONCLUSION
Match rates have increased in the HOM but remain competitive especially for non-US allopathic graduates. Future investigation is needed to understand disparities in match outcomes by additional applicant and fellowship program characteristics. Ongoing surveillance of HOM outcomes remains critical given the projected shortages in the US hematology and oncology workforce.
Enhancing relay synchronization in multiplex networks by repulsive relay layer
Authors: Wei Zhouchao , Sriram Gokulakrishnan , Rajagopal Karthikeyan , Jafari Sajad 
Published: January 2024

Abstract
Relay synchronization, which is the interlayer synchronization of two indirectly connected layers, is an important phenomenon in multiplex networks. In this study, relay synchronization is investigated through a triplex network of Hindmarsh-Rose neurons while considering attractive and repulsive intralayer couplings. Relay synchronization is improved when the remote layers have attractive coupling, and the relay layer has repulsive coupling. The essential conditions for the local stability of relay synchronization is found within the framework of master stability function approach. The analytical results are supported by numerical data on synchronization error. Furthermore, enhanced relay synchronization is also shown for larger networks and different internal couplings. Finally, the generality of the results is confirmed by investigating a triplex network of Rössler systems.
Dynamic modeling of neuromodulation techniques: Towards elaboration and individual specificity
Authors: Yu Ying , Han Fang , Wang Qingyun 
Published: January 2024

Abstract
Neurological disorders place a significant burden on patients, their families, and society, posing immense scientific challenges in terms of treatment and mechanistic research. Neuromodulation involves the application of invasive or non-invasive technologies to externally manipulate the nervous system of the brain, aiming to provide excitatory or inhibitory modulation that can improve abnormal neural activity. In the previous studies, neurodynamic analysis methods have not only provided novel tools for the study of neuromodulation techniques, but also provided new modulation strategies for the diagnosis and treatment of neurological diseases. In this paper, we present a brief overview of the current state of dynamic modeling and analysis for various neuromodulation techniques, including electrical, optical, magnetical, and ultrasonic approaches, and discuss the future prospects of modeling and analysis developments in neuromodulation.
Cholam Talks: The Origins of Migueleño in a Multilingual Region
Authors: Scharlotta Ian 
Published: January 2024

Abstract
Archaeological settlement CA-MNT-2328 (Cholame Valley, California) is likely the named Migueleño Salinan Rancheria of Cholam. Several areas of uncertainty about the origin of the Migueleño dialect and how it related to regional trade language(s) became apparent while trying to clarify this attribution. Multiple Salinan dialects were recognized in use at Missions San Antonio, San Miguel, and San Luis Obispo during the eighteenth and nineteenth centuries, with variable interpretations of their associated ethnogeography. Missing or contradictory information in historical and ethnographic records cloud attribution of linguistic or cultural affiliation to archaeological settlements in areas known as travel and trade corridors.
Non-invasive methods for heart rate measurement in fish based on photoplethysmography
Authors: Deng Yacheng , Hu Tianyu , Chen Jia , Zeng Junjia , Yang Jinqian , Ke Qiaozhen , Miao Lingwei , Chen Yujia , Li Rui , Zhang Rongxin , Xu Peng 
Published: January 2024

ABSTRACT
Heart rate is a crucial physiological indicator for fish, but current measurement methods are often invasive or require delicate manipulation. In this study, we introduced two non-invasive and easy-to-operate methods based on photoplethysmography, namely reflectance-type photoplethysmography (PPG) and remote photoplethysmography (rPPG), which we applied to the large yellow croaker (Larimichthys crocea). PPG showed perfect synchronization with electrocardiogram (ECG), with a Pearson's correlation coefficient of 0.99999. For rPPG, the results showed good agreement with ECG. Under active provision of green light, the Pearson's correlation coefficient was 0.966, surpassing the value of 0.947 under natural light. Additionally, the root mean square error was 0.810, which was lower than the value of 1.30 under natural light, indicating not only that the rPPG method had relatively high accuracy but also that green light may have the potential to further improve its accuracy.
NCLB Alternate Assessment Policies and Postschool Employment Outcomes for Individuals With Significant Cognitive Disabilities
Authors: Shepley Collin , Waddington R. Joseph 
Published: January 2024

Abstract
The participation of students with significant cognitive disabilities in accountability assessments aligned with general education standards is a heavily debated topic in the field of special education. Attempts to understand the impact of these assessments have generally been limited to correlational methods. We employed a difference-in-differences approach using select waves of the National Longitudinal Transition Study-2 dataset to estimate the impact of alternate assessment policies from the No Child Left Behind Act of 2001 on the employment outcomes of individuals with significant cognitive disabilities. Our hypothesis was that these policies would produce a detrimental effect. Analyses suggested that alternate assessment policies resulted in descriptively positive employment outcomes, yet estimates were highly imprecise, which yields a complicated picture requiring more research.
Factors That Influence the Tenure of Direct Support Professionals in New York State Provider Agencies
Authors: Mir Hirah A. , Liu Qingyang , Rosca Oxana , Blakeslee Emily 
Published: January 2024

Abstract
The New York State Office for People With Developmental Disabilities seeks to better understand the direct support professional (DSP) workforce and offer data-informed strategies for DSP retention. We used the 2018 NCI-IDD Staff Stability Survey (now called State of the Workforce Survey) to investigate agency-level factors influencing DSP tenure. A total 303 provider agencies completed the survey in New York State, representing 72,252 DSPs. Multiple linear regression analysis revealed that selected agency-level variables explained 12.6% of the variance in DSP tenure, R2 = .16, Radj2 = .126, F (11, 260) = 4.54, p &lt; .05. This study yielded strong empirical evidence consistent with existing national reports and research on the role that wages, benefits, and supervisory support play on DSP tenure.