bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized, multi-center, phase 2 study of ivaltinostat (Ival) plus capecitabine (Cape) versus capecitabine alone in the maintenance setting in patients with metastatic pancreatic adenocarcinoma (mPDAC).
Authors: Fountzilas Christos , Ko Andrew H. , Borazanci Erkut Hasan , D'Olimpio James Thomas , Hecht J. Randolph , Tang Shou-Ching , Shields Anthony F. , Salkeni Mohamad Adham , Michelson Glenn , Cho Gene , Liganor Lorna , Cho Sangsook Ahn , Walker Evan Justin 
Published: July 2024

TPS4206 Background: Front-line chemotherapy for patients (pts) with advanced or mPDAC typically consists of mFOLFIRINOX or gemcitabine/nab-paclitaxel given until disease progression or intolerable toxicity. For pts with durable disease control on front-line treatment, maintenance therapy that can effectively delay disease progression while preserving quality of life with minimal cumulative toxicity is highly desirable. Ivaltinostat (ival) is a pan-histone deacetylase inhibitor that increases histone acetylation, suppresses PDAC cell proliferation, and promotes apoptosis in PDAC cell lines. Preclinical data demonstrated synergy with 5-FU/cape in mouse models. RP2D of the Phase 1b combination study of ival and cape in advanced pancreatic cancer was ival 250mg/m2 IV on days 1 and 8 with cape 1000mg/m2 po days 1-14 of a 21-day cycle. Both ival and cape treatment-related AEs >15% were fatigue, nausea, diarrhea, and decreased appetite. Palmar-plantar erythrodysaesthesia syndrome was also commonly observed; all events were attributed to cape. PK and PD demonstrated dose proportionality. Overall and progression-free survival (PFS) were immature, but 70% of pts who enrolled with measurable disease had stable disease as best response. Several pts remained on study with the longest duration of response about 10 months, as of the data cut off for ASCO GI 2024. Based on this data, a randomized phase 2 study is being conducted comparing the combination of ival and cape versus cape alone in the maintenance setting for pts with mPDAC after first line FOLFIRINOX, mFOLFIRINOX or NALFIRINOX therapy. Methods: Key eligibility criteria for the randomized Phase 2 study include: mPDAC; no evidence of disease progression following at least 16 weeks of front-line FOLFIRINOX or NALIRIFOX at full or modified doses; ECOG PS 0-1; and no known germline BRCA1/2 mutation. A total of 52 pts will be randomized 1:1 to receive cape with or without ival until disease progression, with tumor assessments occurring at 6-week intervals. The primary endpoint is investigator-adjudicated PFS, and the primary analysis will compare PFS distributions in the ival/cape and cape alone arms using a one-sided log rank test with an alpha=0.10. The assumed 6-mo PFS rates are 35% (cape), based on historic data, and 60% (ival/cape), corresponding to an HR of 0.487. Enrollment in the phase 2 study began in January 2024 across multiple sites in the US. Accrual is anticipated to complete 4Q2024. Clinical trial information: NCT05249101 .
CheMo4METPANC: A randomized phase 2 study with combination chemotherapy (gemcitabine and nab-paclitaxel), chemokine (C-X-C) motif receptor 4 inhibitor (motixafortide), and immune checkpoint blockade (cemiplimab) compared to chemotherapy alone in metastatic treatment-naïve pancreatic adenocarcinoma.
Authors: Manji Gulam Abbas , May Michael S. , Chalabi Morteza , Pellicciotta Ilenia , Sta Ana Sarah , Sender Naomi , Pan Samuel M , Ross Isabelle , Wang Shikun , Izar Benjamin , Wu Linda , Labadie Brian William , Bates Susan Elaine , Shi Qian , Raufi Alexander G 
Published: July 2024

TPS4208 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) carries a 5-year relative survival of 3%. Immune checkpoint inhibitors have thus far failed to improve outcomes due to an immunosuppressive tumor microenvironment (TME). Signaling through the C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12) axis results in exclusion of anti-tumor immune cells in mouse PDAC models. Longitudinal survival studies testing combinations of CXCR4i, aPD-1, and gemcitabine in the KPC mouse model of PDAC demonstrated a survival benefit with the combination of all three agents. Results from a multicenter, investigator-initiated, single arm pilot study evaluating the preliminary safety and efficacy ofMotixafortide (CXCR4i), Cemiplimab (aPD1), Gemcitabine, and Nab-paclitaxel (MCGN) in 11 patients with treatment-naïve mPDAC were recently presented. Seven patients (64%) achieved a partial response, including 6 confirmed partial responses, and 10 patients (91%) had disease control, compared to historic partial response and disease control rates of 23% and 48%, respectively, with gemcitabine and nab-paclitaxel (GN). Preliminary median progression-free survival (PFS) was 9.6 months compared to historic median PFS of 5.5 months with GN. Analysis of paired pre- and on-treatment biopsy samples from demonstrated an increase in CD8+ T-cell density in tumors from all 11 patients treated with MCGN (p=0.007). Based on these promising results, the protocol was amended from a single arm expansion totaling 40 patients to a randomized phase 2 study. Methods: This is an open-label, multicenter, investigator-initiated phase 2 clinical trial. Patients are randomized 2:1 to receive MCGN or GNalone (N=108). The primary endpoint is progression free survival. The study has 80% power to detect an improvement in PFS from 6 to 9.2 months (HR 0.65) with a one-sided alpha of 0.20. One interim analysis for futility is planned when 50% of the PFS events are observed. Secondary objectives include response rate, disease control rate, duration of clinical benefit and overall survival. Patients will undergo optional paired biopsies which will be analyzed in conjunction with samples collected from the phase I pilot study. Exploratory studies include interrogation of the TME using quantitative multiplex immunofluorescence and single-cell RNA sequencing. The randomized phase 2 trial is open to enrollment and one patient has been randomized as of 1/29/2024. Clinical trial information: NCT04543071 .
A phase II study of cadonilimab plus mFOLFIRINOX as induction therapy for locally advanced pancreatic adenocarcinoma (LAPC).
Authors: Jiang Kuirong , Tu Min , Xu Dong , Lv Nan , Wang Qianqian 
Published: July 2024

TPS4213 Background: Locally advanced pancreatic adenocarcinoma (LAPC) constitutes a significant proportion of pancreatic cancer, which ranks among the most lethal malignancies globally. Treatment options specifically tailored for LAPC patients (pts) are scarce, and chemotherapy alone yields limited efficacy. Various studies have provided supportive evidence for the synergistic effects of combining immunotherapy with chemotherapy in the context of pancreatic cancer. Cadonilimab, a novel recombinant humanized bispecific antibody, holds the capability to concurrently inhibit PD-1 and CTLA-4 pathways, thereby restoring T-cell immune response to the tumor. This study aims to assess the efficacy and safety of combining cadonilimab with modified FOLFIRINOX for the treatment of LAPC. Methods: This ongoing phase II trial is enrolling pts with histologically or cytologically confirmed unresectable LAPC who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 and have not previously received systemic anti-tumor therapy. Eligible pts will be administered cadonilimab (6mg/kg, intravenous drip, Day 1, every 2 weeks) plus mFOLFIRINOX (oxaliplatin 85mg/m2, Day 2 + leucovorin 400mg/ m2, Day 2 + irinotecan 150mg/ m2, Day 2 + 5-fluorouracil 2,400mg/ m2, continuous infusion for 46 hours) for a total of 4 cycles (8 weeks). After the completion of every 4 treatment cycles, pts will undergo imaging examinations of tumor lesions. Pts will receive treatment continuously until surgical resection, disease progression, intolerable toxic reactions, initiation of new anticancer drug treatments, withdrawal from the study, death, or loss of follow-up. Following the 12th cycle of treatment, maintenance treatment will consist of capecitabine or S-1 in combination with cadonilimab. The primary endpoint of this study was the R0/R1 resection rate. The main secondary endpoints include the objective response rate (ORR) per RECIST 1.1, progression-free survival (PFS), overall survival (OS), and safety assessments. Additionally, pts will undergo peripheral blood next-generation sequencing (NGS) panel analysis before and after treatment to investigate the correlation between circulating tumor DNA (ctDNA) changes, surgical decisions, and prognosis. Enrollment is ongoing. Clinical trial information: NCT06153368 .
A phase II study evaluating the effect of IMNN-001 on second-look laparoscopy (SLL) when administered in combination with bevacizumab (BEV) and neoadjuvant chemotherapy (NACT) in patients newly diagnosed with advanced epithelial ovarian cancer (EOC).
Authors: Jazaeri Amir A. , Grisham Rachel N. , Gaillard Stephanie , How Jeffrey Andrew , Hazard Sebastien , Musso Lauren , Kyi Chrisann 
Published: July 2024

TPS5633 Background: IMNN-001, an interleukin-12 (IL-12) DNA plasmid formulated with a DNA carrier, polyethyleneglycol-polyethyleneimine cholesterol lipopolymer, has been shown to exhibit a favorable benefit/risk ratio when administered intraperitoneally (IP), in combination with intravenous platinum-taxane chemotherapy, up to doses of 100 mg/m2 in women with advanced EOC in earlier Phase I & II studies. The 201-21-202 study (NCT05739981) is a multi-center, randomized, open-label phase I/II study which hypothesizes the addition of IMNN-001 to neoadjuvant & adjuvant carboplatin-paclitaxel and bevacizumab (chemo + BEV) reduces the risk of histologically documented minimal residual disease (MRD) as determined by SLL by 50%. Methods: Patients with newly diagnosed stage III and IV high grade serous EOC who are candidates for NACT will be enrolled into the trial. Initial safety lead-in will evaluate at least 6 patients randomized to the experimental arm. Upon confirmation of safety by the DSMB, a target of ~50 patients will be randomized 1:1 to receive either chemo + BEV with or without IMNN-001. Patients receive at least 4 cycles of NACT followed by interval cytoreductive surgery (ICS), and 3 additional adjuvant cycles of study treatments will be administered. BEV will be included with each cycle except cycle 1, the last cycle of NACT immediately preceding ICS, and the first cycle of adjuvant chemotherapy. In the experimental arm, IMNN-001 will be administered on C1D15 and continue weekly though the last cycle of adjuvant therapy. Following adjuvant therapy, all patients will undergo SLL with peritoneal washing and multiple biopsies. Pathologic detection of residual tumor in any biopsies or peritoneal cytology constitutes presence of MRD. All patients will receive maintenance therapy with Olaparib + BEV, IMNN-001 + BEV, or BEV alone based on their homologous recombination deficiency status and treatment randomization. Translational:All subjects will undergo biospecimen collection and organoid preparation prior to treatment, at the time of ICS and SLL for comprehensive longitudinal genomic, circulating tumor DNA, immune, and microbiome profiling. Subjects in the experimental arm will also undergo peritoneal lavage and collection of fluid and cells for assessment of the peritoneal tumor environment. Endpoints: The primary endpoint is the rate of MRD at SLL. Secondary endpoints include progression-free survival, overall survival, objective response rate, chemotherapy response score, surgical response, and serologic response. All patients will be evaluated for safety. Status: The study is actively enrolling and is in the safety lead-in portion. We plan to enlist approximately 4 sites in USA. Clinical trial information: NCT05739981 .
Phase II/III study of paclitaxel/carboplatin alone or combined with either trastuzumab and hyaluronidase-oysk or pertuzumab, trastuzumab, and hyaluronidase-zzxf in HER2 positive, stage I-IV endometrial serous carcinoma or carcinosarcoma (NRG-GY026).
Authors: Erickson Britt Kristina , Enserro Danielle , Lankes Heather A. , Dockery Lauren E. , ghamande sharad A. , Oliver Matthew T. , Gressel Gregory M. , Castellano Tara , Ratner Elena , Deery Amy , Bishop Erin , Bradford Leslie Siriya , Thomes Pepin Jessica , Burton Elizabeth , Blank Stephanie V. , Santin Alessandro , Havrilesky Laura J , Aghajanian Carol , Nickles Fader Amanda , Powell Matthew A. 
Published: July 2024

TPS5641 Background: Uterine serous carcinoma and uterine carcinosarcoma are rare, high-risk uterine cancer subtypes that overexpress HER2 in up to 40% and 10% of cases, respectively. Phase II data demonstrated a benefit in adding trastuzumab in HER2 positive advanced and recurrent uterine serous carcinoma. Dual anti-HER2 therapy has the potential for further improvement in survival. Methods: This is a non-blinded, three-arm randomized phase II/III study. The primary objective is to evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) or a fixed dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive uterine serous carcinoma or carcinosarcoma. The primary outcome of the phase II component is PFS. Depending on the phase II results, the study will progress to a phase III study of either two or three study arms. Patients in the control arm (Arm 1) receive carboplatin and paclitaxel every 3 weeks for 6 cycles. Patients on Arm 2 receive carboplatin and paclitaxel with trastuzumab and hyaluronidase-oysk every 3 weeks for 6 cycles plus one year of maintenance trastuzumab and hyaluronidase-oysk. Patients enrolled on Arm 3 receive carboplatin and paclitaxel with trastuzumab, pertuzumab, and hyaluronidase-zzxf every 3 weeks for 6 cycles plus one year of maintenance trastuzumab, pertuzumab, and hyaluronidase-zzxf . Those with an ongoing partial response may continue maintenance therapy for up to three years. Patients are eligible if they are diagnosed with chemo-naïve, non-recurrent stage IA-IVB myoinvasive uterine serous or carcinosarcoma. All tumors must be HER2 positive as defined by the ASCO/CAP Breast Cancer 2018 guidelines (testing performed locally). Tumors may also be HER2 positive based on next generation sequencing testing. Patients may have measurable, non-measurable, or no measurable disease and may have a plan for vaginal brachytherapy . Key exclusion criteria include severe heart disease or interstitial lung disease. The phase II portion of this study is open and enrolling. Clinical trial information: NCT05256225 .
Renewable, Flexible, and Storage Capacities: Friends or Foes?
Authors: Peng Xiaoshan , Wu Owen Q. , Souza Gilvan C. 
Published: July 2024

Problem definition: More than 99% of the new power generation capacity to be installed in the United States from 2023 to 2050 will be powered by wind, solar, and natural gas. Additionally, large-scale battery systems are planned to support power systems. It is paramount for policymakers and electric utilities to deepen the understanding of the operational and investment relations among renewable, flexible (natural gas-powered), and storage capacities. In this paper, we optimize both the joint operations and investment mix of these three types of resources, examining whether they act as investment substitutes or complements. Methodology/results: Using stochastic control theory, we identify and prove the structure of the optimal storage control policy, from which we determine various pairs of charging and discharging operations. We find that whether storage complements or substitutes other resources hinges on the operational pairs involved and whether executing these pairs is constrained by charging or discharging. Through extensive numerical analysis using data from a Florida utility, government agencies, and industry reports, we demonstrate how storage operations drive the investment relations among renewable, flexible, and storage capacities. Managerial implications: Storage and renewables substitute each other in meeting peak demand; storage complements renewables by storing surplus renewable output; renewables complement storage by compressing peak periods, facilitating peak shaving and displacement of flexible capacity. These substitution and complementary effects often coexist, and the dominant effect can alternate as costs change. A thorough understanding of these relations at both operational and investment levels empowers decision makers to optimize energy infrastructure investments and operations, thereby unlocking their full potential. Funding: This research was supported in part by Lilly Endowment, Inc., through its support for the Indiana University Pervasive Technology Institute. This research was also supported by Kelley School of Business, Indiana University, and Haslam College of Business, University of Tennessee. O. Q. Wu thanks Grant Thornton for their generous support. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0068 .
Empowering Education: Unveiling The Transformative Potential of Pedagogical Competence for Educator and Learners
Authors: Bagea Ishak , Bagea Arfin , Bakar Abu 
Published: July 2024

Paper writing aims to explain the empowering education unveiling the transformative potential of pedagogical competence for educator and learners. Pedagogics is a science that discusses education, namely the science of children's education. So pedagogic explains the ins and outs of children's education, pedagogic is a theory of children's education. Pedagogics as a science is needed by teachers. The task of the teacher is not only to teach to convey or transform knowledge to students at school, but the teacher has the task of developing the personality of his students in an integrated manner.
The teacher develops the child's mental attitude, develops the child's conscience or the child's heart so that the child will be sensitive to humanitarian issues, human dignity, as well as the teacher only develops children's skills, life skills in society so that he is able to face all the problems of his life.
Conclusion in writing papers: pedagogy competence is a set of knowledge, skills, and behaviors that must be possessed, lived and mastered by teachers or lecturers in carrying out professional duties.
This type of research uses qualitative research by means of researchers conducting observations, interviews and documentation with key informants and supporting informants, namely, teachers and students at the Muhammadiyah Kendari Private High School, and the novelty of the results of this research will be useful for the development of science, especially related educational sciences. how teachers and lecturers must master pedagogical competence, social competence, personality competence and social competence.
Conclusion: pedagogical competence has a central role in shaping quality and relevant education. The transformative potential of pedagogical competence not only enriches students' learning experiences, but is also the key to the sustainability and success of the education system in the future. Therefore, continuous efforts in developing and strengthening pedagogical competence need to be implemented as a long-term investment to improve the quality of education.
Optical design and development of an underwater dual-channel microlens array integral field snapshot hyperspectral imager
Authors: Lu Fengqin , Ma Jun , Su Kun , Xue Qingsheng , Miao Qinxuan , Cao Diansheng 
Published: July 2024

Compared to push-scan hyperspectral imagers, snapshot hyperspectral imagers offer an advantage by minimizing sensitivity to attitude jitter in underwater mobile platforms. Here we present the optical design and development of an underwater microlens array integral field hyperspectral imager. The system comprises a panchromatic imaging channel with a high spatial resolution and a spectral imaging channel with a lower spatial resolution. Through the fusion of high-resolution panchromatic images and low-resolution spectral images, we achieve high spatial resolution hyperspectral images. Both the panchromatic imaging channel and the spectral imaging channel share a common front objective, featuring a 25 mm focal length and a wide 36° field of view angle. Utilizing prism dispersion, the spectral imaging system spans a band range from 465 to 700 nm with a spectral resolution of less than 10 nm. Specialized algorithms for spectral image reconstruction and image fusion have been developed. The experimental results across diverse scenes confirm the exemplary spectral imaging performance of the system, positioning it as a robust solution for underwater snapshot hyperspectral imaging.
Twenty-milliwatt, high-power, high-efficiency, single-mode, multi-junction vertical-cavity surface-emitting lasers using surface microstructures
Authors: Xiao Yao , Miao Pei , Wang Jun , Liu Heng , Gou Yudan , Zhang Zhicheng , Wang Bangguo , Liu Wuling , Wang Qijie , Deng Guoliang , Zhou Shouhuan 
Published: July 2024

High-power, high-efficiency single-mode vertical-cavity surface-emitting lasers (VCSELs) are crucial in the realm of green photonics for high-speed optical communication. However, in recent years, the power and efficiency of single-mode VCSELs have remained relatively low and have been progressing slowly. This study combines theoretical models with experiments to show that multi-junction cascaded 940 nm VCSELs based on surface microstructures can achieve high power, high efficiency, and low divergence in single-mode laser output. Simulations show multi-junction VCSELs with surface microstructures can boost mode modulation capabilities, power, and efficiency, potentially allowing high-power single-mode VCSELs to surpass 60% efficiency. Using this technique, the 6 μm oxide aperture VCSELs with surface relief of different diameters were fabricated. The single-mode VCSELs with the output power of 20.2 mW, side-mode suppression ratios greater than 35 dB, 42% electro-optical efficiency, and a 9.8° divergence angle (at 1/e2) under continuous-wave operation were demonstrated. Near-field images verified its fundamental mode operation. To the best of the authors’ knowledge, this is the highest single-mode power recorded for a single-unit VCSEL to date, almost twice the currently known record, while still maintaining a very high electro-optical conversion efficiency. This research will provide valuable references for the further development and application of high-power, high-efficiency single-mode semiconductor lasers.