bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) in patients (pts) with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): 64-month (mo) follow-up from CheckMate 142.
Authors: Lenz Heinz-Josef , Overman Michael J. , Van Cutsem Eric , Limon Maria Luisa , Wong Ka Yeung Mark , Hendlisz Alain , Aglietta Massimo , Garcia-Alfonso Pilar , Neyns Bart , Gelsomino Fabio , Cardin Dana Backlund , Dragovich Tomislav , Shah Usman , McCraith Stephen , Wang Rui , Lei Ming , Yao Jin , Jin Lixian , Lonardi Sara 
Published: January 2024

97 Background: NIVO + IPI demonstrated robust, durable clinical benefit and was well tolerated as a 1L therapy in pts with MSI-H/dMMR mCRC in the phase 2 CheckMate 142 study (NCT02060188), leading to the inclusion of NIVO + IPI in the NCCN guidelines as an initial therapy option for these pts. At 52-mo median follow-up, 1L NIVO + IPI continued to demonstrate durable clinical benefit, and no new safety signals were identified. Here we report longer follow-up results. Methods: Pts with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by investigator assessment (INV) per RECIST v1.1. Other key endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), all by INV; overall survival (OS); and safety. Results: In total, 45 pts received 1L NIVO + IPI. With median follow-up of 64.2 mo (range, 59.4–68.9 mo), ORR by INV was 71% (95% CI, 56–84%). The proportion of pts with a best overall response of complete response (CR) was 20%, partial response (PR) was 51%, stable disease (SD) was 13%, and progressive disease was 16%. Median DOR (mDOR) was not reached, and the 60-mo DOR rate was 72%. Median PFS (mPFS) by INV and median OS (mOS) were not reached, with 60-mo PFS and OS rates of 55% and 67%, respectively (Table). Among pts alive at the data cutoff (n = 31), 30 remained treatment-free after initial study treatment without receiving any subsequent systemic therapy, with a median treatment-free interval of 34.7 mo (range, 1.6–61.4 mo). Exploratory analysis by tumor mutational burden status will be presented. Safety data are shown in the Table. Conclusions: At 64-mo follow-up, NIVO + IPI continued to demonstrate clinically meaningful survival and durable responses, with mPFS, mOS, and mDOR still not reached, suggesting the potential for long-term clinical benefit. Safety remained consistent with previous data. These findings further support current recommendations for NIVO + IPI as a 1L treatment for pts with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188 . [Table: see text]
mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer (FROST trial): Study protocol for an open label, multicenter, randomized, phase II study.
Authors: Lee Kyung-ha , Kim Ji Yeon , Yang In Jun 
Published: January 2024

TPS230 Background: Patients with high-risk stage III colon cancer have a significantly poorer prognosis than those with stage II or low-risk stage III colon cancer. Despite this distinction, most guidelines recommend similar adjuvant treatment approaches for all stages, and there is a dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis through more intensive adjuvant treatment. Given the proven efficacy of triplet chemotherapy in metastatic colorectal cancer, this study aims to assess the effectiveness and toxicity of modified 5-fluoropyrimidine (5-FU)/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) in comparison with the current standard of care—modified oxaliplatin and 5-FU (mFOLFOX-6)—as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer. Methods: This multicenter, randomized (1:1), open-label, phase II trial aims to compare the adjuvant treatment efficacy of mFOLFIRINOX and mFOLFOX-6 in patients with high-risk stage III colon cancer. The trial aimed to enroll 312 eligible patients aged between 20 and 70 years with an Eastern Cooperative Oncology Group performance status of 0-2, or between 70 and 75 years with an Eastern Cooperative Oncology Group performance status of 0. All patients underwent radical resection and were randomized into two arms: Arm A experimental arm, received 12 cycles of mFOLFIRINOX every 2 weeks, while arm B, the reference arm, received 12 cycles of mFOLFOX 6 every 2 weeks. The primary endpoint of this study was the 3-year disease-free survival, whereas the secondary endpoints included assessing the 3-year overall survival and treatment toxicity. Discussion: The Frost trial is expected to elucidate the safety and oncologic efficacy of mFOLFIRINOX compared to mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancers, and provide evidence about this treatment, and contribute to improve the prognoses ultimately. Clinical trial information: NCT05179889 .
Atezolizumab and bevacizumab in combination with TACE for patients with BCLC B HCC.
Authors: Stein Stacey , Cheng Wei , Wiess Christina , Pollak Jeffrey , Perez Lozada JuanCarlos , Chapiro Julius , Madoff David C. 
Published: January 2024

TPS584 Background: The combination of atezolizumab and bevacizumab (AB) is an effective regimen for patients with advanced HCC1. Moving effective systemic therapy to earlier stages of HCC is a priority in improving outcomes. Assessing the safety of the combination of AB and TACE is essential to evaluating this regimen. Methods: This is an open-label, single arm pilot study. The primary objective of this study is to examine the safety and tolerability of AB with TACE. The secondary objectives are response rate, time to progression, overall survival, time to TACE progression (TTTP), and time to untaceable progression. Approximately 24 patients will be enrolled. AB will be given every 3 weeks (A: 1200 mg; 15 mg/kg) weeks and TACE will be planned for each patient to be completed in up to 4 treatments. B will be held for cycles that are within 4 weeks before or after each TACE. Imaging will be every 8 weeks for the first year, then every 12 weeks for the second year. Based on data from the GO30140 and the IMbrave 150 studies, we assume the rate of grade 3 or higher AEs is approximately 55% for AB and will likely be higher with the addition of TACE. Safety will be continuously monitored using the Bayesian Predictive Probability (PP) approach2. The PP that the rate of grade 3 or higher AEs is related to the combination is greater than 70% by the end of the trial based on toxicity data in the current stage will be continuously updated. Inclusion criteria includes patients over 18 years old with an ECOG PS of 0 or 1, no cirrhosis or Child-Pugh A cirrhosis, diagnosis of HCC by imaging or biopsy, and EGD within 6 months with no evidence of gastroesophageal varices with bleeding or high risk of bleeding unless treated. Patients are excluded if they are candidates for curative intent therapy, have had hepatic encephalopathy in the last 12 months, have occlusion of the hepatic artery or main portal vein, or have history of significant autoimmune disease. 1. Finn, Richard S., et al. New England Journal of Medicine 382.20 (2020): 1894-1905. 2 Lee J and Liu D. Clinical Trials. 2008; 5(2): 93-106. Clinical trial information: NCT05776875 .
Epidemiological characteristics of gastric and pancreatic cancers in Latin America: The LACOG 0222 GASPAR study.
Authors: Peixoto Renata D'Alpino , Diniz Gomes Diogo Bugano , Jesus Victor Hugo Fonseca , Weschenfelder Rui Fernando , Dias Jr Antonio Soares , Kruschewsky Coutinho Araujo Anelisa , de Jesus Rafaela Gomes , Rocha Matheus Soares , Gössling Gustavo Cartaxo de Lima 
Published: January 2024

TPS710 Background: Gastric and pancreatic tumors remain among the cancers with the poorest prognoses in both high and low/middle-income countries. Data on the clinicopathological characteristics, standard treatments, and outcomes of these tumors are scarce in Latin America. This study is the first comprehensive effort to report epidemiological and clinical data in this region. Methods: The LACOG 0222 GASPAR trial ( NCT05924789 ) is a retrospective and prospective (bidirectional) observational cohort study. Enrollment of 200 patients across 15 sites in Latin America is planned, 120 patients in cohort A (gastric cancer) and 80 patients in cohort B (pancreatic cancer). No interventions are proposed. Eligibility criteria include age ≥18 years, histological diagnosis of gastric and gastroesophageal junction cancer (cohort A) or pancreatic cancer (cohort B), advanced disease diagnosis since January 2019, and availability of adequate medical data for data collection. The primary objective is to describe the clinical characteristics, treatment patterns, and outcomes of patients with gastric and pancreatic cancer in Latin America. Data on patients’ clinical characteristics, demographics, tumor pathological features, surgical therapy, radiotherapy, chemotherapy, and target therapy will be collected. Patient outcomes, such as recurrence-free survival, progression-free survival, and overall survival will also be collected. Patients will be followed up for up to 3 years after diagnosis. No a priori sample-size calculations were performed. The demographic and underlying disease characteristics will be evaluated using descriptive statistics. Time-to-event outcomes (disease-free survival, progression-free survival, and overall survival) will be estimated using the Kaplan-Meier method. From August 2023 to September 2023, 34 pts were included. The target accrual is expected to be completed by February 2024. The results are expected to be presented in August 2024.
A phase 1b/2 trial of pepinemab and avelumab as second line therapy for patients with metastatic pancreatic adenocarcinoma.
Authors: Hilty Bailey , Ruffolo Luis I. , Belt Brian A. , Byrne Matthew , Dave Yatee A. , Burchard Paul R. , Fisher Terrence Lee , Evans Elizabeth E. , Mallow Crystal L. , Boise Megan , Zauderer Maurice , Mulkerin Daniel , Yeh Jen Jen , Linehan David 
Published: January 2024

TPS712 Background: Pancreatic adenocarcinoma (PDAC) is a leading cause of cancer-related mortality with poor prognosis despite maximal therapy and is unresponsive to immune checkpoint blockade (ICB). This failure of response is hypothesized to be driven in part by the characteristic immunosuppressive tumor microenvironment. In PDAC, Semaphorin 4D (SEMA4D) expression is prognostic in patients who have undergone surgical resection and correlates with tumor infiltration of activated CD8+ T-cells. Additionally, preclinical models suggest that antibody-mediated SEMA4D blockade promotes tumoral infiltration and activation of CD8+ T-cells and sensitizes PDAC to ICB, with improved overall survival with standard of care chemotherapy and ICB in combination with pepinemab (humanized anti-SEMA4D). Thus, we hypothesized that pepinemab may improve clinical outcomes in PDAC by sensitizing tumors to ICB. Methods: We designed a phase Ib/II single-arm clinical trial to evaluate the safety, tolerability, and efficacy of humanized anti-SEMA4D (pepinemab) with anti-PD-L1 (avelumab) in patients with chemotherapy-refractory PDAC. Patients must have failed first-line 5-fluorouracil or gemcitabine-based combination chemotherapy. The study follows a dose de-escalation schema starting at a dose combination of 20mg/kg pepinemab and 800mg avelumab every two weeks. Patient accrual for phase 1b utilizes the Bayesian Optimal Interval Design (BOIN) targeting a dose-limiting toxicity rate of 30% or less. After 16 subjects receive a given combination dose, a Simon’s two stage assessment of futility will be undertaken with expansion to phase 2 if 2 or more subjects demonstrate response. The trial is designed to evaluate a total cohort of 40 subjects and powered to detect a response rate of 23% or greater, with alpha set at 0.1% and 80% power. Treatment response is assessed via RECIST 1.1 criteria with surveillance CT prior to enrollment and after completion of two cycles (8 weeks). Baseline and on-treatment tumor biopsies (after completion of one cycle, 4 weeks) are performed to analyze changes in immune, stromal, and genomic profiles to elucidate mechanisms of treatment response and failure. Patient reported outcomes are incorporated (FACT-Hep and FAACT subdomains) to assess disease-specific symptoms. To date, 7 patients have been enrolled (Clinical Trial NCT05102721). Clinical trial information: NCT05102721 .
Prevalence, Molecular Landscape, and Clinical Impact of DICER1 and DGCR8 Mutated Follicular-Patterned Thyroid Nodules
Authors: Condello Vincenzo , Poma Anello M , Macerola Elisabetta , Vignali Paola , Paulsson Johan O , Zedenius Jan , Basolo Fulvio , Juhlin C Christofer 
Published: January 2024

Abstract

Background
Mutations in micro-RNA (miRNA) regulators DICER1 and DGCR8 have recently been uncovered, revealing a potential novel mechanism driving thyroid tumor development. However, the true frequency of these hotspot mutations in follicular-patterned thyroid tumors (FTs) and their relation to established driver gene events remain elusive.

Methods
A total of 440 FTs from 2 institutions were interrogated for DICER1, DGCR8, and RAS family hotspot mutations using Sanger sequencing. Whole-exome sequencing was also performed to identify additional driver gene aberrations in DICER1/DGCR8-mutant cases. Subsets of cases were further analyzed using miRNA expression profiling, and key dysregulated miRNAs were validated as markers of DICER1 mutations using quantitative RT-PCR analysis. The Cancer Genome Atlas (TCGA) database was also probed for DICER1/DGCR8 mutations and miRNA dysregulation.

Results
Fourteen (3.2%) and 4 (1%) FTs harbored DICER1 and DGCR8 hotspot mutations, respectively, in the combined cohort, and no cases with normal tissue available were found to exhibit a constitutional variant. Two DGCR8-mutant cases also harbored oncogenic RAS mutations. Whole-exome sequencing analysis did not identify additional driver gene events in DICER1/DGCR8-positive cases. Comprehensive miRNA expression profiling revealed a unique pattern of dysregulated miRNAs in DICER1/DGCR8-mutant cases compared with wild-type lesions. Moreover, DICER1-mutant cases showed a remarkable reduction of 5′ arm miRNAs, findings corroborated in the TCGA cohort.

Conclusion
DICER1 and DGCR8 hotspot mutations are rare in unselected cohorts of FTs, and mutated cases exhibit a specific miRNA profile. Although DGCR8 mutations may coexist with established RAS gene alterations, FTs with DICER1 variants were devoid of other driver gene events.
Effect of microbial transglutaminase addition on reconstructed frozen rainbow trout (Oncorhynchus mykiss) meatballs’ quality
Authors: Kocatepe D , Corapci B , Altan CO , Kőstekli B , Turan H 
Published: January 2024

In this study, MTGase (Control (without enzyme), A-0.5% MTGase (Group A), and B-0.8% MTGase (Group B) were added to rainbow trout meatballs at two different rates and the samples were stored at -18±1°C. The chemical (TVB-N, TBARS), physical (pH, water activity, color, texture, and cooking loss), microbiological (TMAB, TPAB, TYM, TCB, TAB, E. coli, and S. aureus), and sensory properties of the trout meatballs were examined for 210 days.
The TVB-N and TBARS values remained within the limit values during frozen storage. The pH and cooking loss values of the control group were different from those of Groups A and B. The water activity values generally remained stable. The L* and a* values were affected by the addition of MTGase. Moreover, the textural properties and sensory quality of the trout meatballs improved. During the frozen storage, the limit values were not exceeded in all groups, except for the TCB values.
Should Pre-Weaning Calf Diets Include Forage?
Authors: Muruz H , Aksu T 
Published: January 2024

The present review article aimed to update and address the biological consequences of forage supply to pre-weaned dairy calves. Early growth and development of a calf play a great role in lifelong performance of the animal. Comprehension of these stages is an important progress achieved in calf nutrition today. Health, milk-solid feed intake and rumen development are the most important factors related to calf growth in pre- and post-weaning periods. It is well understood that fermentation by-products of grain-based starter feeds are essential for increased growth and absorptive capacity of the rumen papillae. In pre-weaned calves, two major hypotheses exist regarding forage feeding. The first hypothesis describes that the rumen was not completely developed in pre-weaned calves and forage supply during this period might increase gut fill and hence, decrease starter intake. It is believed that depressed starter intake may limit energy intake and finally suppress calf growth rate. The second hypothesis indicates that rumen pH may decline as calf age and starter intake increases. Accordingly, forage supplementation into calf starter diets could prevent further rumen pH decline and subsequent negative consequences while improving starter intake and calf growth. Because research data regarding these hypotheses are controversial, there is no universally accepted standard for feeding calves with forage as a part of starter diets. Many factors, such as milk feeding method, grain, forage type and experimental conditions, could affect calf response to dietary forage. However, there is an evidence that limited consumption of forage may be beneficial on rumen health and behavior of calves consuming highly processed (pelleted or finely ground) starter feed in pre-weaning period.
Keywords: Forage; Growth performance; Pre-weaned calf; Rumen development
Technology and Disintermediation in Online Marketplaces
Authors: Gu Grace Y. 
Published: January 2024

With the development of communication technology that makes online transactions easier, there is also an increased risk of disintermediation—sellers and buyers circumventing a platform to transact directly—in online two-sided marketplaces. Such disintermediation may lead to significant revenue loss for online platforms. However, it remains unclear how the characteristics of platforms affect their vulnerability to disintermediation. Using the blockade of Skype in mainland China as a natural experiment, this study examines how online communication technologies affect disintermediation and transaction outcomes in a large U.S. online freelance marketplace. The results show that restricting this alternative communication technology, which platforms struggle to monitor, reduces disintermediation by around 18%. This effect is potentially due to economic frictions in transactions, as the reduction in disintermediation is greater for high-transaction-cost jobs, such as time-sensitive jobs, communication-intensive jobs, and high-skilled jobs, as well as for cost-sensitive users, such as experienced users and personal users as opposed to enterprise users. With these results, platforms can reduce disintermediation risks when making investment and market entry decisions. This paper was accepted by D. J. Wu, information systems. Funding: This work was supported by the Strategic Management Society [SRF Dissertation Research Grant]. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2021.02736 .
Values and Participation of Individuals Without Mental Capacity in Hong Kong
Authors: Cheung Daisy 
Published: January 2024

Mental capacity law in Hong Kong, much like most areas of law pertaining to those with mental disability, is riddled with deficiencies, both in terms of its theoretical basis and the problematic values that underpin its regimes. This chapter examines the latter, exploring in particular the role of the subjective values of the individual without capacity, as well as the participation of such individuals in hearings granting the power to make decisions on their behalf. The chapter begins with a brief introduction to the two key mental capacity law regimes in Hong Kong, the Part II Committee regime and the Part IVB adult guardianship regime of the Mental Health Ordinance (Cap 136) (MHO). It then examines the extent to which the views and wishes of the individual without capacity are ascertained and considered in decisions under both regimes. The chapter further considers whether such individuals take part in these decisions, and where they do, what the nature of this participation involves. A critical evaluation of these aspects of the two regimes is then provided, and the chapter ends with a brief conclusion.
Multi-wavelength confocal displacement sensing using a highly dispersive flat-field concave grating
Authors: Zhao Jiaqi , Cheng Haobo , Feng Yunpeng , Yan Saisai , Cheng Weizhe 
Published: January 2024

A multi-wavelength confocal displacement sensor based on a flat-field concave grating (FFCG) was proposed and designed; the large dispersion and small volume of the FFCG make it an ideal candidate for replacing the complex dispersive lens group. The designed displacement sensor was calibrated by displacement meter, and the characteristics were measured. Consequently, for the proposed displacement sensor, the displacement range of 6.8 mm was measured with the R-square linearity evaluation coefficient of 0.998, and the sensitivity preceded 17.1 nm/mm. The resolution of the displacement sensor was characterized by 70 µm, as well as a full width at half maximum (FWHM) fluctuating around 1.63 nm, indicating high precision and accuracy in displacement measurement. Moreover, the stability and reliability of the sensor were verified within 20 min, with no significant wavelength shifts, and gentle power fluctuations of 557.73 counts at 520 nm and 563.67 counts at 545.05 nm, respectively.
How to choose the intraocular lens power calculation formulas in eyes with extremely long axial length? A systematic review and meta-analysis
Authors: Li Xiaoyu , Wang Xiaodong , Liao Xuan 
Published: January 2024

Objective
To evaluate the accuracy of 10 formulas for calculating intraocular lens (IOL) power in cataract eye with an axial length (AL) of more than 28.0 mm.

Methods
We searched scientific databases including PubMed, EMBASE, Web of Science and Cochrane Library for research published over the past 5 years, up to Sept 2023. The inclusion criteria were case series studies that compared different formulas (Barrett II, EVO, Kane, Hill-RBF, Haigis, Hoffer Q, Holladay 1, SRK/T, Holladay 1 w-k and SRK/T w-k), in patients with extremely long AL undergoing uncomplicated cataract surgery with IOL implantation. The mean difference (MD) of mean absolute error (MAE) and the odds ratio (OR) of both the percentage of eyes within ±0.50D of prediction error (PPE±0.50D) and the percentage of eyes within ±1.00D of prediction error (PPE±1.00D) among different formulas were pooled using meta-analysis.

Results
A total of 11 studies, involving 1376 eyes, were included to evaluate the 10 formulas mentioned above. Among these formulas, Barrett II, EVO, Kane, and Hill-RBF demonstrated significantly lower MAE values compared to SRK/T. Furthermore, Kane and Hill-RBF had lower MAE values than EVO. Additionally, Barrett II and Kane yielded significantly lower MAE values than Haigis while Hill-RBF showed significantly lower MAE values than Holladay 1. Moreover, Hill-RBF showed the highest values for both PPE±0.50D and PPE±1.00D, followed by Kane. Both EVO and Kane had higher values of PPE±0.50D and PPE±1.00D compared to Haigis and SRK/T.

Conclusion
The Wang-Koch adjusted formulas and new-generation formulas have shown potential for higher accuracy in predicting IOL power for cataract patients with extremely long AL compared to traditional formulas. Based on the current limited clinical studies, Hill-RBF and Kane formulas seem to be a better choice for eyes with extremely long AL.