bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line sintilimab combined with platinum-based chemotherapy in extensive stage small cell lung cancer: A phase II study and post-hoc biomarker analysis.
Authors: Su ChunXia , Xie Mengqing , Zhao Jing , Chu Xiangling , Liu Li 
Published: August 2024

e20127 Background: Immune checkpoint inhibitors (ICIs) combined with etoposide and platinum-based chemotherapy improves prognosis of patients with extensive-stage small-cell lung cancer (ES-SCLC). However, nearly 40% of patients do not benefit from Immunochemotherapy. Herein, this phase II study of first-line immunochemotherapy was conducted aiming to investigate potential biomarkers associated with therapeutic efficacy. Methods: A multi-center, single-arm, prospective phase II trial (ChiCTR2000038354) was designed and conducted to evaluate the efficacy and safety of sintilimab combined with platinum-based chemotherapy in patients with ES-SCLC who had not previously received treatment. The primary endpoint of this study is progression-free survival (PFS), with patients being defined as disease progression according to RECIST 1.1. Pre-treatment FFPE samples were analyzed using whole exome sequencing (WES) and whole transcriptome sequencing (WTS) to investigate biomarkers. Results: A total of 44 patients were included in the study, with a median follow-up of 10 months and a median PFS of 7.57 months. 8 patients with a PFS greater than 6 months were defined as the responder group (R group) and 5 patients with a PFS less than 6 months belonged to the non-responder group (NR group). WES and WTS were performed on the pre-treatment samples of these 13 patients. WES results revealed mutation frequencies of TP53 (69%), RB1 (31%) and FAT1 (31%) aligning with prior research. Significantly, ZFHX4 mutations correlated with R group (p = 0.05). Genomic instability, as defined by Homologous Recombination Deficiency (HRD) scores, displayed higher scores in NR group than in R group (p = 0.023), which suggests potential benefits of PARP inhibition in the NR group. WTS data revealed that higher M2/M1 macrophage ratio (p = 0.028) in NR group. Additionally, the NR group demonstrated significant VEGFA overexpression. Besides, NOTCH-signaling (p = 0.034), KRAS-signaling-DN (p<0.001), Angiogenesis (p<0.001) and EMT (p<0.001) pathway were also enriched in NR group. Conversely, M1 macrophages (p = 0.079), CD4+T cells (p = 0.093), Mast cells (p = 0.045), NK cells (p = 0.045) and neutrophils (p = 0.06) was higher in R group. Conclusions: This study highlights genomic instability as well as activation of cancer hallmarks such as angiogenesis, EMT may result the resistance to immunotherapy in ES-SCLC patients. These findings may shed light on combinational strategy overcoming therapeutic resistance. Clinical trial information: ChiCTR2000038354.
Cost-effectiveness of an oral THC: CBD cannabis extract for secondary prevention of refractory, chemotherapy-induced nausea and vomiting.
Authors: Dieng Mbathio , Grimison Peter S. , Kirby Adrienne , Mersiades Antony , Pokorski Izabella , Stockler Martin R , Morton Rachael L 
Published: August 2024

TPS11188 Background: The CannabisCINV trial showed the incorporation of a THC:CBD (tetrahydrocannabinol:cannabidiol) cannabis extract in addition to usual, guideline-recommended antiemetic prophylaxis, reduced the incidence of refractory chemotherapy-induced nausea and vomiting. The aim of this within-trial cost-effectiveness analysis was toassess the incremental costs and benefits of oral THC: CBD versus placebo, for preventing chemotherapy-induced nausea and vomiting. Methods: The analysis was performed from a health system perspective, using prospectively collected data from the CannabisCINV trial and linked Medicare data. The evaluation focused on the costs and benefits associated with oral THC: CBD cannabis extract versus placebo in addition to usual care, on complete response: defined as no emesis and no use of rescue medications during the overall treatment phase (0-120 h, cycle 1). The primary economic outcome was an incremental cost-effectiveness ratio (ICER) of achieving a complete response. One-way sensitivity analyses and non-parametric bootstrapping (with 1,000 replications) were conducted to assess the robustness of results. Results: Of 147 participants randomized, 60 of 73 assigned THC:CBD and 66 of 74 assigned placebo consented to Medicare data linkage. The incidence of complete response was higher for THC:CBD than placebo (24% vs 5%, absolute difference 19%, 95%CI 13 to 26%). The mean cost (AUD) of hospitalisation was $580 (SD $7,831) for the intervention group and $1,873 (SD $7,235) for placebo. The mean healthcare costs (AUD) were $1,464 (SD $4,667) for THC:CBD group and $2,725 (SD $9,237) for the placebo. The THC:CBD group had a mean total healthcare cost saving of $1,261 per patient (95% CI -$3,550 to $1029) compared with the placebo group. THC:CBD was less expensive and more effective than placebo (i.e. dominant), in the primary analysis, and over the range of pre-specified sensitivity analyses. Conclusions: This within-trial analysis indicates oral THC: CBD is cost-effective for the treatment of refractory, chemotherapy-induced nausea and vomiting from a health system perspective and supports reimbursement in this setting. The trial and economic evaluation were prospectively registered in the Australian and New Zealand. Clinical trial information: ACTRN12616001036404.
A first-in-human study of IK-595, an oral MEK/RAF molecular glue, in patients with RAS- or RAF-altered advanced solid tumors.
Authors: Lakhani Nehal J. , Spira Alexander I. , Tolcher Anthony W. , Lingaraj Trupti , Timothy Marissa , Bartolini Wilmin , Ortiz-Otero Nerymar , Kacena Katherine , Santillana Sergio 
Published: August 2024

TPS3185 Background: Alterations in the RAS/RAF/MEK/ERK pathway are the most common drivers of oncogenesis. MEK is a clinically validated cancer target and despite FDA approval of several MEK inhibitors, their clinical utility has been limited to BRAF V600 mutant cancers and NF1 mutant neurofibromas mostly due to early emergence of resistance and low therapeutic indices. IK-595, a potent novel MEK-RAF molecular glue, is being developed to overcome these limitations. IK-595 traps MEK in an inactive complex with all RAF isoforms and blocks RAF-dependent MEK phosphorylation, thereby alleviating CRAF-mediated MEK reactivation that hinders the efficacy of approved MEK inhibitors in RAS/RAF-driven tumors, in addition to kinase independent CRAF activity. IK-595 exhibits potent single agent activity in a wide range of in vivo cancer models harboring various RAS/RAF alterations, including, but not limited to, lung, pancreatic, colorectal cancer (CRC), melanoma, and AML. The preclinical pharmacokinetic profile of IK-595 also enables flexible dosing schedules resulting in a broader therapeutic window. Methods: This is a phase 1, first-in-human, open-label, multicenter study to evaluate IK-595 as monotherapy in patients with RAS- or RAF-altered advanced solid tumors for whom there are no other further treatment options known to confer clinical benefit. Dose escalation uses a Bayesian Optimal Interval Design (BOIN) in patients with advanced and unresectable, or metastatic solid tumors with confirmed RAS/RAF gene alterations. Backfilling of cleared dose levels with key target indications will initiate upon achievement of efficacious plasma exposures. Dose expansion will occur in genetically defined cohorts, for example NRAS-mutant CRC and malignant melanoma, as well as BRAF non-V600 and KRAS mutant tumors using a Simon 2-stage adaptive design. IK-595 will initially be administered on an intermittent dosing schedule in 30-day cycles. Additional dosing schedules may be explored. Primary objectives of the study are to evaluate safety and tolerability of IK-595 and to determine the recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD). Secondary objectives include evaluation of preliminary antitumor activity by RECIST 1.1, pharmacokinetic (PK) parameters, and pharmacodynamic effects of IK-595 on pERK in paired tumor biopsies. Key exploratory endpoints include changes in pERK in peripheral blood cells, changes in pERK target genes in tumor biopsies, and assessment of candidate baseline response biomarkers. The study began in December 2023 and enrollment in Cohort 1 was completed with no DLTs; dose escalation continues to enroll. Clinical trial information: NCT.
MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET).
Authors: Banys-Paluchowski Maggie , Kuehn Thorsten , Masannat Yazan , Ditsch Nina , Cabioglu Neslihan , Harvey James , Pankratjevaite Lina , Murawa Dawid , Gasparri Maria Luisa , Karadeniz Cakmak Guldeniz , Kontos Michalis , Khan Mah Muneer , Lowery Aoife J , Rebaza Lia Pamela , Esgueva Antonio J , Rody Achim , Krawczyk Natalia , Hartmann Steffi , Aktas Sezen Bilge , Tvedskov Tove Filtenborg ,   MELODY Study Group
Published: August 2024

TPS623 Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency, and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins, and re-operations are limited. In most studies, the patient perspective, addressing e.g. discomfort and pain, has not been evaluated. The aim of MELODY (Methods for Localization of Different Types of Breast Lesions) is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://eubreast.org/melody ). MELODY is a prospective intergroup cohort study which enrolls female and male patients. planned for breast-conserving surgery with imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal and 2) Negative resection margin rates. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, patient-reported outcomes, rates of “lost markers”, radiologist and surgeon satisfaction, and health economic evaluation of the different techniques. Target accrual: 7,416 patients. The study will be conducted in 30 countries. Clinical trial information: NCT05559411 .
Reducing Cancer Drug Cost: 3-Year Analysis of Automated Dose Rounding in Electronic Health Records
Authors: Shah Vishal S. , Irvine Clayton , McWilliams Robert R. , Singh Parminder , Soefje Scott A. 
Published: August 2024

PURPOSE Globally, cancer drug expenditure exceeds $185 in US dollars (USD) billion, with the United States contributing $75 (USD) billion. Many cancer drug doses are calculated on the basis of body weight or body surface area, which often results in leftover drug in partially used single-dose vials (SDVs). The cost of wasted drug is a huge financial burden on the US health care system. We evaluated the cost savings resulting from the reduction of SDV wastage, achieved through the implementation of automated dose rounding rules in electronic health records (EHRs). METHODS Mayo Clinic implemented automated dose rounding rules within the EHR. These rules were designed to round calculated doses to the nearest SDV if the vial size closely matched the original calculated dose, within a 10% threshold. We assessed doses administered between January 2019 and December 2021, and computed cost-savings, waste reduction, and cost of waste for chemotherapy drugs. RESULTS In 3 years, 36.1% of doses were rounded down, 35.8% were rounded up, and 28.1% were exact doses. By rounding doses down to a vial size, we achieved cost-savings of $39.75 (USD) million and prevented 62,065 SDV of cancer drugs from going to waste. By rounding doses up, we avoided wasting $9.95 (USD) million worth of drugs. However, there were still instances where the rounding fell outside of the 10%, resulting in wasted drugs worth $25 (USD) million. CONCLUSION The substantial burden imposed on patients and the US health care system because of cancer drug wastage is of significant concern. Although the automated dose rounding system represents a partial solution for this issue, a comprehensive approach involves the imperative development of policy and legislative solutions to effectively mitigate the challenges associated with cancer drug waste.
Koopmans, Dantzig, and the Wartime Origins of Activity Analysis
Authors: Dimand Robert W. 
Published: August 2024

Abstract
In the introduction to Activity Analysis of Production and Allocation (Cowles Monograph No. 13), Tjalling C. Koopmans recalled that he developed the model of his “Optimal Utilization of the Transportation System” (in the proceedings of 1947 International Statistical Congress, which were reissued as an Econometrica supplement, 1949) “under the stimulation of statistical work for the Combined Shipping Adjustment Board, the British-American board dealing with merchant shipping problems during the second world war.” Similarly, the contributions of George B. Dantzig and Marshall K. Wood to Cowles Monograph No. 13 (two revised journal articles and five new chapters) emerged from wartime work for the US Army Air Force and postwar work for the Department of the Air Force. This article examines the context and consequences of the wartime roots of these foundational contributions to activity analysis and linear programming, with particular attention to Koopmans's 1942 memorandum for the Combined Shipping Adjustment Board titled “Exchange Ratios between Cargoes on Various Routes” (first published in his Scientific Papers, 1970).
Japanese Wartime Economics and Economists
Authors: Bollard Alan 
Published: August 2024

Abstract
The Japanese prewar intellectual and policy environment was dominated by officials with law degrees and increasingly by the military. There were important schools of economics, both Marxist, and neoclassical, but their influence was mainly confined to academia. During wartime they suffered severe intellectual repression. The wartime economy relied on an allocation policy led by technocratic planners working under the “reform bureaucrats.” Immediately postwar there was a revival: economists were able to display moral leadership and play a leading role in adapting the MacArthur reforms and devising the formula for modern Japanese growth.
Ethical Antinomies
Authors: Ozdemir Mehtap 
Published: August 2024

Abstract
Building on recent scholarship on the novel and Middle Eastern modernities, this article examines how Ottoman intellectuals theorized the novel as a realist genre in the nineteenth century as a way of including Ottoman literary knowledge within global novel theories. In the late Ottoman context, the novel was articulated in terms of conceptual separations (primarily as truth/imitation–fiction/creation, which then develops into nature-beauty and romance-realism binaries). Such conceptual divides inform both the history and the theory of the novel by Ottoman intellectuals. Revisiting the problem of realism in light of the dialectics that these divides built up, this article argues that they dialogically establish realism as a symbiotic regime of representation that merges mimeticism and transcendentalism, which had aesthetic as well as political implications. More importantly, negotiating the tension between imitation and creation through Ottoman-Islamicate terms, Ottoman realism complicates the relation between literature and secularization as it speaks to the institutionalization of modern literature.
Outcomes After Definitive Surgery for Spinal and Sacral Chordoma in 101 Patients Over 20 Years
Authors: Xia Yuanxuan , Papali Pritika , Al-Mistarehi Abdel-Hameed , Hansen Landon J. , Azad Tej D. , Ahmed A. Karim , Meyer Christian , Gross John , Khan Majid , Bettegowda Chetan , Mukherjee Debraj , Witham Timothy , Bydon Ali , Theodore Nicholas , Wolinsky Jean-Paul , Gokaslan Ziya , Larry Lo Sheng-Fu , Sciubba Daniel , Lee Sang H. , Redmond Kristin J. , Lubelski Daniel 
Published: August 2024

BACKGROUND AND OBJECTIVES:
Spinal chordomas are primary bone tumors where surgery remains the primary treatment. However, their low incidence, lack of evidence, and late disease presentation make them challenging to manage. Here, we report the postoperative outcomes of a large cohort of patients after surgical resection, investigate predictors for overall survival (OS) and local recurrence-free survival (LRFS) times, and trend functional outcomes over multiple time periods.

METHODS:
Retrospective review of all patients followed for spinal chordoma at a quaternary spinal oncology center from 2003 to 2023 was included. Data were collected regarding demographics, preoperative and perioperative management, and follow-up since initial definitive surgery. Primary outcomes were OS and LRFS, whereas secondary outcomes were functional deficits.

RESULTS:
One hundred one patients had an average follow-up of 6.0 ± 4.2 years. At the time of census, 25/101 (24.8%) had experienced a recurrence and 10/101 (9.9%) had died. After surgery, patients experienced a significant decrease in pain over time, but rates of sensory deficits, weakness, and bowel/bladder dysfunction remained static. Tumors ≥100 cm3 (hazard ratio (HR) = 5.89, 95% CI 1.72-20.18, P = .005) and mobile spine chordomas (HR = 7.73, 95% CI 2.09-28.59, P = .002) are related to worse LRFS, whereas having neoadjuvant radiotherapy is associated with improved LRFS (HR = 0.09, 95% CI 0.01-0.88, P = .038). On the other hand, being age ≥65 years was associated with decreased OS (HR = 16.70, 95% CI 1.54-181.28, P = .021).

CONCLUSION:
Surgeons must often weigh the pros and cons of en bloc resection and sacrificing important but affected native tissues. Our findings can provide a benchmark for counseling patients with spinal chordoma. Tumors ≥100 cm3 appear to have a 5.89-times higher risk of recurrence, mobile spine chordomas have a 7.73 times higher risk, and neoadjuvant radiotherapy confers an 11.1 times lower risk for local recurrence. Patients age ≥65 years at surgery have a 16.70 times higher risk of mortality than those <65 years.
Using Wearable Technologies to Monitor Physical Activity and Exercise in Patients: A Narrative Review
Authors: Sher Jessica , Lewis Christopher W. , Lin Cindy 
Published: August 2024

Abstract
With an increasing prevalence of sedentary lifestyles driving a prominent public health crisis, digital health tools such as wearable technologies are revolutionizing clinicians’ ability to track physical activity and exercise. Despite their ubiquity in the consumer market, these technologies have not yet been fully incorporated into clinical practice. Though these tools promise efficacy and accessibility, a careful review of the current literature is important to understand the challenges and future promise of clinical implementation. Important considerations of implementation include health maintenance and disease prevention, ease of use by patients and providers, incorporation into the electronic health record, cost considerations, safety, privacy, and ethical considerations. This narrative review describes the recent literature on the implementation of wearable technologies in the prescription of physical activity and exercise. Application of these technologies is promising for this field’s future.
role of lactoferrin in the treatment of upper respiratory tract infections
Authors: Cąkała Marlena , Kozioł Magdalena , Błaszczak Karolina , Podgórniak Kamila , Piotrowska Julia , Skotnicka Joanna , Zajkowska Aleksandra , Witkowska Maria 
Published: August 2024

Introduction
Lactoferrin is a glycoprotein belonging to the group of transferrins found in most body fluids. It has been shown to possess antimicrobial, anti-inflammatory, immunomodulatory and anticancer properties. The increasing availability and widespread use of dietary supplements containing lactoferrin have been observed as supportive measures in managing various infections.

Aim of the study
The objective of this study is to summarize the current knowledge regarding the anti-infective - mostly antiviral - effects of lactoferrin and the justification for its use in the treatment of upper respiratory tract infections.

Knowledge summary
Scientific research has consistently confirmed the effectiveness of lactoferrin against pathogenic microorganisms. The antibacterial effect of this protein is based mainly on the management of available iron resources - an ingredient necessary for bacterial growth. On the other hand, the antiviral activity of this protein is based on the induction of interferon production.

Conclusion
Dietary supplements containing lactoferrin are approved by the US Food and Drug Administration (FDA) for supportive use in infections. Lactoferrin exhibits antimicrobial activity supported by research in specific infections. It has a good tolerance and safety profile, therefore it seems that it can be used adjunctively in this indication.
Maximizing Engagement in Large-Scale Social Networks
Authors: Kroger Samuel , Validi Hamidreza , Hicks Illya V. 
Published: August 2024

Motivated by the importance of user engagement as a crucial element in cascading leaving of users from a social network, we study identifying a largest relaxed variant of a degree-based cohesive subgraph: the maximum anchored k-core problem. Given graph [Formula: see text] and integers k and b, the maximum anchored k-core problem seeks to find a largest subset of vertices [Formula: see text] that induces a subgraph with at least [Formula: see text] vertices of degree at least k. We introduce a new integer programming (IP) formulation for the maximum anchored k-core problem and conduct a polyhedral study on the polytope of the problem. We show the linear programming relaxation of the proposed IP model is at least as strong as that of a naïve formulation. We also identify facet-defining inequalities of the IP formulation. Furthermore, we develop inequalities and fixing procedures to improve the computational performance of our IP model. We use benchmark instances to compare the computational performance of the IP model with (i) the naïve IP formulation and (ii) two existing heuristic algorithms. Our proposed IP model can optimally solve half of the benchmark instances that cannot be solved to optimality either by the naïve model or the existing heuristic approaches. Funding: This work is funded by the National Science Foundation (NSF) [Grant DMS-2318790] titled AMPS: Novel Combinatorial Optimization Techniques for Smartgrids and Power Networks. Supplemental Material: The online appendix is available at https://doi.org/10.1287/ijoo.2022.0024 .