bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).
Authors: Arend Rebecca Christian , Monk Bradley J. , Herzog Thomas J. , Ledermann Jonathan A. , Moore Kathleen N. , Secord Angeles Alvarez , Shapira-Frommer Ronnie , Tewari Krishnansu Sujata , Rachmilewitz Minei Tamar , Harats Dror , Penson Richard T. 
Published: June 2021

TPS5599 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism of action that includes a broad antiangiogenic effect and induction of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer showed that VB-111 in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58% with a trend for improved survival. The favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent platinum-resistant epithelial ovarian cancer with measurable disease (RECIST 1.1), and may have been previously treated with up to 5 prior lines of therapy. Patient are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The efficacy endpoints are OS, PFS and ORR by RECIST 1.1 and by CA-125 (GCIG criteria). A pre-planned interim analysis was performed by the DSMC in the first 60 patients evaluable for CA-125 response. The analysis met the pre-defined criteria of a CA-125 ORR (GCIG) in the treatment arm at least 10% higher than in the control arm. Study enrolment is ongoing and over 220 patients were enrolled in the US, EU, and Israel. Enrolment of the full sample size of 400 patients is expected to complete by the end of 2021. Clinical trial information: NCT03398655.
CMP-001-007: Open-label, phase 2 study of intratumoral CMP-001 + pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma.
Authors: Wong Deborah J.L. , Panwar Aru , Rosenberg Ari , Karivedu Vidhya , Laux Douglas Earl , Zandberg Dan Paul , Bobilev Dmitri , Zhao Luping , Wooldridge James , Krieg Art M. , Cohen Ezra E.W. 
Published: June 2021

TPS6089 Background: PD-1 blockade ± chemotherapy has recently become a primary systemic therapy recommended by NCCN guidelines for patients (pts) with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, most pts still do not respond to treatment, indicating a large unmet need for pts with unresectable disease. CMP-001 is a toll-like receptor 9 (TLR9) agonist comprising a CpG-A oligodeoxynucleotide packaged in a virus-like particle that can induce type I interferon secretion from tumor-associated plasmacytoid dendritic cells, promoting a Th1-like chemokine milieu in the tumor microenvironment and inducing an antitumor CD8+ T-cell response. In a phase (ph) 1b study in pts with metastatic melanoma, intratumoral (IT) injection of CMP-001 + intravenous (IV) pembrolizumab (pembro) reversed PD-1 blockade resistance, induced responses in injected and noninjected lesions, and had an acceptable safety profile (Milhem et al, SITC 2020). This combination is therefore being tested in pts with HNSCC. Methods: CMP-001-007 (NCT04633278) is an open-label, multicenter, ph 2 study designed to investigate the efficacy and safety of CMP-001 + IV pembro in adult pts with histologically or cytologically confirmed R/M HNSCC considered incurable by local therapies. Eligible pts have undergone a pretreatment tumor biopsy, received no prior systemic therapy in the R/M setting, and have primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. In addition, pts must have PD-L1-positive tumors (combined positive score ≥1), known tumor human papillomavirus (HPV) status (for oropharyngeal cancer), and measurable disease per RECIST v1.1 with ≥1 lesion amenable to IT injection. Pts with primary tumors in the nasopharynx are excluded. Enrolled pts will receive CMP-001 10 mg once weekly for 7 doses and every 3 weeks (Q3W) thereafter. The first dose may be administered subcutaneously or via IT injection, with all subsequent doses administered IT. All pts will also receive pembro 200 mg IV Q3W after the CMP-001 injection. Treatment continues until unacceptable toxicity or disease progression. The primary endpoint is investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints include safety, duration of response (DOR), progression-free survival (PFS), overall survival, and effects of HPV infection and PD-L1 expression on ORR, DOR, and PFS. Exploratory endpoints include analyses of baseline and changes from baseline in tumor or serum biomarkers related to TLR9, immune checkpoints, and potential predictors of response, as well as serum concentrations of CXCL10 and CMP-001. Refer to clinicaltrials.gov/ct2/show/NCT04633278 for the most current information on enrolling sites. Clinical trial information: NCT04633278.
A phase 1 dose escalation and cohort expansion study of the safety and efficacy of allogeneic CRISPR-Cas9–engineered T cells (CTX110) in patients (Pts) with relapsed or refractory (R/R) B-cell malignancies (CARBON).
Authors: McGuirk Joseph , Bachier Carlos R. , Bishop Michael Russell , Ho P. Joy , Murthy Hemant S. , Dickinson Michael J. , Maakaron Joseph E. , Andreadis Charalambos , Ghobadi Armin , Waller Edmund K. , Benton Mark Daniel , Suh Susanna , Xu Huansheng , Morawa Ewelina , Awan Farrukh Tauseef , Shaughnessy Paul , Tam Constantine Si Lun , Kroeger Nicolaus , Maziarz Richard T. 
Published: June 2021

TPS7570 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma (NHL), and although > 50% of pts achieve long-term remission with first-line therapy, pts with R/R disease as well as those with R/R grade 3b follicular lymphoma (FL), double-, or triple-hit high-grade lymphomas have poor long-term outcomes (Crump 2017; Kahl 2016; Jain 2012). Autologous (auto) chimeric antigen receptor (CAR) T cell therapy has provided additional options for pts with R/R disease, but only when leukapheresis and manufacturing prove feasible (Jacobson 2020). Allogeneic (allo) CAR-T cells were designed specifically to address these unmet needs by using healthy donor T cells to produce a readily available product and remove the need for bridging chemotherapy. We are currently investigating the safety and efficacy of CTX110, an allo anti-CD19 CAR-T cell product modified by using CRISPR/Cas9-editing to disrupt the endogenous T-cell receptor (TCR) alpha constant (TRAC) locus in order to remove TCR expression and disrupt β2-microglobulin, which eliminates major histocompatibility complex (MHC) class I expression. Disruption of the TCR should significantly reduce or eliminate risks of graft-versus-host disease and elimination of MHC class I expression may increase CAR-T cell persistence by mitigating CTX110 rejection. In addition, the anti-CD19 CAR transgene construct is precisely inserted into the TRAC locus. Methods: The Phase 1 CARBON trial (NCT04035434) is an open-label, multicenter, global study evaluating the safety and efficacy of CTX110 in pts ≥18 y with R/R DLBCL NOS, double- or triple-hit DLBCL, or transformed or grade 3b FL with ≥2 prior lines of therapy or who are ineligible for/refused prior auto hematopoietic stem cell transplant (HSCT). Pts who received prior auto CAR-T or allo HSCT are excluded. Pts will receive lymphodepleting chemotherapy with fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 for 3 days, followed by CTX110 infusion. In part A, dose escalation will be performed using a 3+3 design. Upon completion of dose finding, the cohort will be expanded to further assess safety signals and efficacy including the primary efficacy endpoint of overall response rate. Key secondary efficacy endpoints include duration of response, progression-free survival, and overall survival. The trial is currently open and enrolling. Clinical trial information: NCT04035434.
Clinical trial in progress: Phase II trial of defactinib (VS-6063) combined with VS-6766 (CH5126766) in patients with metastatic uveal melanoma.
Authors: Seedor Rino S. , Orloff Marlana , Gutkind J. Silvio , Aplin Andrew E. , Terai Mizue , Sharpe-Mills Erin , Klose Haley , Mastrangelo Michael J. , Sato Takami 
Published: June 2021

TPS9588 Background: Despite successful treatment of primary uveal melanomas (UM), up to 50% of patients subsequently develop systemic metastasis, with the liver involved in up to 90% of patients. Currently there is no US FDA-approved treatment for metastatic uveal melanoma (MUM). Activating mutations in genes encoding alpha subunits of the heterotrimeric G proteins, GNAQ and GNA11, are found in 80-90% of UM. Recent information suggests that GNAQ/GNA11-oncogenic signaling involves a non-canonical pathway conferring the activation of YAP1, distinct from the activation of PLCβ and PKC-MEK-ERK, which may explain the failure of MEK inhibitors in MUM patients. Focal Adhesion Kinase (FAK) is a tyrosine kinase that provides a direct link between Gαq and tyrosine phosphorylation networks controlling YAP and UM growth. Interestingly, UM represents the human cancer harboring the highest level of FAK overexpression. Recent kinome-wide CRISPR-Cas9 screens revealed that FAK and RAF/MEK co-targeting may provide a new network-based precision therapeutic strategy for MUM treatment. Methods: This is an investigator-initiated, prospective, single arm, single-institution, phase II trial evaluating the combination of a FAK inhibitor (defactinib, VS-6063) with a RAF/MEK inhibitor (VS-6766, CH5126766) for the treatment of patients with metastatic uveal melanoma [NCT04720417]. The primary endpoint of the study is disease control rate (DCR) of 50% including complete response (CR), partial response (PR), and stable disease (SD) as determined by RECIST criteria version 1.1. Secondary endpoints include progression free survival, overall survival, and causality of adverse events. Exploratory endpoints include analysis of the pharmacodynamic profile, mechanism of resistance to the combination, and investigation of circulating free DNA as a biomarker. The efficacy of this combination treatment will be assessed using the Simon’s two stage design. In stage I, a total number of 8 patients are accrued and if there are 2 or fewer overall responses among these 8 patients, further enrollment of patients may be stopped with the conclusion that DCR cannot be 50% or greater. Otherwise, an additional 10 patients will be accrued in stage II, resulting in a total sample size of 18 patients. Patients at 18 years or older with metastases from uveal melanoma will be eligible (any line of therapy). Defactinib (200 mg) will be administered orally twice a day in combination with VS-6766 (3.2 mg) administered orally twice a week for 3 weeks, in 28-day cycles. Dose modification will be considered based on toxicity. Treatment will be continued until maximum clinical benefit is obtained; disease progression or the development of intolerable side effects. Enrollment to stage 1 began in February 2021. Clinical trial information: NCT04720417.
Out-of-Pocket Costs of Complementary Medicine Following Cancer and the Financial Impact in a Setting With Universal Health Coverage: Findings From a Prospective Cohort Study
Authors: Bhoo-Pathy Nirmala , Subramaniam Shridevi , Khalil Sadia , Kimman Merel , Kong Yek-Ching , Ng Chiu-Wan , Bustamam Ros Suzanna , Yip Cheng-Har 
Published: June 2021

PURPOSE: To determine household spending patterns on complementary medicine following cancer and the financial impact in a setting with universal health coverage. METHODS: Country-specific data from a multinational prospective cohort study, Association of Southeast Asian Nations Costs in Oncology Study, comprising 1,249 cancer survivors were included. Household costs of complementary medicine (healthcare practices or products that are not considered as part of conventional medicine) throughout the first year after cancer diagnosis were measured using cost diaries. Study outcomes comprised (1) shares of household expenditures on complementary medicine from total out-of-pocket costs and health costs that were respectively incurred in relation to cancer, (2) incidence of financial catastrophe (out-of-pocket costs related to cancer ≥ 30% of annual household income), and (3) economic hardship (inability to pay for essential household items or services). RESULTS: One third of patients reported out-of-pocket household expenditures on complementary medicine in the immediate year after cancer diagnosis, accounting to 20% of the total out-of-pocket costs and 35% of the health costs. Risk of financial catastrophe was higher in households reporting out-of-pocket expenditures on complementary medicine (adjusted odds ratio: 1.39 [95% CI, 1.05 to 1.86]). Corresponding odds ratio within patients from low-income households showed that they were substantially more vulnerable: 2.28 (95% CI, 1.41 to 3.68). Expenditures on complementary medicine were, however, not associated with economic hardship in the immediate year after cancer diagnosis. CONCLUSION: In settings with universal health coverage, integration of subsidized evidence-based complementary medicine into mainstream cancer care may alleviate catastrophic expenditures. However, this must go hand in hand with interventions to reduce the use of nonevidence-based complementary therapies following cancer.
Associations Between Fruit Intake and Risk of Diabetes in the AusDiab Cohort
Authors: Bondonno Nicola P , Davey Raymond J , Murray Kevin , Radavelli-Bagatini Simone , Bondonno Catherine P , Blekkenhorst Lauren C , Sim Marc , Magliano Dianna J , Daly Robin M , Shaw Jonathan E , Lewis Joshua R , Hodgson Jonathan M 
Published: June 2021

Abstract

Context
Fruit, but not fruit juice, intake is inversely associated with type 2 diabetes mellitus (T2DM). However, questions remain about the mechanisms by which fruits may confer protection.

Objective
The aims of this work were to examine associations between intake of fruit types and 1) measures of glucose tolerance and insulin sensitivity and 2) diabetes at follow-up.

Methods
Among participants of the Australian Diabetes, Obesity and Lifestyle Study, fruit and fruit juice intake was assessed by food frequency questionnaire at baseline. Associations between fruit and fruit juice intake and 1) fasting plasma glucose, 2-hour postload plasma glucose, updated homeostasis model assessment of insulin resistance of β-cell function (HOMA2-%β), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin levels at baseline and 2) the presence of diabetes at follow-up (5 and 12 years) were assessed using restricted cubic splines in logistic and linear regression models.

Results
This population of 7675 Australians (45% males) had a mean ± SD age of 54 ± 12 years at baseline. Total fruit intake was inversely associated with serum insulin and HOMA2-%β, and positively associated with HOMA2-%S at baseline. Compared to participants with the lowest intakes (quartile 1), participants with moderate total fruit intakes (quartile 3) had 36% lower odds of having diabetes at 5 years (odds ratio, 0.64; 95% CI, 0.44-0.92), after adjusting for dietary and lifestyle confounders. Associations with 12-year outcomes were not statistically significant.

Conclusion
A healthy diet including whole fruits, but not fruit juice, may play a role in mitigating T2DM risk.
Compliance to mineral supplementation among pregnant women at a public health clinic in Malaysia
Authors: Fadzil Nurul Nabilah Ahmad , Halain Azura Abdul , Nee Santhi A/P Yew Roan , Lam Soh Kim , Japar Salimah 
Published: June 2021

Background Prenatal supplementation has been introduced to pregnant women during early pregnancy to prevent complication to both mother and fetus. The complications include anaemia, postpartum haemorrhage, low birth weight and fetal defects. Aim To assess compliance with vitamin and mineral supplementation in pregnant women. Methods A cross-sectional design with simple random sampling was used in this study with 100 respondents who attended the maternal and child clinic in Selangor, Malaysia. Findings The findings showed that 86 respondents (86%) were compliance towards vitamin and mineral supplementation, whereas 35 respondents (35%) were non-compliance mainly due to forgetfulness. The result indicated a significant association between compliance with race (p=0.02), occupation (p<0.01), household income (p=0.02), education (p<0.01), parity (p<0.01) and trimester (p=0.02). Conclusion Majority of the respondents acknowledge that side effects and forgetfulness were the main influencing factors towards non-compliance.
Investigating the effect of training on health behaviours of breastfeeding mothers in Iran
Authors: Ghasemi Afsaneh , Harsini Pooyan Afzali , Jeihooni Ali Khani 
Published: June 2021

Aim This article aims to investigate the effect of training based on Pender's model on health promotion behaviours in breastfeeding mothers. Methodology In this quasi-experimental interventional study, 97 breastfeeding mothers referred to Fasa clinics were randomly studied in two case (n=48) and control (n=49) groups. To collect data, Walker et al's health promotion lifestyle questionnaire, including 52 questions, was used. After distributing the questionnaires in the first stage, the case group received five sessions of training. Data analysis was performed using SPSS20 software and independent t-test and paired t-test. Results According to the results, the highest and lowest scores were related to the areas of spiritual growth (23.29±6.16 before training and 24.65±6.56 after training) and interpersonal relationships (4.70±1.57 before training and 1.57±1.76 after training), respectively. In all six areas, a significant increase was found in scores after the training in the case group or between the case and control groups. Conclusion With this small sample and just one month training, the researchers demonstrated that it is possible to make changes in all areas of health. This can not only have an immediate effect but also a ‘snowball effect’ down the generations, through mother-children transfer, as well as mother-to-other family members transfer.
The role of the practice nurse in cancer care reviews
Authors: Dyer Sandra 
Published: June 2021

Recent changes to the Quality and Outcomes Framework provide an ideal opportunity to improve the quality of cancer care reviews and cancer patients' experiences. Sandra Dyer explains the important role practice nurses can play in improving care Improved outcomes for people diagnosed with cancer have led to increasing numbers of people living with and beyond the disease, and for many, cancer has transitioned to a long-term condition. There is a greater need for models of care that best meet these patients' needs, with the role of primary care becoming increasingly important. Recent changes to the Quality and Outcomes Framework (QOF) provide an ideal opportunity to improve the quality of cancer care reviews and improve cancer patients' experiences. More education and training for general practice nurses on cancer is urgently required to allow them to lead on quality improvement in this important area of care.
Factors affecting prehospital time delay of the injured patients arriving at the Emergency Department of Beni-Suef University Hospital in Egypt: A cross-sectional study
Authors: Khalil Doaa Mahmoud , Elmorsy Elmorsy , Arafa Ahmed , Nafady Hesham Ahmed , Saleh Lamiaa 
Published: June 2021

Purpose
This study aimed to assess the factors affecting the prehospital time delay of the injured patients arriving at the Emergency Department of Beni-Suef University Hospital in Upper Egypt.

Materials and methods
In this cross-sectional study, the following data were retrieved from the hospital records of 632 injured patients between 1/1/2018 and 31/3/2018: age, sex, residence, means of transportation to the hospital, prehospital time delay, consciousness level on admission, source of injury, and type of worst injury.

Results
The prehospital time delay (>one hour) of the injured patients was positively associated with age >60 years and rural residence but inversely associated with consciousness level with odds ratios (95% confidence intervals) of 5.14 (2.26–11.68), 3.49 (2.22–5.48), and 0.56 (0.32–0.96), respectively.

Conclusion
The prehospital time delay of the injured patients arriving at the Emergency Department of Beni-Suef University Hospital in Egypt was associated with old age, rural residence, and consciousness level.
Preface
Authors: Alexandre dit Sandretto Julien , Mullier Olivier , Chapoutot Alexandre 
Published: June 2021

The Summer Workshop on Interval Methods (SWIM) is an annual meeting initiated in 2008 by the French MEA working group on Set Computation and Interval Techniques of the French research group on Automatic Control. A special focus of the MEA group is on promoting interval analysis techniques and applications to a broader community of researchers, facilitated by such multidisciplinary workshops. Since 2008, SWIM has become a keystone event for researchers dealing with various aspects of interval and set-based methods.
In 2019, the 12th edition in this workshop series was held at ENSTA Paris, France, with a total of 25 talks.
Traditionally, workshops in the series of SWIM provide a platform for both theoretical and applied researchers who work on the development, implementation, and application of interval methods, verified numerics, and other related (set-membership) techniques.For this edition, given talks were in the fields of

the verified solution of initial value problems for ordinary differential equations, differential-algebraic system models, and partial differential equations,
scientific computing with guaranteed error bounds,
the design of robust and fault-tolerant control systems,
the implementation of corresponding software libraries, and
the usage of the mentioned approaches for a large variety of system models in areas such as control engineering, data analysis, signal and image processing.

Seven papers were selected for submission to this Acta Cybernetica special issue. After a two turn peer-review process, six high-quality articles were selected for publication in this special issue. Three papers propose a contribution regarding differential equations, two papers focus on robust control, and one paper considers fault detection.