Efficacy of Ibandronate Loading Dose on Rapid Pain Relief in Patients With Non-Small Cell Lung Cancer and Cancer Induced Bone Pain: The NVALT-9 Trial

Introduction: Approximately 80% of non-small cell lung cancer (NSCLC) patients with bone metastases have cancer induced bone pain (CIBP). Methods: The NVALT-9 was an open-label, single arm, phase II, multicenter study. Main inclusion criterion: bone metastasized NSCLC patients with uncontrolled CIBP [brief pain inventory [BPI] ≥ 5 over last 7 days]. Patients were treated with six milligram ibandronate intravenously (day 1–3) once a day. Main exclusion criteria: active secondary malignancy, systemic anti-tumor treatment and radiotherapy ≤4 weeks before study start, previous bisphosphonate treatment. Statistics: Simon's Optimal two-stage design with a 90% power to declare the treatment active if the pain response rate is ≥ 80% and 95% confidence to declare the treatment inactive if the pain response rate is ≤ 60%. If pain response is observed in ≤ 12 of the first 19 patients further enrollment will be stopped. Primary endpoint: bone pain response, defined as 25% decrease in worst pain score (PSc) over a 3-day period (day 5–7) compared to baseline PSc with maximum of 25% increase in mean analgesic consumption during the same period. Secondary endpoints: BPI score, quality of life, toxicity and World Health Organization Performance Score. Results: Of the 19 enrolled patients in the first stage, 18 were evaluable for response. All completed ibandronate treatment according to protocol. In 4 (22.2%), a bone pain response was observed. According to the stopping rule, further enrollment was halted. Discussion: Ibandronate loading doses lead to insufficient pain relief in NSCLC patients with CIBP

The Audible Universe Workshop: an Interdisciplinary Approach to the Design and Evaluation of Tools for Astronomical Data Sonification

Even if images of astrophysical objects are used by professional astronomers for research and by the public for outreach, we are all basically blind to the Universe. Challenging the idea that we should always use visualisations, there has been a growing interest in converting astronomical phenomena into sound, motivated by: making astronomy more accessible to people who are blind or visually impaired (BVI); creating more engaging educational resources, and enabling a deeper understanding of complex astronomical data. The Audible Universe (AU) workshop focuses on consolidating what has been done in the field so far and identifying the areas where most effort is required to make progress over the coming years. The second edition of the AU workshop (AU2) took place in 2022, and brought together 50 experts, among whom astronomers interested in sonification, sound designers, experts in sound perception and educators. This community started a multi-disciplinary discussion about how to properly design and evaluate sonification tools. In this methodological and position paper, we present and discuss the main activities of the AU2 workshop, with a particular focus on activities concerned with the development of collaborative design processes, and the implementation of methods for evaluation. While this workshop was dedicated to fostering exchanges between the sonification community and astronomers, the structure and the methods used within the workshop are transferable to other application areas, and a contribution to the effort to develop interdisciplinary strategies for the development of the field of sonification.QC 20230705</p

The Audible Universe Workshop: an Interdisciplinary Approach to the Design and Evaluation of Tools for Astronomical Data Sonification

Even if images of astrophysical objects are used by professional astronomers for research and by the public for outreach, we are all basically blind to the Universe. Challenging the idea that we should always use visualisations, there has been a growing interest in converting astronomical phenomena into sound, motivated by: making astronomy more accessible to people who are blind or visually impaired (BVI); creating more engaging educational resources, and enabling a deeper understanding of complex astronomical data. The Audible Universe (AU) workshop focuses on consolidating what has been done in the field so far and identifying the areas where most effort is required to make progress over the coming years. The second edition of the AU workshop (AU2) took place in 2022, and brought together 50 experts, among whom astronomers interested in sonification, sound designers, experts in sound perception and educators. This community started a multi-disciplinary discussion about how to properly design and evaluate sonification tools. In this methodological and position paper, we present and discuss the main activities of the AU2 workshop, with a particular focus on activities concerned with the development of collaborative design processes, and the implementation of methods for evaluation. While this workshop was dedicated to fostering exchanges between the sonification community and astronomers, the structure and the methods used within the workshop are transferable to other application areas, and a contribution to the effort to develop interdisciplinary strategies for the development of the field of sonification.QC 20230705</p

Sequencing and chromosomal localization of Fabp6 and an intronless Fabp6 segment in the rat

The fatty acid binding protein 6 gene (Fabp6) codes for ileal lipid binding protein. After sequencing of rat Fabp6, the gene was localized in a radiation hybrid (RH) map on chromosome 10. An intronless Fabp6 segment was found in four related rat inbred strains (SHR; SHRSP; WKY; and OKA), but not in 62 other rat inbred strains. The intronless Fabp6 segment, which might be a pseudogene of Fabp6, was localized on rat chromosome 15

The tumor suppressor gene FBXW7 is disrupted by a constitutional t(3;4)(q21;q31) in a patient with renal cell cancer

FBXW7 (alias CDC4) is a p53-dependent tumor suppressor gene that exhibits mutations or deletions in a variety of human tumors. Mutation or deletion of the FBXW7 gene has been associated with an increase in chromosomal instability and cell cycle progression. In addition, the FBXW7 protein has been found to act as a component of the ubiquitin proteasome system and to degrade several oncogenic proteins that function in cellular growth regulatory pathways. By using a rapid breakpoint cloning procedure in a case of renal cell cancer (RCC), we found that the FBXW7 gene was disrupted by a constitutional t(3;4)(q21;q31). Subsequent analysis of the tumor tissue revealed the presence of several anomalies, including loss of the derivative chromosome 3. Upon screening of a cohort of 29 independent primary RCCs, we identified one novel pathogenic mutation, suggesting that the FBXW7 gene may also play a role in the development of sporadic RCCs. In addition, we screened a cohort of 48 unrelated familial RCC cases with unknown etiology. Except for several known or benign sequence variants such as single nucleotide polymorphisms (SNPs), no additional pathogenic variants were found. Previous mouse models have suggested that the FBXW7 gene may play a role in the predisposition to tumor development. Here we report that disruption of this gene may predispose to the development of human RCC.status: publishe

Efficacy of Ibandronate Loading Dose on Rapid Pain Relief in Patients With Non-Small Cell Lung Cancer and Cancer Induced Bone Pain:The NVALT-9 Trial

Introduction:Approximately 80% of non-small cell lung cancer (NSCLC) patients with bone metastases have cancer induced bone pain (CIBP). Methods:The NVALT-9 was an open-label, single arm, phase II, multicenter study. Main inclusion criterion: bone metastasized NSCLC patients with uncontrolled CIBP [brief pain inventory [BPI] >= 5 over last 7 days]. Patients were treated with six milligram ibandronate intravenously (day 1-3) once a day. Main exclusion criteria: active secondary malignancy, systemic anti-tumor treatment and radiotherapy = 80% and 95% confidence to declare the treatment inactive if the pain response rate i

Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis

Tissue-resident and recruited macrophages contribute to both host defense and pathology. Multiple macrophage phenotypes are represented in diseased tissues, but we lack deep understanding of mechanisms controlling diversification. Here, we investigate origins and epigenetic trajectories of hepatic macrophages during diet-induced non-alcoholic steatohepatitis (NASH). The NASH diet induced significant changes in Kupffer cell enhancers and gene expression, resulting in partial loss of Kupffer cell identity, induction of Trem2 and Cd9 expression, and cell death. Kupffer cell loss was compensated by gain of adjacent monocyte-derived macrophages that exhibited convergent epigenomes, transcriptomes, and functions. NASH-induced changes in Kupffer cell enhancers were driven by AP-1 and EGR that reprogrammed LXR functions required for Kupffer cell identity and survival to instead drive a scar-associated macrophage phenotype. These findings reveal mechanisms by which disease-associated environmental signals instruct resident and recruited macrophages to acquire distinct gene expression programs and corresponding functions