Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.

Purpose: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.

Methods: This is an investigator-initiated, multicenter, phase I trial.

An update on the status of HSP90 inhibitors in cancer clinical trials.

The evolutionary conserved molecular chaperone heat shock protein 90 (HSP90) plays an indispensable role in tumorigenesis by stabilizing client oncoproteins. Although the functionality of HSP90 is tightly regulated, cancer cells exhibit a unique dependence on this chaperone, leading to its overexpression, which has been associated with poor prognosis in certain malignancies. While various strategies targeting heat shock proteins (HSPs) involved in carcinogenesis have been explored, only inhibition of HSP90 has consistently and effectively resulted in proteasomal degradation of its client proteins.

Tofacitinib to prevent anti-drug antibody formation against LMB-100 immunotoxin in patients with advanced mesothelin-expressing cancers.

Background: LMB-100 is a mesothelin (MSLN)-targeting recombinant immunotoxin (iTox) carrying a Pseudomonas exotoxin A payload that has shown promise against solid tumors, however, efficacy is limited by the development of neutralizing anti-drug antibodies (ADAs). Tofacitinib is an oral Janus Kinase (JAK) inhibitor that prevented ADA formation against iTox in preclinical studies.

Methods: A phase 1 trial testing LMB-100 and tofacitinib in patients with MSLN-expressing cancers (pancreatic adenocarcinoma, n=13; cholangiocarcinoma, n=1; appendiceal carcinoma, n=1; cystadenocarcinoma, n=1) was performed to assess safety and to determine if tofacitinib impacted ADA formation.

The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial.

The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR).

A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma.

Background: ONC201 is a small molecule that can cause nonapoptotic cell death through loss of mitochondrial function. Results from the phase I/II trials of ONC201 in patients with refractory solid tumors demonstrated tumor responses and prolonged stable disease in some patients.

Methods: This single-arm, open-label, phase II clinical trial evaluated the efficacy of ONC201 at the recommended phase II dose (RP2D) in patients with recurrent or refractory metastatic breast or endometrial cancer.

Comparison of soccer instep kicking kinematics with and without elastic taping.

The present study aimed to determine the effect of elastic taping on soccer instep kicking kinematics. Fifteen male university soccer players performed maximal instep kicking with and without Y-shaped elastic taping on the skin surface of the rectus femoris muscle. Their kicking motions were captured at 500 Hz using a motion capture system.

Improving reliability and validity in hip-hop dance assessment: Judging standards that elevate the sport and competition.

This study examined the reliability and validity of judging system scores of past hip-hop dance competitions in Japan. The analysis focused on the scores for each assessment category separately. Judges' scores were obtained from national dance competitions held annually in Japan between 2014 and 2019.

Judges' evaluation reliability changes between identifiable and anonymous performance of hip-hop dance movements.

Hip-hop competitions are performed across the world. In the recent inclusion in the 2018 Youth Olympic Games, the assessment of hip-hop performance is undertaken by a panel of judges. The purpose of this study was to determine the reliability of different visualisation tools utilised in the assessment of the hip-hop dance movements.

Effect of individual ankle taping components on the restriction of ankle external inversion moment.

The efficacy of individual taping components to restrain ankle inversion sprain has not been fully understood to date. We aimed to clarify specific taping components that can effectively restrain the amount of angular impulse due to external ankle inversion moments during dynamic ankle motion. Nine participants with chronic ankle instability performed a side-jump with five taping conditions: stirrup, figure eight, heel lock, basketweave, and without taping (control).

Correlation between degree of hallux valgus and kinematics in classical ballet: A pilot study.

Hallux valgus is a serious medical concern for classical ballet dancers. Although it is well-known that progression of hallux valgus is related to inappropriate movement techniques in classical ballet, the kinematic relationship between the degree of hallux valgus and ballet techniques has not been substantiated. To develop proper training methods that prevent progression of hallux valgus, this study aimed to investigate the relationship between the degree of hallux valgus and movement techniques in classical ballet.

Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis.

Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions. Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis.

Disorder of Coagulation-Fibrinolysis System: An Emerging Toxicity of Anti-PD-1/PD-L1 Monoclonal Antibodies.

A disruption of immune checkpoints leads to imbalances in immune homeostasis, resulting in immune-related adverse events. Recent case studies have suggested the association between immune checkpoint inhibitors (ICIs) and the disorders of the coagulation-fibrinolysis system, implying that systemic immune activation may impact a balance between clotting and bleeding. However, little is known about the association of coagulation-fibrinolysis system disorder with the efficacy of ICIs.

Protective effect of bevacizumab on chemotherapy-related acute exacerbation of interstitial lung disease in patients with advanced non-squamous non-small cell lung cancer.

Background: Acute exacerbation of interstitial lung disease (AE-ILD) is the most serious complication in lung cancer patients with pre-existing ILD receiving chemotherapy. The role of vascular endothelial growth factor (VEGF) in pathogenesis of AE-ILD is conflicting. The influence of bevacizumab (Bev), a monoclonal antibody against VEGF, on lung cancer patients with pre-existing ILD remains unclear.

A potential mechanism of the onset of acute eosinophilic pneumonia triggered by an anti-PD-1 immune checkpoint antibody in a lung cancer patient.

Introduction: The impact of immune checkpoint blockade on immunity in cancer patients is not completely elucidated due to the complexity of the immune network. Recent studies have revealed a significant role of programed cell death-ligand 2 (PD-L2) in negatively controlling the production of CD4+ T helper type 2 (Th2) cytokines and airway hypersensitiveness, suggesting hypo-responsive Th2 cells via the PD-1/PD-L2 inhibitory pathway in lung could be reawaken by PD-1 blockade therapy.

Methods: We describe the first report of acute eosinophilic pneumonia (AEP), which is known as Th2-associated pulmonary disease, triggered by nivolumab, an anti-PD-1 antibody, in an advanced non-small cell lung cancer patient.

PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis.

Cigarette smoke (CS)-induced accumulation of mitochondrial damage has been widely implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Mitophagy plays a crucial role in eliminating damaged mitochondria, and is governed by the PINK1 (PTEN induced putative protein kinase 1)-PRKN (parkin RBR E3 ubiquitin protein ligase) pathway. Although both increased PINK1 and reduced PRKN have been implicated in COPD pathogenesis in association with mitophagy, there are conflicting reports for the role of mitophagy in COPD progression.

Novel mathematical model to estimate ball impact force in soccer.

To assess ball impact force during soccer kicking is important to quantify from both performance and chronic injury prevention perspectives. We aimed to verify the appropriateness of previous models used to estimate ball impact force and to propose an improved model to better capture the time history of ball impact force. A soccer ball was fired directly onto a force platform (10 kHz) at five realistic kicking ball velocities and ball behaviour was captured by a high-speed camera (5,000 Hz).

Ankle taping can reduce external ankle joint moments during drop landings on a tilted surface.

Ankle taping is commonly used to prevent ankle sprains. However, kinematic assessments investigating the biomechanical effects of ankle taping have provided inconclusive results. This study aimed to determine the effect of ankle taping on the external ankle joint moments during a drop landing on a tilted surface at 25°.

Kinematic repeatability of a multi-segment foot model for dance.

The purpose of this study was to determine the intra and inter-assessor repeatability of a modified Rizzoli Foot Model for analysing the foot kinematics of ballet dancers. Six university-level ballet dancers performed the movements; parallel stance, turnout plié, turnout stance, turnout rise and flex-point-flex. The three-dimensional (3D) position of individual reflective markers and marker triads was used to model the movement of the dancers' tibia, entire foot, hindfoot, midfoot, forefoot and hallux.

Azithromycin attenuates myofibroblast differentiation and lung fibrosis development through proteasomal degradation of NOX4.

Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis.

Pirfenidone inhibits myofibroblast differentiation and lung fibrosis development during insufficient mitophagy.

Background: Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis.

Subinterlobular Pleural Location Is a Risk Factor for Pneumothorax After Bronchoscopy.

Background: Pneumothorax is one of the most important complications after bronchoscopy. This study was conducted to determine the risk factors for post-bronchoscopy pneumothorax.

Methods: We retrospectively reviewed the medical records of 23 consecutive subjects who were diagnosed with iatrogenic pneumothorax after bronchoscopy between August 2010 and February 2014.

Single-leg squats can predict leg alignment in dancers performing ballet movements in "turnout".

The physical assessments used in dance injury surveillance programs are often adapted from the sports and exercise domain. Bespoke physical assessments may be required for dance, particularly when ballet movements involve "turning out" or external rotation of the legs beyond that typically used in sports. This study evaluated the ability of the traditional single-leg squat to predict the leg alignment of dancers performing ballet movements with turnout.

Metformin attenuates lung fibrosis development via NOX4 suppression.

Background: Accumulation of profibrotic myofibroblasts in fibroblastic foci (FF) is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis (IPF) pathogenesis, and transforming growth factor (TGF)-β plays a key regulatory role in myofibroblast differentiation. Reactive oxygen species (ROS) has been proposed to be involved in the mechanism for TGF-β-induced myofibroblast differentiation. Metformin is a biguanide antidiabetic medication and its pharmacological action is mediated through the activation of AMP-activated protein kinase (AMPK), which regulates not only energy homeostasis but also stress responses, including ROS.

Key motion characteristics of side-step movements in hip-hop dance and their effect on the evaluation by judges.

In hip-hop dance, the elements of motion that discriminate the skill levels of dancers and that influence the evaluations by judges have not been clearly identified. This study set out to extract these motion characteristics from the side-step movements of hip-hop dancing. Eight expert and eight non-expert dancers performed side-step movements, which were recorded using a motion capture system.