Therapeutic benefits of maintaining CDK4/6 inhibitors and incorporating CDK2 inhibitors beyond progression in breast cancer.

The combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy has revolutionized treatment for hormone receptor-positive (HR+) metastatic breast cancer. However, the emergence of resistance in most patients often leads to treatment discontinuation with no consensus on effective second-line therapies. The therapeutic benefits of maintaining CDK4/6i or incorporating CDK2 inhibitors (CDK2i) after disease progression remain unclear.

[What are the considerations for medium prematurity?].

Despite its high prevalence, moderate prematurity has been little studied in comparison with great or very great prematurity. In order to better understand the causes of this under-representation in the literature and in post-hospital care, this article proposes to analyze the historical and medical issues surrounding prematurity, and to investigate the different representations, by caregivers and parents, of the subject of intermediate prematurity. A necessary step in the evolution of practices.

Demonstrating Agreement between Radio and Fluorescence Measurements of the Depth of Maximum of Extensive Air Showers at the Pierre Auger Observatory.

We show, for the first time, radio measurements of the depth of shower maximum (X_{max}) of air showers induced by cosmic rays that are compared to measurements of the established fluorescence method at the same location. Using measurements at the Pierre Auger Observatory we show full compatibility between our radio and the previously published fluorescence dataset, and between a subset of air showers observed simultaneously with both radio and fluorescence techniques, a measurement setup unique to the Pierre Auger Observatory. Furthermore, we show radio X_{max} resolution as a function of energy and demonstrate the ability to make competitive high-resolution X_{max} measurements with even a sparse radio array.

Conserved cellular patterning in the mesophyll of rice leaves.

The mesophyll cells of grass leaves, such as rice, are traditionally viewed as displaying a relatively uniform pattern, in contrast to the clear distinctions of palisade and spongy layers in typical eudicot leaves. This quantitative analysis of mesophyll cell size and shape in rice leaves reveals that there is an inherent pattern in which cells in the middle layer of the mesophyll are larger and less circular and have a distinct orientation of their long axis compared to mesophyll cells in other layers. Moreover, this pattern was observed in a range of rice cultivars and species.

Corrigendum: Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.

[This corrects the article DOI: 10.3389/fmicb.2023.

Sequential activation of E2F via Rb degradation and c-Myc drives resistance to CDK4/6 inhibitors in breast cancer.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are key therapeutic agents in the management of metastatic hormone-receptor-positive breast cancer. However, the emergence of drug resistance limits their long-term efficacy. Here, we show that breast cancer cells develop CDK4/6i resistance via a sequential two-step process of E2F activation.

A Modified-Herringbone Micromixer for Assessing Zebrafish Sperm (MAGS).

Sperm motility analysis of aquatic model species is important yet challenging due to the small sample volume, the necessity to activate with water, and the short duration of motility. To achieve standardization of sperm activation, microfluidic mixers have shown improved reproducibility over activation by hand, but challenges remain in optimizing and simplifying the use of these microdevices for greater adoption. The device described herein incorporates a novel micromixer geometry that aligns two sperm inlet streams with modified herringbone structures that split and recombine the sample at a 1:6 dilution with water to achieve rapid and consistent initiation of motility.

Grasses exploit geometry to achieve improved guard cell dynamics.

Stomata are controllable micropores formed between two adjacent guard cells (GCs) that regulate gas flow across the plant surface. Grasses, among the most successful organisms on the planet and the main food crops for humanity, have GCs flanked by specialized lateral subsidiary cells (SCs). SCs improve performance by acting as a local pool of ions and metabolites to drive changes in turgor pressure within the GCs that open/close the stomatal pore.

Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.

species, , and are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.

An economic evaluation of vagus nerve stimulation as an adjunctive treatment to anti-seizure medications for the treatment of drug resistant epilepsy in the United States.

Introduction: People with recurrent epileptic seizures are typically treated with anti-seizure medications (ASMs). Around a third of epilepsy patients fail to achieve an adequate response to ASMs and may be eligible to receive vagus nerve stimulation (VNS) therapy for their drug-resistant epilepsy (DRE) if they are unsuited to surgery. VNS received approval from the United States (US) Food and Drug Administration agency.

An international multicentric phase Ⅲ randomized controlled trial of time-acupoints-space acupuncture for the prevention of chemotherapy-induced fatigue in patients with early stage breast cancer: a study protocol.

Objective: To determine the difference in prevention of chemotherapy-induced fatigue between time-acupoints-space acupuncture (ATAS) administered weekly compared to sham acupuncture and non-acupuncture in patients with early breast cancer receiving adjuvant chemotherapy by epirubicine-cyclophosphamide (EC) followed by paclitaxel, as measured by the multi-dimensional fatigue inventory (MFI) over the previous week and Visual Analogue Scale measuring fatigue (VAS-F), and to evaluate the effects of ATAS on self-reported neuropathy pain, sleep, anxiety and depression.

Methods: In this multicenter clinical trial, we have randomized patients into 3 groups: ATAS, Sham and non-acupuncture with an unequal randomization of 2∶1∶1. A cloud related electronical clinical report form and smartphone platform was established for data entry.

Radiological patterns of tumour progression in patients treated with a combination of immune checkpoint blockers and antiangiogenic drugs.

Background: Immune checkpoint blockers (ICBs) in combination with antiangiogenic drugs showed synergistic efficacy in several tumour types. New patterns of progression have recently been defined upon treatment with ICB alone including atypical responses such as pseudoprogression (PsPD), dissociated response and hyperprogressive disease (HPD). This study aimed to describe the patterns of response observed in patients treated with combination ICB with antiangiogenic drugs.

Citizen science and niche modeling to track and forecast the expansion of the brown marmorated stinkbug Halyomorpha halys (Stål, 1855).

Halyomorpha halys (Stål, 1855), the Brown Marmorated StinkBug (BMSB) is a highly successful invasive species native to eastern Asia that managed to spread into North America and Europe in recent decades. We set up a citizen science survey to monitor BMSB expansion in France in 2012 and analyzed the data it yielded between 2012 and 2019 to examine the local expansion of the insect. These data were gathered with occurrences form various sources (GBIF, literature) to calibrate a species niche model and assess potential current BMSB range.

A crowdsourcing approach to track the expansion of the brown marmorated stinkbug (Stål, 1855) in France.

Background: (Stål, 1855), the brown marmorated stinkbug (BMSB) is a highly successful invasive species, native to eastern Asia. It has managed to spread into North America and Europe in recent decades, causing severe damage to various crops. BMSB has been detected in Europe in 2004 and has since expanded in more than 20 countries from Sweden to Greece and Spain to Turkey, the South European Territory of Russia (Krasnodar region) and Abkhazia.

Patterns of progression in patients treated for immuno-oncology antibodies combination.

Background: New patterns of progression under immune-oncology (IO) antibodies (mAb) have been described such as pseudoprogression. Except for melanoma, variations between studies reveal difficulties to establish their prevalence.

Methods: This retrospective study enrolled patients participating in IO phase I trials at Gustave Roussy cancer center for solid tumors excluding melanoma.

A modelling approach for the nonlinear dynamics of assembled structures undergoing fretting wear.

Assembled structures tend to exhibit nonlinear dynamic behaviour at high excitation levels due to the presence of contact interfaces. The possibility of building predictive models relies on the ability of the modelling strategy to capture the complex nonlinear phenomena occurring at the interface. One of these phenomena, normally neglected, is the fretting wear occurring at the frictional interface.

Intestinal bacterial β-glucuronidase as a possible predictive biomarker of irinotecan-induced diarrhea severity.

Irinotecan is an anticancer drug with a broad spectrum of activity, characterized by multistep and complex pharmacology. Regardless of its schedule of administration, neutropenia and delayed-type diarrhea are the most common side effects. The latter was the dose-limiting toxicity in phase I trials, and its prediction by pharmacogenetic (UGT1A1*28/*28) testing remains sub-optimal.

Time to progression ratio in cancer patients enrolled in early phase clinical trials: time for new guidelines?

Background: Reliable evaluation of treatment benefit in early phase clinical trials is necessary. The time to progression ratio (TTPr), which compares successive TTP in a single patient, is a powerful criteria for determining targeted or immune therapies efficacy.

Methods: We evaluated 205 TTPr in a large cohort of 177 advanced cancer patients enrolled in at least two Phase 1/1b trials (out of 2827 phase 1/1b-treated patients) at Gustave Roussy.

Outcomes of long-term responders to anti-programmed death 1 and anti-programmed death ligand 1 when being rechallenged with the same anti-programmed death 1 and anti-programmed death ligand 1 at progression.

Background: Long-term responders have been observed with anti-programmed death 1 and anti-programmed death ligand 1 (anti-PD(L)1). Optimal duration of therapy in responding and stable disease (SD) patients is unclear with various attitudes encompassing treatment until progression disease, stopping therapy after a defined timeframe.

Patients And Methods: We report the experience of 13 patients who discontinued immune checkpoint inhibitor in phase I trials as per protocol while experiencing a tumour-controlled disease.

Organisational factors influencing early clinical trials enrollment: Gustave Roussy experience.

Purpose: Enrolment process influences the likelihood of patients' inclusion in early clinical trials (ECT) through social, medical and organisational factors.

Patients And Methods: All patients referred from 2008 to 2016 to the Drug Development Department (DITEP) of Gustave Roussy (GR) were reviewed. Referring physician, organisational factors, medical and socioeconomic characteristics for patients were analysed.

Therapeutics discovery: From bench to first in-human trials.

The 'Therapeutics discovery: From bench to first in-human trials' conference, held at the King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Kingdom of Saudi Arabia (KSA) from October 10-12, 2017, provided a unique opportunity for experts worldwide to discuss advances in drug discovery and development, focusing on phase I clinical trials. It was the first event of its kind to be hosted at the new research center, which was constructed to boost drug discovery and development in the KSA in collaboration with institutions, such as the Academic Drug Discovery Consortium in the United States of America (USA), Structural Genomics Consortium of the University of Oxford in the United Kingdom (UK), and Institute of Materia Medica of the Chinese Academy of Medical Sciences in China. The program was divided into two parts.

Efficacy of histology-agnostic and molecularly-driven HER2 inhibitors for refractory cancers.

A targeted therapy is recommended in case of alteration for breast and gastric carcinomas, but miscellaneous other tumor types are altered at low prevalence. Broadening the administration of HER2 inhibitors across tumor types and genomic alterations could benefit to patients with refractory metastatic tumors. Targeted next-generation-sequencing (tNGS) and comparative genomic hybridization array (CGH) have been performed on fresh tumor biopsies of patients included in the MOSCATO-01 and ongoing MOSCATO-02 trials to administrate HER2 inhibitors in case of pathogenic mutation of amplification.

Human epidermal receptor family inhibitors in patients with ERBB3 mutated cancers: Entering the back door.

Introduction: Therapeutic inhibition of the human epidermal receptor 3 (ERBB3, HER3) has been challenged by the low frequency of ERBB3 somatic alterations across cancer types. We have evaluated the clinical utility to use available inhibitors of the HER family in the context of ERBB3 mutations.

Patients And Methods: In this study, we have selected patients with somatic ERBB3 alterations detected in their tumours from the molecular screening programs running at our institution.