Proximal tubule-on-chip as a model for predicting cation transport and drug transporter dynamics.

Deciphering the sources of variability in drug responses requires to understand the processes modulating drug pharmacokinetics. However, pharmacological research suffers from poor reproducibility across clinical, animal, and experimental models. Predictivity can be improved by using Organs-on-Chips, which are more physiological, human-oriented, micro-engineered devices that include microfluidics.

Gut microbiota biotransformation of drug glucuronides leading to gastrointestinal toxicity: Therapeutic potential of bacterial β-glucuronidase inhibition in mycophenolate-induced enteropathy.

Aims: Drug-induced enteropathy is often associated with the therapeutic use of certain glucuronidated drugs. One such drug is mycophenolic acid (MPA), a well-established immunosuppressant of which gastrointestinal adverse effects are a major concern. The role of bacterial β-glucuronidase (β-G) from the gut microbiota in MPA-induced enteropathy has recently been discovered.

DICER1 syndrome and embryonal rhabdomyosarcoma of the cervix: a case report and literature review.

Background: Embryonal rhabdomyosarcomas (ERMS) of the uterine cervix and corpus are rare pediatric tumors usually associated with a late age of onset and frequent somatic DICER1 mutation. It may also develop in the context of a familial predisposition such as DICER1 syndrome requiring specific medical care for children and young adults at risk for a broad range of tumors.

Case Presentation: This is a case of a prepubescent 9-year-old girl who was presented to our department for metrorrhagias due to a vaginal cervical mass, initially classified as a müllerian endocervical polyp on negative myogenin immunostaining.

Fibroblast growth factor-2 bound to specific dermal fibroblast-derived extracellular vesicles is protected from degradation.

Fibroblast growth factor-2 (FGF2) has multiple roles in cutaneous wound healing but its natural low stability prevents the development of its use in skin repair therapies. Here we show that FGF2 binds the outer surface of dermal fibroblast (DF)-derived extracellular vesicles (EVs) and this association protects FGF2 from fast degradation. EVs isolated from DF cultured in the presence of FGF2 harbor FGF2 on their surface and FGF2 can bind purified EVs in absence of cells.

Lipid desaturation regulates the balance between self-renewal and differentiation in mouse blastocyst-derived stem cells.

Stem cells are defined by their ability to self-renew and differentiate, both shown in multiple studies to be regulated by metabolic processes. To decipher metabolic signatures of self-renewal in blastocyst-derived stem cells, we compared early differentiating embryonic stem cells (ESCs) and their extra-embryonic counterparts, trophoblast (T)SCs to their self-renewing counterparts. A metabolomics analysis pointed to the desaturation of fatty acyl chains as a metabolic signature of differentiating blastocyst-derived SCs via the upregulation of delta-6 desaturase (D6D; FADS2) and delta-5 desaturase (D5D; FADS1), key enzymes in the biosynthesis of polyunsaturated fatty acids (PUFAs).

Extracellular Vesicle-Mediated Metastasis Suppressors NME1 and NME2 Modify Lipid Metabolism in Fibroblasts.

Nowadays, extracellular vesicles (EVs) raise a great interest as they are implicated in intercellular communication between cancer and stromal cells. Our aim was to understand how vesicular NME1 and NME2 released by breast cancer cells influence the tumour microenvironment. As a model, we used human invasive breast carcinoma cells overexpressing NME1 or NME2, and first analysed in detail the presence of both isoforms in EV subtypes by capillary Western immunoassay (WES) and immunoelectron microscopy.

Quantitative Ubiquitylome Analysis Reveals the Specificity of RNF111/Arkadia E3 Ubiquitin Ligase for its Degradative Substrates SKI and SKIL/SnoN in TGF-β Signaling Pathway.

RNF111/Arkadia is an E3 ubiquitin ligase that activates the transforming growth factor-β (TGF-β) pathway by degrading transcriptional repressors SKIL/SnoN and SKI. Truncations of the RING C-terminal domain of RNF111 that abolish its E3 function and subsequently activate TGF-β signaling are observed in some cancers. In the present study, we sought to perform a comprehensive analysis of RNF111 endogenous substrates upon TGF-β signaling activation using an integrative proteomic approach.

[IgG4-Related Disease: A rare cause of severe interstitial lung disease].

Background: The intrathoracic manifestations of IgG4-related disease include a range of conditions and severity, and can on occasion cause acute respiratory failure as reported in the case described here.

Observation: A 69-year-old male former smoker, was admitted to our hospital with dyspnea, fever, cough, fatigue, and a 3-month history of weight loss. He received high flow oxygen therapy and non-invasive ventilation for severe respiratory failure.

Hospital-at-Home Expands Hospital Capacity During COVID-19 Pandemic.

A Coronavirus Disease 2019 (COVID-19)-specific Hospital-at-Home was implemented in a 400-bed tertiary hospital in Barcelona, Spain. Senior or immune-compromised physicians oversaw patient care. The alternative to inpatient care more than doubled beds available for hospitalization and decreased the risk of transmission among patients and health care professionals.

Looking into the dynamics of molecular crystals of ibuprofen and terephthalic acid using O and H nuclear magnetic resonance analyses.

Oxygen-17 and deuterium are two quadrupolar nuclei that are of interest for studying the structure and dynamics of materials by solid-state nuclear magnetic resonance (NMR). Here, O and H NMR analyses of crystalline ibuprofen and terephthalic acid are reported. First, improved O-labelling protocols of these molecules are described using mechanochemistry.

Stem cell donor registry activities during the COVID-19 pandemic: a field report by DKMS.

The COVID-19 pandemic has serious implications also for patients with other diseases. Here, we describe the effects of the pandemic on unrelated hematopoietic stem cell donation and transplantation from the perspective of DKMS, a large international donor registry. Especially, we cover the development of PBSC and bone marrow collection figures, donor management including Health and Availability Check (HAC), transport and cryopreservation of stem cell products, donor recruitment and business continuity measures.

[Familial pulmonary veno-occlusive disease with a composite biallelic heterozygous EIF2AK4 mutation].

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Heritable and sporadic forms have been distinguished. Hypoxemia, profound reduction in the diffusion of carbon monoxide and haemodynamic confirmation of pre-capillary pulmonary hypertension are the major diagnostic criteria.

Efficacy of Chest CT for COVID-19 Pneumonia Diagnosis in France.

Background The role and performance of chest CT in the diagnosis of the coronavirus disease 2019 (COVID-19) pandemic remains under active investigation. Purpose To evaluate the French national experience using chest CT for COVID-19, results of chest CT and reverse transcription polymerase chain reaction (RT-PCR) assays were compared together and with the final discharge diagnosis used as the reference standard. Materials and Methods A structured CT scan survey (NCT04339686) was sent to 26 hospital radiology departments in France between March 2, 2020, and April 24, 2020.

[Eosinophilic pneumonia: A rare complication of sodium divalproate].

Introduction: Eosinophilic pneumonias are characterized by an increase in lung eosinophils. These disorders can be induced by drug reactions.

Case Report: A 57-year-old woman suffering from bipolar disorder and treated by sodium divalproate for more than 2 years was hospitalised in the department of respiratory medicine for dyspnoea and cough.

COVID-19 impact assessment on the French radiological centers: a nationwide survey.

Purpose: To determine the impact of the COVID-19 on the CT activities in French radiological centers during the epidemic peak.

Materials And Methods: A cross-sectional prospective CT scan survey was conducted between March 16 and April 12, 2020, in accordance with the local IRB. Seven hundred nine radiology centers were invited to participate in a weekly online survey.

Purification of Extracellular Microvesicles Secreted by Dermal Fibroblasts.

Extracellular vesicles (EVs) secreted by all cells are key players in information transfer within a tissue or organism. With their highly cell-specific protein and RNA content, EVs can propagate cellular signals and modulate distant cells' behavior. Dermal fibroblasts are supportive cells for all skin cells and the roles of their EVs start to come to light only recently.

Single-cell RNA-seq identifies a reversible mesodermal activation in abnormally specified epithelia of p63 EEC syndrome.

Mutations in transcription factor p63 are associated with developmental disorders that manifest defects in stratified epithelia including the epidermis. The underlying cellular and molecular mechanism is however not yet understood. We established an epidermal commitment model using human induced pluripotent stem cells (iPSCs) and characterized differentiation defects of iPSCs derived from ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome patients carrying p63 mutations.

Extracellular Vesicles from Activated Dermal Fibroblasts Stimulate Hair Follicle Growth Through Dermal Papilla-Secreted Norrin.

Dermal papilla cells (DPCs) play a pivotal role in the regulation of hair follicle (HF) growth, formation, and cycling, mainly through paracrine mechanisms. In the last decade, extracellular vesicles (EVs) have been recognized as a new paracrine mechanism that can modify the physiological state of recipient cells by transferring biological material. Herein, we investigated the effect of EVs isolated from stimulated human dermal fibroblasts (DFs) on DPC activation and HF growth.

[Drug-induced interstitial pneumonitis due to avelumab: A case report].

Introduction: The anti programmed death-1 (PD-1) and the programmed death ligand 1 (PD-L1) antibodies are used as immunotherapies in the treatment of many solid tumours. Cases of interstitial pneumonitis induced by anti PD-1 have been widely described, but there are fewer data with anti PD-L1. Avelumab is a new immunotherapy of the anti PD-L1 class.

Heterogeneity of ecological patterns, processes, and funding of marine manipulative field experiments conducted in Southeastern Pacific coastal ecosystems.

Ecological manipulative experiments conducted in marine coastal ecosystems have substantially improved ecological theory during the last decades and have provided useful knowledge for the management and conservation of coastal ecosystems. Although different studies report global trends in ecological patterns worldwide, Southeastern Pacific coastal ecosystems have been poorly considered. Given that the SE Pacific coast encompasses diverse coastal ecosystems, consideration of studies conducted along this range can shed light on the heterogeneity of processes regulating coastal communities.

Computed tomographic perfusion with 160-mm coverage: comparative analysis of hepatocellular carcinoma treated by two transarterial chemoembolization courses relative to magnetic resonance imaging findings.

Purpose: The aim of this study was to assess hepatocellular carcinoma (HCC) response with CT perfusion parameters before and after two transarterial chemo embolization (TACE) courses compared with MRI, and to search for predictive factors of response.

Methods: 37 lesions (19 patients) were included between October 2015 and September 2017, based on the Barcelona Clinic Liver Cancer guidelines. CT perfusion with 160-mm coverage and MRI were performed before and after the first TACE course, and after the second TACE course.