Human inner ear tissue derived from pluripotent stem cells could provide a powerful platform for drug discovery or a source of sound-or motion-sensing cells for patients with hearing loss or balance dysfunction. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and Wnt signaling to generate multiple otic vesicle-like structures from a single stem-cell aggregate. Over two months, the vesicles develop into inner ear organoids with sensory epithelia that are innervated by sensory neurons. Additionally, using CRISPR/Cas9, we generate an ATOH1-2A-eGFP cell line to detect hair cell induction and demonstrate that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells. Our culture system will be useful for elucidating mechanisms of human inner ear development and testing potential inner ear therapies.The human inner ear contains ∼75,000 sensory hair cells that detect sound and movement via mechanosensitive stereocilia bundles 1,2 . Genetic mutations or environmental insults, such as loud noises and ototoxic drugs, can cause irreparable damage to these hair cells, Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Background Navigating the world of qualitative thematic analysis can be challenging. This is compounded by the fact that detailed descriptions of methods are often omitted from qualitative discussions. While qualitative research methodologies are now mature, there often remains a lack of fine detail in their description both at submitted peer reviewed article level and in textbooks. As one of research’s aims is to determine the relationship between knowledge and practice through the demonstration of rigour, more detailed descriptions of methods could prove useful. Rigour in quantitative research is often determined through detailed explanation allowing replication, but the ability to replicate is often not considered appropriate in qualitative research. However, a well described qualitative methodology could demonstrate and ensure the same effect. Methods This article details the codebook development which contributed to thematic analysis of qualitative data. This analysis formed part of a mixed methods multiphase design research project, with both qualitative and quantitative inquiry and involving the convergence of data and analyses. This design consisted of three distinct phases: quantitative, qualitative and implementation phases. Results and conclusions This article is aimed at researchers and doctoral students new to thematic analysis by describing a framework to assist their processes. The detailed description of the methods used supports attempts to utilise the thematic analysis process and to determine rigour to support the establishment of credibility. This process will assist practitioners to be confident that the knowledge and claims contained within research are transferable to their practice. The approach described within this article builds on, and enhances, current accepted models.

ObjectiveTo better understand the origins, manifestations and current policy responses to patient–physician mistrust in China.DesignQualitative study using in-depth interviews focused on personal experiences of patient–physician mistrust and trust.SettingGuangdong Province, China.ParticipantsOne hundred and sixty patients, patient family members, physicians, nurses and hospital administrators at seven hospitals varying in type, geography and stages of achieving goals of health reform. These interviews included purposive selection of individuals who had experienced both trustful and mistrustful patient–physician relationships.ResultsOne of the most prominent forces driving patient–physician mistrust was a patient perception of injustice within the medical sphere, related to profit mongering, knowledge imbalances and physician conflicts of interest. Individual physicians, departments and hospitals were explicitly incentivised to generate revenue without evaluation of caregiving. Physicians did not receive training in negotiating medical disputes or humanistic principles that underpin caregiving. Patient–physician mistrust precipitated medical disputes leading to the following outcomes: non-resolution with patient resentment towards physicians; violent resolution such as physical and verbal attacks against physicians; and non-violent resolution such as hospital-mediated dispute resolution. Policy responses to violence included increased hospital security forces, which inadvertently fuelled mistrust. Instead of encouraging communication that facilitated resolution, medical disputes sometimes ignited a vicious cycle leading to mob violence. However, patient–physician interactions at one hospital that has implemented a primary care model embodying health reform goals showed improved patient–physician trust.ConclusionsThe blind pursuit of financial profits at a systems level has eroded patient–physician trust in China. Restructuring incentives, reforming medical education and promoting caregiving are pathways towards restoring trust. Assessing and valuing the quality of caregiving is essential for transitioning away from entrenched profit-focused models. Moral, in addition to regulatory and legal, responses are urgently needed to restore trust.

These studies identify a previously uncharacterized and ubiquitously expressed immunosuppressive ligand CD70 in GBMs that also holds potential for serving as a novel CAR target for cancer immunotherapy in gliomas.

Chinese goldthread (Coptis chinensis Franch.), a member of the Ranunculales, represents an important early-diverging eudicot lineage with diverse medicinal applications. Here, we present a high-quality chromosome-scale genome assembly and annotation of C. chinensis. Phylogenetic and comparative genomic analyses reveal the phylogenetic placement of this species and identify a single round of ancient whole-genome duplication (WGD) shared by the Ranunculaceae. We characterize genes involved in the biosynthesis of protoberberine-type alkaloids in C. chinensis. In particular, local genomic tandem duplications contribute to member amplification of a Ranunculales clade-specific gene family of the cytochrome P450 (CYP) 719. The functional versatility of a key CYP719 gene that encodes the (S)-canadine synthase enzyme involved in the berberine biosynthesis pathway may play critical roles in the diversification of other berberine-related alkaloids in C. chinensis. Our study provides insights into the genomic landscape of early-diverging eudicots and provides a valuable model genome for genetic and applied studies of Ranunculales.