Kjeldgaardjohnsen4472

Human pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provide unprecedented opportunities for cell therapies against intractable diseases and injuries. Both ESCs and iPSCs are already being used in clinical trials. However, we continue to encounter practical issues that limit their use, including their inherent properties of tumorigenicity, immunogenicity, and heterogeneity. Here, I review two decades of research aimed at overcoming these three difficulties.Upcoming clinical trials assessing transplantation of stem cell-derived dopaminergic neurons into the striatum in patients with Parkinson's disease could generate groundbreaking results on neuronal replacement in the human brain. However, as highlighted here, the road toward a clinically competitive treatment for this multisystem disorder will probably be long and winding.The Japanese conditional and time-limited (CTL) approval framework, a tiered system for regenerative medical products, was initiated in 2014. Here, we compare the dossiers of six regenerative medical products with either direct full approval or CTL approval, and we discuss the regulatory considerations for obtaining approval under the CTL approval framework.China's stem cell research policies are based on a cultural understanding that grants special protection to human embryos but does not assign them equivalent moral or legal status as fully developed humans. We discuss ethical considerations for embryo research and policy changes as China moves toward adopting internationally recognized rules.COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers.Type 1 diabetes mellitus results from autoimmune destruction of pancreatic β cells. Insulin treatment is often inadequate in preventing devastating complications. Replacing β cells using stem cell-derived islets while fostering immune tolerance, exemplified in Yoshihara et al., holds the promise of a curative therapy for this disease.Among the common flaviviruses that infect humans, Zika virus, and the contemporary Asian strain in particular, is distinctively associated with microcephaly. Zeng et al. buy IDN-6556 (2020) report in this issue of Cell Stem Cell that strong binding and inhibition of human Dicer enzyme by the capsid protein is a potential mechanism for this unique pathogenic potential.The role of Hippo pathway in colorectal cancer (CRC) initiation and progression has been controversial. In this issue of Cell Stem Cell, Cheung et al. (2020) shed new light on a distinct function of the transcriptional co-activator YAP as a tumor suppressor and Wnt pathway inhibitor in CRC.Discovered as a proto-oncogene 40 years ago, mutations in KRAS exist in ∼30% of all human cancers. In this issue of Cell Stem Cell,Dost et al. (2020) combine the power of analyzing organoid cultures, patient samples, and mouse models with scRNA-seq to elucidate early events occurring with oncogenic KRAS activation.

It is unclear whether tenofovir disoproxil fumarate and entecavir differ in their association with risk of hepatocellular carcinoma in patients with chronic hepatitis B, and previous meta-analyses have shown conflicting conclusions with substantial heterogeneity. We aimed to analyse the updated data and elucidate the source of heterogeneity.

We searched PubMed, Embase, Web of Science, and the Cochrane library for relevant studies with time-to-event data for incident hepatocellular carcinoma occurring in patients with chronic hepatitis B who received tenofovir disoproxil fumarate or entecavir monotherapy with follow-up of at least 1 year. Studies published between Jan 1, 2006, and April 17, 2020, and abstracts from international conferences in 2018 and 2019 were included. We pooled covariate adjusted hazard ratios (HRs) for hepatocellular carcinoma using a random-effects model, assessed heterogeneity among included studies using the I

statistic and Cochran's Q test, and identified the source of heterogensted HR 1·03, 95% CI 0·88-1·21; I

=0%). However, tenofovir disoproxil fumarate was associated with a lower risk of hepatocellular carcinoma compared with entecavir in administrative database research (adjusted HR 0·67, 0·59-0·76; I

=0%).

Our study found no significant difference between tenofovir disoproxil fumarate and entecavir in their association with incident hepatocellular carcinoma. We suggest that treatment should be guided by patient tolerability and affordability rather than whether one drug is more effective than the other.

Supported in part by E-DA Hospital (EDAHP 106008; EDAHP 103046).

Supported in part by E-DA Hospital (EDAHP 106008; EDAHP 103046).The lack of childcare infrastructure in the COVID-19 pandemic has highlighted many systemic problems faced by academic caregivers, and particularly new parents. This commentary uses the lessons from the pandemic to highlight the potential role of mentors in supporting caregiver responsibilities.Jails and prisons are exceptionally susceptible to viral outbreaks, such as severe acute respiratory syndrome coronavirus 2. The USA has extremely high rates of incarceration and COVID-19 is causing an urgent health crisis in correctional facilities and detention centres. Epidemics happening in prisons are compounding the elevated risks that COVID-19 poses to people of colour, older people, and those with comorbidities. Intersectoral community re-entry efforts in the USA and other countries have shown that releasing people from correctional facilities as a pandemic-era public health intervention is safe and can support both public safety and community rebuilding. Therefore, substantial decarceration in the USA should be initiated. A point of focus for such efforts is that many people in prison are serving excessively long sentences and pose acceptable safety risks for release. Properly managed, correctional depopulation will prevent considerable COVID-19 morbidity and mortality and reduce prevailing socioeconomic and health inequities.