Polycystic ovary syndrome affects up to 17% of women of reproductive age and is associated with reduced fertility, type 2 diabetes and other detrimental health effects. In this issue, Stenor-Victorin and colleagues show that daughters of women with this syndrome are at five times greater risk of developing the disease. Prenatal exposure to androgen hormones, not obesity during pregnancy, may be the culprit of this transgenerational effect.

See: Stenor-Victorin and colleagues

Chromosomal instability is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization. In this issue, Andres Salumets and colleagues find that these chromosomal changes are not preserved at later stages of prenatal development, and therefore the rates of de novo numerical aberrations or large structural DNA imbalances are similar between IVF and naturally conceived live-born neonates.

See: Salumets and colleagues

Lung cancer is the leading cause of cancer-related deaths worldwide, with a five-year relative survival rate of 4% in the metastatic setting. In this issue, three reports from the TRACERx (TRAcking Cancer Evolution through therapy (Rx)) lung study provide insights into tumor evolution and intratumor heterogeneity that may facilitate the development of biomarkers and improve therapeutic outcomes for patients.

See: Dive and colleagues, Swanton and colleagues and Chain and colleagues.

Conventional leg prostheses do not convey sensory information about motion or interaction with the ground, to above-knee amputees, limiting their ability to recover confident prosthetic-assisted walking capacity. In this issue, Raspopovic et al report the development of a neuroprosthestic leg equipped with foot sensors of motion and ground touching that improves walking speed, confidence in walking, and reduces mental and physical fatigue associated with movement in two transfemoral amputees.

See: Raspopovic et al

Exclusive breastfeeding —giving infants only breast-milk with no additional food or drink for their first six months of life—is one of the most effective strategies for preventing child mortality. In this issue, Simon Hay and colleagues report that exclusive breastfeeding in Africa is highly varied within and between countries, with many countries unlikely to reach World Health Organization 2025 targets without urgent action.

See: Hay and colleagues and N&Vs by Reimers and colleagues

The therapeutic potential of immunotherapies is often limited by systemic adverse side effects. In this issue, Danino et al. engineer non-pathogenic E. coli designed to lyse within the tumor microenvironment and release therapeutic payloads locally that increases immune activation and facilitates tumor regression. The cover art depicts the concept of Russian dolls, where bacteria are programmed to produce immunotherapeutic nanobodies inside solid tumors.

See: Danino and colleagues and N&Vs by Dougan

The Pregnancy Initiative, part of the National Institutes of Health Integrative Human Microbiome Project, followed over 1,500 pregnant women longitudinally in the United States through pregnancy, aiming to understand how the microbiome changes during pregnancy and how it may impact the risk of premature birth.

See: Serrano and colleagues, Buck and colleagues and N&Vs by Dominguez-Bello

Premature infants often undergo repeated episodes of hypoxia and can develop a condition called encephalopathy of prematurity with long-term neurodevelopmental impairments. In this issue, Paşca et al. use human pluripotent stem cells to develop a three-dimensional brain-organoid-based model of early brain injury and investigate the cellular effects of oxygen deprivation on human cortical development. The cover illustrates efforts to generate in vitro cellular models of the developing human brain to study and prevent injury.

Nonalcoholic fatty liver disease ranges from steatosis to nonalcoholic steatohepatitis (NASH), potentially progressing to cirrhosis and hepatocellular carcinoma. In this issue, Mathias Heikenwalder and colleagues report the identification of a platelet-dependent mechanism that can potentially be targeted to stall the progress of liver steatosis to NASH and liver cancer. The cover shows an artistic rendition of an electron microscopy image of a NASH liver and activated platelets filled with granules ready to be secreted.

Reducing the burden of cancer remains a critical global health challenge. Ahead of the 2019 meeting of the American Association of Cancer Research, we bring our readers a special Focus on Cancer Therapy that highlights opportunities and challenges in our understanding of the disease, the development of new therapeutic approaches and the need for improved care and early diagnosis. The cover image is an artistic rendition of the combination of multiplex immunofluorescence and CyTOF analyses of glioblastoma samples from patients treated with neoadjuvant pembrolizumab, reported by Rob Prins and colleagues in this issue.

Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. In this issue of Nature Medicine, Artur Cideciyan and colleagues report that RNA antisense oligonucleotide therapy restores normal splicing of a ciliopathy-associated gene and shows promising safety and efficacy results in patients with Leber’s amaurosis. In an independent study, Morgan Maeder and colleagues report the development of a gene-editing approach to restore vision in preclinical models of this disease.

See Cideciyan and colleagues, Maeder and colleagues and News & Views by Sahel and Dalkara

As Nature Medicine celebrates its 25th anniversary, we bring our readers a special Focus on Digital Medicine that highlights the new technologies transforming medicine and healthcare, as well as the related regulatory challenges ahead.

See Focus