Volume 24 Issue 12, December 2018

We take stock of who made headlines this year for enlightening us and making us think.

From the cancellation of a massive alcohol study to the dissolution of Theranos, 2018 was a year fraught with shutdowns. But amid all the shake-ups, the year also saw a few firsts, including approval of an artificial intelligence–based medical platform that helps clinicians diagnose strokes.

In 2018, drugs for rare conditions such as beta-thalassemia and forms of amyloidosis made it onto the approval mainstage in addition to drugs for more common diseases such as cancer. The gene-editing technology CRISPR slowly made strides into the therapeutic realm, while drugs for Alzheimer’s disease continued to falter, leaving a wide gap that is still in need of filling.

StrainSifter is a tool that is able to identify the relatedness of a blood-borne infection to the gut microbiome using single-nucleotide variant data.

Metformin functions through a gut microbiome–bile acid–farnesoid X receptor axis to lower glucose in type 2 diabetes, revealing a new therapeutic target in this disease.

Protein-specific and shared genetic pathways influence the spread of amyloid-β and tau pathology. Hence, distinct gene expression profiles may induce regional vulnerability of the human cortex to the specific proteinopathies of Alzheimer’s disease.

Analysis of the UK Biobank genetic and phenotypic data demonstrate the power of including a large population and detailed phenotyping in a prospective study to identify genetic and lifestyle factors related to health and disease.

Disruption of the circadian clock has been linked to cancer and alterations in cancer metabolism and this has implications for therapeutic development.

Preliminary evidence from two cases suggests that fecal microbiota transplantation may provide a viable treatment option for a severe adverse effect of immune checkpoint blockade therapy in patients with cancer.

A new bioinformatic tool identifies a candidate source of bloodstream infection for better management and prevention of hospital-acquired infections.

Skin from individuals with a rare immunodeficiency harbors more eukaryotic viruses than healthy skin, highlighting the role of immune surveillance in modulating the skin microbiome.

Infant nutrition and maternal weight gain during pregnancy impact early-life acquisition and function of the gut microbiome .

A biocompatible device built from naturally dissolving components and controlled by wireless technology enables programmable electrical stimulation of injured rodent peripheral nerves to accelerate regeneration and recovery.

Single-cell RNA-seq of a mouse model of multiple sclerosis uncovers new oligodendrocyte populations and putative disease markers and suggests new mechanisms underlying the pathogenesis of the disease.

Radiotherapy-induced abscopal responses enhance the efficacy of anti-CTLA-4 in patients with non-small-cell lung cancer.

Initial results from a first-in-human study show that PET imaging with PD-L1 antibodies outperforms immunohistochemistry- or RNA-sequencing-based biomarkers for prediction of clinical response to immunotherapy.

Targeting of mitochondrial metabolism in combination with BCL-2 inhibition eradicates leukemia stem cells and induces long-lasting responses in patients with acute myeloid leukemia.

Single cell dissection of plasma cell heterogeneity in myeloma patients reveals new insights into disease that may inform early diagnosis and clinical management.

The translation initiation complex mediates tumor immune escape in melanoma by controlling STAT1 mRNA levels and T lymphocyte–induced PD-L1 expression.

ONECUT2 is a targetable transcription factor that antagonizes androgen receptor signaling and drives androgen independence and neuroendocrine differentiation in castration-resistant prostate cancer.

Systemic administration of human PBGD mRNA encapsulated in lipid nanoparticles ameliorates disease phenotypes in mouse and rabbit models of acute hepatic porphyria and is safe in nonhuman primates.

Cross-sectional and longitudinal PET imaging of amyloid beta and tau in the human brain is combined with gene expression profiles to define the interactions between Alzheimer’s disease-related pathology propagation and brain-region-specific vulnerability.

Metformin decreases the levels of Bacteroides fragilis while increasing the bile acid GUDCA to antagonize intestinal FXR and improves the metabolic health of humans and mice.

Personal ‘omics’ analysis of a single individual over a period of 3 years reveals that different types of omics data associate with episodes of acute and chronic disease.