A metagenome-assembled genome inventory for children reveals early-life gut bacteriome and virome dynamics.

Existing microbiota databases are biased toward adult samples, hampering accurate profiling of the infant gut microbiome. Here, we generated a metagenome-assembled genome inventory for children (MAGIC) from a large collection of bulk and viral-like particle-enriched metagenomes from 0 to 7 years of age, encompassing 3,299 prokaryotic and 139,624 viral species-level genomes, 8.5% and 63.

Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE.

The ALPINE trial established the superiority of zanubrutinib over ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma; here, we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n = 327) or ibrutinib (n = 325). At an overall median follow-up of 42.

Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring.

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period.

Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

Background: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA.

Patients And Methods: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389).

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia.

Background: In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available.

Affordable, portable and self-administrable electrical impedance tomography enables global and regional lung function assessment.

Accessibility of diagnostic screening and treatment monitoring devices for respiratory diseases is critical in promoting healthcare and reducing sudden complications and mortality. Spirometry is the standard for diagnosing and monitoring several lung diseases. However, it lacks regional assessment capabilities necessary for detecting subtle regional changes in certain diseases.

Targeting the hepatitis B cccDNA with a sequence-specific ARCUS nuclease to eliminate hepatitis B virus in vivo.

Persistence of chronic hepatitis B (CHB) is attributed to maintenance of the intrahepatic pool of the viral covalently closed circular DNA (cccDNA), which serves as the transcriptional template for all viral gene products required for replication. Current nucleos(t)ide therapies for CHB prevent virus production and spread but have no direct impact on cccDNA or expression of viral genes. We describe a potential curative approach using a highly specific engineered ARCUS nuclease (ARCUS-POL) targeting the hepatitis B virus (HBV) genome.

High Incidence of Arterial and Venous Thrombosis in Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Objective: To determine the incidence of arterial thrombotic events (ATE) and venous thromboembolism (VTE) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods: This is a retrospective cohort study presenting the incidence of ATE (coronary events or ischemic stroke) and VTE [pulmonary embolism (PE) or deep venous thrombosis (DVT)] in patients diagnosed with AAV between 2005 and 2014.

Results: There were 204 patients with AAV who were identified.

A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.

Background: Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking.

Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia.

Background: Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma.

Methods: We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil.

Onset of severe nitrification in mildly nitrifying chloraminated bulk waters and its relation to biostability.

Triggers of severe nitrification in distribution systems are still not clearly understood. Recently, the biostability concept was proposed to explain the chloramine residual below which signs of nitrification would be seen. To improve understanding, mildly nitrifying bulk water samples (nitrite less than 0.