Identification of as a Potential Locus Associated with Inhaled Corticosteroid Response in Childhood Asthma.

Inhaled corticosteroids (ICS) are the most common asthma controller medication. An important contribution of genetic factors in ICS response has been evidenced. Here, we aimed to identify novel genetic markers involved in ICS response in asthma.

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation.

Irritable bowel syndrome and risk of glaucoma: An analysis of two independent population-based cohort studies.

Objective: Irritable bowel syndrome (IBS) is a chronic disorder associated with an abnormal gastrointestinal microbiome. Microbiome-host interactions are known to influence organ function including in the central nervous system; thus, we sought to identify whether IBS may be a risk factor for the development of glaucoma.

Design: Two prospective cohort studies.

No association between recent antibiotic use and risk of rheumatoid arthritis: results from two prospective cohort studies.

Background: Retrospective research partly characterizes the link between antibiotic use and rheumatoid arthritis (RA) development. This prospective cohort study may help reassess the association.

Research Design And Methods: We included 133,125 participants from the Nurses' Health Study (NHS) and NHS II databases.

MICA/B antibody induces macrophage-mediated immunity against acute myeloid leukemia.

Acute myeloid leukemia (AML) is a clonal hematopoietic stem and progenitor cell malignancy characterized by poor clinical outcomes. Major histocompatibility complex class I polypeptide-related sequence A and B (MICA/B) are stress proteins expressed by cancer cells, and antibody-mediated inhibition of MICA/B shedding represents a novel approach to stimulate immunity against cancers. We found that the MICA/B antibody 7C6 potently inhibits the outgrowth of AML in 2 models in immunocompetent mice.

Healthful and Unhealthful Plant-Based Diets and Risk of Breast Cancer in U.S. Women: Results from the Nurses' Health Studies.

Background: Plant-based diets have been associated with lower risk of various diseases, including type 2 diabetes, cardiovascular disease, and other cardiometabolic risk factors. However, the association between plant-based diet quality and breast cancer remains unclear.

Methods: We prospectively followed 76,690 women from the Nurses' Health Study (NHS, 1984-2016) and 93,295 women from the NHSII (1991-2017).

Long-term weight changes and risk of rheumatoid arthritis among women in a prospective cohort: a marginal structural model approach.

Objective: To examine the association of long-term weight change with RA risk in a large prospective cohort study.

Methods: The Nurses' Health Study II started in 1989 (baseline); after exclusions, we studied 108 505 women 25-42 years old without RA. Incident RA was reported by participants and confirmed by medical record review.

Cyclic AMP does double duty to support parallel signaling in primary cilium and cytosol.

The primary cilium maintains all of the necessary machinery to generate and interpret cAMP signals within its tiny volume, leading to the supposition that ciliary cAMP provides unique biological instructions separate from those derived from the rest of the cell body. A new paper by Truong et al. has used optogenetic and chemogenetic tricks to selectively manipulate cAMP signaling within the primary cilium.

Intracellular HS production is an autophagy-dependent adaptive response to DNA damage.

Hydrogen sulfide (HS) is a gasotransmitter with broad physiological activities, including protecting cells against stress, but little is known about the regulation of cellular HS homeostasis. We have performed a high-content small-molecule screen and identified genotoxic agents, including cancer chemotherapy drugs, as activators of intracellular HS levels. DNA damage-induced HS in vitro and in vivo.

The association between vitamin K and medial tibial-femoral knee osteoarthritis progression: Data from the osteoarthritis initiative.

Objective: We sought to examine the prospective association of vitamin K with radiographic progression of knee osteoarthritis.

Methods: In OAI, 1977 participants with radiographic knee OA and having dietary data at baseline were followed up to 12, 24, 36 and 48 months. Vitamin K was assessed with a Block Brief Food Frequency Questionnaire completed at baseline.

Coordinated β-globin expression and α2-globin reduction in a multiplex lentiviral gene therapy vector for β-thalassemia.

A primary challenge in lentiviral gene therapy of β-hemoglobinopathies is to maintain low vector copy numbers to avoid genotoxicity while being reliably therapeutic for all genotypes. We designed a high-titer lentiviral vector, LVβ-shα2, that allows coordinated expression of the therapeutic β-globin gene and of an intron-embedded miR-30-based short hairpin RNA (shRNA) selectively targeting the α2-globin mRNA. Our approach was guided by the knowledge that moderate reduction of α-globin chain synthesis ameliorates disease severity in β-thalassemia.

Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation.

Background And Aims: Very early onset inflammatory bowel disease [VEOIBD] is characterized by intestinal inflammation affecting infants and children less than 6 years of age. To date, over 60 monogenic aetiologies of VEOIBD have been identified, many characterized by highly penetrant recessive or dominant variants in underlying immune and/or epithelial pathways. We sought to identify the genetic cause of VEOIBD in a subset of patients with a unique clinical presentation.

A form of muscular dystrophy associated with pathogenic variants in JAG2.

JAG2 encodes the Notch ligand Jagged2. The conserved Notch signaling pathway contributes to the development and homeostasis of multiple tissues, including skeletal muscle. We studied an international cohort of 23 individuals with genetically unsolved muscular dystrophy from 13 unrelated families.

Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer.

Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism of adaptive resistance to targeted therapy in cancer. An archetypal example is the development of neuroendocrine prostate cancer (NEPC) after treatment of prostate adenocarcinoma (PRAD) with inhibitors of androgen signaling. NEPC is an aggressive variant of prostate cancer that aberrantly expresses genes characteristic of neuroendocrine (NE) tissues and no longer depends on androgens.

Creb5 establishes the competence for Prg4 expression in articular cartilage.

A hallmark of cells comprising the superficial zone of articular cartilage is their expression of lubricin, encoded by the Prg4 gene, that lubricates the joint and protects against the development of arthritis. Here, we identify Creb5 as a transcription factor that is specifically expressed in superficial zone articular chondrocytes and is required for TGF-β and EGFR signaling to induce Prg4 expression. Notably, forced expression of Creb5 in chondrocytes derived from the deep zone of the articular cartilage confers the competence for TGF-β and EGFR signals to induce Prg4 expression.

Understanding and treating the inflammatory adverse events of cancer immunotherapy.

During the past decade, immunotherapies have made a major impact on the treatment of diverse types of cancer. Inflammatory toxicities are not only a major concern for Food and Drug Administration (FDA)-approved checkpoint blockade and chimeric antigen receptor (CAR) T cell therapies, but also limit the development and use of combination therapies. Fundamentally, these adverse events highlight the intricate balance of pro- and anti-inflammatory pathways that regulate protective immune responses.

Polygenic adaptation of rosette growth in Arabidopsis thaliana.

The rate at which plants grow is a major functional trait in plant ecology. However, little is known about its evolution in natural populations. Here, we investigate evolutionary and environmental factors shaping variation in the growth rate of Arabidopsis thaliana.

Occupational use of high-level disinfectants and asthma incidence in early- to mid-career female nurses: a prospective cohort study.

Objectives: Occupational use of disinfectants among healthcare workers has been associated with asthma. However, most studies are cross-sectional, and longitudinal studies are not entirely consistent. To limit the healthy worker effect, it is important to conduct studies among early- to mid-career workers.

Adolescent alcohol, nuts, and fiber: combined effects on benign breast disease risk in young women.

Adolescent drinking is associated with higher risks of proliferative benign breast disease (BBD) and invasive breast cancer (BC). Furthermore, adolescent nut and fiber consumptions are associated with lower risks of benign lesions and premenopausal BC. We hypothesize that diet (nuts, fiber) may mitigate the elevated BBD risk associated with alcohol.

Sweetened beverages and risk of frailty among older women in the Nurses' Health Study: A cohort study.

Background: Consumption of sugar-sweetened beverages (SSBs) has been consistently associated with a higher risk of obesity, type 2 diabetes, cardiovascular disease, and premature mortality, whereas evidence for artificially sweetened beverages (ASBs) and fruit juices on health is less solid. The aim of this study was to evaluate the consumption of SSBs, ASBs, and fruit juices in association with frailty risk among older women.

Methods And Findings: We analyzed data from 71,935 women aged ≥60 (average baseline age was 63) participating in the Nurses' Health Study (NHS), an ongoing cohort study initiated in 1976 among female registered nurses in the United States.

Electronic whiteboard implementation as a quality management tool optimizes IVF laboratory standardization and improves clinical outcomes.

Purpose: To test whether an electronic whiteboard in the IVF laboratory increases the likelihood that critical evaluation procedures are performed within optimum pre-set time ranges.

Methods: A retrospective cohort study of oocyte retrievals in our IVF clinic between 06/01/2012 and 05/31/2018 was included. The electronic whiteboard was introduced on 04/06/2014.

The Double-Edged Sword of Immunosuppressive Therapy in Kidney Transplantation: A Rare Case Report of Pulmonary Mucormycosis Post-Transplant and Literature Review.

Immunosuppressive therapy is improving the graft survival of kidney transplant recipients and increasing the potential risk of infection. Pulmonary mucormycosis is a rare post-operative infection complication characterized with rapid deterioration and high mortality. In this case, a 33-year-old patient underwent a kidney transplantation with regular immunosuppressive therapy.

Fruit and vegetable intake and risk of frailty in women 60 years old or older.

Background: Prior research has suggested that the antioxidative and anti-inflammatory potential of fruits and vegetables may ameliorate aging-related frailty.

Objective: We sought to prospectively examine the association between fruit and vegetable intake and incident frailty in older women.

Design: We followed 78,366 nonfrail women aged ≥60 y from the Nurses' Health Study from 1990 to 2014.