Abdominal Obesity in Comparison with General Obesity and Risk of Developing Rheumatoid Arthritis in Women.

Objective: Being overweight or obese increases rheumatoid arthritis (RA) risk among women, particularly among those diagnosed at a younger age. Abdominal obesity may contribute to systemic inflammation more than general obesity; thus, we investigated whether abdominal obesity, compared to general obesity, predicted RA risk in 2 prospective cohorts: the Nurses' Health Study (NHS) and NHS II.

Methods: We followed 50,682 women (1986-2014) in NHS and 47,597 women (1993-2015) in NHS II, without RA at baseline.

Involvement of fine particulate matter exposure with gene expression pathways in breast tumor and adjacent-normal breast tissue.

Background: Fine particulate matter (PM) has been associated with breast cancer specific mortality, particularly for women with Stage I cancer. We examined the biological pathways that are perturbed by PM exposures by analyzing gene expression measurements from breast tissue specimens.

Methods: The Nurses' Health Studies (NHS and NHSII) are prospective cohorts with archival breast tissue specimens from breast cancer cases.

A comparison of macronutrient-based methods for deriving energy values in human milk.

Objective: Energy values for human milk are increasingly available clinically, though there are no standards for deriving these values. We compared published calorie methods using a common set of samples.

Study Design: Ten human milk samples were measured for gross and digestible macronutrients using laboratory methods.

Gold/alpha-lactalbumin nanoprobes for the imaging and treatment of breast cancer.

Theranostic agents should ideally be renally cleared and biodegradable. Here, we report the synthesis, characterization and theranostic applications of fluorescent ultrasmall gold quantum clusters that are stabilized by the milk metalloprotein alpha-lactalbumin. We synthesized three types of these nanoprobes that together display fluorescence across the visible and near-infrared spectra when excited at a single wavelength through optical colour coding.

Intramuscular progesterone versus 8% Crinone vaginal gel for luteal phase support following blastocyst cryopreserved single embryo transfer: a retrospective cohort study.

Background: The optimal route of progesterone administration for luteal support in cryopreserved embryo transfer (CET) has been the subject of much debate. While most published research has pertained to day 3 transfers, recent data on blastocyst CET has suggested that intramuscular progesterone (IMP) is superior to twice daily vaginal Endometrin suppositories for luteal phase support, resulting in significantly higher ongoing pregnancy rates. This study aimed to determine whether IMP is similarly superior to 8% Crinone vaginal gel for luteal phase support following blastocyst CET.

Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy.

Checkpoint blockade with antibodies specific for the PD-1 and CTLA-4 inhibitory receptors can induce durable responses in a wide range of human cancers. However, the immunological mechanisms responsible for severe inflammatory side effects remain poorly understood. Here we report a comprehensive single-cell analysis of immune cell populations in colitis, a common and severe side effect of checkpoint blockade.

The Afirma Xpression Atlas for thyroid nodules and thyroid cancer metastases: Insights to inform clinical decision-making from a fine-needle aspiration sample.

Recent analytical and clinical validation of the Afirma Xpression Atlas (XA) demonstrates test reliability and the identification of genomic alterations that may inform patient management. The updated Afirma Genomic Sequencing Classifier and XA reports aim to optimize the understanding of these contributions, including decisions about observation versus surgery, the need for disease‐specific preoperative testing, associated neoplasm types, prognostics, the identification of molecular targets for systemic therapy, and the recognition of potential hereditary syndromes.

High-Resolution In Vivo Identification of miRNA Targets by Halo-Enhanced Ago2 Pull-Down.

The identification of microRNA (miRNA) targets by Ago2 crosslinking-immunoprecipitation (CLIP) methods has provided major insights into the biology of this important class of non-coding RNAs. However, these methods are technically challenging and not easily applicable to an in vivo setting. To overcome these limitations and facilitate the investigation of miRNA functions in vivo, we have developed a method based on a genetically engineered mouse harboring a conditional Halo-Ago2 allele expressed from the endogenous Ago2 locus.

Composite quantitative knee structure metrics predict the development of accelerated knee osteoarthritis: data from the osteoarthritis initiative.

Background: We aimed to determine if composite structural measures of knee osteoarthritis (KOA) progression on magnetic resonance (MR) imaging can predict the radiographic onset of accelerated knee osteoarthritis.

Methods: We used data from a nested case-control study among participants from the Osteoarthritis Initiative without radiographic KOA at baseline. Participants were separated into three groups based on radiographic disease progression over 4 years: 1) accelerated (Kellgren-Lawrence grades [KL] 0/1 to 3/4), 2) typical (increase in KL, excluding accelerated osteoarthritis), or 3) no KOA (no change in KL).

Inhibition of MICA and MICB Shedding Elicits NK-Cell-Mediated Immunity against Tumors Resistant to Cytotoxic T Cells.

Resistance to cytotoxic T cells is frequently mediated by loss of MHC class I expression or IFNγ signaling in tumor cells, such as mutations of or genes. Natural killer (NK) cells could potentially target such resistant tumors, but suitable NK-cell-based strategies remain to be developed. We hypothesized that such tumors could be targeted by NK cells if sufficient activating signals were provided.

Copy number assessment in the genomic analysis of CNS neoplasia: An evidence-based review from the cancer genomics consortium (CGC) working group on primary CNS tumors.

The period from the 1990s to the 2010s has witnessed a burgeoning sea change in the practice of surgical neuropathology due to the incorporation of genomic data into the assessment of a range of central nervous system (CNS) neoplasms. This change has since matured into the adoption of genomic information into the definition of several World Health Organization (WHO)-established diagnostic entities. The data needed to accomplish the modern diagnosis of CNS neoplasia includes DNA copy number aberrations that may be assessed through a variety of mechanisms.

Targeted resequencing reveals rare variants enrichment in multiple sclerosis susceptibility genes.

Although genome-wide association studies have identified a number of common variants associated with multiple sclerosis (MS) susceptibility, little is known about the relevance of rare variants. Here, we aimed to explore the role of rare variants in 14 MS risk genes (FCRL1, RGS1, TIMMDC1, HHEX, CXCR5, LTBR, TSFM, GALC, TRAF3, STAT3, TNFSF14, IFI30, CD40, and CYP24A1) by targeted resequencing in an Iberian population of 524 MS cases and 546 healthy controls. Four rare variants-enriched regions within CYP24A1, FCRL1, RGS1, and TRAF3 were identified as significantly associated with MS.

COMPSRA: a COMprehensive Platform for Small RNA-Seq data Analysis.

Small RNA-Seq is a common means to interrogate the small RNA'ome or the full spectrum of small RNAs (<200 nucleotide length) of a biological system. A pivotal problem in NGS based small RNA analysis is identifying and quantifying the small RNA'ome constituent components. For example, small RNAs in the circulatory system (circulating RNAs) are potential disease biomarkers and their function is being actively investigated.

Adiposity Change Over the Life Course and Mammographic Breast Density in Postmenopausal Women.

Mammographic breast density is a strong risk factor for breast cancer. We comprehensively investigated the associations of body mass index (BMI) change from ages 10, 18, and 30 to age at mammogram with mammographic breast density in postmenopausal women. We used multivariable linear regression models, adjusted for confounders, to investigate the associations of BMI change with volumetric percent density, dense volume, and nondense volume, assessed using Volpara in 367 women.

Diet quality and risk of frailty among older women in the Nurses' Health Study.

Background: The frailty syndrome is associated with higher risk of disability and death after accounting for multimorbidity. Therefore, the determinants of frailty need to be identified to ensure older adults live not only longer but also healthier lives. However, the effect of diet quality on frailty is mostly unknown.

Ascl2-Dependent Cell Dedifferentiation Drives Regeneration of Ablated Intestinal Stem Cells.

Ablation of LGR5 intestinal stem cells (ISCs) is associated with rapid restoration of the ISC compartment. Different intestinal crypt populations dedifferentiate to provide new ISCs, but the transcriptional and signaling trajectories that guide this process are unclear, and a large body of work suggests that quiescent "reserve" ISCs contribute to regeneration. By timing the interval between LGR5 lineage tracing and lethal injury, we show that ISC regeneration is explained nearly completely by dedifferentiation, with contributions from absorptive and secretory progenitors.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper on the Evaluation and Management for Patients With Very Early-onset Inflammatory Bowel Disease.

The rate of pediatric inflammatory bowel disease (IBD) has been increasing over the last decade and this increase has occurred most rapidly in the youngest children diagnosed <6 years, known as very early-onset inflammatory bowel disease (VEO-IBD). These children can present with more extensive and severe disease than older children and adults. The contribution of host genetics in this population is underscored by the young age of onset and the distinct, aggressive phenotype.

Dietary Patterns and Progression of Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

Background: While some individual foods and nutrients have been associated with knee osteoarthritis (KOA) progression, the association between dietary patterns and KOA progression has received little research attention.

Objective: The objective of this study was to determine whether dietary patterns, derived by principal components analysis (PCA), are associated with KOA progression.

Methods: In the Osteoarthritis Initiative (OAI), a prospective cohort with clinical centers in Maryland, Ohio, Pennsylvania, and Rhode Island, 2757 participants with existing KOA (mean age 62 y) and diet assessed at baseline were followed for ≤72 mo.

Effect of Hypopnea Scoring Criteria on Noninvasive Assessment of Loop Gain and Surgical Outcome Prediction.

Unstable ventilatory control (high loop gain) is a causal factor in the development of obstructive sleep apnea. Methods for quantifying loop gain using polysomnography have been developed that predict favorable responses to upper airway surgery. However, this method is reliant on respiratory event scoring and hence may be affected by hypopnea scoring criteria.

Adults With Incident Accelerated Knee Osteoarthritis Are More Likely to Use Pharmacological Treatment Options and Receive Arthroscopic Knee Surgery: Data From the Osteoarthritis Initiative.

Objective: To determine if people with incident accelerated knee osteoarthritis (AKOA) were more likely to receive a pharmacological treatment or arthroscopic knee surgery than those with typical knee osteoarthritis (KOA) or no KOA.

Methods: We conducted a nested cohort study using data from baseline and the first 8 years of the Osteoarthritis Initiative. Eligible participants had no radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2).