Changes in Breast Cancer Risk Associated with Benign Breast Disease from 1967 to 2013.

Background: Benign breast disease (BBD) increases breast cancer (BC) risk progressively for women diagnosed with non-proliferative (NP) change, proliferative disease without atypia (PDWA), and atypical hyperplasia (AH). Leveraging data from 18,704 women in the Mayo BBD Cohort (1967-2013), we evaluated temporal trends in BBD diagnoses and how they have influenced associated BC risk over four decades.

Methods: BC risk trends associated with BBD were evaluated using standardized incidence ratios (SIRs) and age-period-cohort modeling across four eras-pre-mammogram (1967-1981), pre-core needle biopsy (CNB) (1982-1992), transition to CNB (1993-2001), and CNB era (2002-2013).

Cancer Cell's Achilles Heels: Considerations for Design of Anti-Cancer Drug Combinations.

Loss of function screens using shRNA (short hairpin RNA) and CRISPR (clustered regularly interspaced short palindromic repeats) are routinely used to identify genes that modulate responses of tumor cells to anti-cancer drugs. Here, by integrating GSEA (Gene Set Enrichment Analysis) and CMAP (Connectivity Map) analyses of multiple published shRNA screens, we identified a core set of pathways that affect responses to multiple drugs with diverse mechanisms of action. This suggests that these pathways represent "weak points" or "Achilles heels", whose mild disturbance should make cancer cells vulnerable to a variety of treatments.

Single-cell multi-omic analysis of fibrolamellar carcinoma reveals rewired cell-to-cell communication patterns and unique vulnerabilities.

Fibrolamellar carcinoma (FLC) is a rare malignancy disproportionately affecting adolescents and young adults with no standard of care. FLC is characterized by thick stroma, which has long suggested an important role of the tumor microenvironment. Over the past decade, several studies have revealed aberrant markers and pathways in FLC.

Meeting report: Hidden links in autoimmunity.

A NIAID-sponsored workshop was held in September 2024, where challenges to understanding common mechanisms in autoimmune disease were discussed as opportunities to advance research.

Cryogenic Electron Microscopy of Rift Valley Fever Virus.

Rift Valley fever virus (RVFV) is an important livestock and human pathogen. It is also a potential bioweapon owing to its ability to spread by aerosols. It is an enveloped virus containing surface protrusions composed of two viral glycoproteins, G and G; the viral core contains ribonucleoprotein complexes.

Extreme LDL-C concentration is associated with increased cardiovascular disease in women with homozygous familial hypercholesterolemia.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease of low-density lipoprotein cholesterol (LDL-C) metabolism. Despite the devastating effect of this disease on atherosclerotic cardiovascular health, the disease phenotype and severity are more heterogeneous than previously thought. The predictors of atherosclerotic cardiovascular disease (ASCVD) in HoFH patients have never been systematically studied.

Surgical Time and Complication Risk in Conversion Total Hip Arthroplasty With Implant Removal: Finding an Optimal Surgical Duration.

Background: Although longer surgical times in primary total hip arthroplasty (THA) are associated with higher complication rates, this has yet to be explored in conversion THA. The purpose of this study is to investigate the relationship between surgical time and complications in the setting of conversion THA with implant removal. We aim to establish a length of surgery after which the risk of complications increases.

Recruitment Strategies and Obstacles During the Zoster Eye Disease Study.

Purpose: The aim of this study was to identify successful recruitment strategies and obstacles reported by principal investigators (PIs) of the Zoster Eye Disease Study (ZEDS).

Methods: A web-based survey was created by a subset of ZEDS PIs and distributed to ZEDS PIs after study enrollment was closed. The survey queried investigators about recruitment strategies and obstacles, use of prophylactic oral antiviral medication, electronic medical records, telemedicine, COVID-19 effect, turnover of research staff, and recruitment outreach to minority and underserved populations.

Occupational Noise Exposure in Foot and Ankle Surgery and the Risk of Noise-Induced Hearing Loss.

Background: Occupational exposure to high levels of noise increases the risk of noise-induced hearing loss (NIHL), resulting in significant long-term quality of life implications. Hearing protection is recommended if occupational noise exposure routinely exceeds 85 decibels (dB). The purpose of this study was to determine if foot and ankle surgeons are exposed to excessive levels of noise, thus putting them at an increased risk for NIHL.

Discovery of biophysical rate laws from the electronic health record enables real-time liver injury estimation from transaminase dynamics.

Alanine (ALT) and aspartate (AST) aminotransferases are standard-of-care biomarkers for liver injury though their temporal dynamics during injury and resolution remain incompletely characterized. Here, we analyze aminotransferase kinetics to determine whether rate laws can be ascertained during acute liver injury agnostic to etiology. From 6.

Preferential occurrence of fast radio bursts in massive star-forming galaxies.

Fast radio bursts (FRBs) are millisecond-duration events detected from beyond the Milky Way. FRB emission characteristics favour highly magnetized neutron stars, or magnetars, as the sources, as evidenced by FRB-like bursts from a galactic magnetar, and the star-forming nature of FRB host galaxies. However, the processes that produce FRB sources remain unknown.

Ten-Year Trends in Venous Thromboembolism Prophylaxis at a High-Volume Arthroplasty Center.

Introduction: Venous thromboembolism (VTE) prophylaxis is the standard of care after total joint arthroplasty. However, there have been changes in the prevalence of certain medication classes used by institutions over time driven by the literature and national clinical practice guidelines. The purpose of this study was to analyze the patterns of VTE medications over the past 10 years at our institution.

Undergoing Meniscectomy Within One Year Before Primary Total Knee Arthroplasty Is Associated With Worse Postoperative Outcomes.

Background: Patients undergoing primary total knee arthroplasty (TKA) who have a history of meniscectomy have worse postoperative functional outcomes, increased rates of early postoperative complications, and higher revision rates. Despite knowing this, to the best of our knowledge, it has not been previously studied whether the timing of meniscectomy before TKA impacts functional outcomes after undergoing TKA. Compared to patients who underwent meniscectomy more than one year before TKA, do patients who have meniscectomy less than one year before TKA have significantly different postoperative outcomes?

Methods: A retrospective cohort study was conducted at an academic medical center.

Polygenic risk scores stratify breast cancer risk among women with benign breast disease.

Purpose: Most breast biopsies are diagnosed as benign breast disease (BBD), with 1.5- to fourfold increased breast cancer (BC) risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in BC risk assessment of these patients.

Oxytocin receptor controls promiscuity and development in prairie voles.

Oxytocin receptor (Oxtr) signaling influences complex social behaviors in diverse species, including social monogamy in prairie voles. How Oxtr regulates specific components of social attachment behaviors and the neural mechanisms mediating them remains unknown. Here, we examine prairie voles lacking Oxtr and demonstrate that pair bonding comprises distinct behavioral modules: the preference for a bonded partner, and the rejection of novel potential mates.

Enriching Clinical Trials Enrolling Children With Cerebral Malaria Using Admission Demographics, Physical Examination and Point-of-care Testing Results.

Background: Multiple clinical trials evaluating therapies for cerebral malaria (CM) have failed to demonstrate improved outcomes. This may derive from inclusion of children at all risk levels, including those at low risk of mortality or neurologic morbidity, limiting power to detect significant differences between intervention arms. One solution is enrichment, enrolling clinical trial participants at higher risk of adverse outcomes.

Acute estradiol and progesterone therapy in hospitalized adults to reduce COVID-19 severity: a randomized control trial.

COVID-19 outcomes are less severe in women than men suggesting that female sex is protective. The steroids estradiol (E2) and progesterone (P4) promote anti-inflammatory immune responses and their therapeutic use for COVID-19 has been under investigation. The aim of the study was to evaluate the efficacy of a short systemic E2 and P4 combination in mitigating COVID-19 severity in hospitalized men and women.

Pancreatic Cancer-Associated Fibroblasts: Where Do We Go from Here?

Pancreatic ductal adenocarcinoma is a deadly disease and is projected to become the second leading cause of cancer-related death by 2030. A major hallmark is the exuberant host response comprising the tumor microenvironment, of which, cancer-associated fibroblasts (CAF) are a prevalent component. Despite the gains in understanding of their heterogeneity and functionality from CAF studies in recent years, there are many unanswered questions surrounding this diverse population of cells.

Exercise as part of survivorship care in metastatic breast cancer: protocol for the randomized EMBody trial.

Background: Exercise is associated with improved survival, physical functioning, treatment tolerability, and quality of life in early-stage breast cancer. These same endpoints matter in metastatic breast cancer (MBC). Prior trials in MBC have found exercise to be not feasible or of limited benefit, possibly due to inclusion of patients with heterogeneous disease trajectories.

Microcalcifications in benign breast biopsies: association with lesion type and risk.

Purpose: To characterize associations of microcalcifications (calcs) with benign breast disease lesion subtypes and assess whether tissue calcs affect risks of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).

Methods: We analyzed detailed histopathologic data for 4,819 BBD biopsies from a single institution cohort (2002-2013) followed for DCIS or IBC for a median of 7.4 years for cases (N = 338) and 11.

The INSIGHT study: a randomized, Phase III study of ripretinib versus sunitinib for advanced gastrointestinal stromal tumor with exon 11 + 17/18 mutations.

Somatic activating mutations drive most gastrointestinal stromal tumors (GISTs). Disease progression eventually develops with first-line imatinib, commonly due to secondary mutations, and different kinase inhibitors have various levels of treatment efficacy dependent on specific acquired resistance mutations. Ripretinib is a broad-spectrum switch-control KIT/PDGFRA tyrosine kinase inhibitor for patients with advanced GIST who received prior treatment with three or more kinase inhibitors, including imatinib.