Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.

Purpose: Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo.

Methods: Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic in KARS1 variants.

Comparison of Survival among Colon Cancer Patients in the U.S. Military Health System and Patients in the Surveillance, Epidemiology, and End Results (SEER) Program.

Background: Access to health care is associated with cancer survival. The U.S.

Timing of Androgen Deprivation Treatment for Men with Biochemical Recurrent Prostate Cancer in the Context of Novel Therapies.

Purpose: There were 3 recent U.S. Food and Drug Administration approvals for drugs to be used in nonmetastatic castration resistant prostate cancer, a state that arises from the unproven start of continuous androgen deprivation therapy (ADT) for biochemical recurrent prostate cancer (BCR), before metastatic disease is evident.

Incidence rates of oral cavity and oropharyngeal cancers among men: a comparison of active-duty military and general populations.

Objectives: This study compared oral cavity and oropharyngeal cancer incidence rates and trends among men in the active-duty military and the general population of the USA.

Methods: Data were from the Department of Defenses' Automated Central Tumor Registry (ACTUR) and the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER-9) registries. Age-adjusted oral cavity and oropharyngeal cancer incidence rates among men aged 20-59 from 1990-2013 were compared between ACTUR and SEER populations.

Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients.

Pathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n = 16; FH-mutation confirmed) and non-syndromic (NS) patients (n = 12) identified a significantly higher protein:transcript correlation in HLRCC (R = 0.35) vs.

Use of electronic cigarettes in the United States service member and Veteran populations: A narrative review (2019).

Electronic Nicotine Delivery Systems (ENDS) are an increasingly popular form of a nicotine delivery device, particularly among young adults and adolescents. The health consequences of long-term ENDS use are not known. Two populations that warrant special consideration are members of the United States Military (service members) and US Veterans.

Effectiveness of antenatal screening of asymptomatic bacteriuria in reduction of prematurity and low birth weight: Evaluating a point-of-care rapid test in a pragmatic randomized controlled study.

Background: Premature babies suffer higher mortality and life-long disabilities. Asymptomatic bacteriuria (ASB) is postulated to induce preterm labor. Routine antenatal screening for ASB using urine culture is not feasible in most developing countries due to long turn-around time, user-unfriendliness, and lack of resources.

Expanding TNM for lung cancer through machine learning.

Background: Expanding the tumor, lymph node, metastasis (TNM) staging system by accommodating new prognostic and predictive factors for cancer will improve patient stratification and survival prediction. Here, we introduce machine learning for incorporating additional prognostic factors into the conventional TNM for stratifying patients with lung cancer and evaluating survival.

Methods: Data were extracted from SEER.

Racial-Ethnic Comparison of Guideline-Adherent Gynecologic Cancer Care in an Equal-Access System.

Objective: To compare receipt of National Comprehensive Cancer Network Guideline-adherent treatment for gynecologic cancers, inclusive of uterine, cervical, and ovarian cancer, between non-Hispanic White women and racial-ethnic minority women in the equal-access Military Health System.

Methods: We accessed MilCanEpi, which links data from the Department of Defense Central Cancer Registry and Military Health System Data Repository administrative claims data, to identify a cohort of women aged 18-79 years who were diagnosed with uterine, cervical, or ovarian cancer between January 1, 1998, and December 31, 2014. Information on tumor stage, grade, and histology was used to determine which treatment(s) (surgery, chemotherapy, radiotherapy) was indicated for each patient according to the National Comprehensive Cancer Network Guidelines during the period of the data (1998-2014).

Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review.

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27.10.

A prognostic system for epithelial ovarian carcinomas using machine learning.

Introduction: Integrating additional factors into the International Federation of Gynecology and Obstetrics (FIGO) staging system is needed for accurate patient classification and survival prediction. In this study, we tested machine learning as a novel tool for incorporating additional prognostic parameters into the conventional FIGO staging system for stratifying patients with epithelial ovarian carcinomas and evaluating their survival.

Material And Methods: Cancer-specific survival data for epithelial ovarian carcinomas were extracted from the Surveillance, Epidemiology, and End Results (SEER) program.

High mRNA expression of LY6 gene family is associated with overall survival outcome in pancreatic ductal adenocarcinoma.

Pancreatic cancer ranks one of the worst in overall survival outcome with a 5 year survival rate being less than 10%. Pancreatic cancer faces unique challenges in its diagnosis and treatment, such as the lack of clinically validated biomarkers and the immensely immunosuppressive tumor microenvironment. Recently, the LY6 gene family has received increasing attention for its multi-faceted roles in cancer development, stem cell maintenance, immunomodulation, and association with more aggressive and hard-to-treat cancers.

Age and Tumor Differentiation-Associated Gene Expression Based Analysis of Non-Familial Prostate Cancers.

Prostate cancer incidence in young men has increased. Patients diagnosed at an earlier age are likely to have aggressive prostate cancer and treatment decisions are continuing to be weighted by patient age and life expectancy. Identification of age-associated gene-expression signatures hold great potential to augment current and future treatment modalities.

Avelumab, a PD-L1 Inhibitor, in Combination with Hypofractionated Radiotherapy and the Abscopal Effect in Relapsed Refractory Multiple Myeloma.

Lessons Learned: Despite the initial optimism for using immune checkpoint inhibition in the treatment of multiple myeloma, subsequent clinical studies have been disappointing. Preclinical studies have suggested that priming the immune system with various modalities in addition to checkpoint inhibition may overcome the relative T-cell exhaustion or senescence; however, in this small data set, radiotherapy with checkpoint inhibition did not appear to activate the antitumor immune response.

Background: Extramedullary disease (EMD) is recognized as an aggressive subentity of multiple myeloma (MM) with a need for novel therapeutic approaches.

Progesterone induces apoptosis by activation of caspase-8 and calcitriol via activation of caspase-9 pathways in ovarian and endometrial cancer cells in vitro.

Previously we have shown inhibition of endometrial cancer cell growth with progesterone and calcitriol. However, the mechanisms by which the two agents attenuate proliferation have not been well characterized yet. Herein, we investigated how progesterone and calcitriol induce apoptosis in cancer cells.

Adult pilocytic astrocytoma in the molecular era: a comprehensive review.

Adult pilocytic astrocytoma (PA) is less prevalent than pediatric PA and is associated with a worse prognosis. In a literature review, we found that 88.3% of the molecular alterations in adult PA are associated with MAPK pathway dysregulation.

Keeping tabs: Reducing postoperative opioid prescriptions for patients after breast surgical procedures.

Background: As the opioid crisis continues, it is critical that health care providers ensure they are not overprescribing opioid medications. At our institution (Walter Reed National Military Medical Center, Bethesda, MD), postoperative patients after breast surgeries are discharged with variable amounts of opioid medications. However, many patients report minimal opioid use.

Heritability of Low ER Staining/HER2-Breast Tumors: Are We Missing an Opportunity for Germline Testing?

In 2010, the genetic testing criteria was changed to allow women diagnosed ≤ 60 years old with triple negative breast cancer (TNBC) to undergo germline testing. In the same year, estrogen receptor (ER) positivity was defined as having ≥1% ER staining cells. While tumors with 1-10% ER staining cells and HER2 negative (HER2-) status share characteristics with TNBC, the utility of germline testing in women with ER low positive/HER2- (ERLP/HER2-) tumors is not well-understood.

Comparative analysis of differentially abundant proteins quantified by LC-MS/MS between flash frozen and laser microdissected OCT-embedded breast tumor samples.

Background: Proteomic studies are typically conducted using flash-frozen (FF) samples utilizing tandem mass spectrometry (MS). However, FF specimens are comprised of multiple cell types, making it difficult to ascertain the proteomic profiles of specific cells. Conversely, OCT-embedded (Optimal Cutting Temperature compound) specimens can undergo laser microdissection (LMD) to capture and study specific cell types separately from the cell mixture.

Functional role of vitronectin in breast cancer.

Breast Cancer is the most common form of cancer in women worldwide, impacting nearly 2.1 million women each year. Identification of new biomarkers could be key for early diagnosis and detection.

Assessment of Discordance Among Smoldering Multiple Myeloma Risk Models.

This cohort study assesses the concordance of 3 models to stratify risk for progression to multiple myeloma in an independent cohort of patients with smoldering multiple myeloma.

Cancer Previvors in an Active Duty Service Women Population: An Opportunity for Prevention and Increased Force Readiness.

Background: The majority of active duty service women (ADS) are young, have access to healthcare, and meet fitness standards set by the U.S. military, suggesting that ADS represent a healthy population at low risk of cancer.

Frequency and spectrum of mutations across 94 cancer predisposition genes in African American women with invasive breast cancer.

African American women are at increased risk of being diagnosed at a young age and/or with triple negative breast cancer, both factors which are included in current guidelines for identifying women who may benefit from genetic testing. Commercial breast cancer predisposition genetic panels, based largely on data derived from women of European ancestry, may not capture the full spectrum of cancer predisposition genes associated with breast cancer in African American women. Between 2001 and 2018, 488 unselected African American women with invasive breast cancer enrolled in the Clinical Breast Care Project.

Uterine clear cell carcinoma risk in White versus non-White US subpopulations: does race matter?

Objective: To determine incidence rates of uterine clear cell carcinoma among non-White US subpopulations.

Methods: Data from the United States Cancer Statistics and National Cancer Database from 2004 to 2016 were analyzed using descriptive statistics.

Results: A total of 488,811 women were diagnosed with uterine cancer from 2004-2016.