The Addition of Systemic Terbinafine to Antifungal Combination Therapy in the Treatment of Disseminated Drug-Resistant Mold Infections in a National Cancer Institute Comprehensive Cancer Center: A Six-Year Study.

Introduction Combination antifungal regimens are frequently employed in the treatment of invasive fungal infections in patients who are immunocompromised, particularly for cancer and transplant patients. Terbinafine is a potential agent of interest for combination regimens. Methods We reviewed data over a six-year period examining patient outcomes in terms of both mortality and distribution of pathogens.

An Event-Driven Approach to Genotype Imputation on a Custom RISC-V Cluster.

This article proposes an event-driven solution to genotype imputation, a technique used to statistically infer missing genetic markers in DNA. The work implements the widely accepted Li and Stephens model, primary contributor to the computational complexity of modern x86 solutions, in an attempt to determine whether further investigation of the application is warranted in the event-driven domain. The model is implemented using graph-based Hidden Markov Modeling and executed as a customized forward/backward dynamic programming algorithm.

Macromolecular Crowding Is Surprisingly Unable to Deform the Structure of a Model Biomolecular Condensate.

The crowded interior of a living cell makes performing experiments on simpler in vitro systems attractive. Although these reveal interesting phenomena, their biological relevance can be questionable. A topical example is the phase separation of intrinsically disordered proteins into biomolecular condensates, which is proposed to underlie the membrane-less compartmentalization of many cellular functions.

JAK inhibitor blocks COVID-19 cytokine-induced JAK/STAT/APOL1 signaling in glomerular cells and podocytopathy in human kidney organoids.

COVID-19 infection causes collapse of glomerular capillaries and loss of podocytes, culminating in a severe kidney disease called COVID-19-associated nephropathy (COVAN). The underlying mechanism of COVAN is unknown. We hypothesized that cytokines induced by COVID-19 trigger expression of pathogenic APOL1 via JAK/STAT signaling, resulting in podocyte loss and COVAN phenotype.

Coupling Bulk Phase Separation of Disordered Proteins to Membrane Domain Formation in Molecular Simulations on a Bespoke Compute Fabric.

Phospholipid membranes surround the cell and its internal organelles, and their multicomponent nature allows the formation of domains that are important in cellular signalling, the immune system, and bacterial infection. Cytoplasmic compartments are also created by the phase separation of intrinsically disordered proteins into biomolecular condensates. The ubiquity of lipid membranes and protein condensates raises the question of how three-dimensional droplets might interact with two-dimensional domains, and whether this coupling has physiological or pathological importance.

Cohabitation, infection and breast cancer risk.

For 50 years, the effect of age at first birth (AFB) has been thought to explain the strong association between breast cancer risk and age at first marriage (AFM), which was first reported in 1926. The independent effects of AFM, AFB and number of sexual partners adjusted for parity and other risk factors were estimated in reanalysis of a large international case-control study conducted in 1979 to 1982 (2274 breast cancers, 18209 controls) by unconditional logistic regression. Respective AFB and AFM breast cancer odds ratios (ORs) for ≥31 years relative to ≤18 years were 3.

Endocarditis Complicated by Pauci-Immune Necrotizing Glomerulonephritis.

Infective endocarditis (IE) is more common in patients with predisposing cardiac lesions and has many potential complications, including stroke and arterial thromboembolisms. Renal manifestations have an estimated prevalence of ∼20%. Rapidly progressive glomerulonephritis (RPGN) is a nephrological emergency manifested by autoimmune-mediated progressive loss of renal function over a relatively short period of time.

APOL1-G0 protects podocytes in a mouse model of HIV-associated nephropathy.

African polymorphisms in the gene for Apolipoprotein L1 (APOL1) confer a survival advantage against lethal trypanosomiasis but also an increased risk for several chronic kidney diseases (CKD) including HIV-associated nephropathy (HIVAN). APOL1 is expressed in renal cells, however, the pathogenic events that lead to renal cell damage and kidney disease are not fully understood. The podocyte function of APOL1-G0 versus APOL1-G2 in the setting of a known disease stressor was assessed using transgenic mouse models.

Occupational exposures and parkinsonism among Shanghai women textile workers.

Background: Endotoxin, a contaminant of cotton dust, is an experimental model for parkinsonism (PS).

Methods: We investigated associations between exposures to endotoxin, solvents, magnetic fields, and night shift work, and neurologist-determined PS among Shanghai women textile workers, including 537 retired cotton factory workers ages ≥50 years and an age-matched reference group of 286 retired textile workers not exposed to cotton dust. Repeat exams were conducted 2.

The potential role of complements in cocaine-induced thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a rare disorder characterized by microvascular injury and occlusion resulting in tissue ischemia and dysfunction. TMA occurs in a variety of settings including cocaine use. Although cocaine is widely used in the United States, cocaine-associated TMA is only rarely reported.

Pharmacological and genetic inhibition of downstream targets of p38 MAPK in experimental nephrotic syndrome.

Nie X, Chanley MA, Pengal R, Thomas DB, Agrawal S, Smoyer WE. Pharmacological and genetic inhibition of downstream targets of p38 MAPK in experimental nephrotic syndrome. Am J Physiol Renal Physiol 314: F602-F613, 2018.

APOL1 variants change C-terminal conformational dynamics and binding to SNARE protein VAMP8.

APOL1 variants in African populations mediate resistance to trypanosomal infection but increase risk for kidney diseases through unknown mechanisms. APOL1 is expressed in glomerular podocytes and does not vary with underlying kidney disease diagnoses or APOL1 genotypes, suggesting that the kidney disease-associated variants dysregulate its function rather than its localization or abundance. Structural homology searches identified vesicle-associated membrane protein 8 (VAMP8) as an APOL1 protein interactor.

Interstitial nephritis in melanoma patients secondary to PD-1 checkpoint inhibitor.

Background: Immune checkpoint inhibitors have become the first line therapy in melanoma treatment and their use is extending to other malignancies. However, we are still learning about immune side effects produced by these drugs and their severity especially in patients with history of inflammatory diseases.

Case Presentation: We present two cases of metastatic melanoma treated with nivolumab and pembrolizumab (anti PD-1).

Plasma equol concentration is not associated with breast cancer and fibrocystic breast conditions among women in Shanghai, China.

Equol (a bacterial metabolite of the soy isoflavone daidzein) is produced by 30% to 50% of humans and may be associated with health outcomes. We hypothesized that plasma equol would be inversely associated with risks of fibrocystic breast conditions (FBC) and breast cancer (BC). Plasma from women in a breast self-examination trial in Shanghai with BC (n=269) or FBC (n=443), and age-matched controls (n=1027) was analyzed for isoflavones.

APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney Disease.

APOL1 risk variants are associated with kidney disease in blacks, but the mechanisms of renal injury associated with APOL1 risk variants are unknown. Because APOL1 is unique to humans and some primates, we created transgenic (Tg) mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a spectrum of APOL1 expression levels. Podocytes from Tg-G0 and Tg-G2 mice did not undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with highly expressed transgenes.

Risk of Pancreatic Cancer in Female Textile Workers in Shanghai, China, Exposed to Metals, Solvents, Chemicals, and Endotoxin: Follow-Up to a Nested Case-Cohort Study.

Objective: We studied associations between pancreatic cancer and occupational exposures to metals, solvents, chemicals, and endotoxin in a cohort of female textile workers in Shanghai, China. To assess the longer-term influences of these agents on pancreatic cancer we extended follow-up of this previously studied cohort.

Methods: We utilized a job exposure matrix to assess occupational exposures for 481 pancreatic cancer cases and a randomly selected sub-cohort of 3191 non-cases.

Increased breast cancer screening and downstaging in Colombian women: A randomized trial of opportunistic breast-screening.

The lack of breast cancer screening in low and middle-income countries results in later stage diagnosis and worsened outcomes for women. A cluster randomized trial was performed in Bogotá, Colombia between 2008 and 2012 to evaluate effects of opportunistic breast cancer screening. Thirteen clinics were randomized to an intervention arm and 13 to a control arm.

Night shift work and lung cancer risk among female textile workers in Shanghai, China.

In 2007, the International Agency for Research on Cancer classified shift work that involves circadian disruption as a probable human carcinogen. Suppression of the anti-neoplastic hormone, melatonin, is a presumed mechanism of action. We conducted a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China.

Occupational exposures and risk of stomach and esophageal cancers: update of a cohort of female textile workers in Shanghai, China.

Background: Associations between stomach and esophageal cancer and exposures to dusts, metals, chemicals, and endotoxin in the workplace are not very well understood, particularly in women.

Methods: We followed 267,400 female textile workers in Shanghai, China for cancer incidence from 1989 to 2006. Stomach (n = 1374) and esophageal (n = 190) cancer cases were identified and a comparison subcohort (n = 3187) was randomly selected.

Tobacco and alcohol in relation to male breast cancer: an analysis of the male breast cancer pooling project consortium.

Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined.

Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies.

Semaphorin3a promotes advanced diabetic nephropathy.

The onset of diabetic nephropathy (DN) is highlighted by glomerular filtration barrier abnormalities. Identifying pathogenic factors and targetable pathways driving DN is crucial to developing novel therapies and improving the disease outcome. Semaphorin3a (sema3a) is a guidance protein secreted by podocytes.

Shift work and breast cancer among women textile workers in Shanghai, China.

Purpose: Although night-shift work has been associated with elevated risk of breast cancer in numerous epidemiologic studies, evidence is not consistent. We conducted a nested case-cohort study to investigate a possible association between shift work including a night shift and risk of breast cancer within a large cohort of women textile workers in Shanghai, China.

Methods: The study included 1,709 incident breast cancer cases and 4,780 non-cases.