Preoperative stereotactic radiosurgery for patients with 1-4 brain metastases: A single-arm phase 2 trial outcome analysis (NCT03398694).

Background: Stereotactic radiosurgery (SRS) following surgical resection is the standard of care for patients with symptomatic oligo brain metastasis (BM), however, it is associated with 10-15% local failure. Targeting a resection cavity is imprecise, thus preoperative radiosurgery where the target is well-defined may be superior, however, the efficacy of preoperative SRS has not yet been tested in a clinical trial.

Methods: We conducted a phase 2, single-arm trial of preoperative SRS followed by surgical resection in patients with 1-4 symptomatic oligo BMs (NCT03398694) with the primary objective of measuring 6-month local control (LC).

Cross-Sectional Melt Pool Geometry of Laser Scanned Tracks and Pads on Nickel Alloy 718 for the 2022 Additive Manufacturing Benchmark Challenges.

The Additive Manufacturing Benchmark Series (AM Bench) is a NIST-led organization that provides a continuing series of additive manufacturing benchmark measurements, challenge problems, and conferences with the primary goal of enabling modelers to test their simulations against rigorous, highly controlled additive manufacturing benchmark measurement data. To this end, single-track (1D) and pad (2D) scans on bare plate nickel alloy 718 were completed with thermography, cross-sectional grain orientation and local chemical composition maps, and cross-sectional melt pool size measurements. The laser power, scan speed, and laser spot size were varied for single tracks, and the scan direction was varied for pads.

Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure.

Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis.

Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

Genetic risk variants for childhood nephrotic syndrome and corticosteroid response.

Introduction: The etiology of most cases of nephrotic syndrome (NS) remains unknown, therefore patients are phenotypically categorized based on response to corticosteroid therapy as steroid sensitive NS (SSNS), or steroid resistant NS (SRNS). Genetic risk factors have been identified for SSNS from unbiased genome-wide association studies (GWAS), however it is unclear if these loci are disease risk loci in other forms of NS such as SRNS. Additionally, it remains unknown if these risk loci are associated with response to therapy.

Subarachnoid haemorrhage associated with pituitary apoplexy and radiographically occult supraclinoid internal carotid artery aneurysms.

In patients with pituitary adenomas, incidental intracranial aneurysms have been documented. Previous studies have highlighted the importance of preoperative imaging in these patients. However, imaging may be limited and fail to show the presence of vascular abnormalities.

Strong protective effect of the p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.

Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge.

Stereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor.

Inaxaplin for the treatment of APOL1-associated kidney disease.

Chronic kidney disease (CKD) is highly prevalent World-Wide and it is an important cause of morbidity and mortality. In 2010, variants in ( gene was identified as a major risk factor for higher prevalence of CKD in individuals of African ancestry. The mechanisms by which toxic gain of function variants cause disease are the subjects of current investigations, and there is currently no effective targeted therapy for associated kidney disease.

The case for treatment of monogenic SRNS with calcineurin inhibitors.

Currently, no evidence-based guidelines exist for treatment of children with monogenic steroid-resistant nephrotic syndrome. A retrospective study on 141 patients from Malakasioti et al. revealed that 27.

Laser spot size and scaling laws for laser beam additive manufacturing.

Laser powder bed fusion (L-PBF) additive manufacturing (AM) requires the careful selection of laser process parameters for each feedstock material and machine, which is a laborious process. Scaling laws based on the laser power, speed, and spot size; melt pool geometry; and thermophysical properties can potentially reduce this effort by transferring knowledge from one material and/or laser system to another. Laser spot size is one critical parameter that is less well studied for scaling laws compared to laser power and scan speed.

Hiding in plain sight: genetics of childhood steroid-resistant nephrotic syndrome in Sub-Saharan Africa.

Steroid-resistant nephrotic syndrome (SRNS) is the most severe form of childhood nephrotic syndrome with an increased risk of progression to chronic kidney disease stage 5. Research endeavors to date have identified more than 80 genes that are associated with SRNS. Most of these genes regulate the structure and function of the podocyte, the visceral epithelial cells of the glomerulus.

Management and outcomes of surgical site tuberculosis infection due to infected bone graft in spine surgery: a single-institution experience and 1-year postoperative follow-up.

Objective: In 2021, several patients across the United States received bone allograft contaminated with Mycobacterium tuberculosis (TB). TB is typically a pulmonary infection with many possible extrapulmonary manifestations, including skeletal tuberculosis. However, TB is a rare causative organism of postoperative surgical site infection.

Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations.

Background: Focal segmental glomerulosclerosis (FSGS) is a major cause of end stage kidney disease, with the collapsing form having the worst prognosis. Study of families with hereditary FSGS has provided insight into disease mechanisms.

Methods: In this report, we describe a sibling pair with mutations and collapsing FSGS (cFSGS).

Anterior Lumbar Interbody Fusion With Robotic-Assisted Percutaneous Screw Placement: A Case Report.

Recently, there has been an increase in robotic-assisted spine fusion for degenerative spondylosis of the lumbar spine. We present the case of a 60-year-old female with grade 1 spondylolisthesis at L4/5 and L5/S1 who underwent L4-S1 anterior lumbar interbody fusion (ALIF) with percutaneous robotic-assisted pedicle screw fixation. We provide a detailed analysis of the procedure including the speed of robotic screw placement and pitfalls of this surgical approach.

Translating Outcomes from the Clinical Setting to Preclinical Models: Chronic Pain and Functionality in Chronic Musculoskeletal Pain.

Fibromyalgia (FM) is a chronic pain disorder characterized by chronic widespread musculoskeletal pain (CWP), resting pain, movement-evoked pain (MEP), and other somatic symptoms that interfere with daily functioning and quality of life. In clinical studies, this symptomology is assessed, while preclinical models of CWP are limited to nociceptive assays. The aim of the study was to investigate the human-to-model translatability of clinical behavioral assessments for spontaneous (or resting) pain and MEP in a preclinical model of CWP.

Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping.

Glomerular diseases (GDs) are a major cause of chronic kidney disease in children. The conventional approach to diagnosis of GDs includes clinical evaluation and, in most cases, kidney biopsy to make a definitive diagnosis. However, in many cases, clinical presentations of different GDs can overlap, leading to uncertainty in diagnosis and management even after renal biopsy.

Measurement Uncertainty of Surface Temperature Distributions for Laser Powder Bed Fusion Processes.

This paper describes advances in measuring the characteristic spatial distribution of surface temperature and emissivity during laser-metal interaction under conditions relevant for laser powder bed fusion (LPBF) additive manufacturing processes. Detailed descriptions of the measurement process, results, and approaches to determining uncertainties are provided. Measurement uncertainties have complex dependencies on multiple process parameters, so the methodology is demonstrated on one set of process parameters and one material.

Transient Laser Energy Absorption, Co-axial Melt Pool Monitoring, and Relationship to Melt Pool Morphology.

Melt pool monitoring (MPM) is a technique used in laser powder bed fusion (LPBF) to extract features from insitu sensor signals that correlate to defect formation or general part fabrication quality. Various melt pool phenomena have been shown to relate to measured transient absorption of the laser energy, which in turn, can be relatable to the melt pool emission measured in MPM systems. This paper describes use of a reflectometer-based instrument to measure the dynamic laser energy absorption during single-line laser scans.

A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 () Gene Confers Enhanced Calcineurin Activity and May Cause FSGS.

Background: Podocyte dysfunction is the main pathologic mechanism driving the development of FSGS and other morphologic types of steroid-resistant nephrotic syndrome (SRNS). Despite significant progress, the genetic causes of most cases of SRNS have yet to be identified.

Methods: Whole-genome sequencing was performed on 320 individuals from 201 families with familial and sporadic NS/FSGS with no pathogenic mutations in any known NS/FSGS genes.

The RGS-RhoGEFs control the amplitude of YAP1 activation by serum.

Actin-dependent mechanisms drive the nuclear translocation of Yap1 to enable its co-activation of transcription factors that induce pro-growth and survival programs. While Rho GTPases are necessary for the nuclear import of YAP1, the relevant Guanine Exchange Factors (GEFs) and GTPase Activating Proteins (GAPs) that connect this process to upstream signaling are not well defined. To this end, we measured the impact of expressing sixty-seven RhoGEFs and RhoGAPs on the YAP1 dependent activity of a TEAD element transcriptional reporter.