Partial Convolution for Padding, Inpainting, and Image Synthesis.

Partial convolution weights convolutions with binary masks and renormalizes on valid pixels. It was originally proposed for image inpainting task because a corrupted image processed by a standard convolutional often leads to artifacts. Therefore, binary masks are constructed that define the valid and corrupted pixels, so that partial convolution results are only calculated based on valid pixels.

Health Care Leaders' Perspectives on the Maryland All-Payer Model.

Importance: Since 2014, all hospitals in Maryland have operated under an all-payer global budget system. Hospital global budgets have gained renewed attention as a strategy for constraining cost growth, improving patient outcomes, and preserving health care access in rural and underserved communities. Lessons from the implementation of the Maryland All-Payer Model (MDAPM) may have implications for policy makers, payers, and hospitals in other settings seeking to adopt global budgets or other value-based payment models.

Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks.

The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm and the nucleus, thereby maintaining cellular function while under mechanical pressure. Intermediate filaments (IFs) are imperative to a plethora of regulatory and signaling functions in mechanotransduction.

Nonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina.

The nuclear lamina-a meshwork of intermediate filaments termed lamins-is primarily responsible for the mechanical stability of the nucleus in multicellular organisms. However, structural-mechanical characterization of lamin filaments assembled in situ remains elusive. Here, we apply an integrative approach combining atomic force microscopy, cryo-electron tomography, network analysis, and molecular dynamics simulations to directly measure the mechanical response of single lamin filaments in three-dimensional meshwork.

Impacts of Maryland's Global Budgets on Medicare and Commercial Spending and Utilization.

In 2014, Maryland incorporated global budgets into its long-running all-payer rate-setting model for hospitals in order to improve health, increase health care quality, and reduce spending. We used difference-in-differences models to estimate changes in Medicare and commercial insurance utilization and spending in Maryland relative to a hospital-based comparison group. We found slower growth in Medicare hospital spending in Maryland than in the comparison group 4.

Racial and Ethnic Disparities in Genetic Testing at a Hereditary Breast and Ovarian Cancer Center.

Background: Prior studies suggest that referral to genetic counseling and completion of genetic testing vary by race/ethnicity; however, the data are limited.

Objective: We sought to evaluate patterns of genetic testing and clinical outcomes across race/ethnicity at a hereditary breast and ovarian cancer center.

Design: The medical records for all patients undergoing genetic assessment at a hereditary breast and ovarian cancer center were reviewed and stratified by self-reported race/ethnicity (non-Hispanic White, Hispanic, non-Hispanic Black, and Asian).

NetExtractor: Extracting a Cerebellar Tissue Gene Regulatory Network Using Differentially Expressed High Mutual Information Binary RNA Profiles.

Bigenic expression relationships are conventionally defined based on metrics such as Pearson or Spearman correlation that cannot typically detect latent, non-linear dependencies or require the relationship to be monotonic. Further, the combination of intrinsic and extrinsic noise as well as embedded relationships between sample sub-populations reduces the probability of extracting biologically relevant edges during the construction of gene co-expression networks (GCNs). In this report, we address these problems via our NetExtractor algorithm.

A comparative study to evaluate quality of data documentation between investigator-initiated and pharmaceutical industry-sponsored studies.

Purpose: In pharmaceutical industry funded clinical studies (PIS), there is rigorous monitoring to ensure adequate and accurate data documentation. In comparison, the investigator-initiated studies (IIS) often lack in resources and may not follow such quality checks. At present, very limited data on the existing deficiencies in documentation for IIS are available.

Conformational Plasticity of Human Protease-Activated Receptor 1 upon Antagonist- and Agonist-Binding.

G protein-coupled receptors (GPCRs) show complex relationships between functional states and conformational plasticity that can be qualitatively and quantitatively described by contouring their free energy landscape. However, how ligands modulate the free energy landscape to direct conformation and function of GPCRs is not entirely understood. Here, we employ single-molecule force spectroscopy to parametrize the free energy landscape of the human protease-activated receptor 1 (PAR1), and delineate the mechanical, kinetic, and energetic properties of PAR1 being set into different functional states.

Imaging and Force Spectroscopy of Single Transmembrane Proteins with the Atomic Force Microscope.

The atomic force microscope (AFM) has opened avenues and provided opportunities to investigate biological soft matter and processes ranging from nanometer (nm) to millimeter (mm). The high temporal (millisecond) and spatial (nanometer) resolutions of the AFM are suited for studying many biological processes in their native conditions. The AFM cantilever-aptly termed as a "lab on a tip"-can be used as an imaging tool as well as a handle to manipulate single bonds and proteins.

Identifying High-Cost Medicare Beneficiaries: Impact of Neighborhood Socioeconomic Disadvantage.

The objective of this observational longitudinal study of Maryland fee-for-service Medicare beneficiaries (2015-2016) was to investigate whether using data on neighborhood socioeconomic disadvantage in addition to individual clinical risk data improves identification of high-cost Medicare beneficiaries. Neighborhood socioeconomic disadvantage is measured using the Area Deprivation Index (ADI), a validated composite measure based on publically-available US census data (2011-2015) for Maryland census block groups. Hierarchical Condition Categories (HCC) score, health care utilization, and spending were obtained from Centers for Medicare & Medicaid Services Chronic Condition Warehouse beneficiary file and Part A and Part B claims data (2015).

Seeing and sensing single G protein-coupled receptors by atomic force microscopy.

G protein-coupled receptors (GPCRs) relay extracellular information across cell membranes through a continuum of conformations that are not always captured in structures. Hence, complementary approaches are required to quantify the physical and chemical properties of the dynamic conformations linking to GPCR function. Atomic force microscopy (AFM)-based high-resolution imaging and force spectroscopy are unique methods to scrutinize GPCRs and to sense their interactions.

Single-Molecule Force Spectroscopy of Transmembrane β-Barrel Proteins.

Single-molecule force spectroscopy (SMFS) has been widely applied to study the mechanical unfolding and folding of transmembrane proteins. Here, we review the recent progress in characterizing bacterial and human transmembrane β-barrel proteins by SMFS. First, we describe the mechanical unfolding of transmembrane β-barrels, which follows a general mechanism dictated by the sequential unfolding and extraction of individual β-strands and β-hairpins from membranes.

Profilin 1-mediated cytoskeletal rearrangements regulate integrin function in mouse platelets.

Profilin 1–mediated cytoskeletal dynamics regulate platelet β1- and β3-integrin function and turnover. Profilin 1 deficiency in platelets impairs hemostasis and results in a marked protection from arterial thrombosis.

Structural Properties of the Human Protease-Activated Receptor 1 Changing by a Strong Antagonist.

The protease-activated receptor 1 (PAR1), a G protein-coupled receptor (GPCR) involved in hemostasis, thrombosis, and inflammation, is activated by thrombin or other coagulation proteases. This activation is inhibited by the irreversible antagonist vorapaxar used for anti-platelet therapy. Despite detailed structural and functional information, how vorapaxar binding alters the structural properties of PAR1 to prevent activation is hardly known.

Time-Varying Effects of Signs and Symptoms on Pregnancy Loss <20 Weeks: Findings from a Preconception Prospective Cohort Study.

Background: Although pregnancy loss affects one-third of pregnancies, the associated signs/symptoms have not been fully described. Given the dynamic nature of maternal physiologic adaptation to early pregnancy, we posited the relationships between signs/symptoms and subsequent loss would vary weekly.

Methods: In a preconception cohort with daily follow-up, pregnancies were ascertained by self-administered sensitive home pregnancy tests on day of expected menses.

Group B Streptococcus and the Vaginal Microbiota.

Background: Streptococcus agalactiae (group B Streptococcus [GBS]) is an important neonatal pathogen and emerging cause of disease in adults. The major risk factor for neonatal disease is maternal vaginal colonization. However, little is known about the relationship between GBS and vaginal microbiota.

Semen quality and pregnancy loss in a contemporary cohort of couples recruited before conception: data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study.

Objective: To study the relationship between semen quality and pregnancy loss in a cohort of couples attempting to conceive.

Design: Observational prospective cohort.

Setting: Not applicable.

Multigene panels in Ashkenazi Jewish patients yield high rates of actionable mutations in multiple non-BRCA cancer-associated genes.

Objective: To evaluate the results of multigene panel testing among Ashkenazi Jewish compared with non-Ashkenazi Jewish patients.

Methods: We reviewed the medical records for all patients who underwent multigene panel testing and targeted BRCA1/2 testing at a single institution between 6/2013-1/2015. Clinical actionability for identified pathogenic mutations was characterized based on the National Comprehensive Cancer Network (NCCN) guidelines and consensus statements and expert opinion for genes not addressed by these guidelines.

Multi-compartment encapsulation of communicating droplets and droplet networks in hydrogel as a model for artificial cells.

Constructing a cell mimic is a major challenge posed by synthetic biologists. Efforts to this end have been primarily focused on lipid- and polymer-encapsulated containers, liposomes and polymersomes, respectively. Here, we introduce a multi-compartment, nested system comprising aqueous droplets stabilized in an oil/lipid mixture, all encapsulated in hydrogel.

The molecular architecture of lamins in somatic cells.

The nuclear lamina is a fundamental constituent of metazoan nuclei. It is composed mainly of lamins, which are intermediate filament proteins that assemble into a filamentous meshwork, bridging the nuclear envelope and chromatin. Besides providing structural stability to the nucleus, the lamina is involved in many nuclear activities, including chromatin organization, transcription and replication.

Low-level environmental metals and metalloids and incident pregnancy loss.

Environmental exposure to metals and metalloids is associated with pregnancy loss in some but not all studies. We assessed arsenic, cadmium, mercury, and lead concentrations in 501 couples upon trying for pregnancy and followed them throughout pregnancy to estimate the risk of incident pregnancy loss. Using Cox proportional hazard models, we estimated hazard ratios (HR) and 95% confidence intervals (CIs) for pregnancy loss after covariate adjustment for each partner modeled individually then we jointly modeled both partners' concentrations.

Planned home births: the need for additional contraindications.

Background: Planned home births in the United States are associated with fewer interventions but with increased adverse neonatal outcomes such as perinatal and neonatal deaths, neonatal seizures or serious neurologic dysfunction, and low 5-minute Apgar scores. The American College of Obstetricians and Gynecologists' Committee on Obstetric Practice states that, to reduce perinatal death and to improve outcomes at planned home births, strict criteria are necessary to guide the selection of appropriate candidates for planned home birth. The committee lists 3 absolute contraindications for a planned home birth: fetal malpresentation, multiple gestations, and a history of cesarean delivery.