Clinical proteomics reveals vulnerabilities in non-invasive breast ductal carcinoma and drives personalized treatment strategies.

Ductal carcinoma in situ (DCIS) is the most common type (80%) of non-invasive breast lesions in women. The lack of validated prognostic markers, limited patient numbers, and variable tissue quality have a significant impact on diagnosis, risk stratification, patient enrolment, and the results of clinical studies. Here, we performed label-free quantitative proteomics on 50 clinical formalin-fixed, paraffin embedded biopsies, validating 22 putative biomarkers from independent genetic studies.

Healthcare Costs Across Diabetic Kidney Disease Stages: A Veterans Affairs Study.

Background: In the United States, diabetic kidney disease (DKD) affects about one-third of individuals with type 2 diabetes, causing significant economic burdens on the health care system and affecting patients' quality of life.

Objective: The aim of the study was to quantify the burden of care in patients at different stages of DKD and to monitor shifts in healthcare costs throughout these stages.

Methods: This study used data from the Veterans Affairs National database, focusing on US veterans diagnosed with DKD between January 2016 and March 2022.

COVID-19 point-of-care tests can identify low-antibody individuals: In-depth immunoanalysis of boosting benefits in a healthy cohort.

The recommended COVID-19 booster vaccine uptake is low. At-home lateral flow assay (LFA) antigen tests are widely accepted for detecting infection during the pandemic. Here, we present the feasibility and potential benefits of using LFA-based antibody tests as a means for individuals to detect inadequate immunity and make informed decisions about COVID-19 booster immunization.

Blood RNA Biomarkers Identify Bacterial and Biofilm Coinfections in COVID-19 Intensive Care Patients.

Secondary opportunistic coinfections are a significant contributor to morbidity and mortality in intensive care unit (ICU) patients, but can be difficult to identify. Presently, new blood RNA biomarkers were tested in ICU patients to diagnose viral, bacterial, and biofilm coinfections. COVID-19 ICU patients had whole blood drawn in RNA preservative and stored at -80°C.

Epidemiology of Diabetic Kidney Disease among US Veterans.

Rationale: With a large number of patients and high mortality, diabetic kidney disease (DKD) imposes a significant burden on US health care. Although diabetes is the leading cause of chronic kidney disease and complications, the epidemiology of DKD in the contemporary US veteran population is generally unknown.

Objective: We aimed to estimate the rate of DKD progression and to measure the general epidemiology of DKD in the United States veteran population.

The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers.

The response of triple-negative breast cancer (TNBC) patients to pre-operative (neoadjuvant chemotherapy) is a critical factor of their outcome. To determine the effects of chemotherapy on the tumor genome and to identify mutations associated with chemoresistance and sensitivity, we performed whole exome sequencing on pre/post-chemotherapy tumors and matched lymphocytes from 26 patients. We observed great inter-tumoral heterogeneity with no gene mutated recurrently in more than four tumors besides TP53.

Welfare brokers and European Union migrants' access to social protection.

In spite of the existence of an extensive national and supranational legal framework, European Union (EU) citizens who exercise their right to freedom of movement to work in another Member State face numerous hurdles in accessing social protection. While recent scholarship on street-level bureaucracy and on migration and welfare has shed light on the role of discretion and stereotypes in access to rights, little is known about the processes through which such hurdles are overcome. In this article, we focus on a specific strategy which is the recourse to what we call "welfare brokers".

Evaluation of a 'plug and play' nanoflow liquid chromatography system for MS-based proteomic characterization of clinical FFPE specimens.

Introduction: Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tumor tissue specimens has gained interest in the last 5 years due to technological advances and improved sample collection, as well as biobanking for clinical trials. The real-world implementation of clinical proteomics to these specimens, however, is hampered by tedious sample preparation steps and long instrument acquisition times.

Areas Covered: To advance the translation of quantitative proteomics into the clinic, we are comparing the performance of the leading commercial nanoflow liquid chromatography (nLC) system (based on literature reviews), the Easy-nLC 1200 (Thermo Fisher Scientific, Waltham, MA, U.

Nanoelectromechanical Infrared Spectroscopy with In Situ Separation by Thermal Desorption: NEMS-IR-TD.

We present a novel method for the quantitative analysis of mixtures of semivolatile chemical compounds. For the first time, thermal desorption is integrated directly with nanoelectromechanical infrared spectroscopy (NEMS-IR-TD). In this new technique, an analyte mixture is deposited via nebulization on the surface of a NEMS sensor and subsequently desorbed using heating under vacuum.

Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake.

Unlabelled: Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations.

Effectiveness of a Diabetes-Focused Electronic Discharge Order Set and Postdischarge Nursing Support Among Poorly Controlled Hospitalized Patients: Randomized Controlled Trial.

Background: Although the use of electronic order sets has become standard practice for inpatient diabetes management, there is limited decision support at discharge.

Objective: In this study, we assessed whether an electronic discharge order set (DOS) plus nurse follow-up calls improve discharge orders and postdischarge outcomes among hospitalized patients with type 2 diabetes mellitus.

Methods: This was a randomized, open-label, single center study that compared an electronic DOS and nurse phone calls to enhanced standard care (ESC) in hospitalized insulin-requiring patients with type 2 diabetes mellitus.

Racial/ethnic health disparities among children with special health care needs in Boston, Massachusetts.

Background: Little is known about the factors that contribute to racial/ethnic disparities among children with special health care needs (CSHCN).

Objective: To quantify the contributions of determinants of racial/ethnic disparities in health and health care among CSHCN in Boston, Massachusetts.

Methods: A sample of 326 Black, Latino, and white CSHCN was drawn from the Boston Survey of Children's Health, a city-wide representative sample of children.

SARS-CoV-2 mRNA vaccine induces robust specific and cross-reactive IgG and unequal neutralizing antibodies in naive and previously infected people.

Understanding vaccine-mediated protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to overcoming the global coronavirus disease 2019 (COVID-19) pandemic. We investigate mRNA-vaccine-induced antibody responses against the reference strain, seven variants, and seasonal coronaviruses in 168 healthy individuals at three time points: before vaccination, after the first dose, and after the second dose. Following complete vaccination, both naive and previously infected individuals developed comparably robust SARS-CoV-2 spike antibodies and variable levels of cross-reactive antibodies to seasonal coronaviruses.

RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections.

Infection with the SARS-CoV2 virus can vary from asymptomatic, or flu-like with moderate disease, up to critically severe. Severe disease, termed COVID-19, involves acute respiratory deterioration that is frequently fatal. To understand the highly variable presentation, and identify biomarkers for disease severity, blood RNA from COVID-19 patient in an intensive care unit was analyzed by whole transcriptome RNA sequencing.

Precision of Medication Therapy Problem Identification and Classification amongst Primary Care Clinic Pharmacists.

This study assesses the level of agreement on medication therapy problem (MTP) identification and classification between primary care, ambulatory care pharmacists within a health-system that recently implemented system-wide pharmacist provision of comprehensive medication management (CMM) services. Twenty standardized case vignettes were created and distributed to pharmacists who reviewed each case and identified and categorized MTPs. Outcomes include the number of MTPs identified, identification (yes/no) of specific MTPs within each case (e.

Early, On-Treatment Levels and Dynamic Changes of Genomic Instability in Circulating Tumor DNA Predict Response to Treatment and Outcome in Metastatic Breast Cancer Patients.

Background: Circulating tumor DNA (ctDNA) offers high sensitivity and specificity in metastatic cancer. However, many ctDNA assays rely on specific mutations in recurrent genes or require the sequencing of tumor tissue, difficult to do in a metastatic disease. The purpose of this study was to define the predictive and prognostic values of the whole-genome sequencing (WGS) of ctDNA in metastatic breast cancer (MBC).

Quality of systematic reviews in HIV: The case of clinical outcomes associated with patient medication adherence.

Aim: Use of systematic reviews (SRs) as first-level evidence for guideline recommendations hinges on review quality. In particular, US guidelines for adherence-related recommendations in the treatment of human immunodeficiency virus (HIV) are not based on available SRs of adherence-outcome relationships; it is unclear why. No published studies report on the quality of SRs on HIV adherence and outcomes, which may be driving the lack of use.

Photocatalytic graphitic carbon nitride-chitosan composites for pathogenic biofilm control under visible light irradiation.

Photocatalysis holds promise for inactivating environmental pathogens. Visible-light-responsive composites of carbon-doped graphitic carbon nitride and chitosan with high reactivity and processability were fabricated, and they can control pathogenic biofilms for environmental, food, biomedical, and building applications. The broad-spectrum biofilm inhibition and eradication of the photocatalytic composites against Staphylococcus epidermidis, Pseudomonas aeruginosa PAO1, and Escherichia coli O157: H7 under visible light irradiation were demonstrated.

COVID-19 infection among emergency department healthcare providers in a large tertiary academic medical center following the peak of the pandemic.

The COVID-19 pandemic has spread through the US during the last few months exposing healthcare providers to possible infection. Here we report testing of emergency department (ED) healthcare providers (HCP) for exposure to COVID-19 through lateral flow point of care (POC) and lab-based enzyme-linked immunosorbent assay (ELISA), and RTq-PCR for evidence of acute infection. 138 ED HCP were tested between May 26th (approximately one month after the peak of COVID-19 first wave of cases) and June 14th.

Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer.

Response to neoadjuvant chemotherapy (NAC) in triple negative breast cancer (TNBC) is highly prognostic and determines whether adjuvant chemotherapy is needed if residual tumor is found at surgery. To evaluate the predictive and prognostic values of circulating tumor DNA (ctDNA) in this setting, we analyzed tumor and serial bloods from 26 TNBC patients collected prior, during, and after NAC. Individual digital droplet PCR assays were developed for 121 variants (average 5/patient) identified from tumor sequencing, enabling ctDNA detection in 96% of patients at baseline.

Chemogenomic profiling of breast cancer patient-derived xenografts reveals targetable vulnerabilities for difficult-to-treat tumors.

Subsets of breast tumors present major clinical challenges, including triple-negative, metastatic/recurrent disease and rare histologies. Here, we developed 37 patient-derived xenografts (PDX) from these difficult-to-treat cancers to interrogate their molecular composition and functional biology. Whole-genome and transcriptome sequencing and reverse-phase protein arrays revealed that PDXs conserve the molecular landscape of their corresponding patient tumors.

An unusual cause of chest pain in a 33 year old male: neurofibromatosis.

Chest pain in low risk patients is a common ED presentation. Rarely, these patients can have life-threatening conditions requiring timely diagnosis and intervention. There are currently standardized protocols for diagnosing cardiac ischemia, pulmonary embolus, and aortic dissection in low risk patients.