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Sepsis is a complex disease due to dysregulated host response to infection. Oxidative stress and mitochondrial dysfunction leading to metabolic dysregulation are among the hallmarks of sepsis. The transcription factor NRF2 (Nuclear Factor E2-related factor2) is a master regulator of the oxidative stress response, and the NRF2 mediated antioxidant response is negatively regulated by BTB and CNC homology 1 (BACH1) protein. This study tested whether Bach1 deletion improves organ function and survival following polymicrobial sepsis induced by cecal ligation and puncture (CLP). We observed enhanced post-CLP survival in Bach1

Additional file 6. Effect of the qPCR filter on HPV genotype read frequencies in paired tumor samples. (A) Consistency in the percentages of HPV16, HPV18, and HPV58 reads was evaluated using three types of tumor-tumor pairs: pairs of FFPE tissue samples from the same patient, as reported in patient records (“FFPE:Both”); pairs of frozen and FFPE tissue samples from the same patient, as reported in patient records (“Mixed:Reported”); and pairs of archived DNA and frozen tissue samples, matched via QC Array data (not reported in sample records, “Mixed:QCarray”). Correlations between the read frequencies for each pair were lower for HPV58 than for HPV16 and HPV18. (B) Same as (A) but excluding samples that did not pass the qPCR filter (amplified DNA concentrations < 2 nM).

Additional file 3. Effect of varying read thresholds for detecting HPV58 and HPV co-infections.

Additional file 4. Effect of varying off-target human read thresholds on HPV genotype.

Additional file 4. Effect of varying off-target human read thresholds on HPV genotype.

Additional file 1. Reference sequences used for HPV genotyping.

Additional file 6. Effect of the qPCR filter on HPV genotype read frequencies in paired tumor samples. (A) Consistency in the percentages of HPV16, HPV18, and HPV58 reads was evaluated using three types of tumor-tumor pairs: pairs of FFPE tissue samples from the same patient, as reported in patient records (“FFPE:Both”); pairs of frozen and FFPE tissue samples from the same patient, as reported in patient records (“Mixed:Reported”); and pairs of archived DNA and frozen tissue samples, matched via QC Array data (not reported in sample records, “Mixed:QCarray”). Correlations between the read frequencies for each pair were lower for HPV58 than for HPV16 and HPV18. (B) Same as (A) but excluding samples that did not pass the qPCR filter (amplified DNA concentrations < 2 nM).

Additional file 3. Effect of varying read thresholds for detecting HPV58 and HPV co-infections.

Sepsis affects microcirculation and tissue perfusion leading to tissue hypoxia and multiple organ dysfunction. Red blood cells (RBCs; erythrocytes) are typically biconcave in shape, transport hemoglobin-bound oxygen and are reversibly deformable facilitating trafficking through capillaries. Decreased deformability of RBCs adversely affects tissue oxygenation. The purpose of this project was to determine RBC deformability in a murine model of polymicrobial sepsis by a method that utilizes laser diffraction and microfluidics, and to identify the causative factors in the plasma that may contribute to loss in RBC deformability. Blood samples from mice subjected to cecal ligation and puncture (CLP) model of sepsis were used. RBC deformability was tested using Rheoscan-AnD 300 under shear stress range of 0-20 Pascal (Pa) that depicts the common rheological behavior of RBCs flowing through blood vessels ranging from major vessels to capillaries. Normal RBCs were treated with plasma-derived extracellular vesicles (EVs) and their effect on RBC deformability was also tested. The experiments demonstrated a significant decrease in RBC deformability following sepsis. RBC deformability recovered in sham-operated animals by the third day, whereas animals with sepsis continued to show decreased levels of deformability. EVs isolated from the plasma of animals from the sepsis group significantly decreased deformability of RBCs ex vivo. Analysis of miRNA cargo in EVs showed distinct molecular profiles for sham-operated and sepsis-induced mice. In summary, sepsis induced a decrease in RBC deformability and the acquired rigidity may have adverse effect on microcirculation, tissue perfusion, and organ function.

Clinical diagnostics is a challenge in resource poor areas. Accessibility to diagnostic laboratories is severely curtailed in areas where resources and infrastructure are limited. There is a need to develop low cost and portable devices to promote healthcare services in such places. The development of low cost paper-based microfluidic devices (μPADS) and thread-based devices have the potential to revolutionize point of care diagnostics in poverty-ridden areas. In this report, we describe how frugal technologies can be used for the detection of biological fluids, and the need for developing low cost wireless and wearable technologies to be deployed in resource poor settings.

Trauma is the major cause of death for Americans under the age of 46 years. Hemorrhagic shock accounts for up to 40% of trauma-related deaths. Hemorrhagic shock evokes an acute, non-specific, systemic inflammatory response syndrome (SIRS) resulting in the damage to multiple organs. Acute lung injury (ALI) is one of the most serious complications in traumatic patients, however, the immunological mechanisms in ALI are still not well understood. Recently studies suggest that mitochondria play an important role in physical injury, leading to the onset of the SIRS. In order to address the mechanistic basis of ALI following hemorrhagic shock, we subjected rats to severe hemorrhage and shock (hemorrhagic injury - HI) or sham procedure and lung tissue was tested. We demonstrate that NLRX1, a mitochondria-targeted protein, that negatively regulates innate immunity and cell death responses, was markedly decreased in HI lung. The decrease of NLRX1 was concomitant with the activation of NF/κB and TBK1 signaling pathways. Lung histochemistry was used to establish pathologic effect on the lung. Significant increases in pulmonary expression of inflammatory signaling molecules IL-6, IL-1β, IL-10, TNF-α and MIP-1α further confirmed HI induced pulmonary inflammation and injury. Our results suggest NLRX1 participate in the pathogenesis of HI related pulmonary diseases and support its important role in the regulation of innate immune response following hemorrhagic shock.

Additional file 1: Figure S1. BC360â„¢ analysis (n=11): A) Relevant gene signatures and biologically significant single genes are shown. Samples were grouped based on stage (stage II, stage III, and de novo stage IV), lines of therapy >2, molecular subtypes (PAM50: basal, HER2+, luminal A, and luminal B); and TNBC subtypes: BLIA, BLIS, LAR, and MES. Signatures scores are mapped to quantiles of TCGA with a 0.5 value approximating the median TCGA value.

Additional file 3: Figure S3. Tile plot showing genomic mutations in mTNBC patients (n=9).

Additional file 1: Figure S1. BC360â„¢ analysis (n=11): A) Relevant gene signatures and biologically significant single genes are shown. Samples were grouped based on stage (stage II, stage III, and de novo stage IV), lines of therapy >2, molecular subtypes (PAM50: basal, HER2+, luminal A, and luminal B); and TNBC subtypes: BLIA, BLIS, LAR, and MES. Signatures scores are mapped to quantiles of TCGA with a 0.5 value approximating the median TCGA value.

Additional file 3: Figure S3. Tile plot showing genomic mutations in mTNBC patients (n=9).

Additional file 2: Figure S2. BC360â„¢ analysis (n=11): A) Forest plot showing differentially expressed signatures comparing SD+PD and PR groups; B) HER2-enriched signature is up-regulated in SD+PD compared with PR group (P=0.02).

Additional file 2: Figure S2. BC360â„¢ analysis (n=11): A) Forest plot showing differentially expressed signatures comparing SD+PD and PR groups; B) HER2-enriched signature is up-regulated in SD+PD compared with PR group (P=0.02).