This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3-6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109 /ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16-0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27-0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15-0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02-0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02-0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.

Circulating tumor cells (CTCs) are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR) using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20) performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer.

Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), but additional chromosomal abnormalities (ACA) and other rearrangements can contribute in the development of the whole leukemic phenotype. We hypothesized that some ACA not detected by conventional techniques may be informative of the onset of APL. We performed the high-resolution SNP array (SNP-A) 6.0 (Affymetrix) in 48 patients diagnosed with APL on matched diagnosis and remission sample. Forty-six abnormalities were found as an acquired event in 23 patients (48%): 22 duplications, 23 deletions and 1 Copy-Neutral Loss of Heterozygocity (CN-LOH), being a duplication of 8(q24) (23%) and a deletion of 7(q33-qter) (6%) the most frequent copy-number abnormalities (CNA). Four patients (8%) showed CNAs adjacent to the breakpoints of the translocation. We compared our results with other APL series and found that, except for dup(8q24) and del(7q33-qter), ACA were infrequent (≤3%) but most of them recurrent (70%). Interestingly, having CNA or FLT3 mutation were mutually exclusive events. Neither the number of CNA, nor any specific CNA was associated significantly with prognosis. This study has delineated recurrent abnormalities in addition to t(15;17) that may act as secondary events and could explain leukemogenesis in up to 40% of APL cases with no ACA by conventional cytogenetics.

Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17 by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%) of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and HER2 amplifications were not associated with prognosis.

Influenza A virus (IAV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV) and Staphylococcus aureus are important swine pathogens capable of being transmitted via aerosols. The electrostatic particle ionization system (EPI) consists of a conductive line that emits negative ions that charge particles electrically resulting in the settling of airborne particles onto surfaces and potentially decreasing the risk of pathogen dissemination. The objectives of this study were to determine the effect of the EPI system on the quantity and viability of IAV, PRRSV, PEDV and S. aureus in experimentally generated aerosols and in aerosols generated by infected animals. Efficiency at removing airborne particles was evaluated as a function of particle size (ranging from 0.4 to 10 µm), distance from the source of ions (1, 2 and 3 m) and relative air humidity (RH 30 vs. 70 %). Aerosols were sampled with the EPI system "off" and "on." Removal efficiency was significantly greater for all pathogens when the EPI line was the closest to the source of aerosols. There was a greater reduction for larger particles ranging between 3.3 and 9 µm, which varied by pathogen. Overall airborne pathogen reduction ranged between 0.5 and 1.9 logs. Viable pathogens were detected with the EPI system "on," but there was a trend to reducing the quantity of viable PRRSV and IAV. There was not a significant effect on the pathogens removal efficiency based on the RH conditions tested. In summary, distance to the source of ions, type of pathogen and particle size influenced the removal efficiency of the EPI system. The reduction in infectious agents in the air by the EPI technology could potentially decrease the microbial exposure for pigs and people in confinement livestock facilities.

Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-kappaB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-kappaB activation by H-Ala-D-gammaGlu-DAP (gammaTriDAP). GEF-H1 is essential for NF-kappaB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens.

When pathogens become airborne, they travel associated with particles of different size and composition. Particle size determines the distance across which pathogens can be transported, as well as the site of deposition and the survivability of the pathogen. Despite the importance of this information, the size distribution of particles bearing viruses emitted by infectious animals remains unknown. In this study we characterized the concentration and size distribution of inhalable particles that transport influenza A virus (IAV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine epidemic diarrhea virus (PEDV) generated by acutely infected pigs and assessed virus viability for each particle size range. Aerosols from experimentally infected pigs were sampled for 24 days using an Andersen cascade impactor able to separate particles by size (ranging from 0.4 to 10 micrometer (μm) in diameter). Air samples collected for the first 9, 20 and the last 3 days of the study were analyzed for IAV, PRRSV and PEDV, respectively, using quantitative reverse transcription polymerase chain reaction (RT-PCR) and quantified as geometric mean copies/m(3) within each size range. IAV was detected in all particle size ranges in quantities ranging from 5.5x10(2) (in particles ranging from 1.1 to 2.1 μm) to 4.3x10(5) RNA copies/m(3) in the largest particles (9.0-10.0 μm). PRRSV was detected in all size ranges except particles between 0.7 and 2.1 μm in quantities ranging from 6x10(2) (0.4-0.7 μm) to 5.1x10(4) RNA copies/m(3) (9.0-10.0 μm). PEDV, an enteric virus, was detected in all particle sizes and in higher quantities than IAV and PRRSV (p < 0.0001) ranging from 1.3x10(6) (0.4-0.7 μm) to 3.5x10(8) RNA copies/m(3) (9.0-10.0 μm). Infectious status was demonstrated for the 3 viruses, and in the case of IAV and PRRSV, viruses were isolated from particles larger than 2.1 μm. In summary, our results indicated that airborne PEDV, IAV and PRRSV can be found in a wide range of particle sizes. However, virus viability is particle size dependent.

Unaddressed occupational stress and trauma contribute to elevated rates of mental illness and suicide in policing, and to violent and aggressive behavior that disproportionately impacts communities of color. Emerging evidence suggests mindfulness training with police may reduce stress and aggression and improve mental health, but there is limited evidence for changes in biological outcomes or the lasting benefits of mindfulness training. We conducted a randomized controlled trial (RCT) of 114 police officers from three Midwestern U.S. law enforcement agencies. We assessed stress-related physical and mental health symptoms, blood-based inflammatory markers, and hair and salivary cortisol. Participants were then randomized to an 8-week mindfulness intervention or waitlist control (WLC), and the same assessments were repeated post-intervention and at 3-month follow-up. Relative to waitlist control, the mindfulness group had greater improvements in psychological distress, mental health symptoms, and sleep quality post-training, gains that were maintained at 3-month follow-up. Intervention participants also had a significantly lower cortisol awakening response (CAR) at 3-month follow-up relative to waitlist control. Contrary to hypotheses, there were no intervention effects on hair cortisol, diurnal cortisol slope, or inflammatory markers. In summary, an 8-week mindfulness intervention for police officers led to self-reported improvements in distress, mental health, and sleep, and a lower CAR. These benefits persisted (or emerged) at 3-month follow-up, suggesting that this training may buffer against the long-term consequences of chronic stress. Future research should assess the persistence of these benefits over a longer period while expanding the scope of outcomes to consider the broader community of mindfulness training for police. Clinical Trial Registration: ClinicalTrials.gov#NCT03488875.

RAS testing is used to select patients with anti-epidermal growth factor receptor (EGFR) therapies sensitivity in metastatic colorectal cancer (mCRC). However, other biomarkers such as BRAF, PIK3CA/PTEN, and p-IGF-1R+/MMP7+ (double positive [DP] phenotype) have not been prospectively assessed to predict anti-EGFR resistance.

Lymphoid neoplasms treatment has recently been renewed to increase antitumor efficacy and conventional chemotherapies toxicities. Limited data have been published about the infection risk associated with these new drugs, therefore this study analyzes the infectious complications in patients with lymphoproliferative diseases (LPD) treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab, or pembrolizumab), BTK inhibitors (ibrutinib and acalabrutinib), PI3K inhibitors (idelalisib) and BCL2 inhibitors (venetoclax).