Wheat seed embryo excision enables the creation of axenic seedlings and Koch’s postulates testing of putative bacterial endophytes

Early establishment of endophytes can play a role in pathogen suppression and improve seedling development. One route for establishment of endophytes in seedlings is transmission of bacteria from the parent plant to the seedling via the seed. In wheat seeds, it is not clear whether this transmission route exists, and the identities and location of bacteria within wheat seeds are unknown. We identified bacteria in the wheat (Triticum aestivum) cv. Hereward seed environment using embryo excision to determine the location of the bacterial load. Axenic wheat seedlings obtained with this method were subsequently used to screen a putative endophyte bacterial isolate library for endophytic competency. This absence of bacteria recovered from seeds indicated low bacterial abundance and/or the presence of inhibitors. Diversity of readily culturable bacteria in seeds was low with 8 genera identified, dominated by Erwinia and Paenibacillus. We propose that anatomical restrictions in wheat limit embryo associated vertical transmission, and that bacterial load is carried in the seed coat, crease tissue and endosperm. This finding facilitates the creation of axenic wheat plants to test competency of putative endophytes and also provides a platform for endophyte competition, plant growth, and gene expression studies without an indigenous bacterial background

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

Evaluating Social Vulnerability Impact on Care & Prognosis of Head & Neck-Nervous System Cancers in the US

Introduction In the current literature, the association between social determinants of health (SDH) and head & neck-nervous system cancer (HNNsC) is limited by the narrow scope of SDH assessed and the broad classifications of HNNsC. Our study utilizes the CDC-Social Vulnerability Index (SVI) to assess both the individual and collective impact of four social determinant themes on various HNNsC in US adults. Methods This retrospective cohort study utilized the SEER database to evaluate 116,373 adult patients from 1975-2017 who presented with various types of HNNsC. Patients were assigned SVI scores based on county-of-residence at the time of diagnosis, encompassing total SVI score and 4 sub-scores of socioeconomic status, minority-language status, household composition, and housing-transportation. Using these scores, univariate linear regressions were used to assess patient care (months of follow-up) and prognosis (months of survival). Results As the total SVI score/overall social vulnerability increased, a significant decrease in months of follow-up was observed for many HNNsC tumors (p\u3c 0.001), ranging from 3.55-36.6% decreases in mean lengths of follow-up when comparing the lowest to highest vulnerability cohorts. Similarly, a decrease in months of survival was observed (p\u3c 0.001), ranging from 6.90-45.81% decreases in the mean survival period when comparing the lowest to highest vulnerability cohorts. Increases in vulnerability within SVI sub-scores/SDH themes contributed significantly to these total-SVI trends in months of follow-up and survival, with each social determinant impacting different disease classes to varying extents. Conclusions The results of this study show that with increasing social vulnerability, there is a significant decrease in both the care (follow-up) and the prognosis (survival) of US adults with HNNsC and highlight which particular SDH contributes more to disparities

The impact of digital inequities on salivary gland cancer disparities in the United States

Introduction: Technology and internet access have become increasingly integrated into healthcare as the primary platform for health-related information and provider-patient communication. Disparities in access to digital resources exist in the United States and have been shown to impact health outcomes in various head and neck malignancies. Our objective is to evaluate the associations of digital inequity on health outcomes in patients with salivary gland cancer (SGC). Methods: The Digital Inequity Index (DII) was developed using 17 census-tract level variables obtained from the American Community Survey and Federal Communications Commission. Variables were categorized as digital infrastructure or sociodemographic (e.g., non-digital) and scored based on relative rankings across all US counties. Scores were assigned to patients from the Surveillance-Epidemiology-End Results (SEER) database diagnosed with SGC between 2013 and 2017 based on county-of-residence. Regressions were performed between DII score and outcomes of surveillance time, survival time, tumor stage at time of diagnosis, and treatment modality. Results: Among 9306 SGC-patients, increased digital inequity was associated with advanced-staging at presentation (OR: 1.04, 95% CI: 1.01–1.07, p = 0.033), increased odds of chemotherapy receipt (OR: 1.05, CI: 1.01–1.10, p = 0.010), and decreased odds of surgical intervention (OR: 0.94, 95% CI: 0.91–0.98, p = 0.003) after accounting for traditional sociodemographic factors. Increased digital inequity was also associated with decreased surveillance time and survival periods. Conclusions: Digital inequity significantly and independently associates with negative health and treatment outcomes in SGC patients, highlighting the importance of directed efforts to address these seldom-investigated drivers of health disparities

Dynamic Transcriptomic and Phosphoproteomic Analysis During Cell Wall Stress in Aspergillus nidulans

The fungal cell-wall integrity signaling (CWIS) pathway regulates cellular response to environmental stress to enable wall repair and resumption of normal growth. This complex, interconnected, pathway has been only partially characterized in filamentous fungi. To better understand the dynamic cellular response to wall perturbation, a-glucan synthase inhibitor (micafungin) was added to a growing A. nidulans shake-flask culture. From this flask, transcriptomic and phosphoproteomic data were acquired over 10 and 120 min, respectively. To differentiate statistically-significant dynamic behavior from noise, a multivariate adaptive regression splines (MARS) model was applied to both data sets. Over 1800 genes were dynamically expressed and over 700 phosphorylation sites had changing phosphorylation levels upon micafungin exposure. Twelve kinases had altered phosphorylation and phenotypic profiling of all non-essential kinase deletion mutants revealed putative connections between PrkA, Hk-8 –4, and Stk19 and the CWIS pathway. Our collective data implicate actin regulation, endocytosis, and septum formation as critical cellular processes responding to activation of the CWIS pathway, and connections between CWIS and calcium, HOG, and SIN signaling pathways

Assessing social vulnerabilities of salivary gland cancer care, prognosis, and treatment in the United States

Background: Salivary gland cancers (SGC)-social determinants of health (SDoH) investigations are limited by narrow scopes of SGC-types and SDoH. This Social Vulnerability Index (SVI)-study hypothesized that socioeconomic status (SES) most contributed to SDoH-associated SGC-disparities. Methods: Retrospective cohort of 24 775 SGCs assessed SES, minority-language status (ML), household composition (HH), housing-transportation (HT), and composite-SDoH measured by the SVI via regressions with surveillance and survival length, late-staging presentation, and treatment (surgery, radio-, chemotherapy) receipt. Results: Increasing social vulnerability showed decreases in surveillance/survival; increased odds of advanced-presenting-stage (OR: 1.12, 95% CI: 1.07, 1.17), chemotherapy receipt (OR: 1.13, 95% CI: 1.03, 1.23); decreased odds of primary surgery (0.89, 0.84, 0.94), radiotherapy (0.91, 0.85, 0.97, p = 0.003) for SGCs. Trends were differentially correlated with SES, ML, HH, and HT-vulnerabilities. Conclusions: Through quantifying SDoH-derived SGC-disparities, the SVI can guide targeted initiatives against SDoH that elicit the most detrimental associations for specific sociodemographics

Assessments of social vulnerability on laryngeal cancer treatment & prognosis in the US: Epidemiology

Background: Previous social determinants of health (SDoH) studies on laryngeal cancer (LC) have assessed individual factors of socioeconomic status and race/ethnicity but seldom investigate a wider breadth of SDoH-factors for their effects in the real-world. This study aims to delineate how a wider array of SDoH-vulnerabilities interactively associates with LC-disparities. Methods: This retrospective cohort study assessed 74,495 LC-patients between 1975 and 2017 from the Surveillance-Epidemiology-End Results (SEER) database using the Social Vulnerability Index (SVI) from the CDC, total SDoH-vulnerability from 15 SDoH variables across specific vulnerabilities of socioeconomic status, minority-language status, household composition, and infrastructure/housing and transportation, which were measured across US counties. Univariate linear and logistic regressions were performed on length of care/follow-up and survival, staging, and treatment across SVI scores. Results: Survival time dropped significantly by 34.37% (from 72.83 to 47.80 months), and surveillance time decreased by 28.09% (from 80.99 to 58.24 months) with increasing overall social vulnerability, alongside advanced staging (OR 1.15; 95%CI 1.13–1.16), increased chemotherapy (OR 1.13; 95%CI 1.11–1.14), decreased surgical resection (OR 0.91; 95%CI 0.90–0.92), and decreased radiotherapy (OR 0.97; 95%CI 0.96–0.99). Discussion: In this SDoH-study of LCs, detrimental care and prognostic trends were observed with increasing overall SDoH-vulnerability. (Figure presented.

Electronic Sensors for Assessing Interactions between Healthcare Workers and Patients under Airborne Precautions

International audienceBackground: Direct observation has been widely used to assess interactions between healthcare workers (HCWs) and patients but is time-consuming and feasible only over short periods. We used a Radio Frequency Identification Device (RFID) system to automatically measure HCW-patient interactions. Methods: We equipped 50 patient rooms with fixed sensors and 111 HCW volunteers with mobile sensors in two clinical wards of two hospitals. For 3 months, we recorded all interactions between HCWs and 54 patients under airborne precautions for suspected (n=40) or confirmed (n=14) tuberculosis. Number and duration of HCW entries into patient rooms were collected daily. Concomitantly, we directly observed room entries and interviewed HCWs to evaluate their self- perception of the number and duration of contacts with tuberculosis patients. Results: After signal reconstruction, 5490 interactions were recorded between 82 HCWs and 54 tuberculosis patients during 404 days of airborne isolation. Median (interquartile range) interaction duration was 2.1 (0.8-4.4) min overall, 2.3 (0.8-5.0) in the mornings, 1.8 (0.8-3.7) in the afternoons, and 2.0 (0.7-4.3) at night (P,1024). Number of interactions/day/HCW was 3.0 (1.0-6.0) and total daily duration was 7.6 (2.4-22.5) min. Durations estimated from 28 direct observations and 26 interviews were not significantly different from those recorded by the network. Conclusions: The RFID was well accepted by HCWs. This original technique holds promise for accurately and continuously measuring interactions between HCWs and patients, as a less resource-consuming substitute for direct observation. The results could be used to model the transmission of significant pathogens. HCW perceptions of interactions with patients accurately reflected reality

The Impact of Digital Inequities on Oropharyngeal Cancer Disparities in the United States

Objective: To assess associations of digital inequity with oropharyngeal cancer (OPC) prognostic and care outcomes in the United States while adjusting for traditional social determinants/drivers of health (SDoH). Study Design: Retrospective cohort study. Setting: United States. Methods: In total, 70,604 patients from 2008 to 2017 were assessed for regression trends in long-term follow-up period, survival, prognosis, and treatment across increasing overall digital inequity, as measured by the Digital Inequity Index (DII). DII is based on 17 census-tract level variables derived from the American Community Survey and Federal Communications Commission. Variables were categorized as infrastructure-access (ie, digital-related variables) or sociodemographic (ie, education, income, and disability status) and weighted-averaged into a composite score. Results: With increasing DII, decreases in length of follow-up (10.22%, 32.9-29.5 months; P \u3c .001) and survival (8.93%, 19-17.3 months; P \u3c .001) were observed. Affordability of internet access displayed the largest influence, followed by device access and internet-service availability. Compared to OPC patients with low digital inequity, high digital inequity was associated with increased odds of diagnosing more than one malignant tumor (odds ratio [OR] 1.01, 95% CI 1.01-1.03; P =.012) and advanced staging (OR 1.01, 95% CI 1.00-1.02; P =.034), while having decreased odds of receiving indicated chemotherapy (OR 0.98, 95% CI 0.97-0.99; P \u3c .001), radiation therapy (OR 0.98, 95% CI 0.97-0.99; P \u3c .001), or primary surgery (OR 0.98, 95% CI 0.97-0.99; P \u3c .001). Conclusion: Digital inequities contribute to detrimental trends in OPC patient care and prognosis in the United States. These findings can inform strategic discourse targeted against the most pertinent disparities in the modern-day environment

Outer Membrane Vesicles Derived from Escherichia coli Induce Systemic Inflammatory Response Syndrome

Sepsis, characterized by a systemic inflammatory state that is usually related to Gram-negative bacterial infection, is a leading cause of death worldwide. Although the annual incidence of sepsis is still rising, the exact cause of Gram-negative bacteria-associated sepsis is not clear. Outer membrane vesicles (OMVs), constitutively secreted from Gram-negative bacteria, are nano-sized spherical bilayered proteolipids. Using a mouse model, we showed that intraperitoneal injection of OMVs derived from intestinal Escherichia coli induced lethality. Furthermore, OMVs induced host responses which resemble a clinically relevant condition like sepsis that was characterized by piloerection, eye exudates, hypothermia, tachypnea, leukopenia, disseminated intravascular coagulation, dysfunction of the lungs, hypotension, and systemic induction of tumor necrosis factor-α and interleukin-6. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of sepsis, suggesting OMVs as a new therapeutic target to prevent and/or treat severe sepsis caused by Gram-negative bacterial infection