Drought responsive gene expression regulatory divergence between upland and lowland ecotypes of a perennial C4 grass.

Climatic adaptation is an example of a genotype-by-environment interaction (G×E) of fitness. Selection upon gene expression regulatory variation can contribute to adaptive phenotypic diversity; however, surprisingly few studies have examined how genome-wide patterns of gene expression G×E are manifested in response to environmental stress and other selective agents that cause climatic adaptation. Here, we characterize drought-responsive expression divergence between upland (drought-adapted) and lowland (mesic) ecotypes of the perennial C4 grass,Panicum hallii, in natural field conditions. Overall, we find that cis-regulatory elements contributed to gene expression divergence across 47% of genes, 7.2% of which exhibit drought-responsive G×E. While less well-represented, we observe 1294 genes (7.8%) with transeffects.Trans-by-environment interactions are weaker and much less common than cis G×E, occurring in only 0.7% oft rans-regulated genes. Finally, gene expression heterosis is highly enriched in expression phenotypes with significant G×E. As such, modes of inheritance that drive heterosis, such as dominance or overdominance, may be common among G×E genes. Interestingly, motifs specific to drought-responsive transcription factors are highly enriched in the promoters of genes exhibiting G×E and transregulation, indicating that expression G×E and heterosis may result from the evolution of transcription factors or their binding sites.P. hallii serves as the genomic model for its close relative and emerging biofuel crop, switchgrass (Panicum virgatum). Accordingly, the results here not only aid in the discovery of the genetic mechanisms that underlie local adaptation but also provide a foundation to improve switchgrass yield under water-limited conditions.

Complex interactions between day length and diurnal patterns of gene expression drive photoperiodic responses in a perennial C4 grass.

Photoperiod is a key environmental cue affecting flowering and biomass traits in plants. Key components of the photoperiodic flowering pathway have been identified in many species, but surprisingly few studies have globally examined the diurnal rhythm of gene expression with changes in day length. Using a cost-effective 3'-Tag RNA sequencing strategy, we characterize 9,010 photoperiod responsive genes with strict statistical testing across a diurnal time series in the C4 perennial grass, Panicum hallii. We show that the vast majority of photoperiod responses are driven by complex interactions between day length and sampling periods. A fine-scale contrast analysis at each sampling time revealed a detailed picture of the temporal reprogramming of cis-regulatory elements and biological processes under short- and long-day conditions. Phase shift analysis reveals quantitative variation among genes with photoperiod-dependent diurnal patterns. In addition, we identify three photoperiod enriched transcription factor families with key genes involved in photoperiod flowering regulatory networks. Finally, coexpression networks analysis of GIGANTEA homolog predicted 1,668 potential coincidence partners, including five well-known GI-interacting proteins. Our results not only provide a resource for understanding the mechanisms of photoperiod regulation in perennial grasses but also lay a foundation to increase biomass yield in biofuel crops.

Promises and Challenges of Eco-Physiological Genomics in the Field: Tests of Drought Responses in Switchgrass.

Identifying the physiological and genetic basis of stress tolerance in plants has proven to be critical to understanding adaptation in both agricultural and natural systems. However, many discoveries were initially made in the controlled conditions of greenhouses or laboratories, not in the field. To test the comparability of drought responses across field and greenhouse environments, we undertook three independent experiments using the switchgrass reference genotype Alamo AP13. We analyzed physiological and gene expression variation across four locations, two sampling times, and three years. Relatively similar physiological responses and expression coefficients of variation across experiments masked highly dissimilar gene expression responses to drought. Critically, a drought experiment utilizing small pots in the greenhouse elicited nearly identical physiological changes as an experiment conducted in the field, but an order of magnitude more differentially expressed genes. However, we were able to define a suite of several hundred genes that were differentially expressed across all experiments. This list was strongly enriched in photosynthesis, water status, and reactive oxygen species responsive genes. The strong across-experiment correlations between physiological plasticity-but not differential gene expression-highlight the complex and diverse genetic mechanisms that can produce phenotypically similar responses to various soil water deficits.

Epithelioid Hemangioendothelioma Presenting as Inferior Vena Cava Obstruction Diagnosed Using an Endovascular Thrombectomy Device.

Epithelioid hemangioendothelioma is a rare vascular sarcoma that arises from the lining (intima) of blood vessels. We report a case of a 43-year-old male patient, who presented with inferior vena cava (IVC) obstruction and acute bilateral lower extremity deep vein thrombosis. Mechanical thrombectomy was performed with an endovascular thrombectomy device, followed by stent placement in the IVC. The initial pathology on the retrieved specimen obtained from the thrombectomy device revealed an undifferentiated neoplasm, and definitive surgical resection of the retroperitoneal soft-tissue tumor of the IVC documented a rare case of epithelioid hemangioendothelioma.

A Colletotrichum graminicola mutant deficient in the establishment of biotrophy reveals early transcriptional events in the maize anthracnose disease interaction.

BACKGROUND: Colletotrichum graminicola is a hemibiotrophic fungal pathogen that causes maize anthracnose disease. It progresses through three recognizable phases of pathogenic development in planta: melanized appressoria on the host surface prior to penetration; biotrophy, characterized by intracellular colonization of living host cells; and necrotrophy, characterized by host cell death and symptom development. A "Mixed Effects" Generalized Linear Model (GLM) was developed and applied to an existing Illumina transcriptome dataset, substantially increasing the statistical power of the analysis of C. graminicola gene expression during infection and colonization. Additionally, the in planta transcriptome of the wild-type was compared with that of a mutant strain impaired in the establishment of biotrophy, allowing detailed dissection of events occurring specifically during penetration, and during early versus late biotrophy. RESULTS: More than 2000 fungal genes were differentially transcribed during appressorial maturation, penetration, and colonization. Secreted proteins, secondary metabolism genes, and membrane receptors were over-represented among the differentially expressed genes, suggesting that the fungus engages in an intimate and dynamic conversation with the host, beginning prior to penetration. This communication process probably involves reception of plant signals triggering subsequent developmental progress in the fungus, as well as production of signals that induce responses in the host. Later phases of biotrophy were more similar to necrotrophy, with increased production of secreted proteases, inducers of plant cell death, hydrolases, and membrane bound transporters for the uptake and egress of potential toxins, signals, and nutrients. CONCLUSIONS: This approach revealed, in unprecedented detail, fungal genes specifically expressed during critical phases of host penetration and biotrophic establishment. Many encoded secreted proteins, secondary metabolism enzymes, and receptors that may play roles in host-pathogen communication necessary to promote susceptibility, and thus may provide targets for chemical or biological controls to manage this important disease. The differentially expressed genes could be used as 'landmarks' to more accurately identify developmental progress in compatible versus incompatible interactions involving genetic variants of both host and pathogen.

Voicing an impact: who does the National Institutes of Health support for voice disorder research?

PURPOSE: Interest in a variety of neoplastic, functional, neurological, and age-related laryngeal disorders has contributed to the development of laryngology as an established subspecialty. Funding support plays a critical role in facilitating scholarship within the field. Our objectives were to evaluate who is receiving funding from the NIH for topics relevant to voice disorders, and further describe temporal trends in grants awarded. METHODS: The NIH RePORTER database was searched for grants relevant to voice disorders. Data were further organized by PI specialty, academic department, and funding totals. Furthermore, PI scholarly impact, as measured by the h-index, was calculated. RESULTS: A total of 830 funded fiscal years (for 232 unique projects) totaling $203 million have supported projects examining voice disorders. A plurality of projects (32.8%) was awarded to PIs in otolaryngology departments, followed by 17.2% to speech pathology/communication sciences departments. Although year-to-year variation was noted, otolaryngology departments received approximately 15% of funding annually. Funded otolaryngologists had similar scholarly impact values to individuals in other specialties. CONCLUSIONS: The study of voice disorders involves an interdisciplinary approach, as PIs in numerous specialties receive NIH funding support. As they receive a considerable proportion of this funding and had similar h-indices compared to other specialties involved, otolaryngologists have just as much scholarly impact despite being a smaller specialty. As speech and language pathologists also comprised a significant proportion of individuals in this analysis, enhanced cooperation and encouragement of interdisciplinary scholarly initiatives may be beneficial.

Program Director Attitudes Toward Acceptance of Pediatric Dentistry Entrustable Professional Activities (EPAs).

Purpose: To acquire comments on pediatric dentistry entrustable professional activities (EPAs) from pediatric dentistry residency program directors (PDs). Methods: An electronic survey invited PDs to evaluate 16 previously developed EPAs on whether they were critical to patient safety, resident education, or both. PDs were asked to evaluate a fully developed EPA to assess structure and clarity and describe barriers to EPA. Descriptive statistics were completed. Results: Forty-one of 103 PDs completed the entire survey. Eighty-five percent (36 of 42) of PDs believed EPAs are critical to pediatric dentistry education, and 81 percent (34 of 42) believed EPAs are critical to patient safety. Eighty-one percent of PDs would likely use EPAs when available. Seventy-five percent (31 of 41) of PDs reported that they have had a resident who would have benefited from a longer duration of training. Conclusions: The majority of pediatric dentistry residency program director participants surveyed reported that entrustable professional activities are critical to patient safety and resident education. EPAs may be a valuable option for assessing residents' readiness for graduation.

Transarterial embolization of symptomatic focal nodular hyperplasia.

PURPOSE: To evaluate the effectiveness of small size trisacryl gelatin microsphere embolization as a minimally invasive treatment option for patients with symptomatic focal nodular hyperplasia (FNH). MATERIALS AND METHODS: A retrospective review was performed of experience with transarterial bland embolization of FNH during the period 2006-2011 in 12 patients (10 women and 2 men; age range, 18-61 y) with a total of 17 lesions presenting with symptoms of pain. FNH was pathologically proven in 11 lesions from 10 patients; the remaining lesions exhibited the classic imaging appearance for FNH. All patients underwent superselective embolization with 100-300 µm trisacryl gelatin microspheres. Lesion size and contrast enhancement before and after treatment were compared to determine success of the procedure. Clinical response was determined by review of the electronic medical record. RESULTS: After embolization, seven patients showed complete resolution and five patients showed partial resolution of symptoms. Compared with imaging performed before the procedure, mean decrease in lesion size after embolization was 61% (range, 26%-90%) on cross-sectional imaging obtained 4-10 weeks after embolization and 87% (range, 54%-98%) on subsequent imaging. Diminished contrast enhancement was universally noted, with 5 of 17 lesions showing complete lack of residual enhancement. CONCLUSIONS: Transarterial bland embolization of FNH with trisacryl gelatin microspheres in symptomatic patients is a suitable treatment alternative to surgical resection.

Development of entrustable professional activities for post-doctorate pediatric dentistry education.

PURPOSE: To identify the core components of pediatric dentistry defining entrustable professional activities (EPAs) representing the profession. METHODS: Potential core components of pediatric dentistry and corresponding domains were identified through review of literature and existing pediatric dentistry standards. A modified Delphi technique was utilized to rate these candidate EPAs to achieve consensus around prioritized EPAs. RESULTS: Eleven participants participated in all three rounds of the Delphi. After three rounds, 16 candidate EPAs reached consensus for pediatric dentistry. Each EPA fell into one of four domains: "assessment and planning," "provision of care," "behavior guidance," and "professional development." An original candidate EPA focused on non-pharmacological behavior guidance was deemed too broad by the Delphi. This EPA was subsequently developed into three separate components on nitrous oxide analgesia, moderate sedation, and general anesthesia. CONCLUSIONS: Prioritized EPAs will help define the essential activities of the profession and provide a framework for creating assessments to ensure that graduating pediatric residents are ready for unsupervised practice.

Sensitivity analysis for unmeasured confounding in principal stratification settings with binary variables.

Within causal inference, principal stratification (PS) is a popular approach for dealing with intermediate variables, that is, variables affected by treatment that also potentially affect the response. However, when there exists unmeasured confounding in the treatment arms--as can happen in observational studies--causal estimands resulting from PS analyses can be biased. We identify the various pathways of confounding present in PS contexts and their effects for PS inference. We present model-based approaches for assessing the sensitivity of complier average causal effect estimates to unmeasured confounding in the setting of binary treatments, binary intermediate variables, and binary outcomes. These same approaches can be used to assess sensitivity to unknown direct effects of treatments on outcomes because, as we show, direct effects are operationally equivalent to one of the pathways of unmeasured confounding. We illustrate the methodology using a randomized study with artificially introduced confounding and a sensitivity analysis for an observational study of the effects of physical activity and body mass index on cardiovascular disease.

The energy glitch: Speculative histories and quantum counterfactuals.

Energy (in all its conceptualizations and connotations) is a glitch, a bug, an error. Energy is presented here as a roadblock in efforts to articulate and formulate a coherent physical model of the universe, as well as an impediment to achieving just and equitable social relations. Energy broke physics and broke society. This article traces conundrums and uncertainties that prevail in physics today, from the irreconcilability of quantum dynamics and gravitational spacetime to the unsatisfactory postulation of dark energy, and the profusion of probabilistic reasoning. I offer a brief history of thermodynamics and its entanglement with industrial capitalism via the steam engine. I explore alternate histories of energy (hydrodynamic and metabolic) and speculate on the potential social implications of these counterfactual trajectories. Finally, building on the novel Constructor Theory paradigm, I entertain the possibility of replacing energy with informed noticing as the undergirding architecture of physics, replacing dynamics with discernment as the underbelly of the discipline. The operation within is not to argue that the current course of energy-based physics is "incorrect," but rather that it is problematic both for reasons of cosmological compatibility and the social disharmony it has wrought.

Pediatric Dentistry Program Directors' Resident Assessment Techniques.

Purpose: The purpose of this study was to determine how pediatric dentistry residency program directors evaluate residents and determine graduation readiness. Methods: A questionnaire containing demographic, multiple answer, and yes/no questions was developed by investigators and piloted to former program directors. An updated survey was distributed electronically to program directors in the United States. Subjects were asked to respond to current resident evaluation strategies and future opportunities. Results: Fifty-seven program directors responded to the survey, for a response rate of 55.9 percent. Most relied on daily observation to determine competence and ability to move to more complex procedures. Most were interested in standardized parameters to determine competence but had concerns about cost and time to implement. Most were not aware of entrustable professional activities as a method to evaluate for competence. Conclusion: Program directors rely primarily on daily observation and formal assessments to evaluate residents and determine readiness for graduation.

Nephrolithiasis associated with embolization material, Lipiodol®, following embolization of large renal angiomyolipoma.

Angiomyolipoma (AML) is a benign renal mass that can be treated with nephron sparing surgery or transarterial embolization. Embolization has been favored due to efficacy and safety profile. This case demonstrates a previously undocumented phenomenon of AML treated with transarterial embolization using Lipiodol® (Guerbet LLC, Princeton, NJ) resulting in nephrolithiasis and retention of Lipiodol® two years after original embolization. Although Lipiodol®-based embolization has not been shown to cause nephrolithiasis, it may have been the nidus for stone formation, and this is an important potential complication worthy of further study.

LGBTQ+ and dental education: Analyzing the present and recommendations for the future.

LGBTQ+ populations constitute increasing proportions of children, adolescents, and adults in the United States. Compared to their heterosexual counterparts, this group suffers from health inequities, including oral health. The report "Oral Health: Advances and Challenges" identified the LGBTQ+ community as an underserved population which faces significant barriers in accessing oral health care. Coverage of LGBTQ+ topics in formal education settings in both dental schools and dental hygiene programs is scarce, which contributes to inequities within this group. Increasing curriculum content related to LGBTQ+ populations is of utmost importance to promote optimal patient-provider interactions while improving oral health outcomes. Ensuring equity in oral health care provision will require deliberate, consistent efforts on the part of all stakeholders. Dental and allied dental education programs have made important strides in enhancing equity and inclusion in their institutions by engaging campus groups that support LGBTQ+ populations, creating mentorship programs, and collaborating with non-profit advocacy groups. Such efforts have successfully empowered LGBTQ+ patients, providers, and allies who are committed to further closing the knowledge gap. Most of the research regarding LGBTQ+ inclusion efforts have been done in the medical arena and there is a void in the data available from the dental profession. To fill this void, recommendations are offered that institutions can easily implement to expand LGBTQ+ diversity and inclusion visibility.

Ultrasound-assisted catheter-directed thrombolysis versus anticoagulation alone for management of submassive pulmonary embolism.

BACKGROUND: Patients with submassive pulmonary embolism (PE) are vulnerable to sudden deterioration, recurrent PE, and progression to pulmonary hypertension and chronic right ventricular (RV) dysfunction. Previous studies have suggested a clinical benefit of using ultrasound-assisted catheter-directed thrombolysis (USCDT) to invasively manage patients with submassive PE. However, there is sparse data comparing the clinical outcomes of these patients when treated with USCDT versus anticoagulation (AC) alone. We sought to compare the outcomes of USCDT versus AC alone in the management of submassive PE. METHODS: 192 consecutive patients who underwent USCDT for submassive PE between January 2013 and February 2019 were identified. ICD9/ICD10 codes were used to detect 2554 patients diagnosed with PE who did not undergo thrombolysis. Propensity matching identified 192 patients with acute PE treated with AC alone. Clinical outcomes were compared between the two groups. Baseline demographics, laboratory values, and pulmonary embolism severity index scores were similar between the two cohorts. RESULTS: There was a significant reduction in mean systolic pulmonary artery pressure (sPAP) in the USCDT group compared to the AC group (∆11 vs ∆3.9 mmHg, p < 0.001). There was significant improvement in proportion of RV dysfunction in all patients, but the difference was larger in the USCDT group (∆43.3% vs ∆17.3%, p < 0.001). Patients who underwent USCDT had lower 30-day (4.3% vs 10.5%, p = 0.03), 90-day (5.5% vs 12.4%, p = 0.03), and 1-year mortality (6.2% vs 14.2%, p = 0.03). CONCLUSIONS: In patients with acute submassive PE, USCDT was associated with improved 30-day, 90-day, and 1 year mortality as compared to AC alone. USCDT also improved RV function and reduced sPAP to a greater degree than AC alone. Further studies are needed to verify these results in both short- and long-term outcomes.

Integrated microRNA and mRNA expression profiling in a rat colon carcinogenesis model: effect of a chemo-protective diet.

We have recently demonstrated that nutritional bioactives (fish oil and pectin) modulate microRNA molecular switches in the colon. Since integrated analysis of microRNA and mRNA expression at an early stage of colon cancer development is lacking, in this study, four computational approaches were utilized to test the hypothesis that microRNAs and their posttranscriptionally regulated mRNA targets, i.e., both total mRNAs and actively translated mRNA transcripts, are differentially modulated by carcinogen and diet treatment. Sprague-Dawley rats were fed diets containing corn oil ± fish oil with pectin ± cellulose and injected with azoxymethane or saline (control). Colonic mucosa was assayed at an early time of cancer progression, and global gene set enrichment analysis was used to obtain those microRNAs significantly enriched by the change in expression of their putative target genes. In addition, cumulative distribution function plots and functional network analyses were used to evaluate the impact of diet and carcinogen combination on mRNA levels induced via microRNA alterations. Finally, linear discriminant analysis was used to identify the best single-, two-, and three-microRNA combinations for classifying dietary effects and colon tumor development. We demonstrate that polysomal profiling is tightly related to microRNA changes when compared with total mRNA profiling. In addition, diet and carcinogen exposure modulated a number of microRNAs (miR-16, miR-19b, miR-21, miR26b, miR27b, miR-93, and miR-203) linked to canonical oncogenic signaling pathways. Complementary gene expression analyses showed that oncogenic PTK2B, PDE4B, and TCF4 were suppressed by the chemoprotective diet at both the mRNA and protein levels.

Understanding and Caring for LGBTQ+ Youth by the Oral Health Care Provider.

With growing visibility, there is an increasing prevalence of lesbian, gay, bisexual, transgender, and queer (LGBTQ+) youth who feel empowered to own their true identity. Members of the oral health team frequently do not receive sufficient education in their training to recognize the nuance that treating this population may require. Although the tooth-level treatment does not materially change, a deeper appreciation of development of sexuality and gender identity, transgender medicine, and the health disparities LGBTQ+ youth face can promote more meaningful, trusting clinical relationships with this vulnerable population. This article aims to provide members of the oral health team with the requisite knowledge to deliver culturally competent care to LGBTQ+ youth.

Contemporary management of chronic indwelling inferior vena cava filters.

OBJECTIVE: Despite increasing retrieval rates of the inferior vena cava (IVC) filter, less than one-third are removed within the recommended timeline. Prolonged filter dwell times may increase the technical difficulty of retrieval and filter-related complications. We sought to evaluate the contemporary outcomes of patients with chronic indwelling IVC filters at a tertiary care center. METHODS: A retrospective analysis was performed from August 2015 through August 2019 of all patients who were referred for removal of a prolonged IVC filter with a dwell time >1 year. Descriptive analysis was used to evaluate patients' characteristics and procedural outcomes, which were reviewed through electronic medical records. Data were expressed as median with interquartile range (IQR) or number and percentage, as appropriate. RESULTS: A total of 47 patients were identified with a median filter dwell time of 10.0 years (IQR, 6-13 years); 34 patients underwent IVC filter removal, and 13 patients refused retrieval. The median age of patients was 54.9 years (IQR, 42.5-64.0 years); the majority were female (57%) and white (53%). The most common indication for filter placement was high risk despite anticoagulation (49%), followed by venous thromboembolism prophylaxis (21%). The majority of patients were symptomatic (72%). If symptomatic, the most common reason for retrieval was IVC penetration (94%), and the chief complaint was pain (56%). Retrieval success was 97%, with a median length of stay of 0 days. The majority of retrievals were performed through an endovascular approach (97%). There was one postprocedural complication (3%). CONCLUSIONS: Despite prolonged dwell times, IVC filter retrieval can be performed safely and effectively in carefully selected patients at a tertiary referral center.