efects in head and neck reconstruction.

Customization of ALT flaps using intraoperative templates is a useful method for flap design which facilitates fitting of the flap to a variety of defects in head and neck reconstruction.For solid tumors, extravasation of cancer cells and their survival in circulation represents a critical stage of the metastatic process that lacks complete understanding. Gaining insight into interactions between circulating tumor cells (CTCs) and other peripheral blood mononuclear cells (PBMCs) may provide valuable prognostic information. The purpose of this study was to use single-cell RNA-sequencing (scRNA-seq) of liquid biopsies from breast cancer patients to begin defining intravascular interactions. We captured CTCs from the peripheral blood of breast cancer patients using size-exclusion membranes followed by scRNA-seq of enriched CTCs and carry-over PBMCs. Transcriptome analysis identified two populations of CTCs one enriched for transcripts indicative of estrogen responsiveness and increased proliferation and another enriched for transcripts characteristic of reduced proliferation and epithelial-mesenchymal transition (EMT). We applied interactome and pathway analysis to determine interactions between CTCs and other captured cells. Our analysis predicted for enhanced immune evasion in the CTC population with EMT characteristics. In addition, PD-1/PD-L1 pathway activation and T cell exhaustion were predicted in T cells isolated from breast cancer patients compared with normal T cells. We conclude that scRNA-seq of breast cancer CTCs generally stratifies them into two types based on their proliferative and epithelial state and differential potential to interact with PBMCs. Better understanding of CTC subtypes and their intravascular interactions may help design treatments directed against CTCs with high metastatic and immune-evasive competence.

The entrustable professional activity (EPA) framework is an assessment approach used to define the educational outcomes of a program by outlining discrete work tasks learners are expected to perform independently upon graduation. This study outlines the development and evaluation of an EPA framework for predoctoral dental education at the University of North Carolina Adams School of Dentistry.

The draft EPA framework was created in collaboration with a group of faculty members and included 15 statements that were mapped to relevant Commission on Dental Accreditation standards. The draft EPA framework was distributed to faculty via an electronic survey, requesting participants to evaluate whether the EPAs were well-defined; observable; measurable; expected of a general dentist; transferable to other practice settings; and required application of relevant knowledge, skills, and attitudes. In addition, participants were asked to identify the percentage of graduates who could perform these tasks independently and whether learners must be able to perform the list of EPAs upon graduation.

Sixty-eight faculty members completed the survey (72% response rate); participants represented all divisions across the school and had extensive dental practice experiences. Overall, participants agreed the EPAs met the defined criteria and were considered important for graduates to be able to demonstrate. Feedback from faculty voiced support for the EPA framework and identified concerns regarding the implementation due to potential faculty calibration and time constraints.

Evidence from this study supports additional research to explore how the EPA framework can be further developed in predoctoral and postgraduate dental education programs.

Evidence from this study supports additional research to explore how the EPA framework can be further developed in predoctoral and postgraduate dental education programs.A general graphene quantum dot-tethering design strategy to synthesize single-atom catalysts (SACs) is presented. The strategy is applicable to different metals (Cr, Mn, Fe, Co, Ni, Cu, and Zn) and supports (0D carbon nanosphere, 1D carbon nanotube, 2D graphene nanosheet, and 3D graphite foam) with the metal loading of 3.0-4.5 wt %. The direct transmission electron microscopy imaging and X-ray absorption spectra analyses confirm the atomic dispersed metal in carbon supports. Our study reveals that the abundant oxygenated groups for complexing metal ions and the rich defective sites for incorporating nitrogen are essential to realize the synthesis of SACs. Furthermore, the carbon nanotube supported Ni SACs exhibits high electrocatalytic activity for CO2 reduction with nearly 100 % CO selectivity. This universal strategy is expected to open up new research avenues to produce SACs for diverse electrocatalytic applications.

Extensive lower extremity soft-tissue defects pose a reconstructive challenge. We present our experience with the conjoined parascapular and latissimus dorsi (CPLD) free flap.

From October 2008 to October 2017, 69 patients (14 female, 55 male) with a mean age of 50 years (range 16-79 years) underwent reconstruction of lower extremity defects with the CPLD free flap. Mean defect size was 24 × 36 cm (range 14 × 20 to 45 × 80 cm).

Mean latissimus dorsi (LD) flap size was 19 × 28 cm (range 14 × 20 to 28 × 42 cm) and mean parascapular (PSC) flap size was 8 × 25 cm (range 5 × 12 to 11 × 33 cm). Six patients (9%) experienced a total of eight microvascular complications arterial thrombosis (n = 1), venous thrombosis (n = 6), combined arterial and venous thrombosis (n = 1). The re-exploration rate was 13%. Major complications of the donor-site were seen in 9 patients (13%), of the flap in 13 patients (19%), and of both in 6 patients (9%). Fifteen patients experienced partial flap necrosis (22%). Three CPLD and one PSC flap were lost (5%). PSC flap length was a significant predictor of distal flap necrosis (χ

(1) = 13.2, p = .004, OR = 1.343, 95% CI [1.098-1.642]). PSC flap width was a significant predictor of donor-site revisions (χ

(1) = 15.9, p = .010, OR = 4.745, 95% CI [1.584-14.213]). Arterio-venous loops (AVLs) tended to increase the risk of microvascular thrombosis (χ

(1) = 3.7, p = .08, OR = 4.1, 95% CI [0.9-18.7]).

The CPLD free flap is an extremely large and highly reliable flap, allowing one-stage reconstruction of extensive lower extremity defects. It may overcome the need for multiple flaps in selected cases.

The CPLD free flap is an extremely large and highly reliable flap, allowing one-stage reconstruction of extensive lower extremity defects. It may overcome the need for multiple flaps in selected cases.Heterogeneity is a hallmark of cancer. For various cancer outcomes/phenotypes, supervised heterogeneity analysis has been conducted, leading to a deeper understanding of disease biology and customized clinical decisions. In the literature, such analysis has been oftentimes based on demographic, clinical, and omics measurements. Recent studies have shown that high-dimensional histopathological imaging features contain valuable information on cancer outcomes. However, comparatively, heterogeneity analysis based on imaging features has been very limited. In this article, we conduct supervised cancer heterogeneity analysis using histopathological imaging features. The penalized fusion technique, which has notable advantages-such as greater flexibility-over the finite mixture modeling and other techniques, is adopted. A sparse penalization is further imposed to accommodate high dimensionality and select relevant imaging features. To improve computational feasibility and generate more reliable estimation, we employ model averaging. Computational and statistical properties of the proposed approach are carefully investigated. Simulation demonstrates its favorable performance. The analysis of The Cancer Genome Atlas (TCGA) data may provide a new way of defining/examining breast cancer heterogeneity.

A variety of models are used for fine needle aspiration biopsy (FNAB) and smear preparation techniques training human, animal and silicon models or combined models. We present fresh animal tissues as models for freehand and ultrasound (US)-guided FNAB technique training, enabling an integrated approach from tumour detection to smear evaluation.

We introduced a novel combined animal tissue model using dietary animal meat with covering skin as a substrate. Animal liver tissue of various sizes, representing tumour, was inserted into the various layers of the substrate (subcutaneous fat, muscle tissue, proximity of bone). Freehand and US-guided FNAB smear preparation, including fixation, was then performed and assessed.

The use of a combined animal tissue model for 6 freehand and 3 US-guided FNAB sessions showed a statistically significant improvement in the US-guided FNAB retrieval of liver tissue (Fisher’s exact test, p =  .0216), in smear preparation technique reflected in a decrease in the number of too thick smears after freehand FNAB (Fisher’s exact test, p  =  .0070), in the overall number of smears satisfactory for evaluation by US-guided FNAB (Fisher’s exact test, p =  .0206) and in the number of flawless smears obtained in the freehand FNAB training sessions (Fisher’s exact test, p =  .0020).

A unique advantage of the presented model encompassing various layers of animal tissues with covering skin, offers an integrated approach for FNAB training from „tumour” detection, puncture precision, to smear preparation and cytological evaluation for a wider audience and does not compromise patient safety.

A unique advantage of the presented model encompassing various layers of animal tissues with covering skin, offers an integrated approach for FNAB training from „tumour” detection, puncture precision, to smear preparation and cytological evaluation for a wider audience and does not compromise patient safety.Since heat shock protein (HSP27) is a prognostic marker in cervical cancer, in the present study, the apoptotic mechanism of lambertianic acid (LA) was investigated in human cervical cancers in association with HSP27/STAT3/AKT signaling axis. LA exerted significant cytotoxicity, induced sub-G1 population, and increased the cleavage of Poly (ADP-ribose) polymerase (PARP) and cysteine aspartyl-specific protease 3 (caspase3) in HeLa and Caski cancer cells. Consistently, LA downregulated anti-apopotic genes such as B-cell lymphoma 2 (Bcl-2) and inhibitors of apoptosis proteins (c-IAP) in HeLa and Caski cells. Furthermore, LA-inhibited phosphorylation of HSP27, signal transducer, and activator of transcription 3 (STAT3) and Protein kinase B (AKT) through disturbing the binding of HSP27 with STAT3 or AKT in HeLa cells. Notably, LA upregulated the level of miR216b in HeLa and Caski cells. Consistently, miR216b mimic suppressed phosphorylation of HSP27 and reduced the expression of pro-PARP, while miR216b inhibitor reversed the ability of LA to attenuate phosphorylation of AKT, HSP27, and STAT3 and to reduce the expression of pro-PARP in HeLa cells. Overall, our findings suggest that miRNA216b mediated inhibition of HSP27/STAT3/ AKT signaling axis is critically involved in LA-induced apoptosis in cervical cancers.

To estimate associations between lower urinary tract symptoms (LUTS) and phenotypic frailty in older men.

Cross-sectional study.

Community-dwelling men recruited from 2000 to 2002 from six U.S. academic centers for the Osteoporotic Fractures in Men Study.

A total of 5,979 men aged 65 and older.

The independent variable was LUTS severity (none/mild, moderate, or severe) assessed with the American Urologic Association Symptom Index. Participants were categorized as frail, intermediate stage, or robust using an adapted Cardiovascular Health Study index (components low lean mass, weakness, exhaustion, slowness, and low physical activity). Associations were estimated with odds ratios and 95% confidence intervals (CIs) from multivariable multinomial logistic regression models adjusted for potential confounders of age, other demographics, health-related behaviors, and comorbidities.

The prevalence of frailty was 7%, 11%, and 18% among men with none/mild, moderate, and severe LUTS, respectively. Moderate ly appropriate.

The prevalence of phenotypic frailty is higher among older community-dwelling men with moderate or severe LUTS compared with those with mild or no LUTS. The positive association between LUTS severity and frailty among older men appears independent of age and known frailty risk factors. Although the temporal direction of this association and the utility of LUTS or frailty interventions in this population remain unclear, the high co-occurrence of these conditions could lead to earlier identification of frailty when clinically appropriate.Gastroesophageal reflux disease (GERD) is primarily a motor disorder, and its pathogenesis is multifactorial. As a consequence, treatment should be able to address the underlying pathophysiology. Proton pump inhibitors (PPIs) are the mainstay of medical therapy for GERD, but these drugs only provide the control of symptoms and lesions without curing the disease. However, continuous acid suppression with PPIs is recommended for patients with Barrett’s esophagus because of their potential chemopreventive effects. In addition to the antisecretory activity, these compounds display several pharmacological properties, often overlooked in clinical practice. PPIs can indeed affect gastric motility, exert a mucosal protective effect, and an antioxidant, anti-inflammatory, and antineoplastic activity, also protecting cancer cells from developing chemo- or radiotherapeutic resistance. Even in the third millennium, current pharmacologic approaches to address GERD are limited. Reflux inhibitors represent a promise unfulfilled, effective and safe prokinetics are lacking, and antidepressants, despite being effective in selected patients, give rise to adverse events in a large proportion of them. While waiting for new drug classes (like potassium-competitive acid blockers), reassessing old drugs (namely alginate-containing formulations), and paving the new avenue of esophageal mucosal protection are, at the present time, the only reliable alternatives to acid suppression.Researches have proved that increasing level of prostate-specific antigen (PSA) is an indicator for the progression of prostate cancer. The present study was focused to determine the PSA level by using anti-PSA antibody conjugated iron oxide nanoparticles, as the probe immobilized on the gap-fingered electrode sensing surface. The detection limit and sensitivity were found at the level of 1.9 pg/mL on the linear regression curve (y = 1.6939x – 0.5671; R² = 0.9878). A dose-dependent liner range was found from 1.9 until 60 pg/mL. Further, PSA was spiked in human serum and did not affect the interaction of PSA and its antibody. This method of detection quantifies the level of PSA, which helps to diagnose prostate cancer at its earlier stage.Behavioral and physiological traits of ectotherms are especially sensitive to fluctuations of environmental temperature. In particular, niche-specialist lizards are dependent on their physiological plasticity to adjust to changing environmental conditions. Lizards of the genus Phymaturus are viviparous, mainly herbivorous, and inhabit only rock promontories in the steppe environments of Patagonia and the Andes. Herein, we examine the vulnerability of the southernmost Phymaturus species to global warming the endemic Phymaturus calcogaster, which lives in a mesic environment in eastern Patagonia. We studied body temperatures in the field (Tb ), preferred body temperatures in a thermogradient (Tpref ), the operative (Te ) and environmental temperatures, and the dependence of running performance on body temperature. P. calcogaster had a mean Tb (27.04°C) and a mean Te (31.15°C) both lower than their preferred temperature (Tpref = 36.61°C) and the optimal temperature for running performance (To = 37.13°C). Lizard activity seems to be restraint during the early afternoon due high environmental temperatures. However, both, the high safety margin and warming tolerance suggest that the expected increase in environmental temperatures due to global warming (IPCC report in 2018) would not threaten, but indeed enhance locomotor performance in this population.A conventional dose-response function can be refitted as additional data become available. A predictive dose-response function in contrast does not require a curve-fitting step, only additional data and presents the unconditional probabilities of illness, reflecting the level of information it contains. In contrast, the predictive Bayesian dose-response function becomes progressively less conservative as more information is included. This investigation evaluated the potential for using predictive Bayesian methods to develop a dose-response for human infection that improves on existing models, to show how predictive Bayesian statistical methods can utilize additional data, and expand the Bayesian methods for a broad audience including those concerned about an oversimplification of dose-response curve use in quantitative microbial risk assessment (QMRA). This study used a dose-response relationship incorporating six separate data sets for Cryptosporidium parvum. A Pareto II distribution with known priors was applied to one of the six data sets to calibrate the model, while the others were used for subsequent updating. While epidemiological principles indicate that local variations, host susceptibility, and organism strain virulence may vary, the six data sets all appear to be well characterized using the Bayesian approach. The adaptable model was applied to an existing data set for Campylobacter jejuni for model validation purposes, which yielded results that demonstrate the ability to analyze a dose-response function with limited data using and update those relationships with new data. An analysis of the goodness of fit compared to the beta-Poisson methods also demonstrated correlation between the predictive Bayesian model and the data.

What is the central question of this study? Is neuromuscular fatigability interrelated between different muscle groups from the same individual during isometric all-out exercise? What is the main finding and its importance? Although the average decrease can vary between muscles, an individual demonstrates interrelated fatigability aetiology regardless of the muscle group tested. The inter-individual variability provides evidence of different profiles common between muscles, which can be regarded as an individual characteristic.

Neuromuscular fatigability is commonly attributed to central and peripheral origins. However, there is strong evidence of interactions between these two mechanisms. According to the idea that peripheral fatigability might be centrally regulated, one can hypothesize that neuromuscular fatigability would be correlated between different muscle groups at the individual level. Thirty-two healthy participants (16 women and 16 men) completed two 5min fatiguing exercises [60 isometric maxiforce (ΔDb100 ), voluntary activation (ΔVA) and central activation ratio (∆CAR) were also investigated. Significant correlations were found between FFs and PFs for FA , ΔDb100 and ΔVA (r = 0.65, r = 0.63 and r = 0.50, respectively). A significant negative correlation between ∆CAR and ∆Db100 was evidenced for both PFs (r = -0.82) and FFs (r = -0.57). Neuromuscular fatigability is correlated between different muscle groups at the individual level. The results support the idea that a restrained motor drive prevents large peripheral perturbations and that individuals exhibit correlated fatigability aetiology regardless of the muscle group tested. Widely different central/peripheral profiles can be found amongst individuals, and a part of the fatigability aetiology can be regarded as an individual characteristic.In Pakistan, annual poliovirus investment decisions drive quantities of supplemental immunization campaigns districts receive. In this article, we assess whether increased spending on poliovirus surveillance is associated with greater likelihood of correctly identifying districts at high risk of polio with assignment of an elevated „risk ranking.” We reviewed programmatic documents from Pakistan for the period from 2012-2017, recording whether districts had been classified as „high risk” or „low risk” in each year. Through document review, we developed a decision tree to describe the ranking decisions. Then, integrating data from the World Health Organization and Global Polio Eradication Initiative, we constructed a Bayesian decision network reflecting investments in polio surveillance and immunization campaigns, surveillance metrics, disease incidence, immunization rates, and occurrence of polio cases. We test these factors for statistical association with the outcome of interest-a change in risk rank between the beginning and the end of the one-year time period. We simulate different spending scenarios and predict their impact on district risk ranking in future time periods. We find that per district spending increases are associated with increased identification of cases of acute flaccid paralysis (AFP). However, the low specificity of AFP investment and the largely invariant ranking of district risk means that even large increases in surveillance spending are unlikely to promote major changes in risk rankings at the current stage of the Pakistan polio eradication campaign.

Apert syndrome is an autosomal, dominant inherited disorder characterized by craniosynostosis and syndactyly caused by gain-of-function mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. Wnt/β-catenin signaling plays critical roles in regulating the skeletal development. Here, we analyzed the role of this pathway in the developing coronal sutures (CS) of a murine Apert syndrome model (Fgfr2

).

We observed aberrantly increased mRNA expression of Lrp5 and Lrp6 in CS of Fgfr2

mice, whereas both wild type (WT) and Fgfr2

mice showed similar expression of other Wnt/β-catenin-related genes, such as Wnt3, Wnt3a, Fzd4, Fzd6, Axin2, and Dkk1 as evidenced by in situ hybridization. Significantly increased Lrp5 and Lrp6 mRNA expression was observed by quantitative PCR analysis of cultured cells isolated from CS of Fgfr2

mice. Phospho-LRP5, phospho-LRP6, and non-phospho-β-catenin were upregulated in Fgfr2

CS compared with that in WT CS. Short-interfering RNA targeting Lrp5 and Lrp6 significantly reduced runt-related transcription factor 2, collagen type 1 alpha 1, and osteocalcin mRNA expression, and alkaline phosphatase activity in cultured cells.

The Wnt/β-catenin pathway was activated in the CS of Fgfr2

mice during craniofacial development, suggesting the involvement of the Wnt/β-catenin pathway in the pathogenesis of CS synostosis in Fgfr2

mice.

The Wnt/β-catenin pathway was activated in the CS of Fgfr2S252W/+ mice during craniofacial development, suggesting the involvement of the Wnt/β-catenin pathway in the pathogenesis of CS synostosis in Fgfr2S252W/+ mice.The Envelope protein (E) is one of the four structural proteins encoded by the genome of SARS-CoV and SARS-CoV-2 Coronaviruses. It is an integral membrane protein, highly expressed in the host cell, which is known to have an important role in Coronaviruses maturation, assembly and virulence. The E protein presents a PDZ-binding motif at its C-terminus. One of the key interactors of the E protein in the intracellular environment is the PDZ containing protein PALS1. This interaction is known to play a key role in the SARS-CoV pathology and suspected to affect the integrity of the lung epithelia. In this paper we measured and compared the affinity of peptides mimicking the E protein from SARS-CoV and SARS-CoV-2 for the PDZ domain of PALS1, through equilibrium and kinetic binding experiments. Our results support the hypothesis that the increased virulence of SARS-CoV-2 compared to SARS-CoV may rely on the increased affinity of its Envelope protein for PALS1.

To describe the caregiving experiences and physical and emotional needs of family members and friends who provide care to veterans with mental, physical, and cognitive comorbidities.

Cross-sectional study.

National telephone surveys administered from 2017 to 2019.

Family caregivers of veterans enrolled in the Veterans Affairs (VA) Program of General Caregiver Support Services between October 2016 and July 2018 who responded to a telephone survey (N = 1,509; response rate = 39%).

We examined caregiver burden, depressive symptoms, financial strain, satisfaction with care, amount and duration of caregiving, life chaos, loneliness, and integration of caregiver with the healthcare team using validated instruments. We also collected caregiver demographic and socioeconomic characteristics and asked caregivers to identify the veteran’s condition(s) and provide an assessment of the veteran’s functioning.

Average caregiver age was 62.2 (standard deviation [SD] = 13.7) and 69.8 (SD = 15.6) for veterans. Amontive benefits for this population and serve as a model for caregiver support programs outside the VA health care system.

Caregivers who care for veterans with trauma-based comorbidities reported intensive caregiving and significant levels of distress, depressive symptoms, and other negative consequences. These caregivers require comprehensive support services including access to health care, financial assistance, and enhanced respite care. Planned expansion of VA caregiver support has the potential to provide positive benefits for this population and serve as a model for caregiver support programs outside the VA health care system.Eosinophilic esophagitis (EoE) is an allergen-driven chronic inflammatory condition, characterized by symptoms related to esophageal dysfunction and confirmed histologically by esophageal mucosal eosinophilia. Since its first description in the 1990s, the incidence and prevalence of EoE have been on the rise. It is known to affect all ages of various ethnic backgrounds and both sexes; however, it is most seen in White males. Children with EoE often present with abdominal pain, nausea, vomiting, and failure to thrive, whereas adults with EoE typically present with dysphagia and food impaction. Diagnosis of EoE requires histologic confirmation of elevated esophageal eosinophils in a symptomatic patient, and only after secondary causes have been excluded. Because EoE is a chronic and progressively fibrostenotic disease, treatment goals include resolution of symptoms, induction and maintenance of disease remission, and prevention and possibly reversal of fibrostenotic complications, while minimizing treatment-related adverse effects and improving quality of life. Treatment strategies include the „3 D’s”-drugs, diet, and dilation. Standard drug therapies include proton-pump inhibitors and topical corticosteroids. Dietary therapies include elemental diet, allergy testing-directed elimination diet, and empiric elimination diets. Endoscopic esophageal dilation for EoE strictures can alleviate esophageal symptoms but has no effect on mucosal inflammation. Recent progress in EoE research has made possible evidence-based clinical guidelines. Ongoing pharmacologic trials show promise for novel biologic agents in the treatment of refractory EoE.

It is unknown whether cone beam computed tomography (CBCT) image reconstruction characteristics, including section thickness, may affect linear bone measurements of periodontal intrabony defects. The aim of this study was to compare intrasurgical and CBCT-based linear measurements of intrabony defects focusing on CBCT section thickness.

Sixty-six intrabony defects were assessed in 21 patients with chronic generalized severe periodontitis. Linear measurements of alveolar bone (radiographic bone level [rBL]), assessed in CBCT images at diverse section thicknesses 0.25mm (voxel size), 1mm, and 3mm, were compared with clinical bone level (cBL) measurements obtained intrasurgically. To provide identical reference points for rBL and cBL measurements, individually adjusted grooves on the reference stent were prepared for each periodontal defect site. CBCT measurements were performed in two rounds by two trained observers. Observer agreement was assessed by intraclass correlation coefficients (ICC). ANOVA assessed the difference among cBL and rBL at different section thicknesses.

Intra- and inter-observer agreement was excellent (ICC>0.99) and highly significant independent of the observer, evaluation round, and CBCT section thickness. Mean rBL in the diverse CBCT section thicknesses was very close to that measured clinically (cBL). There was no statistically significant difference between cBL and rBL for any section thickness, neither for the overall evaluated sites, nor the maxilla or mandible separately.

No statistically significant difference between clinical and radiographic bone level for 0.25-, 1-, and 3-mm CBCT section thicknesses were observed when assessing intrabony periodontal defects.

No statistically significant difference between clinical and radiographic bone level for 0.25-, 1-, and 3-mm CBCT section thicknesses were observed when assessing intrabony periodontal defects.A 66-year-old man, implanted Abbott dual-chamber pacemaker, was admitted to our hospital due to recurrent palpitation. ECG was recorded on admission, which created a diagnostic confusion What accounts for the appearance of the VP in the setting of a stable intrinsic atrioventricular (AV) conduction? In this case, we will focus on the logical reasoning in the analysis of Pacing ECG.Knowing how switchgrass (Panicum virgatum L.) responds and adapts to phosphorus (P)-limitation will aid efforts to optimize P acquisition and use in this species for sustainable biomass production. This integrative study investigated the impacts of mild, moderate, and severe P-stress on genome transcription and whole-plant metabolism, physiology and development in switchgrass. P-limitation reduced overall plant growth, increased root/shoot ratio, increased root branching at moderate P-stress, and decreased root diameter with increased density and length of root hairs at severe P-stress. RNA-seq analysis revealed thousands of genes that were differentially expressed under moderate and severe P-stress in roots and/or shoots compared to P-replete plants, with many stress-induced genes involved in transcriptional and other forms of regulation, primary and secondary metabolism, transport, and other processes involved in P-acquisition and homeostasis. Amongst the latter were multiple miRNA399 genes and putative targets of these. Metabolite profiling showed that levels of most sugars and sugar alcohols decreased with increasing P stress, while organic and amino acids increased under mild and moderate P-stress in shoots and roots, although this trend reversed under severe P-stress, especially in shoots.Alterations of B-cell lymphoma 2 (BCL-2) family proteins contribute to the survival of B-cell malignancies. Recently, venetoclax, a BCL-2 inhibitor, was approved for B-cell chronic lymphocytic leukemia therapy and is being investigated in clinical trials for a variety of hematologic cell malignancies. Furthermore, combination therapy with other molecularly targeted drugs was reported to be more effective than monotherapy. However, combining venetoclax with immunotherapy based on T-cells has not been tested. Because both venetoclax and granzyme B activate the mitochondrial apoptosis pathway by targeting different BCL-2 family molecules, it is possible that combinations of venetoclax with immunotherapy will be effective treatments. We examined the effect of combining venetoclax with immunotherapy using an in vitro model system involving cytomegalovirus (CMV) pp65 antigen-specific cytotoxic T-cells (CMV-CTLs) as the effector cells and CMVpp65 antigen-expressing B-cell lines as the target cells. Cytotoxicity of CMV-CTLs to the target B-cell lines was enhanced by venetoclax with combination index values of 0.47-0.83. This suggests that venetoclax synergizes with T-cell-based immunotherapy to affect B-cell malignancies. Interestingly, venetoclax synergized not only with antigen-specific cytotoxicity but also with nonspecific cytotoxicity. Importantly, CMV-CTLs could be expanded in the presence of venetoclax at the maximum concentration (5 μM) that induced apoptosis in resting CMV-CTLs. B-cell lymphoma-extra large (BCL-xL) expression in CMV-CTLs increased transiently after activation by CMVpp65-transfected B-cell lines, indicating that the expression of BCL-xL was important for the effectiveness of combination treatment with venetoclax. These findings suggest that T-cell-based immunotherapy combined with venetoclax is effective against B-cell malignancies.

Proprioceptive sensory information from the ankle joint is critical for the control of upright posture and balance. We examined the influence of age (n=54 healthy adults, 20-82 years old) on lower limb muscle responses to proprioceptive perturbations evoked by Achilles tendon vibration during standing. The frequency bandwidth of the muscle response became narrower, and the gain (the muscle response relative to the stimulus) and scaling (increases in response amplitude with increases in stimulus amplitude) decreased with age. Mechanics of the muscle-tendon unit (mechanical admittance) did not differ with age during standing, and thus probably did not mediate the age-related changes observed in soleus muscle responses to vibration. These findings add to our understanding of how altered proprioceptive responses may contribute to impaired mobility and falls with ageing.

Proprioceptive information from the ankle joint plays an important role in the control of upright posture and balance. Ageing influences many could contribute to poorer mobility and falls.Sarcomeric gene mutations are associated with the development of hypertrophic cardiomyopathy (HCM). Current drug therapeutics for HCM patients are effective in relieving symptoms, but do not prevent or reverse disease progression. Moreover, due to heterogeneity in the clinical manifestations of the disease, patients experience variable outcomes in response to therapeutics. Mechanistically, alterations in calcium handling, sarcomeric disorganization, energy metabolism and contractility participate in HCM disease progression. While some similarities exist, each mutation appears to lead to mutation-specific pathophysiology. Furthermore, these alterations may precede or proceed development of the pathology. This review assesses the efficacy of HCM therapeutics from studies performed in animal models of HCM and human clinical trials. Evidence suggests that a preventative rather than corrective therapeutic approach may be more efficacious in the treatment of HCM. In addition, a clear understanding of mutation-specific mechanisms may assist in informing the most effective therapeutic mode of action.

The purpose of this study was to survey the current status of orthodontic education at pediatric dental residencies in the United States. A similar survey was conducted >10 years ago. With changing healthcare politics, social demands, and technology, it is important to have current information about dental education.

A 23-item anonymous survey was sent to individual pediatric dental residency program directors via Qualtrics email software. The survey was sent a total of 4 times over an 8-week period. If the surveys were not completed in a predetermined amount of time, they were resent to those who had not yet completed them.

There were 34 responders for a 24% response rate. Of the respondents, 73% reported teaching biomechanics of tooth movement, and 45% reported teaching 2×4 mechanics to „marginally acceptable” level. Early (91%) to late mixed dentition (77%) is the most commonly treated orthodontic case. While most programs do not require a minimum number of orthodontic cases for graduation (85%), residents’ understanding of growth and development is mostly (71%) evaluated through the results of the American Board of Pediatric Dentistry Qualifying Examination.

This study summarizes the current climate of the orthodontic education component in U.S. pediatric dental residencies.

This study summarizes the current climate of the orthodontic education component in U.S. pediatric dental residencies.

The aim of this prospective study is to evaluate the clinical applicability of the entire papilla preservation (EPP) technique in the regenerative treatment of isolated deep intrabony defects using native collagen membrane and bone grafting materials.

Fifteen healthy and non-smoker patients (nine males and six females; mean age 47.73 ± 12.18; range 21 to 63 years) with one isolated deep intrabony defect each (baseline probing depth (PD) 9.03 ± 1.62mm; clinical attachment level (CAL) 11.16 ± 1.81mm) were treated with guided tissue regeneration. Surgical access to the defect was provided by a single buccal vertical incision with an interdental tunneling flap. Following the granulation tissue removal, intrabony defect was filled with bone substitutes. A collagen barrier was trimmed and placed under the intact defect-associated papilla with palatal positioning suture. Microsurgical sutures were used for primary closure.

At 1week, healing of the 15 sites was uneventful. During the study, all sites showed 100% primary closure rate. At 1-year follow-up, an average CAL gain of 5.86 ± 1.28mm (P<0.0001), PD reduction of 6.1 ± 1.47mm (P<0.0001), and minimal increase in gingival recession of 0.23 ± 0.62mm (P=0.168) were observed.

This novel surgical technique, that keeps the interdental papilla intact, seems promising to provide optimal biomaterial protection and healing conditions, even when a collagen barrier and bone substitutes are applied.

This novel surgical technique, that keeps the interdental papilla intact, seems promising to provide optimal biomaterial protection and healing conditions, even when a collagen barrier and bone substitutes are applied.Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global pandemic with a wide spectrum of clinical signs and symptoms. Neurologic manifestations are relatively common, with severe cases often demonstrating striking findings on neuroimaging. Because the neuroradiologic findings may be the first evidence of COVID-19, the emergency radiologist has a critical role to play in not only the detection and management of the disease but also in the safety of other patients and hospital staff. Therefore, radiologists, especially those who specialize in emergency radiology, need to be aware of the neuroradiologic manifestations of COVID-19.

To assess the association of demographic and clinical factors with the clinical decision of tapering biologic disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) in daily practice.

All RA patients receiving bDMARDs were documented by 14 rheumatologists when presenting in 9 specialized private practices. Statistical analyses employed multivariable logistic models for dose reduction with the covariates age, gender, disease duration until bDMARD start, smoking status, disease activity, comorbidity, functional capacity, radiographic damage, concomitant methotrexate (MTX) treatment, rheumatoid factor positivity, and glucocorticoid use. In the multivariable model (MVM), missing values were imputed.

Data of 586 RA patients on bDMARD treatment were available, 171 of which (29%) received a reduced dose. The highest rates of patients with dose reduction were seen for rituximab (67%) and infliximab (50%). The degree of dose reduction was most prominent for rituximab (57%). Int methotrexate is positively associated with dose tapering of biologic disease modifying antirheumatic drugs.

DAS 28 remission, concomitant MTX, and lower glucocorticoid doses were positively associated with dose tapering of bDMARDs in RA patients. While this could be expected, the reason for the association with age, comorbidity, and the time between disease onset and bDMARD start is less clear. Key points • In rheumatology practice, tapering of biologic disease modifying antirheumatic drugs is feasible in nearly 30% of patients with rheumatoid arthritis. • The degree of dose reduction may exceed 50% of the recommended dose. • In a multivariable model, concomitant methotrexate is positively associated with dose tapering of biologic disease modifying antirheumatic drugs.

The purpose of this study was to compare and contrast the prevalence of rheumatoid arthritis in Northern Alberta estimated by health administrative data and data from a rheumatologist-based prescription database.

The study was performed using administrative health data from the province of Alberta through the local health authority. The cases and population identified in the database were reported from the year 2016. Rheumatology prescribing data was accessed through the Physician Learning Program and based on Alberta health billing data of actively practicing rheumatologists between the years 2012 and 2016. Ethics was provided by the Conjoint Health Research Ethics Boards at the University of Calgary (REB 13-0459).

The total population of the area examined was determined to be 2,086,181. The administrative health database identified 42,354 cases of RA based on their case definition with a prevalence of 2.08%. Based on rheumatologist diagnosis and prescribing data, the number of cases identified was 11,regions.

In conclusion, this study compares and contrasts the prevalence of rheumatoid arthritis reported by administrative data versus identification by specialists. Our study again illustrates that accuracy of case definitions when studying chronic conditions such as rheumatoid arthritis is paramount. The results also suggest a lack of access to rheumatologist services in Northern Alberta and reiterate the need for ongoing recruitment of new rheumatologists as has been highlighted previously. Key Points • The main contribution of this paper is to compare and contrast the prevalence of rheumatoid arthritis as reported by administrative data versus identification by specialists. • Our study also shows the distribution of rheumatoid arthritis in a large geographical area and illustrates a lack of access to subspecialty care in certain regions.

It is of high clinical importance to identify the primary lesion and its pathological types for patients with brain metastases (BM). The purpose of this study is to investigate the feasibility and accuracy of differentiating the primary adenocarcinoma (AD) and squamous cell carcinoma (SCC) of non-small-cell lung cancer (NSCLC) for patients with BM based on radiomics from brain contrast-enhanced computer tomography (CECT) images.

A total of 144 BM patients (94 male, 50 female) were enrolled in this study with 102 with primary lung AD and 42 with SCC, respectively. Radiomics features from manually contoured tumors were extracted using python. Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) logistic regression were applied to select relative radiomics features. Binary logistic regression and support vector machines (SVM) were applied to build models with radiomics features alone and with radiomics features plus age and sex.

Fourteen features were selected from a total ofng primary AD and SCC to achieve optimal therapeutic management in patients with BM from NSCLC with a highest area under the curve (AUC) of 0.828 and an accuracy of 0.758, respectively.

To evaluate texture analysis in nonenhanced 3-T MRI for differentiating pulmonary fungal infiltrates and lymphoma manifestations in hematological patients and to compare the diagnostic performance with that of signal intensity quotients („nonenhanced imaging characterization quotients,” NICQs).

MR scans were performed using a speed-optimized imaging protocol without an intravenous contrast medium including axial T2-weighted (T2w) single-shot fast spin-echo and T1-weighted (T1w) gradient-echo sequences. ROIs were drawn within the lesions to extract first-order statistics from original images using HeterogeneityCAD and PyRadiomics. NICQs were calculated using signal intensities of the lesions, muscle, and fat. The standard of reference was histology or clinical diagnosis in follow-up. Statistical testing included ROC analysis, clustered ROC analysis, and DeLong test. Intra- and interrater reliability was tested using intraclass correlation coefficients (ICC).

Thirty-three fungal infiltrates in 16 patientsents. • T1w entropy, uniformity, and energy along with T2w energy show the best performances for differentiating pulmonary lymphoma from fungal pneumonia. • The results of the texture analysis should be checked for their intrinsic consistency to identify possible incongruities of single parameters.

• Texture analysis in nonenhanced pulmonary MRI improves the differentiation of pulmonary lymphoma and fungal pneumonia compared with signal intensity quotients. • T1w entropy, uniformity, and energy along with T2w energy show the best performances for differentiating pulmonary lymphoma from fungal pneumonia. • The results of the texture analysis should be checked for their intrinsic consistency to identify possible incongruities of single parameters.

To compare two established software applications in terms of apparent diffusion coefficient (ADC) lesion volumes, volume of critically hypoperfused brain tissue, and calculated volumes of perfusion-diffusion mismatch in brain MRI of patients with acute ischemic stroke.

Brain MRI examinations of 81 patients with acute stroke due to large vessel occlusion of the anterior circulation were analyzed. The volume of hypoperfused brain tissue, ADC volume, and the volume of perfusion-diffusion mismatch were calculated automatically with two different software packages. The calculated parameters were compared quantitatively using formal statistics.

Significant difference was found for the volume of hypoperfused tissue (median 91.0ml vs. 102.2ml; p < 0.05) and the ADC volume (median 30.0ml vs. 23.9ml; p < 0.05) between different software packages. The volume of the perfusion-diffusion mismatch differed significantly (median 47.0ml vs. 67.2ml; p < 0.05). Evaluation of the results on a single-subject basis criteria derived from randomized trials. • Infarct volume segmentation plays a crucial role and lead to significantly different result for different computer programs. • Perfusion-diffusion mismatch estimation from different computer programs may influence the decision for or against mechanical thrombectomy.

To investigate biomechanical changes in lumbar disc herniations.

Patients with lumbar disc herniation verified on a 1.5-3-T magnetic resonance imaging (MRI) scanner were imaged in a weight-bearing 0.25-T MRI scanner in (1) standing position, (2) conventional supine position with relative lumbar flexion, and (3) supine position with a forced lumbar extension by adding a lumbarpillow. The L2-S1 lordosis angle, the disc cross-sectional area, the disc cross-sectional diameter, and the spinal canal cross-sectional diameter were measured for each position. Disc degeneration and nerve root compression were graded, and the pain intensity was reported during each scan position.

Forty-three herniated discs in 37 patients (36.7 ± 11.9 years) were analyzed in each position. The L2-S1 lumbar angle increased in the standing position (mean difference [MD] 5.61°, 95% confidence interval [95% CI] 3.44 to 7.78) and with the lumbar pillow in the supine position (MD 14.63°, 95% CI 11.71 to 17.57), both compared with the co size in the axial plane during standing. • Increased nerve root compression grades for paracentral herniated discs were found during standing. • Weight-bearing MRI may increase the diagnostic sensitivity of nerve root compression in lumbar disc herniations.There is increasing interest in understanding the pathological role of DNA methylation changes in disease by profiling genome-wide methylation changes. This includes both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The typical profiling study is designed to measure 5mC and/or 5hmC levels alongside gene expression in a set of samples and controls to determine a list of candidate genes whose 5mC and/or 5hmC changes are associated with expression changes. We recently showed that ME-Class2 substantially outperforms other bioinformatic approaches at accurately identify genes with highly associated methylation and expression changes. ME-Class2 further illuminated how synergistic changes in 5mC and 5hmC potentially contribute to gene silencing and activation. Here we present a detailed protocol for using ME-Class2 to analyze genome-wide methylation (5mC and/or 5hmC) and expression data. Further, we provide advice about extending ME-Class2 to study the relationships between other epigenetic marks.High-throughput sequencing technologies are increasingly used in molecular cell biology to assess genome-wide chromatin dynamics of proteins bound to DNA, through techniques such as chromatin immunoprecipitation sequencing (ChIP-seq). These techniques often rely on an analysis strategy based on identifying genomic regions with increased sequencing signal to infer the binding location or chemical modifications of proteins bound to DNA. Peak calling within individual samples has been well described, however relatively little attention has been devoted to the merging of replicate samples, and the cross-comparison of many samples. Here, we present a generalized strategy to enable the unification of ChIP-seq datasets, enabling enhanced cross-comparison of binding patterns. The strategy works by merging peak data between different (even unrelated) samples, and then using a local background to recalculate enrichment. This strategy redefines the peaks within each experiment, allowing for more accurate cross-comparison of datasets.DNA methylation plays an important role in the regulation of gene expression as one of the epigenetic modifications. The bisulfite sequencing is widely used to determine the patterns of genomic methylation as a gold standard technology allowing conversion of the unmethylated cytosines to uracils that are represented as Ts in the sequencing reads. This chapter introduces the methodology for analyzing bisulfite sequencing data using various bioinformatics tools.Genome-wide profiling of DNA modifications has advanced our understanding of epigenetics in mammalian biology. Whereas several different methods for profiling DNA modifications have been developed over the last decade, DNA-immunoprecipitation coupled with high-throughput sequencing (DIP-seq) has proven a particularly adaptable and cost-effective approach. DIP-seq was especially valuable in initial studies of the more recently discovered DNA modifications, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine. As an enrichment-based profiling method, analysis of DIP-seq data poses several unique, and often unappreciated bioinformatics challenges, which if unmet, can profoundly affect the results and conclusions drawn from the data. Here, we outline key considerations in both the design of DIP-seq assays and analysis of DIP-seq data to ensure the accuracy and reproducibility of DIP-seq based studies.