Morphological and Molecular Characterization of \u3ci\u3eDiscocriconemella inarata\u3c/i\u3e, an Endemic Nematode from North American Native Tallgrass Prairies

Discocriconemella inarata, a plant parasitic nematode species originally discovered in a virgin tallgrass prairie in northwest Iowa, was re-examined by molecular and morphological analyses of topotype material. This species has never been recorded in cultivated fields and could potentially serve as an indicator for high quality prairie habitats. DNA sequence from a conserved 3’ portion of the 18S ribosomal gene exhibited an identical match between D. inarata topotype specimens and topotype specimens of Mesocriconema xenoplax from Fresno, California. Higher resolution sequence analyses using the internal transcribed spacer 1 (ITS1) and a portion of the mitochondrial gene cytochrome b (cytb) allowed discrimination of D. inarata apart from M. xenoplax. This pair of species formed a well-supported clade with other Mesocriconema species exclusive of tropical Discocriconemella species. Scanning electron microscopy confirmed the absence of submedian lobes on D. inarata, suggesting a secondary loss of this defining morphological characteristic for Mesocriconema. Observations and measurements of D. inarata juveniles were added for the first time. Surveys of other prairies within the Great Plains expanded the known distribution of this species

T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics

‘Targeted’ or ‘biological’ cancer treatments rely on differential gene expression between normal tissue and cancer, and genetic changes that render tumour cells especially sensitive to the agent being applied. Problems exist with the application of many agents as a result of damage to local tissues, tumour evolution and treatment resistance, or through systemic toxicity. Hence, there is a therapeutic need to uncover specific clinical targets which enhance the efficacy of cancer treatment whilst minimising the risk to healthy tissues. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase which plays a role in cell cycle regulation and mitotic progression. As a consequence, TOPK expression is minimal in differentiated cells, although its overexpression is a pathophysiological feature of many tumours. Hence, TOPK has garnered interest as a cancer-specific biomarker and biochemical target with the potential to enhance cancer therapy whilst causing minimal harm to normal tissues. Small molecule inhibitors of TOPK have produced encouraging results as a stand-alone treatment in vitro and in vivo, and are expected to advance into clinical trials in the near future. In this review, we present the current literature pertaining to TOPK as a potential clinical target and describe the progress made in uncovering its role in tumour development. Firstly, we describe the functional role of TOPK as a pro-oncogenic kinase, followed by a discussion of its potential as a target for the treatment of cancers with high-TOPK expression. Next, we provide an overview of the current preclinical progress in TOPK inhibitor discovery and development, with respect to future adaptation for clinical use

The effect of autocorrelation length on the real area of contact and friction behavior of rough surfaces

Autocorrelation length (ACL) is a surface roughness parameter that provides spatial information of surfacetopography that is not included in amplitude parameters such as root-mean-square roughness. This paper presents a relationship between ACL and the friction behavior of a rough surface. The influence of ACL on the peak distribution of a profile is studied based on Whitehouse and Archard’s classical analysis [Whitehouse and ArchardProc. R. Soc. London, Ser. A316, 97 (1970)] and their results are extended to compare profiles from different surfaces. The probability density function of peaks and the mean peak height of a profile are given as functions of its ACL. These results are used to estimate the number of contact points when a rough surface comes into contact with a flat surface, and it is shown that the larger the ACL of the rough surface, the less the number of contact points. Based on Hertzian contact mechanics, it is shown that the real area of contact increases with increasing of number of contact points. Since adhesivefriction force is proportional to the real area of contact, this suggests that the adhesivefriction behavior of a surface will be inversely proportional to its ACL. Results from microscale friction experiments on polished and etchedsiliconsurfaces are presented to verify the analysis

Overexpression of POLQ Confers a Poor Prognosis in Early Breast Cancer Patients

Depletion of POLQ (DNA polymerase theta) has recently been shown to render tumour cells more sensitive to radiotherapy whilst having little or no effect on normal tissues. This finding led us to investigate whether tumours that overexpress POLQ are associated with an adverse outcome. We therefore correlated the clinical outcomes of two retrospective series of patients with early breast cancer with the expression levels of POLQ, as determined by microarray gene expression analysis. We found that a significant number of tumours overexpressed POLQ and that overexpression was correlated with ER negative disease (p=0.047) and high tumour grade (p=0.004), both of which are associated with poor clinical outcomes. POLQ overexpression was associated with poor relapse free survival rates on both univariate (HR 5.80; 95% CI, 2.220 to 15.159; p<0.001) and multivariate analysis (HR 8.086; 95% CI 2.340 to 27.948 p=0.001). Analysis of other published clinical series confirmed that POLQ overexpression is associated with adverse clinical outcomes. The poor prognosis associated with POLQ is independent of other clinical or pathological features. The mechanism that causes this adverse outcome remains to be elucidated but may in part arise from resistance to adjuvant treatment. These findings, combined with the limited normal tissue expression of POLQ, make it a very appealing target for possible clinical exploitation

Aseptically processed and chemically sterilized BTB allografts for anterior cruciate ligament reconstruction: a prospective randomized study.

PURPOSE: To compare the clinical outcomes of bone-patellar tendon-bone (BTB) allografts processed via a novel sterilization system with the traditional aseptically processed BTB allografts for anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 67 patients undergoing ACL reconstruction at 6 independent investigation sites were randomized into one of two intervention groups, BioCleanse-sterilized or aseptic BTB allografts. Inclusion criteria included an acute, isolated, unilateral ACL tear, and exclusion criteria included prior ACL injury, multi-ligament reconstruction, and signs of degenerative joint disease. Post-op examiners and patients were blinded to graft type. Patients were evaluated at 6, 12, and 24 months. Clinical outcomes were compared using the IKDC, a KT-1000 knee arthrometer, level of effusion, and ranges of motion (ROM). RESULTS: After randomization, 24 patients received aseptic BTB allografts and 43 patients received BioCleanse-sterilized allografts. Significant improvement in IKDC scores (P \u3c 0.0001) as well as KT-1000 results (P \u3c 0.0001) was noted over the 24-month period for both groups. IKDC or KT-1000 results were not significantly different between groups at any time point. Active flexion ROM significantly improved from pre-op to 24-month follow-up (P \u3c 0.0001) with no difference between groups at any time point. Active extension ROM did not differ significantly between the two groups. CONCLUSIONS: These results indicate that the sterilization process, BioCleanse, did not demonstrate a statistical difference in clinical outcomes for the BTB allograft at 2 years. The BioCleanse process may provide surgeons with allografts clinically similar to aseptically processed allograft tissue with the benefit of addressing donor-to-recipient disease. LEVEL OF EVIDENCE: II

Correlations of Online Search Engine Trends with Coronavirus Disease (COVID-19) Incidence: Infodemiology Study

Background: The coronavirus disease (COVID-19) is the latest pandemic of the digital age. With the internet harvesting large amounts of data from the general population in real time, public databases such as Google Trends (GT) and the Baidu Index (BI) can be an expedient tool to assist public health efforts. Objective: The aim of this study is to apply digital epidemiology to the current COVID-19 pandemic to determine the utility of providing adjunctive epidemiologic information on outbreaks of this disease and evaluate this methodology in the case of future pandemics. Methods: An epidemiologic time series analysis of online search trends relating to the COVID-19 pandemic was performed from January 9, 2020, to April 6, 2020. BI was used to obtain online search data for China, while GT was used for worldwide data, the countries of Italy and Spain, and the US states of New York and Washington. These data were compared to real-world confirmed cases and deaths of COVID-19. Chronologic patterns were assessed in relation to disease patterns, significant events, and media reports. Results: Worldwide search terms for shortness of breath, anosmia, dysgeusia and ageusia, headache, chest pain, and sneezing had strong correlations (r>0.60, P<.001) to both new daily confirmed cases and deaths from COVID-19. GT COVID-19 (search term) and GT coronavirus (virus) searches predated real-world confirmed cases by 12 days (r=0.85, SD 0.10 and r=0.76, SD 0.09, respectively, P<.001). Searches for symptoms of diarrhea, fever, shortness of breath, cough, nasal obstruction, and rhinorrhea all had a negative lag greater than 1 week compared to new daily cases, while searches for anosmia and dysgeusia peaked worldwide and in China with positive lags of 5 days and 6 weeks, respectively, corresponding with widespread media coverage of these symptoms in COVID-19. Conclusions: This study demonstrates the utility of digital epidemiology in providing helpful surveillance data of disease outbreaks like COVID-19. Although certain online search trends for this disease were influenced by media coverage, many search terms reflected clinical manifestations of the disease and showed strong correlations with real-world cases and deaths

Simulation of Fixed– and Variable–Rate Application of Granular Materials

Research has shown that application errors exist with variable–rate technology (VRT) systems. Consequently, using prescription maps for economic and agronomic analyses can generate misleading results. The intent of this article was to develop and validate a spatial data model for generating “as–applied” maps to support the advancement of precision agriculture practices. Previous research modified ASAE Standard S341.2 to include a 2–D matrix of collection pans to assess fixed–rate and variable–rate (VR) deposition of granular fertilizers and agricultural lime from a spinner disc spreader. The “as–applied” spatial data model uses GIS functionality to generate “as–applied” surfaces by merging distribution patterns and a spatial field application file (FAF) into an “as–applied” surface representing the actual distribution of granular fertilizer or agricultural lime across a field. To validate the “as–applied” spatial data model, field studies were conducted by randomly placing collection pans across two fields. Murate of potash was then applied using a VR spinner spreader. The “as–applied” spatial data model was used to predict the amount of material each pan should have received. Comparisons were made between the actual and predicted application rates for two fields, with R2 values of 0.45 (field A) and 0.58 (field B) computed. However, R2 values of 0.16 (field A) and 0.21 (field B) were observed when comparing the actual application rates and prescription maps. These low R2 values indicated poor application by the spinner spreader but demonstrated that the “as–applied” model did a better job of representing the distribution of murate of potash when contrasted with the prescription maps. “As–applied” surfaces provide a means for evaluating fixed–rate and VR application of granular products while enhancing researchers’ ability to compare VR management approaches