bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive Features of Thymic Carcinoma and High-Risk Thymomas Using Random Forest Analysis
Authors: Dai Haiyang , Huang Yong , Xiao Gang , Lan Bowen , Jiang Guihua , Tian Junzhang 
Published: January 2020

Purpose
To determine the predictive features of thymic carcinomas and high-risk thymomas using random forest algorithm.

Methods
A total of 137 patients with pathologically confirmed high-risk thymomas and thymic carcinomas were enrolled in this study. Three clinical features and 20 computed tomography features were reviewed. The association between computed tomography features and pathological patterns was analyzed by univariate analysis and random forest. The predictive efficiency of the random forest algorithm was evaluated by receiver operating characteristic curve analysis.

Results
There were 92 thymic carcinomas and 45 high-risk thymomas in this study. In univariate analysis, patient age, presence of myasthenia gravis, lesion shape, enhancement pattern, presence of necrosis or cystic change, mediastinal invasion, vessel invasion, lymphadenopathy, pericardial effusion, and distant organ metastasis were found to be statistically different between high-risk thymomas and thymic carcinomas (all P < 0.01). Random forest suggested that tumor shape, lymphadenopathy, and the presence of pericardial effusion were the key features in tumor differentiation. The predictive accuracy for the test data and whole data was 94.73% and 96.35%, respectively. Further receiver operating characteristic curve analysis showed the area under the curve was 0.957 (95% confidence interval, 0.986–0.929).

Conclusions
The random forest model in the present study has high efficiency in predictive diagnosis of thymic carcinomas and high-risk thymomas. Tumor shape, lymphadenopathy, and pericardial effusion are the key features for tumor differentiation. Thymic tumors with irregular shape, the presence of lymphadenopathy, and pericardial effusion are highly indicative of thymic carcinomas.
Effects of Changes in Analytic Variables and Contrast Material on Measurement of Computed Tomography Glomerular Filtration Rates in Healthy Candidates
Authors: Kim See Hyung 
Published: January 2020

Purpose
This study aimed to prospectively assess the effects of changes in analytic variables and contrast material (CM) osmolality when measuring glomerular filtration rate using computed tomography (CT-GFR).

Methods
One hundred healthy participants were included in this analysis. Glomerular filtration rate was measured by technetium-99m diethylene-triamine-penta-acetic acid (99mTc-DTPA), and each participant underwent CT-GFR with iodinated CM (iohexol 240 or iobitridol 400) following a crossover study design. Dynamic renal CT scanning was performed. Patlak plot analysis was used to calculate GFR, selecting either the renal cortex or the whole kidney as the region of interest. The renal cortex was analyzed just before time of the second cortical attenuation peak. The whole kidney was analyzed 60, 80, 100, and 120 seconds after the appearance of CM. Automated GFR calculations were performed using perfusion software at 2 noise reduction levels (medium and strong). The CT-GFRs were compared with GFR measured by 99mTc-DTPA.

Results
There was no significant difference in CT-GFR with iohexol 240 versus iobitridol 400. The CT-GFR at the renal cortex, for the whole kidney 60 seconds after appearance of CM and calculated by perfusion software with medium noise reduction, did not differ significantly from GFR measured by 99mTc-DTPA. Whole-kidney CT-GFR at ≥80 seconds after CM appearance and CT-GFR calculated using perfusion CT software with strong noise reduction were lower when compared with GFR measured by 99mTc-DTPA.

Conclusion
Results from CT-GFR were most accurate when the kidney cortex was selected as the region of interest or when using 60-second time point for whole-kidney assessment, regardless of CM osmolarity.
Anastomotic Technique and Preoperative Imaging in Microsurgical Lower-Extremity Reconstruction
Authors: Carney Martin J. , Samra Fares , Momeni Arash , Bauder Andrew R. , Weissler Jason M. , Kovach Stephen J. 
Published: January 2020

Background
The need for preoperative imaging as well as anastomotic technique (ie, end-to-side [ETS] vs end-to-end [ETE]) are areas of controversy in microsurgical lower-extremity reconstruction. The objective of this study was to (1) investigate whether preoperative imaging is mandatory and (2) to elicit if the type of anastomosis impacts clinical outcomes.

Methods
A retrospective review of all patients who underwent microvascular lower-extremity reconstruction between 2007 and 2015 by a single surgeon was performed. Patients were categorized into groups based on anastomotic technique, that is, ETE versus ETS anastomosis. Patients in the ETE group were further subclassified into those who had preoperative imaging (computed tomography angiography [CTA]+) versus those who did not (CTA−). Parameters of interest included flap type, thrombosis rate, flap loss, length of stay (LOS), return to ambulation, and rate of secondary amputation. Two-sided statistical analysis was performed using Kruskal-Wallis rank-sum test and Fisher exact test.

Results
One hundred twenty-eight patients were analyzed: ETE (n = 40) and ETS (n = 88). Mean follow-up for both groups was 20 ± 19 months. Anterolateral thigh flaps were most commonly performed (71%). Overall flap loss rate was 3.1% without any significant differences noted with respect to thrombosis (arterial, P = 0.09; venous, P = 0.56), flap loss (P = 0.33), LOS (P = 0.28), amputation (P = 1.00), or return to ambulation (P = 0.77). Furthermore, the availability of preoperative imaging (CTA+: N = 11 vs CTA−: N = 29) did not impact rates of thrombosis (arterial, P = 0.29; venous, P = 0.31), flap loss (P = 1.00), LOS (P = 0.26), or return to mobility (P = 0.62).

Conclusions
In light of similar reconstructive outcomes, we prefer to preserve distal extremity perfusion via ETS anastomoses whenever possible. Furthermore, preoperative vascular imaging angiography might not be necessary in patients with palpable pedal pulses on preoperative examination. An actionable algorithm for determining ETS versus ETE anastomosis in lower-extremity reconstruction is presented.
Turnover modulates the need for a cost of resistance in adaptive therapy
Authors: Strobl Maximilian , West Jeffrey , Viossat Yannick , Damaghi Mehdi , Robertson-Tessi Mark , Brown Joel , Gatenby Robert , Maini Philip , Anderson Alexander 
Published: January 2020

Abstract“Control and conquer” - this is the philosophy behind adaptive therapy, which seeks to exploit intra-tumoural competition to avoid, or at least, delay the emergence of therapy resistance in cancer. Motivated by promising results from theoretical, experimental and, most recently, a clinical study in prostate cancer, there is an increasing interest in extending this approach to other cancers. As such, it is urgent to understand the characteristics of a cancer which determine whether it will respond well to adaptive therapy, or not. A plausible candidate for such a selection criterion is the fitness cost of resistance. In this paper, we study a simple competition model between sensitive & resistant cell populations to investigate whether the presence of a cost is a necessary condition for adaptive therapy to extend the time to progression beyond that of a standard-of-care continuous therapy. We find that for tumours close to their environmental carrying capacity such a cost of resistance is not required. However, for tumours growing far from carrying capacity, a cost may be required to see meaningful gains. Notably, we show that in such cases it is important to consider the cell turnover in the tumour and we discuss its role in modulating the impact of a cost of resistance. Overall, our work helps to clarify under which circumstances adaptive therapy may be beneficial, and suggests that turnover may play an unexpectedly important role in the decision making process.
Spatial and epidemiological drivers of P. falciparum malaria among adults in the Democratic Republic of the Congo
Authors: Deutsch-Feldman Molly , Brazeau Nicholas F. , Parr Jonathan B. , Thwai Kyaw L. , Muwonga Jérémie , Kashamuka Melchior , Tshefu Antoinette K. , Aydemir Ozkan , Bailey Jeffrey A. , Edwards Jessie K. , Verity Robert , Emch Michael , Gower Emily W. , Juliano Jonathan J. , Meshnick Steven R. 
Published: January 2020

AbstractBackgroundMalaria remains a significant public health problem in sub-Saharan Africa. Adults are frequently infected and may serve as a reservoir for further transmission, yet we know relatively little about risk factors for adult infections. In this study, we assessed malaria risk factors amongst adults using samples from the nationally representative, cross-sectional 2013-2014 Demographic and Health Survey (DHS) conducted in the Democratic Republic of Congo (DRC). We further explored differences in risk factors by urbanicity.MethodsPlasmodium falciparum infection was determined by polymerase chain reaction (PCR). Covariates were drawn from the DHS to model individual, community, and environmental level risk factors for infection. Additionally, we used deep sequencing data to estimate the community-level proportions of drug resistant infections and included these estimates as potential risk factors. All identified factors were assessed for differences in associations by urbanicity.ResultsA total of 16,126 adults were included. Overall prevalence of malaria was 30.3% (SE = 1.1) by PCR; province-level prevalence ranged from 6.7-58.3%. Only 17% of individuals lived in households with at least one bednet for every two people, as recommended by the World Health Organization. Protective factors included increasing within-household bednet coverage (PR = 0.85, 95% CI = 0.76 - 0.95) and modern housing (PR = 0.58, 95% CI = 0.49 - 0.69). Community level protective factors included: increased average education and wealth (PR = 0.77, 95% CI = 0.65-0.91; PR - 0.84, 95% CI = 0.80 - 0.89). Education, wealth, and modern housing showed protective associations in cities but not in rural areas.ConclusionsThe DRC continues to suffer from a high burden of malaria; interventions that target high-risk groups and sustained investment in malaria control are sorely needed. Differences in risk factors by urbanicity may be due to differences in transmission intensity or access to resources.
Quantifying the Dynamics of Migration after a Disaster: Impact of Hurricane Maria in Puerto Rico
Authors: Acosta Rolando J. , Kishore Nishant , Irizarry Rafael A. , Buckee Caroline 
Published: January 2020

AbstractPopulation displacement may occur after natural disasters, permanently altering the demographic composition of the affected regions. Measuring this displacement is vital for both optimal post-disaster resource allocation and calculation of measures of public health interest such as mortality estimates. Here, we analyzed data generated by mobile phones and social media to estimate the weekly island-wide population at risk and within-island geographic heterogeneity of migration in Puerto Rico after Hurricane Maria. We compared these two data sources to population estimates derived from air travel records and census data. We observed a loss of population across all data sources throughout the study period, however, the magnitude and dynamics differ by data source. Census data predict a population loss of just over 129,000 from July 17 to July 2018, a 4% decrease; air travel data predicts a population loss of 168,295 for the same period of time, a 5% decrease; mobile phone based estimates predicts a loss of 235,375 form July 2017 to May 2018, an 8% decrease; and social media based estimates predict a loss of 476,779 from August 2017 to August 2018; a 17% decrease. On average, municipalities with smaller population size lost a bigger proportion of their population. Moreover, we infer that these municipalities experienced greater infrastructure damage as measured by the proportion of unknown locations stemming from these regions. Finally, our analysis measures a general shift of population from rural to urban centers within the island.
Detecting substrate glycans of fucosyltransferases on glycoproteins with fluorescent fucose
Authors: Wu Zhengliang L , Whitaker Mark , Person Anthony D , Kalabokis Vassili 
Published: January 2020

AbstractLike sialylation, fucose usually locates at the non-reducing ends of various glycans on glycoproteins and constitutes important glycan epitopes. Detecting the substrate glycans of fucosyltransferases is important for understanding how these glycan epitopes are regulated in response to different growth conditions and external stimuli. Here we report the detection of these glycans via enzymatic incorporation of fluorescent tagged fucose using fucosyltransferases including FUT2, FUT6, FUT7, and FUT8 and FUT9. More specifically, we describe the detection of substrate glycans of FUT8 and FUT9 on therapeutic antibodies and the detection of high mannose glycans on glycoproteins by enzymatic conversion of high mannose glycans to the substrate glycans of FUT8. By establishing a series of precursor glycans, we also demonstrate the substrate specificities of FUT8. Furthermore, using simultaneous enzymatic incorporation of both fluorescent sialic acids and fluorescent fucoses, we demonstrate the interplay between fucosylation and sialylation.
Composition of the North American wood frog (Rana sylvatica) skin microbiome and seasonal variation in community structure
Authors: Douglas Alexander J. , Hug Laura. A. , Katzenback Barbara A. 
Published: January 2020

AbstractWhile a number of amphibian microbiomes have been characterized, it is unclear how microbial communities might vary in response to seasonal changes in the environment and the behaviors which many amphibians exhibit. Given recent studies demonstrating the importance of the skin microbiome in frog innate immune defenses against pathogens, investigating how changes in the environment impact the microbial species present, and thus their potential contribution to skin host defense, will provide a better understanding of conditions that may alter host susceptibility to pathogens in their environment. We sampled the skin microbiome of North American wood frogs (Rana sylvatica) from two breeding ponds in the spring, along with the microbial community present in their vernal breeding pools, and frogs from the nearby forest floor in the summer and fall to determine whether the microbial composition differs by sex, vernal pond site, or temporally across season (spring, summer, fall). Taxon abundance data reveals a profile of bacterial phyla similar to those previously described on anuran skin, with Proteobacteria, Bacteroidetes, and Actinobacteria dominating the wood frog skin microbiome. Our results indicate that sex had no significant effect on skin microbiota diversity, however, this may be due to our limited female sample size. Vernal pool site had a small but significant effect on skin microbiota, but skin-associated communities were more similar to each other than to the communities observed in the frogs’ respective pond water. Across seasons, diversity analyses suggest there are significant differences between the skin microbiome of frogs from spring and summer/fall groups while the average α-diversity per frog remained consistent. Bacterial genera known to have antifungal properties such asPseudomonasspp. andRhizobiumspp. were prevalent, and several were considered core microbiota during at least one season. These results illustrate seasonal variation in wood frog skin microbiome structure and highlight the importance of considering temporal trends in an amphibian microbiome, particularly for species whose life history requires recurrent shifts in habitat and behavior.
KALRNMutations Promote Anti-tumor Immunity and Immunotherapy Response in Cancer
Authors: Li Mengyuan , Ma Yuxiang , Zhong You , Qiang Lei , Wang Xiaosheng 
Published: January 2020

ABSTRACTBackgroundKALRN(kalirin RhoGEF kinase) is mutated in a wide range of cancers. Nevertheless, the association betweenKALRNmutations and the pathogenesis of cancer remains unexplored. The identification of biomarkers for cancer immunotherapy response is important considering that immunotherapies show beneficial effects only in a subset of cancer patients.MethodsWe explored the correlation betweenKALRNmutations and anti-tumor immunity in 10 cancer cohorts from The Cancer Genome Atlas (TCGA) program by the bioinformatics approach. Moreover, we verified the findings from bioinformatics analysis by in vitro experiments. Furthermore, we explored the correlation betweenKALRNmutations and immunotherapy response in four cancer cohorts receiving immune checkpoint blockade therapy.ResultsWe found that anti-tumor immune signatures were stronger inKALRN-mutated than inKALRN-wildtype cancers. Moreover,KALRNmutations correlated with increased tumor mutation burden and the microsatellite instability or DNA damage repair deficiency genomic properties which may explain the elevated anti-tumor immunity inKALRN-mutated cancers. Furthermore, we found that PD-L1 expression was significantly upregulated inKALRN-mutated versusKALRN-wildtype cancers. The enhanced anti-tumor immune signatures and PD-L1 expression inKALRN-mutated cancers may favor the response to immune checkpoint blockade therapy in this cancer subtype, as evidenced in four cancer cohorts receiving anti-PD-1/PD-L1/CTLA-4 immunotherapy. We further revealed that the significant association betweenKALRNmutations and increased anti-tumor immunity was attributed to thatKALRNmutations compromised the function of KALRN target Rho GTPases on regulating DNA damage repair pathways.ConclusionsTheKALRNmutation is a useful biomarker for predicting the response to immunotherapy in cancer patients.
Pharmaceutical-grade Rigosertib is a Microtubule-destabilizing Agent
Authors: Jost Marco , Chen Yuwen , Gilbert Luke A. , Horlbeck Max A. , Krenning Lenno , Menchon Grégory , Rai Ankit , Cho Min Y. , Stern Jacob J. , Prota Andrea E. , Kampmann Martin , Akhmanova Anna , Steinmetz Michel O. , Tanenbaum Marvin E. , Weissman Jonathan S. 
Published: January 2020

SummaryWe recently used CRISPRi/a-based chemical-genetic screens and targeted cell biological, biochemical, and structural assays to determine that rigosertib, an anti-cancer agent in phase III clinical trials, kills cancer cells by destabilizing microtubules. In a recent manuscript, Reddy and co-workers suggest that this microtubule-destabilizing activity of rigosertib is mediated not by rigosertib itself but by a contaminating degradation product of rigosertib, ON01500, present in formulations obtained from commercial vendors (Baker et al., 2019). Here, we demonstrate that treatment of cells with pharmaceutical-grade rigosertib (>99.9% purity) results in qualitatively indistinguishable phenotypes as treatment with commercially obtained rigosertib across multiple assays. The two compounds have indistinguishable chemical-genetic interactions with genes involved in modulating the microtubule network (KIF2CandTACC3), both destabilize microtubules in cells andin vitro, and both show substantially reduced toxicity in cell lines expressing a rationally-designed mutant of tubulin (L240FTUBBmutant), in which the rigosertib binding site in tubulin is mutated. Importantly, the specificity of the L240FTUBBmutant for microtubule-destabilizing agents, which is disputed by Reddy and co-workers, was recently confirmed by an independent research group (Patterson et al., 2019). We conclude that rigosertib kills cancer cells by destabilizing microtubules, in agreement with our original findings.
Horizontal gene transfer in the human and skin commensalMalassezia: a bacterially-derived flavohemoglobin is required for NO resistance and host interaction
Authors: Ianiri Giuseppe , Coelho Marco A. , Ruchti Fiorella , Sparber Florian , McMahon Timothy J. , Fu Ci , Bolejack Madison , Donovan Olivia , Smutney Hayden , Myler Peter , Dietrich Fred , Fox David , LeibundGut-Landmann Salomé , Heitman Joseph 
Published: January 2020

AbstractThe skin of humans and animals is colonized by commensal and pathogenic fungi and bacteria that share this ecological niche and have established microbial interactions.Malasseziaare the most abundant fungal skin inhabitant of warm-blooded animals, and have been implicated in skin diseases and systemic disorders, including Crohn’s disease and pancreatic cancer. Flavohemoglobin is a key enzyme involved in microbial nitrosative stress resistance and nitric oxide degradation. Comparative genomics and phylogenetic analyses within theMalasseziagenus revealed that flavohemoglobin-encoding genes were acquired through independent horizontal gene transfer events from different donor bacteria that are part of the mammalian microbiome. Through targeted gene deletion and functional complementation inM. sympodialis, we demonstrated that bacterially-derived flavohemoglobins are cytoplasmic proteins required for nitric oxide detoxification and nitrosative stress resistance under aerobic conditions. RNAseq analysis revealed that endogenous accumulation of nitric oxide resulted in upregulation of genes involved in stress response, and downregulation of the MalaS7 allergen-encoding genes. Solution of the high-resolution X-ray crystal structure ofMalasseziaflavohemoglobin revealed features conserved with both bacterial and fungal flavohemoglobins.In vivopathogenesis is independent ofMalasseziaflavohemoglobin. Lastly, we identified additional 30 genus- and species-specific horizontal gene transfer candidates that might have contributed to the evolution of this genus as the most common inhabitants of animal skin.Significance statementMalasseziaspecies are the main fungal components of the mammalian skin microbiome and are associated with a number of skin disorders. Recently,Malasseziahas also been found in association with Crohn’s Disease and with pancreatic cancer. The elucidation of the molecular bases of skin adaptation byMalasseziais critical to understand its role as commensal and pathogen. In this study we employed evolutionary, molecular, biochemical, and structural analyses to demonstrate that the bacterially-derived flavohemoglobins acquired byMalasseziathrough horizontal gene transfer resulted in a gain of function critical for nitric oxide detoxification and resistance to nitrosative stress. Our study underscores horizontal gene transfer as an important force modulatingMalasseziaevolution and niche adaptation.
Complete Reconstitution and Deorphanization of the 3 MDa NOCAP (NOCardiosis-Associated Polyketide) Synthase
Authors: Yuet Kai P. , Liu Corey W. , Lynch Stephen R. , Kuo James , Michaels Wesley , Lee Robert B. , McShane Abigail E. , Zhong Brian L. , Fischer Curt R. , Khosla Chaitan 
Published: January 2020

ABSTRACTSeveralNocardiastrains associated with nocardiosis, a potentially life-threatening disease, house a nonamodular assembly-line polyketide synthase (PKS) that presumably synthesizes an unknown natural product. Here, we report the discovery and structure elucidation of the NOCAP (NOCardiosis-Associated Polyketide) aglycone by first fully reconstituting the NOCAP synthasein vitrofrom purified protein components followed by heterologous expression inE. coliand spectroscopic analysis of the purified products. The NOCAP aglycone has an unprecedented structure comprised of a substituted resorcylaldehyde headgroup linked to a 15-carbon tail that harbors two conjugated all-transtrienes separated by a stereogenic hydroxyl group. This report is the first example of reconstituting atrans-acyltransferase assembly-line PKS eitherin vitroor inE. coli, and of using these approaches to “deorphanize” a complete assembly-line PKS identified via genomic sequencing. With the NOCAP aglycone in hand, the stage is set for understanding how this PKS and associated tailoring enzymes confer an advantage to their native hosts during humanNocardiainfections.