Explore the vast range of titles available.

Accurate diagnosis of osteomyelitis underlying diabetic foot ulcers is essential to optimize outcomes. We undertook a meta-analysis of the accuracy of diagnostic tests for osteomyelitis in diabetic patients with foot ulcers. Pooled sensitivity and specificity, the summary measure of accuracy (Q*), and diagnostic odds ratio were calculated. Exposed bone or probe-to-bone test had a sensitivity of 0.60 and a specificity of 0.91. Plain radiography had a sensitivity of 0.54 and a specificity of 0.68. MRI had a sensitivity of 0.90 and a specificity of 0.79. Bone scan was found to have a sensitivity of 0.81 and a specificity of 0.28. Leukocyte scan was found to have a sensitivity of 0.74 and a specificity of 0.68. The diagnostic odds ratios for clinical examination, radiography, MRI, bone scan, and leukocyte scan were 49.45, 2.84, 24.36, 2.10, and 10.07, respectively. The presence of exposed bone or a positive probe-to-bone test result is moderately predictive of osteomyelitis. MRI is the most accurate imaging test for diagnosis of osteomyelitis.

Background Subfertility decreases the efficiency of the cattle industry because artificial insemination employs spermatozoa from a single bull to inseminate thousands of cows. Variation in bull fertility has been demonstrated even among those animals exhibiting normal sperm numbers, motility, and morphology. Despite advances in research, molecular and cellular mechanisms underlying the causes of low fertility in some bulls have not been fully elucidated. In this study, we investigated the metabolic profile of bull spermatozoa using non-targeted metabolomics. Statistical analysis and bioinformatic tools were employed to evaluate the metabolic profiles high and low fertility groups. Metabolic pathways associated with the sperm metabolome were also reported. Results A total of 22 distinct metabolites were detected in spermatozoa from bulls with high fertility (HF) or low fertility (LF) phenotype. The major metabolite classes of bovine sperm were organic acids/derivatives and fatty acids/conjugates. We demonstrated that the abundance ratios of five sperm metabolites were statistically different between HF and LF groups including gamma-aminobutyric acid (GABA), carbamate, benzoic acid, lactic acid, and palmitic acid. Metabolites with different abundances in HF and LF bulls had also VIP scores of greater than 1.5 and AUC- ROC curves of more than 80%. In addition, four metabolic pathways associated with differential metabolites namely alanine, aspartate and glutamate metabolism, β-alanine metabolism, glycolysis or gluconeogenesis, and pyruvate metabolism were also explored. Conclusions This is the first study aimed at ascertaining the metabolome of spermatozoa from bulls with different fertility phenotype using gas chromatography-mass spectrometry. We identified five metabolites in the two groups of sires and such molecules can be used, in the future, as key indicators of bull fertility.

Inadequate drinking water quality is among the major causes of preventable mortality, predominantly in young children. Identifying contaminated water sources remains a significant challenge, especially where resources are limited. The current methods for measuring Escherichia coli ( E. coli ), the WHO preferred indicator for measuring fecal contamination of water, involve overnight incubation and require specialized training. In 2016, UNICEF released a Target Product Profile (TPP) to incentivize product innovations to detect low levels of viable E. coli in water samples in the field in less than 6 h. Driven by this challenge, we developed a phage-based assay to detect and semi-quantify E. coli . We formulated a phage cocktail containing a total of 8 phages selected against an extensive bacterial strain library and recombined with the sensitive NanoLuc luciferase reporter. The assay was optimized to be processed in a microfluidic chip designed in-house and was tested against locally sourced sewage samples and on drinking water sources in Nairobi, Kenya. With this assay, combined with the microfluidic chip platform, we propose a complete automated solution to detect and semi-quantify E. coli at less than 10 MPN/100 mL in 5.5 h by minimally trained personnel.

T cell scarcity in tumor tissues poses a critical challenge to cancer immunotherapy. Here we manipulate the tumor vasculature, an essential regulator of immune cell trafficking, to reinvigorate anti-tumor T cell responses in “cold” tumors. We show that ectopic pan-endothelial expression of COUP-TFII, a master transcription factor for venous development, induces molecular programs of post-capillary venules in tumor endothelium. Venular reprogramming selectively promotes T cell recruitment into tumors, inhibits tumor growth in mouse models of breast and pancreatic cancers, and sensitizes tumors to immune checkpoint blockade and adoptive T cell transfer therapies. Mechanistic studies show that enhanced recruitment of anti-tumor T cells and tumor inhibition are mediated by COUP-TFII-induced vascular adhesion receptors. Our study supports a pivotal role of vascular endothelial cells in governing tumor immune evasion, and proposes venular reprogramming as a therapeutic strategy to bolster anti-tumor immunity and immunotherapy. The transcription factor COUP-TFII plays a critical role in regulating endothelial cell (EC) identity. Here the authors report that the ectopic expression of COUP-TFII in endothelial cells induces molecular programs of post-capillary venules in tumor EC, associated with enhanced recruitment of anti-tumour T cells, inhibition of tumour growth, and sensitized responses to immune checkpoint blockade and adoptive T cell transfer therapies.

Corrosion of iron presents a serious economic problem. Whereas aerobic corrosion is a chemical process 1 , anaerobic corrosion is frequently linked to the activity of sulphate-reducing bacteria (SRB) 2 , 3 , 4 , 5 , 6 . SRB are supposed to act upon iron primarily by produced hydrogen sulphide as a corrosive agent 3 , 5 , 7 and by consumption of ‘cathodic hydrogen’ formed on iron in contact with water 2 , 3 , 4 , 5 , 6 , 8 . Among SRB, Desulfovibrio species—with their capacity to consume hydrogen effectively—are conventionally regarded as the main culprits of anaerobic corrosion 2 , 3 , 4 , 5 , 6 , 8 , 9 , 10 ; however, the underlying mechanisms are complex and insufficiently understood. Here we describe novel marine, corrosive types of SRB obtained via an isolation approach with metallic iron as the only electron donor. In particular, a Desulfobacterium -like isolate reduced sulphate with metallic iron much faster than conventional hydrogen-scavenging Desulfovibrio species, suggesting that the novel surface-attached cell type obtained electrons from metallic iron in a more direct manner than via free hydrogen. Similarly, a newly isolated Methanobacterium -like archaeon produced methane with iron faster than do known hydrogen-using methanogens, again suggesting a more direct access to electrons from iron than via hydrogen consumption.

The impact of high-frequency fluctuations of temperature on homogeneous nucleation of ice crystals in the vicinity of the tropical tropopause is investigated using a bin microphysics scheme for air parcels. The imposed temperature fluctuations come from measurements during isopycnic balloon flights near the tropical tropopause. The balloons collected data at high frequency, guaranteeing that gravity wave signals are well resolved.With the observed temperature time series, the numerical simulations with homogeneous freezing show a full range of ice number concentration (INC) as previously observed in the tropical upper troposphere. In particular, a low INC may be obtained if the gravity wave perturbations produce a non-persistent cooling rate (even with large magnitude) such that the absolute change in temperature remains small during nucleation. This result is explained analytically by a dependence of the INC on the absolute drop in temperature (and not on the cooling rate). This work suggests that homogeneous ice nucleation is not necessarily inconsistent with observations of low INCs.

This paper explores the attitudes of the ethnic minorities in Cat Tien National Park (CTNP) towards the biodiversity conservation and collaborative management of nature resources. In total, 170 households from six sampled hamlets in the CTNP were interviewed. In-depth interviews carried out using participatory rural appraisal (PRA) method and chi-square test and one-sample t test were used for the analysis. The result showed that the conservation attitudes of the ethnic minorities had significant association with various different socio-economic characteristics. Migration status, participation level and resource-use pattern affected their conservation attitudes (p = 0.000 0.05). Collaborative management practice was closely related to conservation attitudes of the ethnic minorities. Based on the findings, biodiversity conservation strategies in CTNP should put emphasis on migrant ethnic groups, natural resource dependents, and nonparticipants. Besides, group-based arrangements would promote positive attitudes towards conservation and collaborative management. Appropriate institutional strategies for effective biodiversity conservation and sustainable development in CTNP are proposed.

This article presents a novel single-variable-based material interpolation scheme for multi-material density-based topology optimization. In the proposed scheme, no additional variables are needed to deal with the multiple materials, i.e., the number of design variables is independent of the number of material candidates, thus it makes the multi-material topology optimization computationally efficient. Moreover, the proposed interpolation function and its first-order derivative are continuous, which is tractable for gradient-based optimization algorithms. Additionally, we also address some weaknesses of single-variable-based interpolation schemes for multimaterial and tailor a new filtering technique to alleviate them. In the optimization process, the method of moving asymptotes is used with the sensitivity analysis obtained from the adjoint method. The proposed multimaterial interpolation scheme and its dedicated filtering technique are employed to find the materials distribution in different two-dimensional structures such that the compliance is minimized under the mass and cost constraints. The obtained results from our proposed method consistently outperform other state-of-the-art methods available in the literature.

KRAS is a frequent driver in lung cancer. To identify KRAS-specific vulnerabilities in lung cancer, we performed RNAi screens in primary spheroids derived from a Kras mutant mouse lung cancer model and discovered an epigenetic regulator Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). In human lung cancer models UHRF1 knock-out selectively impaired growth and induced apoptosis only in KRAS mutant cells. Genome-wide methylation and gene expression analysis of UHRF1-depleted KRAS mutant cells revealed global DNA hypomethylation leading to upregulation of tumor suppressor genes (TSGs). A focused CRISPR/Cas9 screen validated several of these TSGs as mediators of UHRF1-driven tumorigenesis. In vivo, UHRF1 knock-out inhibited tumor growth of KRAS-driven mouse lung cancer models. Finally, in lung cancer patients high UHRF1 expression is anti-correlated with TSG expression and predicts worse outcomes for patients with KRAS mutant tumors. These results nominate UHRF1 as a KRAS-specific vulnerability and potential target for therapeutic intervention. Identifying KRAS-specific vulnerabilities helps to target KRAS-driven cancer. Here the authors perform RNA interference screens in 3D cultures of primary tumour cells with KRAS activation and p53 loss and identify UHRF1 as a vulnerability of KRAS-mutant lung cancers

Medicare has reinforced its commitment to voluntary bundled payment by building upon the Bundled Payments for Care Improvement (BPCI) initiative via an ongoing successor program, the BPCI Advanced Model. Although lower extremity joint replacement (LEJR) is the highestvolume episode in both BPCI and BPCI Advanced, there is a paucity of independent evidence about its long-term impact on outcomes and about whether improvements vary by timing of participation or arise from patient selection rather than changes in clinical practice. We found that over three years, compared to no participation, participation in BPCI was associated with a 1.6 percent differential decrease in average LEJR episode spending with no differential changes in quality, driven by early participants. Patient selection accounted for 27 percent of episode savings. Our findings have important policy implications in view of BPCI Advanced and its two participation waves.