Miracle-dz/UniFAR-FTUs huggingface dataset:
A Curated Resource for Phosphosite-specific Signature Analysis*

Pathway analysis of PTM data sets is typically performed at a gene-centric level because of the lack of appropriately curated PTM signature databases. We have developed a PTM signatures database (PTMsigDB) providing curated phosphorylation signatures of kinases, perturbations and signaling pathways to enable site-specific PTM signature enrichment analysis (PTM-SEA). Application of PTM-SEA to phosphoproteomes of several cell lines perturbed with growth factors, cell cycle inhibitors, or a specific PI3K inhibitor demonstrated the potential of our site centric approach to study dysregulated pathways in cancers. Graphical Abstract Highlights Database of PTM site-specific phosphorylation signatures of kinases, perturbations and signaling pathways (PTMsigDB). PTM signature enrichment analysis (PTM-SEA) outperformed gene-centric analysis in detection of EGF induced phospho signaling events. PI3K perturbation signatures were readily detected in PI3Ka inhibited human breast cancer cells. PTMsigDB and PTM-SEA can be freely accessed at https://github.com/broadinstitute/ssGSEA2.0. Signaling pathways are orchestrated by post-translational modifications (PTMs) such as phosphorylation. However, pathway analysis of PTM data sets generated by mass spectrometry (MS)-based proteomics is typically performed at a gene-centric level because of the lack of appropriately curated PTM signature databases and bioinformatic tools that leverage PTM site-specific information. Here we present the first version of PTMsigDB, a database of modification site-specific signatures of perturbations, kinase activities and signaling pathways curated from more than 2,500 publications. We adapted the widely used single sample Gene Set Enrichment Analysis approach to utilize PTMsigDB, enabling PTM Signature Enrichment Analysis (PTM-SEA) of quantitative MS data. We used a well-characterized data set of epidermal growth factor (EGF)-perturbed cancer cells to evaluate our approach and demonstrated better representation of signaling events compared with gene-centric methods. We then applied PTM-SEA to analyze the phosphoproteomes of cancer cells treated with cell-cycle inhibitors and detected mechanism-of-action specific signatures of cell cycle kinases. We also applied our methods to analyze the phosphoproteomes of PI3K-inhibited human breast cancer cells and detected signatures of compounds inhibiting PI3K as well as targets downstream of PI3K (AKT, MAPK/ERK) covering a substantial fraction of the PI3K pathway. PTMsigDB and PTM-SEA can be freely accessed at https://github.com/broadinstitute/ssGSEA2.0.
Fibroblast Growth Factor 23 to Alpha-Klotho Index Correlates with Systemic Sclerosis Activity: A Proposal for Novel Disease Activity Marker

Systemic sclerosis, a connective tissue disease, is characterized by thickening of the skin, massive fibrosis of internal organs, vasculopathy, and immune system functioning aberration. Recently, vitamin D (VD) deficit, seen almost universally in patients with systemic sclerosis (SSc), has gained much attention. VD metabolism is precisely orchestrated at the level of the kidney by regulators: parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) and their receptors with a FGF23 co-receptor—α-Klotho. The aim of this study was to assess the levels of VD, α-Klotho, FGF23 in SSc patients and to find the relationship between those parameters and disease activity. We enrolled 48 SSc patients with a diffuse variant of SSc and 23 sex- and age-matched healthy volunteers that served as the control group (CG). Patients were characterized by lower level of VD in comparison to CG (19.8 (12.6–28.9) vs. 24.5 (21.3–31.5) ng/mL; p < 0.01), significantly reduced levels of iFGF23 (19.3 (12.1–30.5) vs. 73.9 (59.7–110.2) pg/mL p < 0.001), and similar α-Klotho concentrations (1415 ± 557 vs. 1526 ± 397 pg/mL), respective. None of these parameters correlated with the extent of skin involvement (modified Rodnan Skin Score) and disease activity according to Eustar 2017 guidelines. The FGF23/α-Klotho index was significantly reduced in SSc patients (0.013 (0.0081–0.025) vs. 0.055 (0.038–0.095); p < 0.001), and its log10 correlated (r = 0.35; p < 0.001) with disease activity score (Eular2017). Our data showed that the FGF23/α-Klotho index may be considered as a novel, potential marker of systemic sclerosis activity.
Randomized Controlled Trial Evaluating Aerobic Training and Common Sport-Related Concussion Outcomes in Healthy Participants.

CONTEXT Aerobic exercise interventions are increasingly being prescribed for concussion rehabilitation, but whether aerobic training protocols influence clinical concussion diagnosis and management assessments is unknown. OBJECTIVE To investigate the effects of a brief aerobic exercise intervention on clinical concussion outcomes in healthy, active participants. DESIGN Randomized controlled clinical trial. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS Healthy (uninjured) participants (n = 40) who exercised ≥3 times/week. INTERVENTION(S) Participants were randomized into the acute concussion therapy intervention (ACTIVE) training or nontraining group. All participants completed symptom, cognitive, balance, and vision assessments during 2 test sessions approximately 14 days apart. Participants randomized to ACTIVE training completed six 30-minute exercise sessions that progressed from 60% to 80% of individualized maximal oxygen consumption (V˙o2max) across test sessions, while the nontraining group received no intervention. MAIN OUTCOME MEASURE(S) The CNS Vital Signs standardized scores, Vestibular/Ocular Motor Screening near-point convergence distance (cm), and Graded Symptom Checklist, Balance Error Scoring System, and Standardized Assessment of Concussion total scores. RESULTS An interaction effect was found for total symptom score ( P = .01); the intervention group had improved symptom scores between sessions (session 1: 5.1 ± 5.8; session 2: 1.9 ± 3.6). Cognitive flexibility, executive functioning, reasoning, and total symptom score outcomes were better but composite memory, verbal memory, and near-point convergence distance scores were worse at the second session (all P values < .05). However, few changes exceeded the 80% reliable change indices calculated for this study, and effect sizes were generally small to negligible. CONCLUSIONS A brief aerobic training protocol had few meaningful effects on clinical concussion assessment in healthy participants, suggesting that current concussion-diagnostic and -assessment tools remain clinically stable in response to aerobic exercise training. This provides normative data for future researchers, who should further evaluate the effect of ACTIVE training on clinical outcomes among concussed populations. TRIAL REGISTRATION NUMBER ClinicalTrials.gov : NCT02872480.
Extended Oral Antibiotic Prophylaxis in High-Risk Patients Substantially Reduces Primary Total Hip and Knee Arthroplasty 90-Day Infection Rate

Background: Total joint arthroplasty (TJA) episodic payment models shift risk and cost of periprosthetic joint infection (PJI) to surgeons and hospitals, causing some to avoid treating high-risk patients. Furthermore, there are little data to support optimization of host factors preoperatively to decrease PJI, and recent literature supports using extended antibiotic prophylaxis following reimplantation TJA. The purpose of this study was to evaluate whether extended oral antibiotic prophylaxis minimized PJI after primary TJA in high-risk patients. Methods: A retrospective cohort study was performed of 2,181 primary total knee arthroplasties (TKAs) and primary total hip arthroplasties (THAs) carried out from 2011 through 2016 at a suburban academic hospital with modern perioperative and infection-prevention protocols. Beginning in January 2015, extended oral antibiotic prophylaxis for 7 days after discharge was implemented for patients at high risk for PJI. The percentages of patients diagnosed with PJI within 90 days were identified and compared between groups that did and did not receive extended oral antibiotic prophylaxis, with p ⩽ 0.05 indicating significance. Results: The 90-day infection rates were 1.0% and 2.2% after the TKAs and THAs, respectively. High-risk patients without extended antibiotic prophylaxis were 4.9 (p = 0.009) and 4.0 (p = 0.037) times more likely to develop PJI after TKA and THA, respectively, than high-risk patients with extended antibiotic prophylaxis. Conclusions: Extended postoperative antibiotic prophylaxis led to a statistically significant and clinically meaningful reduction in the 90-day infection rate of selected patients at high risk for infection. We encourage further study and deliberation prior to adoption of a protocol involving extended oral antibiotic prophylaxis after high-risk TJA, with the benefits weighed appropriately against potential adverse consequences such as increasing the development of antimicrobial resistance. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Farmers’ preferred tree species and their potential carbon stocks in southern Burkina Faso: Implications for biocarbon initiatives

The success of terrestrial carbon sequestration projects for rural development in sub-Saharan Africa lies in the (i) involvement of local populations in the selection of woody species, which represent the biological assets they use to meet their daily needs, and (ii) information about the potential of these species to store carbon. Although the latter is a key prerequisite, there is very little information available. To help fill this gap, the present study was undertaken in four pilot villages (Kou, Dao, Vrassan and Cassou) in Ziro Province, south-central Burkina Faso. The objective was to determine carbon storage potential for top-priority woody species preferred by local smallholders. We used (i) participatory rural appraisal consisting of group discussions and key informant interviews to identify priority species and functions, and (ii) landscape assessment of carbon stocks in the preferred woody species. Results revealed 79 priority tree and shrub species grouped into six functions, of which medicine, food and income emerge as the most important ones for the communities. For these functions, smallholders overwhelmingly listed Vitellaria paradoxa, Parkia biglobosa, Afzelia africana, Adansonia digitata, Detarium microcarpum, and Lannea microcarpa among the most important tree species. Among the preferred woody species in Cassou and Kou, the highest quantity of carbon was stored by V. paradoxa (1180 ±209 kg C ha-1 to 2089±522 kg C ha-1) and the lowest by Grewia bicolor (5±1.2 kg C ha-1). The potential carbon stored by the preferred tree communities was estimated at 587.9 Mg C ha-1 (95% CI: 456.7; 719.1 Mg C ha-1) in Kou and256.8 Mg C ha-1 (95% CI: 67.6; 324.4 Mg C ha-1) in Cassou. The study showed that the species that farmers preferred most stored more carbon than species that were less preferred.
Abandoned Object Detection in Video-Surveillance: Survey and Comparison

During the last few years, abandoned object detection has emerged as a hot topic in the video-surveillance community. As a consequence, a myriad of systems has been proposed for automatic monitoring of public and private places, while addressing several challenges affecting detection performance. Due to the complexity of these systems, researchers often address independently the different analysis stages such as foreground segmentation, stationary object detection, and abandonment validation. Despite the improvements achieved for each stage, the advances are rarely applied to the full pipeline, and therefore, the impact of each stage of improvement on the overall system performance has not been studied. In this paper, we formalize the framework employed by systems for abandoned object detection and provide an extensive review of state-of-the-art approaches for each stage. We also build a multi-configuration system allowing one to select a range of alternatives for each stage with the objective of determining the combination achieving the best performance. This multi-configuration is made available online to the research community. We perform an extensive evaluation by gathering a heterogeneous dataset from existing data. Such a dataset allows considering multiple and different scenarios, whereas presenting various challenges such as illumination changes, shadows, and a high density of moving objects, unlike existing literature focusing on a few sequences. The experimental results identify the most effective configurations and highlight design choices favoring robustness to errors. Moreover, we validated such an optimal configuration on additional datasets not previously considered. We conclude the paper by discussing open research challenges arising from the experimental comparison.
Tuberculosis Mortality by Occupation in South Africa, 2011–2015

Work-related tuberculosis (TB) remains a public health concern in low- and middle-income countries. The use of vital registration data for monitoring TB deaths by occupation has been unexplored in South Africa. Using underlying cause of death and occupation data for 2011 to 2015 from Statistics South Africa, age-standardised mortality rates (ASMRs) were calculated for all persons of working age (15 to 64 years) by the direct method using the World Health Organization (WHO) standard population. Multivariate logistic regression analysis was performed to calculate mortality odds ratios (MORs) for occupation groups, adjusting for age, sex, year of death, province of death, and smoking status. Of the 221,058 deaths recorded with occupation data, 13% were due to TB. ASMR for TB mortality decreased from 165.9 to 88.8 per 100,000 population from 2011 to 2015. An increased risk of death by TB was observed among elementary occupations: agricultural labourers (MORadj = 3.58, 95% Confidence Interval (CI) 2.96–4.32), cleaners (MORadj = 3.44, 95% CI 2.91–4.09), and refuse workers (MORadj = 3.41, 95% CI 2.88–4.03); among workers exposed to silica dust (MORadj = 3.37, 95% CI 2.83–4.02); and among skilled agricultural workers (MORadj = 3.31, 95% CI 2.65–4.19). High-risk TB occupations can be identified from mortality data. Therefore, TB prevention and treatment policies should be prioritised in these occupations.
Point Spread Function Reconstruction for Integrated 18F-FET PET/MRI in Patients With Glioma: Does It Affect SUVs and Respective Tumor-to-Background Ratios?

Purpose Semiquantitative 18F-FET PET assessment using the tumor's SUV or tumor-to-background ratios (TBRs) can separate gliomas from peritumoral tissue or progression from pseudoprogression. This study investigated if point spread function (PSF) reconstruction of 18F-FET PET data affects SUV-based dignity assessment. Materials and Methods This study is a retrospective analysis of 87 glioma patients (female, 36; male, 51; age, 48 [13–81] years) undergoing 18F-FET PET/MRI for staging (n = 17) or restaging (n = 70). PET was reconstructed using ordered-subset expectation maximization with and without PSF. Lesions were delineated with semiautomated background-adapted thresholding relative to SUVmax; background was delineated contralaterally. Comparative measurements with a National Electrical Manufacturers Association International Electrotechnical Commission PET body phantom (sphere-to-background ratios, 8:1 and 4:1) were performed. Results PSF showed significantly higher tumor SUVmax (median difference, +0.1; interquartile range, 0.04–0.18), SUVmean (+0.05; 0.03–0.08), TBRmax|mean (+0.1; 0.04–0.2), and TBRmean|mean (+0.06; 0.03–0.09) than non-PSF (P < 0.001). Background SUVmean was unaffected. In patients and phantom, differences between PSF and non-PSF increased with TBR and decreased with lesion's PET volume. Differences only exceeded 0.2 SUV for SUVmax or 0.1 SUV for SUVmean if TBR was greater than 3 and lesion's PET volume was less than 10 mL (d = 27 mm). Dignity assessment by PSF and non-PSF was concordant in all patients examined for staging (cutoff, TBRmean|mean > 1.6; positive, 14; negative, 3) and restaging (cutoff, TBRmax|mean > 2.0; positive, 67; negative, 3). Conclusions PSF increased tumor SUVmax and SUVmean compared with non-PSF 18F-FET PET/MRI data, especially in small lesions with high TBR (>3). However, dignity assessment using established TBR cutoffs was not affected.
Association between Colorectal Adenoma and Carotid Atherosclerosis in Korean Adults

Background: Colorectal neoplasm, including colorectal adenoma, is associated with old age, cigarette smoking, and the presence of metabolic syndromes. These are also risk factors for cardiovascular disease. Carotid ultrasonography is a noninvasive test that can predict the risk of cardiovascular disease and may be another test that may provide indications of these risk factors. This study aimed to investigate the association between colorectal adenomatous polyps and carotid atherosclerosis. Methods: This study included 548 adults who underwent colonoscopy and carotid ultrasonography for a health examination between March 2013 and December 2017 at a university hospital in South Korea. Abnormal carotid sonography findings included either increased carotid intima-media thickness or presence of carotid plaques. Results: The proportion of subjects with overall colorectal adenomatous polyps was 31.0% (170/548). Colorectal adenoma was more prevalent in the presence of abnormal carotid ultrasonography findings (38.6% vs. 27.6%, p = 0.013). Colorectal adenomatous polyp was significantly associated with abnormal carotid ultrasonography findings (OR = 1.65; 95% CI, 1.12–2.42, p = 0.011) in a multivariate analysis after adjusting for age, sex, cigarette smoking, alcohol consumption, and presence of metabolic syndrome. Conclusion: Colorectal adenoma is significantly associated with carotid atherosclerosis.
Seston Fatty Acid Responses to Physicochemical Changes in Subalpine Lake Lunz, Austria

Rapid increase in lake temperature can cause a shift toward the dominance of warm temperature tolerant species, including Cyanobacteria that are deficient in polyunsaturated fatty acids (PUFA) supporting consumer growth and reproduction. To increase our understanding of how changes in physicochemical lake parameters affect phytoplankton composition and the provision of dietary quality to consumers in subalpine oligotrophic lakes, we conducted a multiannual study (2013–2015) in the 34‐m‐deep Lake Lunz and investigated interannual changes in (a) water temperature, transparency, and lake inflow; (b) seston (<30‐μm particle size class) biomass and taxonomy; and (c) seston nutritional quality, assessed by its PUFA composition. The phytoplankton taxonomic composition within this seston size class varied mostly by changes in physical parameters (temperature, conductivity, lake transparency, and days of full ice cover). The dietary quality of seston varied mostly with lake physical parameters and, to a lesser extent, with phytoplankton taxonomic composition, suggesting that the nutritional quality at the base of the food web in Lake Lunz is likely to respond directly to changes in lake physical parameters. This multiannual data set, combining monthly values for physicochemical variables, grazable phytoplankton composition, and fatty acids in seston, provides nutritional information of how annual weather changes may induce changes at the base of the food web in this and perhaps also other oligotrophic subalpine lakes.
Larger Food Portion Sizes Are Associated with Both Positive and Negative Markers of Dietary Quality in Irish Adults

Reduction in portion size, particularly for energy-dense foods, is increasingly addressed in healthy eating guidelines in a bid to tackle the obesity epidemic. The effect of portion size on other aspects of dietary quality, such as nutrient intakes, is less studied. The aim of the current work was to investigate associations between food portion sizes and key indicators of dietary quality, namely energy-adjusted intakes of saturated fat, dietary fibre, sodium, calcium, iron, folate and vitamin D, and dietary energy density (DED), in Irish adults on the days the foods were consumed. Data from the Irish National Adult Nutrition Survey (2008–2010) (n = 1274, 18–64 years, 4-day semi-weighed record) were used for the analysis. DED was lower on the days larger portions of boiled potatoes, fruit, vegetables and baked beans were consumed, and higher on the days larger portions of white bread, ready-to-eat breakfast cereals (RTEBCs), frying meats, cheese, butter, biscuits, chocolate and sugar-sweetened beverages were consumed. Micronutrient intakes were higher on the days larger portions of brown bread, RTEBCs, vegetables and low-fat spreads were consumed, and lower on the days larger portions of white bread, butter, biscuits, chocolate, sugar-sweetened beverages and beer/cider were consumed, with the exception of folate. The study identifies foods for which larger portion sizes may be associated with positive dietary attributes, as well as the opposite. It provides an important evidence base from which more specific dietary guidance on food portion sizes might be developed for Irish adults.
tRNA-Derived Small RNAs: Biogenesis, Modification, Function and Potential Impact on Human Disease Development

Transfer RNAs (tRNAs) are abundant small non-coding RNAs that are crucially important for decoding genetic information. Besides fulfilling canonical roles as adaptor molecules during protein synthesis, tRNAs are also the source of a heterogeneous class of small RNAs, tRNA-derived small RNAs (tsRNAs). Occurrence and the relatively high abundance of tsRNAs has been noted in many high-throughput sequencing data sets, leading to largely correlative assumptions about their potential as biologically active entities. tRNAs are also the most modified RNAs in any cell type. Mutations in tRNA biogenesis factors including tRNA modification enzymes correlate with a variety of human disease syndromes. However, whether it is the lack of tRNAs or the activity of functionally relevant tsRNAs that are causative for human disease development remains to be elucidated. Here, we review the current knowledge in regard to tsRNAs biogenesis, including the impact of RNA modifications on tRNA stability and discuss the existing experimental evidence in support for the seemingly large functional spectrum being proposed for tsRNAs. We also argue that improved methodology allowing exact quantification and specific manipulation of tsRNAs will be necessary before developing these small RNAs into diagnostic biomarkers and when aiming to harness them for therapeutic purposes.