Miracle-dz/UniFAR-FTUs huggingface dataset:
Bayesian Weighted Sums: A Flexible Approach to Estimate Summed Mixture Effects

Objectives: Methods exist to study exposure mixtures, but each is distinct in the research question it aims to address. We propose a new approach focused on estimating both the summed effect and individual weights of one or multiple exposure mixtures: Bayesian Weighted Sums (BWS). Methods: We applied BWS to simulated and real datasets with correlated exposures. The analytic context in our real-world example is an estimation of the association between polybrominated diphenyl ether (PBDE) congeners (28, 47, 99, 100, and 153) and Autism Spectrum Disorder (ASD) diagnosis and Social Responsiveness Scores (SRS). Results: Simulations demonstrate that BWS performs reliably. In adjusted models using Early Autism Risk Longitudinal Investigation (EARLI) data, the odds of ASD for a 1-unit increase in the weighted sum of PBDEs were 1.41 (95% highest posterior density 0.82, 2.50) times the odds of ASD for the unexposed and the change in z-score standardized SRS per 1 unit increase in the weighted sum of PBDEs is 0.15 (95% highest posterior density −0.08, 0.38). Conclusions: BWS provides a means of estimating the summed effect and weights for individual components of a mixture. This approach is distinct from other exposure mixture tools. BWS may be more flexible than existing approaches and can be specified to allow multiple exposure groups based on a priori knowledge from epidemiology or toxicology.
Measurable residual disease in elderly acute myeloid leukemia: results from the PETHEMA-FLUGAZA phase 3 clinical trial.

The value of measurable residual disease (MRD) in elderly patients with acute myeloid leukemia (AML) is inconsistent between those treated with intensive vs hypomethylating drugs, and unknown after semi-intensive therapy. We investigated the role of MRD in refining complete remission (CR) and treatment duration in the phase 3 FLUGAZA clinical trial, which randomized 283 elderly AML patients to induction and consolidation with fludarabine plus cytarabine (FLUGA) vs 5-azacitidine. After consolidation, patients continued treatment if MRD was ≥0.01% or stopped if MRD was <0.01%, as assessed by multidimensional flow cytometry (MFC). On multivariate analysis including genetic risk and treatment arm, MRD status in patients achieving CR (N = 72) was the only independent prognostic factor for relapse-free survival (RFS) (HR, 3.45; P = .002). Achieving undetectable MRD significantly improved RFS of patients with adverse genetics (HR, 0.32; P = .013). Longer overall survival was observed in patients with undetectable MRD after induction though not after consolidation. Although leukemic cells from most patients displayed phenotypic aberrancies vs their normal counterpart (N = 259 of 265), CD34 progenitors from cases with undetectable MRD by MFC carried extensive genetic abnormalities identified by whole-exome sequencing. Interestingly, the number of genetic alterations significantly increased from diagnosis to MRD stages in patients treated with FLUGA vs 5-azacitidine (2.2-fold vs 1.1-fold; P = .001). This study supports MRD assessment to refine CR after semi-intensive therapy or hypomethylating agents, but unveils that improved sensitivity is warranted to individualize treatment and prolong survival of elderly AML patients achieving undetectable MRD.
Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation

The SARS-CoV-2 coronavirus responsible for the global pandemic contains a unique furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation. Here, we show that O-glycosylation near the furin cleavage site is mediated by specific members of the GALNT enzyme family and is dependent on the novel proline at position 681 (P681). We further demonstrate that O-glycosylation of S decreases furin cleavage. Finally, we show that GALNT family members capable of glycosylating S are expressed in human respiratory cells that are targets for SARS-CoV-2 infection. Our results suggest that O-glycosylation may influence viral infectivity/tropism by modulating furin cleavage of S and provide mechanistic insight into the potential role of P681 mutations in the recently identified, highly transmissible B.1. 1.7 variant.
Impact of Pleistocene Eustatic Fluctuations on Evolutionary Dynamics in Southeast Asian Biodiversity Hotspots.

Pleistocene Climatic Fluctuations (PCF) are frequently highlighted as important evolutionary engines that triggered cycles of biome expansion and contraction. While there is ample evidence of the impact of PCF on biodiversity of continental biomes, the consequences in insular systems depend on the geology of the islands and the ecology of the taxa inhabiting them. The idiosyncratic aspects of insular systems are exemplified by the islands of the Sunda Shelf in Southeast Asia (Sundaland), where PCF-induced eustatic fluctuations had complex interactions with the geology of the region, resulting in high species diversity and endemism. Emergent land in Southeast Asia varied drastically with sea level fluctuations during the Pleistocene. Climate-induced fluctuations in sea level caused temporary connections between insular and continental biodiversity hotspots in Southeast Asia. These exposed lands likely had freshwater drainage systems that extended between modern islands: the Paleoriver Hypothesis. Built upon the assumption that aquatic organisms are among the most suitable models to trace ancient river boundaries and fluctuations of landmass coverage, the present study aims to examine the evolutionary consequences of PCF on the dispersal of freshwater biodiversity in Southeast Asia. Time-calibrated phylogenies of DNA-delimited species were inferred for six species-rich freshwater fish genera in Southeast Asia (Clarias, Channa, Glyptothorax, Hemirhamphodon, Dermogenys, Nomorhamphus). The results highlight rampant cryptic diversity and the temporal localization of most speciation events during the Pleistocene, with 88% of speciation events occurring during this period. Diversification analyses indicate that sea level-dependent diversification models poorly account for species proliferation patterns for all clades excepting Channa. Ancestral area estimations point to Borneo as the most likely origin for most lineages, with two waves of dispersal to Sumatra and Java during the last 5 Myr. Speciation events are more frequently associated with boundaries of the paleoriver watersheds, with 60%, than islands boundaries, with 40%. In total, one-third of speciation events are inferred to have occured within paleorivers on a single island, suggesting that habitat heterogeneity and factors other than allopatry between islands substantially affected diversification of Sundaland fishes. Our results suggest that species proliferation in Sundaland is not wholly reliant on Pleistocene sea-level fluctuations isolating populations on different islands.
Trauma patients at risk for venous thromboembolism who undergo routine duplex ultrasound screening experience fewer pulmonary emboli: A prospective randomized trial

Supplemental digital content is available in the text. BACKGROUND Although guidelines are established for the prevention and management of venous thromboembolism (VTE) in trauma, no consensus exists regarding protocols for the diagnostic approach. We hypothesized that at-risk trauma patients who undergo duplex ultrasound (DUS) surveillance for lower extremity deep venous thrombosis (DVT) will have a lower rate of symptomatic or fatal pulmonary embolism (PE) than those who do not undergo routine surveillance. METHODS Prospective, randomized trial between March 2017 and September 2019 of trauma patients admitted to a single, level 1 trauma center, with a risk assessment profile score of ≥5. Patients were randomized to receive either bilateral lower extremity DUS surveillance on days 1, 3, and 7 and weekly during hospitalization ultrasound group (US) or no surveillance no ultrasound group (NoUS). Rates of in-hospital and 90-day DVT and PE were reported as was DVT propagation and all-cause mortality. Standard care for the prevention and management of VTE per established institutional protocols was provided to all patients. RESULTS A total of 3,236 trauma service admissions were screened, and 1,989 moderate- and high-risk patients were randomized (US, 995; NoUS, 994). The mean ± SD age was 62 ± 20.1 years, Injury Severity Score was 14 ± 9.7, risk assessment profile was 7.1 ± 2.4, and 97% suffered blunt trauma. There was no difference in demographics or VTE risk factors between the groups. There were significantly fewer in-hospital PE in the US group than the NoUS group (1 [0.1%] vs. 9 [0.9%], p = 0.01). The US group experienced more in-hospital below-knee DVTs (124 [12.5%] vs. 8 [0.8%], p < 0.001) and above-knee DVTs (19 [1.9%] vs. 8 [0.8%], p = 0.05). There was no difference in 90-day PE or DVT, or overall mortality. CONCLUSION The implementation of a selective routine DUS protocol was associated with significantly fewer in-hospital PE. More DVTs were identified with routine screening; however, surveillance bias appears to exist primarily with distal DVT. Larger trials are needed to further characterize the relationship between routine DUS screening and VTE outcomes in the high-risk trauma population. LEVEL OF EVIDENCE Therapeutic/care management, level II.
Comparison of the ATRIA, CHA2DS2-VASc, and Modified Scores ATRIA-HSV, CHA2DS2-VASc-HS, for the Prediction of Coronary Artery Disease Severity

Many parameters included in the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex category) scores also predict coronary artery disease (CAD). We modified the ATRIA score (ATRIA-HSV) by adding hyperlipidemia, smoking, and vascular disease and also male sex instead of female. We evaluated whether the CHA2DS2-VASc, CHA2DS2-VASc-HS, ATRIA, and ATRIA-HSV scores predict severe CAD. Consecutive patients with coronary angiography were prospectively included. A ≥50% stenosis in ≥1epicardial coronary artery (CA) was defined as severe CAD. Patient with normal CA (n = 210) were defined as group 1, with <50% CA stenosis (n = 178) as group 2, and with ≥50% stenosis (n = 297) as group 3. The mean ATRIA, ATRIA-HSV, CHA2DS2-VASc, and CHA2DS2VASc-HS scores increased from group 1 to group 3. A correlation was found between the Synergy between PCI with Taxus and Cardiac Surgery score and ATRIA (r = 0.570), ATRIA-HSV (r = 0.614), CHA2DS2-VASc (r = 0.428), and CHA2DS2-VASc-HS (r = 0.500) scores (Ps < .005). Pairwise comparisons of receiver operating characteristics curves showed that ATRIA-HSV (>3 area under curve [AUC]: 0.874) and ATRIA (>3, AUC: 0.854) have a better performance than CHA2DS2-VASc (>1, AUC: 0.746) and CHA2DS2-VASc-HS (>2, AUC: 0.769). In conclusion, the ATRIA and ATRIA-HSV scores are simple and may be useful to predict severe CAD.
Vertical decoupling of soil nutrients and water under climate warming reduces plant cumulative nutrient uptake, water use efficiency and productivity.

Warming-induced desiccation of the fertile topsoil layer could lead to decreased nutrient diffusion, mobility, mineralization and uptake by roots. Increased vertical decoupling between nutrients in topsoil and water availability in subsoil/bedrock layers under warming could thereby reduce cumulative nutrient uptake over the growing season. We used a Mediterranean semiarid shrubland as model system to assess the impacts of warming-induced topsoil desiccation on plant water and nutrient use patterns. A 6-year manipulative field experiment examined the effects of warming (2.5 ºC), rainfall reduction (30%) and their combination on soil resource utilization by Helianthemum squamatum shrubs. A drier fertile topsoil ("growth pool") under warming led to greater proportional utilization of water from deeper, wetter, but less fertile subsoil/bedrock layers ("maintenance pool") by plants. This was linked to decreased cumulative nutrient uptake, increased non-stomatal (nutritional) limitation of photosynthesis and reduced water use efficiency, aboveground biomass growth and drought survival. Whereas a shift to greater utilization of water stored in deep subsoil/bedrock may buffer the negative impact of warming-induced topsoil desiccation on transpiration, this plastic response cannot compensate for the associated reduction in cumulative nutrient uptake and carbon assimilation, which may compromise the capacity of plants to adjust to a warmer and drier climate.
Traceable Reference Full Metrology Chain for Innovative Aspheric and Freeform Optical Surfaces Accurate at the Nanometer Level

The design of innovative reference aspheric and freeform optical elements was investigated with the aim of calibration and verification of ultra-high accurate measurement systems. The verification is dedicated to form error analysis of aspherical and freeform optical surfaces based on minimum zone fitting. Two thermo-invariant material measures were designed, manufactured using a magnetorheological finishing process and selected for the evaluation of a number of ultra-high-precision measurement machines. All collected data sets were analysed using the implemented robust reference minimum zone (Hybrid Trust Region) fitting algorithm to extract the values of form error. Agreement among the results of several partners was observed, which demonstrates the establishment of a traceable reference full metrology chain for aspherical and freeform optical surfaces with small amplitudes.
Determination of the Chemical, Physical and Mechanical Characteristics of Electric Arc Furnace Slags and Environmental Evaluation of the Process for Their Utilization as an Aggregate in Bituminous Mixtures

Road construction is an activity that demands a significant amount of aggregates for bituminous mixtures. In addition, these aggregates must be of a suitable quality for use, even more so on high traffic roads. In response to this problem, and in order to avoid the extraction of new raw materials, research is being carried out using industrial waste as a substitute for conventional aggregates. In this way, the extraction of raw materials is reduced and landfilling of waste is avoided. However, these wastes must have certain properties and environmental advantages over natural aggregates. Otherwise, the use of waste would not be environmentally beneficial but would be more damaging to the environment. For this reason, this research evaluates the viability of using electric arc furnace slag as aggregates for bituminous mixtures, the main objectives being the determination of the characteristics of the by-product, the particularities and the critical points to be taken into account for its subsequent use in mixtures. At the same time, the environmental advantages of treating this waste to obtain a usable aggregate are evaluated in comparison with the processing of a natural aggregate. The results showed that electric arc furnace slags have a suitable chemical composition and excellent physical and mechanical properties for use in bituminous mixtures, even on high traffic roads. At the same time, it was determined that their use produces a considerable reduction in environmental afflictions. Therefore, it could be affirmed that the use of electric arc furnace slags in bituminous mixtures is recommendable as a way to develop more sustainable materials for construction.
Discovery of a macromolecular complex mediating the hunger suppressive actions of cocaine: Structural and functional properties

Cocaine not only increases brain dopamine levels but also activates the sigma1 receptor (σ1R) that in turn regulates orexigenic receptor function. Identification of interactions involving dopamine D1 (D1R), ghrelin (GHS‐R1a), and σ1 receptors have been addressed by biophysical techniques and a complementation approach using interfering peptides. The effect of cocaine on receptor functionality was assayed by measuring second messenger, cAMP and Ca2+, levels. The effect of acute or chronic cocaine administration on receptor complex expression was assayed by in situ proximity ligation assay. In silico procedures were used for molecular model building. σ1R KO mice were used for confirming involvement of this receptor. Upon identification of protomer interaction and receptor functionality, a unique structural model for the macromolecular complex formed by σ1R, D1R, and GHS‐R1a is proposed. The functionality of the complex, able to couple to both Gs and Gq proteins, is affected by cocaine binding to the σ1R, as confirmed using samples from σ1R−/− mice. The expression of the macromolecular complex was differentially affected upon acute and chronic cocaine administration to rats. The constructed 3D model is consistent with biochemical, biophysical, and available structural data. The σ1R, D1R, and GHS‐R1a complex constitutes a functional unit that is altered upon cocaine binding to the σ1R. Remarkably, the heteromer can simultaneously couple to two G proteins, thus allowing dopamine to signal via Ca2+ and ghrelin via cAMP. The anorexic action of cocaine is mediated by such complex whose expression is higher after acute than after chronic administration regimens.
Clinical characteristics and risk factors for mortality in patients with coronavirus disease 2019 in intensive care unit: a single- center, retrospective, observational study in China.

BACKGROUND Coronavirus disease 2019 (COVID-19) is a potentially life-threatening contagious disease which has spread all over the world. Risk factors associated with the clinical outcomes of COVID-19 pneumonia in intensive care unit (ICU) have not yet been well determined. METHODS This was a retrospective, single-centered, observational study, in which 47 patients with confirmed COVID-19 were consecutively enrolled from February 24 to April 5, 2020. The patients were registered from the ICU of Leishenshan Hospital in Wuhan, China. Clinical characteristics and outcomes were collected and compared between survivors and non-survivors. Multivariable logistic regression was performed to analyze the risk factors of death in patients with COVID-19. RESULTS The study cohort included 47 adult patients with an average age of 70.55±12.52 years, and 30 (63.8%) patients were men. Totally 15 (31.9%) patients died. When compared to survivors, nonsurvivors showed a higher proportion of septic shock [6 (40%) patients vs. 3 (9.4%) patients], disseminated intravascular coagulation [3 (21.4%) vs. 0], and had higher score of APACHE II (25.07±8.03 vs. 15.56±5.95), CURB-65 {3 [2-4] vs. 2 [1-3]}, Sequential Organ Failure Assessment (SOFA) {7 [5-9] vs. 3 [1-6]}, higher level of D-dimer {5.74 [2.32-18] vs 2.05 [1.09-4.00]} and neutrophil count {9.4 [7.68-14.54] vs. 5.32 [3.85-9.34]}. SOFA score (OR 1.47; 95% CI: 1.01-2.13; P=0.0042) and the lymphocyte count (OR 0.02; 95% CI: 0.00-0.86; P=0.042) on admission were independently risk factors for mortality. Patients with higher lymphocyte count (>0.63×109 /L) and lower SOFA score (≤4) on admission had a significantly better prognosis than those with lower lymphocyte count (≤0.63×109 /L) and higher SOFA score (>4) in overall survival. CONCLUSIONS Higher SOFA score and lower lymphocyte count at admission were connected with poor prognosis of patients with COVID-19 in ICU. Lymphocyte count may serve as a promising prognostic biomarker.
Impact of DaTscan Imaging on Clinical Decision Making in Clinically Uncertain Parkinson’s Disease

Background: The diagnosis of Parkinson’s disease (PD) is primarily clinical, but in cases of diagnostic uncertainty, evaluation of nigrostriatal dopaminergic degeneration (NSDD) by imaging of the dopamine transporter using DaTscan with single-photon emission computed tomography (SPECT) brain imaging may be helpful. Objective/Methods: In the current paper, we describe clinical scenarios for which DaTscan imaging was used in a prospective case series of 201 consecutive patients in whom a movement disorder specialist ordered DaTscan imaging to clarify NSDD. We describe the impact of DaTscan results on changing or confirming pre-DaTscan clinical diagnosis and on post-DaTscan treatment changes. Results/Conclusion: DaTscan imaging can be useful in several clinical scenarios to determine if NSDD is present. These include in patients with early subtle symptoms, suboptimal response to levodopa, prominent action tremor, drug-induced parkinsonism, and in patients with lower extremity or other less common parkinsonism clinical presentations. We also found DaTscan imaging to be useful to determine underlying NSDD in patients with PD diagnosis for 3-5 years but without apparent clinical progression or development of motor fluctuations. Overall, in 201 consecutive patients with clinically questionable NSDD, DaTscan was abnormal in 58.7% of patients, normal in 37.8%, and inconclusive in 3.5%. DaTscan imaging changed clinical diagnosis in 39.8% of patients and led to medication therapy changes in 70.1% of patients.
Scapular length estimation from anatomical landmarks: an osteometry and radiographic evaluation using regression equations

Estimation of body length has been achieved from the measurements of the scapular with relative accuracy by researches in recent times. This research hypothesized that the landmarks on the scapular and on the x-ray radiographs could be used to predict scapular length and elucidated the landmarks that best estimate the scapular length. A total of 600 scapulae and 600 anterior-posterior x-ray radiographs were used for the study. Positive correlation was observed between the measured variables and the scapular length with the males showing significantly higher mean length compared to females. The length of axillary boarder of the scapula was the best predictor of the scapular length. No significant difference (P>0.05) existed in the mean length derived from the scapular and the x-ray radiographs of scapular. We therefore conclude that measurements from the radiographs of scapular were as reliable in estimating scapular length as those from the scapular bones.