Miracle-dz/UniFAR-FTUs huggingface dataset:
Revisiting factors associated with blood culture positivity: Critical factors after the introduction of automated continuous monitoring blood culture systems

Blood culture is the main tool used to identify causative pathogens. Adequate volume and number of culture sets are considered key to blood culture positivity rate. It is not known whether these factors remain critical to the positivity rate after the introduction of automated continuous blood culture system monitoring. We measured blood volume per bottle and described the distribution of blood volume and number of culture sets. Multivariate logistic regression was performed to determine the independent association of blood volume, number of culture sets, diagnosis of sepsis in a patient, and other covariates with blood culture results. Only 6.9% of the blood culture bottle volumes complied with the guidance (8–10 mL), with the highest culture positivity rate (18%). Of the culture events, only one set of blood was cultured in 60.9% of events. In the multivariate analysis, blood culture volume per event (odds ratio [OR], 1.09 [95% confidence interval [CI], 1.06–1.11]), patients with a diagnosis of sepsis (OR, 2.86 [95% CI, 2.06–3.98]), and samples from the emergency department (OR, 2.29 [95% CI, 1.72–3.04]), but not the number of culture sets (OR, 0.74 [95% CI, 0.50–1.12]), were observed to be statistically significant with respect to blood culture positivity rate. Our results revealed that the total blood culture volume and the diagnosis of sepsis were critical factors affecting blood culture positivity rate. However, the proportion of blood culture bottles with the optimal blood volume was very low, and optimizing blood volume would be key to increasing blood culture positivity rate.
Stress accumulation by confined ice in a temperature gradient

Significance Ice almost always causes damage when soft, wet materials freeze. This poses a tremendous, unsolved challenge across a huge variety of scientific disciplines. This damage is not typically caused by freezing water expanding but by the process of cryosuction—which continues after ice’s initial growth. Here, we characterize how stresses build up in this process with unprecedented microscale resolution. Our technique shows how stresses are extremely localized and with great damage potential. Stresses globally increase while locally stalling at a value that is set by the local undercooling. Beyond freezing, our work allows us to measure local disjoining pressures with micrometer-scale resolution and has strong ties with the science of confined crystal growth, such as in salt weathering.
Viral load dynamics in SARS-CoV-2 Omicron breakthrough infections

Abstract In order to determine viral dynamics in Omicron breakthrough infections, we measured SARS-CoV-2 RNA in 206 double vaccinated or boostered individuals. During the first three days following the onset of symptoms, viral loads were significantly higher (Ct 21.76) in vaccinated compared to boostered (Ct 23.14) individuals (p = 0.029). However, by performing a longitudinal analysis on 32 individuals over 14 days, no difference in the viral load trajectory was observed between double vaccinated and boostered patients. Our results indicate that booster immunization results in a small reduction in detectable viral loads without significantly changing viral load dynamics over time.
European Working Group on Sarcopenia in Older People 2010 (EWGSOP1) and 2019 (EWGSOP2) criteria or slowness: which is the best predictor of mortality risk in older adults?

Abstract Objectives to analyse the accuracy of grip strength and gait speed in identifying mortality; to compare the association between mortality and sarcopenia defined by the EWGSOP1 and EWGSOP2 using the best cut-off found in the present study and those recommended in the literature and to test whether slowness is better than these two definitions to identify the risk of death in older adults. Methods a longitudinal study was conducted involving 6,182 individuals aged 60 or older who participated in the English Longitudinal Study of Ageing. Sarcopenia was defined based on the EWGSOP1 and EWGSOP2 using different cut-off for low muscle strength (LMS). Mortality was analysed in a 14-year follow-up. Results compared with the LMS definitions in the literature (<32, <30, <27 and < 26 kg for men; <21, <20 and < 16 kg for women), the cut-off of <36 kg for men (sensitivity = 58.59%, specificity = 72.96%, area under the curve [AUC] = 0.66) and < 23 kg for women (sensitivity = 68.90%, specificity = 59.03%, AUC = 0.64) as well as a low gait speed (LGS) ≤0.8 m/s (sensitivity = 53.72%, specificity = 74.02%, AUC = 0.64) demonstrated the best accuracy for mortality. Using the cut-off found in the present study, probable sarcopenia [HR = 1.30 (95%CI: 1.16–1.46)], sarcopenia [HR = 1.48 (95%CI: 1.24–1.78)] and severe sarcopenia [HR = 1.78 (95%CI: 1.49–2.12)] according to EWGSOP2 were better predictors of mortality risk than EWGSOP1. LGS ≤0.8 m/s was a better mortality risk predictor only when LMS was defined by low cut-off. Conclusions using LMS <36 kg for men and < 23 kg for women and LGS ≤ 0.8 m/s, EWGSOP2 was the best predictor for mortality risk in older adults.
Challenges in measuring nitrogen isotope signatures in inorganic nitrogen forms: An interlaboratory comparison of three common measurement approaches

Rationale Stable isotope approaches are increasingly applied to better understand the cycling of inorganic nitrogen (Ni) forms, key limiting nutrients in terrestrial and aquatic ecosystems. A systematic comparison of the accuracy and precision of the most commonly used methods to analyze δ15N in NO3 − and NH4 + and interlaboratory comparison tests to evaluate the comparability of isotope results between laboratories are, however, still lacking. Methods Here, we conducted an interlaboratory comparison involving 10 European laboratories to compare different methods and laboratory performance to measure δ15N in NO3 − and NH4 +. The approaches tested were (a) microdiffusion (MD), (b) chemical conversion (CM), which transforms Ni to either N2O (CM‐N2O) or N2 (CM‐N2), and (c) the denitrifier (DN) methods. Results The study showed that standards in their single forms were reasonably replicated by the different methods and laboratories, with laboratories applying CM‐N2O performing superior for both NO3 − and NH4 +, followed by DN. Laboratories using MD significantly underestimated the “true” values due to incomplete recovery and also those using CM‐N2 showed issues with isotope fractionation. Most methods and laboratories underestimated the at%15N of Ni of labeled standards in their single forms, but relative errors were within maximal 6% deviation from the real value and therefore acceptable. The results showed further that MD is strongly biased by nonspecificity. The results of the environmental samples were generally highly variable, with standard deviations (SD) of up to ± 8.4‰ for NO3 − and ± 32.9‰ for NH4 +; SDs within laboratories were found to be considerably lower (on average 3.1‰). The variability could not be connected to any single factor but next to errors due to blank contamination, isotope normalization, and fractionation, and also matrix effects and analytical errors have to be considered. Conclusions The inconsistency among all methods and laboratories raises concern about reported δ15N values particularly from environmental samples.
Development and validation of a machine learning-based model for postoperative ischemic stroke in middle-aged and elderly patients with hip or knee arthroplasty

Postoperative ischemic stroke in middle-aged and elderly patients with hip or knee arthroplasty remains a major postoperative challenge, little is known about its incidence and risk factors. This study sought to create a nomogram for precise prediction of ischemic stroke after hip or knee arthroplasty. Discharge data of all middle-aged and elderly patients undergoing primary hip or knee arthroplasty from May 2013 to October 2020 were queried. These patients were then followed up over time to determine their risk of ischemic stroke. Clinical parameters and blood biochemical features were analyzed by the use of univariable and multivariable generalized logistic regression analysis. A nomogram to predict the risk of ischemic stroke was constructed and validated with bootstrap resampling. Eight hundred twenty-eight patients were included for analysis; Fifty-one were diagnosed with ischemic stroke. After final regression analysis, age, the neutrophil-to-lymphocyte ratio (NLR), a standard deviation of red blood cell distribution width, American Society of Anesthesiologists, low-density lipoprotein, and diabetes were identified and were entered into the nomogram. The nomogram showed an area under the receiver operating characteristic curve of 0. 841 (95% confidence interval [CI], 0.809–0.871). The calibration curves for the probability of ischemic stroke showed optimal agreement between the probability as predicted by the nomogram and the actual probability (Hosmer-Lemeshow test: P = .818). We developed a practical nomogram that can predict the risk of ischemic stroke for middle-aged and elderly patients with hip or knee arthroplasty. This model has the potential to assist clinicians in making treatment recommendations.
Dopamine plays a critical role in the olfactory adaptive learning pathway in Caenorhabditis elegans

Encoding and consolidating information through learning and memory is vital in adaptation and survival. Dopamine (DA) is a critical neurotransmitter that modulates behavior. However, the role of DA in learning and memory processes is not well defined. Herein, we used the olfactory adaptive learning paradigm in Caenorhabditis elegans to elucidate the role of DA in the memory pathway. Cat‐2 mutant worms with low DA synthesis showed a significant reduction in chemotaxis index (CI) compared to the wild type (WT) after short‐term conditioning. In dat‐1::ICE worms, having degeneration of DA neurons, there was a significant reduction in adaptive learning and memory. When the worms were trained in the presence of exogenous DA (10 mM) instead of food, a substantial increase in CI value was observed. Furthermore, our results suggest that both dop‐1 and dop‐3 DA receptors are involved in memory retention. The release of DA during conditioning is essential to initiate the learning pathway. We also noted an enhanced cholinergic receptor activity in the absence of dopaminergic neurons. The strains expressing GCaMP6 in DA neurons (pdat‐1::GCaMP‐6::mCherry) showed a rise in intracellular calcium influx in the presence of the conditional stimulus after training, suggesting DA neurons are activated during memory recall. These results reveal the critical role of DA in adaptive learning and memory, indicating that DA neurons play a crucial role in the effective processing of cognitive function.
The experience of one pediatric geneticist with telemedicine‐based clinical diagnosis

Telemedicine has long been considered as an attractive alternative methodology in clinical genetics to improve patient access and convenience. Given the importance of the dysmorphology physical examination and anthropometric measurement in clinical genetics, many have wondered if lost information would hamper diagnosis. We previously addressed this question by analyzing thousands of diagnostic encounters in a single practice involving multiple practitioners and found no evidence for a difference in new molecular diagnosis rates. However, our previous study design resulted in variability in providers between in‐person and telemedicine evaluation groups. To address this in our present study, we expanded our analysis to 1104 new patient evaluations seen by one highly experienced clinical geneticist across two 10‐month periods before and after the start of the COVID‐19 pandemic. Comparing patients seen in‐person to those seen by telemedicine, we found significant differences in race and ethnicity, preferred language, and home zip code median income. The clinical geneticist intended to send more genetic testing for those patients seen by telemedicine, but due to issues with test authorization and sample collection, there was no difference in ultimate completion rate between groups. We found no significant difference in new molecular diagnosis rate. Overall, we find telemedicine to be an acceptable alternative to in‐person evaluation for routine pediatric clinical genetics care.
Serum levels of apolipoprotein A-I and E are associated with postoperative delirium: A post hoc analysis

Postoperative delirium is a common complication for elderly patients. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage with postoperative delirium. Although it has been implicated that serum apolipoprotein levels might be associated with senile cognitive disorder, its role in the development of delirium has not been fully investigated. This study examined the association of apolipoproteins with delirium after surgery. This was a post hoc analysis of 117 patients who participated in a prospective observational study of delirium in patients undergoing cancer surgery. Patients were clinically assessed for delirium within the first 5 days of surgery. Serum levels of apolipoprotein A-I, B, and E were measured on postoperative day 3. Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Serum levels of apolipoprotein A-I and B were increased in patients with delirium whereas those of apolipoprotein E were decreased. These changes in apolipoprotein A-I and E levels were associated with the presence of phosphorylated neurofilament heavy subunit in the serum, and were significantly associated with delirium (A-I: adjusted odds ratio [aOR], 6.238; 95% confidence interval [CI], 2.766–20.68; P < .0001; E: aOR, 0.253; 95% CI, 0.066–0.810; P = .0193). A combination of apolipoprotein A-I and E offers significant discrimination between delirium and nondelirium with high accuracy (area under the curve, 0.8899). Serum apolipoprotein A-I and E levels were associated with delirium and the presence of phosphorylated neurofilament heavy subunit in serum. Therefore, apolipoproteins might be useful biomarkers of postoperative delirium.
Serum proteomic profiling of rheumatoid arthritis–interstitial lung disease with a comparison to idiopathic pulmonary fibrosis

Although interstitial lung disease (ILD) causes significant morbidity and mortality in rheumatoid arthritis (RA), it is difficult to predict the development or progression of ILD, emphasising the need for improved discovery through minimally invasive diagnostic tests. Aptamer-based proteomic profiling was used to assess 1321 proteins from 159 patients with rheumatoid arthritis with interstitial lung disease (RA-ILD), RA without ILD, idiopathic pulmonary fibrosis and healthy controls. Differential expression and gene set enrichment analyses revealed molecular signatures that are strongly associated with the presence and severity of RA-ILD and provided insight into unexplored pathways of disease. These warrant further study as non-invasive diagnostic tools and future therapeutic targets.
Seeing Through the Character’s Eyes: Examining Phenomenological Experiences of Perspective-Taking During Reading

ABSTRACT Despite substantive work on the cognitive processes underlying comprehension, little research has examined the “phenomenological” nature of reading. We investigated how readers’ experiences of visual and verbal thought related to their transportation into the narrative text and whether these were influenced by perspective-taking. Specifically, readers reported the nature of their thoughts while reading and then completed a transportation assessment. Study 1 (n = 147) manipulated perspective-taking via explicit instructions, whereas Study 2 (n = 200) varied point of view within the text. Additionally, Study 2 examined whether reports varied across descriptive and dialogue text segments. Results suggested that visual and verbal reports were consistently negatively correlated. Further, transportation was positively associated with visual reports and negatively associated with verbal reports. We found no differences in thought reports for dialogue and descriptive text segments or across the perspective-taking manipulations. These findings suggest that phenomenological reading experiences are stable across a variety of reading situations.
It’s Contagious! Examining Gamified Refutation Texts, Emotions, and Knowledge Retention in a Real-World Public Health Education Campaign

ABSTRACT The current study investigated the relations between gamified refutations of COVID-19 misconceptions and individuals’ emotional reactions and knowledge retention within a large-scale public health education campaign. Refutations have a substantial body of evidence supporting their use to correct misconceptions, yet reduced efficacy has been observed for some topics that generate negative emotional responses. We tested whether gamification could mitigate these limits given that it capitalizes on positive affective engagement. From May to December 2020, approximately 200,000 individuals were recruited from social media in Canada to engage with a nongame interactive survey as a control or a fully gamified platform focused on correcting COVID-19 misconceptions. Gamification was associated with a greater number of happiness and anxiety responses and fewer responses of anger and skepticism in reaction to having misconceptions corrected by refutations. Further, participants who engaged with gamified refutations retained correct information after a brief period. Finally, happiness and anxiety were positively associated with and anger and skepticism were negatively associated with retention of refutation information and support for related public health policies. Implications for scaling up and reinforcing the benefits of refutations for public engagement with science are discussed.
Assembly mechanism and cryoEM structure of RecA recombination nucleofilaments from Streptococcus pneumoniae

RecA-mediated Homologous Recombination (HR) is a key mechanism for genome maintenance and plasticity in bacteria. It proceeds through RecA assembly into a dynamic filament on ssDNA, the presynaptic filament, which mediates DNA homology search and ordered DNA strand exchange. Here, we combined structural, single molecule and biochemical approaches to characterize the ATP-dependent assembly mechanism of the presynaptic filament of RecA from Streptococcus pneumoniae (SpRecA), in comparison to the Escherichia coli RecA (EcRecA) paradigm. EcRecA polymerization on ssDNA is assisted by the Single-Stranded DNA Binding (SSB) protein, which unwinds ssDNA secondary structures that block EcRecA nucleofilament growth. We report that neither of the two paralogous pneumococcal SSBs could assist SpRecA polymerization on ssDNA. Instead, we found that the conserved RadA helicase promotes this SpRecA nucleofilamentation in an ATP-dependent manner. This allowed us to solve the atomic structure of such a long native SpRecA nucleopolymer by cryoEM stabilized with ATPγS. It was found to be equivalent to the crystal structure of the EcRecA filament with a marked difference in how RecA mediates nucleotide orientation in the stretched ssDNA. Then, our results show that SpRecA and EcRecA HR activities are different, in correlation with their distinct ATP-dependent ssDNA binding modes.
Durable alveolar engraftment of PSC-derived lung epithelial cells into immunocompetent mice

Durable reconstitution of the injured distal lung epithelium with pluripotent stem cell (PSC) derivatives, if realized, would represent a promising potential therapy for diseases that result from alveolar damage. Here we differentiate murine PSCs in vitro into self-renewing lung epithelial progenitors able to engraft into the injured distal lung epithelium of immunocompetent, syngeneic mouse recipients. Emulating the roadmap of the developing embryo, we generate transplantable PSC-derived Nkx2-1+/Sox9+ lung epithelial progenitors that are highly similar to cultured primary embryonic distal lung bud tip progenitors. These cells display a stable phenotype after frozen archiving or extensive expansion in culture, providing a nearly inexhaustible source of cells that can be engrafted into syngeneic injured mouse lungs without the need for immunosuppression. After transplantation PSC-derived tip-like progenitors downregulate Sox9 and mature in the distal lung, upregulating alveolar type 2 cell markers or assuming the flat morphology and molecular phenotype of terminally differentiated alveolar type 1 cells. After months in vivo, donor-derived cells retain their alveolar epithelial type 2-like and type 1-like phenotypes, as characterized by single cell RNA sequencing, ultrastructural analyses, in vivo histologic profiling, and ex vivo organoid assays that demonstrate continued capacity of the engrafted cells to proliferate and differentiate. These results indicate durable reconstitution of the distal lung’s facultative progenitor and differentiated epithelial cell compartments in vivo with PSC-derived cells, thus establishing a novel model for pulmonary cell therapy which can be utilized to better understand the mechanisms and utility of engraftment prior to future clinical studies.
Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes

CENP-A is a histone variant found in high abundance at the centromere. The centromere chromatin similar to the bulk chromatin consist of nucleosomes, but H3 histone of the bulk chromatin nucleosomes (H3 nucleosomes) is replaced with CENP-A histone. Additionally, the centromere comprises tandem repeats of α-satellite DNA which CENP-A nucleosomes assemble upon. However, the effect of the DNA sequence on the nucleosome assembly and centromere formation remains poorly understood. Here we investigated the structure of nucleosomes assembled with the CENP-A variant using Atomic Force Microscopy. We assembled both CENP-A nucleosomes and H3 nucleosomes on a DNA substrate containing an α-satellite motif and characterized their positioning and wrapping efficiency. We also studied CENP-A nucleosomes on the 601-positioning motif and non-specific DNA to compare their relative positioning and stability. CENP-A nucleosomes assembled on α-satellite DNA did not show any positional preference along the substrate, which is similar to H3 nucleosomes and CENP-A nucleosomes on non-specific DNA. The range of nucleosome wrapping efficiency was narrower on α-satellite DNA compared with non-specific DNA, suggesting a more stable complex. These findings indicate that DNA sequence and histone composition may be two of many factors required for accurate centromere assembly.
Tumor landscape of epithelial ovarian cancer highlights that EGR1 drives tumor invasion at single-cell resolution

Identifying underlying molecular mechanisms and biomarkers of epithelial ovarian carcinoma (EOC) proliferation and metastasis remains challenging. Patients of EOC are usually diagnosed at an advanced stage and the availability of invasion-related targets is limited. Herein, we explored the single-cell RNA sequencing (scRNA-seq) dataset of EOC and defined tumor physiological reprograming compared to bulk RNA-seq. The energy metabolism and anti-apoptotic pathway was found as critical contributors to intratumor heterogeneity. Moreover, hypoxia, oxidative phosphorylation (OXPHOS) and glycolysis were positively correlated, which have biologically activity trajectories during epithelial mesenchymal transition (EMT). The HMGH1, EGR1 and RUNX1 were found to be critical inducers of the EMT process in EOC. Experimental validation revealed that suppressed EGR1 decreased the expression of FAS and HSPG2 and associating with EMT progression in EOC. In tumor microenvironment (TME), CAFs were found have significant contribution to tumor immune infiltration and metastasis and accumulation of CAFs was associated with poorer patient survival. In conclusion, physiological features and molecular mechanisms in the TME of EOC were revealed and provided effective targets for the suppression of tumor metastasis.