Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of automated electron microscopy imaging and machine learning to characterise and quantify nanoparticle dispersion in aqueous media

Summary For many nanoparticle applications it is important to understand dispersion in liquids. For nanomedicinal and nanotoxicological research this is complicated by the often complex nature of the biological dispersant and ultimately this leads to severe limitations in the analysis of the nanoparticle dispersion by light scattering techniques. Here we present an alternative analysis and associated workflow which utilises electron microscopy. The need to collect large, statistically relevant datasets by imaging vacuum dried, plunge frozen aliquots of suspension was accomplished by developing an automated STEM imaging protocol implemented in an SEM fitted with a transmission detector. Automated analysis of images of agglomerates was achieved by machine learning using two free open‐source software tools: CellProfiler and ilastik. The specific results and overall workflow described enable accurate nanoparticle agglomerate analysis of particles suspended in aqueous media containing other potential confounding components such as salts, vitamins and proteins. Lay Description In order to further advance studies in both nanomedicine and nanotoxicology, we need to continue to understand the dispersion of nanoparticles in biological fluids. These biological environments often contain a number of components such as salts, vitamins and proteins which can lead to difficulties when using traditional techniques to monitor dispersion. Here we present an alternative analysis which utilises electron microscopy. In order to use this approach statistically relevant large image datasets were collected from appropriately prepared samples of nanoparticle suspensions by implementing an automated imaging protocol. Automated analysis of these images was achieved through machine learning using two readily accessible freeware; CellProfiler and ilastik. The workflow presented enables accurate nanoparticle dispersion analysis of particles suspended in more complex biological media.
Single Ventricle Physiology Patients and Coagulation Abnormalities: Is There a Relationship With Hemodynamic Data and Postoperative Course? A Pilot Study

This study evaluates coagulation profiles of single ventricle (SV) patients in relationship to liver function, hemodynamic variables and outcome. Twenty-six children with SV anatomy were included. Advanced coagulation profiles, invasive preoperative hemodynamic parameters and clinical course were retrospectively analyzed. Median (interquartile range) age and weight at the time of blood sampling was 25.5 (31) months and 10.5 (6.9) kg. Sixteen patients (16/26; 62%) showed decreased antithrombin and/or protein C (PC) and/or free protein S (PS) function and/or free PS antigen. Two patients showed abnormal activated PC resistance ratio due to heterozygous factor V Leiden mutation and 1 heterozygous prothrombin G20210A mutation. Group comparison (abnormal coagulation profile [group 1; n = 16] versus normal coagulation profile [group 2; n = 10]) showed longer postoperative hospitalization time (p = .04), longer postoperative catecholamine support (p = .01), a higher incidence of thromboembolic events (p = .04), and chylothoraxes (p = .007) in group 1. In 5 (31%) of 16 group 1 patients, thromboembolic complications occurred: cerebral stroke (n = 1), intestinal ischemia (n = 2), thrombus formation in inferior caval vein (n = 1), and pulmonary vein (n = 1). Abnormalities in coagulation parameters are common in SV patients. Coagulation abnormalities constitute a preoperative risk factor and affect postoperative course.
Do Cell Membranes Flow Like Honey or Jiggle Like Jello?

Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor of ≈106. This study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here https://youtu.be/T6K7AIAqqBs.
Brachial‐Ankle Pulse Wave Velocity Versus Its Stiffness Index β‐Transformed Value as Risk Marker for Cardiovascular Disease

Background The difference in the predictive ability of the brachial‐ankle pulse wave velocity (baPWV) and its stiffness index β‐transformed value (β‐baPWV, ie, baPWV adjusted for the pulse pressure) for the development of pathophysiological abnormalities related to cardiovascular disease or future occurrence of cardiovascular disease was examined. Methods and Results In study 1, a 7‐year prospective observational study in cohorts of 3274 men and 3490 men, the area under the curve in the receiver operator characteristic curve analysis was higher for baPWV than for β‐baPWV for predicting the development of hypertension (0.73, 95% CI=0.70 to 0.75 versus 0.59, 95% CI=0.56 to 0.62; P<0.01) and/or the development of retinopathy (0.78, 95% CI=0.73 to 0.82 versus 0.66, 95% CI=0.60 to 0.71; P<0.01) by the end of the study period. During study 2, a 3‐year observation period on 511 patients with coronary artery disease, 72 cardiovascular events were confirmed. The C statistics of both markers for predicting the development of cardiovascular events were similar. Conclusions Stiffness index β transformation of the baPWV may attenuate the significance of the baPWV as a risk marker for development of pathophysiological abnormalities related to cardiovascular disease in male subjects.
Estimating Equilibrium Exchange Rates for the New Member Countries of the European Union

This paper estimates real equilibrium exchange rates for the new members of the European Union. First, an out-of-sample method is applied using a cointegrated panel of 25 OECD countries to estimate common coefficients for the panel. Next, individual constants for each of the new member countries are derived by a new methodology. Then these constants and the panel coefficients are combined to calculate the real equilibrium exchange rate for nine of the ten new members. Of these nine, only Slovenia’s and the Czech Republic’s rates are at or near their real equilibrium exchange rate.
Effects of butylphthalide injection on treatment of transient ischemic attack as shown by diffusion-weighted magnetic resonance imaging abnormality

Abstract Background and Objective: Transient ischemic attack (TIA) is a serious condition that is often called a warning stroke. The risk of cerebral infarction in patients with TIA and positive DWI findings is greater than that in patients with TIA and normal DWI findings. Butylphthalide injection is a new type of brain protective drug. The study aimed to determine the efficacy and safety of butylphthalide injection for treating TIA as shown by DWI abnormality progressing to infarction. Methods: We studied 98 patients with positive DWI findings among 260 patients with TIA, and randomly divided into the experimental (treatment with butylphthalide injection) and control (treatment with aspirin) groups. The number of cerebral infarctions in the two groups was recorded on 7th, 14th, 30th and 90th day, and adverse reactions were observed. The number of cerebral infarctions was compared among the different ABCD2 scores of patients with TIA and positive DWI findings. Results: The incidence of cerebral infarction in the experimental group was significantly lower than that in the control group (p < .05). The incidence of cerebral infarction with an ABCD2 score less than 3 points was significantly lower than that with an ABCD2 score of more than 3 points (p < .05), with less adverse reactions. Conclusion: Butylphthalide injection is helpful and safe for preventing stroke following TIA, and treating TIA with positive DWI and progression to infarction.
Serum procalcitonin as an independent diagnostic markers of bacteremia in febrile patients with hematologic malignancies

Background Serum procalcitonin (PCT) and C-reactive protein (CRP) are biomarkers of infection. In patients with hematologic disorders with or without hematopoietic stem cell transplantation (HSCT), it is difficult to distinguish bloodstream infections from aseptic causes of febrile episodes. The objective of this study was to investigate diagnostic values of PCT and CRP in predicting systemic bacterial infection in patients with hematologic malignancies. Methods Clinical and laboratory data of 614 febrile episode cases from 511 patients were analyzed. Febrile episodes were classified into four groups: (1) culture-positive bacterial infection by Gram-positive cocci (GPC), (2) culture-positive bacterial infection by Gram-negative bacilli (GNB), (3) fungal infection, and (4) viral infection or a noninfectious etiology. Results Of 614 febrile cases, systemic bacterial infections were confirmed in 99 (16.1%) febrile episodes, including 38 (6.2%) GPC and 61 (9.9%) GNB infections. PCT levels were significantly higher in GNB infectious episodes than those in febrile episodes caused by fungal infection (0.58 ng/mL (95% CI: 0.26–1.61) vs. 0.22 ng/mL (0.16–0.38), P = 0.047). Bacterial infectious episodes showed higher PCT and CRP levels than non-bacterial events (PCT: 0.49 (0.26–0.93) ng/mL vs. 0.20 (0.18–0.22) ng/mL, P < 0.001; CRP: 76.6 (50.5–92.8) mg/L vs. 58.0 (51.1–66.5) mg/L, P = 0.036). For non-neutropenic febrile episodes, both PCT and CRP discriminated bacteremia from non-bacteremia. However, in neutropenic febrile episodes, PCT only distinguished bacteremia from non-bacteremia. In non-neutropenic episode, both PCT and CRP showed good diagnostic accuracy (AUC: 0.757 vs. 0.763). In febrile neutropenia, only PCT discriminated bacteremia from non-bacterial infection (AUC: 0.624) whereas CRP could not detect bacteremia (AUC: 0.500, 95% CI: 0.439–0.561, P > 0.05). Conclusions In this single-center observational study, PCT was more valuable than CRP for discriminating between bacteremia and non-bacteremia independent of neutropenia or HSCT.
Role of miR-124 in the regulation of retinoic acid-induced Neuro-2A cell differentiation

Retinoic acid can cause many types of cells, including mouse neuroblastoma Neuro-2A cells, to differentiate into neurons. However, it is still unknown whether microRNAs (miRNAs) play a role in this neuronal differentiation. To address this issue, real-time polymerase chain reaction assays were used to detect the expression of several differentiation-related miRNAs during the differentiation of retinoic acid-treated Neuro-2A cells. The results revealed that miR-124 and miR-9 were upregulated, while miR-125b was downregulated in retinoic acid-treated Neuro-2A cells. To identify the miRNA that may play a key role, miR-124 expression was regulated by transfection of miRNA mimics or inhibitors. Morphological analysis results showed that inhibition of miR-124 expression reversed the effects of retinoic acid on neurite outgrowth. Moreover, miR-124 overexpression alone caused Neuro-2A cells to differentiate into neurons, and its inhibitor could block this effect. These results suggest that miR-124 plays an important role in retinoic acid-induced differentiation of Neuro-2A cells.
NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2.

PURPOSE Adjuvant trastuzumab reduces invasive breast cancer (IBC) recurrence and risk for death in patients with HER2-amplified or overexpressing IBC. A subset of patients in the landmark trastuzumab adjuvant trials who originally tested HER2-positive but were HER2-negative by central HER2 testing appeared to possibly benefit from trastuzumab. The objective for the NSABP B-47 trial was to determine whether the addition of trastuzumab to adjuvant chemotherapy (CRx) would improve invasive disease-free survival (IDFS) in patients with HER2-negative breast cancer. PATIENTS AND METHODS A total of 3,270 women with high-risk primary IBC were randomly assigned to CRx with or without 1 year of trastuzumab. Eligibility criteria included immunohistochemistry (IHC) score 1+ or 2+ with fluorescence in situ hybridization ratio (FISH) < 2.0 or, if ratio was not performed, HER2 gene copy number < 4.0. CRx was either docetaxel plus cyclophosphamide or doxorubicin and cyclophosphamide followed by weekly paclitaxel for 12 weeks. RESULTS At a median follow-up of 46 months, the addition of trastuzumab to CRx did not improve IDFS (5-year IDFS: 89.8% with CRx plus trastuzumab [CRxT] v 89.2% with CRx alone; hazard ratio [HR], 0.98; 95% CI, 0.76 to 1.25; P = .85). These findings did not differ by level of HER2 IHC expression, lymph node involvement, or hormone-receptor status. For distant recurrence-free interval, 5-year estimates were 92.7% with CRxT compared with 93.6% for CRx alone (HR, 1.10; 95% CI, 0.81 to 1.50; P = .55) and for overall survival (OS) were 94.8% with CRxT and 96.3% in CRx alone (HR, 1.33; 95% CI, 0.90 to 1.95; P = .15). There were no unexpected toxicities from the addition of trastuzumab to CRx. CONCLUSION The addition of trastuzumab to CRx did not improve IDFS, distant recurrence-free interval, or OS in women with non-HER2-overexpressing IBC. Trastuzumab does not benefit women without IHC 3+ or FISH ratio-amplified breast cancer.
Ecological and social determinants of association and proximity patterns in the fission–fusion society of spider monkeys (Ateles geoffroyi)

Some social species exhibit high levels of fission–fusion dynamics (FFD) that improve foraging efficiency. In this study, we shed light on the way that FFD allows animal groups to cope with fluctuations in fruit availability. We explore the relative contribution of fruit availability and social factors like sex in determining association and proximity patterns in spider monkeys. We tested the influence of fruit availability and social factors on the association and proximity patterns using three‐year data from a group of spider monkeys in the Yucatan Peninsula of Mexico. We identified subgroup members and estimated their Interindividual distances through instantaneous scan sampling. We evaluated fruit availability by monitoring the phenology of the 10 most important food tree species for spider monkeys in the study site. Social network analyses allowed us to evaluate association and proximity patterns in subgroups. We showed that association patterns vary between seasons, respond to changes in fruit availability, and are influenced by the sex of individuals, likely reflecting biological and behavioral differences between sexes and the interplay between ecological and social factors. In contrast, proximity patterns were minimally affected by changes in fruit availability, suggesting that social factors are more important than food availability in determining cohesion within subgroups.
Direct Validation of Model-predicted Muscle Forces in the Cat Hindlimb During Walking.

Various methods are available for simulating the movement patterns of musculoskeletal systems and determining individual muscle forces, but the results obtained from these methods have not been rigorously validated against experiment. The aim of this study was to compare model predictions of muscle force derived for a cat hindlimb during locomotion against direct measurements of muscle force obtained in vivo. The cat hindlimb was represented as a 5-segment, 13-degree-of-freedom, articulated linkage actuated by 25 Hill-type muscle-tendon units (MTUs). Individual muscle forces were determined by combining gait data with two widely used computational methods - static optimization and computed muscle control - available in OpenSim, an open-source musculoskeletal modeling and simulation environment. The forces developed by the soleus, medial gastrocnemius, and tibialis anterior muscles during free locomotion were measured using buckle transducers attached to the tendons. Muscle electromyographic activity and MTU length changes were also measured and compared against corresponding data predicted by the model. Model-predicted muscle forces, activation levels, and MTU length changes were consistent with corresponding quantities obtained from experiment. The calculated values of muscle force obtained from static optimization agreed more closely with experiment than those derived from computed muscle control.
STABILIZING ADVERSARIAL INVARIANCE INDUCTION

Incorporating the desired invariance into representation learning is a key challenge in many situations, e.g., for domain generalization and privacy/fairness constraints. An adversarial invariance induction (AII) shows its power on this purpose, which maximizes the proxy of the conditional entropy between representations and attributes by adversarial training between an attribute discriminator and feature extractor (Xie et al., 2017). However, the practical behavior of AII is still unclear as the previous analysis assumes the optimality of the attribute classifier, which is rarely held in practice. This paper first analyzes the practical behavior of AII both theoretically and empirically, indicating that AII has theoretical difficulty as it maximizes variational upper bound of the actual conditional entropy, and AII catastrophically fails to induce invariance even in simple cases as suggested by the above theoretical findings. We then argue that a simple modification to AII can significantly stabilize the adversarial induction framework and achieve better invariant representations. Our modification is based on the property of conditional entropy; it is maximized if and only if the divergence between all pairs of marginal distributions over z between different attributes is minimized. The proposed method, invariance induction by discriminator matching, modify AII objective to explicitly consider the divergence minimization requirements by defining a proxy of the divergence by using the attribute discriminator. Empirical validations on both the toy dataset and four real-world datasets (related to applications of user anonymization and domain generalization) reveal that the proposed method provides superior performance when inducing invariance for nuisance factors.
Dynamics of Physicians’ Trust in Fellow Health Care Providers and the Role of Health Information Technology

Physicians are expected and incentivized to coordinate patient care with other providers, including nonphysician clinician (NPC) members of care teams, requiring trust. Trust in the context of care teams has not been well-studied; even less is known about how health information technologies (HIT) may modify trust in these relationships. We conducted semistructured interviews with 30 physicians at a Midwestern academic center to examine how physicians determine they can trust NPCs, and how technology modifies these relationships. A majority of physicians base trust in NPCs on cognitive factors such as competence and reliability. Technology enhances trust between physicians and NPCs by supporting evidence-based decision making; it can also erode trust by limiting opportunities for developing familiarity and comfort with fellow providers. Our work has implications for enhancing HIT to promote trust between providers, and for developing more robust measures of trust that can be used in evaluating and improving teamwork within practices.
Regional respiratory movement of the tongue is coordinated during wakefulness and is larger in severe obstructive sleep apnoea

Coordination of the neuromuscular compartments of the tongue is critical to maintain airway patency. Currently, little is known about the extent to which regional tongue dilatory motion is coordinated in heathy people and if this coordination is altered in people with obstructive sleep apnoea (OSA). We show that regional tongue muscle coordination in people with and without OSA during wakefulness is associated with effective airway dilatation during inspiration, using dynamic tagged magnetic resonance imaging. The maximal movement of four compartments of the tongue were correlated and occurred concurrently towards the end of inspiration. If tongue movement was observed, people with more severe OSA had larger movement and moved more compartments (up to four) to maintain airway patency, while people without OSA moved only one compartment. These results suggest that airway patency is preserved during wakefulness in people with OSA via active dilatory movement of the genioglossus.
Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.