Miracle-dz/UniFAR-FTUs huggingface dataset:
An Unprecedented Tolerance to Deletion of the Periplasmic Chaperones SurA, Skp, and DegP in the Nosocomial Pathogen Acinetobacter baumannii

Acinetobacter baumannii is a major threat to human health due to its ability to persist in the hospital environment, resistance to antibiotic treatment, and ability to deploy multiple and redundant virulence factors. In a rising number of cases, infections with multidrug-resistant A. baumannii end up fatally, because all antibiotic treatment options fail. ABSTRACT The outer membrane (OM) of Gram-negative bacteria efficiently protects from harmful environmental stresses such as antibiotics, disinfectants, or dryness. The main constituents of the OM are integral OM β-barrel proteins (OMPs). In Gram-negative bacteria such as Escherichia coli, Yersinia enterocolitica, and Pseudomonas aeruginosa, the insertion of OMPs depends on a sophisticated biogenesis pathway. This comprises the SecYEG translocon, which enables inner membrane (IM) passage; the chaperones SurA, Skp, and DegP, which facilitate the passage of β-barrel OMPs through the periplasm; and the β-barrel assembly machinery (BAM), which facilitates insertion into the OM. In E. coli, Y. enterocolitica, and P. aeruginosa, the deletion of SurA is particularly detrimental and leads to a loss of OM integrity, sensitization to antibiotic treatment, and reduced virulence. In search of targets that could be exploited to develop compounds that interfere with OM integrity in Acinetobacter baumannii, we employed the multidrug-resistant strain AB5075 to generate single gene knockout strains lacking individual periplasmic chaperones. In contrast to E. coli, Y. enterocolitica, and P. aeruginosa, AB5075 tolerates the lack of SurA, Skp, or DegP with only weak mutant phenotypes. While the double knockout strains ΔsurAΔskp and ΔsurAΔdegP are conditionally lethal in E. coli, all double deletions were well tolerated by AB5075. Strikingly, even a triple-knockout strain of AB5075, lacking surA, skp, and degP, was viable. IMPORTANCE Acinetobacter baumannii is a major threat to human health due to its ability to persist in the hospital environment, resistance to antibiotic treatment, and ability to deploy multiple and redundant virulence factors. In a rising number of cases, infections with multidrug-resistant A. baumannii end up fatally, because all antibiotic treatment options fail. Thus, novel targets have to be identified and alternative therapeutics have to be developed. The knockout of periplasmic chaperones has previously proven to significantly reduce virulence and even break antibiotic resistance in other Gram-negative pathogens. Our study in A. baumannii demonstrates how variable the importance of the periplasmic chaperones SurA, Skp, and DegP can be and suggests the existence of mechanisms allowing A. baumannii to cope with the lack of the three periplasmic chaperones.
Adverse pregnancy outcomes in women with systemic lupus erythematosus: can we improve predictions with machine learning?

Objectives Nearly 20% of pregnancies in patients with SLE result in an adverse pregnancy outcome (APO). We previously developed an APO prediction model using logistic regression and data from Predictors of pRegnancy Outcome: bioMarkers In Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE), a large multicentre study of pregnant women with mild/moderate SLE and/or antiphospholipid antibodies. Our goal was to determine whether machine learning (ML) approaches improve APO prediction and identify other risk factors. Methods The PROMISSE data included 41 predictors from 385 subjects; 18.4% had APO (preterm delivery due to placental insufficiency/pre-eclampsia, fetal/neonatal death, fetal growth restriction). Logistic regression with stepwise selection (LR-S), least absolute shrinkage and selection operator (LASSO), random forest (RF), neural network (NN), support vector machines (SVM-RBF), gradient boosting (GB) and SuperLearner (SL) were compared by cross-validated area under the ROC curve (AUC) and calibration. Results Previously identified APO risk factors, antihypertensive medication use, low platelets, SLE disease activity and lupus anticoagulant (LAC), were confirmed as important with each algorithm. LASSO additionally revealed potential interactions between LAC and anticardiolipin IgG, among others. SL performed the best (AUC=0.78), but was statistically indistinguishable from LASSO, SVM-RBF and RF (AUC=0.77 for all). LR-S, NN and GB had worse AUC (0.71–0.74) and calibration scores. Conclusions We predicted APO with reasonable accuracy using variables routinely assessed prior to the 12th week of pregnancy. LASSO and some ML methods performed better than a standard logistic regression approach. Substantial improvement in APO prediction will likely be realised, not with increasingly complex algorithms but by the discovery of new biomarkers and APO risk factors.
Interpreting patient-rated outcome measures in adolescent patients following concussion

ABSTRACT Objective To estimate scale scores for patient-reported outcome (PRO) measures that classify patients as improved or unimproved at days 3 and 10 post-concussion. Methods Data from 187 adolescent patients who sustained a concussion (150 males, 32 females, 5 not reported) were analyzed. Patients completed the Pediatric Quality of Life Inventory (PedsQL), PedsQL Multidimensional Fatigue Scale (MFS), Headache Impact Test (HIT-6), and Global Rating of Change (GROC) on days 3 and 10 post-concussion. Dependent variables: PedsQL total score, 3 MFS subscale scores [general (MFS-GF), sleep (MFS-SLF), cognitive (MFS-CF) fatigue], and HIT-6 total score. Higher scores on PedsQL and MFS indicate better health; lower scores on HIT-6 indicate less impact on headache-related health. GROC ascertained patient-perceived magnitude of change in health status since concussion. Receiver Operating Characteristic Curve analyses estimated PRO cut-point scores that classified patients as improved or unimproved. Results Day 3 PRO cut-points: PedsQL total = 90; MFS-GF = 73; MSF-CF = 85; MFS-SLF = 81; and HIT-6 total = 54. Day 10 PRO cut-points: PedsQL total = 91; MFS-GF = 85; MFS-CF = 85; MFS-SLF = 90; and HIT-6 total = 51. Conclusions Our results define PedsQL, MFS, and HIT-6 scores as they relate to perceived improvement following concussive injuries. Cut-point scale scores help clinicians interpret concussion PROs and make informed decisions during the management of patients with concussion.
Temporal Change in Pro-Inflammatory Cytokine Expression from Immortalized Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress

Abstract Purpose To determine the metabolic activity, and cytokine expression over time from immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress. Methods HCECs were cultured and expanded in DMEM/F-12 with 10% FBS. The cells were exposed to either normal media (295 mmol/kg) or hyperosmolar media (500 mmol/kg) for 0.25, 3, 6, and 12 hours. After each exposure duration, metabolic activity was quantified using alamarBlue, and a panel of pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, IFN-γ, and IL-17A) was quantified using multiplexed electrochemiluminescence (Meso Scale Diagnostics, Rockville, MD). Results Metabolic activity of the HCEC exposed to hyperosmolar conditions was significantly reduced at the 3-, 6-, and 12-hour mark compared to the control (all p < 0.01). There was no significant difference in cytokine expression between the hyperosmolar media and control at the 0.25- and 3-hour mark for all cytokines (all p ≥ 0.28). The difference in cytokine expression between the hyperosmolar media and the control was significant for IL-1β, IL-4, IL-6, IL-8, IL-12p70, IL-13, and TNF-α at the 6-hour mark (all p ≤ 0.02). No significant change in cytokine expression between the hyperosmolar media and control was noted for IL-2, IL-10, IL-17A, and IFN-γ (all p ≥ 0.74) at the 6-hour mark. Conclusion Hyperosmolar stress reduced cell metabolic activity and increased expression of IL-1β, IL-4, IL6, IL8, IL-12p70, IL-13, and TNF-α over a 6-hour period in an immortalized HCEC line.
The Impact of Image Processing Algorithms on Optical Coherence Tomography Angiography Metrics and Study Conclusions in Diabetic Retinopathy

Purpose The purpose of this study was to evaluate the impact of image processing on quantitative metrics in optical coherence tomography angiography (OCTA) images and study conclusions in patients with diabetes. Methods This was a single center, retrospective cross-sectional study. OCTA imaging with the Cirrus HD-OCT 5000 AngioPlex of patients with diabetes was performed. The 8 × 8 mm superficial slab images underwent 4 different preprocessing methods (none, background subtraction [BGS], foveal avascular zone brightness adjustment, and contrast limited adaptive histogram equalization [CLAHE]) followed by 4 different binarization algorithms (global Huang, global Otsu, local Niblack, and local Phansalkar) in ImageJ. Vessel density (VD), skeletonized VD (SVD), and fractal dimension (FD) were calculated. Mixed-effect multivariate linear regressions were performed. Results Two hundred eleven scans from 104 patients were included. Of these scans, 67 (31.8%) had no diabetic retinopathy (DR), 99 (46.9%) had nonproliferative DR (NPDR), and 45 (21.3%) had proliferative DR (PDR). Forty-eight of 211 (22.7%) scans had diabetic macular edema (DME). The image processing method used significantly impacted values of VD, SVD, and FD (all P -values < 0.001). On multivariate analysis, the image processing method changed the clinical variables significantly associated with VD, SVD, and FD. However, BGS and CLAHE yielded more consistent significant covariates across multiple binarization algorithms. Conclusions The image processing method can impact the conclusions of any given study analyzing quantitative OCTA metrics. Thus, caution is urged in the interpretation of such studies. Background subtraction or CLAHE may play a role in the standardization of image processing. Translational Relevance This work proposes strategies to achieve robust and consistent analysis of OCTA imaging, which is especially important for clinical trials.
Analysis of the topological motifs of the cellular structure of the tri-spine horseshoe crab (Tachypleus tridentatus) and its associated mechanical properties

Topological motifs in pore architecture can profoundly influence the structural properties of that architecture, such as its mass, porosity, modulus, strength, and surface permeability. Taking the irregular cellular structure of the tri-spine horseshoe crab as a research model, we present a new approach to the quantitative description and analysis of structure-property-function relationships. We employ a robust skeletonization method to construct a curve-skeleton that relies on high-resolution 3D tomographic data. The topological motifs and mechanical properties of the long-range cellular structure were investigated using the Grasshopper plugin and uniaxial compression test to identify the variation gradient. Finite element analysis was conducted for the sub-volumes to obtain the variation in effective modulus along the three principal directions. The results show that the branch length and node distribution density varied from the tip to the base of the sharp corner. These node types formed a low-connectivity network, in which the node types 3-N and 4-N tended to follow the motifs of ideal planar triangle and tetrahedral configurations, respectively, with the highest proportion of inter-branch angles in the angle ranges of 115–120° and 105–110°. In addition, mapping the mechanical gradients to topological properties indicated that narrower profiles with a given branch length gradient, preferred branch orientation, and network connectedness degree are the main factors that affect the mechanical properties. These factors suggest significant potential for designing a controllable, irregularly cellular structure in terms of both morphology and function.
The effect of probiotics on postsurgical complications in patients with colorectal cancer: a systematic review and meta-analysis.

CONTEXT Clinical trials have investigated the effect of probiotics on postsurgical complications in colorectal cancer (CRC). However, so far, there are no systematic reviews evaluating the effect of probiotics and synbiotics on the clinical or infectious postsurgical complications of colorectal cancer. OBJECTIVE The objective of this review was to synthesize the best available evidence on the effects of the use of probiotics or synbiotics on pre-, peri-, and post-operative complications of CRC surgical resection. DATA SOURCES A search of the PubMed, Embase, LILACS, Scopus, Cochrane, Web of Science, ProQuest, and Google Scholar databases was conducted for clinical trials published up until January 2022. DATA EXTRACTION The population characteristics, period and protocol of supplementation, and postoperative complications were extracted and reported. A random-effects model was used to estimate the effect of probiotic and synbiotic treatment on these variables. DATA SYNTHESIS In total, 2518 studies were identified, of which 16 were included in the qualitative synthesis and 13 in the meta-analysis. Overall, probiotic supplementation reduced the incidence of ileus (odds ratio [OR] = .13, 95% confidence interval [CI]: .02, .78), diarrhea (OR = .32, 95% CI: .15, .69), abdominal collection (OR: .35, 95% CI: .13, .92), sepsis (OR = .41, 95% CI: .22, .80), pneumonia (OR = .39, 95% CI: .19, .83), and surgical site infection (OR = .53, 95% CI: .36, .78). The results of the subgroup analysis indicated that lower dose (<109 colony-forming units), higher duration of supplementation (>14 days), and being administrated ≤5 days before and >10 days after surgery was more effective at reducing the incidence of surgical site infection. CONCLUSION Probiotics and synbiotics seem to be a promising strategy for the prevention of postoperative complications after CRC surgery. Larger, high-quality randomized controlled trials are needed to establish the optimal treatment protocol for the use of probiotics and synbiotics in preventing postoperative complications for CRC surgery.
Synthetic Oligodeoxynucleotide CpG Motifs Activate Human Complement through Their Backbone Structure and Induce Complement-Dependent Cytokine Release

Bacterial and mitochondrial DNA, sharing an evolutionary origin, act as danger-associated molecular patterns in infectious and sterile inflammation. They both contain immunomodulatory CpG motifs. Interactions between CpG motifs and the complement system are sparsely described, and mechanisms of complement activation by CpG remain unclear. Lepirudin-anticoagulated human whole blood and plasma were incubated with increasing concentrations of three classes of synthetic CpGs: CpG-A, -B, and -C oligodeoxynucleotides and their GpC sequence controls. Complement activation products were analyzed by immunoassays. Cytokine levels were determined via 27-plex beads-based immunoassay, and CpG interactions with individual complement proteins were evaluated using magnetic beads coated with CpG-B. In whole blood and plasma, CpG-B and CpG-C (p < 0.05 for both), but not CpG-A (p > 0.8 for all), led to time- and dose-dependent increase of soluble C5b-9, the alternative complement convertase C3bBbP, and the C3 cleavage product C3bc. GpC-A, -B, and -C changed soluble fluid-phase C5b-9, C3bBbP, and C3bc to the same extent as CpG-A, -B, and -C, indicating a DNA backbone–dependent effect. Dose-dependent CpG-B binding was found to C1q (r = 0.83; p = 0.006) and factor H (r = 0.93; p < 0.001). The stimulatory complement effect was partly preserved in C2-deficient plasma and completely preserved in MASP-2–deficient serum. CpG-B increased levels of IL-1β, IL-2, IL-6, IL-8, MCP-1, and TNF in whole blood, which were completely abolished by inhibition of C5 and C5aR1 (p < 0.05 for all). In conclusion, synthetic analogs of bacterial and mitochondrial DNA activate the complement system via the DNA backbone. We suggest that CpG-B interacts directly with classical and alternative pathway components, resulting in complement-C5aR1–dependent cytokine release. Key Points CpG ODNs activate the complement system dependent on their backbone structure. CpG ODNs bind to C1q and factor H, indicating initial CP and direct AP activation. CpG ODNs induced C5-C5aR1–dependent proinflammatory cytokines and chemokines.
On network backbone extraction for modeling online collective behavior

Collective user behavior in social media applications often drives several important online and offline phenomena linked to the spread of opinions and information. Several studies have focused on the analysis of such phenomena using networks to model user interactions, represented by edges. However, only a fraction of edges contribute to the actual investigation. Even worse, the often large number of non-relevant edges may obfuscate the salient interactions, blurring the underlying structures and user communities that capture the collective behavior patterns driving the target phenomenon. To solve this issue, researchers have proposed several network backbone extraction techniques to obtain a reduced and representative version of the network that better explains the phenomenon of interest. Each technique has its specific assumptions and procedure to extract the backbone. However, the literature lacks a clear methodology to highlight such assumptions, discuss how they affect the choice of a method and offer validation strategies in scenarios where no ground truth exists. In this work, we fill this gap by proposing a principled methodology for comparing and selecting the most appropriate backbone extraction method given a phenomenon of interest. We characterize ten state-of-the-art techniques in terms of their assumptions, requirements, and other aspects that one must consider to apply them in practice. We present four steps to apply, evaluate and select the best method(s) to a given target phenomenon. We validate our approach using two case studies with different requirements: online discussions on Instagram and coordinated behavior in WhatsApp groups. We show that each method can produce very different backbones, underlying that the choice of an adequate method is of utmost importance to reveal valuable knowledge about the particular phenomenon under investigation.
Psychotherapeutic treatments for generalized anxiety disorder: cognitive and behavioral therapies, enhancement strategies, and emerging efforts

ABSTRACT Introduction Generalized anxiety disorder (GAD) is common and disabling. Different versions of cognitive behavioral therapy (CBT) have been tested, but no treatment works for everyone. Therefore, researchers have attempted approaches to enhance CBT. Areas covered The current narrative review examines meta-analyses and individual trials of CBT-based treatments for GAD. We focus on CBT and its cognitive and behavioral components as well as efforts to enhance CBT and its dissemination and generalizability. Enhancement efforts included interpersonal and emotional processing therapy, mindfulness-based CBT, emotion regulation therapy, intolerance of uncertainty therapy, the unified protocol, metacognitive therapy, motivational interviewing, and contrast avoidance targeted treatment. Emerging strategies to enhance dissemination have focused on technologically based treatments. Attempts at generalizability have included examination of efficacy within diverse racial and ethnic groups. Expert opinion We conclude that CBT is efficacious, and a number of enhancement efforts have shown some promise in improving upon CBT in single trials. However, more research is needed, particularly efforts to determine which enhancements work best for which individuals and what are the mechanisms of change. Furthermore, few technological interventions have been compared to active treatments. Finally, much more attention needs to be paid to ethnic and racial diversity in randomized controlled trials.
Lienard-Wiechert solution revisited

A self-consistent consideration of the Lienard-Wiechert solition is given including its heuristic deduction, which involves a future light cone (thus the lightlike propagation of information from an arbitrarily moving pointlike charge), and physical interpretation of this field via application of three distinct reference frames (of an inertial observer, then a non-inertial one retardedly co-moving with the charged source, and finally, co-moving with the electromagnetic field). In the last frame the magnetic part of the Lienard-Wiechert field identically (though not asymptotically) vanishes in all spacetime together with the Poynting vector. In the second frame, the properties of energy redistribution and radiation of the field are discussed. The dynamically caused propagation velocity of the Lienard-Wiechert electromagnetic field in a vacuum at any final distance from the source is less than that of light.
Metastable Quantum Phase Transitions in a One-Dimensional Bose Gas

This is a chapter for a book. The first paragraph of this chapter is as follows: "Ultracold quantum gases offer a wonderful playground for quantum many body physics, as experimental systems are widely controllable, both statically and dynamically. One such system is the one-dimensional (1D) Bose gas on a ring. In this system binary contact interactions between the constituent bosonic atoms, usually alkali metals, can be controlled in both sign and magnitude; a recent experiment has tuned interactions over seven orders of magnitude, using an atom-molecule resonance called a Feshbach resonance. Thus one can directly realize the Lieb-Liniger Hamiltonian, from the weakly- to the strongly-interacting regime. At the same time there are a number of experiments utilizing ring traps. The ring geometry affords us the opportunity to study topological properties of this system as well; one of the main properties of a superfluid is the quantized circulation in which the average angular momentum per particle, L/N, is quantized under rotation. Thus we focus on a tunable 1D Bose system for which the main control parameters are interaction and rotation. We will show that there is a critical boundary in the interaction-rotation control-parameter plane over which the topological properties of the system change. This is the basis of our concept of \textit{metastable quantum phase transitions} (QPTs). Moreover, we will show that the finite domain of the ring is necessary for the QPT to occur at all because the zero-point kinetic pressure can induce QPTs, i.e., the system must be finite; we thus seek to generalize the concept of QPTs to inherently finite, mesoscopic or nanoscopic systems. "