Miracle-dz/UniFAR-FTUs huggingface dataset:
Why Visualize? Untangling a Large Network of Arguments

Visualization has been deemed a useful technique by researchers and practitioners, alike, leaving a trail of arguments behind that reason why visualization works. In addition, examples of misleading usages of visualizations in information communication have occasionally been pointed out. Thus, to contribute to the fundamental understanding of our discipline, we require a comprehensive collection of arguments on “why visualize? ” (or “why not? ”), untangling the rationale behind positive and negative viewpoints. In this paper, we report a theoretical study to understand the underlying reasons of various arguments; their relationships (e.g., built-on, and conflict); and their respective dependencies on tasks, users, and data. We curated an argumentative network based on a collection of arguments from various fields, including information visualization, cognitive science, psychology, statistics, philosophy, and others. Our work proposes several categorizations for the arguments, and makes their relations explicit. We contribute the first comprehensive and systematic theoretical study of the arguments on visualization. Thereby, we provide a roadmap towards building a foundation for visualization theory and empirical research as well as for practical application in the critique and design of visualizations. In addition, we provide our argumentation network and argument collection online at https://whyvis.dbvis. de, supported by an interactive visualization.
The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study

Rationale: There is conflicting evidence on harm related to exposure to supraphysiologic PaO2 (hyperoxemia) in critically ill patients. Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to ICUs in five United Kingdom university hospitals. Methods: A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia. Measurements and Main Results: Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio [OR], 1.15; 95% compatibility interval [CI], 0.95–1.38; P = 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04–1.74; P = 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07–2.13; P = 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11–2.72; P = 0.02). However, a dose–response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation. Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose–response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.
Lamellipodium tip actin barbed ends serve as a force sensor

Cells change direction of migration by sensing rigidity of environment and traction force, yet its underlying mechanism is unclear. Here, we show that tip actin barbed ends serve as an active “force sensor” at the leading edge. We established a method to visualize intracellular single‐molecule fluorescent actin through an elastic culture substrate. We found that immediately after cell edge stretch, actin assembly increased specifically at the lamellipodium tip. The rate of actin assembly increased with increasing stretch speed. Furthermore, tip actin polymerization remained elevated at the subsequent hold step, which was accompanied by a decrease in the load on the tip barbed ends. Stretch‐induced tip actin polymerization was still observed without either the WAVE complex or Ena/VASP proteins. The observed relationships between forces and tip actin polymerization are consistent with a force–velocity relationship as predicted by the Brownian ratchet mechanism. Stretch caused extra membrane protrusion with respect to the stretched substrate and increased local tip polymerization by >5% of total cellular actin in 30 s. Our data reveal that augmentation of lamellipodium tip actin assembly is directly coupled to the load decrease, which may serve as a force sensor for directed cell protrusion.
Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer.

PURPOSE In the CLASSIC and MAGIC trials, microsatellite instability (MSI)-high status was a favorable prognostic and potential negative predictive factor for neoadjuvant/adjuvant chemotherapy in resectable gastric cancer (GC). Given the low prevalence of MSI-high status in GC and its association with other positive prognostic variables, large data sets are needed to draw robust evidence of its prognostic/predictive value. PATIENTS AND METHODS We performed a multinational, individual-patient-data meta-analysis of the prognostic/predictive role of MSI in patients with resectable GC enrolled in the MAGIC, CLASSIC, ARTIST, and ITACA-S trials. Prognostic analyses used multivariable Cox models (MVM). The predictive role of MSI was assessed both in an all-comer population and in MAGIC and CLASSIC trials by MVM testing of the interaction of treatment (chemotherapy plus surgery v surgery) with MSI. RESULTS MSI status was available for 1,556 patients: 121 (7.8%) had MSI-high status; 576 were European, and 980 were Asian. In MSI-high versus MSI-low/microsatellite stable (MSS) comparisons, the 5-year disease-free survival (DFS) was 71.8% (95% CI, 63.8% to 80.7%) versus 52.3% (95% CI, 49.7% to 55.1%); the 5-year overall survival (OS) was 77.5% (95% CI, 70.0% to 85.8%) versus 59.3% (95% CI, 56.6% to 62.1%). In MVM, MSI was associated with longer DFS (hazard ratio [HR], 1.88; 95% CI, 1.28 to 2.76; P < .001) and OS (HR, 1.78; 95% CI, 1.17 to 2.73; P = .008), as were pT, pN, ethnicity, and treatment. Patients with MSI-low/MSS GC benefitted from chemotherapy plus surgery: the 5-year DFS compared with surgery only was 57% versus 41% (HR, 0.65; 95% CI, 0.53 to 0.79), and the 5-year OS was 62% versus 53% (HR, 0.75; 95% CI, 0.60 to 0.94). Conversely, those with MSI-high GC did not: the 5-year DFS was 70% versus 77% (HR, 1.27; 95% CI, 0.53 to 3.04), and the 5-year OS was 75% versus 83% (HR, 1.50; 95% CI, 0.55 to 4.12). CONCLUSION In patients with resectable primary GC, MSI is a robust prognostic marker that should be adopted as a stratification factor by clinical trials. Chemotherapy omission and/or immune checkpoint blockade should be investigated prospectively in MSI-high GCs according to clinically and pathologically defined risk of relapse.
Sulfonamide Allergies

As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic options for the empiric and definitive treatment of various infectious diseases. In the general population, approximately 3–8% of patients are reported to experience a sulfonamide allergy. Sulfonamide allergies can result in various physical manifestations; however, rash is reported as the most frequently observed. In patients with human immunodeficiency virus (HIV), dermatologic reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently compared to immunocompetent patients. This article describes the incidence, manifestations, and risk factors associated with sulfonamide allergies. The potential for cross-reactivity of allergies to sulfonamide antimicrobials with nonantimicrobial sulfonamide medications is also reviewed. Data suggest that substitutions at the N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiety. For patients with an indication for a sulfonamide antimicrobial with a listed allergy, it is important for healthcare practitioners to adequately assess the allergic reaction to determine appropriate management. Rechallenge and desensitization strategies may be appropriate for patients with delayed maculopapular eruptions, while alternative treatment options may be prudent for more severe reactions. Available data suggests a low risk of cross-allergenicity between sulfonamide antimicrobial and nonantimicrobial agents.
Home Videos as a Cost-Effective Tool for the Diagnosis of Paroxysmal Events in Infants: Prospective Study

Background The diagnosis of paroxysmal events in infants is often challenging. Reasons include the child’s inability to express discomfort and the inability to record video electroencephalography at home. The prevalence of mobile phones, which can record videos, may be beneficial to these patients. In China, this advantage may be even more significant given the vast population and the uneven distribution of medical resources. Objective The aim of this study is to investigate the value of mobile phone videos in increasing the diagnostic accuracy and cost savings of paroxysmal events in infants. Methods Clinical data, including descriptions and home videos of episodes, from 12 patients with paroxysmal events were collected. The investigation was conducted in six centers during pediatric academic conferences. All 452 practitioners present were asked to make their diagnoses by just the descriptions of the events, and then remake their diagnoses after watching the corresponding home videos of the episodes. The doctor’s information, including educational background, profession, working years, and working hospital level, was also recorded. The cost savings from accurate diagnoses were measured on the basis of using online consultation, which can also be done easily by mobile phone. All data were recorded in the form of questionnaires designed for this study. Results We collected 452 questionnaires, 301 of which met the criteria (66.6%) and were analyzed. The mean correct diagnoses with and without videos was 8.4 (SD 1.7) of 12 and 7.5 (SD 1.7) of 12, respectively. For epileptic seizures, mobile phone videos increased the mean accurate diagnoses by 3.9%; for nonepileptic events, it was 11.5% and both were statistically different (P=.006 for epileptic events; P<.001 for nonepileptic events). Pediatric neurologists with longer working years had higher diagnostic accuracy; whereas, their working hospital level and educational background made no difference. For patients with paroxysmal events, at least US $673.90 per capita and US $128 million nationwide could be saved annually, which is 12.02% of the total cost for correct diagnosis. Conclusions Home videos made on mobile phones are a cost-effective tool for the diagnosis of paroxysmal events in infants. They can facilitate the diagnosis of paroxysmal events in infants and thereby save costs. The best choice for infants with paroxysmal events on their initial visit is to record their events first and then show the video to a neurologist with longer working years through online consultation.
Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles

Neurodegenerative diseases are characterized by oxidative stress, mitochondrial damage, and death of neuronal cells. To counteract such damage and to favor neurogenesis, neurotrophic factors could be used as therapeutic agents. Octadecaneuropeptide (ODN), produced by astrocytes, is a potent neuroprotective agent. In N2a cells, we studied the ability of ODN to promote neuronal differentiation. This parameter was evaluated by phase contrast microscopy, staining with crystal violet, cresyl blue, and Sulforhodamine 101. The effect of ODN on cell viability and mitochondrial activity was determined with fluorescein diacetate and DiOC6(3), respectively. The impact of ODN on the topography of mitochondria and peroxisomes, two tightly connected organelles involved in nerve cell functions and lipid metabolism, was evaluated by transmission electron microscopy and fluorescence microscopy: detection of mitochondria with MitoTracker Red, and peroxisome with an antibody directed against the ABCD3 peroxisomal transporter. The profiles in fatty acids, cholesterol, and cholesterol precursors were determined by gas chromatography, in some cases coupled with mass spectrometry. Treatment of N2a cells with ODN (10−14 M, 48 h) induces neurite outgrowth. ODN-induced neuronal differentiation was associated with modification of topographical distribution of mitochondria and peroxisomes throughout the neurites and did not affect cell viability and mitochondrial activity. The inhibition of ODN-induced N2a differentiation with H89, U73122, chelerythrine and U0126 supports the activation of a PKA/PLC/PKC/MEK/ERK-dependent signaling pathway. Although there is no difference in fatty acid profile between control and ODN-treated cells, the level of cholesterol and some of its precursors (lanosterol, desmosterol, lathosterol) was increased in ODN-treated cells. The ability of ODN to induce neuronal differentiation without cytotoxicity reinforces the interest for this neuropeptide with neurotrophic properties to overcome nerve cell damage in major neurodegenerative diseases.
Clinical illness and outcomes in Nigerian children with persistent early-appearing anaemia following initiation of artemisinin-based combination treatments of uncomplicated falciparum malaria

In non-anaemic children with malaria, early-appearing anaemia (EAA) is common following artemisinin-based combination treatments (ACTs) and it may become persistent (PEAA). The factors contributing to and kinetics of resolution of the deficit in haematocrit from baseline (DIHFB) characteristic of ACTs-related PEAA were evaluated in 540 consecutive children with malaria treated with artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine. Asymptomatic PEAA occurred in 62 children. In a multiple logistic regression model, a duration of illness ≤3 days before presentation, haematocrit <35% before and <25% one day after treatment initiation, drug attributable fall in haematocrit ≥6%, and treatment with dihydroartemisinin-piperaquine independently predicted PEAA. Overall, mean DIHFB was 5.7% (95% CI 4.8–6.6) 7 days after treatment initiation and was similar for all treatments. Time to 90% reduction in DIHFB was significantly longer in artemether-lumefantrine-treated children compared with other treatments. In a one compartment model, declines in DIHFB were monoexponential with overall mean estimated half-time of 3.9 days (95% CI 2.6–5.1), Cmax of 7.6% (95% CI 6.7–8.4), and Vd of 0.17 L/kg (95% CI 0.04–0.95). In Bland-Altman analyses, overall mean anaemia recovery time (AnRT) of 17.4 days (95% CI 15.5–19.4) showed insignificant bias with 4, 5 or 6 multiples of half-time of DIHFB. Ten children after recovery from PEAA progressed to late-appearing anaemia (LAA). Progression was associated with female gender and artesunate-amodiaquine treatment. Asymptomatic PEAA is common following ACTs. PEAA or its progression to LAA may have implications for case and community management of anaemia and for anaemia control efforts in sub-Saharan Africa where ACTs have become first-line antimalarials. Trial registration: Pan Africa Clinical Trial Registration PACTR201709002064150, 1 March 2017 http://www.pactr. org
Variation in Performance and Resistance to Parasitism of Plutella xylostella Populations

Two major ecological factors determine the fitness of an insect herbivore: the ability to overcome plant resistance strategies (bottom-up effects) and the ability to avoid or resist attack by natural enemies such as predators and parasitoids (top-down effects). In response to differences in selection pressure, variation may exist in host-plant adaptation and immunity against parasitism among populations of an insect herbivore. We investigated the variation in larval performance of six different Plutella xylostella populations originating from four continents when feeding on a native Dutch plant species, Brassica rapa. One of the used populations has successfully switched its host plant, and is now adapted to pea. In addition, we determined the resistance to attack by the endoparasitoid Diadegma semiclausum originating from the Netherlands (where it is also native) and measured parasitoid performance as a proxy for host resistance against parasitism. Pupal mortality, immature development times, and adult biomass of P. xylostella differed significantly across populations when feeding on the same host plant species. In addition, parasitism success differed in terms of parasitoid adult emergence and their biomass, but not their development times. Variation among natural populations of insects should be considered more when studying interactions between plants and insects up the food chain.
Optimizing Contact Precautions to Curb the Spread of Antibiotic-resistant Bacteria in Hospitals: A Multicenter Cohort Study to Identify Patient Characteristics and Healthcare Personnel Interactions Associated With Transmission of Methicillin-resistant Staphylococcus aureus

Abstract Background Healthcare personnel (HCP) acquire antibiotic-resistant bacteria on their gloves and gowns when caring for intensive care unit (ICU) patients. Yet, contact precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA) remains controversial despite existing guidelines. We sought to understand which patients are more likely to transfer MRSA to HCP and to identify which HCP interactions are more likely to lead to glove or gown contamination. Methods This was a prospective, multicenter cohort study of cultured HCP gloves and gowns for MRSA. Samples were obtained from patients’ anterior nares, perianal area, and skin of the chest and arm to assess bacterial burden. Results Among 402 MRSA-colonized patients with 3982 interactions, we found that HCP gloves and gowns were contaminated with MRSA 14.3% and 5.9% of the time, respectively. Contamination of either gloves or gowns occurred in 16.2% of interactions. Contamination was highest among occupational/physical therapists (odds ratio [OR], 6.96; 95% confidence interval [CI], 3.51, 13.79), respiratory therapists (OR, 5.34; 95% CI, 3.04, 9.39), and when any HCP touched the patient (OR, 2.59; 95% CI, 1.04, 6.51). Touching the endotracheal tube (OR, 1.75; 95% CI, 1.38, 2.19), bedding (OR, 1.43; 95% CI, 1.20, 1.70), and bathing (OR, 1.32; 95% CI, 1.01, 1.75) increased the odds of contamination. We found an association between increasing bacterial burden on the patient and HCP glove or gown contamination. Conclusions Gloves and gowns are frequently contaminated with MRSA in the ICU. Hospitals may consider using fewer precautions for low-risk interactions and more for high-risk interactions and personnel.
A New Approach to Polycystic Ovary Syndrome: The Gut Microbiota

Abstract Polycystic ovary syndrome (PCOS) is a widespread endocrine disease that affects 6% to 20% of women of reproductive age and is associated with high risk of infertility, obesity, and insulin resistance. Although genetic, neuroendocrine, and metabolic causes have been stated to lead to PCOS, the etiology of PCOS remains unclear. Recent studies in humans and rodent models have shown an association between changes in the gut microbiome and the metabolic and clinical parameters of PCOS. In addition, it has been proposed that dysbiosis of gut microbiota may be a potential pathogenetic factor in the development of PCOS. In this context, modification of gut microbiota with probiotic, prebiotic, and synbiotic agents suggests that these products may serve as new treatment options for PCOS. In this review, it is aimed to explain the relationship between PCOS and gut microbiota with possible mechanisms and to examine the new treatment approaches that can be developed in this direction. Key teaching points Studies have shown that gut microbiota may be a potential pathogenetic factor in the development of PCOS. Dysbiosis of gut microbiota in women with PCOS appears to be associated with PCOS phenotypes. Studies suggest that insulin resistance, sex hormone concentrations, and obesity may affect the diversity and composition of gut microbiota in women with PCOS. With better understanding of the role of intestinal microbiota in PCOS, interventions including prebiotics, probiotics, and synbiotics can be considered as future treatment options.
Quantitative detection of ALK fusion breakpoints in plasma cell-free DNA from patients with non-small cell lung cancer using PCR-based target sequencing with a tiling primer set and two-step mapping/alignment

Background Tyrosine kinase inhibitors targeted to anaplastic lymphoma kinase (ALK) have been demonstrated to be effective for lung cancer patients with an ALK fusion gene. Application of liquid biopsy, i.e., detection and quantitation of the fusion product in plasma cell-free DNA (cfDNA), could improve clinical practice. To detect ALK fusions, because fusion breakpoints occur somewhere in intron 19 of the ALK gene, sequencing of the entire intron is required to locate breakpoints. Results We constructed a target sequencing system using an adapter and a set of primers that cover the entire ALK intron 19. This system can amplify fragments, including breakpoints, regardless of fusion partners. The data analysis pipeline firstly detected fusions by alignment to selected target sequences, and then quantitated the fusion alleles aligning to the identified breakpoint sequences. Performance was validated using 20 cfDNA samples from ALK-positive non-small cell lung cancer patients and samples from 10 healthy volunteers. Sensitivity and specificity were 50 and 100%, respectively. Conclusions We demonstrated that PCR-based target sequencing using a tiling primer set and two-step mapping/alignment quantitatively detected ALK fusions in cfDNA from lung cancer patients. The system offers an alternative to existing approaches based on hybridization capture.
Targeting Autophagy by MPT0L145, a Highly Potent PIK3C3 Inhibitor, Provides Synergistic Interaction to Targeted or Chemotherapeutic Agents in Cancer Cells

Anticancer therapies reportedly promote pro-survival autophagy in cancer cells that confers drug resistance, rationalizing the concept to combine autophagy inhibitors to increase their therapeutic potential. We previously identified that MPT0L145 is a PIK3C3/FGFR inhibitor that not only increases autophagosome formation due to fibroblast growth factor receptor (FGFR) inhibition but also perturbs autophagic flux via PIK3C3 inhibition in bladder cancer cells harboring FGFR activation. In this study, we hypothesized that combined-use of MPT0L145 with agents that induce pro-survival autophagy may provide synthetic lethality in cancer cells without FGFR activation. The results showed that MPT0L145 synergistically sensitizes anticancer effects of gefitinib and gemcitabine in non-small cell lung cancer A549 cells and pancreatic cancer PANC-1 cells, respectively. Mechanistically, drug combination increased incomplete autophagy due to impaired PIK3C3 function by MPT0L145 as evidenced by p62 accumulation and no additional apoptotic cell death was observed. Meanwhile, drug combination perturbed survival pathways and increased vacuolization and ROS production in cancer cells. In conclusion, the data suggest that halting pro-survival autophagy by targeting PIK3C3 with MPT0L145 significantly sensitizes cancer cells to targeted or chemotherapeutic agents, fostering rational combination strategies for cancer therapy in the future.