Miracle-dz/UniFAR-FTUs huggingface dataset:
Differentiated skeletal cells contribute to blastema formation during zebrafish fin regeneration

The origin of cells that generate the blastema following appendage amputation has been a long-standing question in epimorphic regeneration studies. The blastema is thought to originate from either stem (or progenitor) cells or differentiated cells of various tissues that undergo dedifferentiation. Here, we investigate the origin of cells that contribute to the regeneration of zebrafish caudal fin skeletal elements. We provide evidence that the process of lepidotrichia (bony rays) regeneration is initiated as early as 24 hours post-amputation and that differentiated scleroblasts acquire a proliferative state, detach from the lepidotrichia surface, migrate distally, integrate into the blastema and dedifferentiate. These findings provide novel insights into the origin of cells in epimorphic appendage regeneration in zebrafish and suggest conservation of regeneration mechanisms between fish and amphibians.
Induced PD-L 1 Expression Mediates Acquired Resistance to Agonistic Anti-CD 40 Treatment

CD40 stimulation on antigen-presenting cells (APC) allows direct activation of CD8þ cytotoxic T cells, independent of CD4þ T-cell help. Agonistic anti-CD40 antibodies have been demonstrated to induce beneficial antitumor T-cell responses in mouse models of cancer and early clinical trials. We report here that anti-CD40 treatment induces programmed death ligand-1 (PD-L1) upregulation on tumor-infiltrating monocytes and macrophages, which was strictly dependent on T cells and IFNg . PD-L1 expression could be counteracted by coadministration of antibodies blocking the PD-1 (programmed death-1)/PD-L1 axis as shown for T cells from tumor models and human donors. The combined treatment was highly synergistic and induced complete tumor rejection in about 50% of mice bearing MC-38 colon and EMT-6 breast tumors. Mechanistically, this was reflected by a strong increase of IFNg and granzyme-B production in intratumoral CD8þ T cells. Concomitant CTLA-4 blockade further improved rejection of established tumors in mice. This study uncovers a novel mechanism of acquired resistance upon agonistic CD40 stimulation and proposes that the concomitant blockade of the PD-1/PD-L1 axis is a viable therapeutic strategy to optimize clinical outcomes. Cancer Immunol Res; 3(3); 1–9. 2015 AACR.
Crowdsourcing Backdoor Identification for Combinatorial Optimization

We will show how human computation insights can be key to identifying so-called backdoor variables in combinatorial optimization problems. Backdoor variables can be used to obtain dramatic speedups in combinatorial search. Our approach leverages the complementary strength of human input, based on a visual identification of problem structure, crowdsourcing, and the power of combinatorial solvers to exploit complex constraints. We describe our work in the context of the domain of materials discovery. The motivation for considering the materials discovery domain comes from the fact that new materials can provide solutions for key challenges in sustainability, e.g., in energy, new catalysts for more efficient fuel cell technology.
Motorcycle Conspicuity: Effects of Age and Daytime Running Lights

Objective:This study investigated variables that may contribute to motorcycle conspicuity within a high-fidelity simulated environment. The variables included motorcycle lighting, vehicular daytime running lights (DRLs), and age of the driver of the other vehicle. Background: Research suggests that decreased levels of conspicuity associated with riding a small two-wheeled vehicle reduce the ability of other drivers to detect and respond to that vehicle effectively. This lack of conspicuity is often responsible for the frequent injuries and fatalities incurred by motorcycle riders. Method: The 75 participants who took part in this study watched a series of video clips of roadway traffic and were asked to indicate when they saw a hazardous situation, such as the presence of pedestrians, motorcycles, or traffic cones. Both motorcycle and following-vehicle lights were manipulated, and participant reaction times were collected and analyzed. Results: Analyses indicated main effects for all three variables as well as interaction effects between motorcycle lighting and vehicle-following conditions. Overall, findings showed a link between DRLs and the effective detection of motorcycles and suggested that age-related changes affect the ability to detect and respond to a motorcycle effectively. Conclusion: Although our laboratory findings corroborated previous correlational studies, further research in real-world settings, such as those with high-density traffic or under adverse environmental conditions, needs to be conducted. Application: Potential applications of this research include the assessment of appropriate lighting technology to enhance conspicuity of motorcycles and reduce the high rate of fatalities and injuries related to motorcycle crashes.
Inhibition of rhinovirus attachment by neutralizing monoclonal antibodies and their Fab fragments

Previous molecular and immunological studies have mapped four neutralization sites on human rhinovirus type 14 (B. Sherry, A. G. Mosser, R. J. Colonno, and R. R. Rueckert, J. Virol. 57:246-257, 1986). Eight monoclonal antibodies, one pair for each of the four target sites and all belonging to a single isotype, immunoglobulin G2a, were studied under conditions which resulted in 95% neutralization of infectious viral particles. All eight antibodies shifted the isoelectric point of virions from 6.7 to much more acidic forms, ranging from pI 1.8 to 3.2. In addition, antibodies targeted against three of the four neutralization sites caused significant aggregation of virions under the neutralization conditions employed. Aggregation could be reversed by digesting virus-antibody complexes with papain. Following papain digestion, the acidic pIs of three of the neutralized virus preparations returned to neutral and infectivity was restored. Membrane-binding assays with virus neutralized with a nonaggregating antibody showed a dose-related inhibition of virus attachment to cellular receptors. Purified Fab fragments at a 13- to 61-fold-higher concentration than intact antibodies caused a comparable isoelectric shift, neutralized virions in the absence of aggregation, and interfered with attachment of virions to host cell receptors in a membrane-binding assay. These findings suggest that neutralizing antibodies interfere with the attachment of rhinoviruses to cellular receptors and that bivalent attachment of antibody is not a prerequisite for neutralization.
Preconditioning with Physiological Levels of Ethanol Protect Kidney against Ischemia/Reperfusion Injury by Modulating Oxidative Stress

Background Oxidative stress due to excessive production of reactive oxygen species (ROS) and subsequent lipid peroxidation plays a critical role in renal ischemia/reperfusion (IR) injury. The purpose of current study is to demonstrate the effect of antecedent ethanol exposure on IR-induced renal injury by modulation of oxidative stress. Materials and Methods Bilateral renal warm IR was induced in male C57BL/6 mice after ethanol or saline administration. Blood ethanol concentration, kidney function, histological damage, inflammatory infiltration, cytokine production, oxidative stress, antioxidant capacity and Aldehyde dehydrogenase (ALDH) enzymatic activity were assessed to evaluate the impact of antecedent ethanol exposure on IR-induced renal injury. Results After bilateral kidney ischemia, mice preconditioned with physiological levels of ethanol displayed significantly preserved renal function along with less histological tubular damage as manifested by the reduced inflammatory infiltration and cytokine production. Mechanistic studies revealed that precondition of mice with physiological levels of ethanol 3 h before IR induction enhanced antioxidant capacity characterized by significantly higher superoxidase dismutase (SOD) activities. Our studies further demonstrated that ethanol pretreatment specifically increased ALDH2 activity, which then suppressed lipid peroxidation by promoting the detoxification of Malondialdehyde (MDA) and 4-hydroxynonenal (HNE). Conclusions Our results provide first line of evidence indicating that antecedent ethanol exposure can provide protection for kidneys against IR-induced injury by enhancing antioxidant capacity and preventing lipid peroxidation. Therefore, ethanol precondition and ectopic ALDH2 activation could be potential therapeutic approaches to prevent renal IR injury relevant to various clinical conditions.
Management of Bleeding Uterine Arteriovenous Malformation with Bilateral Uterine Artery Embolization

Purpose To evaluate the technical feasibility and clinical outcome of bilateral uterine artery embolization (UAE) as a first-line therapeutic option for bleeding uterine arteriovenous malformation (AVM). Materials and Methods Between 2002 and 2012, 19 patients were diagnosed with acquired uterine AVM clinically and through imaging studies. The clinical characteristics, angiographic features, technical success rate of embolization, procedure-related complications, imaging, and clinical follow-up data were assessed. Clinical success was defined as immediate symptomatic resolution with disappearance of vascular abnormality on subsequent imaging studies. Results A total of 20 bilateral UAE, with or without embolization of extra-uterine feeders, were performed as the first-line treatment. Technical and clinical success rate was 90.0% (18/20) and 89.5% (17/19), respectively. Embolization was incomplete in two patients who had residual extra-uterine fine feeders to the AVM or a procedure-related complication (ruptured uterine artery); the former showed slow regression of the vascular malformation during the observation period, while the latter underwent a successful second bilateral UAE. Immediate clinical success was achieved in the remaining 17 patients after a single session and no recurrence of bleeding was found. Recovery to normal menstrual cycle was seen in all 17 patients with clinical success within one or two months, two of whom subsequently had uneventful intrauterine pregnancies carried to term. Conclusion Bilateral UAE is a safe and effective first-line therapeutic option for the management of bleeding uterine AVMs. However, incomplete embolization due to unembolizable feeders or difficult access into the uterine artery may lead to suboptimal treatment.
Evaluation and Refinement of Chlorophyll-a Algorithms for High-Biomass Blooms in San Francisco Bay (USA)

A massive bloom of the raphidophyte Heterosigma akashiwo occurred in summer 2022 in San Francisco Bay, causing widespread ecological impacts including events of low dissolved oxygen and mass fish kills. The rapidly evolving bloom required equally rapid management response, leading to the use of near-real-time image analysis of chlorophyll from the Ocean and Land Colour Instrument (OLCI) aboard Sentinel-3. Standard algorithms failed to adequately capture the bloom, signifying a need to refine a two-band algorithm developed for coastal and inland waters that relates the red-edge part of the remote sensing reflectance spectrum to chlorophyll. While the bloom was the initial motivation for optimizing this algorithm, an extensive dataset of in-water validation measurements from both bloom and non-bloom periods was used to evaluate performance over a range of concentrations and community composition. The modified red-edge algorithm with a simplified atmospheric correction scheme outperformed existing standard products across diverse conditions, and given the modest computational requirements, was found suitable for operational use and near-real-time product generation. The final version of the algorithm successfully minimizes error for non-bloom periods when chlorophyll a is typically <30 mg m−3, while also capturing bloom periods of >100 mg m−3 chlorophyll a.
The place of culture in sustainable development of European countries – homogeneity or diversity of the phenomenon?

The aim of this paper is to evaluate the level of sustainable development in selected European countries – taking into account its economic, social, environmental and cultural dimensions, as well as the level of diversification of the phenomenon in the entities under analysis. The analysis assumes that culture has a positive impact on sustainable development measures. The selection of countries was based on indicators of their ethnic and cultural diversity. The time range of the analysis is 2012 and 2019, and the data source was the Eurostat database. A taxonomic method (linear ordering method) was used in the analysis of the research problem. The achievement of the aim was determined by limitations in the selection of indicators and the availability and validity of data in European statistics. Based on research to date, it can be concluded that, in the cultural aspect, the same number of countries presented a very high and high level of sustainable development (5) as those presenting a low and very low level (5). The cultural aspect has substantially greater meaning for the sustainability development of the countries characterised by high cultural diversity.Taking this aspect into account while conducting analyses makes it possible use the most valuable, endogenous characteristics of a given population for forging an effective relationship with the other elements of sustainable development.
Type of anaesthesia and patient quality of recovery: a randomized trial comparing propofol-remifentanil total i.v. anaesthesia with desflurane anaesthesia.

BACKGROUND Two common general anaesthetic methods are total i.v. anaesthesia (TIVA) and inhalation anaesthesia, but it is unclear whether this affects the patient's perception of their quality of recovery. The Quality of Recovery-40 questionnaire (QoR-40) is a valid and reliable method to evaluate the extent of functional recovery after surgery with general anaesthesia. This study therefore compared patient recovery using the QoR-40 in surgical patients who received TIVA with those who received desflurane anaesthesia. METHODS Eighty females (20-65 years old) undergoing thyroid surgery were prospectively recruited and randomized to either the TIVA (effect-site target controlled infusion using propofol and remifentanil) or DES (desflurane inhalation with manual infusion of remifentanil) groups. The QoR-40 was administered by an investigator blind to group allocation before surgery, and postoperative days 1 and 2 (POD1 and POD2). Additional data including the incidence of nausea or vomiting, the consumption of antiemetic and analgesic agents in the post-anaesthesia care unit, and the duration of the hospital stay, were collected in all cases. RESULTS The QoR-40 score on POD1 was significantly higher in the TIVA group compared with the DES group (174 vs 161, respectively; P=0.004), indicating a better quality of recovery in the TIVA group. Among the five dimensions of the QoR-40, physical comfort and physical independence were significantly better on POD1 and POD2 in the TIVA group. CONCLUSION This study demonstrates that the quality of recovery for female thyroid surgery patients is significantly better with TIVA compared with desflurane anaesthesia. CLINICAL TRIAL REGISTRATION www.clinicaltrials. org; ref. : NCT01760018.
Cancer Dormancy: A Regulatory Role for Endogenous Immunity in Establishing and Maintaining the Tumor Dormant State

The significant contribution of host immunity in early tumorigenesis has been recently recognized as a result of our better understanding of the molecular pathways regulating tumor cell biology and tumor-lymphocyte interactions. Emerging evidence suggests that disseminated dormant tumor cells derived from primary tumors before or after immune surveillance, are responsible for subsequent metastases. Recent trends from the field of onco-immunology suggest that efficiently stimulating endogenous anticancer immunity is a prerequisite for the successful outcome of conventional cancer therapies. Harnessing the immune system to achieve clinical efficacy is realistic in the context of conventional therapies resulting in immunogenic cell death and/or immunostimulatory side effects. Targeted therapies designed to target oncogenic pathways in tumor cells can also positively regulate the endogenous immune response and tumor microenvironment. Identification of T cell inhibitory signals has prompted the development of immune checkpoint inhibitors, which specifically hinder immune effector inhibition, reinvigorating and potentially expanding the preexisting anticancer immune response. This anticancer immunity can be amplified in the setting of immunotherapies, mostly in the form of vaccines, which boost naturally occurring T cell clones specifically recognizing tumor antigens. Thus, a promising anticancer therapy will aim to activate patients’ naturally occurring anticancer immunity either to eliminate residual tumor cells or to prolong dormancy in disseminated tumor cells. Such an endogenous anticancer immunity plays a significant role for controlling the balance between dormant tumor cells and tumor escape, and restraining metastases. In this review, we mean to suggest that anticancer therapies aiming to stimulate the endogenous antitumor responses provide the concept of the therapeutic management of cancer.
Interaction of toxic and non-toxic HypF-N oligomers with lipid bilayers investigated at high resolution with atomic force microscopy

Protein misfolded oligomers are considered the most toxic species amongst those formed in the process of amyloid formation and the molecular basis of their toxicity, although not completely understood, is thought to originate from the interaction with the cellular membrane. Here, we sought to highlight the molecular determinants of oligomer-membrane interaction by atomic force microscopy. We monitored the interaction between multiphase supported lipid bilayers and two types of HypF-N oligomers displaying different structural features and cytotoxicities. By our approach we imaged with unprecedented resolution the ordered and disordered lipid phases of the bilayer and different oligomer structures interacting with either phase. We identified the oligomers and lipids responsible for toxicity and, more generally, we established the importance of the membrane lipid component in mediating oligomer toxicity. Our findings support the importance of GM1 ganglioside in mediating the oligomer-bilayer interaction and support a mechanism of oligomer cytotoxicity involving bilayer destabilization by globular oligomers within GM1-rich ordered raft regions rather than by annular oligomers in the surrounding disordered membrane domains.
Angiotensin-converting enzyme inhibitors and change in aortic valve calcium.

BACKGROUND Calcium accumulation in the aortic valve is a hallmark of aortic sclerosis and aortic stenosis. Because lipoproteins, angiotensin-converting enzyme, and angiotensin II colocalize with calcium in aortic valve lesions, we hypothesized an association between angiotensin-converting enzyme inhibitor (ACEI) use and lowered aortic valve calcium (AVC) accumulation, as measured by electron beam computed tomography. METHODS Rates of change in volumetric AVC scores were determined retrospectively for 123 patients who had undergone 2 serial electron beam computed tomographic scans. The mean (+/-SD) interscan interval was 2.5 (+/-1.7) years; 80 patients did not receive ACEIs and 43 received ACEIs. The relationship of ACEI use to median rates of AVC score change (both unadjusted and adjusted for baseline AVC scores and coronary heart disease risk factors) was determined. We also examined the relationship of ACEI use to the likelihood of and adjusted odds ratio for definite progression (AVC change >2 times the median interscan variability). RESULTS Unadjusted and adjusted median rates of AVC score change were significantly higher in the no-ACEI group than in the ACEI group (adjusted median AVC changes [95% confidence interval]: relative, 28.7%/y [18.9%-38.5%/y] vs 11.0%/y [-1.9% to 24.0%/y], P = .04; absolute: 25.1/y [19.7-30.5/y] vs 12.2/y [4.5-19.9/y], P = .02). The adjusted odds ratio (95% confidence interval) for definite AVC progression was significantly lower for patients who received ACEIs (0.29 [0.11-0.75], P = .01). CONCLUSIONS This retrospective study finds a significant association between ACEI use and a lower rate of AVC accumulation. The results support the need for prospective, randomized trials of ACEIs in calcific aortic valve disease.
Rivaroxaban for Stroke Prevention in East Asian Patients From the ROCKET AF Trial

Background and Purpose— In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants. Methods— Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed. Results— A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30–49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non–East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non–East Asians (interaction P=0.867). Conclusions— Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT00123456.
Effects of poverty and lack of insurance on perceptions of racial and ethnic bias in health care.

OBJECTIVE To investigate whether poverty and lack of insurance are associated with perceived racial and ethnic bias in health care. DATA SOURCE 2001 Survey on Disparities in Quality of Health Care, a nationally representative telephone survey. We use data on black, Hispanic, and white adults who have a regular physician (N=4,556). STUDY DESIGN We estimate multivariate logistic regression models to examine the effects of poverty and lack of health insurance on perceived racial and ethnic bias in health care for all respondents and by racial, ethnic, and language groups. PRINCIPAL FINDINGS Controlling for sociodemographic and other factors, uninsured blacks and Hispanics interviewed in English are more likely to report racial and ethnic bias in health care compared with their privately insured counterparts. Poor whites are more likely to report racial and ethnic bias in health care compared with other whites. Good physician-patient communication is negatively associated with perceived racial and ethnic bias. CONCLUSIONS Compared with their more socioeconomically advantaged counterparts, poor whites, uninsured blacks, and some uninsured Hispanics are more likely to perceive that racial and ethnic bias operates in the health care they receive. Providing health insurance for the uninsured may help reduce this perceived bias among some minority groups.