NIR-triggered upconversion and sensitized NIR-emission in Yb-based Eosin Y lake doped latex nanoparticles.

Here, Yb-based Eosin Y lakes (EOS-Yb) have been encapsulated in organic nanoparticles (NPs) by microemulsion radical polymerization of methacrylate-based copolymers. These photoactive EOS-Yb NPs emit in the visible and near infrared (NIR) upon excitation at 530 nm and can also display NIR-to-visible upconversion emission upon excitation at 980 nm.

Emergence and evolution of standardization systems in medical biology laboratories.

Introduction: The history of standardization relating to the activities of medical laboratories traces the development of quality system standards in the world, and their evolution. Content: In this study, we have included the key benchmarks that represent the stages of the quality system's evolution in recent decades. Accreditation of medical laboratories has become compulsory in most countries, regarding national or international standards. International acknowledgment of the effectiveness of the results delivered to the many stakeholders, particularly patients and prescribers, is conferred through the use of standards. Summary: The ISO 15189 standard represents the latest and most specific international standards for medical laboratories of all types. Outlook: More research is necessary to study if laboratory practices reflect the evolution of standards within the medical laboratory field.

Neisseria meningitidis: The Unforeseen Agent of Acute Neonatal Conjunctivitis.

Acute conjunctivitis is a common disease in the neonatal period. Although often underestimated, Neisseria meningitidis is an uncommon but potentially severe cause of acute neonatal conjunctivitis. We describe a case of a 14-day-old healthy female newborn who presented with fever, runny nose, cough, and bilateral purulent ocular discharge. A nasopharyngeal swab tested positive for SARS-CoV-2, and the infant was discharged after becoming afebrile 24 hours later. Four days later, ocular exudate culture revealed the presence of N. meningitidis and Staphylococcus aureus. Blood and cerebrospinal fluid tests were unremarkable. The infant was treated with intravenous cefotaxime and topical azithromycin, with no signs of invasive disease or reported complications. This case highlights noninvasive neonatal acute conjunctivitis caused by a coinfection of N. meningitidis and S. aureus, with a favorable outcome. The ocular exudate culture was crucial in identifying the causative bacteria, which might otherwise have gone undetected and improperly treated. Clinicians should consider N. meningitidis as a potential agent in neonatal acute conjunctivitis.

Impact of the redox-active MnTnHex-2-PyP5+ and cisplatin on the metabolome of non-small cell lung cancer cells.

Redox-based cancer therapeutic strategies aim to raise reactive oxygen species (ROS) levels in cancer cells, thus modifying their redox status, and eventually inducing cell death. Promising compounds, known as superoxide dismutase mimics (SODm), e.g. MnTnHex-2-Py5+ (MnTnHex), could increase intracellular H2O2 in cancer cells with deficient ROS removal systems and therefore enhance radio- and chemotherapy efficacy. We have previously shown that MnTnHex was cytotoxic either alone or combined with cisplatin to non-small cell lung cancer (NSCLC) cells. To gain a deeper understanding of the effects and safety of this compound, it is crucial to analyze the metabolic alterations that take place within the cell. Our goal was thus to study the intracellular metabolome (intracellular metabolites) of NSCLC cells (A549 and H1975) using nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to evaluate the changes in cellular metabolism upon exposure to MnTnHex per se or in combination with cisplatin. 1H NMR metabolomics revealed a higher number of significantly altered metabolites in A549 cells exposed to MnTnHex alone or combined with cisplatin in comparison with non-treated cells (nine dysregulated metabolites), suggesting an impact on aminoacyl-tRNA biosynthesis, glycolysis/gluconeogenesis, taurine, hypotaurine, glycerophospholipid, pyruvate, arginine and proline metabolisms. Regarding H1975 cells, significant alterations in the levels of six metabolites were observed upon co-treatment with MnTnHex and cisplatin, suggesting dysregulations in aminoacyl-tRNA biosynthesis, arginine and proline metabolism, pyruvate metabolism, and glycolysis/gluconeogenesis. These findings help us to understand the impact of MnTnHex on NSCLC cells. Importantly, specific altered metabolites, such as taurine, may contribute to the chemosensitizing effects of MnTnHex.

Assessing the impact of inland navigation on the faecal pollution status of large rivers: A novel integrated field approach.

The contribution of ships to the microbial faecal pollution status of water bodies is largely unknown but frequently of human health concern. No methodology for a comprehensive and target-orientated system analysis was available so far. We developed a novel approach for integrated and multistage impact evaluation. The approach includes, i) theoretical faecal pollution source profiling (PSP, i.e., size and pollution capacity estimation from municipal vs. ship sewage disposal) for impact scenario estimation and hypothesis generation, ii) high-resolution field assessment of faecal pollution levels and chemo-physical water quality at the selected river reaches, using standardized faecal indicators (cultivation-based) and genetic microbial source tracking markers (qPCR-based), and iii) integrated statistical analyses of the observed faecal pollution and the number of ships assessed by satellite-based automated ship tracking (i.e., automated identification system, AIS) at local and regional scales. The new approach was realised at a 230 km long Danube River reach in Austria, enabling detailed understanding of the complex pollution characteristics (i.e., longitudinal/cross-sectional river and upstream/downstream docking area analysis). Faecal impact of navigation was demonstrated to be remarkably low at regional and local scale (despite a high local contamination capacity), indicating predominantly correct disposal practices during the investigated period. Nonetheless, faecal emissions were sensitively traceable, attributable to the ship category (discriminated types: cruise, passenger and freight ships) and individual vessels (docking time analysis) at one docking area by the link with AIS data. The new innovative and sensitive approach is transferrable to any water body worldwide with available ship-tracking data, supporting target-orientated monitoring and evidence-based management practices.

Is parental overcontrol a specific form of child maltreatment? Insights from a resting state EEG connectivity study.

INTRODUCTION: Recent studies suggest that parental overcontrol could be considered a specific form of childhood trauma (CT). Although previous research has shown that CT alters the functional and structural architecture of large-scale networks in the brain, the neural basis associated with parental overcontrol has not been sufficiently explored. Therefore, the main aim of the current study was to investigate the relationship between parental overcontrol and electroencephalography (EEG) triple network (TN) functional connectivity during the resting state (RS) condition in a non-clinical sample (N = 71; 39 females, mean age 23.94 ± 5.89 SD). METHODS: EEG was recorded during 5 min of RS with eyes closed. All participants were asked to self-report maternal and paternal overcontrol, CT and general psychopathology. All EEG analyses were performed using the exact low-resolution electromagnetic tomography software (eLORETA). RESULTS: Our results showed a significant positive correlation between maternal overcontrol and theta connectivity between the salience network and the central executive network. This connectivity pattern was independently associated with maternal overcontrol even when controlling for relevant confounding variables, including the severity of CT and the general level of psychopathology. This neurophysiological pattern may reflect a predisposition to detect and respond to potentially threatening stimuli in the environment, which is typically associated with excessive overcontrol. CONCLUSIONS: Our findings support the hypothesis that parental overcontrol should be considered a form of CT in all respects independent of the forms traditionally studied in the literature (i.e., emotional abuse, physical abuse, sexual abuse, and physical and emotional neglect).

Emotion Processing in Peripheral Neuropathic Pain: An Observational Study.

BACKGROUND: In clinical practice, the implementation of tailored treatment is crucial for assessing the patient's emotional processing profile. Here, we investigate all three levels of analysis characterizing emotion processing, i.e., recognition, representation, and regulation, in patients with peripheral neuropathic pain (PNP). METHODS: Sixty-two patients and forty-eight healthy controls underwent quantitative sensory testing, i.e., psychophysical tests to assess somatosensory functions such as perception of cold (CDT), heat-induced pain (HPT), and vibration (VDT), as well as three standardized tasks to assess emotional processing: (1) the Ekman 60-Faces Test (EK-60F) to assess recognition of basic facial emotions, (2) the Reading the Mind in the Eyes Test (RME) to assess the ability to represent the feelings of another person by observing their eyes, and (3) the 20-item Toronto Alexithymia Scale (TAS-20) to assess emotional dysregulation, i.e., alexithymia. RESULTS: General Linear Model analysis revealed a significant relationship between left index finger VDT z-scores in PNP patients with alexithymia. The RME correlated with VDT z-scores of the left little finger and overall score for the EK-60F. CONCLUSIONS: In patients with PNP, emotion processing is impaired, which emphasizes the importance of assessing these abilities appropriately in these patients. In this way, clinicians can tailor treatment to the needs of individual patients.

The pathogenicity of Plasmopara viticola: a review of evolutionary dynamics, infection strategies and effector molecules.

Oomycetes are filamentous organisms that resemble fungi in terms of morphology and life cycle, primarily due to convergent evolution. The success of pathogenic oomycetes lies in their ability to adapt and overcome host resistance, occasionally transitioning to new hosts. During plant infection, these organisms secrete effector proteins and other compounds during plant infection, as a molecular arsenal that contributes to their pathogenic success. Genomic sequencing, transcriptomic analysis, and proteomic studies have revealed highly diverse effector repertoires among different oomycete pathogens, highlighting their adaptability and evolution potential.The obligate biotrophic oomycete Plasmopara viticola affects grapevine plants (Vitis vinifera L.) causing the downy mildew disease, with significant economic impact. This disease is devastating in Europe, leading to substantial production losses. Even though Plasmopara viticola is a well-known pathogen, to date there are scarce reviews summarising pathogenicity, virulence, the genetics and molecular mechanisms of interaction with grapevine.This review aims to explore the current knowledge of the infection strategy, lifecycle, effector molecules, and pathogenicity of Plasmopara viticola. The recent sequencing of the Plasmopara viticola genome has provided new insights into understanding the infection strategies employed by this pathogen. Additionally, we will highlight the contributions of omics technologies in unravelling the ongoing evolution of this oomycete, including the first in-plant proteome analysis of the pathogen.

Psychometric Properties of the Detachment and Compartmentalization Inventory (DCI) in an Italian Community Sample.

The Detachment and Compartmentalization Inventory (DCI) is a valid and reliable self-report instrument that assesses these two distinct forms of dissociative symptoms. However, there is limited research on the cross-cultural validation of the DCI. Therefore, this study aimed to develop an Italian translation of the DCI and examine its internal structure and psychometric properties (including internal consistency, convergent validity, and test-retest reliability) within an Italian-speaking community sample. The sample consisted of 1276 adults (887 females; mean age: 29.57 ± 10.96 years), who completed the DCI and other self-report measures evaluating dissociative experiences and childhood trauma. Confirmatory factor analyses supported the original two-factor model (χ2169 = 1312.80, RMSEA = 0.073, 95%CI 0.069-0.077; CFI = 0.94; TLI = 0.94; SRMR = 0.04). Additionally, the DCI exhibited good internal consistency, test-retest reliability, and convergent validity with another measure of dissociation. The study also confirmed the association between DCI scores and the severity of childhood trauma. Finally, a Receiver Operating Characteristic (ROC) curve analysis demonstrated that the DCI effectively distinguishes individuals who screened positively for dissociative disorders. Overall, these findings indicate that the Italian translation of the DCI possesses satisfactory psychometric properties, suggesting its utility as a screening tool for assessing detachment and compartmentalization experiences.

Altered EEG Patterns in Individuals with Disorganized Attachment: An EEG Microstates Study.

Over the past years, different studies provided preliminary evidence that Disorganized Attachment (DA) may have dysregulatory and disintegrative effects on both autonomic arousal regulation and brain connectivity. However, despite the clinical relevance of this construct, few studies have investigated the specific alterations underlying DA using electroencephalography (EEG). Thus, the main aim of the current study was to investigate EEG microstate parameters of DA in a non-clinical sample (N = 50) before (pre) and after (post) the administration of the Adult Attachment Interview (AAI). Two EEG eyes-closed Resting State (RS) recordings were performed before and after the AAI, which was used for classifying the participants [i.e., Disorganized/Unresolved (D/U) or Organized/Resolved (O/R) individuals] and to trigger the attachment system. Microstates parameters (i.e., Mean Duration, Time Coverage and Occurrence) were extracted from each recording using Cartool software. EEG microstates clustering analysis revealed 6 different maps (labeled A, B, C, D, E, F) in both groups (i.e., D/U and O/R individuals) and in both conditions (i.e., pre-AAI and post-AAI). In the pre-AAI condition, compared to O/R individuals, D/U participants showed a shorter Mean Duration and Time Coverage of Map F; in the post-AAI condition, a significant reduction in the Mean Duration of Map E was also observed in D/U individuals. Finally, in the "within" statistical analysis (i.e., pre-AAI vs. post-AAI), only the D/U group exhibited a significant increase in Time Coverage of Map F after the AAI. Since these maps are associated with brain networks involved in emotional information processing and mentalization (i.e., Salience Network and Default Mode Network), our result might reflect the deficit in the ability to mentalize caregiver's interaction as well as the increased sensitivity to attachment-related stimuli typically observed in individuals with a D/U state of mind.

Linking antibiotic resistance gene patterns with advanced faecal pollution assessment and environmental key parameters along 2300 km of the Danube River.

The global spread of antimicrobial resistance (AMR) in the environment is a growing health threat. Large rivers are of particular concern as they are highly impacted by wastewater discharge while being vital lifelines serving various human needs. A comprehensive understanding of occurrence, spread and key drivers of AMR along whole river courses is largely lacking. We provide a holistic approach by studying spatiotemporal patterns and hotspots of antibiotic resistance genes (ARGs) along 2311 km of the navigable Danube River, combining a longitudinal and temporal monitoring campaign. The integration of advanced faecal pollution diagnostics and environmental and chemical key parameters allowed linking ARG concentrations to the major pollution sources and explaining the observed patterns. Nine AMR markers, including genes conferring resistance to five different antibiotic classes of clinical and environmental relevance, and one integrase gene were determined by probe-based qPCR. All AMR targets could be quantified in Danube River water, with intI1 and sul1 being ubiquitously abundant, qnrS, tetM, blaTEM with intermediate abundance and blaOXA-48like, blaCTX-M-1 group, blaCTX-M-9 group and blaKPC genes with rare occurrence. Human faecal pollution from municipal wastewater discharges was the dominant factor shaping ARG patterns along the Danube River. Other significant correlations of specific ARGs were observed with discharge, certain metals and pesticides. In contrast, intI1 was not associated with wastewater but was already established in the water microbiome. Animal contamination was detected only sporadically and was correlated with ARGs only in the temporal sampling set. During temporal monitoring, an extraordinary hotspot was identified emphasizing the variability within natural waters. This study provides the first comprehensive baseline concentrations of ARGs in the Danube River and lays the foundation for monitoring future trends and evaluating potential reduction measures. The applided holistic approach proved to be a valuable methodological contribution towards a better understanding of the environmental occurrence of AMR.

Altered connectivity between the central executive network and the salience network in delusion-prone individuals: A resting state eLORETA report.

Although the Triple Network (TN) model has been proposed as a valid neurophysiological framework for conceptualizing delusion-like experiences, the neurodynamics of TN in relation to delusion proneness have been relatively understudied in nonclinical samples so far. Therefore, the main aim of the current study was to investigate the functional connectivity of resting state electroencephalography (EEG) in subjects with high levels of delusion proneness. Twenty-one delusion-prone (DP) individuals and thirty-seven non-delusion prone (N-DP) individuals were included in the study. The exact Low-Resolution Electromagnetic Tomography (eLORETA) software was used for all EEG analyses. Compared to N-DP participants, DP individuals showed an increas of theta connectivity (T = 3.618; p = 0.045) between the Salience Network (i.e., the left anterior insula) and the Central Executive Network (i.e., the left posterior parietal cortex). Increased theta connectivity was also positively correlated with the frequency of delusional experiences (rho = 0.317; p = 0.015). Our results suggest that increased theta connectivity between the Salience Network and the Central Executive Network may underline brain correlates of altered resting state salience detection, information processing, and cognitive control processes typical of delusional thinking.

Unveiling Novel ERCC1-XPF Complex Inhibitors: Bridging the Gap from In Silico Exploration to Experimental Design.

Modifications in DNA repair pathways are recognized as prognostic markers and potential therapeutic targets in various cancers, including non-small cell lung cancer (NSCLC). Overexpression of ERCC1 correlates with poorer prognosis and response to platinum-based chemotherapy. As a result, there is a pressing need to discover new inhibitors of the ERCC1-XPF complex that can potentiate the efficacy of cisplatin in NSCLC. In this study, we developed a structure-based virtual screening strategy targeting the inhibition of ERCC1 and XPF interaction. Analysis of crystal structures and a library of small molecules known to act against the complex highlighted the pivotal role of Phe293 (ERCC1) in maintaining complex stability. This residue was chosen as the primary binding site for virtual screening. Using an optimized docking protocol, we screened compounds from various databases, ultimately identifying more than one hundred potential inhibitors. Their capability to amplify cisplatin-induced cytotoxicity was assessed in NSCLC H1299 cells, which exhibited the highest ERCC1 expression of all the cell lines tested. Of these, 22 compounds emerged as promising enhancers of cisplatin efficacy. Our results underscore the value of pinpointing crucial molecular characteristics in the pursuit of novel modulators of the ERCC1-XPF interaction, which could be combined with cisplatin to treat NSCLC more effectively.

Psychophysiological and Neurophysiological Correlates of Dropping Objects from Hands in Carpal Tunnel Syndrome.

BACKGROUND: Dropping objects from hands (DOH) is a common symptom of carpal tunnel syndrome (CTS). We evaluated the clinical, neurophysiological, and psychophysiological features of 120 CTS patients to elucidate the DOH pathophysiology. Forty-nine healthy controls were included. METHODS: In the patients, the Boston Carpal Tunnel Questionnaire (BCTQ), the Douleur Neuropathique 4 questions (DN4), and a numeric rating scale for pain (NRS) were evaluated. In patients and controls, we evaluated bilateral median and ulnar motor and sensory nerve conduction studies, cutaneous silent period and cutaneomuscular reflexes (CMR) of the abductor pollicis brevis, cold-detection threshold (CDT) and heat-pain detection threshold (HPT) at the index, little finger, and dorsum of the hand, and vibratory detection threshold at the index and little finger by quantitative sensory testing. RESULTS: CTS with DOH had higher BCTQ, DN4 and NRS, lower median sensory action potential, longer CMR duration, lower CDT and higher HPT at all tested sites than controls and CTS without DOH. Predictive features for DOH were abnormal CDT and HPT at the right index and dorsum (OR: 3.88, p: 0.03) or at the little finger (OR: 3.27, p: 0.04) and a DN4 higher than 4 (OR: 2.16, p < 0.0001). CONCLUSIONS: Thermal hypoesthesia in median and extra-median innervated territories and neuropathic pain are predictive of DOH in CTS.

Short-Term Effects of Climate Change on Planktonic Heterotrophic Prokaryotes in a Temperate Coastal Lagoon: Temperature Is Good, Ultraviolet Radiation Is Bad, and CO2 Is Neutral.

Planktonic heterotrophic prokaryotes (HProks) are a pivotal functional group in marine ecosystems and are highly sensitive to environmental variability and climate change. This study aimed to investigate the short-term effects of increasing carbon dioxide (CO2), ultraviolet radiation (UVR), and temperature on natural assemblages of HProks in the Ria Formosa coastal lagoon during winter. Two multi-stressor microcosm experiments were used to evaluate the isolated and combined effects of these environmental changes on HProk abundance, production, growth, and mortality rates. The isolated and combined effects of increased CO2 on HProks were not significant. However, HProk production, cellular activity, instantaneous growth rate, and mortality rate were negatively influenced by elevated UVR and positively influenced by warming. Stronger effects were detected on HProk mortality in relation to specific growth rate, leading to higher HProk net growth rates and abundance under elevated UVR and lower values under warming conditions.

Parental overcontrol is associated with dysmorphic concern severity: A cross-sectional study.

BACKGROUND: Dysmorphic concern (DC) is a symptom affecting both clinical and non-clinical populations, with a severe impact on individuals' physical and psychological well-being. While Childhood Trauma (CT) has been identified as a risk factor for DC, there is a lack of research on a specific form of CT, that is, parental overcontrol. Therefore, the current study aimed to investigate the association between DC and parental overcontrol in a community sample of adults, controlling for other forms of CT and potential confounding variables. METHOD: 714 adults (508 females; mean age: 30.29 ± 11.67 years; age range: 18-77) participated in an online survey including the Body Image Concern Inventory (BICI), the Overcontrol subscale of the Measure Of Parental Style, and the Childhood Trauma Questionnaire - Short Form (CTQ-SF). RESULTS: Parental overcontrol was independently associated with DC symptoms (ß = 0.111; p = .005; CI = [0.119;0.666]), even after controlling for other forms of CT and sociodemographic and clinical confounding variables. LIMITATIONS: The cross-sectional design of the study, the unbalanced sex ratio, the retrospective self-reported data about parental overcontrol and CT should be considered. CONCLUSIONS: This finding suggests that parental overcontrol may play a role in the development and maintenance of DC symptoms, remarking the urge to take more into account parental overcontrol in the assessment of CT.

Effects of gear modifications in a North Atlantic pelagic longline fishery: A multiyear study.

The threat of population declines caused by pelagic longline fisheries in the Atlantic has increased the concern to find strategies that minimize the bycatch and mortality of non-target marine animals. Gear modification, such as the use of circle hooks instead of conventional J-hooks, has been identified as an effective bycatch reduction strategy in different pelagic longline fisheries around the world. This study aimed to verify the effectiveness of the use of circle hooks by quantifying catch rates, relative size selectivity, and anatomical hooking position for the most common target species (swordfish, Xiphias gladius, and blue shark, Prionace glauca), and some bycatch species (loggerhead sea turtles, Caretta caretta, and shortfin mako, Isurus oxyrinchus) caught by the Azorean longline fishing fleet. The trial was conducted for five consecutive years (2000-2004) using eight different types of hooks. In general, the blue shark catches using circle hooks were significantly higher compared to J (Mustad 9/0). The circle hooks also showed high probabilities of catching juvenile blue sharks. Conversely, the circle hooks were efficient in reducing the loggerhead sea turtle bycatch and were related to fewer catches of small sea turtle individuals. The use of circle hooks was also associated with reduced swordfish catches compared to J (Mustad 9/0), and the effect of hook types on length at capture was only significant for Circle (L. & P. 18/0-CLP18) and Ringed Tuna (RT). No significant differences were observed comparing hook type to either catch rates or size selectivity for shortfin mako. Additionally, circle hooks were more likely to lodge in the mouth than in deeper anatomical positions, when compared to J (Mustad 9/0), for the four species analysed. The present study demonstrated that the use of circle hooks could mitigate the impact of the pelagic longline fisheries in the Azores by decreasing the bycatch of sea turtles and reducing animal injuries caused by deep hooking.

Amino-Alcohol Organic-Inorganic Hybrid Sol-Gel Materials Based on an Epoxy Bicyclic Silane: Synthesis and Characterization.

Organic-inorganic hybrids (OIHs) are a type of material that can be obtained using the sol-gel process and has the advantages of organic and inorganic moieties in a single material. Polyetheramines have been widely used in the preparation of this type of material, particularly in combination with epoxy-based alkoxysilanes. Nevertheless, epoxyciclohexylethyltrimethoxysilane (ECHETMS) is a promising alkoxysilane with an epoxy terminal group that is quite unexplored. In this work, four novel OIH materials were synthesized using the sol-gel method. The OIHs were based on Jeffamines® of different molecular weights (D-230, D-400, ED-600, and ED-900), together with ECHETMS. The materials were characterized using multinuclear solid state NMR, FTIR, BET, UV/Vis spectroscopy, EIS, and TGA. The influence of the Jeffamine molecular weight and the suitability of these materials to act as a supporting matrix for heteroaromatic probes were assessed and discussed. The materials show interesting properties in order to be applied in a wide range of sensing applications.

Single accessory pathway with multiple insertions? First-in-human 3D visualization using dipole charge density mapping: a case report.

Background: Accessory pathways (APs) with multiple atrial insertions are often unrecognized and associated with initial catheter ablation (CA) failure. Recently, a novel dipole charge density mapping (DCDM) system was developed that allows mapping of complex arrhythmias based on a single beat. We aim to present the first-in-human report of 3D visualization of a single AP with two atrial insertion sites using high-resolution DCDM. Case summary: A 43-year-old man with recurrent symptomatic atrioventricular re-entrant tachycardia and previously failed CA attempts underwent repeated CA using DCDM. Dipole charge density mapping identified two quasi-simultaneous early atrial activation sites at the left lateral and left anterolateral atrial aspects of the mitral annulus, suggesting the presence of a single AP with dual atrial insertion sites. Successful radiofrequency CA was performed at the mid-body of the AP. Discussion: The true prevalence of APs with multiple atrial insertion sites may be higher than currently reported. This is the first-in-human report of 3D visualization of a single AP with two atrial insertion sites using high-resolution DCDM. Dipole charge density mapping allows the accurate localization of APs with multiple insertion sites based on a single beat.