Labeling Procedure Research Articles

Comparison of Different Organometallics Towards Electrophilic Aromatic 211At-Astatinations of Highly Reactive Tetrazines.

Organometallics can be used as precursors for electrophilic 211At-statinations. In this report, we compared the potential of aryl trimethylsilanes, -germanes, or -stannanes to be used as precursors to 211At-label highly reactive tetrazines. Tetrazines can be used for pretargeted radioligand therapies or be applied as synthons to radiolabel rapidly and orthogonally a broad set of precursors such as peptides, mAbs or nanomedicines. All precursors could successfully be synthesized and radiolabeled. The reactivity of organogermanium reagents ranged between those of respective organotin and organosilicon precursors. Moreover, organogermanium reagents proved promising for accessing more complex and polar tetrazine scaffolds. In contrast to organotin derivatives, the use of protecting groups could be avoided for organogermanium and -silicon precursors. The developed 211At-labeled tetrazines could be labeled in radiochemical conversions of 60-90%. Organogermanium and -silicon precursors were clearly advantaged as additional deprotection steps could avoided. Reported labeling procedures allow astatinations of highly reactive tetrazines to be used for pretargeted approaches or to applied as highly reactive synthons to label the next-generation of 211At-labeled radiopharmaceuticals.

Broadband surface enhanced infrared absorption with multiple Fano resonance by metallic oblique-wire-bundle metamaterial absorbers

Higher sensitivity with specific recognition of a sensor could ease the burden of sample purification or labelling procedure for specific testing and detection and there appear two methods including surface enhanced infrared absorption (SEIRA) and surface enhanced Raman scattering (SERS), promising better sensitivity and specificity, simultaneously, via detection of molecular footprints. Furthermore, researchers employ Fano resonance to further boost the detection limit of SEIRA by coupling between two absorption bands from molecules and metamaterials. Still, the current metamaterial absorbers are almost narrow band and require a specific design, only suitable for limited chemicals. Thus, in this work, we would like to design a broadband oblique-wire-bundle (OWB) metamaterial absorber (MA) which could interact with multiple functional groups’ absorption from a sample, thus easing the burden of custom-made resonators. In experiments, indeed, our designed OWB MA developed four Fano resonance responses with three PMMAs’ functional groups and one function group from carbon dioxide. The counterpart planar MA also performed SEIRA yet without occurrence of Fano resonance as a comparison. We believe this proposed OWB MA could facilitate the development of rapid detection in the field of food safety and chemical detection.

A Novel Dynamic Multiobjective Optimization Algorithm With Non-Inductive Transfer Learning Based on Multi-Strategy Adaptive Selection.

In this article, a novel multi-strategy adaptive selection-based dynamic multiobjective optimization algorithm (MSAS-DMOA) is proposed, which adopts the non-inductive transfer learning (TL) paradigm to solve dynamic multiobjective optimization problems (DMOPs). In particular, based on a scoring system that evaluates environmental changes, the source domain is adaptively constructed with several optional groups to enrich the knowledge. Along with a group of guide solutions, the importance of historical experiences is estimated via the kernel mean matching (KMM) method, which avoids designing strategies to label individuals. The proposed MSAS-DMOA is comprehensively evaluated on 14 DMOPs, and the results show an overwhelming performance improvement in terms of both convergence and diversity as compared with other four popular DMOAs. In addition, ablation studies are also conducted to validate the superiority of the applied strategies in MSAS-DMOA, which can effectively alleviate the negative transfer phenomenon. Without the conventional labeling procedure, the proposed method also yields satisfactory results, which can provide valuable reference for designing other evolutionary transfer optimization (ETO) algorithms.

Information mismatch in PHH3-assisted mitosis annotation leads to interpretation shifts in H&E slide analysis

The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker, as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. In a computer-aided setting, deep learning algorithms can help to mitigate this, but they require large amounts of annotated data for training and validation. Furthermore, label noise introduced during the annotation process may impede the algorithms’ performance. Unlike H&E, where identification of MFs is based mainly on morphological features, the mitosis-specific antibody phospho-histone H3 (PHH3) specifically highlights MFs. Counting MFs on slides stained against PHH3 leads to higher agreement among raters and has therefore recently been used as a ground truth for the annotation of MFs in H&E. However, as PHH3 facilitates the recognition of cells indistinguishable from H&E staining alone, the use of this ground truth could potentially introduce an interpretation shift and even label noise into the H&E-related dataset, impacting model performance. This study analyzes the impact of PHH3-assisted MF annotation on inter-rater reliability and object level agreement through an extensive multi-rater experiment. Subsequently, MF detectors, including a novel dual-stain detector, were evaluated on the resulting datasets to investigate the influence of PHH3-assisted labeling on the models’ performance. We found that the annotators’ object-level agreement significantly increased when using PHH3-assisted labeling (F1: 0.53 to 0.74). However, this enhancement in label consistency did not translate to improved performance for H&E-based detectors, neither during the training phase nor the evaluation phase. Conversely, the dual-stain detector was able to benefit from the higher consistency. This reveals an information mismatch between the H&E and PHH3-stained images as the cause of this effect, which renders PHH3-assisted annotations not well-aligned for use with H&E-based detectors. Based on our findings, we propose an improved PHH3-assisted labeling procedure.

A Labeling Intercomparison of Retrogressive Thaw Slumps by a Diverse Group of Domain Experts

ABSTRACTDeep‐learning (DL) models have become increasingly beneficial for the detection of retrogressive thaw slumps (RTS) in the permafrost domain. However, comparing accuracy metrics is challenging due to unstandardized labeling guidelines. To address this, we conducted an experiment with 12 international domain experts from a broad range of scientific backgrounds. Using 3 m PlanetScope multispectral imagery, they digitized RTS footprints in two sites. We evaluated label uncertainty by comparing manually outlined RTS labels using Intersection‐over‐Union (IoU) and F1 metrics. At the Canadian Peel Plateau site, we see good agreement, particularly in the active parts of RTS. Differences were observed in the interpretation of the debris tongue and the stable vegetated sections of RTS. At the Russian Bykovsky site, we observed a larger mismatch. Here, the same differences were documented, but several participants mistakenly identified non‐RTS features. This emphasizes the importance of site‐specific knowledge for reliable label creation. The experiment highlights the need for standardized labeling procedures and definition of their scientific purpose. The most similar expert labels outperformed the accuracy metrics reported in the literature, highlighting human labeling capabilities with proper training, site knowledge, and clear guidelines. These findings lay the groundwork for DL‐based RTS monitoring in the pan‐Arctic.

Reduced Non-Specific Binding of Super-Resolution DNA-PAINT Markers by Shielded DNA-PAINT Labeling Protocols.

The DNA-based single molecule super-resolution imaging approach, DNA-PAINT, can achieve nanometer resolution of single targets. However, the approach can suffer from significant non-specific background signals originating from non-specifically bound DNA-conjugated DNA-PAINT secondary antibodies as shown here. Using dye-modified oligonucleotides the location of DNA-PAINT secondary antibody probes can easily be observed with widefield imaging prior to beginning a super-resolution measurement. This reveals that a substantial proportion of DNA probes can accumulate, non-specifically, within the nucleus, as well as across the cytoplasm, of cells. Here, Shielded DNA-PAINT labeling is introduced, a method using partially or fully double-stranded docking strand sequences, prior to labeling, in buffers with increased ionic strength to greatly reduce non-specific interactions in the nucleus as well as the cytoplasm. This new labeling approach is evaluated against various conditions and it is shown that applying Shielded DNA-PAINT can reduce non-specific events approximately five-fold within the nucleus. This marked reduction in non-specific binding of probes during the labeling procedure is comparable to results obtained with unnatural left-handed DNA albeit at a fraction of the cost. Shielded DNA-PAINT is a straightforward adaption of current DNA-PAINT protocols and enables nanometer precision imaging of nuclear targets with low non-specific backgrounds.

A critical appraisal of South African oncology pharmacy standards: A comparison with international best practice standards.

The demand for oncology pharmacy services is set to increase as the burden of cancer rises in sub-Saharan Africa. Oncology pharmacists may be exposed to antineoplastic drugs (ADs) and need comprehensive health and safety guidelines. The objective of the study was to assess the effectiveness of the local oncology pharmacy practice standards, by critically evaluating them against international best practice standards. We compared the Independent Clinical Oncology Network (ICON) administration of ADs standards resource document (ICON standards) and Good Pharmacy Practice (GPP) standards with the International Society of Oncology Pharmacy Practitioners (ISOPP) Standards for the safe handling of cytotoxics, and the Quality standard for the oncology pharmacy service (QuaPos), using 10 domains: transport of ADs, working arrangements, education and training, engineering controls, use of personal protective equipment, risk management, medical monitoring of personnel, cleaning procedures, accident management and documentation, labelling and checking procedures. The ICON standards align closely with international best practice standards, but the GPP standards focus only briefly on the compounding of ADs.The GPP standards are outdated and some of the stipulations are erroneous. Oncology pharmacists would do better to adhere to the more comprehensive ICON standards, although these standards also need to be updated in line with best practice. Revising and improving both these local standards in consultation with key role players in the oncology pharmacy industry will go a long way in protecting the health and safety of oncology pharmacists in South Africa.

Preclinical evaluation of a new technetium-99m labeled neurotensin analogue for NTSR1 targeted radionuclide imaging

Neurotensin is a regulatory peptide that can act as a growth factor on different types of normal and cancerous cells. Binding of Neurotensin to relevant receptors leads to cell proliferation, survival, migration and invasion by changing intracellular enzyme activity. Therefore, the design of a neurotensin-based radiopeptide plays an important role in targeted imaging or therapy of neurotensin receptor-positive tumors. A [Lys8]-neurotensin (7–13) peptide was synthesized and attached to HYNIC as a chelator via a linker. The labeling procedure was carried out at 100 °C for 10 min using 99mTc as a radionuclide and EDDA/tricine as coligands. Stability of the labeled peptide in human serum was determined using RTLC and HPLC methods. The receptor binding internalization was studied using HT-29 colon carcinoma cells, and tissue biodistribution was evaluated in mice bearing CT-26 tumors. The [99mTc]Tc-Tricine/EDDA/HYNIC-GABA-[Lys8]-neurotensin (7–13) peptide demonstrated a labeling yield of over 98 %, a specific activity of 37.00 GBq/µmol, high stability in human serum, a nanomolar range of Kd, and a tumor uptake of 0.36 ± 0.15 % ID/g at 1-h post-injection. These results suggest that the labeled peptide is a suitable imaging agent for neurotensin receptor-positive tumors.

The actual issues of mandatory labeling of certain types of medical items

Mandatory labeling of medical items plays key role in establishing uniform standards and requirements for all market participants. This promotes increasing of protection of consumer rights, excluding possibility of buying unreliable or counterfeit products. The normative documents regulating labeling of medical items set important requirements to manufacturers, importers and retailers. The unique identifiers, information about origin and other data provided for inclusion in labeling ensure product identification and control of its quality. The article considers normative legal base regulating procedure of mandatory labeling of certain types of medical items from their production and putting into use up to moment of their sale and withdrawal from market turnover. Besides, mechanism of state regulation of procedure of labeling of medical items targeted to increasing of traceability of products, reducing spread of counterfeit goods, ensuring patient safety and improving quality of medical services in general is considered.

A Comparative Performance Evaluation of YOLO-Type Detectors on a New Open Fire and Smoke Dataset.

The paper introduces a new FireAndSmoke open dataset comprising over 22,000 images and 93,000 distinct instances compiled from 1200 YouTube videos and public Internet resources. The scenes include separate and combined fire and smoke scenarios and a curated set of difficult cases representing real-life circumstances when specific image patches may be erroneously detected as fire/smoke presence. The dataset has been constructed using both static pictures and video sequences, covering day/night, indoor/outdoor, urban/industrial/forest, low/high resolution, and single/multiple instance cases. A rigorous selection, preprocessing, and labeling procedure has been applied, adhering to the findability, accessibility, interoperability, and reusability specifications described in the literature. The performances of the YOLO-type family of object detectors have been compared in terms of class-wise Precision, Recall, Mean Average Precision (mAP), and speed. Experimental results indicate the recently introduced YOLO10 model as the top performer, with 89% accuracy and a mAP@50 larger than 91%.

Label-Free Imaging of Mesenchymal Stem Cell Spheroid Differentiation with Flexible-Probe SECM and a Microfluidic Device.

Mesenchymal stem cells (MSCs) have emerged as an indispensable source for stem cell research and preclinical studies due to their capacity for in vitro proliferation and their potential to differentiate into mesodermal lineages, particularly into osteoblasts. This capability has propelled their application in the fields of bone regeneration and osteochondral repair. Traditional methodologies for assessing the differentiation status of MSCs necessitate invasive procedures such as cell lysis or fixation. In this study, we introduce a nondestructive technique that utilizes an integrated label-free approach to evaluate the osteogenic maturation of MSC spheroid aggregates. This method employs scanning electrochemical microscopy (SECM) with a flexible probe in conjunction with a top-removable microfluidic device designed for easy SECM access. By tracking the production rate of p-aminophenol (PAP) in the generation/collection mode and assessing morphological changes via the negative feedback mode using [Ru(NH3)6]Cl3 (Ruhex), we can discern variations in the alkaline phosphatase (ALP) activity indicative of osteogenic differentiation. This innovative strategy enables the direct evaluation of osteogenic differentiation in MSC spheroids cultured within microwell arrays without necessitating any labeling procedures. The utilization of a flexible microelectrode as the probe that scans in contact mode (with probe-substrate distances potentially as minimal as 0 μm) affords enhanced resolution compared to the traditional stiff-probe technique. Furthermore, this method is compatible with subsequent molecular biology assays, including gene expression analysis and immunofluorescence, thereby confirming the electrochemical findings and establishing the validity of this integrative approach.

Translation Strategies of Nusantara Food Menu

The research aims to analyze the translation strategies and the use of Culture-Specific Items (CSIs) in nusantara food menus in Indonesia. Translators usually use their perception to translate the menu without the involvement of the chefs. As a result, the translation of food menus can vary from one restaurant to another because each chef has their unique way of preparing their food. Collaboration between translators and chefs is necessary to ensure that the translated menus highlight the characteristics and uniqueness of each dish. The results show that the translation strategies used are Reduction and Expansion (81 data), Couplets (34 data), Cultural Equivalence (8 data), Transference (7 data), Descriptive Equivalence (5 data), Functional Equivalence (4 data), and Naturalization (2 data). The use of CSIs found in the data are Ingredients (186 data), Cooking Techniques (113 data), Seasoning (83 data), Proper Name (39 data), Flavor (9 data), Color (7 data), and Texture (4 data). However, the translation strategy of Synonymy, Through-Translation, Shift or Transposition, Modulation, Recognised Translation, Translation Label, Compensation, Componential Analysis, Paraphrase, and Other Procedures are not found in the data.

Column generation for the collaborative multi-stop truckload shipping problem in daily regional distribution

Multi-stop truckload shipping offers less-than-truckload shippers a promising way to reduce their freight costs by consolidating freights en route, which is similar to ridesharing in the mobility industry. One significant challenge in practical implementation is designing attractive multi-stop routes that to shippers while conforming to carriers' requirements. It is crucial to develop an efficient optimisation algorithm to automate bundling decisions. However, this routeing problem is complicated by a nonlinear inseparable cost structure and new routeing decisions in the first pickup and last delivery points. We introduce a new variant of pickup and delivery model and propose a column generation algorithm to efficiently solve real-world multi-stop routeing problems. The algorithm utilises a new specialised labelling procedure that exclusively generates labels for pickup sequences and establishes new dominance rules. Theoretical results on the label dominance, algorithm complexity, and optimality gap are also established. We conduct a real-world case study, comparing our methodology against the enumeration method and a heuristic method documented in the literature. The computational results demonstrate the high efficiency of our method and reveal important insights for practitioners.

A dual-labeling molecule for efficient drug discovery of mitochondrial-lysosomal interactions

The close association between organelle interactions, such as mitochondrial–lysosomal interactions, and various diseases, including tumors, remains a challenge for drug discovering and identification. Conventional evaluation methods are often complex and multistep labeling procedures often generate false positives, such as cell damage. To overcome these limitations, we employed a single dual-color reporting molecule called Coupa, which labels mitochondria and lysosomes as blue and red, respectively. This facilitates the evaluation and discovering of drugs targeting mitochondria–lysosome contact (MLC). Using Coupa, we validated the effectiveness of various known antitumor drugs in intervening MLC by assessing their effect on key aspects, such as status, localization, and quantity. This provides evidence for the accuracy and applicability of our dual-color reporting molecule. Notably, we observed that several structural isomers of drugs, including Urolithin (A/B/C), exhibited distinct effects on MLC. In addition, Verteporfin and TEAD were found to induce anti-tumor effects by controlling MLC at the organelle level, suggesting a potential new mechanism of action. Collectively, Coupa offers a novel scientific tool for discovering drugs that target mitochondrial–lysosomal interactions. It not only distinguished the differential effects of structurally similar drugs on the same target, but also reveals new mechanisms underlying the reported antitumor properties of existing drugs. Ultimately, our findings contribute to the advancement of drug discovery and provide valuable insights into the complex interactions between organelles in a disease context.

Illness representation in patients with multiple sclerosis: A preliminary narrative medicine study.

The development of personalized interventions aimed at coping with multiple sclerosis is enriched by the understanding of patients' representations of the illness. The aim of this study was to investigate the association between patients' illness representations versus contextual factors (i.e. presence/absence and type of caregiver, engagement, frequency and type of rehabilitation), fatigue, pain, and neurological impairment. Interviews of 28 patients were analysed through an automated text analysis procedure. After a systematic labelling procedure four illness representations were identified: daily life, search for meaning of the disease, relationship to people and the diagnosis, coping and physical growth. Findings showed that the representation of the relational aspects of the illness was associated with the caregiver's presence, while the representation related to coping and growth tended to be associated with participation in rehabilitation programs. Moreover, the representation related to daily life was associated with lower levels of fatigue compared to the representation related to coping and growth, and with higher levels of neurological impairment compared to the representations related to coping and growth and the relational aspects of the illness. Exploring illness representations is a key step that can help health professionals to get an integrated perspective that could be useful in designing and calibrating interventions according to specific patient needs.

Peptide derived from plant defensins: A promising 68Ga radiolabelled agent for diagnostic of infection foci in PET.

The development of new radiopharmaceuticals for the detection of hidden infection foci has great relevance for early detection and the selection of the correct treatment, particularly in immunosuppressed patients. In that sense, the labelling of antimicrobial peptides (AMPs) that are capable of binding specifically to the pathogenic microorganism which causes the infection, should provide a sufficiently specific agent, able to distinguish an infection from a sterile inflammation. Defensins are particularly interesting molecules with antimicrobial activity, the EcgDf1 defensin was identified from the genome of a Uruguayan native plant, Erythrina crista-galli, the 'Ceibo' tree. Our group has previously reported a synthetic biologically active short analogue EcgDf21 (ERFTGGHCRGFRRRCFCTKHC) successfully labelled with 99mTc. Herein we present a shorter analogue which also preserves the γ-core domain, as a pharmacophore for a potential infection detection agent. This peptide was derivatized with the bifunctional chelating agent 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through a lysine linker in the amino-terminal group (NOTA-KGHCRGFRRRC) and radiolabelled with 68Ga ([68Ga]Ga-NOTA-K-EcgDf1(10)). The [68Ga]Ga-NOTA-K-EcgDf1(10) labelling procedure rendered a product with high radiochemical purity and stability in the labelling milieu. The Log P value indicated that the complex has a hydrophilic behaviour, confirmed by the biodistribution profile. The [68Ga]Ga-NOTA-K-EcgDf1(10) complex demonstrated specific binding to cultures of Candida albicans and Aspergillus niger. Its biodistribution showed renal elimination and low accumulation in the rest of the body. It was possible to successfully differentiate sterile inflammation from infection by PET images in nude mice with a target/non-target ratio of 3.3 for C. albicans and 3.7 for A. niger, respectively.

Increasing the Reproducibility and Replicability of Supervised AI/ML in the Earth Systems Science by Leveraging Social Science Methods

AbstractArtificial intelligence (AI) and machine learning (ML) pose a challenge for achieving science that is both reproducible and replicable. The challenge is compounded in supervised models that depend on manually labeled training data, as they introduce additional decision‐making and processes that require thorough documentation and reporting. We address these limitations by providing an approach to hand labeling training data for supervised ML that integrates quantitative content analysis (QCA)—a method from social science research. The QCA approach provides a rigorous and well‐documented hand labeling procedure to improve the replicability and reproducibility of supervised ML applications in Earth systems science (ESS), as well as the ability to evaluate them. Specifically, the approach requires (a) the articulation and documentation of the exact decision‐making process used for assigning hand labels in a “codebook” and (b) an empirical evaluation of the reliability” of the hand labelers. In this paper, we outline the contributions of QCA to the field, along with an overview of the general approach. We then provide a case study to further demonstrate how this framework has and can be applied when developing supervised ML models for applications in ESS. With this approach, we provide an actionable path forward for addressing ethical considerations and goals outlined by recent AGU work on ML ethics in ESS.

Educating Banten's culinary MSMEs on the value of nutritional information and halal labeling

Many consumers seek nutritional information and halal certification on food packaging to make informed choices and build trust. However, culinary MSMEs in Banten often lack the knowledge on proper labeling procedures. To address this gap, a community service program was initiated to educate Banten's culinary MSMEs on the significance of including nutritional value and halal labels on their products. The program utilized online counseling sessions (Zoom Meetings) with discussions, Q&A sessions, and e-questionnaires. Evaluation results highlighted a high level of understanding among participants, with an average score of 91.22% for knowledge (cognitive aspect), 92.36% for attitude (affective aspect), and 90.97% for willingness to act (behavioral aspect).

Amplification-free and label-free rapid detection of Staphylococcus aureus using solution-gated graphene transistor-based DNA biosensor with hybridization enhancement by interface engineering

Staphylococcus aureus (S. aureus) is one of the leading causes of foodborne illnesses worldwide, posing a significant risk to food quality and safety. However, conventional detection methods often require complex amplification and labeling procedures, which are time consuming and expensive. In this study, an extremely sensitive electrochemical biosensor using a solution-gated graphene transistor (SGGT) was constructed for the amplification-free and label-free rapid detection of S. aureus by utilizing specific single-stranded DNA (ssDNA) to modify the gold (Au) sensing gate. This modified ssDNA was designed to hybridize with the target S. aureus DNA sequence. Interface engineering of the ssDNA-modified sensing gate via optimization of specific target and probe sequences was proposed to improve its hybridization efficiency. This enabled the sensitive quantitative detection of S. aureus DNA. The resulting biosensor exhibited excellent specificity in distinguishing non-complementary, 3-base/9-base DNA mismatch targets of S. aureus DNA and the specific DNA sequences of other common pathogenic bacteria. It also enabled the rapid detection of extracted target DNA sequences in solution (within 27 min) and had a low limit of detection (LoD) of 10−17 M over a wide linear detection range (10−17–10−8 M). Furthermore, the newly-developed biosensor facilitated the real-time and on-site detection of the S. aureus genome (ATCC 6538) with LoD of 10−17 M (103 CFU/mL) in a portable smart-sensing system. This suggests a promising future for the development of rapid, label-free, and amplification-free detection of foodborne illnesses using low-cost, highly sensitive SGGT DNA biosensors with appropriate functionalization and interface engineering of the sensing electrode.

Rapid Construction of 18F-Triazolyl-tetrazines through the Click Reaction.

Due to the fast reaction rate, 18F-labeled tetrazines have been widely applied in positron emission tomography (PET) imaging in cancer research and drug discovery. In this work, several functional 18F-triazolyl-tetrazines were rapidly obtained through an optimized copper-catalyzed alkyene-azide cycloaddition reaction system in >99% radiochemical conversions. Notably, the commonly used 18F-labeled azides were isolated through cartridges and directly used for cycloadditions, which greatly simplified the labeling procedure. The assembled triazolyl-tetrazines demonstrated high in vitro stability and reaction kinetics, exhibiting considerable potential for the development of PET agents.