Screening Scheme Research Articles

Clinical utility of HPV typing and quantification combined with PAX1/ZNF582 methylation detection in accurate cervical cancer screening.

This article aims at exploring the clinical value of high-risk human papillomavirus (HPV) positive and paired boxed 1 (PAXI)/zinc finger protein 582 (ZNF582) gene methylation shunt as a new approach for accurate cervical cancer screening. Selecting 115 patients were treated in the Cervical Department of Xuzhou Matemal and Child Health Hospital from October 2018-October 2020. All patients underwent cervical exfoliated cell thinprep cytologic test (TCT) detection, HPV typing quantitative detection, and PAX1/ZNF582 gene methylation level Detection. Taking the biopsy pathological diagnosis under colposcopy as the gold standard, analyzing the test results statistically, and the sensitivity, specificity, and accuracy of the three screening methods alone and combined screening schemes were compared. Comparison of the three methods of cervical exfoliated cell TCT, HPV typing and quantification, and PAX1/ZNF582 methylation gene detection showed that the gene detection method has the highest specificity, 97.30%; The HPV typing quantitative detection has the highest sensitivity, 89.71%, but its specificity is poor; and the PAX1/ZNF582 gene detection has the highest accuracy. For patients with high-grade cervical lesions and cervical cancer, PAX1/ZNF582 gene methylation level can be used as an important biomarker for the diagnosis and classification of cervical cancer. PAX1/ZNF582 methylation gene detection is effective in high-grade cervical lesions and cervical cancer. Screening has high clinical value and can become a new way of accurate cervical cancer screening.

Solid-State Au Nanocone Arrays Substrate for Reliable SERS Profiling of Serum for Disease Diagnosis.

Surface-enhanced Raman scattering (SERS) is a widely used rapid and noninvasive method for detecting biological substances in serum samples and is commonly employed in disease screening and diagnosis. Solid-state nanoarray SERS substrates used in serum detection may cause spectral instability due to imperfections in the detection method. For the purpose of identifying optimal detection conditions, various dilution levels of the serum were tested in this study. The study found that a complete and stable serum SERS spectrum can be obtained when the serum is diluted by a factor of 50. The study reports the successful preparation of an Au nanocone array (Au NCA) plasmonic substrate with a uniform, controllable microstructure and high activity, achieved through a combination of PS colloidal sphere template-assisted reactive ion etching (RIE) process and magnetron sputtering deposition technology. Based on this substrate, a standard detection scheme was developed to obtain highly stable and repeatable serum SERS spectra. The study verified the reliability of the optimized serum detection scheme by comparing the SERS spectra of serum samples from healthy individuals and gastric cancer patients, and confirmed the potential benefits of the scheme for disease screening and diagnosis.

Early childhood eye diseases and perinatal risk factors: potential of record linkage between current information flows.

The aim of this study was to analyze the occurrence of specific maternal, obstetric or neonatal factors, by performing a comparison between children with refractive error, strabismus and/or amblyopia (cases) and unaffected children (controls) in the province of Trento (North-East Italy). In 2012-2014, 14,346 children attending the second year of nursery school were assessed through the preschool orthoptic screening scheme (covering 91% of the preschool population). Record linkage was performed between the orthoptic screening database and birth records (birth confirmation certificate database) for the corresponding birth cohorts (2008-2010), to examine specific maternal factors (age, smoking, nationality/race), obstetric factors (type of delivery) and neonatal factors (gestational age, weight at birth, Apgar Score, congenital birth defects, hospitalization at birth). The correlations were investigated using univariate and multivariate analysis in accordance with the logistic regression method. During orthoptic screening, 6.4% of children were found to have at least one refractive error, with astigmatism being the most common condition (5.1%). 1.9% of children were found to have strabismus and 1.8% amblyopia. Multivariate logistic regression analysis showed that the risk of developing a refractive error is associated with: maternal age ≥45 years, foreign nationality, vacuum-assisted delivery and neonatal weight <1500 grams. An excessive risk of strabismus was observed in children whose mother had smoked during pregnancy (adjusted OR=1.64). Preschool orthoptic screening is a well-consolidated practice in the province of Trento, with adhesion values consistently over 90%. Studies of this type show the potential of record linkage between current information flows.

Breaking Alert Fatigue: AI-Assisted SIEM Framework for Effective Incident Response

Contemporary security information and event management (SIEM) solutions struggle to identify critical security incidents effectively due to the overwhelming number of false alerts generated by disparate security products, which results in significant alert fatigue and hinders effective incident response. To overcome this challenge, we propose a next-generation SIEM framework that integrates security orchestration automation and response capabilities and utilizes a divide-and-conquer strategy to mitigate the impact of low-quality IDS alerts. The proposed framework leverages advanced machine learning and data visualization tools—including a cost-sensitive learning method and an event segmenting algorithm—to filter and correlate alerts plus an augmented visualization tool to expedite the triage process. The proposed framework was evaluated experimentally on a dataset collected from a real-world enterprise network, and we report highly convincing results. The alert screening scheme demonstrates significant potential for real-world security operations. We believe that our findings will contributing to the development of a next-generation SIEM system that effectively addresses alert fatigue and lays the foundation for future research in this field.

Chemical screening approach using single leaves identifies compounds that affect cold signaling in Arabidopsis.

The identification of chemical compounds that affect intracellular processes has greatly contributed to our understanding of plant growth and development. In most cases, these compounds have been identified in germinated seedlings. However, chemical screening using mature plants would benefit and advance our understanding of environmental responses. In this study, we developed a high-throughput screening method using single leaves of mature plants to identify small molecules that affect cold-regulated gene expression. A single excised leaf of Arabidopsis (Arabidopsis thaliana) grown in submerged cultures responded to low temperatures in terms of COLD-REGULATED (COR) gene expression. We used transgenic Arabidopsis harboring a COLD-REGULATED 15A (COR15A) promoter::luciferase (COR15Apro::LUC) construct to screen natural compounds that affect the cold induction of COR15Apro::LUC. This approach allowed us to identify derivatives of 1,4-naphthoquinone as specific inhibitors of COR gene expression. Moreover, 1,4-naphthoquinones appeared to inhibit the rapid induction of upstream C-REPEAT BINDING FACTOR (CBF) transcription factors upon exposure to low temperature, suggesting that 1,4-naphthoquinones alter upstream signaling processes. Our study offers a chemical screening scheme for identifying compounds that affect environmental responses in mature plants. This type of analysis is likely to reveal an unprecedented link between certain compounds and plant environmental responses.

Discovery of selective HDAC6 inhibitors based on a multi-layer virtual screening strategy

The abnormal enhancement of histone deacetylase 6 (HDAC6) has been demonstrated to be closely related to the occurrence and development of various malignant tumors, attracting extensive attention as a promising target for cancer therapy. Currently, only limited selective HDAC6 inhibitors have entered clinical trials, making the rapid discovery of selective HDAC6 inhibitors with safety profiles particularly urgent. In this study, a multi-layer virtual screening workflow was established, and the representative compounds screened were biologically evaluated in combination with enzyme inhibitory and anti-tumor cell proliferation experiments. The experimental results showed that the screened compounds L-25, L-32, L-45 and L-81 exhibited nanomolar inhibitory activity against HDAC6, and exerted a certain degree of anti-proliferative activities against tumor cells, especially the cytotoxicity of L-45 to A375 (IC50 = 11.23 ± 1.27 μM) and the cytotoxicity of L-81 against HCT-116 (IC50 = 12.25 ± 1.13 μM). Additionally, the molecular mechanisms underlying the subtype selective inhibitory activities of the selected compounds were further elucidated using computational approaches, and the hotspot residues on HDAC6 contributing to the ligands’ binding were identified. In summary, this study established a multi-layer screening scheme to quickly and effectively screen out hit compounds with enzyme inhibitory activity and anti-tumor cell proliferation, providing novel scaffolds for the subsequent anti-tumor drug design based on HDAC6 target.

115 Fibre-Aerogel-Mats for façade Insulation: How to Guide SSbD Development by Screenings?

Abstract The HARMLESS project focusses upon assessment approaches to support Safe-and-Sustainable-by-Design (SSbD) development of advanced materials (AdMa). Case studies comprise several industry sectors. Specifically for the construction sector we study façade insulation by fibre-aerogel-mats. Beyond the relatively simpler mono-component organic aerogels presented earlier (Keller et al. 2021), here we deal with multi-component materials: Glass fibers provide structural integrity for the silica-based aerogel that provides the thermal insulation performance, though is coated by organosilane as a hydrophobizing agent to prevent moisture uptake. Optionally, an additional inorganic coating can be applied to enhance mechanical stability. Here we explored this wide SSbD design space by four industrially relevant SSbD-versions of fibre-aerogel-mats; these were ranked and compared against each other as well as conventional insulation material (i.e. stone wool). We assessed the release by performing several typical occupational operations under clean-air conditions within a laboratory setting. Up to 106/ccm particles are released, with respirable aerodynamic diameters. We collected the dust and assessed the structure and behavior with respect to its biological reactivity and biodissolution, focusing on the screening and ranking of inhalation hazards. The data on exposure and hazard was complemented by data on functionality in the intended use, where all SSbD versions performed significantly better than the conventional alternative. The new data refines the risk screening and categorisation schemes for advanced materials, including Early4AdMa (RIVM 2022), AdmGRID (Kennedy et al. 2019), InnoMat.Life (Wohlleben et al. 2022) and an environmental risk screening (Arvidsson et al. 2022).

172P Early impact of a personalised cancer interception programme for women at non-genetic high risk of breast cancer (BC)

Risk-based cancer prevention is a major future strategy. “Interception” is a French pilot, mixed community-hospital and digital-physical programme based on 4 pillars: 1. community-based identification of people at high risk of cancer; 2. a One-Stop Shop (OSS) including individual visits and group workshops to inform and empower patients and design their shared personalised prevention plan; 3. Implementation of this plan in community practice; 4. Fast cancer care pathway if required. We assessed the pathway dedicated to women at increased non-genetic risk of BC (CANRISK-based 5-year risk of invasive BC >2.5%). We analysed data of women at high risk of BC non linked to a germline variant seen between 02/2021 and 12/2022. Nutritional habits and physical activity assessments used the WCRF score. Perception of knowledge on risk, prevention and screening, and self-evaluated lifetime probability and compared probability of BC, were assessed before and 8 days after OSS (analogue visual scales); comparisons used paired Wilcoxon tests. 141 women at high non-genetic BC risk entered the programme. Mean age was 40.5 years [32.2-49], 81% had tertiary education. Recommended BC screening scheme was modified in 64% (increased mammography frequency: 36 (50%), addition of yearly MRI: 36 (50%)). Identified BC prevention targets were: insufficient physical activity (83%), overweight or obesity (36%), alcohol consumption (57% incl. 5% with >1 alcohol drink/day), current smoking (21%). 97% had at least 1 prevention target. The mean perceived knowledge on BC risk improved (58.0% before vs 87.4% after, p<0.05). Self-evaluated risk of BC dropped significantly after OSS (Perceived lifetime risk 70% (σ=17.1) before vs 35% (σ=22.5) after, p<0.05). Compared perceived probability of BC remained unchanged. 98% of women were highly or very highly satisfied with the programme. A programme dedicated to women at high BC risk has the ability to improve screening measures in conformity with current guidelines (51%), identify relevant prevention targets (97%), improve knowledge on one’s individual situation by 50%, and improve perceived cancer risk’s accuracy.

Preventing rheumatoid arthritis: Lessons from that of type 1 diabetes

Preventing rheumatoid arthritis: Lessons from that of type 1 diabetes

Challenges Facing Viral Hepatitis C Elimination in Lebanon.

Hepatitis C is a hepatotropic virus that causes progressive liver inflammation, eventually leading to cirrhosis and hepatocellular carcinoma if left untreated. All infected patients can achieve a cure if treated early. Unfortunately, many patients remain asymptomatic and tend to present late with hepatic complications. Given the economic and health burdens of chronic hepatitis C infection, the World Health Organization (WHO) has proposed a strategy to eliminate hepatitis C by 2030. This article describes the epidemiology of hepatitis C in Lebanon and highlights the challenges hindering its elimination. An extensive search was conducted using PubMed, Medline, Cochrane, and the Lebanese Ministry of Public Health-Epidemiologic Surveillance Unit website. Obtained data were analyzed and discussed in light of the current WHO recommendations. It was found that Lebanon has a low prevalence of hepatitis C. Incidence is higher among males and Mount Lebanon residents. A wide variety of hepatitis C genotypes exists among various risk groups, with genotype 1 being the most predominant. In Lebanon, many barriers prevent successful hepatitis C elimination, including the absence of a comprehensive screening policy, stigma, neglect among high-risk groups, economic collapse, and a lack of proper care and surveillance among the refugees. Appropriate screening schemes and early linkage to care among the general and high-risk populations are essential for successful hepatitis C elimination in Lebanon.

The Value of Immunocytochemical Staining for the HPV E7 Protein in the Diagnosis of Cervical Lesions.

To investigate the value of immunocytochemical (ICC) staining for human papillomavirus (HPV) E7 protein (E7-ICC staining) as a new-generation immunological method in the cytological diagnosis of cervical lesions. The exfoliated cervical cell samples of 690 women were subjected to a liquid-based cytology test (LCT), high-risk HPV (HR-HPV) test, E7-ICC staining, and cervical biopsy for pathological diagnosis. E7-ICC staining as a preliminary screening scheme for cervical precancerous lesions was comparable to the HR-HPV test in sensitivity and to the LCT in specificity. E7-ICC staining was advantageous in facilitating the secondary triage of HR-HPV-positive patients; therefore, this method can be used as an auxiliary scheme to routine LCT for diagnostic grading to improve the accuracy of cervical cytology. E7-ICC staining as a primary or auxiliary cytological screening scheme can effectively reduce the colposcopy referral rate.

A Versatile Strategy for Screening Custom-Designed Warhead-Armed Cyclic Peptide Inhibitors.

Demand for peptide-based pharmaceuticals has been steadily increasing, but only limited success has been achieved to date. To expedite peptide-based drug discovery, we developed a general scheme for cell-based screening of cyclic peptide inhibitors armed with a user-designed warhead. We combined unnatural amino acid incorporation and split intein-mediated peptide cyclization techniques and integrated a yeast-based colorimetric screening assay to generate a new scheme that we call the custom-designed warhead-armed cyclic peptide screening platform (CWCPS). This strategy successfully discovered a potent inhibitor, CY5-6Q, that targets human histone deacetylase 8 (HDAC8) with a KD value of 15 nM. This approach can be a versatile and general platform for discovering cyclic peptide inhibitors.

Super-resolution microscopy based on denoised conventional raw images with wide spectrum denoising

Subject of study. A scheme of screening better super-resolution reconstruction based on denoising conventional raw images with wide spectrum denoising is studied. Purpose of the work. The purpose is to improve the reconstruction effect of ultra-high-resolution images. To this end, reconstruction with noise reduction and compression of ordinary raw images and high-resolution images has been investigated. Method. A binned high-resolution raw image is a conventional raw image. Conventional raw images and high-resolution raw images are denoised with wide spectrum denoising, respectively. The conventional raw images and high-resolution raw images before and after denoising are reconstructed by compressed sensing. Main Results. The denoising ability of wide spectrum denoising based on high-resolution raw images is very stable and does not change with molecular density. The signal-to-noise ratio improves by approximately 8 dB. The denoising ability of wide spectrum denoising based on conventional raw images is not good. The signal-to-noise ratios of conventional raw images is 6 dB higher than that of high-resolution raw images. The signal-to-noise ratios of denoised high-resolution and conventional raw images are almost the same. Compressed sensing reconstruction of the denoised conventional raw images is inferior to that of denoised high-resolution raw images; however, it is better than that of high-resolution and conventional raw images. Practical significance. In conventional single-molecule localizations and super-resolution microscopy, the pixel size of a raw image is about equal to the standard deviation of the point spread function. Wide spectrum denoising can improve the conventional raw image denoising and reconstruction. However, better super-resolution microscopy can be achieved based on wide spectrum denoising and high-resolution raw images. Super-resolution microscopy of high-resolution raw images will become a new research point.

Brain organoids are new tool for drug screening of neurological diseases.

At the level of in vitro drug screening, the development of a phenotypic analysis system with high-content screening at the core provides a strong platform to support high-throughput drug screening. There are few systematic reports on brain organoids, as a new three-dimensional in vitro model, in terms of model stability, key phenotypic fingerprint, and drug screening schemes, and particularly regarding the development of screening strategies for massive numbers of traditional Chinese medicine monomers. This paper reviews the development of brain organoids and the advantages of brain organoids over induced neurons or cells in simulated diseases. The paper also highlights the prospects from model stability, induction criteria of brain organoids, and the screening schemes of brain organoids based on the characteristics of brain organoids and the application and development of a high-content screening system.

Theoretical screening of a graphyne-supported transition metal single-atom catalyst for the N2 reduction reaction.

The electrocatalytic nitrogen reduction reaction (NRR) is a promising technology for the synthesis of NH3 in an ambient environment. However, developing low-cost and high-efficiency electrocatalysts still remains a long-standing challenge. In this work, density function theory (DFT) calculations are done to systematically investigate the NRR catalytic activity of transition metals (TM = Sc-Cu, Y-Ag, and Hf-Au) supported on monolayer graphyne (GY). TM@GY (TM = Sc, V, Mn, Y, Tc, and Os) with excellent NRR performance are demonstrated. The mixed pathway is the most favorable for Sc, V, Y, and Os@GY with the potentials of -0.37, -0.27, -0.40, and -0.36 V, respectively, while the distal reaction pathway is most favorable for Mn and Tc@GY with the potentials of -0.37 and -0.42 V. Most strikingly, Mn, Tc, and Os@GY exhibit high NRR selectivity. This work provides a screening scheme for exploring highly efficient electrocatalysts for the electrochemical NRR under ambient conditions.

Modern Psychoactive Substances and Their Detection in Biomedical Samples

Scientific and technological advancement of the mid- and late twentieth century led to the creation of a large number of new psychoactive substances (NPS), diverse in composition and spectrum of action. The primary stages of fight the spread of NPS are awareness of their characteristics, as well as the possibility of detecting both the substances themselves and biomarkers of their use (metabolites) in human biological objects. The purpose of the work is to review psychoactive compounds and methods of their detection performed for diagnostic purposes. The paper presents brief characteristics of the most common NPS, as well as features of their metabolism in the human. It is shown that the analysis of biological specimens collected from susceptive drug users is difficult due to the low content of analytes, the matrix influences, metabolism and the formation of various artifacts. The general scheme of screening of biological objects assumes the presence of two stages – a preliminary express analysis performed using immunochemical test systems, and a confirmatory analysis performed by gas and liquid chromatography-mass spectrometry. The article discusses the possibilities and limitations of targeted and non-targeted screening. The subject of special consideration was the problems of using chromatography-mass spectrometry methods of NPS analysis in Russian – issues of accessibility of standard substances, search libraries, etc. The article also presents brief characteristics of individual families of NPS, such as stimulants, synthetic cannabinoids, synthetic opioids and hallucinogens. In addition, the article shows that in a number of foreign armies, in particular, in the Armed forces of Ukraine (AFU), drugs and psychostimulants are used to create «fearless soldiers». Thus, methadone, amphetamine and other psychoactive substances, as well as a psychotomimetic – a structural and pharmacological similarity of the prohibited BZ – were found in objects delivered from the positions of the AFU for analysis.

How to Unmask Hidden Cardiovascular Diseases through Preparticipation Screening in Master Athletes?

Cardiovascular disease (CVD) is the most common cause of death globally in general population. Sport activity is an effective and recommended non-pharmacological method of CVD prevention. Presently, the group of people practicing sport regularly is constantly growing due to increasing awareness of its health benefits. However, vigorous-intensity exercises can reveal previously undetected disease. Master athletes over 35 years old are particularly exposed to sudden cardiac death (SCD) mainly in the course of coronary artery disease (CAD). Another common disease in veteran athletes is hypertension. It is known that regular endurance training can lower blood pressure at rest, so arterial hypertension in athletes is usually masked by adaptation to effort. Despite of normal or high-normal blood pressure in the office, the values during exercises and in ambulatory blood pressure monitoring (ABPM) can exceed the norm. Hidden hypertension have the same negative impact on cardiovascular system. It increases the risk of (1) atherosclerosis and therefore myocardial infarction or stroke, (2) left ventricular hypertrophy with diastolic and/or systolic heart failure, myocardial fibrosis and ventricular arrhythmias, (3) left atrial enlargement increasing the risk of atrial fibrillation and stroke and (4) aortic dilation/dissection. Through these complications hypertension can lead to SCD during sport activities, therefore it is important to recognize this disease early and start a proper treatment. To enable safe participation in sports competition detailed guidelines for screening were created, but they mainly concern CAD. We propose an additional scheme of screening in master athletes including the detection of hidden hypertension to prevent its consequences.

Selecting the most appropriate formulation excipient for manufacture of amorphous solid dispersions: a case study of lumefantrine

This work demonstrated the importance of pre-formulation studies and proposed a generalised scheme for excipient screening in the early stage of amorphous solid dispersion(ASD) system development by profiling the excipients’ capability to solubilise, amorphisise, and stabilise the chosen active pharmaceutical ingredient (API) in an effort to rank their suitability. Lumefantrine, an antimalarial active compound with both poor solubility and permeability, was used as a model API and solvent evaporation film casting was used to prepare the candidate ASD matrices in this work.&amp;nbsp;

Multi-criteria screening of carbon dioxide utilization products combined with process optimization and evaluation

Climate change induced by the increasing concentration of carbon dioxide (CO2) in the atmosphere has exhibited widespread impacts to ecosystems. The carbon dioxide utilization (CDU) technology is forecasted to significantly contribute towards decarbonization, providing new pathways for chemical production with carbon dioxide as feedstock. The key challenge that affects the identification of a promising CDU technology is its efficient integration with chemical process design. To this end, this study proposes a multi-criteria screening framework of carbon dioxide utilization technologies combined with process optimization and evaluation. The proposed framework combines process evaluation method and multi-criteria decision analysis (MCDA) method with the aim to identify the most promising technologies, where process evaluation provides process data for multi-criteria decision analysis and multi-criteria decision analysis reaches comprehensive decision. In developing this framework, a thermodynamic-based process model is established to obtain the screening criteria, return on investment (ROI) and carbon dioxide utilization ratio (CDUR), through process simulation, optimization and evaluation. A multi-level screening scheme is presented to assess the technical, economic and environmental performance. The multi-criteria decision analysis method based on Technique of order preference similarity to the ideal solution (TOPSIS) is adopted to obtain the ranking results. The results show that ethanol, methanol and ethylene carbonate are the most promising carbon dioxide utilization products in chemical process. This study provides serviceable guidelines for future development of carbon dioxide utilization technologies combined with chemical process design.

Dual-targeting cyclic peptides of receptor-binding domain (RBD) and main protease (Mpro) as potential drug leads for the treatment of SARS-CoV-2 infection.

The receptor-binding domain (RBD) and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) play a crucial role in the entry and replication of viral particles, and co-targeting both of them could be an attractive approach for the treatment of SARS-CoV-2 infection by setting up a "double lock" in the viral lifecycle. However, few dual RBD/Mpro-targeting agents have been reported. Here, four novel RBD/Mpro dual-targeting peptides, termed as MRs 1-4, were discovered by an integrated virtual screening scheme combining molecular docking-based screening and molecular dynamics simulation. All of them possessed nanomolar binding affinities to both RBD and Mpro ranging from 14.4 to 39.2nM and 22.5-40.4nM, respectively. Further pseudovirus infection assay revealed that the four selected peptides showed >50% inhibition against SARS-CoV-2 pseudovirus at a concentration of 5µM without significant cytotoxicity to host cells. This study leads to the identification of a class of dual RBD/Mpro-targeting agents, which may be developed as potential and effective SARS-CoV-2 therapeutics.