KLEPTOSE® CRYSMEB is a methylated cyclodextrin derivative displaying less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases. linked in part to cholesterol complexation and immune response, but the impact on inflammatory cascade pathways was not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells in physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® Panel. Finally, the anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects driven by pro-inflammatory cytokine secretion inhibition and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Finally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by well-known anti-inflammatory molecules.

Newborn screening (NBS) is hailed as a public health success, but little is known about long-term outcomes following a positive newborn screen. There has been difficulty gathering long-term follow-up (LTFU) data consistently, reliably, and with minimal effort. Six programs developed and tested a core set of minimal LTFU data elements. After an iterative data collection process and the development of a data collection tool, the group agreed on minimal LTFU data elements. The denominator captured all infants with an NBS diagnosis, accounting for children who moved or died prior to the follow-up year. They also agreed on three LTFU outcomes: if the child was still alive, had contact with a specialist, and received appropriate care specific to their diagnosis within the year. The six programs representing NBS public health programs, clinical providers, and research programs provided data across multiple NBS disorders. In 2022, 83.8% (563/672) of the children identified by the LTFU programs were alive and living in the jurisdiction; of those, 92.0% (518/563) saw a specialist, and 87.7% (494/563) received appropriate care. The core LTFU data elements can be applied as a foundation to address the impact of early diagnosis by NBS within and across jurisdictions.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

A higher incidence of primary congenital hypothyroidism (CH) has been related to in-creased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the cost-benefit of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n= 162,730; incidence = 1:1,323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical symptoms (p=0.02), lower serum TSH (p

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.

We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as an alternative enabled by these platforms to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test and still one more for the p16/Ki67 dual stain cytology. A total of 4,499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% got a positive HR HPV-PCR result. Dual staining with the p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Of the PCR results positive for any of these high-risk HPV subtypes, n 68.3% we did not to find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR, to avoid unnecessary colposcopies. Encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists, we still believe that colposcopy continues to be a preferred procedure over dual staining protocol.

Thromboembolic conditions, such as stroke and myocardial infarction [MI], are the primary causes of mortality globally. High efficiency was demonstrated by fibrinolytic enzymes isolated from microbial sources in dissolving various blood clots. The study aimed to investigate and produce bacterial fibrinolytic enzymes from various Egyptian soil conditions using recombinant DNA technology. Fifty soil samples were examined to determine the production of fibrinolytic enzymes. The plasmin plate technique assessed the thrombolytic activities of the strong fibrinolytic enzyme-producing bacterial isolates. In addition to determining the molecular mass using a mass spectrometer and the western blot method, the activity and thermostability of the enzymes were characterized. An affinity chromatography approach was used to purify the fibrinolytic enzymes. However, bacterial recombinant DNA technology produced the pure bacterial fibrinolytic enzyme. Several dosage formulations for the formulation of fibrinolytic enzymes were tested. By using affinity chromatography and the SDS-PAGE test, the isolated bacterial fibrinolytic enzyme in this investigation was almost 83% pure. Bacillus cereus ATCC 4342 was identified as the predominant bacterial isolate secreting fibrinolytic enzymes. It was discovered that the fibrinolytic enzyme activity of fifty soil samples ranged from 0.167 U/ml to 1.853 U/ml. The extracellular enzyme extracted from Bacillus cereus culture supernatant demonstrated a relatively stable fibrinolytic activity over 18 hours at a pH range of 7.4–10, as well as stability with maximum productivity at 43℃ for over 60 minutes. In this investigation, the enzyme was referred to as Fibrin-proteinase[ FP]. The fibrin clots were directly thrombolyzed by the FP. The calculated values for the specific activity and molecular mass of the FP were approximately 40.71 units/mg of protein and approximately 30 KDa, respectively. It was observed that the presence of Fe+3 marginally boosted protease activity, but the presence of EDTA decreased it. On the other hand, adding monovalent cations like K+1 and Na+1 significantly increased the fibrinolytic activity of FP. The enzyme exhibited activity throughout the temperature range of 20 to 65℃, peaking at 55℃. The ideal range for the generation of protease was 35–43℃ and 8.0–10. The thermostable fibrinolytic enzyme FP, which was isolated from Bacillus cereus ATCC 4342 in various soil environments in Egypt during the current study, was a promising fibrinolytic enzyme because it demonstrated a more extensive and effective fibrinolytic activity and fewer side effects than the fibrinolytic enzymes that are currently available worldwide. It is advised that further research be done on optimizing the right formulation of bacterial fibrinolytic enzymes in the future to help dissolve different types of blood clots and, as a result, lower the high death rate that exists worldwide.

(1) Background: The aim of the research was to present and emphasize the importance of magnetic resonance imaging (MRI) in diagnosing Achilles tendon (AT) ruptures by presenting case reports. (2) Materials and Methods: The sample of respondents included 7 patients (4 males and 3 females, 2 athletes and 5 non-athletes), aged 25 to 58 years, with AT injuries, who were examined and treated at the Institute for Treatment and Rehabilitation "Niška Banja", Niš, Serbia. Ankle examinations with MRI were conducted using the Esaote O-scan 0.3 T machine. The examinations were performed without the application of a paramagnetic contrast agent and without the use of anesthesia. Results: The MRI method's sensitivity and overall diagnostic accuracy were excellent, with 100% true positives. In our study, the method accurately detected the presence, location, and severity of AT injuries in all cases. MRI is an important and reliable method for detecting AT injuries, classifying them, monitoring the course of recovery, and assessing the effects of therapy. Conclusions: An unrecognized or delayed diagnosis of an AT injury can lead to chronic changes. Timely diagnosis (clinical examination, ultrasonography, magnetic resonance imaging) and appropriate treatment (conservative or operative) enable patients to return to normal activities, including sports. Unfortunately, the use of MRI is limited by restricted access and the cost of the examination.

The blood counts of α thalassemia carriers (α-thal) are similar to those of β thalassemia carriers, except for Hgb A2 that is not elevated. The objective of this study was to determine whether mathematical formulas are effective for detecting suspected α-thal. The data were obtained from the database of the prevention program for detecting couples at risk for having a child with hemoglobinopathy. RBC indices were analyzed using mathematical formulas and the sensitivity and negative predictive value (NPV) calculated. Among 1334 blood counts suspected α-thal analyzed, only the Shine&Lal and the Support Vector Machine formulas revealed high sensitivity and NPV. Sensitivity was 85.54 and 99.33% and NPV 98.93 and 99.93%, respectively. Molecular defects were found in 291, 81 had normal α genes. Molecular analysis was not performed in 962. Based on these results, mathematical formulas incorporating one of these reliable formulas for detecting suspected α or β thalassemia carriers in the program of the automatic analyzers can flag these results and increase the awareness of the primary physicians about the carrier risk and send an alert with a recommendation for further testing.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Despite advancements in treatment, the prognosis for patients with GBM remains poor due to its aggressive nature and resistance to therapy. CRISPR-based genetic screening has emerged as a powerful tool for identifying genes crucial for tumor progression and treatment resistance, offering promising targets for tumor therapy. In this review, we provide an overview of the recent advancements in CRISPR-based genetic screening approaches and their applications in GBM. We highlight how these approaches have been used to uncover genetic determinants of GBM progression and susceptibility to various therapies. Furthermore, we discuss ongoing challenges and future directions of CRISPR-based screening methods in advancing GBM research.

Sarcopenia is associated with clinical complications, which increase mortality. Effective sarcopenia risk screening in the elderly should be grounded in a comprehensive assessment, encompassing both nutritional status and medication use. Current screening tools, while emphasizing muscular per-formance, exhibit limited sensitivity in identifying elderly individuals at risk of sarcopenia. This cross-sectional study aimed to develop a sarcopenia risk screening tool, named Sarc-Global, with enhanced sensitivity, incorporating factors pertinent to the overall health of the elderly. Utilizing the criteria established by EWGSOP2 for diagnosing sarcopenia, we evaluated 395 communi-ty-dwelling elderly individuals. This evaluation served as a reference for assessing the efficacy of two validated questionnaires, Sarc-F and Sarc-CalF, and our newly developed Sarc-Global. Con-structed through multiple logistic regression, Sarc-Global integrates variables such as sex, age, medication use, body mass index, arm circumference, and handgrip strength – all significantly associated with sarcopenia (p

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

Background: We assessed the pertinence of yearly updating the International Working Group on the Diabetic Foot (IWGDF) risk classification in people with diabetes by quantifying the changes in the risk group and its accuracy in identifying those developing an ulcer (DFU) in a primary care setting. Methods: In our retrospective cohort study, we included all people with diabetes with a foot as-sessment registry between January 2016 and December 2018 in the Baixo Alentejo Local Health Unit. Foot-related data was collected at baseline after one and two years. DFU and/or death until December 2019 were registered. The proportion of people changing their risk status each year was calculated. Accuracy measures of the IWGDF classification to predict DFU occurrence at one, two, and three years were calculated. Results: A total of 2097 people were followed for three years, during which 0.1% died, and 12.4% developed a DFU. After two years, 3.6% of the participants had progressed to a higher-risk group. The IWGDF classification presented specificity values superior to 90% and negative predictive values superior to 99%. Conclusion: Foot risk status can be safely updated every two years instead of yearly. The IWGDF classification can accurately identify those not at risk of DFU.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

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Cardiovascular diseases (CVDs) remain the leading cause of mortality. Traditional approaches to diagnosing and treating CVDs often involve interpretation, which can lead to errors. The emergence of Artificial Intelligence (AI) and Machine Learning aids the management of CVDs. AI examines amounts of data and identifies patterns offering solutions for disease detection, risk prediction, and patient care. The American Heart Association's 2023 Scientific Sessions (AHA23) showcased studies that highlight AIs potential to revolutionize cardiac healthcare. This article presents a review of these cutting-edge studies exploring how AI is applied in health, the outcomes of these applications, and their implications for clinical practice. The insights gained from this review will contribute to the discussion on AI's role in healthcare and its capacity to enhance outcomes.

A screening questionnaire for autism symptoms is not yet available in Poland, and there are no recommendations regarding screening for developmental disorders in Polish primary health care. The aim of the study was to assess the opinions of parents and physicians on the legitimacy and ne-cessity of screening for autism spectrum disorders, potential barriers to the implementation of the screening program, and the evaluation and presenting the process of the online ASD screen-ing, which was part of the validation program of the Polish version of one of the screening tools. The study involved 418 parents whose children were screened online and 95 primary care physi-cians who expressed their opinions in prepared surveys. The results indicate that both parents and doctors perceive the need to screen children for ASD in general population without a clear preference as to the screening method (online or in-person). Online screening may prove to be at least a partial method of solving numerous indicated systemic difficulties - including: time con-straints, lack of experienced specialists in the field of developmental disorders or related to the organizational difficulties of health care.

Introduction: The Get Active Questionnaire (GAQ), developed by the Canadian Society for Ex-ercise Professionals (CSEP) was recently recommended for pre-participation screening for the general population in Singapore before increasing exercise levels. This review examines the evi-dence behind the GAQ and relevance to our tropical environment. Methods: Searches were done via Pubmed, MEDLINE and the Cochrane Central Register of Controlled Trials. Resources referenced by the CSEP were hand-searched. The CSEP was also contacted for further information. Evidence behind each GAQ question was compared to inter-national literature and guidelines, where applicable. Results: Out of 273 studies, 49 were suitable for analysis. Two GAQ studies commissioned by the CSEP showed a high negative predictive value but high false negative rate. Of the nine GAQ questions, those on dizziness, joint pains and chronic diseases appear justified. Those on heart disease/stroke, hypertension, breathlessness and concussion require modification. That on syncope can be amalgamated into the dizziness question. The remaining question may be deleted. No long-term studies were available to validate use of the GAQ. Heat disorders were not considered in the GAQ. Conclusions: Modification of the GAQ, including inclusion of environmental factors, may make it more suitable for the general population and should be considered.

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), rare disease, and genomics. Over fifteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. A key component of these efforts has been the development of resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI). This paper presents findings from a survey conducted by the NBSTRN team with input from one of theNBSTRN's expert workgroups, the Bioethics and Legal Workgroup. With responses from 88 members of the NBS community including researchers and state NBS programs, the survey found that individuals rely on internal and collegial ELSI resources and highlighted a substantial demand for structured, accessible training and resources. The survey’s insights emphasize the importance of privacy and informed consent in NBS research, and suggested a need for improved collaborative tools and educational programs focused on ELSI for the NBS community. The survey results may inform future efforts in ELSI and NBS research including the development of expanded ELSI tools that leverage digital platforms and consultative services.

The shikimate pathway is crucial for the biosynthesis of aromatic amino acids in plants and represents a promising target for developing new herbicides. This work aimed to identify inhibitors of shikimate dehydrogenase (SDH), a key enzyme of the shikimate pathway that catalyzes the conversion of 3-dehydroshikimate to shikimate. Virtual screening and molecular docking were performed on the SDH active site of Arabidopsis thaliana (AtSDH), and 6-nitroquinazoline-2,4-diol (NQD) was identified as a potential inhibitor. In vitro assays showed that NQD decreased the activity of AtSDH by reducing Vmax while keeping KM unchanged, indicating noncompetitive inhibition. In vivo, hydroponic experiments revealed that NQD reduced the root length of soybean and maize. Additionally, NQD increased the total protein content and certain amino acids. Soybean roots uptake NQD more efficiently than maize roots. Furthermore, NQD reduced shikimate accumulation in glyphosate-treated soybean roots, suggesting its potential to restrict the flow of metabolites along the shikimate pathway in soybean. Simultaneous treatment of maize seedlings with glyphosate and NQD accumulated gallic acid in the roots, indicating that NQD inhibits SDH in vivo. Overall, the data indicate that NQD inhibits SDH both in vitro and in vivo, providing valuable insights into the potential development of herbicides targeting SDH.

Introduction: Contrast-enhanced spectral mammography (CESM) is a novel technique employed in breast cancer screening and detection. In this systematic review, we aim to compare the diagnostic performance of CESM with magnetic resonance imaging (MRI) in the context of breast cancer diagnosis. Material and Method: We have searched for paper in Pubmed and Scopus from July 2023 to February 2024, finding 256 suitable papers according to our selection criteria (perspective or retrospective studies, women diagnosed with breast cancer, comparison of Contrast-enhanced Spectral Mammography and Magnetic Resonance Imaging, sensitivity and specificity metrics provided). Every paper was then checked for quality using the QUADAS 2 assesement score. Sensibility, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and accuracy were recorded. Results: 15 studies were selected for analysis. CESM demonstrated comparable sensitivity to MRI, with values ranging from 36.4% to 100% for CESM and 0% to 100% for MRI. Specificity varied between the modalities, with CESM showing specificity ranges of 17% to 100% compared to 23% to 92.31% for MRI. Discussion and Conclusion: CESM has comparable diagnostic validity to MRI, and is a valuable tool in detecting breast cancer.

Aim: M. oleifera, a tree that have medicinal applications. A.hispidum has been utilized in traditional medicine as a cure for microbial and other infections. The aim of this study is to evaluate the bioactive compounds of A.hispidum and M.oleifera and determination of Antioxidant, Anticancer, Antifungal and Antibacterial for their pharmaceutical importance. Methods: Fresh leaves of these plants were collected from Akinmoorin and Awe in Nigeria. Particles Induced X-Ray Emission method was carried out via a 2.5MeV proton beam. Detection of phytochemicals was carried out by HPLC analysis. Disc diffusion method was used to determine MIC for fungi and MIC for bacteria. DPPH radical scavenging activity of these plant leaves was determined. Cancer cells were cultivated using 5% CO2 with 95% air in 100% relative humidity. The adherent cells were seeded and subjected to treatment with increase concentrations of the plant extracts from 48–72 h for anti-cancer activity. Results: The mean ± S.E. of the mean (S.E.M.) for all data were displayed. Three copies of the invitro experiment data were collected. For unpaired data, the student's t-test was applied at P < 0.05, the differences in the data were deemed significant. The ethanolic extracts showed on the average a 50% reduction in cancer cell viability at 24.5μg mL−1 for MO and 16.0μg mL−1 for AH respectively. Conclusions: The results of this study indicated these two plants have Antioxidant, Antitumor, Antifungal and Antibacterial activity and it is recommended that the active constituents be isolated and formulated into suitable dosage form. Keywords: Phytochemical Screening; pharmacological activities; Acanthospermum hispidum; Moringa oleifera.

Newcastle disease (ND) is a viral infection that affects domestic and wild type birds especially poultry and establishing serious economic costs for poultry industry. Newcastle disease virus’ (NDV) HN membrane receptor is attractive therapeutic candidate, contributes to pathogenicity with various functions such as fusion and prevent viral self-agglutination to permit viral spread. No validated HN inhibitor has been reported yet. However, the purpose of current study was to determine potential compounds via pharmacophore-based screening of natural molecules to inhibit HN receptor of NDV. Physicochemical characteristics and phylogenetic analysis were determined to elucidate structural information and phylogeny of target protein across different species as well as members of gene family. Fill missing residues of HN target protein and evaluated via PROCHECK and VERIFY 3D. We employed shape and feature-based pharmacophore model and screen natural compound’s library through numerous scoring schemes. Top 48 hits with 0.8860 pharmacophore fit score were subjected towards structure-based molecular docking. Top 9 compounds was observed witihin the range of -8.9 to -7.5 kcal/mol binding score. Five best-fitting compounds in complex with HN receptor were subjected to predict biological activity and ADMET analysis. Top two hits were selected for MD simulations to validate binding modes and structural stability. Upon scrutinization, A1 (ZINC05223166) emerges as potential HN inhibitor to treat ND, necessitating further validation via clinical trials.

Hepatitis B and C are major health issues in developing countries such as Pakistan and Afghan-istan. The aim of this study was to determine the prevalence and effectiveness of a screening program for hepatitis B and C in a region with no existing programs, and to estimate their prev-alence in the general population in Khyber Pakhtunkhwa Province, Pakistan, as well as in Afghan refugees or migrants. A prospective cohort study was done in the general population of Peshawar and its adjacent districts, as well as migrants from neighboring provinces of Afghani-stan, who presented to our tertiary-care health facility. A Microsoft Excel registry was created for data collection, which were analyzed using IBM SPSS via descriptive analysis, normal distribution curve histograms, and chi-squared tests. A total of 9563 individuals were screened for hepatitis (5894 males and 3669 females), including Afghan migrants in Peshawar and surrounding districts. 876 individuals tested positive for hepatitis, with 538 positive for hepatitis B (383 males and 155 females) and 330 positive for hepatitis C (198 males and 134 females). Eight individuals had a hepatitis B and C co-infection. Among the study population, the prevalence rates were 2.2% for hepatitis B and 2.3% for hepatitis C, of which the Afghan migrants accounted for 2.7% and 0.5%, respectively. According to the gender-based distribution, hepatitis B was more prevalent in males, whereas there was no significant gender-based difference for hepatitis C. Our results highlight the need for a comprehensive approach to control hepatitis B and C in Pakistan and Afghanistan. Increased awareness, improved healthcare, and preventive measures such as screening and elimination programs to prevent severe liver diseases and eradicate hepatitis are necessary.

We delve into nonrelativistic quantum electrodynamics within a background magnetic field, ensuring gauge invariance via a vector potential. Our exploration extends to the Lagrangian, which incorporates electron self-interactions and electromagnetic field interactions. Through the path integral formalism, we elucidate the effective action, with a specific focus on the photon propagator and screening effects. Examining density and current components reveals Laurent expansions in the hydrodynamic limit. The equations of motion in real space are derived, leading to discussions on phenomena such as Poiseuille-like flow and the Navier-Stokes equation. To ground our theoretical framework at practical contexts, we consider applications such as the fluid dynamics at binary star systems. Depending on the velocity of the expelled fluid, our analysis allows for both nonrelativistic and relativistic treatments, providing a versatile tool for understanding the intricacies of fluid behavior at astrophysical scenarios. Additionally, we recognize that at the presence of a magnetic field, magnetohydrodynamics becomes crucial. While our current focus is at nonrelativistic quantum electrodynamics, the insights gained here contribute to a broader understanding, offering a comprehensive foundation for quantum electrodynamics analysis at diverse physical systems.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Cutaneous melanoma (CM) is a candidate for screening programs, since its prognosis is excellent when diagnosed in an early disease stage. Targeted screening of those at high risk for developing CM, a cost-effective alternative to population-wide screening, requires valid procedures to identify the high-risk group. Self-assessment of the number of nevi has been suggested as a component of such procedures, but its validity has not yet been established. We analyzed the level of agreement between self-assessments and expert assessments of the number of melanocytic nevi in the area between the wrist and the shoulder of both arms based on 4548 study subjects in whom mutually blinded double counting of nevi was performed. Nevus counting followed the IARC protocol. Study subjects received written instructions, photographs, a mirror, and a “nevometer” to support self-assessment of nevi larger than 2 mm. Nevus counts were categorized based on the quintiles of the distribution into five levels defining a nevus score. Cohen’s weighted kappa-coefficient was estimated to measure the level of agreement. In the total sample, agreement between self-assessments and expert-assessments was moderate (raw agreement: 50.29%, weighted κ=0.596). Self-assessed nevus counts were higher than those determined by experts (mean differ-ence: 3.33 nevi). The level of agreement was independent of sociodemographic and cutaneous factors; however, participants’ eye color had a significant impact on the level of agreement. Our findings show that even with comprehensive guidance, only a moderate level of agreement between self-assessed and expert-assessed nevus counts can be achieved. Self-assessed nevus information does not appear to be reliable enough to be used in individual risk assessment to target screening activities.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

Sexual Violence (SV) can deeply impact victims' physical and psychosocial well-being. Yet many healthcare providers, including registered nurses (RNs), hesitate to screen patients due to a lack of confidence and knowledge. The SATELLITE Sexual Violence Assessment and Care Guide was developed to address this gap; however, the guide’s educational effectiveness remained untested. This pilot study aimed to assess the feasibility, acceptability, and efficacy of an education program based on the SATELLITE guide among RNs in clinical settings, using a pre- and post-test design. Results indicated that the education was not only feasible and acceptable, but also demonstrated the effects as desired with significant increases in RNs' knowledge and confidence in SV screening and care. The program's assessment tool was valid and reliable, and participant recruitment was feasible. Based on these findings, it is recommended that the SATELLITE education program be further tested with a larger RN sample and extended to other healthcare providers. Additionally, exploring different regions, cultural contexts, and healthcare settings would enhance understanding of the program's broader applicability and effectiveness.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Tandem mass spectrometry (MS/MS) for diagnosing inborn errors of metabolism (IEM) is recognized as an ethical, safe, simple, and reliable screening test. Presented bibliometric analysis aims to describe the network structure of the scientific community in the study area at the level of countries, institutions, authors, papers, keywords, and sources; scientific productivity, directions, and collaboration efforts in a considered period (1991–2023.) Using the PRISMA method, we conducted a systematic search for articles reporting using MS/MS to screen for inherited metabolic disorders and inborn errors of metabolism collected from the Web of Science Core Collection (WOSCC.) A total of 451 articles out of 546, by 2,682 authors, published in 190 journals, with 15,440 citations in 8,181 citing articles, with an average citation of 34.24 per article, and an H-index of 64 were retrieved from the WOSCC. The research status of MS/MS in IEM screening was identified. The most relevant current research directions and future areas of interest were revealed: "selective screening for IEM," "new treatments for IEM," "new disorders considered for MS/MS testing," "ethical issues associated with newborn screening," "new technologies that may be used for newborn screening," "use of a combination of MS/MS and gene sequencing," etc.

Structures inevitably suffer damages after an earthquake, with their severity ranging from minimal damages to non-structural elements to partial or even total collapse, possibly with loss of human lives. Thus, it is essential for engineers to understand the crucial factors that drive a structure towards suffering higher degrees of damage, so that preventative measures can be taken. In the present study, we focus on three well-known damage thresholds, namely Collapse Limit State, Ultimate Limit State and Serviceability Limit State and analyze which of the features obtained via Rapid Visual Screening, determine whether or not a given structure will cross that threshold. To this end, we use Machine Learning to perform binary classification for each damage threshold, as well as Explainability via SHAP values (acronym for SHapley Additive exPlanations) to quantify the effect of each parameter. The quantitative results obtained demonstrate the potential applicability of ML methods to re-calibrate the computation of structural vulnerability indices using data from recent earthquakes.

Advances in gastric cancer screening and endoscopic technology have made it possible to detect and treat gastric cancer at an early stage. As a result, about 40% of all gastric cancers have now been resected by endoscopic treatment in Japan. In endoscopic diagnosis, magnifying endoscopic observation using band-limited light such as narrow band imaging (NBI) has significantly improved the accuracy of gastric cancer diagnosis. At the same time, in endoscopic treatment, endoscopic submucosal dissection (ESD) has contributed to increase explosively the number of gastric cancers which could be resected endoscopically. In recent years, the construction of algorism for endoscopic diagnosis and treatment with a view to personalized medicine has been explored, and endoscopic use for gastric cancer managements is expected to develop further in the future. Keywords (5 words):

Background. Implementing mammogram screening means that clinicians are seeing many breast cancers that will never develop metastases. The purpose of this study was to identify subgroups of breast cancer patients who did not present events related to long-term breast cancer mortality, taking into account diagnosis at breast screening, absence of palpability and axillary involvement, and genomic analysis with PAM50. Patients and Methods. To identify them, a retrospective observational study was carried out selecting patients without palpable tumour, without axillary involvement, and a genomic analysis was performed with PAM50. Results. The probability of distant metastasis-free interval (DMFI) of 337 patients was 0.92 (95% CI, 0.90-0.93) at 20 years and 0.96 (95% CI, 0.92-1.00) in 95 patients (28%) with available PAM50 tests. In 22 (23.15%) luminal A tumours and in 9 (9.47%) luminal B tumours smaller than 1 cm and in HER2 and basal type tumours there were no metastatic events (20-year DMFI of 1.00). Conclusion. Patients with nonpalpable breast cancer found at screening with negative nodes are at very low risk. It is possible to identify subgroups without metastatic events by determining the intrinsic subtype and tumour size less than 1 cm. De-escalation of treatment should be considered.

OBJECTIVE: Cervical cancer is a major cause of cancer-related mortality, necessitating effective screening and diagnostic methods. This study aimed to assess the performance of cervicovaginal smear (CVS) and Human papilloma virus (HPV)-DNA cotest. STUDY DESIGN: The pathology results of 225 female patients who underwent HPV-DNA testing with CVS between 2014 and 2022 and were subsequently diagnosed by colposcopic cervical biopsy or second CVS were retrospectively analyzed. RESULTS: CVS samples showed Atypical Squamous Cells of Undetermined Significance (ASCUS), Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL) and cervical cancer. Concordance between the first and second diagnoses demonstrated moderate agreement for LSIL. ASCUS cases exhibited a significant correlation with HPV-DNA positivity and higher-grade cervical lesions. In biopsy, sensitivity and specificity for CIN 2 were 67.8% and 67.9%, respectively, while for CIN 3, they were 81.8% and 58.5%. HPV testing showed significant correlation with histopathologic results. In women over 40 years, more intraepithelial lesions were diagnosed compared to younger women (p<0.005). The conventional smear technique proved reliable in detecting high-grade lesions. CONCLUSION: Despite the limitations of our study, our results emphasize the value of HPV-DNA testing to avoid unnecessary interventions and to establish appropriate follow-up strategies.

Background: Breast cancer remains a significant health concern among women globally. Despite advancements in awareness and diagnostic techniques, it persists as a leading cause of death, with profound impacts on affected individuals' quality of life. Primary and secondary prevention, including regular screenings and practices like Breast Self-Examination (BSE), are pivotal in ensuring early diagnosis. The NHS in Italy offers screenings for women aged 50-69 every two years, managed by the Local Health Authority. However, the participation rates, especially among the Chinese female population residing in Italy, are not well-understood. Methods: Using a snowball method, we electronically disseminated a survey to investigate how Chinese women living in Italy engage with available NHS screening programs. The survey also explores their practice of BSE, the use and impact of technological tools on prevention, and aims to understand their depth of knowledge and misconceptions about breast cancer. Results: The data revealed a significant gap in breast cancer screening adherence and knowledge among Chinese women in Italy, with a notable discrepancy between the general population and those who have previously encountered cancer. Conclusions: The results highlight the urgent need for interventions that are culturally sensitive, stressing that these actions are not only desirable but essential.

Alzheimer's disease (AD) is the first cause of dementia worldwide and represents a public health challenge. Current diagnostic methods still rely on extended interviews and paper tests. We aim to create a novel, quick cognitive-screening tool on a numerical tablet. This program, built and edited with Unity®, runs on Android® for the Samsung Galaxy Tab S7 FE®. Composed of seven tasks inspired by the Mini-Mental Status Examination and the Montréal Cognitive Assessment, it browses several cognitive functions. The architectural design of this tablet application is distinguished by its multifaceted capabilities, encompassing not only seamless offline functionality but also a mechanism to ensure the singularity of data amalgamated from diverse sites. Additionally, a paramount emphasis is placed on safeguarding the confidentiality of patient information in the healthcare domain. Furthermore, the application empowers individual site managers by allowing them to access and peruse specific datasets, thereby enhancing their operational efficacy and decision-making processes. We performed a usability assessment among 24 healthy patients with a final F-SUS score of "excellent". Participants perceived the tool as simple to use and achieved the test in a mean time of 142 seconds, confirming that a short assessment on a numerical tablet is possible.

The World Health Organization (WHO) documents malaria as one of the leading causes of high morbidity and mortality worldwide. The disease affects millions and kills thousands of people annually. Efforts to reduce the global burden of malaria have prompted WHO to recommend prevention strategies like using anti-malarial drugs. However, these strategies have been ineffective because of anti-malarial drug resistance. The only efficacious malaria treatment is Artemisinin-based Combination Therapy (ACT). However, the extended ACTs clearance times, linked to the emergence of artemisinin monotherapy resistance recorded most recently in Africa and the Great Mekong region, pose a danger to its efficacy. Therefore, better efficacious malaria drugs are required. Since P. falciparum heat shock protein 90 (PfHsp90) is a well-characterized malaria drugs target, this study uses it to discover more efficacious malaria drugs. An in-silico approach was used to discover PfHsp90 inhibitors with pharmacological properties against Plasmodium malaria using molecular dynamics simulation (MDS) and hierarchical virtual screening. Geldanamycin (GDM), a well-known anti-PfHsp90 compound, was used to identify PfHsp90 inhibitors with pharmacological properties against Plasmodium malaria by screening it against the ZINC database via the ZINCPHARMER web server. This virtual screening process resulted in 17 hits. These ZINCPHARMER hits were subjected to drug-likeness and pharmacokinetics properties analysis in the SwissADME web server, and 9 of them satisfied the requirements. The 9 ZINC compounds were docked with PfHsp90 using the PyRx software to understand their interactions. From the molecular docking results, ZINC09060002 (-8.2 kcal/mol), ZINC72133064 (-7.8 kcal/mol), ZINC72163401 (-7.7 kcal/mol), ZINC72358537 (-8.1 kcal/mol), and ZINC72358557 (-7.6 kcal/mol) had better binding affinities to PfHsp90 than GDM (-7.5 kcal/mol). The stability of these molecularly docked protein-inhibitor complexes was assessed through MDS using GROMACS 2022. ZINC72163401, ZINC72358537, and ZINC72358557 formed stable complexes with PfHsp90. The lead compounds were subjected to in vitro validation for their inhibitory capability. They showed promising inhibition of parasite growth with IC50 values ranging between 200 – 400 ng/ml. In this regard, the three PfHsp90 inhibitors can be used as anti-malarial drugs. However, further structural optimization studies and clinical (in vivo) tests are necessary to ascertain the antimalarial activity of these compounds in humans.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015-22 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0 - 9.6) and 4.0 (1.8 - &gt;70) µmol/L respectively and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C, in ‘asymptomatic’ individuals (n=17), demonstrating a median (range) C5C of 3.0 (1.8 – 7.1) whilst ‘clinically affected’ patients (n=7), showed a median (range) C5C of 13.9 (7.7 - &gt; 70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those &gt; 2.0 and &lt; 5.0 µmol/L prompting 2nd tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.

Lifestyle interventions halt the progression of prediabetes to frank type 2 diabetes (T2D). However, the feasibility of a diabetes prevention program promoting tailored interventions on a national scale and conducted by primary care physicians is unclear. To explore this issue, general practitioners dislocated in ten different regions throughout Italy enrolled random subjects without known metabolic diseases to identify individuals with prediabetes and prescribe them an intervention based on physical activity. Using a simple stepwise approach, people referring to their primary care physician for any reason were screened for their diabetes risk with a web-based app of the Findrisc questionnaire. Those at risk for T2D, i.e. with a Findrisc score > 9, were invited to come back after overnight fasting to measure fasting glycaemia (FG). Those with 100 ≤ FG < 126 mg/dL were considered as people with prediabetes and compiled the Physical Activity Readiness Questionnaire (PAR-Q) to then receive a personalized prescription of physical activity. Overall, 5928 people were enrolled and compiled the questionnaire. Of these, 2895 (48.8 %) were at risk for T2D. Among these, FG was measured in 2168 subjects (participation rate 75%). The numbers of individuals with undetected prediabetes and T2D according to FG were 755 and 79 (34.8% and 3.6% of those assessing FG), respectively. Of the 755 subjects in the prediabetes range, 739 compiled the PAR-Q and started a personalized program of physical activity (participation rate 97%). Physicians involved in the study reported a mean of 6 minutes to perform the screening. Overall, these data suggest the feasibility of a national diabetes prevention program developed by general practitioners using a simple stepwise approach starting from a web-app to intercept individuals with prediabetes.

In conclusion, this review highlights the challenges in the current screening pathway and the potential for AI, particularly LLM, to revolutionize DR screening in Japan. The future direction will depend on leadership from ophthalmologists and stakeholders to address long-standing challenges in DR screening so that all people have access to accessible and effective screening.

According to the guidelines of the European Association of Urology (EAU), it is recommended to exclude PSA testing when the expected remaining lifespan is less than 10 years. In this study, we provide a comprehensive analysis of the impact of prostate-specific antigen (PSA) testing on the quality of life of elderly men who are frail. We conducted a comprehensive literature review to identify publications that examine the use of PSA as a screening and prognostic tool for prostatic illnesses in frail men. Our search included the following keywords: Prostate-specific antigen, Frailty, Prostate cancer screening, Hypogonadism, and Benign Prostatic Obstruction (BPO). Prostate-specific antigen (PSA) testing can be used to identify prostate cancer in its early and treatable stages in fragile men with a life expectancy of over 15 years. Additionally, PSA testing allows for the evaluation of the effectiveness of various prostate cancer treatments and the monitoring of testosterone replacement therapy for hypogonadism. PSA is also indicative of the clinical development of patients with benign prostatic obstruction (BPO). Nevertheless, PSA is being extensively provided without individualised patient assessment, contributing to the economic strain on healthcare systems. Conducting a frailty evaluation on men to determine the potential advantages of PSA tests on their quality of life will help minimise avoidable expenses.

Tea infusions are the most consumed beverages in the world after water, their pleasant yet peculiar flavor profile drives consumer choice and acceptance and becomes a fundamental benchmark for industry. Any qualification method capable of objectifying the product's sensory features effectively supports industrial quality control laboratories guaranteeing high sample throughputs even without the human panel intervention. The current study presents an integrated analytical strategy acting as an Artificial Intelligence decision tool for black tea infusion aroma and taste blueprinting. Key markers validated by sensomics are accurately quantified in a wide dynamic range of concentrations. Thirteen key aromas are quantitatively assessed by standard addition with in-solution solid-phase microextraction sampling followed by GC-MS. On the other hand, nineteen key taste and quality markers are quantified by external standard calibration and LV-UV/DAD. The large dynamic range of concentration for sensory markers is reflected in the selection of seven high-quality teas from different geographical areas (Ceylon, Darjeeling Testa Valley and Castleton, Assam, Yunnan, Azores, and Kenya). The strategy acts as an AI smelling and taste machine predicting teas sensory features without the human panel intervention.

Spectral image analysis has the potential to replace traditional approaches for assessing plant responses to different types of stress including herbicide, through non-destructive and high-throughput screening (HTS). Therefore, this study was conducted to develop a rapid bioassay method using a multi-well plate and spectral image analysis for diagnosis of herbicide activity and mode of action. Crabgrass (Digitaria ciliaris) as a model weed was cultivated in multi-well plates and subsequently treated with 6 herbicides with different modes of action when they reached the 1-leaf stage, using only a quarter of the recommended dose. To detect plant response to herbicides, plant spectral images were acquired after herbicide treatment using RGB, infrared (IR) thermal, and chlorophyll fluorescence (CF) sensors and analyzed for diagnosing herbicide efficacy and mode of action. Principal Component Analysis (PCA) using all spectral data successfully distinguished herbicides and clustered depending on their modes of action. The performed experiments have shown that the multi-well plate assay combined with spectral image analysis can be successfully applied for herbicide bioassay. In addition, the use of spectral image sensors, especially in CF image, would facilitate HTS by enabling rapid observation of herbicide response, as early as 3 hours after herbicide treatment.

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is an important target for monoclonal antibody (mAb) therapy. All therapeutic mAbs, including anti-HER2 mAbs, exhibit adverse effects probably due to the recognition of antigens expressed in normal cells. Therefore, tumor-selective or specific mAbs can be beneficial in reducing the adverse effects. In this study, we established a novel cancer-specific anti-HER2 antibody, named H₂Mab-250/H₂CasMab-2 (IgG₁, kappa). H₂Mab-250 reacted with HER2-positive breast cancer BT-474 and SK-BR-3 cells. Importantly, H₂Mab-250 did not react with non-transformed normal epithelial cells (HaCaT and MCF 10A) and immortalized normal epithelial cells in flow cytometry. In contrast, most anti-HER2 mAbs including H₂Mab-119 (IgG₁, kappa) reacted with both cancer and normal epithelial cells. Furthermore, a core-fucose deleted IgG_2a-type H₂Mab-250 (H₂Mab-250-mG_2a-f) could trigger the antibody-dependent cellular cytotoxicity activity to BT-474, but not to HaCaT cells. Furthermore, H₂Mab-250-mG_2a-f exhibited an in vivo antitumor effect against BT-474 xenograft. Immunohistochemical analysis demonstrated that H₂Mab-250 possesses much higher reactivity to the HER2-positive breast cancer tissues compared to H₂Mab-119, and did not react with normal tissues, including heart, breast, stomach, lung, colon, kidney, and esophagus. The epitope mapping demonstrated that the Trp614 of HER2 domain IV mainly contributes to the recognition by H₂Mab-250. H₂Mab-250 could contribute to the development of chimeric antigen receptor-T or antibody-drug conjugates without adverse effects for breast cancer therapy.

This paper proposes a new method for network screening on rural low-volume roads. These roads are important as they provide critical access to agricultural land and tourist attractions. Most low-volume roads belong to the lowest functional class (local rural roads) and thus are built to lower design standards. The conventional hot spot network screening techniques may not be appropriate for low-volume roads due to the sporadic nature of crashes occurring on these roads. Contrarily sophisticated network screening approaches require extensive roadway and traffic data that are often unavailable to local agencies for lack of resources, and/or lack of technical expertise. This research attempts to address these obstacles in low-volume roads network screening which aims to identify candidate sites for safety improvements. The research used an extensive low-volume road sample from the state of Oregon and the Empirical Bayes expected number of crashes in developing the proposed models for network screening. The proposed models do not require exact measurement of roadway geometric features as all geometric variables were classified into categories that are easy to compile by local agencies. Further, the method could be used with and without traffic data, without compromising the effectiveness of the network screening process.

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labour, and preeclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This review summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidenced-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

Genetic engineering and directed evolution are effective methods to address the low yield and poor industrialization level of microbial target products. The current research focus is on how to efficiently and rapidly screen beneficial mutants from constructed large-scale mutation libraries. Traditional screening methods such as plate screening and well plate screening are severely limited in their development and application due to their low efficiency and high costs. In the past decade, microfluidic technology has become an important high-throughput screening technology due to its fast speed, low cost, high automation, and high screening throughput, and it has developed rapidly. Droplet-based microfluidic high-throughput screening has been widely used in various fields such as strain/enzyme activity screening, pathogen detection, single-cell analysis, drug discovery, and chemical synthesis, and has been widely applied in industries such as materials, food, chemicals, textiles, and biomedicine. In particular, in the field of enzyme research, droplet-based microfluidic high-throughput screening has shown excellent performance in discovering enzymes with new functions, improved catalytic efficiency or stability, acid-base tolerance, etc. Currently, droplet-based microfluidic high-throughput screening technology has achieved high-throughput screening of enzymes such as glycosidase, lipase, peroxidase, protease, amylase, oxidase, and transaminase, as well as high-throughput detection of products such as riboflavin, coumarin, 3-dehydroquinate, lactic acid, and ethanol. This article reviews the application of droplet-based microfluidics in high-throughput screening, with a focus on high-throughput screening strategies based on UV, visible, and fluorescence spectroscopy, including labeled optical signal detection screening, as well as label-free electrochemical detection, mass spectrometry, Raman spectroscopy, nuclear magnetic resonance, etc. Furthermore, the research progress and development trends of droplet-based microfluidic technology in enzyme modification and strain screening are also introduced.

Aim: Nepal’s medicinal plants are culturally important and have diverse benefits. Senna alata belongs to the family Leguminosae and is a valuable plant utilized for medicinal and ornamental purposes. The aim of the research was to extract Senna alata leaves by successive maceration with various solvents. Methods: In this study, various methods were utilized to evaluate phytochemistry, overall phenolic and flavonoid content, in-vitro antioxidant, anti-inflammatory, cytotoxicity assay, anti-thrombolytic activity, and antibacterial activities. Results: The extractive values of Senna alata were determined as 1.58%, 0.78%, and 5.92% in hexane, ethyl acetate, and methanol, respectively. GC-MS analysis revealed major compounds such as 3-Methylmannoside, Neophytadiene, Campesterol, and Vitamin E in the leaf extract. Qualitative phytochemical screening verified the tannin content, carbohydrates, flavonoids, cardiac glycosides, glycosides, and saponins in the methanol extract. The total phenolic and flavonoid values were 46.36±4.5 mg GAE/gm and 480.4±3.055 QE/gm of dried extract, respectively. The extract exhibited significant antioxidant and anti-inflammatory activities, with IC50 values of 29.81 and 9.93, respectively. Furthermore, it demonstrated cytotoxic activity with an LC50 value of 767.85 in the brine shrimp bioassay. In terms of thrombolytic activity, the extract showed clot lysis percentages of 7.89% and 10.13% at concentrations of 10 mg/ml and 25 mg/ml, respectively. Conclusion: In conclusion, the methanolic extract of Senna alata leaves displayed therapeutic potential, including antioxidant, anti-inflammatory, cytotoxic, thrombolytic, and antibacterial effects. The existence of several chemicals via GC-MS analysis also verified plant's potential for therapeutic use.

Post-extubation dysphagia (PED) can lead to serious health problems in critically ill patients. Contrasting its high incidence rate of 12.4% reported in a recent observational study, many ICUs lack routine bedside screening, likely due to limited awareness. This study aimed to establish baseline data on the current approaches and the status of perceived best practices in PED screening and treatment, as well as to assess awareness of PED. A nationwide cross-sectional, online survey was conducted in all fourteen adult ICUs in the Republic of Cyprus in June 2018, with a 100% response rate. Over 85% of ICUs lacked a standard screening protocol for PED. The most commonly reported assessment methods were cough reflex testing and the water swallow test. Treatment approaches included muscle strengthening exercises without swallowing and swallowing exercises. Only 28.6% of ICUs acknowledged PED as a common issue. The study identified significant gaps in awareness and knowledge regarding PED screening and treatment in Greek-Cypriot ICUs. Urgent implementation of comprehensive dysphagia education programs within the units is necessary, and interdisciplinary collaboration among nurses, intensivists, and speech and language therapists is crucial to improve the quality of care provided.

Improving HIV testing efficiency saves financial and material resources for health. We conducted a retrospective secondary data analysis of routinely collected HIV risk screening program data in Uganda, from October to November 2019, to determine the performance characteristics of the adolescent and adult HIV risk screening tool in public health facility settings. A total of 19,854 clients had been screened for HIV testing eligibility and tested for HIV. The overall positivity rate (cluster weighted prevalence of HIV) among those screened was 4.5% (95% CI: 4.1%-4.8%) versus 3.71% (95% CI: 3.06-4.50) among those not screened. The sensitivity and specificity of the risk screening tool were 90.7% (95% CI: 88.4%, 92.7%) and 75.8%, (75.2-76.4) respectively. With screening, the number needed to test to identify one PLHIV was reduced from 27 to 22. Although risk screening would have led to a 24.5% (4,825/19,704) reduction in testing volume, 9.3% (68/732) of PLHIV would have been missed, being misclassified as not eligible for testing. The cost per PLHIV identified fell by 3% from $69 without screening to $66.9 with screening. We recommend the use of scientifically validated HIV risk screening tools, and a need to explore the use of HIV self-testing as a test for tirage.

The research presented in this paper examines a new proposed approach for identifying safety improvement sites on rural highways. Unlike conventional approaches, the proposed approach does not require crash history, but rather utilizes classified variables for traffic volume, geometric features, and roadside characteristics that do not require access to exact data or extensive technical expertise. The research validates the performance of the proposed approach using field data from a large sample of rural two-lane highway segments in the state of Oregon including traffic, roadway, and crash data. Using observed crash history as a reference, the performance of the proposed ap-proach was compared to two of the well-established methods in practice, namely: the Empirical Bayes (EB) and the Potential for Safety Improvement (PSI) methods. The study results suggest that, using crash density for highway segments, the performance of the proposed method was lower than that of the EB and PSI methods. This is despite the high R-square value of the predictive model used in the proposed method. However, when using crash frequencies for highway segments, the per-formance of the proposed method was found comparable to the well-established EB and PSI methods.

Oxidoreductase (OXR) enzymes are in high demand for biocatalytic applications in food industry and cosmetics: glucose oxidase (GOx), cellobiose dehydrogenase (CBDH), bioremediation: horseradish peroxidase (HRP), laccase (LAC), and medicine for biosensors and miniature biofuel cells (GOx, CBDH, LAC, HRP). They can be used in a soluble form and/or within the yeast cell walls expressed as chimeras on the surface of yeast cells (YSD), such as P. pastoris and S. cerevisiae. However, most of the current studies suffer from either low yield for soluble enzyme expression or low enzyme activity when expressed as chimeric proteins using YSD. This is always the case in studies dealing with heterologous expression of oxidoreductase enzymes, since there is requirement not only for multiple OXR genes integrations into the yeast genome (super transformations), and codon optimization, but also very careful design of fermentation media composition, and fermentation conditions during expression due to need for adding transition metals (copper, iron), and metabolic precursors of FAD and heme. Therefore, scientists are still trying to find optimal formula using above mentioned approaches, and most recently also using protein engineering and directed evolution for additional increase in the yield of recombinant enzyme production. In this review article we will cover all the current state of the art technologies and most recent advances in the field that yielded high expression level for some of these enzymes in specially designed expression/fermentation systems. We will also tackle and discuss new possibilities for further increase in fermentation yield by the cutting-edge technologies such are directed evolution, protein and strain engineering, high-throughput screening methods based on in vitro compartmentalization, flow cytometry and microfluidics.

Alzheimer's disease (AD) is characterized by abnormal amyloid beta (Aβ) plaques and hyperphosphorylated tau in the brain. Aβ plaques precede cognitive impairments and can be detected through amyloid-PET or in cerebrospinal fluid (CSF). Assessing the plasma Aβ42/Aβ40 ratio seems promising for non-invasive and cost-effective detection of brain Aβ accumulation. This approach involves some challenges, including the accuracy of blood-based biomarker measurements and the establishment of clear, standardized thresholds to categorize the risk of developing brain amyloid pathology. Plasma Aβ42/Aβ40 ratio was measured in 277 volunteers without dementia, 70 AD patients and 18 non-AD patients using single-molecule array. Patients (n=88) and some volunteers (n=66) were subject to evaluation of amyloid status by CSF Aβ quantification or PET analysis. Thresholds of plasma Aβ42/Aβ40 ratio were determined based on a Gaussian mixture model, a decision tree, and the Youden index. The 0.0472 threshold, the one with the highest sensitivity, was retained for general population without dementia screening, and the 0.0450 threshold was retained for research and clinical trials recruitment, aiming to minimize the need for CSF or PET analyses to identify amyloid-positive individuals. These findings offer a promising step towards a cost-effective method for identifying individuals at risk of developing AD.

Background: Cognitive for patients with neurocognitive disorders are mostly measured by Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT) as screening tools. These cognitive scores are usually left skewed and the results of association analysis might not be robust. This study aims to study the distribution of the cognitive outcomes and to discuss potential solutions. Materials and Methods: The inverse transformed cognitive outcomes are modelled using different statistical distributions. Robustness of the proposed models are checked under different scenarios: with intercept only, models with covariate, with and without bootstrapping. Results: Main results were based on VCAT score, and validated via MoCA score. Findings suggested that the inverse transformation method improves modelling the cognitive scores compared to the conventional methods using the original cognitive scores. Association of baseline characteristics (age, gender and years of education) and the cognitive outcomes were reported as estimates and 95% confidence intervals. Bootstrap methods improved the estimate precision and the bootstrapped standard errors of the estimates are more robust. Cognitive outcomes are widely analyzed using linear regression models with default normal distribution as a conventional method. We compared the results of our suggested models with the normal distribution under various scenarios. Goodness-of-fit measurements were compared between proposed models and conventional methods. Conclusions: The findings support the use of the inverse transformation method to model the cognitive outcomes instead of the original cognitive scores for early stage neurocognitive disorders where the cognitive outcomes are left skewed.

Free-of-charge HCV screening in some key populations and in 1969–1989 birth cohorts have been funded in Italy as the first step to diagnosing individuals unaware of their infection. The aim of this study is to use available in-hospital routine screening data to understand the inpatients HCV screening in a region of North Italy. A retrospective search of in-hospital patients tested for HCV-antibody (HCV-Ab) from January 2017 to the end of December 2022, was conducted according to age categories (older than 76 years, birth group 1947-1968; birth group1969-1989 and two other categories with patients younger than 33 years) using the TriNetX network. Of 42,805 in-hospital patients tested, 1,297 (3.03%) resulted HCV-Ab positive. The proportion decreased from 2017 to 2022 (from 2.03% to 0.36%) years). The higher prevalence of HCV-Ab was in patients older than 76 years (5.3%) while, the lowest was in the younger birth cohort (2000-2022, 0.16%). Of 1,297 patients found HCV-Ab positive, only 198 (15.3%) were tested for the presence of HCV RNA. Although the birth cohort 1969-1989 had a lower seroprevalence (1.5%), they represented the most affected age group with 44.4% of HCV RNA positivity. The in-hospital HCV screening including birth cohort 1947-1989 could be a valuable option respect to the screening for birth group 1969-1989 in the general population. Since a high proportion of patients were not tested for HCV RNA during hospitalization, reflex testing promptly ascertaining an active infection could facilitate linkage to care to stop the burden of HCV.

Abstract: Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial-myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, the condition remains undiagnosed before delivery because of the lacking clear evaluation criteria for each of the three grades of PAS. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. While using deep sequencing, miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profile in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or preeclampsia, were obtained. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset preeclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to literature data, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for 1st trimester screening pregnant women, subject to validation on independent test samples.

The oxidative coupling of methane (OCM) to produce ethane and ethylene (C2 compounds) as platform chemicals involves complex chemistry with reactions both in the gas phase and on the catalyst surface, resulting in a distribution of products at the expense of C2 selectivity. This work uses experimental data from a variety of mixed metal oxides on supports at different reaction conditions (temperature, contact time, and reactant flow rates) to train a random forest regressor that predicts methane conversion and C2 selectivity (key performance indicators (KPIs)), and deploys it to locate optimal conditions that maximize C2 yield for a catalyst. Investigating the regressor interpretability via feature importance reveals that the choice of metals and support are crucial to C2 selectivity predictions, while the predictions of methane conversion are driven by the reaction conditions. The machine learning (ML) regressor is used as a surrogate to develop performance curves for each of the catalysts via a multi-objective optimization routine that seeks to maximize the KPIs in the decision space of reaction conditions, is seen to locate optimal conditions at which the maximum C2 yields for catalysts are predicted to be 15%, higher on average. Analyzing the catalysts in the space of their performance curves with respect to a popular OCM catalyst, Mn-Na2WO4/SiO2, reveals distinct patterns based on intrinsic properties of metals and supports. Further, the decision space with catalyst descriptors and reaction conditions is optimized for high C2 yields using the ML surrogate, in a static multi-objective optimization routine, and an adaptive Bayesian routine, where the latter was found to have a wider field focus in proposing catalyst formulations and conditions. Transition metal oxides on a variety of supports were proposed but not their lanthanide oxide counterparts.

The expedited development of drugs targeting gene products associated with insulin resistance holds the potential to enhance our comprehension of type 2 diabetes mellitus (T2DM). The virtual screening based on a three-dimensional (3D) protein structure has been expected as potential technique to accelerate a development of molecular target drugs. Among the targets implicated in insulin resistance, genetic characterization and protein function of Grb14 have been clarified without contradiction. The Grb14 gene displays notable variations in T2DM, and its gene product known to inhibit the function of the insulin receptor (IR) by directly binding to the tyrosine kinase domain. In the present study, a virtual screening, based on 3D structure of IR tyrosine kinase domain (IRβ) in complex with part of Grb14, was conducted to find compounds that can disrupt the complex formation between Grb14 and IRβ. First, ten compounds were selected from 154,118 compounds via hierarchical in silico structure-based drug screening, composed of grid docking-based and genetic algorithm-based programs. The experimental validations suggested that the one compound can affect blood glucose level. The molecular dynamics simulations and co-immunoprecipitation analysis showed that the compound did not completely suppress the protein–protein interaction between Grb14 and IR, though competitively bound to IR with the tyrosine kinase pseudosubstrate region in Grb14.

Gangliosides are highly abundant in the human brain where they are involved in major biological events. In brain cancers, alterations of ganglioside pattern occur, some of which being correlated with the neoplastic transformation, while others with the tumor proliferation. Of all the techniques, mass spectrometry (MS) has proven to be one of the most effective in gangliosidomics, due to its ability to characterize heterogeneous mixtures and discover species with biomarker value. This review highlights the most significant achievements of MS in the analysis of gangliosides in human brain cancers. The first part presents the state-of-the-art in the MS development for discovery of ganglioside markers in primary brain tumors, with a particular emphasis on the ion mobility separation (IMS) MS and its contribution to the elucidation of the gangliosidome associated with aggressive tumors. The second part is focused on the MS of gangliosides in brain metastases, highlighting the ability of matrix-assisted laser desorption/ionization (MALDI)-MS, microfluidics-MS and tandem MS to decipher and structurally characterize species involved in the metastatic process. In the end, several conclusions and perspectives are presented, among which the need for development of a reliable software and a user-friendly structural database as a search platform in brain tumor diagnostics.

Hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to treat with hypothermic therapy is critical. Differentiating HIE from other neonatal conditions, such as sepsis, further complicates the diagnosis. This study investigated the utility of a metabolomic-based approach using the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice-Vannucci model of HIE in rats. We evaluated the diagnostic accuracy of this method between 3 and 6 hours after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic accuracy with areas under the curve (AUC) of 0.94 at 3 hours and 0.96 at 6 hours after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 hours of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness.

Tumor biomarkers have great potential in screening and their role could extend further from general population risk assessment to treatment response estimation and recurrence monitoring. Different molecular and cellular elements in blood, which give information about the status of an individual, make it a perfect compartment to develop noninvasive diagnostics approaches for cancer. The present study aimed to screen the most frequent tumor markers in the Angolan population according to age and gender. A whole blood sample was collected for each patient. Serum levels were measured using the electrochemiluminescence method, using the automated Cobas e411 equipment (Roche®) according to the manufacturer's instructions. The results of our study elucidated the relevance of tumor biomarkers in screening for different types of cancer. These results also highlight the robustness of the mean in suspected cases, which is 15 to 17 times higher in some markers than in non-suspected cases. More research is needed to elucidate the relevance of these biomarkers in the Angolan population.

The purpose of this study was to explore and develop high-resolution infrared thermal (HRIT) imaging for screening toddler’s fracture. A Toddler’s fracture is a common tibial fracture of children younger than 6 years old. Initial x-ray radiographs may not show the fracture and another x-ray during a follow-on visit is usually required. The study included 39 participants admitted to an emergency department with a suspected toddler’s fracture. X-ray confirmed 8 cases with a toddler’s fracture (20.5%). Infrared images of participants were recorded on their index visit, focusing on region-of-interests on the injured and the contralateral (uninjured) legs. The uninjured leg acted as a thermal reference. Nine statistical measures were extracted from the images: maximum, mini-mum, mean, standard deviation, median, mode, interquartile range, skewness, and kurtosis. Wilcoxon rank sum test indicated that maximum, mean, standard deviation, median, and inter quartile range temperature measures were significantly different (p<0.05) when comparing fractured and non-fractured legs. Principal component analysis of these measures highlighted distinct separation of toddler’s fracture and non-fracture cases. Similarly, plots of the statistical measures further confirmed clustering of toddler’s fracture cases. The study demonstrated that HRIT imaging can be a valuable tool for screening for toddler’s fracture.

1) Background: The screening of preeclampsia (PE) and intrauterine growth restriction (IUGR) represents a constant challenge for obstetricians. The aim of this study was to determine and compare the predictive performance of 4 machine learning-based algorithms for the prediction of PE, IUGR, and their association in a cohort of singleton pregnancies; (2) Methods This prospective study was conducted at a tertiary maternity hospital in Romania, and included 210 pregnancies that underwent first trimester screening. We included clinical and paraclinical data into 4 machine learning-based algorithms decision tree (DT), naïve Bayes (NB), support vector machine (SVM), and random forest (RF), and calculated their predictive performance; (3) Results: RF performed the best when used to predict PE, IUGR, and its subtypes, as well as the association between PE and IUGR. The overall predictive performance of DT for all these disorders was inferior to RF, NB, and SVM. Both SVM and NB had similar accuracy for the prediction of PE, while NB performed better than SVM for the prediction of IUGR; (4) Conclusions: Machine-learning-based algorithms could be useful for the prediction of ischemic placental disease and need to be validated on large cohorts of patients.

Pregnancy at advanced maternal age is considered a risk factor for adverse maternal, fetal, and neonatal outcomes. Here we investigated whether maternal age could be associated with differences in the blood levels of newborn screening (NBS) markers for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP). Population-level NBS data from screen-negative singleton infants were examined, which included blood metabolic markers and covariates such as gestational age, birth weight, age at blood collection, infant sex, parent-reported ethnicity, and maternal age at delivery. Marker levels were compared between maternal age groups (age range: 15-44 years) using effect size analyses, which controlled for group size differences and potential confounding from other covariates. Our results showed that 13% of the markers had maternal age-related differences including newborn metabolites with either increased (C14, C16, C18, C18:1, C3DC) or decreased (C5OH) levels at advanced maternal age group (≥35 years, absolute Cohen’s d ≥ 0.2). The increased C3DC levels in this group correlated with a higher false-positive rate in newborn screening for malonic acidemia (p-value < 0.001), while no significant difference in screening performance was seen for other markers. Maternal age at delivery is associated with inborn metabolic differences and should be considered together with other clinical variables in genetic disease screening.

Recent dramatic reductions in the timeframe in which genomic sequencing can deliver results means its application in time-sensitive screening programs such as newborn screening (NBS) is becoming a reality. As genomic NBS (gNBS) programs are developed around the world, there is an increasing need to address the ethical and social issues that such initiatives raise. This study therefore aimed to explore the Australian public’s perspectives and values regarding key gNBS characteristics and preferences for service delivery. We recruited English-speaking members of the Australian public over 18 years of age via social media; 75 people aged 23-72 participated in one of 15 focus groups. Participants were generally supportive of introducing genomic sequencing into newborn screening, with several stating that adoption of such revolutionary and beneficial technology was a moral obligation. Participants consistently highlighted receiving an early diagnosis as the leading benefit, which was frequently linked to the potential for early treatment and intervention, or access to other forms of assistance, such as peer support. Informing parents about the test during pregnancy was considered important. This study provides insights into the Australian public’s views and preferences to inform the delivery of a gNBS program in the Australian context.

Background: Malnutrition was associated with worse survival outcomes, impaired quality of life, and deteriorated performance status across various cancer types. We aimed to identify risk factors for malnutrition in patients with epithelial ovarian(EOC) and impact on survival. Methods: In our prospective study, we included the patients with primary and recurrent EOC, tubal or peritoneal cancer conducted. We assessed serum laboratory parameters, body mass index, nutritional risk index, nutritional risk screening score(NRS-2002), and bio-electrical impedance analysis. Results: We recruited a total of 152. Patients >65 years-old, with ascites of >500 ml, or with platinum-resistant EOC showed statistically significant increased risk of malnutrition when evaluated by NRS-2002(p-values = 0.014, 0.001, and 0.007, respectively). An NRS-2002<3 was an independent predictive factor for complete tumor resectability (p=0.009). The patients with NRS-2002≥3 had a median overall survival(OS) of seven months (95% CI=0-24 months), as compared to the patients with NRS-2002<3 where median OS was 46 months(p=0,001). Phase angle(PhAα)≤ 4.5 was the strongest predictor of OS. Conclusion: Malnutrition is an independent predictor of incomplete cytoreduction in study population. It is an independent prognostic factor for poor OS. Preoperative nutritional assessment is an effective tool in identification of high-risk groups within EOC characterized by poor clinical outcome.

In the last two decades, the development of high-throughput diagnostic methods and availabil-ity of effective treatments has increased interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report our 8-year experience of screening and follow up on about 250,000 neonates screened for four lysosomal storage diseases (Pompe disease, mucopolysaccharidosis type I, Fabry dis-ease, Gaucher disease), using enzyme activity assay by tandem mass spectrometry, and bi-omarker quantification as second tier test. Among the 126 positive newborns (0.051%), 51 infants were confirmed as affected (positive pre-dictive value 40%), with an overall incidence of 1:4,874. Of these, 3 infantile-onset Pompe dis-ease, 2 neonatal-onset Gaucher disease and 4 mucopolysaccharidosis type I patients were imme-diately treated. Furthermore, another four Gaucher disease patients needed treatment in the first years of life. Our study demonstrated the feasibility and effectiveness of newborn screening for lysosomal storage diseases. Early diagnosis and treatment allow the achievement of better patient out-comes. Challenges such as false positive rates, the diagnosis of variants of uncertain significance or late-onset forms, and the lack of treatment for neuronopathic forms, should be addressed.

The genus Colias Fabricius, 1807 includes numerous taxa and forms with uncertain status and taxonomic position. Among such taxa are Colias mongola Alphéraky, 1897 and Colias tamerlana Staudinger, 1897, interpreted in the literature either as conspecific forms, as subspecies of different but morphologically somewhat similar Colias species, or as distinct species-level taxa. Based on mitochondrial and nuclear DNA markers, we reconstruct a phylogeographic pattern of the taxa in question. We recover and include in our analysis DNA barcodes of the century-old type specimens, the lectotype of C. tamerlana deposited in the Natural History Museum (Museum für Naturkunde), Berlin, Germany (ZMHU), the paralectotype of C. tamerlana and the lectoptype of C. mongola deposited in the Zoological Institute, Russian Academy of Sciences, Saint-Petersburg, Russia (ZISP). Our analysis grouped all specimens within four (HP_I-HP-IV) deeply divergent but geographically poorly structured clades which did not support nonconspecifity of C. mongola–C. tamerlana. We also show that all studied females of the widely distributed haplogroup HP_II were infected with a single Wolbachia strain belonging to the supergroup B, while the males of this haplogroup, as well as all other investigated specimens, were not infected. Our data underline the relevance of large-scale sampling dataset analysis and the need of testing for Wolbachia infection to avoid erroneous phylogenetic reconstructions and species misidentification.

Background: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population. Methods: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed. Results: HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) (p&lt;0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women. Conclusion: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.

Drug discovery utilizes high-throughput screening (HTS) methods applying target and cell-based assays. This review discusses the challenges and benefits associated with these assays in HTS. Discussed the strategies that can be applied for the development of screening assays through primary and secondary screens for target identification. Further discussion on identify-ing the most efficacious drugs following these approaches in cancer. Even though various drugs have been identified to treat cancer, there is high demand of more relevant phenotypic assays to produce desired diseased phenotype to only highlighting the specific targets instead of off-targets. Hopefully, the new developing strategies could provide innovative drugs to treat cancer patients to reduce mortality rate.

Preconception or prenatal carrier screening for hereditary deafness is an effective early intervention strategy to reduce the incidence of newborn deafness, but current research is limited. This study aimed to investigate the carrier frequencies of common deafness genes in the Chinese population and to follow up on pregnancy outcomes in high-risk couples. Carrier screening for common deafness genes in the Chinese population, including the GJB2 and SLC26A4 genes, was performed using next-generation sequencing technology. Of the 9,993 subjects screened, the carrier rate was 2.86% for the GJB2 gene and 2.63% for the SLC26A4 gene. Of the six high-risk couples, four made alternative reproductive decisions (three with prenatal diagnosis and one with preimplantation genetic testing), with consequent successful termination of the birth of two affected fetuses. The frequencies of preconception or prenatal carrier screening for the deafness genes GJB2 and SLC26A4 in 9,993 subjects from China in this study were 2.86% and 2.63%, respectively. In addition, four out of six high-risk couples made alternative reproductive decisions, followed by the successful prevention of the birth of two affected fetuses. These findings confirmed the clinical utility of preconception or prenatal carrier screening for hereditary deafness.

Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In last years the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality and survival rate for CRC.

Background: Chronic Hepatitis B Virus (HBV) infection is a global health concern, associated with severe liver diseases, necessitating ongoing research on novel drug candidates. This study aims to identify potential drug candidates targeting HBV core protein (HBcAg) and disrupting capsid assembly, a critical step in the virus's life cycle. Methods: HBcAg in complex with HBV inhibitors were obtained from the Protein Data Bank (PDB). CavityPlus server was used for analysis of druggable cavity. Structure-based pharmacophores were extracted from identified cavities, and potential allosteric ligand binding sites were assessed using CavPharmer, CorrSite, and CovCys. LigandScout was employed for ligand-based pharmacophore screening against an FDA-approved library. The ZINC database was screened with features extracted from CavPharmer. Molecular docking studies were conducted using Autodock Vina. Lead compounds were selected based on docking scores, binding modes, and interactions within the druggable cavity. Results: Strong druggable pockets were found for Ciclopirox, while Compound 24, NVR10-001E2, and others showed medium to weak pockets. Ligand-based pharmacophores varied in size and complexity. Screening revealed potential hits matching these pharmacophores, including Ciclopirox olamine, Voriconazole, Enasidenib, and Statins. A large compound database search yielded additional hits like ZINC86859997 and ZINC63280172. Docking analyses confirmed these hits' potential, highlighting their interactions with critical HBc protein residues, offering promising leads for hepatitis B drug development. Conclusions: Voriconazole, Enasidenib, and Lovastatin have shown promises. These hits displayed favorable interactions with crucial HBc protein residues, indicating their potential as lead compounds The mechanism of action of statins with anti-HBV activities also highlighted. This comprehensive approach offers valuable insights into targeting HBc protein for antiviral drug discovery.

Sleep apnea is common in professional truck drivers. As undiagnosed and/or untreated sleep apnea is a risk factor for sleepiness-related traffic accidents, it should be recognized. We develop a new, simple tool to screen sleep apnea in this population. Altogether, 2066 professional truck drivers received a structured questionnaire. 175 drivers had a clinical examination and were invited to sleep laboratory studies, including cardiorespiratory polygraphy. We studied associations of different risk factors with the presence of sleep apnea. We established a new simple screening tool for sleep apnea that was compared to other existing screening tools. 1095 drivers filled in the questionnaire. 172 drivers had successful cardiorespiratory polygraphy. Full data was available for 160 male drivers, who were included in the analyses. The following five risk factors for sleep apnea formed the BAMSA-score (0 to 5): BMI>30 kgm-2, Age>50 years, Male gender, Snoring at least on one night per week and presence of Apneas at least sometimes. BAMSA showed a sensitivity of 85.7% and a specificity of 78.8% in detecting AHI≥15, when using a cut point of 4 and the ROC area was 0.823. BAMSA is a sensitive and easy-to-use tool in predicting sleep apnea in male professional drivers.

The purpose of this article is to highlight the new advancements in molecular and diagnostic genetic testing as well as properly classify all ovarian cancers. In this article we address statistics, histopathological classification, molecular pathways implicated in ovarian cancer, genetic screening panels and details about the genes, and also candidate genes. We hope to bring new information in the medical field as to better prevent and diagnose ovarian cancer.

Rapid advances in the screening, diagnosis, and treatment of genetic disorders has increased the number of conditions that could be detected through universal newborn screening (NBS). However, addition of conditions to the Recommended Uniform Screening Panel (RUSP) and implementation of nationwide screening has been a slow process taking several years to accomplish for individual conditions. Here we describe web-based tools and resources developed and implemented by the newborn screening translational research network (NBSTRN) to advance newborn screening research and support NBS stakeholders. NBSTRN’s tools include the Longitudinal Pediatric Data Resource (LPDR), the NBS Condition Resource (NBS-CR), the NBS Virtual Repository (NBS-VR), and the Ethical, Legal, and Social Issues (ELSI) Advantage. Research programs including the Inborn Errors of Metabolism Information System (IBEM-IS), BabySeq, EarlyCheck, and Family Narratives Use Cases have utilized NBSTRN’s tools, and in turn contributed research data to further expand and refine these this resource. Additionally, we discuss ongoing tool development to facilitate expansion of genetic disease screening in increasingly diverse populations. In conclusion, NBSTRN’s tools and resources provide a trusted platform to enable NBS stakeholders to advance NBS research and improve clinical care for patients and their families.

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. We also used multivariable analyses to identify factors associated with patient interest in test use. In 2023, we surveyed 159 (32%) of 500 identified patients. Among respondents, 125 (79%) reported a high level of interest in having an MCED test. Interest was not associated with personal background characteristics, but was positively associated with the following expectations: testing would be recommended for cancer screening, be convenient, and be effective in finding early-stage disease (OR=11.70, 95% CI: 4.02, 34.04, p < 0.001). Research is needed to assess patient interest and actual uptake when detailed information on testing is presented in routine care.

Background: The potential impact of the pandemic on mental health should not be overlooked, especially among vulnerable populations such as women who gave birth during the COVID-19 pandemic. The aim of the study was to assess the mental health status of women who gave birth during a pandemic and to examine the possible links between the onset of depressive disorder symptoms in close proximity to the time of delivery and the socio-demographic conditions, health status and obstetric circumstances of the patients. Materials and Methods: The study is a cross-sectional survey conducted from 01.03.2020 to 01.03.2023, during the period of SARS-CoV-2 (COVID-19) pandemic, based on a retrospective evaluation of 860 postpartum women. The screening tool used to assess symptoms of postpartum depression was the Edinburgh Postnatal Depression Rating Scale (EPDS) questionnaire. The questionnaire was completed both in the Obstetrics and Gynaecology Clinical Sections I and II of the "Pius Brînzeu" County Emergency Hospital from Timisoara, Romania and online using Google Forms. Results: The highest severity of postpartum depression symptoms was observed during the COVID-19 pandemic. The results of the study conducted during the period of SARS-CoV-2 pandemic (COVID-19) showed that the prevalence of major postpartum depressive disorder (EPDS ≥ 13) was 54.2% (466 patients), while 15.6% (134) had minor depressive disorder (10 &lt; EPDS ≤ 12) in the first year after delivery. Comparing these results with those obtained in research conducted before the onset of the pandemic period shows an alarming increase in the prevalence of postpartum depression. Risk factors associated with postpartum depression included type of delivery, level of education, socio-economic conditions, health status, age, background, personal obstetric history (number of abortions on demand, parity). Conclusions: The effects of the pandemic on mental health are of particular concern for women in the first year after childbirth. Observing these challenges and developing effective measures to prepare our health system early can help and facilitate effective mental health screening for postpartum women, promoting maternal and child health.

Because of ambiguous and widely debated observations concerning incidence trend and management of TC, we performed this analysis. We drew attention to some events, such as “cancer screening activity,” introduction of noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) to TC types, possibility of papillary thyroid microcarcinoma (PTMC) active surveillance (AS), occurrence of personalized medicine in TC management and finally COVID-19 pandemic time. Because of the opinion that all changes have been made mostly by PTC, we compared it to the rest of types of TC in terms of incidence, clinical and pathological characteristics and treatment. The prevalence of TC significantly increased from 5.15% in 2008 to 13.84% in 2015 and then significantly decreased to 1.33% in 2022 when the pandemic lasted (p<0.0001). A similar trend was observed for PTC, when the incidence significantly increased to 13.99% in 2015 and then decreased to 1.38% in 2022 (p<0.0001). At that time, the NIFTP category was introduced, and observation of PTMC began. The prevalence of FTC and MTC also increased until 2015 and then decreased. Significant differences in age, types of surgery, necessity of reoperation, pTNM, between PTCs and other types of TCs were observed. The average age was significantly lower in PTC patients than in patients with the remaining types of TC (p<0.0001). Four milestones, including NIFTP introduction, the possibility of PTMC AS, personalized cancer medicine and the COVID-19 pandemic, may have influenced the general statistics of TC.

BRCA1 and 2 pathogenic variants increase lifetime risks of breast (50-75%) and ovarian cancer (15-20%). Guidelines recommend breast screening (MRI and mammogram) or risk-reducing mastectomy with salpingo-oophorectomy for ovarian cancer prevention. We sought to 1) characterize the population of BRCA1/2 carriers in Newfoundland and Labrador (NL) 2) evaluate risk-reducing interventions 3) identify factors influencing screening and prevention adherence. Methods: This is a retrospective study from a population-based provincial cohort of BRCA1/2 carriers. Eligibility criteria for risk-reducing interventions were defined for each case and patients were categorized based on their level of adherence with recommended screening or prevention. Chi-squared and regression analyses were used to determine which factors influenced uptake and level of adherence. Results: 276 BRCA1/2 carriers were identified; 156 living NL females composed the study population. Unaffected females were younger at testing than those with a cancer diagnosis (44.4 y versus 51.7 y; p=0.002). Categorized by eligibility, 61.0%, 61.6%, 39.0% and 75.7% of patients underwent MRI, mammogram, risk-reducing mastectomy, and risk-reducing salpingo-oophorectomy, respectively. Individuals with breast cancer were more likely to have risk-reducing mastectomy (64.7% versus 35.3%; p<0.001), and those who attended specialty hereditary cancer clinic were more likely to be adherent with breast/ovarian cancer recommendations (73.2% versus 13.4%; p<0.001) and to undergo risk-reducing salpingo-oophorectomy(84.1% versus 15.9%; p<0.001). Conclusions: Nearly 40% of female BRCA1/2 carriers were not receiving breast surveillance according to evidence-based recommendations. Cancer risk reduction and uptake of breast imaging and prophylactic breast and pelvic surgeries are significantly higher in patients who receive dedicated specialty care. Organized hereditary cancer prevention programs will be a valuable component of Canadian health care systems and have the potential to reduce the burden of disease country-wide.

Background and Objectives: Romania ranks among the countries with a notably high rate of preventable deaths due to inadequacies in prevention, screening, early detection, and timely management processes. Cervical cancer (CC) is a significant contributor to these preventable deaths, particularly affecting patients from marginalized backgrounds, rural regions, and the Roma population. The purpose of this article was to identify correct and consistent information of the Roma population about the risk of CC, as well as the importance of understanding the causes of the disease and awareness of the available prevention methods. Materials and methods: A cross-sectional study was conducted using a self-administered questionnaire applied only to Roma women in Romania. Results: We enrolled 759 patients in the study. These were divided into 2 groups, Group 1 comprised 289 (38.1%) women who had been tested for HPV infection, while Group 2 included 470 (61.9%) women who had never been tested for HPV infection. Characterization of women in Group 1: mostly aged between 25-54 years, with high school education, married, who started sexual activity under the age of 18 years, with only one sexual partner and with over 5 pregnancies. Regarding contraceptive methods, 35.7% of women do not know/ use any contraceptive method, and 32.2% use hormonal contraceptives. Two thirds of the women tested had heard of HPV, and 19.7% were vaccinated against HPV with at least 2-3 doses. A percentage of 8.7 had a diagnosis of CC, compared to those who were not tested (p-0.0001), whereas 63% of the tested women do not know much about CC, as opposed to 85.7% of the group of untested women. Conclusion: Cervical cancer (CC) continues to be a public health issue in Romania, particularly in patients belonging to vulnerable groups. Promotion campaigns for HPV vaccination and CC screening are necessary to reduce the associated mortality and morbidity.

The 3D/3D+ multidimensional geriatric assessment tool provides an optimal model of emergency care for patients aged 75 and over who attend the Emergency Department (ED). The baseline, or static, component (3D) stratifies the degree of frailty prior to the acute illness, while the current, or dynamic, component (3D+) assesses the multidimensional impact caused by the acute illness and helps to guide the choice of care facility for patients upon their discharge from the ED. The objective of this study was to evaluate the prognostic value of the 3D/3D+ to predict short- and long-term adverse outcomes in ED patients aged 75 years and older. Multivariable logistic regression models were used to identify the predictors of mortality 30 days after 3D/3D+ assessment. Two hundred and seventy-eight patients (59.7% women) with a median age of 86 years (interquartile range: 83-90) were analysed. According to the baseline component (3D), 83.1% (95%CI: 78.2-87.3) presented some degree of frailty. The current component (3D+) presented alterations in 60.1% (95%CI: 54.1-65.9). The choice of care facility at ED discharge indicated by the 3D/3D+ was considered appropriate in 96.4% (95%CI: 93.0-98.0). Thirty-day all-cause mortality was 19.4%. Delirium and functional decline were the dimensions on the 3D/3D+ that were independently associated with 30-day mortality. These two dimensions had an area under receiver operating characteristic of 0.80 (95%CI: 0.73-0.86) for predicting 30-day mortality. 3D/3D+ enhances the provision of comprehensive care by ED professionals, guides them in the choice of patients’ discharge destination, and has a prognostic validity that serves to establish future therapeutic objectives.

Preterm birth (PB) is a leading cause of perinatal morbidity and mortality. PB prediction is per-formed by measuring cervical length, with a detection rate of around 70%. Although it is known that a cytokine-mediated inflammatory process is involved in the pathophysiology of PB, no screening method implemented in clinical practice includes cytokine levels as a predictor varia-ble. Here, we quantified cytokines in cervical-vaginal mucus of pregnant women (18-23.6 weeks of gestation) with high- or low-risk for PB determined by cervical length, collecting relevant obstetric information. IL-2, IL-6, IFN-γ, IL-4, and IL-10 were significantly higher in the high-risk group, while IL-1ra was lower. Two different models for PB prediction were created using the Random Forest machine-learning algorithm: the full model with 12 clinical variables and cyto-kine values, and the adjusted model, including the most significant variables -maternal age, IL-2, and cervical length- (detection rate 66 vs 87%, false positive rate 12 vs 3.33%, false negative rate 28 vs 6.66%, and area under the curve 0.722 vs 0.875, respectively). The adjusted model integrat-ing cytokines showed a detection rate 8 points higher than the gold standard calculator, which may allow us to identify PB risk more accurately and implement strategies for preventive in-terventions

Enzymatic hydrolysis of bovine and human hemoglobin yields a diversity of bioactive peptides, some of which are recognized for their antimicrobial properties. Certain small antimicrobial and anticancer peptides target protein synthesis inhibition. This study aims to produce bioactive peptides through enzymatic hemoglobin hydrolysis and evaluate their effects on cell growth inhibition, potentially serving as candidates for biological anticancer drugs. Rapid screening of candidate anticancer peptides derived from enzymatic hydrolysis of bovine and human hemoglobin was conducted using the Lepidium sativum radicle growth technique. The results demonstrate that: 1) the degree of hydrolysis (DH) significantly influences the production of bioactive peptides. DH levels of 3-10% yield considerably stronger radicle growth inhibition compared to DH 0 (native hemoglobin form), exhibiting three to four times greater intensity. 2) Certain peptide fractions from bovine hemoglobin exhibit higher activity than those from human hemoglobin. 3) The structural characteristics of peptides play a crucial role in the observed biological effects. 4) The α137-141 peptide is the most active among the fractions obtained from bovine (IC₅₀ = 29 ± 1 µg/mL) and human hemoglobin (IC₅₀ = 48 ± 2 µg/mL), standing out 10 to 15 times more potent than other hemoglobin fractions. In conclusion, these findings affirm the bioactivity of peptide fractions obtained from bovine and human hemoglobin. The study highlights how enzymatic hydrolysis of bovine and human hemoglobin can yield peptides that inhibit protein synthesis. Ultimately, these results suggest the feasibility of obtaining candidate peptides for biological anticancer drugs from both human and bovine hemoglobin sources. These scientific advances show new hope in the fight against cancer which affects a large number of people around the world.

The Necessity of Human resources beyond perception of human understanding towards the Evaluation of video quality or Data screening methodology is conducted based on human perception level since it is concerned with how visual content is perceived by a observer based on observations with his/ her perception on a particular video sequence. Therefore, we considered that the subject has to grade the encoded video sequences under certain test environment conditions based on ITU-Recommendations. Since Human perception is considered as the true judgment and precise measurement of visual content, data screening has became quite essential and quite comfortable to general public due to introduction of User Experience(UX) concept by User Experience community. The translations of A recurrent neural network is based on certain principles, for instance we considered natural language processing which is certainly adaptable towards understanding sequential data and use patterns to predict the consistency within observers. In our research, we adapted principles based on Recurrent Neural Networks while assuming consistency within observers for predicting video quality within data screening environment towards subjective experiments. Moreover,this research work explores the trade offs between Human perception on visual content and consistency of observations within individual observer.

The creation of nano-zero-valent iron (nZVI) by implementing plant extracts is an environmentally friendly process. High antioxidant capacity and phenol content indicated the possibility of oak-nZVI synthesis using oak leaf extract as a stable material with minimal agglomeration. Simultaneously removal of Cd and phosphates and Ni and phosphates was optimized by a statistically designed experiment with a definitive screening design. In terms of significance, 4 input parameters on process productivity were monitored: initial metal concentration (1 - 9 mgL-1), initial ion concentration (1- 9 mgL-1), pH value (2 - 10) and oak-nZVI dosage (2 - 16 ml). Phosphate removal efficiency, in the presence of cadmium, was the most influenced by oak-nZVI dose and cadmium concentration, while pH gave three statistically significant interactions with oak-nZVI dosage, cadmium concentration, and phosphate concentration. Phosphate removal efficiency, in the presence of Ni, is the most influenced by nickel concentration, phosphate concentration, pH, two-factor interaction between nZVI dose and Ni concentration, and quadratic phosphate interaction. The process optimization yielded the highest simultaneous removal efficiency of 98.99% and 87.30% for cadmium and phosphate ions, respectively. Also, the highest simultaneous removal efficiency of nickel and phosphates ion was 93.44% for 96.75%, respectively. The optimization process fits into the confidence intervals, confirming the assumption that the adopted regression model describes the process well. This work demonstrated an enormous potential and prosperous application for the Cd(II), Ni(II), and phosphate removal from water matrices.

Abstract: The ability to detect several types of cancer using a non-invasive, blood-based test holds the potential to revolutionize oncology screening. We mined tumor methylation array data from the Cancer Genome Atlas (TCGA) covering 14 cancer types and identified two novel, broadly oc-curring methylation markers at TLX1 and GALR1. To evaluate their performance as a general-ized blood-based screening approach, along with our previously reported methylation bi-omarker, ZNF154, we rigorously assessed each marker individually or combined. Utilizing the TCGA methylation data and applying logistic regression models within each individual cancer type, we found that the three-marker combination significantly increased the average area under the ROC curve (AUC) across the 14 tumor types compared to single markers (p= 1.158e-10; Friedman test). Furthermore, we simulated dilutions of tumor DNA into healthy blood cell DNA and demonstrated increased AUC of combined markers across all dilution levels. Finally, we evaluated assay performance in bisulfite sequenced DNA from patient tumors and plasma, in-cluding early-stage samples. When combining all three markers the assay achieved 100% sensi-tivity and specificity, as demonstrated in lung cancer plasma samples. In patient plasma from hepatocellular carcinoma, ZNF154 alone yielded the highest combined sensitivity and specificity values averaging 68% and 72%, whereas multiple markers could achieve higher sensitivity or specificity, but not both. Altogether this study presents a comprehensive pipeline for the identifi-cation, testing and validation of multi-cancer methylation biomarkers with a considerable poten-tial for detecting a broad range of cancer types in patient blood samples.

Background: We aimed to investigate the effectiveness of postnatal ultrasonography in determining congenital anomalies of the kidney and urinary tract in term infants with or without a history of congenital anomalies of the kidney and urinary tract in the prenatal period. Methods: In this retrospective cohort study, the records of term infants aged between six weeks and three months undergoing urinary system ultrasonography during routine child care were examined. Results: Congenital anomalies of the kidney and urinary tract was determined in 121 (4.62%) of the 2620 cases included in the study. The most common anomaly was hydronephrosis (in 69.4% of the congenital anomalies of the kidney and urinary tract cases and 3.21% of all cases). Thirty-two of the 84 (38.1%) hydronephrosis cases detected by postnatal ultrasonography, three of the nine (33.3%) renal agenesis cases, four of the seven (57.1%) horseshoe kidneys cases, one of the four (25%) multicystic dysplastic kidney cases and two of the two (100%) duplex system cases could not be detected by prenatal ultrasonography. On the other hand, hydronephrosis was not detected at postnatal ultrasonography in 29 (1.1%) cases which detected mild or moderate hydronephrosis by prenatal ultrasonography scanning. Conclusions: In our study, it was observed that approximately one-third of the cases of hydronephrosis, unilateral renal agenesis, duplex system, horseshoe kidney, and ectopic kidney could not be detected at prenatal ultrasonography screening. We therefore believe that, in addition to prenatal ultrasonography screening, postnatal ultrasonography screening of all children for urinary tract anomalies would be beneficial.

To learn what mothers know on newborn bloodspot screening (NBS), the procedure, and sources used, a pilot study was performed. An online questionnaire was developed, with a first part fo-cused on characteristics and the NBS procedure, a second on knowledge, information sources, and health care providers (HCP). This questionnaire was accessible until 200 answers were received. Characteristics of respondents were representative for the population. Mothers recalled verbal consent in 69.5%, 12.5% did not, 18% stated that no consent was requested. The ‘knowledge’ part contained 12 closed questions, 5 multiple-choice questions on sources, and assessment (5-point Likert) of the information transfer. The mean knowledge level was 7.2/12. Screening concepts (consequences, likelihood, sensitivity, carrier) and absence of notification of normal findings were well known. The fact that NBS is not compulsory and post-analysis sample handling were poorly known. Key HCPs were midwifes (80.5%) and nurses (38.5%). When the leaflet (44%) was pro-vided, the majority read it. Mean Likert scores were 3.36, 3.38, 3.11 and 3.35 (clarity, timing ap-propriateness, sufficiency, usefulness). The knowledge level and consent practices were reasonable well. Key HCP were midwives and nurses, leaflets were supporting. This should enable a quality improvement program to a sustainable NBS program in Flanders.

Introduction: Intimate partner violence occurring during pregnancy has a similar prevalence as usual obstetrical disorders routinely screened for. Referenced publications insist on the importance of adequate screening but the proper course of action has yet to be defined. Aim of study: We qualitatively explored the different resources and concepts that emerge from the discourse of maternity staff across professions. Material and methods: We led a semi structured interview with professionals included following their involvement with preselected patients. Nine professionals provided a sample of 19 interviews. The data was analysed using IPA methodology. Results We highlight the investigative importance of navigating the patient’s initial demand or lack thereof and the baby’s importance within, mindful of mechanisms of maternal disqualification. Creating an atmosphere prone to patient empowerment was the final theme to emerge from the study as the most beneficial tactic both in the short and long term. Conclusion: HCPs need to enable patients’ trust on a personal and an institutional level. As well as empowering the patient in the moment and respecting their values and choices, HCPs also convey the stability of the institution that has to become a reference of refuge and assistance for patients from their pregnancy onwards.

Background: The interruption of the activity of the population-based organized colorectal cancer (CRC) screening programs due to the COVID pandemic may have affected their results in terms of detection of preneoplastic lesions and CRC. We evaluated the impact of the COVID pandemic on the delays, participation, adherence to colonoscopies, lesions detected, and CRC stage at di-agnosis in a CRC screening program. Methods: We analyzed all the invitations between January 1, 2019, and December 31, 2021. We defined the pandemic period as the period after March 12, 2020. We calculated the delay intervals (successive and all rounds), the rates of participation, adherence to colonoscopy after a positive fecal immunochemical test (FIT), and the diagnostic yield of colonoscopy, specifically CRC and colorectal neoplasia (CRC and/or adenoma), as well as CRC stage at diagnosis. Results: In the period analyzed, 976,187 invitations were sent (61.0% pandemic), 439,687 FIT were returned (62.4% pandemic) and 23,092 colonoscopies were performed (59.1% pandemic). Colon-oscopies were normal in 7,378 subjects (32.4%) and a CRC was detected in 916 subjects (4.0%). In successive rounds, the delay increased significantly seven months during the pandemic period (p<0.001). In all the invitations, the delay from the invitation to the colonoscopy increased sig-nificantly by 8 days (p<0.001). Once adjusted for the confounding variables, participation in the screening program increased significantly (OR=1.1; 95% CI=1.09-1.11), with no changes in the adherence to colonoscopy (OR=0.9; 95% CI=0.8-1.0). We found no differences in the diagnostic yield of colonoscopy in terms of CRC (OR=0.90; 95% CI=0.78-1.02) or colorectal neoplasia (OR=0.98; 95% CI=0.92-1.03) detection. Finally, we found no differences in CRC stage at diagnosis (p=0.2). Conclusions: Although the interruption of the CRC screening program due to the COVID pan-demic increased the delays, it did not reduce participation, adherence to colonoscopy, or the di-agnostic yield of colonoscopy.

Introduction: Mucopolysaccharidosis type I (MPSI) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and nonspecific symptoms resulting in high morbidity and mortality. The incidence of MPSI in US is estimated to be 0.26:100,000, however, it is unknown in Kuwait. This pilot study was undertaken to screen MPSI in all Kuwaiti neonates born at Farwaniya Hospital over a period of 12-months. This study examined the incidence of MPSI in a major center in Kuwait for inclusion in the national newborn screening program to enable its early detection and adequate treatment. Methods: All Kuwaiti neonates born at Farwaniya Hospital, Kuwait from December 2021 to December 2022, were screened for MPSI. The screening consisted of determining IDUA enzyme activity in dried blood spots (DBS)-derived samples by Tandem Mass Spectrometry. A follow-up genetic analysis of IDUA gene is planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. Results: A total of 618 newborns, including 331 (54%) males and 287 (46%) females, were screened. Twenty of them had deficient IDUA enzyme activity but showed negative genetic testing for IDUA. However, we have diagnosed one additional female baby with MPSI, who belonged to Farwaniya Hospital, but the parents chose to deliver in a private hospital. She presented at age three months with recurrent upper airway infections, snoring and extensive Mongolian spots. The molecular study revealed previously reported pathogenic nonsense variant in IDUA c.1882C>T; p.(Arg628Ter), associated with severe phenotype. That being included, MPSI is estimated to be about 0.3% among tested females and 0.2% of all screened cases in Kuwait. Conclusion: Our study is the first to evaluate the incidence of MPSI in Kuwait. Given the single center, small number of screened babies and the short study duration thus far, it is premature to calculate the incidence of MPSI. It is anticipated that as the study continues and more infants are examined, we would be able to estimate the incidence of this disease in our population correctly. Further studies including screening newborns in all maternity hospitals in Kuwait are needed to calculate the actual incidence of MPSI. Our data supports including MPSI in national newborn screening program to allow early initiation of treatment and thus improve disease outcome.

Gastric cancer (GC) is a highly heterogeneous, complex disease and the fifth most common cancer worldwide (about one million cases and 784 000 deaths worldwide in 2018). CG is lately diagnosed and guarantees a poor prognosis for GC (the 5-year survival rate is less than 20%, but in early detection can reach 90%). This study evaluated the transcriptional profile in tumor gastric samples to find genes highly expressed during tumor establishment and use the related proteins as targets to find new anticancer molecules. Data was collected at Gene Expression Omnibus (GEO) bank to obtain 3 dataset matrices that analyze gastric tumor tissue versus normal gastric tissue, performed microarray using GPL570 platform, and from different sources. The genes found in silico analysis were confirmed in several lines of GC cells by RT-qPCR. The protein data bank was used to find the correspondent proteins. Then a structural-based virtual screening was done to find molecules, and docking analysis was done using the DockThor server. Our results of transcriptomic analysis, together with RT-qPCR, confirm the high expression of the genes AJUBA, FBXL13, CCDC69, CD80 and NOLC1 in GC lines. Based on that, the correspondent proteins were used in SBVS analysis. Five molecules, one each target, MCULE-2386589557-0-6, MCULE-7343047040-0-1, MCULE-5230409338-0-3, MCULE-9178344200-0-1 and MCULE -5881513100-0-29. All molecules have favorable pharmacokinetic, pharmacodynamic and toxicological properties. Molecular docking analysis revealed that the molecules interact with proteins in critical sites for their activity. Using a virtual screening approach, a molecular docking study was performed for proteins encoded by genes that play important roles in cellular functions for carcinogenesis. Combining a systematic collection of public microarray data with a comparative meta-profiling, RT-qPCR, SBVS, and molecular docking analysis provided a suitable approach to find genes involved in GC and work the correspondent protein to strive for new molecules with anticancer properties.

Covid-19 is one of humanity’s biggest threat in the 21st century with WHO figures reporting 636 million cases and up to 6.6 million deaths globally. SARS-CoV-2, the virus that causes the Covid-19 disease, is characterized by high mutation which contributes to its rapid spread. While several vaccines have been produced to minimize the severity of the coronavirus and diverse treatment regimens have been approved by the US FDA under Emergency Use Authorization (EUA), SARS-CoV-2 viral mutations continue to derail the efforts of scientists as the emerging variants evade the recommended therapies. Nonetheless, diverse computational models exist that offer an opportunity to overcome the barriers involved in developing new drugs. In this review, the focus is on the use of various virtual screening techniques like molecular docking, molecular dynamics simulations, QSAR, pharmacophore modeling, and homology modeling in repurposing SARS-CoV-2 therapeutics. The results have been promising from the computer-aided drug design (CADD) studies in suggesting potential compounds for treatment of Covid-19 and helping in bringing the pandemic under control.

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten time to antibiotic administration in the Emergency Department. We retrospectively evaluated all patients above 18 years of age that were diagnosed with sepsis or severe infection in our Emergency Department between 2018 and 2020. We recorded the suspected diagnosis at time of presentation, type of referring healthcare provider and time until initiation of antibiotic treatment. Differences between groups were calculated using Kruskal-Wallis rank sum test. Of the 277 patients that were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well described outcome benefits to early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce time to antibiotic administration and improve patient outcomes.

COVID-19 pandemic has spurred intense research efforts to identify effective treatments for SARS-CoV-2. In silico studies have emerged as a powerful tool in the drug discovery process, particularly in the search for drug candidates that interact with various SARS-CoV-2 receptors. These studies involve the use of computer simulations and computational algorithms to predict the potential interaction of drug candidates with target receptors. The primary receptors targeted by drug candidates include the RNA polymerase, main protease, spike protein, ACE2 receptor, TMPRSS2, and AP2-associated protein kinase 1. In silico studies have identified several promising drug candidates, including Remdesivir, Favipiravir, Ribavirin, Ivermectin, Lopinavir/Ritonavir, and Camostat mesylate, among others. The use of in silico studies offers several advantages, including the ability to screen a large number of drug candidates in a relatively short amount of time, thereby reducing the time and cost involved in traditional drug discovery methods. Additionally, in silico studies allow for the prediction of the binding affinity of drug candidates to target receptors, providing insight into their potential efficacy. However, it is crucial to consider both the advantages and limitations of these studies and to complement them with experimental validation to ensure the efficacy and safety of identified drug candidates.

The RNA-binding protein Human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. The protein has been progressively recognized as a relevant therapeutic target for several pathologies like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatics approaches, high throughput virtual screening and RNA–protein pull-down assays, we show that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits dose-dependent HuR inhibition in binding experiments. Importantly, the chemical scaffold is new with respect to the so-far known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.