Selective Screening Research Articles

Long term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis

Abstract Background Evaluation of the cardiotoxic effects from cancer is most commonly evaluated at the time of chemotherapy. Although cancer survivorship populations are rapidly expanding, there is a paucity of evidence regarding the frequency and causes of heart failure (HF) >5 years after cardiotoxic therapy. Objectives This systematic review sought to investigate the relationship between cardiotoxic cancer therapies and late-onset HF. Methods We searched the EMBASE and MEDLINE databases for studies reporting HF in adult survivors (≥50 years old), who were ≥5 years post-breast/lymphoma cancer therapy. A random effects model was used to examine the associations of HF. A meta-regression analysis was implemented to determine causes of heterogeneity. Results Thirteen papers were included in the review and meta-analysis (Figure 1), comprising 190,259 participants (mean age 53.5 years, 93% female). The risk of HF was increased (overall log risk-ratio 0.39 (95%CI (0.16-0.62)), (Figure 2). Cardiotoxic treatment, compared with cancer alone, provided a similar risk (log risk ratio of 0.38 [95% CI 0.02-0.77]). In the breast cancer population ratio (11 studies) the overall heart failure log risk was 0.41 [95% CI 0.13-0.69]). Although heterogeneity was significant (I²=77.17), this was explained by differences in patient characteristics; once multivariable analysis accounted for follow up (0.99, 95%CI (0.97-0.99), p=0.047), age (1.14, 95%CI (1.04-1.25), p=0.003) and hypertension (0.95, 95%CI (0.92-0.98), p<0.001), residual heterogeneity was low (I²=28.73). Conclusions HF is increased in adult cancer survivors, associated with cardiotoxic cancer therapy and standard risk factors. Consideration should be given for selective screening for HF in this at-risk population.Fig 1:Literature Search Flow DiagramFig 2:Incident HF in Cancer Survivors

A New Algorithm for Predicting Dam Deformation Using Grey Wolf-Optimized Variational Mode Long Short-Term Neural Network

To solve the problems of difficult-to-model parameter selections, useful-signal extraction and improper-signal decomposition in nonlinear, non-stationary dam displacement time series prediction methods, we propose a new predictive model for grey wolf optimization and variational mode decomposition and long short-term memory (GVLSTM). Firstly, we used the grey wolf optimization (GWO) algorithm to optimize the parameters of variable mode decomposition (VMD), obtaining the optimal parameter combination. Secondly, we used multiscale permutation entropy (MPE) as a standard to select signal screening, determining and recon-structing the effective modal components. Finally, the long short-term memory neural network (LSTM) was used to learn the dam deformation characteristics. The result shows that the GVLSTM model can effectively reduce the estimation deviation of the prediction model. Compared with VMDGRU and VMDANN, the average RMSE and MAE value of each station is increased by 19.11%~28.58% and 27.66%~29.63%, respectively. We used determination (R2) coefficient to judge the performance of the prediction model, and the value of R2 was 0.95~0.97, indicating that our method has good performance in predicting dam deformation. The proposed method has outstanding advantages of high accuracy, reliability, and stability for dam deformation prediction.

Synthetic Cathinones' Comprehensive Screening and Classification by Voltammetric and Chemometric Analyses: A Powerful Method for On-Site Forensic Applications.

The use of synthetic cathinones (SCs) has increased in recent years, posing significant public health problems due to their adverse effects and potential for fatal poisonings. The structural diversity and rapid emergence of new SC analogues create challenges for law enforcement and drug screening techniques. This work presents for the first time the electrochemical detection of SCs using differential pulse voltammetry (DPV) on a boron-doped diamond electrode (BDDE). We analyzed 15 SCs, including well-known compounds such as mephedrone, methylone, and ephylone, revealing distinct electrochemical profiles with two characteristic reduction peaks (R1 and R2). The method was optimized in Britton-Robinson buffer (0.1 mol L-1, pH 8.0) and demonstrated a high selectivity and sensitivity. Multivariate statistical methods, including principal component analysis and hierarchical cluster analysis, classified SCs into six distinct groups. The DPV optimization and analytical parameter determination, including the limit of detection (LOD), were performed for the least electroactive SC, 4'-methyl-α-pyrrolidinohexanophenone, yielding an LOD of 3.8 μmol L-1, suitable for screening street samples. Interference studies with common illicit drugs and adulterants confirmed the selectivity of the DPV-BDDE method. Preliminary identification of SCs in 46 real seized samples was successfully performed using this method with results validated by liquid chromatography-mass spectrometry (LC-MS). The method also identified three SCs not included in the original set: bupropion, benzylone, and dipentylone. The DPV-BDDE method offers a rapid, robust, and portable approach for the selective screening of SCs in forensic applications, demonstrating significant advantages over traditional colorimetric tests.

Selective screening for celiac disease in patients with gastrointestinal symptoms: a retrospective study

Background. Currently, the effectiveness of various screening programs for celiac disease remains a matter of debate. According to most researchers, selective screening among patients with characteristic symptoms or at-risk groups is most effective. Aim. To evaluate the effectiveness of selective screening for celiac disease in patients with gastrointestinal symptoms. Materials and methods. In an open retrospective clinical study, the rate of celiac disease among 1,482 children who were examined in the Bashlyaeva Children's City Clinical Hospital and the most significant symptoms of the disease depending on age were identified. Results. The mean rate of celiac disease was 8.26%: from 6 months to 3 years 7.25%, from 4 to 7 years 10.28%, from 8 to 14 years 9.33%, and in adolescents from 15 years and older 4.05%. The most significant symptoms of the disease in young children were abdominal distension/flatulence, asthenia, and weight loss; preschool children had stool disorders (constipation, diarrhea), abdominal distension/flatulence, and anemia. At the age of 8–14 years, only nausea was statistically significantly associated with celiac disease. We have not identified any significant symptoms in the older age group. Conclusion. Our study has shown the high effectiveness of selective screening for celiac disease. The selective screening program is most effective in children of early and preschool age, which defines this age category as a target for introducing screening programs in medical check-ups before enrollment to preschool institutions and schools.

Serological profile of voluntary blood donors in a blood bank of tertiary health care centre- An institution-based study

Background: The safe transfusion of blood facilities is an essential component of an efficient, excellent healthcare sector. Unsafe blood transfusions can be a cause of transfusion-transmitted infections and can be lethal. The present study was conducted to find out the seroprevalence of HBsAg, HCV, HIV, malarial parasites, and syphilis in voluntary blood donors in a tertiary care center. Materials and methods: This prospective study was conducted at the blood bank of the Shri Mahant Indiresh Hospital, Dehradun. 16413 samples from all blood donations were screened for HBsAg, HCV, HIV 1 and 2, malaria, and syphilis. Samples were collected in vacutainers at the time of blood donation and screened for HIV 1and2, HBsAg, and HCV using the fourth-generation enzyme-linked immunosorbent assay technique. Syphilis was tested by Treponema antibodies using the VITROS Syphilis TPA Reagent Pack. Malaria was tested by pan malaria card, monoclonal anti-pan specific parasite lactate dehydrogenase antibody conjugated to colloidal gold, and another monoclonal anti-pan specific parasite lactate dehydrogenase antibody immobilized on a nitrocellulose strip in a thin line. Results: Out of 16413 blood donors 342(2.1%) were found to be seropositive and 16071 (97.9%) were found to be seronegative. The total number of donors, who were found positive for HBsAg/Anti HCV was 1 (0.3%). Out of the seropositive cases, HBsAg, HCV, HIV, and Syphilis infections constituted 28.9%, 27.5, 14.6, and 28.7% cases respectively. Conclusions: There is a need for the development and implementation of stringent donor selection and sensitive screening tests to reduce the risk of acquiring transfusion-transmitted illnesses.

Marker assisted selection and genome recovery for heat tolerance in segregants of rice (Oryza sativa L.)

Abstract In the present global warming scenario, it is urgent to impart heat tolerance into the popular high yielding rice (Oryza sativa L.) varieties to reduce yield loss to a great extent. Uma (a prevalent red-grained rice variety in Kerala) was crossed with Nagina 22 (N22), the popular donor for heat tolerance. From the seven promising heat-tolerant F3 plants previously identified through marker assisted selection and field screening, F4 lines (58 nos.) were raised and characterised morphologically. Heat tolerance was scored under natural heat stress during hot summer months in field conditions. Among the evaluated F4 progenies, 26 promising plants registered >75% spikelet fertility. Double panicles were observed in some of the tillers of fourteen F4 plants. During the selection with reported polymorphic markers between parents, all the 26 F4 plants produced the corresponding amplicon for RM5749 (linked marker for heat tolerance in the parental cross Uma x N22) and also for RM9, RM201, RM208, RM225, RM242, RM495, RM3586, RM6100, RM6836, and RM26212, corresponding to the heat tolerant parent N22. Genomic analysis revealed 64% recovery of the Uma genome in seven F4 plants, with maximum genomic regions of Uma on the chromosomes 3 and 5. These promising F4 plants could be forwarded to generate stable and high yielding heat tolerant rice varieties. The identified markers could be used for linkage analysis and QTL mapping in future. Keywords: Heat stress; Rice; spikelet fertility; SSR; QTL

Enhanced power generation by carbonized microsphere embedded with bimetallic carbides nanoparticles as efficient electrocatalyst in bioenergy harvesting systems

The performance and preparation method of anode are the key factors for power generation and magnified application of microbial fuel cell (MFC). This is because the anode plays an essential role in whole process for extracellular electron transfer (EET) as the carrier of exoelectrogens. In this work, dual-phased Mo2C-W2C microsphere are prepared on carbon-based matrices as binder-free anode by in-situ pyrolysis of Mo/W precursors. As expected, the Mo2C-W2C/CC anode exhibits brilliant electrocatalytic activity, electron harvesting capacity and improved EET rate, thus the maximum power density of corresponding MFC achieves 4.89 W/m2. The above enhancement can be attributed to the microspherical three-dimensional structure consisting of numerous carbon nanosheets embedded with Mo2C-W2C heterogeneous nanoparticles, which will provide more catalytic active sites for microbial metabolic reactions. The microbial community analysis indicates that the formation of electroactive biofilms has been promoted by the selective screening of Mo2C-W2C for exoelectrogens and other bacteria related to sulfur metabolism. Finally, the bioenergy harvesting system assembled with Mo2C-W2C electrocatalyst successfully charges the 12 V battery. This study provides a facile, low-cost modification method for the development of high-performance MFC anodic materials conducive to large-scale preparation and has a promising effect in practical application.

Understanding Insulin Resistance in NAFLD: A Systematic Review and Meta-Analysis Focused on HOMA-IR in South Asians.

Non-alcoholic fatty liver disease (NAFLD), a metabolic condition, is becoming increasingly common in South Asia. While its clinical diagnosis primarily relies on sonography and altered hepatic biomarkers, the significance of non-hepatic indicators, such as Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), in relation to NAFLD requires further examination in the South Asian population due to ethnic differences in these markers. This study examined the relationship between insulin resistance, quantified using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and NAFLD, along with other non-hepatic biomarkers. A thorough literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, and Google Scholar databases, yielding 287 articles. After applying the selection criteria and screening, 22 studies were selected for inclusion in the analysis. We extracted and meta-analyzed the data on HOMA-IR in patients with NAFLD, along with other relevant parameters. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of observational studies, whereas the RoB 2.0 tool was employed for randomized controlled trials (RCTs). The systematic review uncovered that individuals with NAFLD demonstrated statistically significant elevations in HOMA-IR levels, with a weighted mean difference (WMD) of 1.28 (95% confidence interval (CI): 1.00-1.58, I² = 98%, p < 0.0001) when compared to healthy subjects. Additionally, NAFLD patients showed markedly higher fasting blood glucose (FBG) levels, with a combined mean difference of 15.64 mg/dL (95% CI: 11.03-20.25, I² = 92%, p < 0.0001). The analysis also revealed increased triglyceride levels in NAFLD patients, with a pooled mean difference of 42.49 mg/dL (95% CI: 29.07-55.91, I² = 97%, p < 0.0001), and elevated C-reactive protein (CRP) levels, with a pooled mean difference of 2.17 mg/L (95% CI: 2.01-2.33, I² = 23%, p < 0.0001). Interestingly, subgroup analysis indicated that obese NAFLD patients exhibited significantly higher HOMA-IR levels than their non-obese counterparts, with a weighted mean difference of 5.85 (95% CI: 4.88-6.81, I² = 0%, p < 0.0001). Variations in study methodology, diagnostic techniques, and subject demographics were identified as sources of heterogeneity. The analysis found little evidence of publication bias, which lends credibility to the results. In South Asian populations, higher HOMA-IR, triglyceride-glucose (TyG) index, and CRP levels are associated with an increased risk of NAFLD. To improve the understanding and treatment of NAFLD in this specific demographic group, it is necessary to establish uniform diagnostic criteria and conduct additional studies, particularly RCTs.

Strontium Isotope Composition of Triassic Coastal and Shallow Marine Carbonates in the Western Balkanides, NW Bulgaria

Whole-rock samples of Triassic coastal and shallow marine carbonates were analyzed for their Sr isotope signatures and trace element concentrations were measured in order to assess the possible impact of diagenetic alteration. The 87Sr/86Sr ratios of Anisian to lower Carnian calcite micrites reproduce the global Triassic seawater variations fairly well. The recorded higher values can be explained by an influence from detrital aluminosilicate phases and a minor postdepositional alteration. The samples of tidal-flat dolomicrites from the base of the Anisian show no significant diagenetic overprint but have considerably more radiogenic 87Sr/86Sr signatures compared to the global Sr isotope curve that corresponds to the Triassic (Mesozoic) maximum. These anomalously high values may have resulted from some interaction between the dolomitizing brines and the underlying fluvial siliciclastics (Buntsandstein facies), but more likely from the high 87Sr/86Sr river waters discharged from a silicate-dominated drainage basin to the coastal area at the beginning of the Middle Triassic. This study demonstrates that bulk micrite can be used as a proxy for seawater 87Sr/86Sr after proper sample selection and diagenetic screening. It also suggests that the 87Sr/86Sr ratios of ancient carbonates precipitated in coastal settings should be interpreted with caution, considering the possible influence of continentally-derived fluids.

Xq12q13.2 duplication detected in a child in selective exome screening

Background. Within the framework of the regional pilot project on selective exome screening of newborn children, which is carried out on the basis of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, we conducted molecular genetic testing of children who meet the criteria for inclusion in the increased group of hereditary diseases. We examine not only children with suspected genetic etiology of the condition, but also children with borderline clinical and laboratory manifestations and minor developmental anomalies.The aim of the study. To describe the clinical and phenotypic features of a patient with a previously undescribed Xq12q13.2 duplication detected in the neonatal period.Materials and methods. The child was examined within the framework of a regional pilot project on selective exome screening of newborn children. DNA was isolated from a biological sample of venous blood of the newborn, and whole exome sequencing and chromosomal microarray analysis were performed. Signed informed voluntary consent for the publication of the examination data and a photograph of the child were obtained from the legal representatives of the proband.Results. Data in favor of the presence of a previously undescribed Xq12q13.2 duplication, confirmed by the reference method were obtained in a patient included in the project in accordance with the clinical criteria for the formation of a risk group according to the data of the conducted whole exome sequencing. Discussion. Xq12q13.2 duplication was detected in the proband from the present clinical observation with non-specific clinical manifestations in the neonatal period. Similar duplications have been described in the literature in three patients with congenital malformations, epilepsy and psychomotor retardation. Early diagnosis of such a copy number variation disorder before the appearance of severe clinical signs of the disease will allow determining the prognosis and tactics of observation and treatment of the patient.Conclusion. The described case of Xq12q13.2 duplication in a patient demonstrates the importance of timely genetic analysis to optimize medical genetic counseling, reduce diagnostic search and improve prognosis for patients.

Prediction of Severe Baseline Asymptomatic Carotid Stenosis and Subsequent Risk of Stroke and Cardiovascular Disease.

Risk models to identify patients at high risk of asymptomatic carotid artery stenosis (ACAS) can help in selecting patients for screening, but long-term outcomes in these patients are unknown. We assessed the diagnostic and prognostic value of the previously published Prevalence of ACAS (PACAS) risk model to detect ACAS at baseline and to predict subsequent risk of stroke and cardiovascular disease (CVD) during follow-up. We validated the discrimination and calibration of the PACAS risk model to detect severe (≥70% narrowing) ACAS with patients from the Reduction of Atherothrombosis for Continued Health registry. We subsequently calculated the incidence rates of stroke and CVD (fatal and nonfatal stroke or myocardial infarction or vascular death) during follow-up in 4 risk groups (low, medium, high, and very high, corresponding to sum scores of ≤9, 10-13, 14-17, and ≥18, respectively). Among 26 384 patients, aged between 45 and 80 years, without prior carotid procedures, 1662 (6.3%) had severe baseline ACAS. During ≈70 000 patient-years of follow-up, 1124 strokes and 2484 CVD events occurred. Discrimination of the PACAS model was 0.67 (95% CI, 0.65-0.68), and calibration showed adequate concordance between predicted and observed risks of severe baseline ACAS after recalibration. Significantly higher incidence rates of stroke (Ptrend<0.011) and CVD (Ptrend<0.0001) during follow-up were found with increasing PACAS risk groups. Among patients with high PACAS sum score of ≥14 (corresponding to 27.7% of all patients), severe baseline ACAS prevalence was 11.4%. In addition, 56.6% of incident strokes and 64.9% of incident CVD events occurred in this group. The PACAS risk model can reliably identify patients at high risk of severe baseline ACAS. Incidence rates of stroke and CVD during follow-up were significantly higher in patients with high PACAS sum scores. Selective screening of patients with high PACAS sum scores may help to prevent future stroke or CVD.

Clinical, biochemical, molecular characteristics and clinical outcome of hyperhomocysteinemia in Malaysian children

BackgroundHyperhomocysteinemia can be due to various abnormalities of the complex interaction of methionine, folate and vitamin B12. It has been known to be a cardiovascular risk factor. This study aims to review the clinical presentation, underlying causes and clinical outcome in paediatric patients diagnosed with significant hyperhomocysteinemia in Malaysia. Design and methodsData were obtained from the medical records and the laboratory information system. Paediatric patients with significant hyperhomocysteinemia were identified from a selective high-risk screening of 96,721 patients, performed between 2010 and 2022. Inclusion criteria for the study were paediatric patients with significant hyperhomocysteinemia (>40 µmol/L). ResultsSixteen patients were identified. The average total homocysteine (tHcy) and methionine were 269 µmol/L and 499 µmol/L in cystathionine β-synthase deficiency (CBS), 127 µmol/L and 29 µmol/L in patients with remethylation defects and 390 µmol/L and 4 µmol/L in congenital B12 deficiency. We found c.609G>A as the most prevalent mutation in MMACHC gene and possible novel mutations for CBS (c.402del, c.1333C>T and c.1031T>G) and MTHFR genes (c.266T>A and c.1249del). Further subclassification revealed CBS was 5/16 patients (31 %), remethylation defects was 9/16 (56 %) and congenital B12 deficiency was 2/16 (13 %). All patients received standard treatment and regular monitoring of the main biomarkers. The average age at the time of diagnosis were 9.2 years (CBS) and 1.2 years (remethylation defects). Congenital B12 deficiency had slight delay in milestones, remethylation defects had mild to moderate learning disabilities, CBS had variable degree of intellectual disability, delayed milestones, ophthalmological abnormalities, and thrombosis at an early adolescent/adulthood. ConclusionsThe majority of significant hyperhomocysteinemia in Malaysian children was due to remethylation defects. Screening for hyperhomocysteinemia in Malaysian children is recommended for earlier treatment and improved clinical outcome.

Long-term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis

BackgroundCancer survivors are at increased risk of heart failure (HF). While cardiotoxicity is commonly sought at the time of cancer chemotherapy, HF develops as a result of multiple ‘hits’ over...

Ultra-fast, selective and pseudo-quantitative analysis of 99Tc in nuclear waste for screening purposes

Controlling radioactivity is essential in various fields, such as the decommissioning of nuclear power plants and nuclear medicine. In some cases, a full characterization of samples is not required; instead, a screening analysis that provides an overall indication of the activity present can be sufficient to determine if a sample is radioactive. This article introduces a new system called PSkits designed specifically for ultra-fast and selective screening detection of 99Tc. PSkits consist of a plastic scintillation layer attached to the bottom of a scintillation vial, coated with aliquat·336® as a selective extractant. In this study, the preparation of PSkits was optimized by adjusting the proportions of crosslinker, porogen, and the type of vial used. The analysis method was developed, and the selectivity against common interferences was tested by optimizing the rinsing media. Finally, PSkits were validated by analysing simulated nuclear waste samples and urine spiked samples, achieving satisfactory results with quantification errors below 50 %, demonstrating their effectiveness for the intended purpose

Physio-biochemical and molecular characterization of wheat cultivars (Triticum aestivum L.) under post-anthesis heat stress

BackgroundHeat stress is one of the abiotic stresses that make wheat crops vulnerable, which significantly impacts crop production around the world. An increase in temperature during the reproductive phase (anthesis) beyond the optimal range of 15–20 °C leads to decreased crop production, poor quality of the grain, and altered physiological and biochemical processes. To study the association between high temperature and physio-biochemical traits under normal and late sown, a set of fifteen genotypes was utilized.ResultsRelative water content under high temperatures had an overall decrease of 8.7%. However, grain protein and malondialdehyde content were higher in the stressed conditions than in the control, with increases of 20.2% and 38.9%, respectively. Marker Xgwm67, located on chromosome 5B, was found to be significantly associated with malondialdehyde content (R2 = 21%) and Xgwm570, located on 6A, was closely linked to relative water content as well as grain protein content (R2 = 16%) revealed by regression analysis. The correlation matrix displays a positive association between the control and stressed condition by R2 = 0.92, 0.82, and 0.53 in malondialdehyde, relative water content, and grain protein, respectively. However, there was a negative correlation between water content–malondialdehyde and malondialdehyde–grain protein, though there was only a 4% correlation between grain protein content (control) and relative water content (stressed). Based on the tolerance matrix, WH730 and RAJ4079 were heat tolerant, and DBW173 and HD3086 were sensitive.ConclusionsThese findings indicate that to identify tolerant genotypes, physiological and biochemical traits can be utilized as an alternate criterion, and these closely associated markers can be applied for improved late-planted wheat production through MAS. The breeding scheme and genome editing by recognizing novel genes through physio-biochemical parameters, marker-assisted selection, and prospective screening of tolerant genotypes are proclaimed by the study.

Efficient Production of an Alginate Lyase in Bacillus subtilis with Combined Strategy: Vector and Host Selection, Promoter and Signal Peptide Screening, and Modification of a Translation Initiation Region.

Alginate lyases (ALys) whose degrading products, alginate oligosaccharides, exhibit various outstanding biochemical activities have aroused increasing interest of researchers in the marine bioresource field. However, their predominant sourcing from marine bacteria, with limited yields and unclear genetic backgrounds, presents a challenge for industrial production. In this study, ALys (Aly01) from Vibrio natriegens SK 42.001 was expressed in Bacillus subtilis (B. subtilis), a nonpathogenic microorganism recognized as generally safe (GRAS). This accomplishment was realized through a comprehensive strategy involving vector and host selection, promoter and signal peptide screening, and engineering of the ribosome binding site (RBS) and the N-terminal coding sequence (NCS). The optimal combination was identified as the pP43NMK and B. subtilis WB600. Among the 19 reported strong promoters, PnprE exhibited the best performance, showing intracellular enzyme activities of 4.47 U/mL. Despite expectations, dual promoter construction did not yield a significant increase. Further, SPydhT demonstrated the highest extracellular activity (1.33 U/mL), which was further improved by RBS/NCS engineering, reaching 4.58 U/mL. Finally, after fed-batch fermentation, the extracellular activity reached 18.01 U/mL, which was the highest of ALys with a high molecular weight expressed in B. subtilis. These findings are expected to offer valuable insights into the heterologous expression of ALys in B. subtilis.

Blood donor questionnaires and infectious disease screening in Latin American countries.

Blood donor questionnaires are tools used to screen prospective blood donors to determine their eligibility. There are limited data regarding blood donor questionnaires and infectious disease screening of the blood supply in Latin American countries. This study aimed to survey donor centres in Latin American countries to learn more about blood donor screening and infection assessment. An international team of transfusion medicine professionals including medical directors and supervisors who work or collaborate with Latin American donor centres, called 'Comité de Investigación en Medicina Transfusional', designed a survey (16 questions) to characterize blood donor eligibility in Latin America. Eighty-two institutions from 14 Latin American countries responded to the survey. Most donor centres (66%; 54 of 82) had a donor deferral percentage between 5% and 25%, and the most common causes of deferrals were low haemoglobin and high-risk behaviour. Most donors in blood centres were directed family donors compared with voluntary donors. Infection evaluation included mostly serologic assessment (81%; 30 of 37) for human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, Treponema pallidum and Trypanosoma cruzi rather than nucleic acid tests (5%; 2 of 37). Heterogeneity exists in donor selection and infectious disease screening in Latin American countries. This survey provides valuable information to understand Latin American blood centre practices.

ECAD study: Evaluating agreement degree among paediatricians in hip dysplasia assessment by the Graf ultrasound method.

Developmental dysplasia of the hip (DDH) is the most common musculoskeletal anomaly of childhood. This study analyses paediatrician's concordance performing hip ultrasound according to Graf's method. An analytical cross-sectional study is designed. Patients' hips are evaluated by Graf's ultrasound method at 4-6 and 12-16weeks of age. Demographic characteristics, pregnancy history, factors related to DDH, hip type, and α and β angles are collected. To assess the agreement degree of hip diagnosis and hip types Kappa index (I. kappa) is used. Intraclass correlation coefficient (ICC) evaluates the concordance of α and β angles. A p value < 0.05 is considered statistically significant. All results are represented with their 95% confidence interval (95% CI). Four hundred sixty-seven neonates are recruited and meet the inclusion criteria. A total of 3182 images were analysed. Agreement between paediatricians according to hip diagnosis and different types ranges from moderate to almost perfect I. kappa 0.6-1.0 (95% CI 0.5-0.7; 95% CI 1.0-1.0). α angle ICC for paediatricians is between 0.75 and 0.88 (95% CI 0.61-0.86; 95% CI 0.80-0.92). β angle value agreement degree among paediatricians at both visits is moderate. The Graf method is the most popular ultrasound technique for hip assessment. In our setting, paediatricians carry out children follow-up; therefore, they should perform universal screening. In this study agreement degree between paediatricians varies between substantial and almost perfect. Conclusion: The Graf ultrasound procedure performed by paediatricians is a reliable test and can be used for DDH screening. What is Known •Developmental dysplasia of the hip (DDH) is the most common congenital musculoskeletal anomaly of childhood. Early diagnosis and treatment improve DDH prognosis. Lack of detection can cause complications such as lameness, early osteoarthritis and need for hip replacement at an early age. What is New •Today, the best screening method is still subject of debate. But it seems that with selective screening many pathological hips go unnoticed. Universal screening implementation may be a challenge in some countries. But the question is if this could be carried out by paediatricians as part of healthy child follow-up.

An automated positive selection screen in yeast provides support for boron-containing compounds as inhibitors of SARS-CoV-2 main protease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to cause severe disease and deaths in many parts of the world, despite massive vaccination efforts. Antiviral drugs to curb an ongoing infection remain a priority. The virus-encoded 3C-like main protease (MPro; nsp5) is seen as a promising target. Here, with a positive selection genetic system engineered in Saccharomyces cerevisiae using cleavage and release of MazF toxin as an indicator, we screened in a robotized setup small molecule libraries comprising ~2,500 compounds for MPro inhibitors. We detected eight compounds as effective against MPro expressed in yeast, five of which are characterized proteasome inhibitors. Molecular docking indicates that most of these bind covalently to the MPro catalytically active cysteine. Compounds were confirmed as MPro inhibitors in an in vitro enzymatic assay. Among those were three previously only predicted in silico; the boron-containing proteasome inhibitors bortezomib, delanzomib, and ixazomib. Importantly, we establish reaction conditions in vitro preserving the MPro-inhibitory activity of the boron-containing drugs. These differ from the standard conditions, which may explain why boron compounds have gone undetected in screens based on enzymatic in vitro assays. Our screening system is robust and can find inhibitors of a specific protease that are biostable, able to penetrate a cell membrane, and are not generally toxic. As a cellular assay, it can detect inhibitors that fail in a screen based on an in vitro enzymatic assay using standardized conditions, and now give support for boron compounds as MPro inhibitors. This method can also be adapted for other viral proteases.IMPORTANCEThe coronavirus disease 2019 (COVID-19) pandemic triggered the realization that we need flexible approaches to find treatments for emerging viral threats. We implemented a genetically engineered platform in yeast to detect inhibitors of the virus's main protease (MPro), a promising target to curb severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Screening molecule libraries, we identified candidate inhibitors and verified them in a biochemical assay. Moreover, the system detected boron-containing molecules as MPro inhibitors. Those were previously predicted computationally but never shown effective in a biochemical assay. Here, we demonstrate that they require a non-standard reaction buffer to function as MPro inhibitors. Hence, our cell-based method detects protease inhibitors missed by other approaches and provides support for the boron-containing molecules. We have thus demonstrated that our platform can screen large numbers of chemicals to find potential inhibitors of a viral protease. Importantly, the platform can be modified to detect protease targets from other emerging viruses.

Selectivity Screening and Structure-Cytotoxic Activity Observations of Selected Oleanolic Acid (OA)-Type Saponins from the Amaranthaceae Family on a Wiade Panel of Human Cancer Cell Lines.

Plants from the Amaranthaceae family are a source of oleanolic acid (OA)-type saponins with cytotoxic activity. Two known OA-type saponins, calenduloside E and chikusetsusaponin IVa, were isolated from the roots of Chenopodium strictum Roth. Their structures were confirmed using MS and NMR techniques. This constitutes the inaugural report of the saponins in Ch. strictum. Both the isolated saponins and structurally similar compounds, momordin Ic and OA, were compared for their cytotoxicity against various cancer and normal cell lines (including skin, breast, thyroid, gastrointestinal, and prostate panels). Their effects were dose- and time-dependent, varying with the specific cell line and compound structure. A chemometric approach demonstrated the effects of the compounds on the cell lines. The study discusses the structure-activity observations. The key structural elements for potent cytotoxic activity included the free carboxyl group 28COOH in the sapogenin structure (OA) and the presence of a sugar moiety. The monodesmosides with glucuronic acid (GlcA) at the C3 position of OA were generally more cytotoxic than bidesmosides or OA alone. The addition of xylose in the sugar chain modified the activity towards the cancer cells depending on the specific cell line. OA-type saponins with GlcA (particularly calenduloside E and momordin Ic) represent a promising avenue for further investigation as potential anticancer agents.