Screening Methodology Research Articles

Detection of antimicrobial residues in animal manure by a microbiological screening methodology: A non-invasive tool in animal production

Detection of antimicrobial residues in animal manure by a microbiological screening methodology: A non-invasive tool in animal production

Comprehensive characterization of volatile and semi-volatile compounds in e-liquids for electronic cigarette using gas chromatography accurate mass spectrometry

The consumption of electronic cigarettes is a habit with an increasing prevalence, particularly among youths. Knowing the composition of e-liquids used in these devices represents the first step to understand the potential impact of e-smoking in the health of consumers. Herein, a non-target screening methodology was applied to the identification of volatile and semi-volatile compounds in a set of e-liquids from different suppliers, with different flavors, and containing different kinds of additives, such as nicotine or cannabidiol. To this end, samples were characterized by gas chromatography accurate mass spectrometry, using a time-of-flight mass analyzer. Combination of deconvoluted electronic ionization mass spectra with linear retention index values, obtained for two columns with different selectivity, permitted the identification of more than 250 chemicals with different confidence levels. Among them, respiratory pro-inflammatory compounds, acetals of propylene glycol and glycerin with aldehydes, nicotine-related and non-related alkaloids, and psychoactive cannabinoids were confirmed as concerning compounds in e-liquid samples. Concentration ratios between propylene glycol acetals and parent aldehydes varied in the range from 2% (ethyl vanillin) to more than 80% (case of benzaldehyde). The ratios between the concentrations of delta-9-tetrahydrocannabinol and cannabidiol in e-liquids stayed in the range from 0.02% to 0.3%.

Sustainable Low-Carbon Production: From Strategy to Reality

The present paper approaches the timely topic of sustainable production with low carbon emissions, investigating the link between existing strategies and policies and the reality that manufacturers must deal with, with the appraisal going from high-level national and international plans to specific firm needs. This is in line with the preoccupations of manufacturers in Europe to retain and regain their market shares under strict environmental excellence, one of the defining features of the continent’s economy. The existing strategies, specialized plans and mechanisms for the reduction of emissions were analyzed to discern their structural relationships and the clarity and palpability of their content when passing through the successive levels of interest. The research methodology employs the MEAL Plan for determining the state of the art, and based on the findings, two specific tools were used for policy analysis and informing a brainstorming and discussion session aimed at future improvements. The instruments used are SWOT-Radar Screen methodology and latent semantic analysis as implemented by the Tropes Zoom software. Structural connections were revealed, together with an improved understanding of the interventions proposed in 5 European-level strategies, 14 national-level strategies (with a focus on Romania) and a case analysis for a generic manufacturing company. Among the main findings, the authors propose improved awareness development for all the stakeholders, strengthened and correlated monitoring of sustainability results and a better implementation of an institutional ecosystem for providing support to companies. The results obtained are intended for the use of policy makers to improve their future planning cycles in a way that supports the companies in achieving these societal goals.

Virtual High‐Throughput Screening of Vapor‐Deposited Amphiphilic Polymers for Inhibiting Biofilm Formation

AbstractAmphiphilic copolymers (AP) represent a class of novel antibiofouling materials whose chemistry and composition can be tuned to optimize their performance. However, the enormous chemistry‐composition design space associated with AP makes their performance optimization laborious; it is not experimentally feasible to assess and validate all possible AP compositions even with the use of rapid screening methodologies. To address this constraint, a robust model development paradigm is reported, yielding a versatile machine learning approach that accurately predicts biofilm formation by Pseudomonas aeruginosa on a library of AP. The model excels in extracting underlying patterns in a “pooled” dataset from various experimental sources, thereby expanding the design space accessible to the model to a much larger selection of AP chemistries and compositions. The model is used to screen virtual libraries of AP for identification of best‐performing candidates for experimental validation. Initiated chemical vapor deposition is used for the precision synthesis of the model‐selected AP chemistries and compositions for validation at solid–liquid interface (often used in conventional antifouling studies) as well as the air–liquid–solid triple interface. Despite the vastly different growth conditions, the model successfully identifies the best‐performing AP for biofilm inhibition at the triple interface.

Evolutionary engineering and chemical mutagenesis of Propionibacterium acidipropionici for improved propionic acid production from sugarcane-derived saccharides

Propionic acid (PA) is a 3-carbon carboxylic acid widely used in the chemical, food and pharmaceutical industries. Current production of PA is primarily via petrochemical routes and alternative sources using renewable feedstocks are desirable. The goal of the present study was to develop bacterial strains for efficient PA production by fermentation of sugarcane-derived saccharides in inverted sugarcane syrup. Adaptive evolution and random chemical mutagenesis of Propionibacterium acidipropionici were individually evaluated. Although evolutionary engineering proved to be a suitable strategy for producing strains tolerant to acid stress, chemical mutagenesis coupled with a novel screening methodology proved to be a superior strategy for strain improvement. The selected strain presented high PA productivity (0.55 g L−1 h−1) and titer (40 g L−1) in relation to the parental strain (0.38 g L−1 h−1 and 27 g L−1, respectively), in fermentations using inverted sugarcane syrup.

Productivity, selectivity performances and fouling control of brewery wastewater micro-ultrafiltration through operation optimization and membrane screening

A brewery wastewater was identified as phenolics-rich stream, representative of agro-food wastewaters. This latter can be used to develop a more sustainable brewery industry by recovering bioactive molecules and reusing water. Seven ceramic (TiO2-ZrO2) and organic (PVDF and PES) membranes with cut-off ranging from 15 kDa to 0.2 μm were assessed for their brewery wastewater clarification capacity, which is a key step allowing high natural resource recovery with further downstream process. Six criteria were used to evaluate membrane productivity (permeate volume), selectivity (turbidity and carbohydrates removal, phenolic compounds preservation) and robustness (inclination to fouling, ease of cleaning) at pH 4 and 10. Membranes with cut-off equal or larger than 0.1 μm were identified as improper due to high and irreversible fouling. With ultrafiltration membranes, pH 4 showed higher fouling propensity, due to reinforced fouling-causing molecules electrostatic interactions, than pH 10. Turbidity-causing compounds retention was higher than 83 %, phenolics were preserved with retention factors lower than 22 %. Carbohydrates retention was between 2 and 23 %. Therefore, through a screening methodology developed to meet a set of industrial requirements, the following classification of global performances is proposed: 15 kDa TiO2-ZrO2 > 70 kDa PVDF >150 kDa TiO2-ZrO2 > 50 kDa PES.

Study on Early Screening of Ganoderma Disease Susceptibility/Tolerance in Pre-nursery Pot-tray System - Part 1

This paper presents a methodology for early screening of Ganoderma disease susceptibility/tolerance in pre-nursery pot-tray system. The controllable parameters for the screening method were tested in the experiment to optimise the data collected and standardise the methodology prior to broadening the scale of testing. Evaluation of the disease was based on external symptoms and included destructive sampling to assess internal symptoms at the end of the trial. From the initial experiment, the effect of the rubberwood block (RWB) inoculum size was considered to be not significant in relation to the pot-tray size and the estimated medium inoculum size of 4.5 x 3 x 3 cm was selected. Subsequently, during the second experiment, through differentiation of resistance and tolerance as distinctly separate traits, the screening method was able to distinguish highly susceptible and less susceptible progenies. Overall, the pot-tray screening method seems adequate in allowing breeders and researchers to characterise the planting material’s response towards Ganoderma infection. Keywords: Ganoderma disease, basal stem rot, early screening, pre-nursery, pot-tray

A simple method for direct mercury analysis in dried blood spots (DBS) samples for human biomonitoring studies

Human exposure to mercury can have serious health effects, especially in vulnerable groups such as children and fetuses. The use of dried blood spot (DBS) samples to collect capillary blood greatly facilitates sample collection and fieldwork, being a less invasive alternative to blood collection by venipuncture, needing a small volume of sample, and does not require specialized medical staff. Moreover, DBS sampling reduces logistical and financial barriers related to transport and storage of blood samples. We propose here a novel method to analyze total mercury in DBS samples in a Direct Mercury Analyzer (DMA) that allow the control of the volume of the DBS samples. This method has shown good results in terms of precision (<6% error), accuracy (<10% coefficient of variation) and recovery (75–106%). The applicability of the method in human biomonitoring (HBM) was demonstrated in a pilot study involving 41 adults aged 18–65. Mercury concentrations of DBS samples from capillary blood collected by finger prick (real DBS samples) were determined in the DMA and compared with those determined in whole blood (venous blood) by ICP-MS, the method usually used in HBM. The sampling procedure was also validated by comparison of real DBS samples and DBS generated artificially in the laboratory by depositing venous samples in cellulose cards (laboratory DBS). There were no statistically significant differences in the results obtained using both methodologies (DMA: Geometric Mean (confidence interval 95%) = 3.87 (3.12–4.79) µg/L; ICP-MS: Geometric Mean (confidence interval 95%) = 3.46 (2.80–4.27) µg/L). The proposed method is an excellent alternative to be applied in clinical settings as screening methodology for assessing mercury exposure in vulnerable groups, such us pregnant woman, babies and children.

Telemedicine remote multidisciplinary questionnaire screening as a tool for early detection of chronic non-communicable diseases

Chronic non-communicable diseases (CNID) are an important problem for health care worldwide. In this connection, there was a need to develop preventive measures aimed at their early detection and timely correction. Taking into account the available evidence base on the effectiveness of preventive measures to reduce risk factors of CNID, special attention should be paid to people with high risks of their development and patients with an already established diagnosis. To improve the quality of preventive medicine, it is necessary to consistently develop and implement modern technologies aimed at early detection of risk factors at all stages of human life using available tests. To date, remote screening is considered as one of the promising areas of telemedicine technologies, which can be successfully used during medical examinations, medical examinations, etc. We have developed a methodology for telemedicine multidisciplinary remote questionnaire screening of the adult population using a system of analysis of unstructured data for population monitoring of CNID. Our telemedicine program was tested based on the city polyclinic for the first stage of medical examination. Depending on the identified risk factors, it was found that patients with the greatest frequency are concerned about complaints from the endocrine, digestive, respiratory, cardiovascular systems and oncological alertness. The interim results of the study once again show that the transition to new social conditions causes an active destabilization of the physical and psycho-emotional capabilities of the human body, which, under excessive loads, are able to increase the degree of activity of the CNID risk factors.

Empirically validated theoretical analysis of visual-spatial perception under change of nervous system arousal.

Visual-spatial perception is a process for extracting the spatial relationship between objects in the environment. The changes in visual-spatial perception due to factors such as the activity of the sympathetic nervous system (hyperactivation) or parasympathetic nervous system (hypoactivation) can affect the internal representation of the external visual-spatial world. We formulated a quantitative model of the modulation of visual-perceptual space under action by hyperactivation or hypoactivation-inducing neuromodulating agents. We showed a Hill equation based relationship between neuromodulator agent concentration and alteration of visual-spatial perception utilizing the metric tensor to quantify the visual space. We computed the dynamics of the psilocybin (hyperactivation-inducing agent) and chlorpromazine (hypoactivation-inducing agent) in brain tissue. Then, we validated our quantitative model by analyzing the findings of different independent behavioral studies where subjects were assessed for alterations in visual-spatial perception under the action of psilocybin and under chlorpromazine. To validate the neuronal correlates, we simulated the effect of the neuromodulating agent on the computational model of the grid-cell network, and also performed diffusion MRI-based tractography to find the neural tracts between the cortical areas involved: V2 and the entorhinal cortex. We applied our computational model to an experiment (where perceptual alterations were measured under psilocybin) and found that for n (Hill-coefficient) = 14.8 and k = 1.39, the theoretical prediction followed experimental observations very well (χ2 test robustly satisfied, p > 0.99). We predicted the outcome of another psilocybin-based experiment using these values (n = 14.8 and k = 1.39), whereby our prediction and experimental outcomes were well corroborated. Furthermore, we found that also under hypoactivation (chlorpromazine), the modulation of the visual-spatial perception follows our model. Moreover, we found neural tracts between the area V2 and entorhinal cortex, thus providing a possible brain network responsible for encoding visual-spatial perception. Thence, we simulated the altered grid-cell network activity, which was also found to follow the Hill equation. We developed a computational model of visuospatial perceptual alterations under altered neural sympathetic/parasympathetic tone. We validated our model using analysis of behavioral studies, neuroimaging assessment, and neurocomputational evaluation. Our quantitative approach may be probed as a potential behavioral screening and monitoring methodology in neuropsychology to analyze perceptual misjudgment and mishaps by highly stressed workers.

Phenotypic Screens Identify Genetic Factors Associated with Gametocyte Development in the Human Malaria Parasite Plasmodium falciparum.

Transmission of the deadly malaria parasite Plasmodium falciparum from humans to mosquitoes is achieved by specialized intraerythrocytic sexual forms called gametocytes. Though the crucial regulatory mechanisms leading to gametocyte commitment have recently come to light, networks of genes that control sexual development remain to be elucidated. Here, we report a pooled-mutant screen to identify genes associated with gametocyte development in P. falciparum. Our results categorized genes that modulate gametocyte progression as hypoproducers or hyperproducers of gametocytes, and the in-depth analysis of individual clones confirmed phenotypes in sexual commitment rates and putative functions in gametocyte development. We present a new set of genes that have not been implicated in gametocytogenesis before and demonstrate the potential of forward genetic screens in isolating genes impacting parasite sexual biology, an exciting step toward the discovery of new antimalarials for a globally significant pathogen. IMPORTANCE Blocking human-to-vector transmission is an essential step toward malaria elimination. Gametocytes are solely responsible for achieving this transmission and represent an opportunity for therapeutic intervention. While these falciform-shaped parasite stages were first discovered in the 1880s, our understanding of the genetic determinants responsible for their formation and molecular mechanisms that drive their development is limited. In this work, we developed a scalable screening methodology with piggyBac mutants to identify genes that influence the development of gametocytes in the most lethal human malaria parasite, P. falciparum. By doing so, we lay the foundation for large-scale functional genomic studies specifically designed to address remaining questions about sexual commitment, maturation, and mosquito infection in P. falciparum. Such functional genetic screens will serve to expedite the identification of essential pathways and processes for the development of novel transmission-blocking agents.

Newborn hearing screening methodology impacts the timing of diagnosis for auditory neuropathy spectrum disorder

IntroductionAuditory Neuropathy Spectrum Disorder (ANSD) accounts for 10 % to 15 % of pediatric hearing loss. In most cases, otoacoustic emissions (OAE) are present as the outer hair cell function is normal, and the auditory brainstem response (ABR) is abnormal. Newborn hearing screen (NBHS) is completed using OAE or ABR depending on the institution. Because OAEs are often present in ANSD, NBHS done solely with OAE can miss and delay diagnosis of patients with ANSD. ObjectivesTo assess whether NBHS methodology impacts the age of diagnosis of ANSD. MethodsThis is a retrospective study of patients, 0–18 years of age, diagnosed with ANSD at two tertiary pediatric hospitals from 1/01/2010 to 12/31/2018 after referral from NBHS performed in the community. Data recorded included patient demographics, method of NBHS, NICU stay, and age at ANSD diagnosis. Results264 patients were diagnosed with ANSD. Of those, 123 (46.6 %) were female, and 141 (53.4 %) were male. Ninety-seven (36.8 %) were admitted to NICU and the mean stay was 6.98 weeks (STD = 10.7; CI = 4.8–9.1). The majority (244, 92.4 %) of patients had NBHS with ABR, and 20 (7.5 %) had NBHS with OAE. Patients screened with ABR were diagnosed with ANSD earlier than those who screened with OAE, with a mean age of 14.1 versus 27.3 weeks (p = 0.0397, CI = 15.2–39.3). Among those screened with ABR, median age at diagnosis was 4 months for NICU infants and 2.5 months for infants with no history of NICU stay over 5 days. In comparison, median diagnosis age was 8 months for non-NICU infants screened with OAEs. ConclusionPatients with ANSD who had NBHS with ABR were diagnosed earlier than those with OAE. Our data suggest that universal screening with ABR may facilitate earlier diagnosis of ANSD and earlier evaluation for aural rehabilitation, especially in high-risk cohorts such as NICU patients. Further research is needed into factors that contribute to earlier diagnosis among patients screened with ABR.

Exploring the Supramolecular Interactions and Thermal Stability of Dapsone:Bipyridine Cocrystals by Combining Computational Chemistry with Experimentation.

The application of computational screening methodologies based on H-bond propensity scores, molecular complementarity, molecular electrostatic potentials, and crystal structure prediction has guided the discovery of novel cocrystals of dapsone and bipyridine (DDS:BIPY). The experimental screen, which included mechanochemical and slurry experiments as well as the contact preparation, resulted in four cocrystals, including the previously known DDS:4,4'-BIPY (2:1, CC44-B) cocrystal. To understand the factors governing the formation of the DDS:2,2'-BIPY polymorphs (1:1, CC22-A and CC22-B) and the two DDS:4,4'-BIPY cocrystal stoichiometries (1:1 and 2:1), different experimental conditions (such as the influence of solvent, grinding/stirring time, etc.) were tested and compared with the virtual screening results. The computationally generated (1:1) crystal energy landscapes had the experimental cocrystals as the lowest energy structures, although distinct cocrystal packings were observed for the similar coformers. H-bonding scores and molecular electrostatic potential maps correctly indicated cocrystallization of DDS and the BIPY isomers, with a higher likelihood for 4,4'-BIPY. The molecular conformation influenced the molecular complementarity results, predicting no cocrystallization for 2,2'-BIPY with DDS. The crystal structures of CC22-A and CC44-A were solved from powder X-ray diffraction data. All four cocrystals were fully characterized by a range of analytical techniques, including powder X-ray diffraction, infrared spectroscopy, hot-stage microscopy, thermogravimetric analysis, and differential scanning calorimetry. The two DDS:2,2'-BIPY polymorphs are enantiotropically related, with form B being the stable polymorph at room temperature (RT) and form A being the higher temperature form. Form B is metastable but kinetically stable at RT. The two DDS:4,4'-BIPY cocrystals are stable at room conditions; however, at higher temperatures, CC44-A transforms to CC44-B. The cocrystal formation enthalpy order, derived from the lattice energies, was calculated as follows: CC44-B > CC44-A > CC22-A.

Proposal to expand the definition of intrauterine growth restriction and introduce two new screening methods

The authors of this publication have developed a new screening method to evaluate the physical development of infants, which identifies growth and developmental restrictions based on their gestational age, gender, weight and length standard positions and nourishment status. This so-called MDN-method (MDN = Maturity, Development, Nourishment) offers several benefits: 1. It enables the expansion of the scope and definition of intrauterine growth restriction (IUGR) and the establishment of five separate condition subtypes. 2. It facilitates the study of the risk of mortality of infants based on their development and nourishment status. 3. The method is suitable for the screening of high-risk IUGR infants and neonates. 4. The MDN method allowed for the development of a new ultrasound screening methodology for high-risk IUGR infants and neonates, based on abdominal circumference (AC) and femur length (FL) standards, which correlate the most with the weight and length of the fetus. The data of 1,244,918 Hungarian live and stillbirths recorded during 2000-2012 were used for these studies. It is believed that these new screening methods may have a significant impact on reducing the frequency of IUGR-related stillbirth and infant mortality cases.

An unbiased AAV-STARR-seq screen revealing the enhancer activity map of genomic regions in the mouse brain in vivo

Enhancers are important cis-regulatory elements controlling cell-type specific expression patterns of genes. Furthermore, combinations of enhancers and minimal promoters are utilized to construct small, artificial promoters for gene delivery vectors. Large-scale functional screening methodology to construct genomic maps of enhancer activities has been successfully established in cultured cell lines, however, not yet applied to terminally differentiated cells and tissues in a living animal. Here, we transposed the Self-Transcribing Active Regulatory Region Sequencing (STARR-seq) technique to the mouse brain using adeno-associated-viruses (AAV) for the delivery of a highly complex screening library tiling entire genomic regions and covering in total 3 Mb of the mouse genome. We identified 483 sequences with enhancer activity, including sequences that were not predicted by DNA accessibility or histone marks. Characterizing the expression patterns of fluorescent reporters controlled by nine candidate sequences, we observed differential expression patterns also in sparse cell types. Together, our study provides an entry point for the unbiased study of enhancer activities in organisms during health and disease.

Awareness of Cervical Cancer Screening Amongst Pakistani Medical Students and Doctors; A Systematic Review

Background Cervical cancer screening is one of the most important public health interventions for cervical cancer prevention, yet awareness among Pakistani medical students and doctors is alarmingly low. Objective: to provide an in-depth understanding of the awareness and attitudes of Pakistani medical students and doctors towards cervical cancer screening Methodology: A systematic review of the literature was conducted, and qualitative and quantitative findings from studies conducted between January 2010 and June 2022 were synthesized. Results: The research found that Pakistani medical students and doctors have limited knowledge of cervical cancer and cervical cancer screening and a generally negative attitude towards cervical cancer screening. The paper also identified numerous influencing factors that contribute to the low awareness and attitudes towards the screening, such as traditional cultural beliefs, lack of training and education, and limited access to health care services. Conclusion, the research found a desperate need for interventions to raise awareness and to create an environment of acceptance and support for cervical cancer screening among Pakistani medical students and doctors. Keywords: Cervical Cancer, Screening, Pakistani Medical Students and Doctors, Knowledge, Pap smear, Human Papilloma Virus (HPV)

Poly-arginine/graphene oxide functionalized disposable sensor for monitoring fenitrothion pesticide residues in water and cucumber samples

The demand for the development of fast, reliable, and cost-effective screening methodologies for pesticide residues is critical. To meet the requirements of on-site monitoring purposes, electrochemical sensors are superior tools. Herein, this work describes the fabrication of a facile, disposable, easy-to-use, and enzymeless sensor platform for the determination of an organophosphorus pesticide, fenitrothion (FNT), in real samples. In this sense, electrosynthesis of poly-arginine (p(Arg)) on graphene oxide (GO) functionalized disposable sensor and its utilization for the voltammetric detection FNT were evaluated for the first time. p(Arg) film was grown onto GO-modified pencil graphite electrode by employing easy, practical, and an eco-friendly electro-polymerization route via cyclic voltammetry using electroactive groups in arginine structure. The p(Arg)-supported GO nanocomposite was further characterized using spectroscopic, microscopic, and electrochemical analyzes. The fabricated (p(Arg)-GO)-based sensor was applied as a recognition element to acquire the direct quantitative electroanalysis of FNT by monitoring its irreversible reduction peak. The combination of p(Arg) and GO led to high affinity, therefore, synergistically contributed to an electrocatalytic effect toward FNT detection in the presence of some interferents. Square wave voltammetry allowed rapid response to reach a linear calibration range as 0.69–20.2 μM for FNT detection under the optimum conditions and the limit of detection was estimated as 0.173 μM. Finally, the assessment of the suggested non-enzymatic electrochemical nanosensor for cucumber and water samples displayed attractive practical ability with satisfactory recovery results making the method useful for the determination of FNT in real matrices. Such p(Arg)-GO-based sensing platform holds considerable promise toward on-site determination of pesticides as a portable decentralized testing system.

Design of high-performance ion-doped CoP systems for hydrogen evolution: From multi-level screening calculations to experiment

Rational design of high-performance electrocatalysts for hydrogen evolution reaction (HER) is vital for future renewable energy systems. The incorporation of foreign metal ions into catalysts can be an effective approach to optimize its performance. However, there is a lack of systematic theoretical studies to reveal the quantitative relationships at the electronic level. Here, we develop a multi-level screening methodology to search for highly stable and active dopants for CoP catalysts. The density functional theory (DFT) calculations and symbolic regression (SR) were performed to investigate the relationship between the adsorption free energy (ΔGH*) and 10 electronic parameters. The mathematic formulas derived from SR indicate that the difference of work function (ΔΦ) between doped metal and the acceptor plays the most important role in regulating ΔGH*, followed by the d-band center (d-BC) of doped system. The descriptor of HER can be expressed as ΔGH∗=1.59×0.188ΔΦ+dBC+0.120-0.166 with a high determination coefficient (R2 = 0.807). Consistent with the theoretical prediction, experimental results show that the Al-CoP delivers superior electrocatalytic HER activity with a low overpotential of 75 mV to drive a current density of 10 mA cm−2, while the overpotentials for undoped CoP, Mo-CoP, and V-CoP are 206, 134, and 83 mV, respectively. The current work proves that the ΔΦ is the most significant regulatory parameter of ΔGH* for ion-doped electrocatalysts. This finding can drive the discovery of high-performance ion-doped electrocatalysts, which is crucial for electrocatalytic water splitting.

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study

Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy13. This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

High-Throughput Screening for the Potential Inhibitors of SARS-CoV-2 with Essential Dynamic Behavior.

Global health security has been challenged by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Due to the lengthy process of generating vaccinations, it is vital to reposition currently available drugs in order to relieve anti-epidemic tensions and accelerate the development of therapies for Coronavirus Disease 2019 (COVID-19), the public threat caused by SARS-CoV-2. High throughput screening techniques have established their roles in the evaluation of already available medications and the search for novel potential agents with desirable chemical space and more cost-effectiveness. Here, we present the architectural aspects of highthroughput screening for SARS-CoV-2 inhibitors, especially three generations of virtual screening methodologies with structural dynamics: ligand-based screening, receptor-based screening, and machine learning (ML)-based scoring functions (SFs). By outlining the benefits and drawbacks, we hope that researchers will be motivated to adopt these methods in the development of novel anti- SARS-CoV-2 agents.