Selective Screening Research Articles

HTLV screening of blood donations in England between 2002 and 2021 - Comparison of screening strategies.

HTLV is associated with adult T-cell leukaemia/lymphoma and myelopathy. Here we present virological and epidemiological data on HTLV screening of blood donations in England between 2002 and 2021, implemented to prevent its transmission via blood transfusion. Data on HTLV testing of blood donations was reviewed; it was initially conducted in pools (2002-2012) and subsequently using individual samples (all donors, 2013-2016; first-time donors and non-leucodepleted component donors, 2017-2021). Data included annual number of donations screened, initial and repeat reactives as well as confirmed positives. Further information, such as likely source of infection, was obtained for HTLV-positives. Over the 20-year study period, a total of 30,679,741 blood donations were screened for HTLV in England. Under pooled screening strategy, the annual rate of repeat reactive donations remained <5:100,000. However, this rate increased to 51:100,000 with individual screening and further to 123:100,000 with selective screening. A total of 5032 samples were repeat reactive, of which 278 were confirmed HTLV-positives. Although the specificity under each scenario exceeded 99.9%, the rate of repeat reactives was around 50-fold higher in individual compared to pooled screening. Most HTLV infected were UK-born, most likely acquired their infection unknowingly through breast feeding or heterosexual intercourse with an individual associated with an HTLV-endemic country. These data highlight that pooled testing can be advantageous in low-prevalence settings due to its high specificity and reduced non-specific reactivity. Whether pooling is an applicable strategy to tackle the burden of HTLV infection in resource poor, HTLV-endemic countries requires further investigations.

Development and implementation of a digiphysical screening model with nationwide reach to diagnose familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a hereditary dyslipidemia that confers a severely elevated risk for development of early atherosclerotic cardiovascular disease if left untreated. FH is underdiagnosed in most countries including Sweden. To develop and evaluate the implementation of a digiphysical screening model to diagnose FH in the clinical routine. A digiphysical screening model for FH, containing digital and physical related activities was developed and fully implemented in routine clinical care in the Stockholm region, Sweden 2022. The centerpiece of the model is a tailormade interactive web-based platform designed to facilitate communication and secure medical information exchange between its participants and the healthcare professionals. The screening model includes, (i) cascade screening of relatives to patients with a confirmed FH diagnosis and (ii) systematic selective screening of patients with established atherosclerotic coronary artery disease. Until October 2023, 338 index patients were included in the cascade screening. They invited 954 relatives nationwide, 616 (64.6%) accepted participation, 346 (36.3%) were completely screened, and 141 (14.8%) have received a FH diagnosis (40.8% of all completely screened). Selective screening was performed in 2867 patients with coronary artery disease, 355 (12.4%) were identified with increased risk for FH and underwent a genetic test. Of these, 153 (3.8%) had a genetic test result and 52 (1.8%) were diagnosed with FH. A digiphysical screening model with a nationwide reach to diagnose FH was successfully implemented in routine clinical care. The model has potential to facilitate FH screening and provide health economic benefits long term.

Carotid Ultrasound Assessment prior to Coronary Artery Bypass Grafting – an Irish Cardiac Surgery Centre’s Experience

IntroductionCarotid stenosis is a risk factor for cerebrovascular accident(CVA) following coronary artery bypass grafting(CABG). Guidelines recommend selective pre-operative screening with Doppler US but non-selective application is commonplace. Recent data has questioned the efficacy of peri-operative carotid intervention, challenging the value of this practice. AimTo analyse the utility of carotid US assessment prior to CABG in our institution. MethodsThis was a retrospective review of all patients over 18 that underwent a non-emergency CABG in a single Irish cardiac surgery centre from January 2019 to December 2022. Results1161 subjects were included. 1084/1161(93.36%) underwent US assessment. 41/1084(3.8%) had ≥70% stenosis and 189/1084(17.5%) had ≥50% stenosis. 32/1084(2.95%) underwent confirmatory imaging and 7/1084(0.64%) underwent carotid intervention. Post-operative CVA occurred in 18/1161(1.55%) and ≥70%(p=0.024) and ≥50%(p<0.001) carotid stenosis were associated with same.Chronic kidney disease (OR=1.66,p=0.01), decreasing haemoglobin (OR=1.13,p=0.019), increasing age (OR=1.03,p=0.011) and being a current (OR=3.21,p<0.001) or ex- smoker (OR=1.82,p=0.004) were risk factors for ≥50% carotid stenosis on logistic regression. Multivessel coronary artery disease was not associated with carotid stenosis (p=0.563).Of those that underwent carotid intervention, 0/7(0%) suffered a CVA, but this protective effect failed to reach statistical significance for those with ≥70%(p=1) or ≥50%(p=1) carotid stenosis. ConclusionCarotid US screening altered the management of only a small proportion of CABG patients despite near universal application, challenging the effectiveness of this practice. Multivessel coronary artery disease was not associated with carotid stenosis despite European guidelines listing it as a screening criteria. Predictive models must be developed using identified risk factors to enable targeted pre-operative screening.

Prevalence and predictive risk factors of hypertensive disorders in pregnant women at high risk for gestational diabetes. The PREeclampsia in DIabetiC gestaTION (PREDICTION) study.

Women with gestational diabetes (GDM) have increased risk of hypertensive disorders in pregnancy (HDP). However, knowledge remains limited for women with high-risk metabolic profiles, regardless of GDM diagnosis. This study aimed to evaluate the prevalence of HDP among women at high risk for GDM, while simultaneously identifying potential predictive clinical risk factors of HDP. Pregnant women who performed a 75-gr Oral Glucose Tolerance Test for the selective screening (based on pre-pregnancy risk factors) of GDM were prospectively enrolled (October 2019-June 2022). The development of HDPwas assessed. Logistic regression and ROC-curve analysis were used to identify predictive risk factors for HDP. Of the 398 women enrolled (53.5% with GDM), 30 (8%) developed HDP. Women developing HDP had more frequently a family history of type 2 diabetes, a personal history of GDM or preeclampsia, and showed higher pregestational BMI and first-trimester fasting plasma glucose. Moreover, at GDM screening, they had higher fasting and 1-hour glucose levels, and higher systolic and diastolic blood pressure. At logistic regression, systolic and diastolic blood pressure were the strongest risk factors for HDP. The risk increased for systolic blood pressure ≥ 127 mmHg (61% sensitivity, 86% specificity, PPV:27%, NPV:86%) and diastolic blood pressure ≥ 82 mmHg (57% sensitivity, 92% specificity, PPV:38%, NPV:96%). Women at high risk for GDM with poor metabolic profile have higher prevalence of HDP. Systolic and diastolic blood pressure at the time of GDM screening may identify women with higher risk of developing HDP, regardless of GDM diagnosis.

P-175. Assessing the Dynamics of Fecal Colonization with Antibiotic-Resistant Bacteria in a Chilean Cohort: A Longitudinal Study

Abstract Background In low- and middle-income countries, the community burden of antibiotic-resistant Gram-negative bacteria (AR-GNB) colonization is high. Understanding factors influencing AR-GNB colonization is crucial for controlling antimicrobial resistance. Methods We conducted a cohort study from December 2019 to November 2020 with community-dwelling adults in Molina, an agricultural town in Central Chile. We collected questionnaires and fecal samples every two weeks for six months to identify colonization by extended-spectrum cephalosporin-resistant Enterobacterales (ESCRE). ESCRE detection involved selective media screening, MALDI-TOF identification, and disk-diffusion antibiotic-susceptibility testing. We assessed the impact of epidemiological and clinical features and exposure to various water sources, foods, and animals on i) baseline ESCRE fecal colonization, ii) ESCRE acquisition during follow-up, and iii) ESCRE clearance. The study included 198 subjects, using multiple imputations for missing predictor values. We used two hidden Markov models for each dataset, with Model 1 assuming perfect sensitivity and specificity and Model 2 estimating sensitivity. A Bayesian approach with Markov chain Monte Carlo algorithms estimated odds ratios (OR) and credible intervals (CI). Results The sample consisted of 198 residents with a mean age of 60.9 and a predominance of women (75%). Model 1 showed that treating drinking water before consumption reduced the risk of baseline ESCRE colonization (OR: 0.38; 95% CI: 0.02 – 0.89). No significant associations were found for ESCRE acquisition during follow-up. Males and individuals with comorbidities had a lower risk of clearing ESCRE (ORs: 0.58, 0.54; CIs: 0.24 – 0.97, 0.258 – 0.88, respectively). Model 2, with imperfect sensitivity, showed similar results. Conclusion This study highlights the significance of environmental and individual health factors in ESCRE colonization. Interventions like treating drinking water could reduce baseline ESCRE colonization risk. The varied impacts of gender and comorbidities on ESCRE clearance provide insights for targeted AR-GNB management strategies. Further research is needed to understand these associations and develop effective community-level interventions against AMR. Disclosures All Authors: No reported disclosures

P-1008. Congenital Cytomegalovirus Infection Screening in the Newborn Nursery: Areas for Improvement in the Absence of Standardized Guidelines

Abstract Background Cytomegalovirus (CMV) is the most common viral cause of congenital defects in the U.S. Early identification of congenital CMV (cCMV) infection allows for optimal antiviral treatment which reduces progression of sensorineural hearing loss and improves neurodevelopmental outcomes. There is varying guidance from expert consensus groups ranging from universal screening to selective screening based on clinical features. With conflicting data, many hospitals have no standardized protocol for cCMV screening. This study aims to detail clinical characteristics and outcomes of infants with cCMV in a tertiary medical center prior to implementation of standardized guidelines. Methods This was a retrospective case study of newborns who screened positive for CMV between June 2017-July 2022 at Rainbow Babies &amp; Children’s Hospital in Cleveland, Ohio. 1900 newborns less than 21 days old were tested for CMV during this period, and newborns who screened positive for CMV were included (n=18). Clinical characteristics of the patients were described using median and interquartile range for continuous variables and frequency and percentages for categorical variables. Results The prevalence rate of cCMV at our center is 9.5 per 1000 live births. The most common associated clinical features were small for gestational age (SGA; n=12), microcephaly (n=9), abnormal neuroimaging findings (n=6), and failed newborn hearing screen (n=4). Two patients had isolated SGA, and neither received treatment nor had clinical sequelae. Saliva PCR tests were used for screening with no confirmatory urine testing. 11 patients received oral valganciclovir with documented side effects of transient neutropenia and transaminitis. 33% of newborns had no infectious disease or audiology follow-up. Conclusion Targeted screening practices for cCMV infection in our institution varies between providers. Our center has a prevalence rate slightly above the national average; however, the yield of screening isolated SGA is shown to be low. This study highlights gaps in current cCMV screening including lack of confirmatory urine CMV testing, and infants lost to follow up. System-level interventions including creation of standardized guidelines and provider education are necessary to improve follow-up and outcomes. Disclosures All Authors: No reported disclosures

Triggered "On/off" Luminescent Polypeptide Bowl-Shaped Nanoparticles for Selective Lighting of Tumor Cells.

Functional polymeric nanoparticles, especially those with anisotropic structures, have shown significant potential and advantages in biomedical applications including detecting, bioimaging, antimicrobial and anticancer. Herein, tetraphenylethylene (TPE) and azobenzene modified polypeptides of poly((L-glutamic acid) tetraphenylethylene-stat-(L-glutamic acid)) (P(GATPE9-stat-GA25)) and poly((L-glutamic acid) azobenzene-stat-(L-glutamic acid)) (P(GAAzo5-stat-GA29) are synthesized, which self-assemble into bowl-shaped nanoparticles (BNPs) with controlled diameter, opening size and fluorescent property individually, or by co-assembly. Due to the quenching effect of azobenzene, the fluorescence of the coassembled BNPs is completely inhibited. Upon incubated under reduction environment, the fluorescence of the BNPs is re-excited owing to the reduction or break of azo bonds. Benefiting from the high-level azo reductase in hypoxic liver cancer cells comparing to normal liver cells, the quenched BNPs exhibit pronounced fluorescence signal in human hepatoma (HepG2) cells under hypoxic condition, demonstrating the high efficiency of the reduction-responsive luminescent BNPs for selective screening of tumor cells. In addition, it is also found that a proper opening size promotes the cellular uptake of the BNPs even with size up to micron. Overall, this study provides a fresh perspective in the controlled preparation of anisotropic polymeric nanoparticles and high efficient cancer cell screening.

A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbs

BackgroundCutaneous hypertrophic scar is a fibro-proliferative hard-curing disease. Recent studies have proved that antagonists of angiotensin II type 1 receptor (AT1R) and agonists of type 2 receptor (AT2R) were able to relieve hypertrophic scar. Therefore, establishing new methods to pursue dual-target lead compounds from Chinese herbs is in much demand for treating scar.MethodsTo this end, we immobilized AT1R or AT2R onto the surface of silica gel from cell lysates through a specific covalent bond by bioorthogonal chemistry. The columns containing immobilized AT1R or AT2R were jointly utilized to pursue potential bioactive compounds simultaneously binding to AT1R and AT2R from the extract of Rhei Radix et Rhizoma. Their functions on AT1R and AT2R expressions were investigated by in vitro and in vivo experiments.ResultsAloe-emodin and emodin were identified as the potential bioactive compounds binding to both of the two receptors, thereby improving the appearance and pathomorphology of hypertrophic scar. They blocked the AT1R pathway to down-regulate the expression of transforming growth factor-β1 (TGF-β1) and stimulate matrix metalloproteinase-1 (MMP-1) expression. As such, the expression of collagen I/III reduced. Conversely, the bindings of the two compounds to AT2R reduced the production of nuclear factor-кB1 (NF-кB1), whereby the generation of interleukin-6 (IL-6) was blocked.ConclusionWe reasoned that aloe-emodin and emodin had the potential to become dual-target candidates against hypertrophic scar through the regulation of AT1R and AT2R signaling pathways. It showed considerable potential to become a universal strategy for pursuing multi-target bioactive compounds from Chinese herbs by the utilization of diverse immobilized receptors in a desired order.

Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023

BackgroundCerebral creatine deficiency disorders (CCDD) are rare diseases caused by defects in the enzymes L-arginine: glycine amidinotransferase (AGAT) or guanidinoacetate-N-methyltransferase (GAMT), which are involved in synthesis of creatine; or by a defect in the creatine transporter (CRTR), which is essential for uptake of creatine as important energy source into the target cells. Patients with CCDD can present with a variety of unspecific symptoms: global developmental delay, speech-language disorder, behavioral abnormalities and seizures. Early treatment initiation is essential in AGAT and GAMT deficiencies to achieve a favorable outcome. This study describes the CCDD patient cohort in a single center, and an analysis of the referrals to two Swiss laboratories in Lausanne and Zurich between 2015 and 2023 for the two marker metabolites guanidinoacetate and creatine.ResultsThe patient cohort comprised 6 patients (defects: 2 GAMT, 4 CRTR), who were initially seen by different subspecialties depending on first symptoms. There was a diagnostic and therapeutic delay between 3 and 32 months (mean 13.8). Numbers of biomarker requests showed a constant increase during the study period, with a majority of tests performed in urine, the preferred sample for CCDD detection. Almost all samples (93.3%) were sent in by large hospitals (mainly from neurology, developmental pediatrics and metabolism) and only few (5.2%) by pediatricians in private practice, although those usually see the patients first.ConclusionsThe data from this study demonstrate a relevant delay in identifying patients with these rare conditions, and a predominance of biomarker analysis requested from pediatric subspecialties that are involved in patient management often long after occurrence of symptoms. To reduce the diagnostic delay and the outcome of patients, the current practice of sample referral should be reflected and first-contact healthcare providers should be encouraged to initiate selective screening.

Cell clone selection-impact of operation modes and medium exchange strategies on clone ranking.

Bioprocessing has been transitioning from batch to continuous processes. As a result, a considerable amount of resource was dedicated to optimising strategies for continuous production. However, the focus has been on developing a suitable and scalable perfusion strategy with little attention given to the selection of optimal cell clones. Cell line development and lead clone selection are critical to bioprocess development. The screening and selection process is typically performed in stages. Microwell plates (MWP) are used to narrow down the number of clone candidates, which will undergo further selective screening in progressively larger small-scale bioreactors (12mL-3L) to identify the top clone for GMP production. Perfusion mode is typically applied at bench-scale for optimisation purposes, while process development and cell clone screening studies at mL-scale still commonly use fed-batch methods. The change of operation mode from bolus feeding to perfusion with a regular exchange of medium, leads to questions regarding the reliability and fit of initial clone selection. Is the early-stage clone ranking impacted by the discrepancy in the operation mode, and does this potentially result in the exclusion of cell clones suitable for perfusion processes? To address this question, we evaluated various CHO cell clones expressing two antibody products using MWP methodologies in fed-batch and semi-perfusion mode. We assessed growth, metabolic, and productivity performance, and ranked cell clones using two different strategies. The first strategy evaluated clones based on a single parameter: the cell-specific productivity (qP). The second considered a collection of multiple parameters using the metric of the Manufacturability index (MICL). Both ranking strategies showed an impact of operation mode and perfusion rate on the clone ranking. Notably, depending on the chosen operation mode, different sets of candidate clones might have been selected for further, more extensive screening. Additionally, we evaluated the reproducibility of our results demonstrating consistency in cell clone growth performance and ranking.

Umbrella review of economic evaluations of interventions for the prevention and management of healthcare-associated infections in adult hospital patients.

Healthcare-associated infections result in worse outcomes for patients and greater financial burden. An estimated 4.8 million HCAIs occurred in hospitals across Europe in 2022-23. Sixty-four percent of antibiotic-resistant infections in Europe are associated with healthcare. It is therefore vital to identify cost-effective interventions. Our objective was to summarise the cost-effectiveness evidence of interventions addressing HCAIs in hospitals. An umbrella review was conducted to identify evidence on the cost-effectiveness of antimicrobial stewardship, infection prevention and control, and microbiology and diagnostic stewardship interventions for the prevention and clinical management of HCAIs in adult hospital patients. Medline, Embase and EconLit databases were searched. A qualitative synthesis was undertaken. Twenty-four systematic reviews met the inclusion criteria, with 101 separate analyses extracted and grouped into 10 intervention and 14 infection/organism categories, across various countries and settings. Most evidence focussed on screening followed by contact precautions, isolation and/or decolonisation, with selective screening most cost-effective. Most IPC bundles were cost-effective, although interventions were heterogeneous. The evidence base was sparse for the remaining intervention categories, with more research required. The limited evidence suggests standalone environmental cleaning, hand hygiene, diagnostics, surveillance, ABS, and decolonisation interventions were mostly cost-effective. The cost-effectiveness of standalone personal protective equipment, and education and training interventions was mixed. Most interventions focussed on methicillin-resistant Staphylococcus aureus and other Gram-positive infections, with more research needed on Gram-negative infections. The comparator was unclear in many extracted analyses. Cost-effective interventions to address HCAIs in hospitals exist, although more evidence is needed for most interventions.

Femoral Head Pathology in Subcapital Hip Fractures: Clinical Value and Cost-Effectiveness in a 230-Patient Case Series.

Background/Objectives: Osteoporotic fractures, particularly subcapital hip fractures (SCF), pose a significant healthcare and economic burden. The routine pathological examination of resected femoral heads in such cases is common practice, aimed at identifying malignancies that may have contributed to bone fragility. This study evaluated the cost-effectiveness and clinical utility of routine femoral head pathology in patients undergoing surgical treatment for SCF. Methods: A retrospective cohort study was conducted at a university-affiliated, tertiary care hospital. Patients undergoing surgical treatment for SCF between 2015 and 2018, with available femoral head pathology reports, were included. Data on demographics, prior or active malignancies, surgical procedures, and pathology results were analyzed. Results: The study included 230 patients with a mean age of 82.4 ± 14.1 years, of whom 57% were female. A total of 72 (31%) patients had a history of malignancy at the time of surgery. Pathological examination identified malignancies in eight patients (3.4%), all of whom had active malignancies at the time of admission. The most common malignancies detected were breast cancer and multiple myeloma (three cases each). None of the findings led to changes in patient management. Conclusions: The routine pathological examination of femoral heads following SCF provided a limited diagnostic yield and did not alter clinical management in this cohort. These findings suggest that routine pathology may not be cost-effective and support the adoption of selective screening approaches based on clinical risk factors such as a history of malignancy or atypical fracture presentations.

Discovery of Human PIM Kinase Inhibitors as a Class of Anthelmintic Drugs to Treat Intestinal Nematode Infections.

Soil-transmitted helminth (STH) infections affect one-fourth of the global population and pose a significant threat to human and animal health, with limited treatment options and emerging drug resistance. Trichuris trichiura (whipworm) stands out as a neglected disease, necessitating new drugs to address this unmet medical need. We discovered that several different chemical series of related human Provirus Integration sites for Moloney murine leukemia virus (PIM) family kinase inhibitors possess potent anthelmintic activity by using whole-worm motility assays. Systematic structure-activity relationship (SAR) studies based on the pan-PIM kinase inhibitor CX-6258 were conducted to identify compounds displaying improved in vitro motility inhibition of both adult hookworm (Ancylostoma ceylanicum) and adult whipworm (Trichuris muris) nematodes. A broad kinase selectivity screen of >450 human kinases confirms PIM1 kinase and others as potential targets for CX-6258 and analogues thereof. In addition, we demonstrated that CX-6258 significantly reduced worm burden and egg counts in the T. muris infection model of mice, establishing it as a new oral small molecule anthelmintic therapeutic.

Normalized Protein-Ligand Distance Likelihood Score for End-to-End Blind Docking and Virtual Screening.

Molecular Docking is a critical task in structure-based virtual screening. Recent advancements have showcased the efficacy of diffusion-based generative models for blind docking tasks. However, these models do not inherently estimate protein-ligand binding strength thus cannot be directly applied to virtual screening tasks. Protein-ligand scoring functions serve as fast and approximate computational methods to evaluate the binding strength between the protein and ligand. In this work, we introduce normalized mixture density network (NMDN) score, a deep learning (DL)-based scoring function learning the probability density distribution of distances between protein residues and ligand atoms. The NMDN score addresses limitations observed in existing DL scoring functions and performs robustly in both pose selection and virtual screening tasks. Additionally, we incorporate an interaction module to predict the experimental binding affinity score to fully utilize the learned protein and ligand representations. Finally, we present an end-to-end blind docking and virtual screening protocol named DiffDock-NMDN. For each protein-ligand pair, we employ DiffDock to sample multiple poses, followed by utilizing the NMDN score to select the optimal binding pose, and estimating the binding affinity using scoring functions. Our protocol achieves an average enrichment factor of 4.96 on the LIT-PCBA data set, proving effective in real-world drug discovery scenarios where binder information is limited. This work not only presents a robust DL-based scoring function with superior pose selection and virtual screening capabilities but also offers a blind docking protocol and benchmarks to guide future scoring function development.

Single-plate kinome screening in live-cells to enable highly cost-efficient kinase inhibitor profiling.

Cancer research, cancer treatment, and the field of chemical biology are examples which heavily rely on the discovery of selective kinase inhibitors. While determining on-target potency is often feasible for most laboratories, the equally critical but frequently neglected selectivity screening remains less accessible to the broader scientific community. This limitation can stem from various factors, such as the unavailability of a large number of purified kinases or the costs associated with commercial screening systems. To address these challenges and enable a wider range of scientists, this protocol leverages a commercial kinome selectivity screen to facilitate a low-cost, two-day, single-plate selectivity screen against 192 kinases.

New public management as an extension of neoliberal ideology

Ideology is invisibly present in economics. Some schools of economic thought, such as Marxism or old institutional ism, admit the fact of researchers having their own value systems. However, proponents of neoliberal ideas insist on the positive and non-ideological nature of economic science. Denying neoliberalism’s ideological foundations affects socio-economic policy in regulating the public sector of the economy. The study aims to reveal the relationship between managerialism and neoliberal ideology. The foundation of research resides in the theory of new public management, old institutional economics theory, and approaches of narrative economics. The selection and full text screening of Russian-language scientific publications were carried out using narrative analysis and the PRISMA method. The evidence base covers an array of studies by Russian researchers on managerialism, new public management, and neoliberalism. The paper reveals that scholars predominantly view managerialism as a continuation of neoliberal ideology. We have traced the evolution of theoretical and practical aspects of neoliberalism, which can be classified as a loose concept subject to heavy criticism, and identified three additional types of neoliberalism specific to Russian economic science. The findings illustrate that the practical implementation of new public management shifts the focus from long-term strategic goals to short-term results.

The application value assessment of CRISPR in screening and optimizing bacteria for industrial production

CRISPR is a gene editing technology derived from bacteria and has been widely used in the current biological field. However, the use range of it is still mainly in laboratories. The industrial production field can rarely see its role, such as the screening and optimization of production strains. This article compares the advantages and disadvantages of CRISPR with traditional natural sampling or mutagenesis breeding combined with selective culture medium screening technology in actual production in technical and non-technical fields, emphasizing that CRISPR technology has great advantages in integrating excellent traits and improving breeding efficiency. However, it is still slightly inferior to traditional technology in terms of breeding costs, experimental conditions, and social acceptance. The significance of this study lies in a relatively comprehensive analysis of the various indicators worth comparing when CRISPR technology is actually applied to industrial breeding, which can provide a certain reference value for whether the technology should be officially put into industrial use. However, there are still many defects of CRISPR technology which is difficult to correct; although the direction of its improvement is fairly clear, its never easy to work, and the development will still need some time.

Unexplained Multi-Site Thrombosis: A Step-by-Step Strategy for Factor V Leiden Detection in a Hypercoagulable Patient

Thrombotic manifestations involve the development of blood clots within blood vessels. These conditions can occur unexpectedly in different areas and are often linked to life-threatening situations, presenting challenges for both diagnosis and treatment. We present a case of multi-site thrombosis in a patient with a confirmed hypercoagulable state, resulting from a positive factor V Leiden mutation. The patient’s medical history included hypertension, chronic obstructive pulmonary disease, previous thrombotic events, and changes in anticoagulant therapy. This case highlights the challenges associated with multisystem thrombosis and underscores the necessity of employing various diagnostic techniques, such as echocardiography, computed coronary angiography, and Doppler ultrasonography. In this instance, the patient presented with a history of unprovoked lower limb deep vein thrombosis and multiple arterial thromboses. The patient’s treatment regimen comprised anticoagulants, antiplatelet drugs, and vasodilators. While a reduction in thrombus size was noted, complete revascularization could not be attained. Effective diagnosis and treatment of venous and arterial thrombosis often require multimodal imaging. Selective blood test screening can be beneficial in diagnosing or detecting inherited or acquired abnormalities linked to thrombosis development.

Characterization of Enterobacterales growing on selective CPE screening plates with a focus on non-carbapenemase-producing strains.

Selective screening plates for carbapenemase-producing Enterobacterales (CPE) are used to detect CPE carriers for infection control purposes. We characterized non-CPE isolates that grew on selective CPE screening plates, which are intended to filter them out. We found that 60% of isolates that grew on these plates were not CPE. They included both meropenem-susceptible and meropenem-resistant isolates and were multidrug-resistant with multiple resistance mechanisms. These test results, which are usually not reported by laboratories, may be clinically valuable.

Top 100 most-cited articles on apoptosis of non-small cell lung cancer over the past two decades: a bibliometrics analysis.

Recently there has been an increasing number of studies have explored apoptosis mechanisms in lung cancer (LC). However, no researchers have conducted a bibliometric analysis of the most cited articles in this field. To examine the top 100 most influential and cited publications on apoptosis in non-small cell lung cancer (NSCLC) from 2004 to 2023, summarizing research trends and key focus areas. This study utilized the Web of Science Core Database (WOSCC) to research NSCLC apoptosis from 2004 to 2023, using keyword selection and manual screening for article searches. Bibliometrix package of R software 4.3.1 was used to generate distribution statistics for the top ten institutions, journals and authors. Citespace6.2. R6 was used to create the visualization maps for keyword co-occurrence and clustering. VOSviewer1.6.19 was used to conduct cluster analysis of publishing countries (regions), with data exported to SCImago Graphica for geographic visualization and cooperation analysis. VOSviewer1.6.19 was used to produced co-citation maps of institutions, journals, authors, and references. From 2004 to 2023, 13316 articles were retrieved, and the top 100 most cited were chosen. These were authored by 934 individuals from 269 institutions across 18 countries and appeared in 45 journals. Citations ranged from 150 to 1,389, with a median of 209.5. The most influential articles appeared in 2005 and 2007 (n=13). The leading countries (regions), institutions, journals and authors were identified as the United States (n=60), Harvard University (n=64), CANCER RESEARCH (n=15), SUN M and YANG JS (n=6). The top five keywords were "expression", "activation", "apoptosis", "pathway" and "gefitinib". This study indicates that enhancing apoptosis through circular RNA regulation and targeting the Nrf2 signaling pathway could become a key research focus in recent years. Apoptosis has been the subject of extensive research over many years, particularly in relation to its role in the pathogenesis, diagnosis, and treatment of NSCLC. This study aims to identify highly influential articles and forecast emerging research trends, thereby offering insights into novel therapeutic targets and strategies to overcome drug resistance. The findings are intended to serve as a valuable reference for scholars engaged in this field of study.