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1.
J Sports Sci ; : 1-12, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967313

RESUMEN

The number of runners and the incidence of running-related injuries (RRIs) are on the rise. Real-time biofeedback gait retraining offers a promising approach to RRIs prevention. However, due to the diversity in study designs and reported outcomes, there remains uncertainty regarding the efficacy of different forms of feedback on running gait biomechanics. Three databases: MEDLINE, PUBMED, and SPORTDiscus were searched to identify relevant studies published up to March 2024, yielding 4646 articles for review. The quality of the included studies was assessed using the Downs and Black Quality checklist. Primary outcomes, including Peak Tibial Acceleration (PTA), Vertical Average Loading Rate (VALR), and Vertical Instantaneous Loading Rate (VILR), were analysed through meta-analysis. 24 studies met the inclusion criteria and were analysed in this review.17 used visual biofeedback (VB) while 14 chose auditory biofeedback (AB). The meta-analysis revealed a reduction in loading variables both immediately following the intervention and after extended training, with both visual and auditory feedback. Notably, the decrease in loading variables was more pronounced post-training and VB proved to be more effective than AB. Real-time biofeedback interventions are effective in lowering loading variables associated with RRIs. The impact is more substantial with sustained training, and VB outperforms AB in terms of effectiveness.

4.
Theranostics ; 14(9): 3760-3776, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948060

RESUMEN

Rationale: Currently, there are occasional reports of health problems caused by sleep deprivation (SD). However, to date, there remains a lack of in-depth research regarding the effects of SD on the growth and development of oocytes in females. The present work aimed to investigate whether SD influences ovarian folliculogenesis in adolescent female mice. Methods: Using a dedicated device, SD conditions were established in 3-week old female mice (a critical stage of follicular development) for 6 weeks and gut microbiota and systemic metabolomics were analyzed. Analyses were related to parameters of folliculogenesis and reproductive performance of SD females. Results: We found that the gut microbiota and systemic metabolomics were severely altered in SD females and that these were associated with parameters of premature ovarian insufficiency (POI). These included increased granulosa cell apoptosis, reduced numbers of primordial follicles (PmFs), correlation with decreased AMH, E2, and increased LH in blood serum, and a parallel increased number of growing follicles and changes in protein expression compatible with PmF activation. SD also reduced oocyte maturation and reproductive performance. Notably, fecal microbial transplantation from SD females into normal females induced POI parameters in the latter while niacinamide (NAM) supplementation alleviated such symptoms in SD females. Conclusion: Gut microbiota and alterations in systemic metabolomics caused by SD induced POI features in juvenile females that could be counteracted with NAM supplementation.


Asunto(s)
Disbiosis , Microbioma Gastrointestinal , Metabolómica , Insuficiencia Ovárica Primaria , Privación de Sueño , Animales , Femenino , Insuficiencia Ovárica Primaria/metabolismo , Ratones , Disbiosis/microbiología , Disbiosis/metabolismo , Metabolómica/métodos , Privación de Sueño/complicaciones , Privación de Sueño/metabolismo , Folículo Ovárico/metabolismo , Oocitos/metabolismo , Trasplante de Microbiota Fecal , Modelos Animales de Enfermedad , Apoptosis
5.
Medicine (Baltimore) ; 103(27): e38822, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968460

RESUMEN

This study aimed to identify highly valuable blood indicators for predicting the clinical outcomes of patients with aortic aneurysms (AA). Baseline data of 1180 patients and 16 blood indicators were obtained from the public Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. The association of blood indicators with 4 types of clinical outcomes was analyzed, and the prediction performance of core indicators on different outcomes was next evaluated. Then, we explored the detailed association between core indicators and key outcomes among subgroups. Finally, a machine learning model was established to improve the prediction performance. Generalized linear regression analysis indicated that only red cell volume distribution width (RDW) was commonly associated with 4 end-points including surgery requirement, ICU stay requirement, length of hospital stay, and in-hospital death (all P < .05). Further, RDW showed the best performance for predicting in-hospital death by receiver operating characteristic (ROC) analysis. The significant association between RDW and in-hospital death was then determined by 3 logistic regression models adjusting for different variables (all P < .05). Stratification analysis showed that their association was mainly observed in unruptured AA and abdominal AA (AAA, all P < .05). We subsequently established an RDW-based model for predicting the in-hospital death only in patients with unruptured AAA. The favorable prediction performance of the RDW-based model was verified in training, validation, and test sets. RDW was found to make the greatest contribution to in-hospital death within the model. RDW had favorable clinical value for predicting the in-hospital death of patients, especially in unruptured AAA.


Asunto(s)
Aneurisma de la Aorta Abdominal , Índices de Eritrocitos , Mortalidad Hospitalaria , Humanos , Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Curva ROC , Aprendizaje Automático
6.
Curr Pharm Des ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38984572

RESUMEN

BACKGROUND: Due to the narrow therapeutic window and large pharmacokinetic variation of valproic acid (VPA), it is difficult to make an optimal dosage regimen. The present study aims to optimize the initial dosage of VPA in patients with bipolar disorder. METHODS: A total of 126 patients with bipolar disorder treated by VPA were included to construct the VPA population pharmacokinetic model retrospectively. Sex differences and combined use of clozapine were found to significantly affect VPA clearance in patients with bipolar disorder. The initial dosage of VPA was further optimized in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. RESULTS: The CL/F and V/F of VPA in patients with bipolar disorder were 11.3 L/h and 36.4 L, respectively. It was found that sex differences and combined use of clozapine significantly affected VPA clearance in patients with bipolar disorder. At the same weight, the VPA clearance rates were 1.134, 1, 1.276884, and 1.126 in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. This study further optimized the initial dosage of VPA in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. CONCLUSION: This study is the first to investigate the initial dosage optimization of VPA in patients with bipolar disorder based on sex differences and the combined use of clozapine. Male patients had higher clearance, and the recommended initial dose decreased with increasing weight, providing a reference for the precision drug use of VPA in clinical patients with bipolar disorder.

7.
ACS Nano ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38988308

RESUMEN

Metal-organic frameworks (MOFs) are a class of porous materials constructed from organic linkers and inorganic building blocks. Coordinative competition labilizes some MOFs under harsh chemical conditions because of their weak bonding. However, instability is not always a negative property of a material. In this study, we demonstrated the use of the acidic lability of MOFs for direct optical patterning. The controllable acid release from the photoacid generator at the exposed area causes bond cleavage between the linkers and metal ions/clusters, leading to solubility changes and pattern formation after development. This process avoids redundant steps and possible contamination in traditional photolithography, while maintaining the original properties of patterned MOFs. The preserved porosity and crystallinity promoted the development of MOFs for gas sensors and solid displays.

8.
Gut Microbes ; 16(1): 2379566, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39013030

RESUMEN

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants with no specific treatments available. We aimed to identify the molecular mechanisms underlying NEC and investigate the therapeutic effects of Bacteroides fragilis on NEC. Clinical samples of infant feces, bile acid-targeted metabolomics, pathological staining, bioinformatics analysis, NEC rat model, and co-immunoprecipitation were used to explore the pathogenesis of NEC. Taxonomic characterization of the bile salt hydrolase (bsh) gene, enzyme activity assays, 16S rRNA sequencing, and organoids were used to explore the therapeutic effects of B. fragilis on NEC-related intestinal damage. Clinical samples, NEC rat models, and in vitro experiments revealed that total bile acid increased in the blood but decreased in feces. Moreover, the levels of FXR and other bile acid metabolism-related genes were abnormal, resulting in disordered bile acid metabolism in NEC. Taurochenodeoxycholic acid accelerated NEC pathogenesis and taurodeoxycholate alleviated NEC. B. fragilis displayed bsh genes and enzyme activity and alleviated intestinal damage by restoring gut microbiota dysbiosis and bile acid metabolism abnormalities by inhibiting the FXR-NLRP3 signaling pathway. Our results provide valuable insights into the therapeutic role of B. fragilis in NEC. Administering B. fragilis may substantially alleviate intestinal damage in NEC.


Asunto(s)
Amidohidrolasas , Bacteroides fragilis , Ácidos y Sales Biliares , Enterocolitis Necrotizante , Microbioma Gastrointestinal , Proteína con Dominio Pirina 3 de la Familia NLR , Receptores Citoplasmáticos y Nucleares , Transducción de Señal , Enterocolitis Necrotizante/metabolismo , Enterocolitis Necrotizante/microbiología , Enterocolitis Necrotizante/tratamiento farmacológico , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Bacteroides fragilis/metabolismo , Bacteroides fragilis/genética , Transducción de Señal/efectos de los fármacos , Ácidos y Sales Biliares/metabolismo , Ratas , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Microbioma Gastrointestinal/efectos de los fármacos , Amidohidrolasas/metabolismo , Amidohidrolasas/genética , Humanos , Ratas Sprague-Dawley , Recién Nacido , Modelos Animales de Enfermedad , Masculino , Femenino , Probióticos/administración & dosificación , Probióticos/farmacología , Recien Nacido Prematuro , Disbiosis/microbiología
9.
Sci Rep ; 14(1): 16457, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014129

RESUMEN

Erectile dysfunction (ED) is the most prevalent consequences in men with diabetes mellitus (DM). Recent studies demonstrates that neutrophil extracellular traps (NETs) play important roles in DM and its complications. Nevertheless, whether NETs are involved in ED remains unknown. This work intended to explore the role and mechanisms of NETs in ED in the context of DM. Here, we observed that NET generation and pyroptosis were promoted in DM rats with ED compared with controls. Mechanistically, NETs facilitated NLRP3 inflammasome activation and subsequently triggered pyroptosis under high glucose stress, ultimately leading to ED. Intriguingly, DNase I (a NET degrading agent) alleviated ED and corpus cavernosum injury in DM rats. Overall, NETs might induce ED in DM by promoting NLRP3-mediated pyroptosis in the corpus cavernosum.


Asunto(s)
Diabetes Mellitus Experimental , Disfunción Eréctil , Trampas Extracelulares , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Animales , Trampas Extracelulares/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Disfunción Eréctil/metabolismo , Disfunción Eréctil/etiología , Ratas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Neutrófilos/metabolismo , Ratas Sprague-Dawley , Inflamasomas/metabolismo , Desoxirribonucleasa I/metabolismo , Pene/metabolismo , Pene/patología
10.
Materials (Basel) ; 17(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38930164

RESUMEN

Orthotropic steel decks (OSDs) are commonly used in the construction of bridges due to their load-bearing capabilities. However, they are prone to fatigue damage over time due to the cyclic loads from vehicles. Therefore, the early structural health monitoring of fatigue damage in OSDs is crucial for ensuring bridge safety. Moreover, Lamb waves, as elastic waves propagating in OSD plate-like structures, are characterized by their long propagation distances and minimal attenuation. This paper introduces a method of emitting high-energy ultrasonic waves onto the OSD surface to capture the nonlinear Lamb waves formed, thereby calculating the nonlinear parameters. These parameters are then correlated with the fatigue damage endured, forming a damage index (DI) for monitoring the fatigue life of OSDs. Experimental results indicate that as fatigue damage increases, the nonlinear parameters exhibit a significant initial increase followed by a decrease. The behavior is distinct from the characteristic parameters of linear ultrasound (velocity and energy), which also exhibit changes but to a relatively smaller extent. The proposed DI and fatigue life based on nonlinear parameters can be fitted with a Gaussian curve, with the R-squared value of the fitting curve being close to 1. Additionally, this paper discusses the influence of rib welds within the OSDs on the DI, whereby as fatigue damage increases, it enlarges the value of the nonlinear parameters without altering their trend. The proposed method provides a more effective approach for monitoring early fatigue damage in OSDs.

12.
ACS Nano ; 18(23): 15055-15066, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38825792

RESUMEN

The stability issue of Sn-based perovskite solar cells (PSCs) is expected to be resolved by involving a two-dimensional (2D) layered structure. However, Sn-based 2D PSCs, especially Dion-Jacobson (DJ)-phase ones with potentially good stability, have rarely been reported. Herein, superior DJ-phase Sn 2D perovskites with 3-aminobenzylamine (3ABA2+) or 4-aminobenzylamine (4ABA2+) π-conjugated short-chain ligands are reported to fabricate efficient 2D lead-free PSCs. Notably, the high dipole moment of the 3ABAI2 organic spacer is approved to possess faster charge transfer for forming (3ABA)FA4Sn5I16 2D perovskite with an extremely low exciton binding energy (only 84 meV). In combination with a diacetate partial substitution and methylamine iodide/bromide (MAI/MABr) post-treatment strategy to delay crystallization and improve compactness and coverage of the perovskite film, a record power conversion efficiency (PCE) of 6.81% and stability of 840 h (less than 5% degradation in a N2 atmosphere for unencapsulated devices) are acquired in eventual (3ABA)FA4Sn5I16 2D PSCs, which are among the highest PCE and the longest stability of Sn-based 2D PSCs reported to date. Our work provides a prospective molecule design and film preparation strategy of 2D Sn perovskites toward nontoxic high-performance tin-based PSCs, which pushes the almost stagnant research forward.

13.
Sci Robot ; 9(91): eadl2007, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38924422

RESUMEN

Cytokines have been identified as key contributors to the development of inflammatory bowel disease (IBD), yet conventional treatments often prove inadequate and carry substantial side effects. Here, we present an innovative biohybrid robotic system, termed "algae-MΦNP-robot," for addressing IBD by actively neutralizing colonic cytokine levels. Our approach combines moving green microalgae with macrophage membrane-coated nanoparticles (MΦNPs) to efficiently capture proinflammatory cytokines "on the fly." The dynamic algae-MΦNP-robots outperformed static counterparts by enhancing cytokine removal through continuous movement, better distribution, and extended retention in the colon. This system is encapsulated in an oral capsule, which shields it from gastric acidity and ensures functionality upon reaching the targeted disease site. The resulting algae-MΦNP-robot capsule effectively regulated cytokine levels, facilitating the healing of damaged epithelial barriers. It showed markedly improved prevention and treatment efficacy in a mouse model of IBD and demonstrated an excellent biosafety profile. Overall, our biohybrid algae-MΦNP-robot system offers a promising and efficient solution for IBD, addressing cytokine-related inflammation effectively.


Asunto(s)
Colon , Citocinas , Enfermedades Inflamatorias del Intestino , Nanopartículas , Robótica , Animales , Citocinas/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Robótica/instrumentación , Ratones , Humanos , Macrófagos/metabolismo , Mucosa Intestinal/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Masculino , Diseño de Equipo , Epitelio
14.
Imeta ; 3(2): e166, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38882497

RESUMEN

Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

15.
Nano Lett ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38855905

RESUMEN

Neurotoxins are known for their extreme lethality. However, due to their enormous diversity, effective and broad-spectrum countermeasures are lacking. This study presents a dual-modal cellular nanoparticle (CNP) formulation engineered for continuous neurotoxin neutralization. The formulation involves encapsulating the metabolic enzyme N-sulfotransferase (SxtN) into metal-organic framework (MOF) nanoparticle cores and coating them with a natural neuronal membrane, termed "Neuron-MOF/SxtN-NPs". The resulting nanoparticles combine membrane-enabled broad-spectrum neurotoxin neutralization with enzyme payload-enabled continuous neurotoxin neutralization. The studies confirm the protection of the enzyme payload by the MOF core and validate the continuous neutralization of saxitoxin (STX). In vivo studies conducted using a mouse model of STX intoxication reveal markedly improved survival rates compared with control groups. Furthermore, acute toxicity assessments show no adverse effects associated with the administration of Neuron-MOF/SxtN-NPs in healthy mice. Overall, Neuron-MOF/SxtN-NPs represent a unique biomimetic nanomedicine platform poised to effectively neutralize neurotoxins, marking an important advancement in the field of countermeasure nanomedicine.

16.
Sci Rep ; 14(1): 13167, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849513

RESUMEN

Exploring the spatial coupling relationship and interaction mechanism between green urbanization (GU) and tourism competitiveness (TC) is of great significance for promoting urban sustainable development. However, the lack of research on the interaction mechanism between GU and TC limits the formulation of effective environmental management policy and urban planning. Taking 734 counties in the Yellow River Basin (YRB) as the study area, this paper analyzes the spatial coupling relationship between GU and TC on the basis of comprehensive evaluation of GU and TC. Then, the interactive mechanism between GU and TC is systematically discussed, and the synergistic development strategy of the two is proposed. The results show that the GU level presents a multicore circle structure, with provincial capitals, prefecture-level urban districts and economically developed counties in east-central regions as high-value centers. The TC at county scale presents a multi-center spatial structure. Additionally, there is a significant positive spatial coupling between GU and TC in the YRB. The analysis further reveals that green urbanization level, social progress, population development, infrastructure construction, economic development quality, and eco-environmental protection has a observably influence on TC. Tourism competitiveness, service competitiveness, location competitiveness, resource competitiveness, market competitiveness, environmental influence, and talent competitiveness has a observably influence on GU. TC can promote GU, and the improvement of green urbanization level can support the development of tourism competitiveness. According to the spatial zoning method, 734 counties are divided into 6 categories, and the coordinated development strategy of GU and TC for each type of district is proposed.

17.
Sci Rep ; 14(1): 12884, 2024 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839838

RESUMEN

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.


Asunto(s)
Edad Gestacional , Recien Nacido Prematuro , Curva ROC , Humanos , Recién Nacido , Femenino , Recien Nacido Prematuro/crecimiento & desarrollo , Embarazo , Masculino , Nomogramas , Peso al Nacer , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Factores de Riesgo , Diabetes Gestacional/diagnóstico , Retardo del Crecimiento Fetal/diagnóstico , Modelos Logísticos
19.
Adv Mater ; : e2406682, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38837816

RESUMEN

The utilization of rare earth elements to regulate the interaction between catalysts and oxygen-containing species holds promising prospects in the field of oxygen electrocatalysis. Through structural engineering and adsorption regulation, it is possible to achieve high-performance catalytic sites with a broken activity-stability tradeoff. Herein, this work fabricates a hierarchical CeO2/NiCo hydroxide for electrocatalytic oxygen evolution reaction (OER). This material exhibits superior overpotentials and enhanced stability. Multiple potential-dependent experiments reveal that CeO2 promotes oxygen-species exchange, especially OH- ions, between catalyst and environment, thereby optimizing the redox transformation of hydroxide and the adsorption of oxygen-containing intermediates during OER. This is attributed to the reduction in the adsorption energy barrier of Ni to *OH facilitated by CeO2, particularly the near-interfacial Ni sites. The less-damaging adsorbate evolution mechanism and the CeO2 hierarchical shell significantly enhance the structural robustness, leading to exceptional stability. Additionally, the observed "self-healing" phenomenon provides further substantiation for the accelerated oxygen exchange. This work provides a neat strategy for the synthesis of ceria-based complex hollow electrocatalysts, as well as an in-depth insight into the co-catalytic role of CeO2 in terms of oxygen transfer.

20.
J Mol Diagn ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38925456

RESUMEN

PMS2 is one of the DNA-mismatch repair genes included in routine genetic testing for Lynch syndrome and colorectal, ovarian, and endometrial cancers. PMS2 is also included in the American College of Medical Genetics and Genomics' List of Secondary Findings Genes in the context of clinical exome and genome sequencing. However, sequencing of PMS2 by short-read-based next-generation sequencing technologies is complicated by the presence of the pseudogene PMS2CL, and is often supplemented by long-range-based approaches, such as long-range PCR or long-read-based next-generation sequencing, which increases the complexity and cost. This article describes a bioinformatics homology triage workflow that can eliminate the need for long-read-based testing for PMS2 in the vast majority of patients undergoing exome sequencing, thus simplifying PMS2 testing and reducing the associated cost.

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