To assess the association between C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and response to first-line fluoropyrimidine-based chemotherapy for metastatic colorectal adenocarcinoma.
 
  A total of 68 patients were prospectively followed up in San Juan de Dios Hospital (San José, Costa Rica) from January 2019 to November 2020. Patients received first-line therapy with capecitabine or 5-fluorouracil in combination with oxaliplatin or irinotecan. Germline and somatic DNA was extracted from blood samples and paraffin-embedded tissue, respectively. Overall response rate (partial response + complete response) was assessed according to RECIST 1.1 criteria. Cox regression models were performed to identify the effect of MTHFR C677T and A1298C SNPs on progression-free survival (PFS) and overall survival (OS) (NCT registration number 03852290).
 
  Patients harboring one or both T alleles of the MTHFR C677T SNP had better overall response than homozygous wild-type individuals [odds ratio (OR) 3.21; 95% confidence interval (CI), 1.05-9.81; P = 0.03]. No association was found between the MTHFR A1298C genotypes and overall response (OR 0.75; 95% CI, 0.26-2.20; P = 0.60). Patients with the MTHFR 677 TT and CT genotypes had longer PFS than CC individuals (hazard ratio 0.53; 95% CI, 0.28-0.98; P = 0.045), even after adjustment for confounders (hazard ratio 0.50; 95% CI, 0.25-0.98; P = 0.04).  https://www.selleckchem.com/products/skf96365.html  We found no association between the MTHFR A1298C SNP and PFS (hazard ratio 1.35; 95% CI, 0.72-2.55; P = 0.34). None of the SNPs was associated with OS.
 
  Patients carrying at least one mutant allele of the MTHFR C677T SNP had a better overall response and longer PFS than wild-type homozygous patients.
 Patients carrying at least one mutant allele of the MTHFR C677T SNP had a better overall response and longer PFS than wild-type homozygous patients.
  The implementation of pharmacogenetics (PGx) in clinical practice is an essential tool for personalized medicine. However, clinical laboratories must validate their procedures before being used to perform PGx studies in patients, in order to confirm that they are adequate for the intended purposes.
 
  We designed a validation process for our in-house pharmacogenetic PCR-based method assay.
 
  The concordance to reference, repeatability and reproducibility was 100%. Sensitivity and specificity were 100% for the detection of variant diplotypes in CYP2C9, CYP3A5, TPMT, DPYD and UGT1A1 genes. The sensitivity was lower in the detection of CYP2C19 variants due to a limitation in the design that prevents the detection of CYP2C19 *2/*10 diplotype.
 
  The success of implementing clinical pharmacogenetic testing into routine clinical practice is dependent on the precision of genotyping. Limitations must be bearing in mind to guarantee the quality of PGx assays in clinical laboratory practice. We provided objective evidence that the necessary requirements in our laboratory-development assay were fulfilled.
 The success of implementing clinical pharmacogenetic testing into routine clinical practice is dependent on the precision of genotyping. Limitations must be bearing in mind to guarantee the quality of PGx assays in clinical laboratory practice. We provided objective evidence that the necessary requirements in our laboratory-development assay were fulfilled.
  Pediatric and adolescent forearm fractures are among the most common injuries treated by orthopaedic surgeons. Recent literature shows that there has been an increased interest in operative management for these injuries. The purpose of the current study was to examine the trends in case volume, patient age, surgeon fellowship training, and postoperative complications of surgically treated pediatric forearm fractures over >15-year period of American Board of Orthopaedic Surgery (ABOS) Part II Oral Examination candidates.
 
  ABOS Part II candidates' Oral Examination Case List data from 2003 to 2019 was queried for all pediatric and adolescent (19 y of age and below) forearm fractures treated operatively. Patient demographics, fracture type, complications, and candidate fellowship type were identified for each case. Linear regression was used to delineate annual trends in patient age, complication rates, and case volume by fellowship type. Analysis of variance was performed to evaluate complication rates by mparative effectiveness of surgical treatment of pediatric forearm fractures compared with closed management.
  Strong relationships and effective communication between clinicians support care coordination and contribute to care quality. As a new mechanism of clinician communication, electronic consultations (e-consults) may have downstream effects on care provision and coordination.
 
  The objective of this study was to understand primary care providers' and specialists' perspectives on how e-consults affect communication and relationships between clinicians.
 
  Qualitative study using thematic analysis of semistructured interviews.
 
  Six of 8 sites in the VISN 1 (Veterans Integrated Service Network) in New England were chosen, based on variation in organization and received e-consult volume. Seventy-three respondents, including 60 clinicians in primary care and 3 high-volume specialties (cardiology, pulmonology, and neurology) and 13 clinical leaders at the site and VISN level, were recruited.
 
  Participants' perspectives on the role and impact of e-consults on communication and relationships between clinicians.
 
  Clnsults in diverse health care settings.In this work, the multilevel resistive random access memories (RRAMs) have been achieved by using the structure of Pt/MoO3/Hf/MoO3/Pt with four stable resistance states. The devices show good retention property of each state (>104s) and large memory window (>104). The simulation and experimental study reveal that the resistive switching mechanism is ascribed to combination of the conductive filament in the stack of MoO3/Hf next to the top electrode and redox reaction at the interface of Hf/MoO3next to bottom electrode. The fitting results of current-voltage characteristics under low sweep voltage indicate that the conduction of HRSs is dominated by the Poole-Frenkel emission and that of LRS is governed by the Ohmic conduction. Based on the RRAM, the tunable high-pass filter (HPF) with configurable filtering characteristics has been realized. The gain-frequency characteristics of the programmable HPF show that the filter has high resolution and wide programming range, demonstrating the viability of the multilevel RRAMs for future spiking neural network and shrinking the programmable filters with low power consumption.