A disordered rock salt anode for fast-charging lithium-ion batteries.

Rechargeable lithium-ion batteries with high energy density that can be safely charged and discharged at high rates are desirable for electrified transportation and other applications1-3. However, the sub-optimal intercalation potentials of current anodes result in a trade-off between energy density, power and safety. Here we report that disordered rock salt4,5 Li3+xV2O5 can be used as a fast-charging anode that can reversibly cycle two lithium ions at an average voltage of about 0.6 volts versus a Li/Li+ reference electrode. The increased potential compared to graphite6,7 reduces the likelihood of lithium metal plating if proper charging controls are used, alleviating a major safety concern (short-circuiting related to Li dendrite growth). In addition, a lithium-ion battery with a disordered rock salt Li3V2O5 anode yields a cell voltage much higher than does a battery using a commercial fast-charging lithium titanate anode or other intercalation anode candidates (Li3VO4 and LiV0.5Ti0.5S2)8,9. Further, disordered rock salt Li3V2O5 can perform over 1,000 charge-discharge cycles with negligible capacity decay and exhibits exceptional rate capability, delivering over 40 per cent of its capacity in 20 seconds. We attribute the low voltage and high rate capability of disordered rock salt Li3V2O5 to a redistributive lithium intercalation mechanism with low energy barriers revealed via ab initio calculations. This low-potential, high-rate intercalation reaction can be used to identify other metal oxide anodes for fast-charging, long-life lithium-ion batteries.

Therapeutic Phage Candidates for Targeting Prevalent Sequence Types of Carbapenem-Resistant Escherichia coli.

Carbapenem-resistant Escherichia coli (CREC) is a global threat to public health; therefore, alternative treatment options are urgently needed. Bacteriophages have emerged as promising candidates for combating CREC infections. This study aimed to investigate the genetic basis of phage sensitivity in CREC by evaluating carbapenem resistance among multidrug-resistant (MDR) E. coli isolated in Daegu, South Korea and analyzing their sequence types (STs) with phage susceptibility spectra. Among the 60 MDR E. coli isolates, 80.4% were identified as CREC, with 77.0% demonstrating resistance to imipenem and 66.6% to meropenem. Moreover, 70 lytic E. coli bacteriophages were isolated from hospital sewage water and evaluated against those 60 E. coli isolates. The phages exhibited lytic activity of 33%-60%, with average titers ranging from 5.6 × 1012 to 2.4 × 1013 PFU/mL (Plaque-Forming Unit). Furthermore, multilocus sequence typing (MLST) analysis of the bacterial isolates revealed 14 distinct STs, mostly belonging to ST131, ST410, and ST648. Notably, the phage susceptibility spectra of ST73, ST13003, ST648, ST2311, ST167, ST405, ST607, ST7962, and ST131 were significantly different. Thus, the isolated phages can effectively lyse CREC isolates, particularly those with clinically dominant STs. Conversely, ST410 exhibited a 14.2%-87.14% susceptibility spectrum, whereas ST1139, ST1487, ST10, and ST206 did not lyse, suggesting the presence of more resistant STs. Future studies are warranted to identify the reasons behind this resistance and address it. Ultimately, this study will aid in developing focused treatments to address these pressing global health issues.

Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses.

High mobility group box 1 (HMGB1), a protein with important functions, has been recognized as a potential therapeutic target for the treatment of sepsis. One possible mechanism for this is that inhibiting HMGB1 secretion can exert antiseptic effects, which can restore the integrity of the vascular barrier. (7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (CGK012) is a newly synthesized pyranocoumarin compound that could function as a novel small-molecule inhibitor of the Wnt/ß-catenin signaling pathway. However, no studies have yet determined the effects of CGK012 on sepsis. We investigated the potential of CGK012 to attenuate the excessive permeability induced by HMGB1 and enhance survival rates in a mouse model of sepsis with reduced HMGB1 levels following lipopolysaccharide (LPS) treatment. In both LPS-stimulated human endothelial cells and a mouse model exhibiting septic symptoms due to cecal ligation and puncture (CLP), we assessed proinflammatory protein levels and tissue damage biomarkers as indicators of reduced vascular permeability. CGK012 was applied after induction in human endothelial cells exposed to LPS and the CLP-induced mouse model of sepsis. CGK012 effectively mitigated excessive permeability and suppressed HMGB1 release, resulting in improved vascular stability, decreased mortality, and enhanced histological conditions in the mouse model of CLP-induced sepsis. In conclusion, our findings indicate that CGK012 treatment in mice with CLP-induced sepsis diminished HMGB1 release and increased the survival rate, suggesting its potential as a pharmaceutical intervention for sepsis.

Impact of media compositions and culture systems on the immunophenotypes of patient-derived breast cancer cells.

BACKGROUND: Heterogeneous tumor cells are thought to be a significant factor in the failure of endocrine therapy in estrogen receptor-positive (ER+) cancers. Culturing patient-derived breast cancer cells (PDBCCs) provides an invaluable tool in pre-clinical and translational research for the heterogeneity of cancer cells. This study aimed to investigate the effects of different media components and culture methods on the BCSC-associated immunophenotypes and gene expression in ER + PDBCCs. METHODS: Ten patients with ER + breast cancer were employed in this study, six of whom had neoadjuvant chemotherapy and four of whom did not. PDBCCs were isolated by enzymatic methods using collagen I and hyaluronidase. PDBCCs were grown as monolayers in mediums with different compositions and as multicellular spheroid in a suspended condition. Collagen I-coated plate and ultralow attachment plate coated with polymer-X were used for monolayer and spheroid culture. Flow cytometry, immunofluorescent staining, RT-PCR, and RNA-sequencing were employed to examine the immunophenotype and genetic profile of PDBCCs. RESULTS: More than 95% of PDBCCs sustain EpCAM high/+/fibroblast marker- phenotypes in monolayer conditions by subculturing 3-4 times. A83-01 removal induced senescent cells with high ß-galactosidase activity. PDBCCs grown as monolayers were characterized by the majority of cells having an EpCAM+/CD49f + phenotype. Compared to full media in monolayer culture, EGF removal increased EpCAM+/CD49f - phenotype (13.8-fold, p = 0.028), whereas R-spondin removal reduced it (0.8-fold, p = 0.02). A83-01 removal increased EpCAM+/CD24 + phenotype (1.82-fold, p = 0.023) and decreased EpCAM low/-/CD44+/CD24- phenotype (0.45-fold, p = 0.026). Compared to monolayer, spheroid resulted in a significant increase in the population with EpCAM-/CD49+ (14.6-fold, p = 0.006) and EpCAM low/-/CD44+/CD24- phenotypes (4.16-fold, p = 0.022) and ALDH high activity (9.66-fold, p = 0.037). ALDH1A and EMT-related genes were upregulated. In RNA-sequencing analysis between spheroids and monolayers, a total of 561 differentially expressed genes (2-fold change, p < 0.05) were enriched in 27 KEGG pathways including signaling pathways regulating pluripotency of stem cells. In a recurrence-free survival analysis based on the Kaplan-Meier Plotter database of the up-and down-regulated genes identified in spheroids, 15 up-, and 14 down-regulated genes were associated with poor prognosis of breast cancer patients. CONCLUSION: The media composition and spheroid culture method change in the BCSCs and EMT markers of PDBCCs, implying the importance of defining the media composition and culture method for studying PDBCCs in vitro.

Dietary patterns are associated with attention-deficit hyperactivity disorder (ADHD) symptoms among preschoolers in South Korea: a prospective cohort study.

OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurobehavioral disorder in children. There are limited studies for diet or dietary supplement effects on ADHD in preschool children in Asia. This study aimed to determine the association between dietary patterns in 4-year-old children and ADHD symptoms in 6-year-old children. METHODS: We estimated dietary intake in 4-year-old children using a food frequency questionnaire. Using 33 food groups, major dietary patterns were identified in relation to the consumption of sweets, vegetables, meats, and carbohydrates. Parents of 6-year-old children used the Korean version of the ADHD Rating Scale for ADHD symptom assessment. RESULTS: A sweet dietary pattern was associated with a higher risk of attention deficit (AD) (relative risk [RR], 1.34; confidence interval [CI], 1.17-1.55), hyperactivity (RR, 1.40; CI, 1.19-1.64), and ADHD symptoms (RR, 1.37; CI, 1.23-1.52). A vegetable dietary pattern was associated with a lower risk of ADHD symptoms (RR, 0.81; CI, 0.72-0.90). Food item analysis of the sweet dietary pattern showed that intake scores for chocolate, chips, and fruit jams positively correlated with AD, hyperactivity, and ADHD symptoms. DISCUSSION: These findings can be useful to further understand the roles of dietary factors in ADHD.

Association Between Sleep Duration and Intelligence Quotient in 6-Year-Old Children.

BACKGROUND: Sufficient sleep during childhood is important for cognitive functions such as learning and successful school performance. This study aimed to investigate the effects of sleep duration on the intelligence quotient (IQ) of 6-year-old children and aimed to analyze whether these effects differed by sex. METHODS: The IQ of 538 6-year-old Korean participants from the cohort study, "The Environment and Development of Children," was measured during follow-up using the Korean Educational Developmental Institute's Wechsler Intelligence Scale for Children. The total, verbal, and performance IQ scores were evaluated. The relationship between sleep duration and IQ scores after adjusting for maternal age, maternal educational level, maternal occupation, maternal IQ, exposure to secondhand smoking, gestational age, and monthly age and birth season was also assessed. RESULTS: Longer sleep duration was significantly associated with improved verbal IQ measures (ß 0.55; p value 0.030). After stratifying participants by sex, a significant association was observed between sleep duration and total, verbal, and performance IQ scores in boys (total IQ 2.49, p value 0.012; verbal IQ 0.75, p value: 0.037; performance IQ 0.73, p value 0.048), but not in girls. CONCLUSIONS: The results indicated that only boys show a significant association between IQ scores and sleep duration. These findings support the hypothesis that sleep duration is associated with IQ, in a sex dependent manner. Future studies are needed for a thorough evaluation of the connection between sleep duration and health outcome in young children.

Prenatal exposure to traffic-related air pollution and risk of congenital diseases in South Korea.

BACKGROUND: Previous studies have suggested links between exposure to ambient air pollutants and increased risk of congenital heart defects. However, few studies have investigated the association between other congenital diseases and traffic-related air pollution. In this study, we assessed the relationship between prenatal exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) with congenital diseases in South Korea. METHODS: Patients with one or more congenital diseases and a control group of patients with non-infective gastroenteritis and colitis with a case:control ratio of 1:3 were obtained from the National Health Insurance Service data for 2008-2013 in South Korea. We estimated the associations of PM2.5 and NO2 exposures with congenital diseases using generalized estimation equations after controlling for covariates. RESULTS: Maternal PM2.5 exposure during the first and second trimester showed positive associations with overall congenital diseases, with changes of 14.7% (95% confidence intervals (CI), 9.3%, 20.3%) and 16.2% (95% CI, 11.0%, 21.7%), respectively, per 11.1 µg/m3 and 10.2 µg/m3 increase of PM2.5 interquartile range (IQR). Similarly, NO2 exposure during the first and second trimester was associated with increased numbers of overall congenital anomalies, with 8.2% (95% CI, 4.2%, 12.3%) and 15.6% (95% CI, 9.3%, 22.2%) more cases, respectively, per 10.6 ppb increase of NO2. We found that maternal PM2.5 exposure during the first and second trimesters of pregnancy was significantly associated with increased risk of specific congenital diseases, including subtypes affecting the circulatory, genitourinary, and musculoskeletal system. However, no significant associations were observed during the third trimester. Maternal NO2 exposure across the entire pregnancy was associated with malformations of the musculoskeletal system. CONCLUSIONS: Our study identified significant links between in utero exposure to PM2.5 and NO2 and certain congenital diseases, and suggests that stricter controls on PM2.5 and NO2 concentrations are required.

Predicting FOXM1-Mediated Gene Regulation through the Analysis of Genome-Wide FOXM1 Binding Sites in MCF-7, K562, SK-N-SH, GM12878 and ECC-1 Cell Lines.

Forkhead box protein M1 (FOXM1) is a key transcription factor (TF) that regulates a common set of genes related to the cell cycle in various cell types. However, the mechanism by which FOXM1 controls the common gene set in different cellular contexts is unclear. In this study, a comprehensive meta-analysis of genome-wide FOXM1 binding sites in ECC-1, GM12878, K562, MCF-7, and SK-N-SH cell lines was conducted to predict FOXM1-driven gene regulation. Consistent with previous studies, different TF binding motifs were identified at FOXM1 binding sites, while the NFY binding motif was found at 81% of common FOXM1 binding sites in promoters of cell cycle-related genes. The results indicated that FOXM1 might control the gene set through interaction with the NFY proteins, while cell type-specific genes were predicted to be regulated by enhancers with FOXM1 and cell type-specific TFs. We also found that the high expression level of FOXM1 was significantly associated with poor prognosis in nine types of cancer. Overall, these results suggest that FOXM1 is predicted to function as a master regulator of the cell cycle through the interaction of NFY-family proteins, and therefore the inhibition of FOXM1 could be an attractive strategy for cancer therapy.

A Machine Learning-Based Identification of Genes Affecting the Pharmacokinetics of Tacrolimus Using the DMETTM Plus Platform.

Tacrolimus is an immunosuppressive drug with a narrow therapeutic index and larger interindividual variability. We identified genetic variants to predict tacrolimus exposure in healthy Korean males using machine learning algorithms such as decision tree, random forest, and least absolute shrinkage and selection operator (LASSO) regression. rs776746 (CYP3A5) and rs1137115 (CYP2A6) are single nucleotide polymorphisms (SNPs) that can affect exposure to tacrolimus. A decision tree, when coupled with random forest analysis, is an efficient tool for predicting the exposure to tacrolimus based on genotype. These tools are helpful to determine an individualized dose of tacrolimus.

Nuclear aconitase antagonizes heterochromatic silencing by interfering with Chp1 binding to DNA.

In Schizosaccharomyces pombe, there are two aconitases, Aco1 and Aco2, involved in the Krebs cycle in mitochondria. Interestingly, Aco2 is localized to nucleus as well. Here, we investigated the nuclear role of Aco2 by deleting its nuclear localization signal. The aco2ΔNLS mutation suppressed the gene-silencing defects of RNAi mutants at the centromere, where heterochromatin formation depends on RNAi pathway. In Δago1, the aco2ΔNLS mutation restored heterochromatin through elevating Chp1 binding. Aco2 physically interacted with Chp1 via the N-terminal chromodomain that binds to methylated histone H3K9. In the sub-telomeric region, where heterochromatin forms independent of RNAi pathway, the single aco2ΔNLS mutation caused extra gene silencing via elevating Chp1 binding, without increasing histone methylation. The anti-silencing effect did not require the catalytic function of aconitase. Taken together, Aco2 functions as an epigenetic regulator of gene expression, through associating with chromodomain of Chp1 to maintain heterochromatin.

The 19S proteasome is directly involved in the regulation of heterochromatin spreading in fission yeast.

Cumulative evidence suggests that non-proteolytic functions of the proteasome are involved in transcriptional regulation, mRNA export, and ubiquitin-dependent histone modification and thereby modulate the intracellular levels of regulatory proteins implicated in controlling key cellular functions. To date, the non-proteolytic roles of the proteasome have been mainly investigated in euchromatin; their effects on heterochromatin are largely unknown. Here, using fission yeast as a model, we randomly mutagenized the subunits of the 19S proteasome subcomplex and sought to uncover a direct role of the proteasome in heterochromatin regulation. We identified a mutant allele, rpt4-1, that disrupts a non-proteolytic function of the proteasome, also known as a non-proteolytic allele. Experiments performed using rpt4-1 cells revealed that the proteasome is involved in the regulation of heterochromatin spreading to prevent its uncontrolled invasion into neighboring euchromatin regions. Intriguingly, the phenotype of the non-proteolytic rpt4-1 mutant resembled that of epe1Δ cells, which lack the Epe1 protein that counteracts heterochromatin spreading. Both mutants exhibited variegated gene-silencing phenotypes across yeast colonies, spreading of heterochromatin, bypassing of the requirement for RNAi in heterochromatin formation at the outer repeat region (otr), and up-regulation of RNA polymerase II. Further analysis revealed Mst2, another factor that antagonizes heterochromatin spreading, may function redundantly with Rpt4. These observations suggest that the 19S proteasome may be involved in modulating the activities of Epe1 and Mst2. In conclusion, our findings indicate that the proteasome appears to have a heterochromatin-regulating function that is independent of its canonical function in proteolysis.

Hrp3 controls nucleosome positioning to suppress non-coding transcription in eu- and heterochromatin.

The positioning of the nucleosome by ATP-dependent remodellers provides the fundamental chromatin environment for the regulation of diverse cellular processes acting on the underlying DNA. Recently, genome-wide nucleosome mapping has revealed more detailed information on the chromatin-remodelling factors. Here, we report that the Schizosaccharomyces pombe CHD remodeller, Hrp3, is a global regulator that drives proper nucleosome positioning and nucleosome stability. The loss of Hrp3 resulted in nucleosome perturbation across the chromosome, and the production of antisense transcripts in the hrp3Δ cells emphasized the importance of nucleosome architecture for proper transcription. Notably, perturbation of the nucleosome in hrp3 deletion mutant was also associated with destabilization of the DNA-histone interaction and cell cycle-dependent alleviation of heterochromatin silencing. Furthermore, the effect of Hrp3 in the pericentric region was found to be accomplished via a physical interaction with Swi6, and appeared to cooperate with other heterochromatin factors for gene silencing. Taken together, our data indicate that a well-positioned nucleosome by Hrp3 is important for the spatial-temporal control of transcription-associated processes.

Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast.

Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5' promoter and 3' termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes. Furthermore, the increase of H3K56Ac and H4K20me1 and antisense RNA production was observed in the absence of the histone H3K36 methyltransferase Set2 and histone deacetylase complex (HDAC) that are involved in the suppression of histone turnover within the coding regions. These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast.

Increased variability of the coupling interval of premature ventricular contractions as a predictor of cardiac mortality in patients with left ventricular dysfunction.

BACKGROUND: The characteristics and prognostic value of the variability of premature ventricular contraction (PVC) coupling intervals (CIs) for cardiac mortality are not yet decisive. METHODS AND RESULTS: In 133 consecutive patients (58±14 years old, 53 women) who had left ventricular dysfunction (LVD: ejection fraction <50%) and frequent PVCs (≥10/h) who underwent 24-h ambulatory electrocardiography (AECG) recording and (123)I-metaiodobenzylguanidine myocardial single-photon emission computed tomography simultaneously, the heart rate turbulence onset, slope, and T-wave alternans were analyzed from the 24-h AECG. The CI of the PVCs (MEANNV), standard deviation of the CI of the PVCs (SDNV) as an index of the variability of the PVC CI, and their ratio to the preceding N-N intervals (SDNV/SDNN) were calculated from constructed Poincaré plots using the annotated 24-h AECG QRS data. The primary endpoint was cardiac mortality. The mean follow-up period was 63 months. Among 133 patients, 114 survived (group 1) and 19 (14%, group 2) died during the follow-up. The MEANNVand SDNVwere higher in group 2 (539±104 vs. 599±114 ms, P=0.021; 64±34 vs. 83±37 ms, P=0.022, respectively). The SDNV, PVC count, and delayed heart/mediastinum ratio remained as significant predictors of cardiac mortality in the binary logistic regression analysis. CONCLUSIONS: These results suggest that the SDNVcould be another adjunctive parameter for predicting cardiac mortality in LVD.

Treatment patterns and their outcomes of acute aortic intramural hematoma in real world: multicenter registry for aortic intramural hematoma.

BACKGROUND: Intramural hematoma of the aorta (IMH), a variant of classic aortic dissection, shows very dynamic process in the early phase. The aim of this study is to evaluate clinical outcomes of patients with acute aortic IMH from real world registry data. METHODS: We analyzed 165 consecutive patients with acute IMH from five medical centers in Korea. All patients were divided into two groups; type A (n = 61, 37.0%) and type B (n = 104, 63.0%) according to the Stanford classification. Clinical outcomes and morphological evolution by CT were analyzed for 2 years. RESULTS: Most of the patients (77.0% of type A and 99.0% of type B, P < 0.001) were treated medically during their initial hospitalization. There were no significant differences in in-hospital mortality (4.9% vs. 2.9%, P = 0.671) and 2-year mortality (13.1% vs. 11.5%, P = 0.765) between two groups. During the 2-year follow up period, progression to aortic dissection (18.0% vs. 6.7%, P = 0.037) and surgical treatment (29.5% vs. 2.9%, P < 0.001) were higher in type A. For the type A patients, there were no significant difference in in-hospital mortality (7.1% of surgery vs. 4.3% of medical, P = 0.428) and 2-year mortality (7.1% of surgery vs. 14.9% of medical, P = 0.450) in terms of initial treatment strategy. CONCLUSION: For real world practice in Korea, most of IMH patients were treated medically at presentation and showed favorable outcomes. Thus, even in type A acute IMH, early medical treatment with alternative surgical conversion for selected, complicated cases would be a favorable treatment option.

Diagnostic performance of shear wave elastography of the breast according to scanning orientation.

OBJECTIVES: To evaluate the influence of the scanning orientation on diagnostic performance measured by the mean elasticity, maximum elasticity, and fat-to-lesion elasticity ratio on ultrasound-based shear wave elastography in differentiating breast cancers from benign lesions. METHODS: In this study, a total of 260 breast masses from 235 consecutive patients were observed from March 2012 to November 2012. For each lesion, the mean elasticity value, maximum elasticity value, and fat-to-lesion ratio were measured along two orthogonal directions, and all values were compared with pathologic results. RESULTS: There were 59 malignant and 201 benign lesions. Malignant masses showed higher mean elasticity, maximum elasticity, and fat-to-lesion ratio values than benign lesions (P < .0001). The areas under the receiver operating characteristic curves were as follows: average mean elasticity on both views, 0.870; mean elasticity on the transverse view, 0.866; maximum elasticity on both views, 0.865; maximum elasticity on the transverse view, 0.864; mean elasticity on the longitudinal view, 0.849; fat-to-lesion ratio on both views, 0.849; maximum elasticity on the longitudinal view, 0.845; fat-to-lesion ratio on the transverse view, 0.841; and fat-to-lesion ratio on the longitudinal view, 0.814. Intraclass correlation coefficients for agreement between the scanning directions were as follows: mean elasticity, 0.852; maximum elasticity, 0.842; fat-to-lesion ratio, 0.746, for masses; and mean elasticity, 0.392, for anterior mammary fat. CONCLUSIONS: Mean elasticity, maximum elasticity, and fat-to-lesion elasticity ratio values were helpful in differentiating benign and malignant breast masses. The scanning orientation did not significantly affect the diagnostic performance of shear wave elastography for breast masses.

Healthcare Professionals' Learning Needs and Perspectives on Essential Information in Genetic Cancer Care: A Systematic Review.

BACKGROUND: The increased demand for genetic testing and counseling necessitates healthcare professionals (HCPs) to improve their genetic competency through training programs. This systematic review identified HCPs' learning needs and their perspectives on essential information for families with hereditary cancer. METHODS: This review covered studies published from 2013 to 2024 across five databases. Data were analyzed using a content analysis. RESULTS: Thirteen studies involving 332 HCPs were analyzed. Most studies focused on the learning needs of physicians caring for families affected by Hereditary Breast and Ovarian Cancer in North America and Europe. HCPs required training emphasizing practical counseling skills over the basics of genetics. Learning needs varied by profession: physicians needed training in assessing cancer risk and supporting decision-making in risk management; nurses required information on resources and the genetic care system; genetic counselors sought guidance on family communication and planning. Essential information identified for families included risk-reducing strategies, personalized cancer risk assessment, family implications, psychological issues, (cascade) genetic testing, and social concerns. CONCLUSIONS: The findings have implications for the development of training programs for HCPs, emphasizing the need for tailored training based on professions. Future research should explore the needs of HCPs caring for families with diverse hereditary cancers and cultural backgrounds.

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer.

PURPOSE: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). MATERIALS AND METHODS: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. RESULTS: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). CONCLUSION: GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

A new assessment of patellar instability using coronal magnetic resonance images of the patella superimposed on the femur and its clinical utility.

OBJECTIVE: This study aimed to evaluate the clinical utility of a new assessment for patellar subluxation using magnetic resonance (MR) images of the patella superimposed on the femur and to determine its correlation with the tibial tuberosity-trochlear groove (TT-TG) distance. MATERIALS AND METHODS: This retrospective study included 81 men and 44 women who underwent MR imaging at our institution. There were 19 cases of patellar dislocation. The control group consisted of 116 patients. An assessment of the distance of subluxation was carried out using coronal superimposed MR images. The results were correlated with the TT-TG distance calculated using the axial combined MR images. The sensitivity and specificity of various distances of subluxation were evaluated as diagnostic thresholds for patellar dislocation, where the clinical diagnosis was used as the standard of reference. RESULTS: The use of the distance of subluxation on coronal superimposed MR images showed discrete difference between patellar dislocation and controls. The mean distance of subluxation was approximately 3 times larger for patients with patellar dislocation compared with controls (P < 0.001). Likewise, the mean TT-TG distance was approximately 50% greater for patients with patellar dislocation compared with controls (P < 0.001). However, there was no correlation between the distance of subluxation and the TT-TG distance. The best diagnostic discrimination was achieved at the 7-mm threshold of subluxation. CONCLUSIONS: The use of the distance of subluxation on coronal superimposed MR images can be a useful method to evaluate patellar dislocation. The best diagnostic discrimination was achieved at a threshold of 7 mm.

A case of extrinsic compression of the left main coronary artery secondary to pulmonary artery dilatation.

Extrinsic compression of the left main coronary artery (LMCA) secondary to pulmonary artery dilatation is a rare syndrome. Most cases of pulmonary artery hypertension but no atherosclerotic risk factors rarely undergo coronary angiography, and hence, diagnoses are seldom made and proper management is often delayed in these patients. We describe a patient that presented with pulmonary hypertension, clinical angina, and extrinsic compression of the LMCA by the pulmonary artery, who was treated successfully by percutaneous coronary intervention. Follow-up coronary angiography showed patent stent in the LMCA in the proximity of the dilated main pulmonary artery. This case reminds us that coronary angiography and percutaneous coronary intervention should be considered in pulmonary hypertension patients presenting with angina or left ventricular dysfunction.