Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001.

ABSTRACT: Lisocabtagene maraleucel (liso-cel) demonstrated significant efficacy with a manageable safety profile as third-line or later treatment for patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) in the TRANSCEND NHL 001 study. Primary end points were adverse events (AEs), dose-limiting toxicities, and objective response rate (ORR) per independent review committee. Key secondary end points were complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). After 2-year follow-up, patients could enroll in a separate study assessing long-term (≤15 years) safety and OS. Liso-cel-treated patients (N = 270) had a median age of 63 years (range, 18-86 years) and a median of 3 prior lines (range, 1-8) of systemic therapy, and 181 of them (67%) had chemotherapy-refractory LBCL. Median follow-up was 19.9 months. In efficacy-evaluable patients (N = 257), the ORR was 73% and CR rate was 53%. The median (95% confidence interval) DOR, PFS, and OS were 23.1 (8.6 to not reached), 6.8 (3.3-12.7), and 27.3 months (16.2-45.6), respectively. Estimated 2-year DOR, PFS, and OS rates were 49.5%, 40.6%, and 50.5%, respectively. In the 90-day treatment-emergent period (N = 270), grade 3 to 4 cytokine release syndrome and neurological events occurred in 2% and 10% of patients, respectively. The most common grade ≥3 AEs in treatment-emergent and posttreatment-emergent periods, respectively, were neutropenia (60% and 7%) and anemia (37% and 6%). Liso-cel demonstrated durable remissions and a manageable safety profile with no new safety signals during the 2-year follow-up in patients with R/R LBCL. These trials were registered at www.ClinicalTrials.gov as #NCT02631044 and #NCT03435796.

Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study.

BACKGROUND: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas. METHODS: We did a seamless design study at 14 cancer centres in the USA. We enrolled adult patients (aged ≥18 years) with relapsed or refractory large B-cell lymphomas. Eligible histological subgroups included diffuse large B-cell lymphoma, high-grade B-cell lymphoma with rearrangements of MYC and either BCL2, BCL6, or both (double-hit or triple-hit lymphoma), diffuse large B-cell lymphoma transformed from any indolent lymphoma, primary mediastinal B-cell lymphoma, and follicular lymphoma grade 3B. Patients were assigned to one of three target dose levels of liso-cel as they were sequentially tested in the trial (50 × 106 CAR+ T cells [one or two doses], 100 × 106 CAR+ T cells, and 150 × 106 CAR+ T cells), which were administered as a sequential infusion of two components (CD8+ and CD4+ CAR+ T cells) at equal target doses. Primary endpoints were adverse events, dose-limiting toxicities, and the objective response rate (assessed per Lugano criteria); endpoints were assessed by an independent review committee in the efficacy-evaluable set (comprising all patients who had confirmed PET-positive disease and received at least one dose of liso-cel). This trial is registered with ClinicalTrials.gov, NCT02631044. FINDINGS: Between Jan 11, 2016, and July 5, 2019, 344 patients underwent leukapheresis for manufacture of CAR+ T cells (liso-cel), of whom 269 patients received at least one dose of liso-cel. Patients had received a median of three (range 1-8) previous lines of systemic treatment, with 260 (97%) patients having had at least two lines. 112 (42%) patients were aged 65 years or older, 181 (67%) had chemotherapy-refractory disease, and seven (3%) had secondary CNS involvement. Median follow-up for overall survival for all 344 patients who had leukapheresis was 18·8 months (95% CI 15·0-19·3). Overall safety and activity of liso-cel did not differ by dose level. The recommended target dose was 100 × 106 CAR+ T cells (50 × 106 CD8+ and 50 × 106 CD4+ CAR+ T cells). Of 256 patients included in the efficacy-evaluable set, an objective response was achieved by 186 (73%, 95% CI 66·8-78·0) patients and a complete response by 136 (53%, 46·8-59·4). The most common grade 3 or worse adverse events were neutropenia in 161 (60%) patients, anaemia in 101 (37%), and thrombocytopenia in 72 (27%). Cytokine release syndrome and neurological events occurred in 113 (42%) and 80 (30%) patients, respectively; grade 3 or worse cytokine release syndrome and neurological events occurred in six (2%) and 27 (10%) patients, respectively. Nine (6%) patients had a dose-limiting toxicity, including one patient who died from diffuse alveolar damage following a dose of 50 × 106 CAR+ T cells. INTERPRETATION: Use of liso-cel resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas, including those with diverse histological subtypes and high-risk features. Liso-cel is under further evaluation at first relapse in large B-cell lymphomas and as a treatment for other relapsed or refractory B-cell malignancies. FUNDING: Juno Therapeutics, a Bristol-Myers Squibb Company.

Method Validation for Determination of Thallium by Inductively Coupled Plasma Mass Spectrometry and Monitoring of Various Foods in South Korea.

Thallium (Tl) is a rare element and one of the most harmful metals. This study validated an analytical method for determining Tl in foods by inductively coupled plasma mass spectrometry (ICP-MS) based on food matrices and calories. For six representative foods, the method's correlation coefficient (R2) was above 0.999, and the method limit of detection (MLOD) was 0.0070-0.0498 µg kg-1, with accuracy ranging from 82.06% to 119.81% and precision within 10%. We investigated 304 various foods in the South Korean market, including agricultural, fishery, livestock, and processed foods. Tl above the MLOD level was detected in 148 samples and was less than 10 µg kg-1 in 98% of the samples. Comparing the Tl concentrations among food groups revealed that fisheries and animal products had higher Tl contents than cereals and vegetables. Tl exposure via food intake did not exceed the health guidance level.

Etch characteristics of Si and TiO2 nanostructures using pulse biased inductively coupled plasmas.

The etch characteristics of Si and TiO2 nanostructures for optical devices were investigated using pulse biased inductively coupled plasmas (ICP) with SF6/C4F8/Ar and BCl3/Ar, respectively, and the results were compared with those etched using continuous wave (CW) biased ICP. By using pulse biasing compared to CW biasing in the etching of the line/pillar nanostructures with various aspect ratios, there was a reduction of the aspect ratio dependent etching (ARDE) and therefore, uniform etch depths for nanostructures with different pattern widths, as well as the improvement of the etch profiles without any notching, were obtained not only for silicon nanostructures but also for TiO2 nanostructures. The investigation has determined that the improvement of etch profiles and reduced ARDE effect when using pulse biasing are related to the decreased surface charging caused by neutralization of the surface and the improved radical adsorption (or etch byproduct removal) on the etched surfaces during the pulse-off period for pulse biasing compared to CW biasing.

Changes in taste and food preferences in breast cancer patients receiving chemotherapy: a pilot study.

PURPOSE: Cancer treatment may relate to appetite reduction and malnutrition. We investigated taste alterations and dish-type preferences during chemo- and/or radiation therapy in breast cancer patients. METHODS: Breast cancer patients (BC, n = 59) scheduled to receive cancer therapy and healthy subjects (control group or CTRL, n = 49) were voluntarily recruited. Taste detection thresholds (DTs) and recognition thresholds (RT) were compared between pre-treatment BC patients and CTRL for sweet (sucrose), salty (NaCl), bitter (caffeine), and sour (citric acid) solutions. Changes in taste thresholds and dish preferences during treatment were monitored in the BC group. Blood chemistry and anthropometric data were collected. RESULTS: At baseline, BC patients demonstrated lower sweet and salty DTs and RTs and a higher sour RT compared to CTRL. Bitter DT and RT were similar in both groups. Mild/soft dishes were preferred over fried/oily dishes by BC patients. Throughout treatment in BC patients, sweet thresholds significantly declined, while salty, bitter, and sour DTs and RTs were not affected, and there was no increase in preference for a dish. However, preference towards mild/soft dishes remained. While sweet-sour fruits and sweetened nuts were not favored during therapy. CONCLUSIONS: Sensitivities to sweet, salty, and sour but not bitter tastes differed between BC patients and CTRL. During treatment, sweet taste sensitivity increased while other tastes were unaffected. BC patients preferred mild/soft dishes over fried and sweetened dishes compared to CTRL. Our findings may contribute to developing dishes for breast cancer patients to increase food intake and thereby lower the risk of malnutrition.

Changes in health behaviours and health status of novice nurses during the first 2 years of work.

AIMS: To explore changes in health behaviours and health status of novice nurses during the first 2 years of work. BACKGROUND: Novice nurses experience many difficulties in maintaining healthy behaviours while adapting to clinical settings. However, studies about the health of novice nurses have not focused on changes over time. DESIGN: Longitudinal descriptive study with self-reported questionnaires. METHODS: Data were collected from 493 novice nurses who started work between September 2014 - December 2015 at a tertiary hospital in Seoul. Dietary behaviours, sleep, depressive symptoms, perceived stress and health status were measured at six time points during the first 2 years of work (the first day of orientation before ward placement, 6 weeks after starting work and 6, 12, 18 and 24 months of work). Changes were examined using means or percentages and 95% confidence intervals. RESULTS: Unhealthy dietary behaviours increased across 6 months, continuing for 2 years. Sleep quality and quantity, depressive symptoms, perceived stress and health status first worsened and then improved; however, they were worse than at baseline. CONCLUSION: Organizational support for novice nurses is urgently needed. Workplace health education programmes will help them adjust to rotating shift work and maintain better health status.

Potential Photoprotective Effect of Dietary Corn Silk Extract on Ultraviolet B-Induced Skin Damage.

Ultraviolet B (UVB) irradiation causes adverse effects on the skin. Corn silk contains flavonoids and other bioactive compounds and antioxidants, which may prevent skin photoaging through antioxidant and anti-inflammatory effects. We aimed to investigate the potential photoprotective effects of dietary corn silk on UVB-induced skin damage in mice and the mechanisms behind these effects on human skin cells. Oral administration of corn silk water extract (CS) (2 or 4 g/kg/day) for 19 weeks decreased epidermal thickness, wrinkle formation, and positive staining for PCNA, Ki67, and 8-OHdG, and increased collagen staining in UVB-irradiated SKH-1 hairless mice compared with controls. The pro-inflammatory NF-κB target genes (IL-1ß, iNOS, and COX-2) and MMP-9 expressions were lower in the CS groups, and TGF-ß/Smad signaling increased. Low skin lipid peroxidation and blood DNA oxidation levels and high blood glutathione were detected. Antioxidant transcription factor Nrf2-related catalase and SOD1 proteins and glutaredoxin mRNA levels increased. The results of CS extract treatment and UVB irradiation in HaCaT cells showed the same results in Nrf2 and NF-κB target genes. An LC-MS/MS analysis showed that the CS extract contained potential antioxidants, which might have contributed to its anti-photoaging effects in tissues and cells. CS extract may reduce UVB-induced skin damage through antioxidant and anti-inflammatory mechanisms.

Time-dependent ROC analysis for censored biomarker data due to limit of detection.

Receiver operating characteristic (ROC) curve is a well-established analysis method to evaluate biomarker's discrimination accuracy for binary outcomes. When the endpoint of interest is time to event outcome such as time to cancer recurrence, a biomarker's time-varying discriminatory performance is often assessed by time-dependent ROC analysis. In practice, biomarkers are often imprecisely measured due to the limitation of assay sensitivity. The values below the limit of detection are not detectable. Ignorance of such data characteristic may lead to inaccurate estimation of marker's potential discriminatory power. The objective of this article is to extend time-dependent ROC method to censored biomarker data by using parameter estimates from the Cox regression model that accommodates censored biomarker measurements. In the simulation study, the proposed methods are shown to outperform the simple substitution method that has been conventionally adopted for handling censored data. Application data are also given to illustrate our methods.

Analysis of Five Arboviruses and Culicoides Distribution on Cattle Farms in Jeollabuk-do, Korea.

Arthropod-borne viruses (Arboviruses) are transmitted by arthropods such as Culicoides biting midges and cause abortion, stillbirth, and congenital malformation in ruminants, apparently leading to economic losses to farmers. To monitor the distribution of Culicoides and to determine their relationship with different environmental conditions (temperature, humidity, wind speed, and altitude of the farms) on 5 cattle farms, Culicoides were collected during summer season (May-September) in 2016 and 2017, and analyzed for identification of species and detection of arboviruses. About 35% of the Culicoides were collected in July and the collection rate increased with increase in temperature and humidity. The higher altitude where the farms were located, the more Culicoides were collected on inside than outside. In antigen test of Culicoides against 5 arboviruses, only Chuzan virus (CHUV) (2.63%) was detected in 2016. The Akabane virus (AKAV), CHUV, Ibaraki virus and Bovine ephemeral fever virus (BEFV) had a positive rate of less than 1.8% in 2017. In antigen test of bovine whole blood, AKAV (12.96%) and BEFV (0.96%) were positive in only one of the farms. As a result of serum neutralization test, antibodies against AKAV were generally measured in all the farms. These results suggest that vaccination before the season in which the Culicoides are active is probably best to prevent arbovirus infections.

Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Bendamustine plus rituximab is a standard of care for the management of patients with relapsed or refractory chronic lymphocytic leukaemia. New therapies are needed to improve clinically relevant outcomes in these patients. We assessed the efficacy and safety of adding idelalisib, a first-in-class targeted phosphoinositide-3-kinase δ inhibitor, to bendamustine plus rituximab in this population. METHODS: For this international, multicentre, double-blind, placebo-controlled trial, adult patients (≥18 years) with relapsed or refractory chronic lymphocytic leukaemia requiring treatment who had measurable lymphadenopathy by CT or MRI and disease progression within 36 months since their last previous therapy were enrolled. Patients were randomly assigned (1:1) by a central interactive web response system to receive bendamustine plus rituximab for a maximum of six cycles (bendamustine: 70 mg/m2 intravenously on days 1 and 2 for six 28-day cycles; rituximab: 375 mg/m2 on day 1 of cycle 1, and 500 mg/m2 on day 1 of cycles 2-6) in addition to either twice-daily oral idelalisib (150 mg) or placebo until disease progression or intolerable study drug-related toxicity. Randomisation was stratified by high-risk features (IGHV, del[17p], or TP53 mutation) and refractory versus relapsed disease. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat population. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT01569295. FINDINGS: Between June 26, 2012, and Aug 21, 2014, 416 patients were enrolled and randomly assigned to the idelalisib (n=207) and placebo (n=209) groups. At a median follow-up of 14 months (IQR 7-18), median progression-free survival was 20·8 months (95% CI 16·6-26·4) in the idelalisib group and 11·1 months (8·9-11·1) in the placebo group (hazard ratio [HR] 0·33, 95% CI 0·25-0·44; p<0·0001). The most frequent grade 3 or worse adverse events in the idelalisib group were neutropenia (124 [60%] of 207 patients) and febrile neutropenia (48 [23%]), whereas in the placebo group they were neutropenia (99 [47%] of 209) and thrombocytopenia (27 [13%]). An increased risk of infection was reported in the idelalisib group compared with the placebo group (grade ≥3 infections and infestations: 80 [39%] of 207 vs 52 [25%] of 209). Serious adverse events, including febrile neutropenia, pneumonia, and pyrexia, were more common in the idelalisib group (140 [68%] of 207 patients) than in the placebo group (92 [44%] of 209). Treatment-emergent adverse events leading to death occurred in 23 (11%) patients in the idelalisib group and 15 (7%) in the placebo group, including six deaths from infections in the idelalisib group and three from infections in the placebo group. INTERPRETATION: Idelalisib in combination with bendamustine plus rituximab improved progression-free survival compared with bendamustine plus rituximab alone in patients with relapsed or refractory chronic lymphocytic leukaemia. However, careful attention needs to be paid to management of serious adverse events and infections associated with this regimen during treatment selection. FUNDING: Gilead Sciences Inc.

A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia.

Idelalisib is a first-in-class oral inhibitor of PI3Kδ that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naïve older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375 mg/m(2) weekly ×8 and idelalisib 150 mg twice daily continuously for 48 weeks. Patients completing 48 weeks without progression could continue to receive idelalisib on an extension study. The median time on treatment was 22.4 months (range, 0.8-45.8+). The overall response rate (ORR) was 97%, including 19% complete responses. The ORR was 100% in patients with del(17p)/TP53 mutations and 97% in those with unmutated IGHV. Progression-free survival was 83% at 36 months. The most frequent (>30%) adverse events (any grade) were diarrhea (including colitis) (64%), rash (58%), pyrexia (42%), nausea (38%), chills (36%), cough (33%), and fatigue (31%). Elevated alanine transaminase/aspartate transaminase was seen in 67% of patients (23% grade ≥3). The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naïve older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL. This study is registered at ClinicalTrials.gov as #NCT01203930.

Measurement of crude-cell-extract glycerol dehydratase activity in recombinant Escherichia coli using coupled-enzyme reactions.

Glycerol dehydratase (GDHt), which converts glycerol to 3-hydroxypropionaldehyde, is essential to the production of 1,3-propanediol (1,3-PDO) or 3-hydroxypropionic acid (3-HP). A reliable GDHt activity assay in crude-cell extract was developed. In the assay, GDHt converted 1,2-propanediol (1,2-PDO) to propionaldehyde, which was further converted to 1-propionic acid by aldehyde dehydrogenase (KGSADH) or to 1-propanol by yeast-alcohol dehydrogenase (yADH), while the NADH concentration change was monitored spectrophotometrically. Cells should be disintegrated by Bead Beater/French Press, not by chemical methods (BugBuster®/B-PER™), because the reagents significantly inactivated GDHt and coupling enzymes. Furthermore, in the assay mixture, a much higher activity of KGSADH (>200-fold) or yADH (>400-fold) than that of GDHt should have been maintained. Under optimal conditions, both KGSADH and yADH showed practically the same activity. The coupled-enzyme assay method established here should prove to be applicable to recombinant strains developed for the production of 3-HP and/or 1,3-PDO from glycerol.

Patient reporting pain intensity immediately after surgery can be associated with underlying depression in women with breast cancer.

OBJECTIVE: The aims of this study were to determine the prevalence of severe, definite depression symptoms, as measured using the Center for Epidemiological Studies Depression Scale (CES-D), and the association between high CES-D scores (i.e., ≥25) and sociodemographic and perioperative factors during perioperative period. METHODS: Among 1690 consecutive breast cancer patients who were admitted for definitive breast surgery during the study period, 1499 patients were included in this study. Patients with a past medical history of psychiatric medication or support, a plan for elective surgery due to locoregional recurrence, or any metastatic disease were excluded. The CES-D score was checked 1 day before definitive surgeries. The sociodemographic data and perioperative data were analyzed. RESULTS: The mean CES-D score was 18.5, with 24.1% (362/1499) and 56.7% (850/1499) having high CES-D scores of ≥25 and ≥16, respectively. Multivariate analysis revealed that the number of family members with any malignancy (≥2 vs. 0), sedative medication (yes vs. no), and postoperative numeric rating scale scores (persistent, severe pain vs. stably mild pain) were significantly associated factors for severe, definite depression symptoms [CES-D score of ≥25: adjusted odds ratio (OR) = 1.56, 95% confidence interval (CI) = 1.10-2.21, p = 0.013; adjusted OR = 1.65, 95% CI = 1.00-2.71, p = 0.048; and adjusted OR = 2.14, 95% CI = 1.15-3.95, p = 0.016, respectively]. CONCLUSION: Depression may increase the intensity of postoperative acute pain. Self-reporting of persistent postoperative pain intensity is potentially useful in detecting hidden depression symptoms in breast cancer patients during the perioperative period.

A Case of Orbital Metastasis of Uterine Leiomyosarcoma With Intracranial Extension Presenting With Proptosis.

A 57-year-old woman presented with protrusion of the OS 2 months in duration and decreased vision 1 month in duration. The patient was diagnosed with uterine leiomyosarcoma approximately 3 years before presentation. Lung and liver metastases were diagnosed by biopsy 1 year prior to this visit. CT revealed a solid mass with central necrosis in the left lateral orbit that resulted in orbital shifting, bony destruction, and intracranial extension. The diagnosis was left orbital metastatic leiomyosarcoma, and the patient died 2 months after receiving the diagnosis.

Genetic characterization of porcine epidemic diarrhea virus in Korea from 1998 to 2013.

The number of porcine epidemic diarrhea (PED) cases has increased over the past 20 years in Korea, with a major outbreak in 2013. A total of 27 Korean strains from 1998 to 2013 were analyzed (excluding the noncoding regions) and divided into two groups for comparison of the spike (S), ORF3, envelope (E), membrane (M), and nucleocapsid (N) genes with those of reference strains, vaccine strains, and previously identified strains based on phylogenetic analysis. Analysis of the selection patterns of PEDV isolated in Korea indicated positive selection of nine nonsynonymous sites in the S and N proteins and negative selection at 97 sites for all of the proteins. Interestingly, eight nonsynonymous mutations in S showed no significant pattern change over the 15-year period, and one of eight mutation sites was found only in IC05TK, GN05DJ, and KNU0802 in the epidemic years 2005 and 2008. These eight mutations were also present during the epidemic years in China. Furthermore, of the signs of positive selection in the S protein, the conservative substitutions were more frequent than radical substitutions in PEDVs, suggesting that the evolution of Korean strains has been slow. Serological cross-reactivity was detected between three field PEDVs and two vaccine strains, with different serum neutralization titers. In conclusion, although Korean PEDVs have been evolving slowly, their diverse antigenicity and genetics imply that multilateral efforts to prevent future PED outbreaks are required.

Estimation of C-index for cox proportional hazards model with censored biomarker covariate subject to limits of detection.

Biomarkers play an important role to predict the time to event of interest. To evaluate the prediction performance of biomarkers, Cox proportional hazards model and Harrell's C-index have been widely used. However, when some of the biomarker measurements are not fully observed due to detection limits of given instrument, evaluation may become complicated. We estimate the Cox model and concordance probability in the presence of censored biomarker data. Simulation study demonstrates that the proposed method outperforms over the simple ad hoc method. Our approach is especially useful to evaluate discrimination potential of the biomarker regardless of variant detection limits.

Serological characteristics of affected cattle during an outbreak of bovine enzootic encephalomyelitis caused by Akabane virus.

During an outbreak of bovine enzootic encephalomyelitis caused by the Akabane virus (AKAV) in 2010, 210 serum samples were collected from the affected cattle, and serological investigations for the AKAV were performed using a serum neutralization test (SNT) and an enzyme-linked immunosorbent assay (ELISA). The seropositive rates for SNT and ELISA were 90.0 and 85.2 %, respectively. The titers of SNT (log2) against the AKAV were higher than 4.0 in the highly affected cattle (80.0 %). This finding indicates that most affected cattle were infected with the AKAV and that strong immune responses against this virus were elicited in affected cattle. The strong immune response to the AKAV in cattle may provide insight into the occurrence of bovine encephalomyelitis caused by the AKAV.

Canine adenovirus type 1 in a fennec fox (Vulpes zerda).

A 10-mo-old female fennec fox (Vulpes zerda) with drooling suddenly died and was examined postmortem. Histologic examination of different tissue samples was performed. Vacuolar degeneration and diffuse fatty change were observed in the liver. Several diagnostic methods were used to screen for canine parvovirus, canine distemper virus, canine influenza virus, canine coronavirus, canine parainfluenza virus, and canine adenovirus (CAdV). Only CAdV type 1 (CAdV-1) was detected in several organs (liver, lung, brain, kidney, spleen, and heart), and other viruses were not found. CAdV-1 was confirmed by virus isolation and nucleotide sequencing.

Influence of Dietary Polyunsaturated Fatty Acid Intake on Potential Lipid Metabolite Diagnostic Markers in Renal Cell Carcinoma: A Case-Control Study.

Non-invasive diagnostics are crucial for the timely detection of renal cell carcinoma (RCC), significantly improving survival rates. Despite advancements, specific lipid markers for RCC remain unidentified. We aimed to discover and validate potent plasma markers and their association with dietary fats. Using lipid metabolite quantification, machine-learning algorithms, and marker validation, we identified RCC diagnostic markers in studies involving 60 RCC and 167 healthy controls (HC), as well as 27 RCC and 74 HC, by analyzing their correlation with dietary fats. RCC was associated with altered metabolism in amino acids, glycerophospholipids, and glutathione. We validated seven markers (l-tryptophan, various lysophosphatidylcholines [LysoPCs], decanoylcarnitine, and l-glutamic acid), achieving a 96.9% AUC, effectively distinguishing RCC from HC. Decreased decanoylcarnitine, due to reduced carnitine palmitoyltransferase 1 (CPT1) activity, was identified as affecting RCC risk. High intake of polyunsaturated fatty acids (PUFAs) was negatively correlated with LysoPC (18:1) and LysoPC (18:2), influencing RCC risk. We validated seven potential markers for RCC diagnosis, highlighting the influence of high PUFA intake on LysoPC levels and its impact on RCC occurrence via CPT1 downregulation. These insights support the efficient and accurate diagnosis of RCC, thereby facilitating risk mitigation and improving patient outcomes.

Disease Course of Korean African Swine Fever Virus in Domestic Pigs Exposed Intraorally, Intranasally, Intramuscularly, and by Direct Contact with Infected Pigs.

African swine fever (ASF) is a fatal contagious disease affecting swine. The first Korean ASF virus (ASFV) isolate (Korea/Pig/Paju1/2019) was used to compare the disease course of ASFV in pigs inoculated via the four routes. In the challenge experiment, domestic pigs were infected via the intraoral (IO) and intranasal (IN) routes with a 106 50% hemadsorbing dose (HAD50) and an intramuscular (IM) injection of 103 HAD50. In the direct contact (DC) group, five naïve pigs were brought into direct contact with two IM-ASFV-infected pigs. IO-, IN-, and IM-inoculated pigs showed similar disease courses, whereas DC pigs had comparable ASF syndrome after a 7-day latent period. The disease course in the DC route, one of the most common routes of infection, was not significantly different from that in the IO and IN routes. IM and DC groups differed in terms of the severity of fever and hemorrhagic lesions in the lymph nodes and spleen, indicating that the IM route, suitable for early vaccine development trials, is not appropriate for studying the ASFV infection mechanism, including early stage of infection, and IO and IN challenges with a designated dose can be alternatives in trials for assessing ASFV pathogenicity and vaccine efficacy investigations.