Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of erecta mutation on leaf serration differs between Arabidopsis accessions

ABSTRACT Serrations or teeth of plant leaves are a morphological trait regulated genetically and environmentally. Very recently, it has been reported that the receptor kinases encoded by three ERECTA (ER)-family genes, ER, ER-LIKE1 (ERL1) and ERL2, redundantly play a role in tooth growth in Arabidopsis thaliana. In the report, Columbia (Col) accession was used for analyses, where none of the signal mutant of the ER-family genes exhibited serration defects. The toothless, smooth leaf margin phenotype was evident only when two out of the three ER-family genes were lost. Interestingly, it has been widely recognized that the Arabidopsis accession Landsberg erecta (L.er), which carries a loss-of-function mutation in ER, develops round leaves with smaller leaf teeth. Here, we show that the functional ER transgene promotes the tooth growth in L.er to the level of Col, indicating that the er mutation in L.er is likely responsible for the reduced growth of leaf teeth. This suggests that er single mutation affects tooth growth in a different manner between Col and L.er backgrounds, though the molecular basis for this background-dependent effect remains to be addressed.
Polo‐like‐kinase 1 is a proviral host factor for hepatitis B virus replication

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) and current treatments for chronic hepatitis B and HCC are suboptimal. Herein, we identified cellular serine/threonine Polo‐like‐kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate PLK1 inhibition a potential antiviral strategy. To this end, we employed physiologically relevant HBV infection models of primary human hepatocytes (PHHs) and differentiated HepaRG cells in conjunction with pharmacologic PLK1 inhibitors, small interfering RNA (siRNA)‐mediated knockdown, and overexpression of constitutively active PLK1 (PLK1CA). In addition, a humanized liver Fah−/−/Rag2−/−/Il2rg−/− (FRG) mouse model was used to determine the antiviral effect of PLK1 inhibitor BI‐2536 on HBV infection in vivo. Finally, in vitro PLK1 kinase assays and site‐directed mutagenesis were employed to demonstrate that HBV core protein (HBc) is a PLK1 substrate. We demonstrated that HBV infection activated cellular PLK1 in PHHs and differentiated HepaRG cells. PLK1 inhibition by BI‐2536 or siRNA‐mediated knockdown suppressed HBV DNA biosynthesis, whereas overexpression of PLK1CA increased it, suggesting that the PLK1 effects on viral biosynthesis are specific and that PLK1 is a proviral cellular factor. Significantly, BI‐2536 administration to HBV‐infected humanized liver FRG mice strongly inhibited HBV infection, validating PLK1 as an antiviral target in vivo. The proviral action of PLK1 is associated with the biogenesis of the nucleocapsid, as BI‐2536 leads to its decreased intracellular formation/accumulation. In this respect, our studies identified HBc as a PLK1 substrate in vitro, and mapped PLK1 phosphorylation sites on this protein. Conclusion: PLK1 is a proviral host factor that could be envisaged as a target for combined antiviral and antitumoral strategies against HBV infection and HBV‐mediated carcinogenesis. (Hepatology 2017;66:1750–1765)
Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice

The Na+‐taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. Mice or healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake kinetics were determined in wild‐type (WT), organic anion transporting polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1‐transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic transporter mRNA levels were assessed in rat hepatoma cells and in mice by peptide injection or adeno‐associated virus–mediated overexpression. NTCP inhibition using myrcludex B had only moderate effects on bile acid kinetics in WT mice, but completely inhibited active transport of conjugated bile acid species in OATP knockout mice. Cholesterol 7α‐hydroxylase Cyp7a1 expression was strongly down‐regulated upon prolonged inhibition of hepatic uptake of conjugated bile acids. Fgf15 (mouse counterpart of FGF19) expression was induced in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B–treated cholestatic mice, whereas plasma FGF19 was not induced in humans treated with myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte‐models and mouse organoids by basolateral incubation with a high concentration (1 mM) of conjugated bile acids. Conclusion: NTCP and OATPs contribute to hepatic uptake of conjugated bile acids in mice, whereas the predominant uptake in humans is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile acids in the systemic circulation to induce FGF15/19, which modulates hepatic bile acid synthesis and uptake. (Hepatology 2017;66:1631–1643).
Safety and efficacy of current direct‐acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV‐TARGET study

Data outside of clinical trials with direct‐acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct‐acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion: In a large prospective observational cohort study, direct‐acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090‐1101).
The C-terminal domains of Arabidopsis GL3/EGL3/TT8 interact with JAZ proteins and mediate dimeric interactions

ABSTRACT The phytohormone jasmonates (JAs) regulate plant development, growth, secondary metabolism, and defense responses. JAs act through CORONATINE INSENSITIVE1 (COI1) to induce the degradation of JA ZIM-domain (JAZ) proteins, and activate JAZ-repressed transcription factors to regulate plant response. We previously showed that the basic helix-loop-helix (bHLH) and MYB members of the WD-repeat/bHLH/MYB complex interacted with JAZs and mediated JA-induced anthocyanin accumulation and trichome initiation. In this study, we showed that the C-terminal domain of the bHLH members (GLABRA3 [GL3], ENHANCER OF GLABRA3 [EGL3] and TRANSPARENT TESTA8 [TT8]) interacted with JAZs in yeast and plant, and mediated dimerizations between the bHLH members. Our study provides further understanding of the bHLH members of the WD-repeat/bHLH/MYB complex in JA pathway.
Vascular Access Recirculation in Hemodialysis Patients With Two Noncuffed, Single‐lumen, Jugular Catheters in the Same Jugular Vein

Having achieved excellent results with single‐lumen temporary hemodialysis catheters as a long‐term vascular access in our center, in this study we examined the amount of vascular access recirculation in the case of using two single‐lumen catheters in a single jugular vein. In 11 adult end‐stage renal disease patients on chronic hemodialysis (HD), vascular access recirculation was studied using a thermodilution technique during dialysis at our center. The vascular access in all patients consisted of two pre‐curved, 15 cm‐long, 8‐Fr catheters inserted in the right jugular vein. Recirculation measurements were performed with the blood flow set to 250 mL/min in all patients. In five patients, additional measurements were performed with the blood flow set to 200 mL/min. During 16 HD procedures, 55 recirculation measurements were taken. The rate of recirculation was <15% in 50 measurements, between 15% and 20% in four measurements, and >20% in one measurement. The average recirculation rate during a single procedure was <15% in 10 patients, and 16.2% in one patient. We did not find any significant differences in the recirculation rates measured either at higher or lower blood flow rates. The clinical importance of vascular access recirculation was noted in a single patient. Vascular access recirculation in hemodialysis patients with two single‐lumen catheters in the same jugular vein is mostly acceptable. Some measures for preventing clinically important recirculation are also suggested.
Does Cinacalcet Improve the Prognosis of Dialysis Patients?

Appropriate control of serum calcium (Ca) and inorganic phosphate (Pi) levels is required for better prognosis of dialysis patients. Cinacalcet is known to reduce not only serum parathyroid hormone (PTH) but also Ca and Pi levels; however, it remains unclear whether cinacalcet can ultimately improve the prognosis of such patients. In this paper, the ongoing prospective observational study (Q Cohort Study) and double‐blind randomized controlled study (EVOLVE Study) are introduced. In the Q Cohort Study, cinacalcet therapy is indicated when intact PTH levels exceed 180 pg/mL, accounting for 31.3% of the study population (N = 3009). In the EVOLVE Study, the primary endpoint is the time to occurrence of composite events including all‐cause mortality or nonfatal cardiovascular events. There is a related pilot study that treated patients over a 6‐month period with cinacalcet. The findings showed that cinacalcet reduced serum PTH, Ca, and Pi levels and that if the patient had lower PTH levels at baseline, the dosage of vitamin D could be greatly reduced. Thus, in some patients concomitant vitamin D and cinacalcet therapy may be preferred to vitamin D alone.
Peritoneal Dialysis‐Related Peritonitis Caused by Vancomycin‐Resistant Enterococcus faecium

1. Vasko R, Koziolek M, Fuzesi L, Konig F, Strutz F, Muller GA. Fulminant plasmapheresis-refractory thrombotic microangiopathy associated with advanced gastric cancer. Ther Apher Dial 2010;14:222–5. 2. Antman KH, Skarin AT, Mayer RJ, Hargreaves HK, Canellos GP. Microangiopathic hemolytic anemia and cancer: a review. Medicine 1979;58:377–84. 3. Howard MA, Williams LA, Terrell DR, Duvall D, Vesely SK, George JN. Complications of plasma exchange in patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. III. An additional study of 57 consecutive patients, 2002–2005. Transfusion 2006;46: 154–6. 4. Fontana S, Gerritsen HE, Hovinga JK, Furlan M, Lämmle B. Microangiopathic haemolytic anaemia in metastasizing malignant tumours is not associated with a severe deficiency of the von Willebrand factor-cleaving protease. Br J Haematol 2001;113:100–2.
Accuracy of a Freezing Point Depression Technique Osmometer

Purpose The purpose of this study was to examine the precision and accuracy of the Fiske 110 Osmolarity System under different protocols to determine the possible applications of this device in tear film research and clinical practice. Methods Three separate studies were performed. In the first, Fiske 110 measurements were made on undiluted and diluted (1:1, 1:4, and 1:9 dilutions) standard samples of different osmolarity values: 50, 290, and 850 mOsm/kg and 297 and 338 mOsm/L. In the second study, measurements were made on different types of contact lens care solutions. Finally, in an agreement study, measurements were made in two sets of 60 subjects to compare TearLab versus Fiske 110 (using both 2- and 4-&mgr;L tear sample). Results Although osmolarity measurements for undiluted solutions differed statistically from reference standard values, all biases were in the tolerance range proposed by the manufacturer except for the 850-mOsm/kg solution. No significant differences from reference osmolarity values were observed for the 1:1 and 1:4 diluted 297- and 338-mOsm/L H2O solutions, respectively, although all diluted solutions showed a possible bias out of the range provided. Osmolarities for the soft contact lens solutions fell within the range 293 to 309 mOsm/kg with the exception of Opti-Free Express (225 mOsm/kg). In the agreement study, significant differences were observed between measurements obtained using the TearLab and both Fiske 110 procedures, although the Fiske 110 (4 &mgr;L) procedure was closer to the TearLab than the Fiske (2 &mgr;L) procedure. Conclusions For undiluted solutions, the Fiske 110 shows good performance, making it a useful device for osmolarity measurements in lens care solutions or eye drops. A worse performance was observed for more diluted standard solution samples. When testing diluted samples, performance was acceptable for osmolarity values close to tear values.
Factors triggering upper airway infections in athletes

Clinical and epidemiological data suggest that strenuous exercise increases the incidence of upper respiratory tract infections (URTI) in athletes. However, little is known if the risk for URT infections is associated with the type of sports performed (e.g., endurance vs. strength exercise, or mixed sports) or whether accompanying lifestyle factors such as dietary behavior, daily stress, and the intake of nutritional supplements or immunostimulants influence the incidence of URT infections. In order to increase our knowledge on such questions, 852 athletes who attended our outpatient department for sports medicine filled out a retrospective questionnaire (1-year self-recalled) dealing with the following questions: number of URTI episodes in the last 12 months; number of training days lost due to URTI; type of exercise (endurance/power/mixed type/swimming); training extent; special procedures for regeneration (e.g., physiotherapy); lifestyle and daily stress; dietary behavior; intake of nutritional supplements; and use of immunostimulants. Of the respondents, 72.1% reported one or more URTI episodes in the last 12 months. In a multiple-regression model, the following variables were positive predictors of an URTI episode: endurance sports [odds ratio, 2.15; CI (95%), 1.51–3.06; p < . 000], daily stress [odds ratio, 1.97; CI (95%), 1.26–3.08; p < . 01], sleep deprivation [odds ratio, 1.69; CI (95%), 1.14–2.5; p < . 01], female gender (odds ratio, 1.5; CI [95%] 1.05–2.13; p < .05),training extent in hour per week [odds ratio, 1.05; CI (95%), 1.02–1.08; p < . 01), and diet control [odds ratio, 0.6; CI (95%), 0.37–0.82; p < . 01]. The positive predictive value of this model for URTI episodes was 76%. Subgroup analysis revealed that in athletes exhibiting the highest rate of infections, use of immunostimulants reduced the number of training days lost (2 days) due to infections. In conclusion, both sports-specific items as well as lifestyle variables contribute substantially in explaining the risk for athletes to develop respiratory infections. These findings should be considered in sports-specific training regimes, particularly in athletes prone to URT infections.
Occult Hepatitis B Virus Infection in Hemodialysis Patients: A Concept for Consideration

Hemodialysis patients potentially have an increased risk of infection with parenterally transmitted viral agents due to an impaired host immune response and multiple transfusion requirements. Viral hepatitis is considered as a problem for hemodialysis patients because 1.9% of all deaths among this population are related to the consequence of viral hepatitis. Hepatitis B virus (HBV) is one of the most important causes of transmitted infections by the parenteral route in hemodialysis patients. Occult HBV infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg), which harbors potential risk of HBV transmission through hemodialysis. There are conflicting reports on the prevalence of occult HBV infection (OBI) in hemodialysis patients. Considering the importance of occult HBV infection in hemodialysis patients and the growing evidence on this subject, the purpose of this review is to provide comprehensive information on OBI prevalence in hemodialysis patients and highlight the most important points in this issue.
Posttraumatic Stress and Panic Psychopathology: Clinical Import, Research Advances, and Future Directions—Introduction to the Special Issue

There has been a relative dearth of empirical attention focused on the study of the co‐occurrence of posttraumatic stress and panic psychopathology. Since these conditions represent two prevalent and impairing psychiatric conditions, the study of their diagnostic and phenomenological comorbidity is clinically meaningful and theoretically warranted. The articles in this series discuss the possible cognitive–affective mechanisms relevant to both conditions and elucidate innovations in applicable clinical intervention approaches. Thus, the overarching purpose of this series is to underscore key empirical questions, to showcase emerging research, and to stimulate further scientific inquiry into the co‐occurrence of posttraumatic stress and panic psychopathology.
Therapeutic Drug Monitoring (TDM) of Antimicrobial Agents

Submitted 21 May 2008, Accepted 26 May 2008 Correspondence : Shin-Woo Kim, M.D. Department of Internal Medicine, Kyungpook National University Hospital 50, Samduk 2-Ga, Chung-Gu, Daegu, Korea 700-721 Tel : +82-053-420-6525, Fax : +82-053-424-5542 E-mail : ksw2kms@knu.ac. kr 개인에게 약제사용량과 방법의 유지 및 변경을 결정하게 도와주는 과정 전체를 therapeutic drug monitoring (TDM)이라 할 수 있다. 항생제 중 β-lactam, macrolide 및 quinolone 등의 약제 종 설
Effect of Short Recovery Periods on Ocular Comfort During Daily Lens Wear

Purpose To assess the impact of lens-free intervals of varying lengths on end-of-day comfort with soft contact lenses. Methods Twenty-five symptomatic lens wearers participated in this randomized, cross-over study involving nine individual 12-hour days: one spectacle (no lens) and eight lens wear days. On each lens wear day, lenses were worn bilaterally in 2-hour intervals, separated by lens-free (recovery) periods of 0, 30, 60, or 80 minutes (repeated throughout the day). For each 2-hour lens wear interval, new lenses were worn. Ocular comfort was rated on a 0 to 100 visual analogue scale (0 = extremely uncomfortable); tear film and ocular parameters were assessed at the beginning and end of each study day. This study involved two different types of silicone hydrogel lenses, and the order of lens type and length of recovery period was randomized. Participants were unaware of the true study purpose and that a new lens pair was used for each lens wear interval. Results End-of-day comfort on lens wear days was significantly worse than on the spectacle day (p < 0.002). There was no significant effect of the recovery periods on end-of-day comfort (p > 0.05). Although lens wear affected noninvasive tear film break-up time and conjunctival staining, there were no effects of recovery period length on noninvasive tear film break-up time (p > 0.05), tear meniscus height (p > 0.05), corneal staining (p > 0.05), conjunctival staining (p > 0.05), bulbar conjunctival redness (p > 0.05), or limbal redness (p > 0.05). There was no consistent effect of recovery period length on lid margin staining. Conclusions Lens-free recovery periods during a 12-hour lens wear day did not positively impact end-of-day comfort in this study. Cumulative lens wear times ranged from 8 to 12 hours, and the results suggest that once the length of lens wear exceeds the usual comfortable wear time, there is no benefit of short recovery periods.
Efficacy of Telehealth Treatments for Posttraumatic Stress-Related Symptoms: A Meta-Analysis

This meta-analysis summarizes the findings of outcome research on the degree to which telehealth treatments reduce posttraumatic stress disorder (PTSD)-related symptoms. In a search of the literature, 13 studies were identified for inclusion in the meta-analysis and were coded for relevant variables. A total of 725 participants were included. Results indicate that telehealth treatments are associated with significant pre- to postreduction in PTSD symptoms (d = 0.99, 95% confidence interval [CI]: 0.87–1.11, p < .001), and result in superior treatment effects relative to a wait-list comparison condition (d = 1.01, 95% CI: 0.76–1.26, p < .001). However, no significant findings were obtained for telehealth intervention relative to a supportive counseling telehealth comparison condition (d = 0.11, 95% CI: − 0.38 to 0.60, p = .67), and telehealth intervention produced an inferior outcome relative to a face-to-face intervention (d = − 0.68, 95% CI: − 0.39 to − 0.98, p < .001). Findings for depression symptom severity outcome were generally consistent with those for PTSD outcome. Telehealth interventions produced a significant within-group effect size (d = 0.98, 95% CI: 0.86 to 1.10, p < .001) and superior effect relative to wait-list comparison condition (d = 0.80, 95% CI: 0.56–1.05, p < .001). Relative to face-to-face interventions, telehealth treatments produced comparable depression outcome effects (d = 0.13, 95% CI: − 0.55 to 0.28, p = .53). Taken together, these findings support the use of telehealth treatments for individuals with PTSD-related symptoms.