Miracle-dz/UniFAR-FTUs huggingface dataset:
Yeast quiescence exit swiftness is influenced by cell volume and chronological age

Quiescence exit swiftness is crucial not only for micro-organisms in competition for an environmental niche, such as yeast, but also for the maintenance of tissue homeostasis in multicellular species. Here we explore the effect of replicative and chronological age on Saccharomyces cerevisiae quiescence exit efficiency. Our study reveals that this step strongly relies on the cell volume in quiescence but is not influenced by cell replicative age, at least for cells that have undergone less than 10 divisions. Furthermore, we establish that chronological age strongly impinges on cell’s capacities to exit quiescence. This effect is not related to cell volume or due to cell’s inability to metabolize external glucose but rather seems to depend on intracellular trehalose concentration. Overall, our data illustrate that the quiescent state is a continuum evolving with time, early and deep quiescence being distinguishable by the cell’s proficiency to re-enter the proliferation cycle.
Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days.

The efficacy of the traditionally recommended ampicillin (Amp) plus gentamicin (GM) regimen was compared with that of a trimethoprim-sulfamethoxazole (TMP/SMZ)-plus-GM regimen and the adequacy of 14 days total therapy for acute uncomplicated pyelonephritis (AUPN). Eighty-five women hospitalized for AUPN were randomly assigned to receive either Amp, 1 g intravenously (iv) every 6 h for 3 days, then 500 mg orally four times daily, or TMP/SMZ, 160/800 mg iv every 12 h for 3 days, then 160/800 mg orally twice daily. Initially, all patients also received GM every 8 h iv (mean, 606 doses). Antimicrobial resistance necessitated modifying therapy of 14 (32%) of the Amp recipients but of none of the TMP/SMZ recipients (P less than .001). Both regimens produced a satisfactory bacteriologic and clinical response in all cases. Reinfection occurred in 11% of Amp and in 8% of TMP/SMZ recipients. No patient experienced relapsing infection. The TMP/SMZ regimen was less costly and less likely to require modification due to antimicrobial resistance.
Development of an internet version of the Lidcombe Program of early stuttering intervention: A trial of Part 1

Abstract Purpose: There is evidence that access to treatment for early stuttering is not available for all who need it. An internet version of the Lidcombe Program for early stuttering (Internet-LP) has been developed to deal with this shortfall. The LP is suitable for such development because it is delivered by parents in the child’s everyday environment, with training by a speech-language pathologist. A Phase I trial of Internet-LP Part 1, comprising parent training, is reported here. Method: Eight parents of pre-schoolers who stutter were recruited and six completed the trial. Result: Post-trial assessment indicated that the parents scored well for identifying and measuring stuttering and for knowledge about conducting practice sessions, including how to present verbal contingencies during practice sessions. Conclusion: The results prompted minor adjustments to Part 1 and guided the construction of Part 2, which instructs parents during the remainder of the treatment process.
Practical Initial Risk Stratification Based on Lymph Node Metastases in Pediatric and Adolescent Differentiated Thyroid Cancer.

BACKGROUND Data on the risk stratification of pediatric differentiated thyroid cancer (DTC) remain scarce. This study aimed to evaluate the predictors of structural persistent/recurrent disease and revise an initial risk-stratification system in pediatric DTC patients. METHODS This retrospective cohort study included 203 patients (aged <20 years) from two tertiary referral centers in Korea. The extent of cervical lymph node (LN) metastasis was classified based on the location or number of metastatic LNs. RESULTS During a median follow-up duration of 5.5 years, structural persistent/recurrent disease was observed in 51 (25%) patients, including 22 (11%) with distant metastases. The presence of extrathyroidal extension (ETE) and lateral cervical LN metastases or more than five metastatic LNs were independent predictors for structural persistent/recurrent disease. The presence of bilateral lateral cervical LN metastases or >10 metastatic LNs were independent predictors for distant metastasis. A total of 67 (33%), 72 (35%), and 64 (32%) patients were classified into the low-, intermediate-, and high-risk groups, respectively, based on the presence of ETE and the extent of cervical LN metastases. Compared to the low-risk group, the intermediate- and high-risk groups had a significantly greater risk of structural persistent/recurrent disease (hazard ratio = 7.32, p = 0.008, and hazard ratio = 24.28, p < 0.001, respectively). CONCLUSIONS This revised initial risk-stratification system based on the presence of ETE and the extent of cervical LN metastasis is useful for predicting the clinical outcomes of pediatric DTC patients. The findings could facilitate the practical use of a risk-stratification system.
Angioedème médicamenteux: un effet secondaire inhabituel de la simvastatine

L'angioedeme histaminique medicamenteux, est une urgence diagnostique et therapeutique car le pronostic vital peut etre mis en jeu a court terme par le risque d’evolution vers un œdeme de Quincke. Il se definit par un gonflement soudain localise non inflammatoire des tissus sous cutanes et/ou sous-muqueux, il se voit surtout avec les penicillines, les produits de contraste iodes, les inhibiteurs de l'enzyme de conversion. Il est rarement observe avec la simvastatine. Nous rapportons le cas d’une patiente âgee de 43 ans, suivie pour hypercholesterolemie sous regime depuis deux ans mal equilibree, a presente 24h apres la prise de la simvastatine un œdeme non inflammatoire au niveau des paupieres et des joues associe a une macrocheilite avec une sensation de tension douloureuse, sans lesions urticariennes ni dysphonie ni dyspnee, le tout evoluant dans un contexte de conservation de l’etat general. La patiente a ete hospitalisee avec arret de toute medication, elle a recu une injection d’hemissuccinate d’hydrocortisone et d’antihistaminique. L’evolution etait favorable, une disparition de l’angioedeme etait observee 48h apres le traitement. Une declaration au centre de pharmacovigilance et une interdiction de la reintroduction des statines etait realisee.
Kuijia: Traffic Rescaling in Software-Defined Data Center WANs

Network faults like link or switch failures can cause heavy congestion and packet loss. Traffic engineering systems need a lot of time to detect and react to such faults, which results in significant recovery times. Recent work either preinstalls a lot of backup paths in the switches to ensure fast rerouting or proactively prereserves bandwidth to achieve fault resiliency. Our idea agilely reacts to failures in the data plane while eliminating the preinstallation of backup paths. We propose Kuijia, a robust traffic engineering system for data center WANs, which relies on a novel failover mechanism in the data plane called rate rescaling. The victim flows on failed tunnels are rescaled to the remaining tunnels and enter lower priority queues to avoid performance impairment of aboriginal flows. Real system experiments show that Kuijia is effective in handling network faults and significantly outperforms the conventional rescaling method.
PI5P4Kγ functions in DTX1-mediated Notch signaling

Significance The Notch signaling pathway performs a vital role in biological processes ranging from stem cell maintenance to cell viability. This highly conserved pathway must be tightly controlled, since defects in signaling can promote disease. The E3 ubiquitin ligase DTX1 has emerged as a key negative regulator of Notch signaling, where Notch ubiquitination by DTX1 is thought to control intracellular sorting decisions of the receptor. Here we show that DTX1 can regulate Notch activity independent of directly ubiquitinating the receptor, suggesting that DTX1 targets other factors involved in Notch transport. Using an activity-based screen for DTX1 substrates, we identify PI5P4Kγ, a lipid kinase, and discover that PI5P4Kγ and DTX1 have opposing activities in regulating Notch transit through recycling endosomes. Notch signaling is an evolutionarily conserved pathway that is essential for development, where it controls processes ranging from cell differentiation to survival. Transport through endosomes is a critical step in regulating Notch signaling capacity, where the E3 ubiquitin ligase DTX1 is thought to control Notch1 intracellular transport decisions by direct receptor ubiquitination. However, how DTX1 regulates Notch1 transport within endosomes and the consequence of Notch1 ubiquitination by DTX1 remain unresolved. Here we demonstrate that DTX1 colocalizes with Notch1 on tubulovesicular recycling endosomes. We find that DTX1 silencing leads to enhanced Notch1 recycling from this compartment to the cell surface via a rab4a-mediated transport route. This, in turn, increases Notch1 cell-surface levels and enhances signaling. Surprisingly, we discovered that DTX1 depletion also elevates Notch1 activity mediated by a mutant form of the receptor that lacks lysine residues for ubiquitination, suggesting that DTX1 targets additional factors. Using an activity-based screen for ubiquitination targets, we identified multiple DTX1 substrates including PI5P4Kγ, a lipid kinase involved in PI(4,5)P2 production. Immunolocalization analysis reveals that PI5P4Kγ, like DTX1 and Notch1, is present on tubulovesicular recycling endosomes. However, in contrast to DTX1, Notch1 signaling is inhibited by pharmacological inactivation or siRNA depletion of PI5P4Kγ. Moreover, loss of PI5P4Kγ activity decreases Notch1 recycling rates and reduces receptor cell-surface levels. Collectively, these findings argue that PI5P4Kγ positively regulates the Notch pathway by promoting receptor recycling. Additionally, they support a model where DTX1 controls Notch1 endosomal sorting decisions by controlling PI5P4Kγ-mediated production of PI(4,5)P2.
High-Power Fractional-Order Capacitor With 1 < α < 2 Based on Power Converter

A fractional-order capacitor (FOC) plays a vital role in fractional-order circuits. However, the FOC with order $1 based on existing manufacturing schemes can be only operated in milliwatt power level. Thus, the applications of an FOC in power conversion are limited. To solve the problem, this paper proposes a novel method for realizing a high-power FOC with order $1 , in which a power converter is applied to emulate the current–voltage characteristic of an ideal FOC, so the rated power of the FOC can be increased greatly and depended on the power converter. The corresponding topology and its control strategy are provided. The available experiments verify the effectiveness of the proposed approach.
Comprehensive drug utilization review in neonates: liposomal amphotericin B

This drug utilization evaluation aims to review current evidence on safety and efficacy of using liposomal amphotericin B (LAMB) in newborns with candidiasis, and compare it to the conventional preparation. Conventional amphotericin B deoxycholate (DAMB) is more commonly used in newborns, but dose‐limiting adverse effects may compromise its efficacy. This review will examine the advantages and disadvantages of liposomal amphotericin B and define its place in current practice.
Statin Effects on Metabolic Profiles: Data From the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial)

Background— Statins lower cholesterol by inhibiting HMG-CoA reductase, the rate-limiting enzyme of the metabolic pathway that produces cholesterol and other isoprenoids. Little is known about their effects on metabolite and lipoprotein subclass profiles. We, therefore, investigated the molecular changes associated with pravastatin treatment compared with placebo administration using a nuclear magnetic resonance–based metabolomics platform. Methods and Results— We performed metabolic profiling of 231 lipoprotein and metabolite measures in the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial) study, a placebo-controlled randomized clinical trial designed to test the effects of pravastatin (40 mg once daily) on cardiovascular risk. Metabolic profiles were assessed at baseline and after 3 months of treatment. Pravastatin lowered low-density lipoprotein cholesterol (change in SD units [95% confidence interval]: −1.01 [−1.14, −0.88]), remnant cholesterol (change in SD units [95% confidence interval]: −1.03 [−1.17, −0.89]), and apolipoprotein B (change in SD units [95% confidence interval]: −0.98 [−1.11, −0.86]) with similar effect magnitudes. In addition, pravastatin globally lowered levels of lipoprotein subclasses, with the exception of high-density lipoprotein subclasses, which displayed a more heterogeneous response pattern. The lipid-lowering effect of pravastatin was accompanied by selective changes in lipid composition, particularly in the cholesterol content of very-low-density lipoproteinparticles. In addition, pravastatin reduced levels of several fatty acids but had limited effects on fatty acid ratios. Conclusions— These randomized clinical trial data demonstrate the widespread effects of pravastatin treatment on lipoprotein subclass profiles and fatty acids. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT03073018.
Etiology Is Linked to the Length of Admission in Patients With Acute Pancreatitis: Is Novel Endoscopy an Unrecognized Cause?

To the Editor: W e read with interest the study by Wadhwa et al that found 110,394 more discharges for acute pancreatitis in 2012 than in 1997 and an increase in the rate of discharges per 100,000 persons from 60.4 to 87.7 (P < 0.001) in the same period. The study also showed an increase in the cost of hospitalization of 118.6% but a decline in average stay of 0.5 days every 5 years (P < 0.001) to approximately 4.7 days by 2012. Consequently, the national bill
Imaging pathological tau in atypical parkinsonian disorders.

PURPOSE OF REVIEW This review examines the current literature on tau imaging in atypical parkinsonian disorders and other tauopathies. RECENT FINDINGS There are a number of tau PET radiotracers that have demonstrated promising preliminary results in atypical parkinsonian disorders, such as progressive supranuclear palsy and corticobasal degeneration. These radiotracers were capable of selectively labeling tau in vitro and in vivo, with high affinity. Other radiotracers tested more extensively in patients with Alzheimer's disease have also been able to successfully image tau deposition. SUMMARY The development of tau radioligands for PET has led to the current testing of these tracers in clinical studies, many of which concentrate on patients with Alzheimer's disease. Atypical parkinsonian disorders such as progressive supranuclear palsy and corticobasal degeneration are now being investigated as well. These disorders can be very difficult to diagnose, because of their clinical overlap with other parkinsonian disorders. Imaging tau using PET could serve as a diagnostic biomarker for these tauopathies and provide a means of assessing treatment that targets tau burden.
Functional Expression and Characterization of the Recombinant N-Acetyl-Glucosamine/N-Acetyl-Galactosamine-Specific Marine Algal Lectin BPL3

Lectins, characterized by their carbohydrate-binding ability, have extensive practical applications. However, their industrial use is limited due to impurity. Thus, quality-controlled production of recombinant lectin is necessary. In this study, the algal lectin BPL3 (Bryopsis plumosa lectin 3) was successfully produced using a bacterial expression system, BL21(DE3), with an artificial repeated structure (dimeric construct). Recombinant dimeric BPL3 (rD2BPL3) was confirmed by LC-MS/MS spectrometry. Expression efficiency was greater for the construct with the repeat structure (rD2BPL3) than the monomeric form (rD1BPL3). Optimal conditions for expression were 1 mM IPTG at 20 °C. Recombinant lectin was purified under denaturing conditions and refolded by the flash dilution method. Recombinant BPL3 was solubilized in 1× PBS containing 2 M urea. rD2BPL3 showed strong hemagglutination activity using human erythrocyte. rD2BPL3 had a similar sugar specificity to that of the native protein, i.e., to N-acetyl-glucosamine (GlcNAc) and N-acetyl-galactosamine (GalNAc). Glycan array results showed that recombinant BPL3 and native BPL3 exhibited different binding properties. Both showed weak binding activity to α-Man-Sp. Native BPL3 showed strong binding specificity to the alpha conformation of amino sugars, and rD2BPL3 had binding activity to the beta conformation. The process developed in this study was suitable for the quality-controlled large-scale production of recombinant lectins.
Author's reply to: Prognosis of sentinel lymph node biopsy in patients with thick melanoma by a propensity score matching prospective study

1 Dermatology Department, Hospital Universitari Germans Trial i Pujol, Universitat Aut onoma de Barcelona, Badalona, Spain 2 Dermatology Department, Instituto Dermatol ogico GlobalDerm, Palma del R ıo, C ordoba, Spain 3 Section of Dermatology, Medical Sciences Department, University of Turin, Turin, Italy 4 Melanoma Unit, Dermatology Department, Hospital Clinic, Universitat de Barcelona, Institut d’investigacions biomèdiques August Pi i Sunyer (IDIBAPS),
Multiple role of 3‐mercaptopyruvate sulfurtransferase: antioxidative function, H2S and polysulfide production and possible SOx production

Rat 3‐mercaptopyruvate sulfurtransferase (MPST) is a 32 808 Da simple protein. Cys247 is a catalytic site, and Cys154 and Cys263 are on the enzyme surface. MPST is found in all tissues, particularly in the kidneys, although the localization of its activity differs in each tissue. In this review, four functions of MPST are reviewed: (i) antioxidative function: Cys247 is redox‐sensitive and serves as a redox‐sensing switch. It is oxidized to cysteine sulfenate, which has a low redox potential, upon which the enzyme is inactivated. Then, reduced thioredoxin (Trx) with a reducing system (Trx reductase and NADPH) reduces the sulfenate to restore activity; meanwhile, Cys154 and Cys263 form an intermolecular disulfide bond, which serves as another redox‐sensing switch. Consequently, Trx specifically cleaves the intermolecular disulfide bond by converting it from the inactive form (dimer) to the active form (monomer). (ii) Hydrogen sulfide and polysulfide production: hydrogen sulfide is produced via reduction of the persulfurated sulfur‐acceptor substrate by reduced Trx or Trx with a reducing system; as an alternative process, stable polysulfurated or persulfurated Cys247 as a reaction intermediate is reduced by Trx with a reducing system to release hydrogen sulfide and polysulfides. (iii) Possible sulfur oxide production: sulfur oxides (SO, SO2 and SO3) can be produced in the redox cycle of sulfane sulfur formed at the catalytic site Cys247 (Cys–SO−, Cys–SO2− and Cys–SO3−) as reaction intermediates and released by reduced Trx or Trx with a reducing system. (iv) Possible anxiolytic‐like effects: MPST‐knockout mice exhibited anxiolytic‐like effects.
Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS)

Importance Sexual dysfunction, an important determinant of women’s health and quality of life, is commonly associated with declining estrogen levels around the menopausal transition. Objective To determine the effects of oral or transdermal estrogen therapy vs placebo on sexual function in postmenopausal women. Design, Setting, and Participants Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS), a 4-year prospective, randomized, double-blinded, placebo-controlled trial of menopausal hormone therapy in healthy, recently menopausal women. Of 727 KEEPS enrollees, 670 agreed to participate in this multicenter ancillary study. Women were 42 to 58 years old, within 36 months from last menstrual period. Data were collected from July 2005 through June 2008 and analyzed from July 2010 through June 2017. Interventions Women were randomized to either 0.45 mg/d oral conjugated equine estrogens (o-CEE), 50 µg/d transdermal 17&bgr;-estradiol (t-E2), or placebo. Participants also received 200 mg oral micronized progesterone (if randomized to o-CEE or t-E2) or placebo (if randomized to placebo estrogens) for 12 days each month. Main Outcomes and Measures Aspects of sexual function and experience (desire, arousal, lubrication, orgasm, satisfaction, and pain) were assessed using the Female Sexual Function Inventory (FSFI; range, 0-36 points; higher scores indicate better sexual function). Low sexual function (LSF) was defined as an FSFI overall score of less than 26.55. Distress related to low FSFI score (required for the diagnosis of sexual dysfunction) was not evaluated. Results The 670 participants had a mean (SD) age of 52.7 (2.6) years. The t-E2 treatment was associated with a significant yet moderate improvement in the FSFI overall score across all time points compared with placebo (average efficacy, 2.6; 95% CI, 1.11-4.10; adjusted P = .002). With o-CEE treatment, there was no significant difference in FSFI overall score compared with placebo (mean efficacy, 1.4; 95% CI, −0.1 to 2.8; adjusted P = .13). There was no difference in FSFI overall score between the t-E2 and o-CEE groups on average across 48 months (adjusted P = .22). In the individual domains of sexual function, t-E2 treatment was associated with a significant increase in mean lubrication (0.61; 95% CI, 0.25-0.97; P = .001) and decreased pain (0.67; 95% CI, 0.25-1.09; P = .002) compared with placebo. Overall, the proportion of women with LSF was significantly lower after t-E2 treatment compared with placebo (67%; 95% CI, 55%-77% vs 76%; 95% CI, 67%-83%; P = .04). For o-CEE there was no significant reduction in the odds of LSF. Conclusions and Relevance Treatment with t-E2 modestly improved sexual function in early postmenopausal women, but whether it relieved symptoms of distress is not known. Trial Registration clinicaltrials.gov Identifier: NCT00154180
Two Roads Diverged: Distinct Mechanisms of Attentional Bias Differentially Predict Negative Affect and Persistent Negative Thought

Attentional biases to threatening stimuli have been implicated in various emotional disorders. Theoretical approaches often carry the implicit assumption that various attentional bias measures tap into the same underlying construct, but attention itself is not a unitary mechanism. Most attentional bias tasks—such as the dot probe (DP)—index spatial attention, neglecting other potential attention mechanisms. We compared the DP with emotion-induced blindness (EIB), which appears to be mechanistically distinct, and examined the degree to which these tasks predicted (a) negative affect, (b) persistent negative thought (i.e., worry, rumination), and (c) each other. The 2 tasks did not predict each other, and they uniquely accounted for negative affect in a regression analysis. The relationship between EIB and negative affect was mediated by persistent negative thought, whereas that between the DP and negative affect was not, suggesting that EIB may be more intimately linked than spatial attention with persistent negative thought. Experiment 2 revealed EIB to have a favorable test–retest reliability. Together, these findings underscore the importance of distinguishing between attentional bias mechanisms when constructing theoretical models of, and interventions that target, particular emotional disorders.