Summary
Erythema nodosum leprosum (ENL) is a severe immune reaction commonly encountered as a complication in patients with multibacillary leprosy. Management of chronic ENL in leprosy is challenging ...and necessitates the use of systemic immunosuppressants, including corticosteroids and thalidomide. No single drug is universally effective and most current therapeutic agents carry a significant risk of systemic toxicity. Apremilast is an orally effective phosphodiesterase‐4 inhibitor with a potent immunomodulatory action and is clinically effective in inflammatory conditions like chronic plaque psoriasis. We report two patients with poorly controlled chronic ENL, despite the use of multiple therapeutic agents. Both patients demonstrated significant clinical improvement with apremilast, without any adverse effects, thereby suggesting its potential as a novel therapeutic option in chronic ENL.
What's already known about this topic?
Erythema nodosum leprosum (ENL) is an immune‐mediated reaction in patients with multibacillary leprosy, with chronicity and recurrences frequently reported.
Management of chronic ENL requires systemic immunosuppressants like corticosteroids, which may not be universally effective and carry a risk of serious toxicity.
Apremilast is an oral immunomodulator with good efficacy in inflammatory conditions like chronic plaque psoriasis.
What does this study?
Apremilast may be an effective therapeutic agent in patients with chronic ENL.
Linked Comment: Walker. Br J Dermatol 2020;182:837–838.
Technologies that rely on quantum bits (qubits) require long coherence times and high-fidelity operations.sup.1. Superconducting qubits are one of the leading platforms for achieving these ...objectives.sup.2,3. However, the coherence of superconducting qubits is affected by the breaking of Cooper pairs of electrons.sup.4-6. The experimentally observed density of the broken Cooper pairs, referred to as quasiparticles, is orders of magnitude higher than the value predicted at equilibrium by the Bardeen-Cooper-Schrieffer theory of superconductivity.sup.7-9. Previous work.sup.10-12 has shown that infrared photons considerably increase the quasiparticle density, yet even in the best-isolated systems, it remains much higher.sup.10 than expected, suggesting that another generation mechanism exists.sup.13. Here we provide evidence that ionizing radiation from environmental radioactive materials and cosmic rays contributes to this observed difference. The effect of ionizing radiation leads to an elevated quasiparticle density, which we predict would ultimately limit the coherence times of superconducting qubits of the type measured here to milliseconds. We further demonstrate that radiation shielding reduces the flux of ionizing radiation and thereby increases the energy-relaxation time. Albeit a small effect for today's qubits, reducing or mitigating the impact of ionizing radiation will be critical for realizing fault-tolerant superconducting quantum computers.
SHAPER: can you hear the shape of a jet? Ba, Demba; Dogra, Akshunna S.; Gambhir, Rikab ...
The journal of high energy physics,
06/2023, Letnik:
2023, Številka:
6
Journal Article
Recenzirano
Odprti dostop
A
bstract
The identification of interesting substructures within jets is an important tool for searching for new physics and probing the Standard Model at colliders. Many of these substructure tools ...have previously been shown to take the form of optimal transport problems, in particular the Energy Mover’s Distance (EMD). In this work, we show that the EMD is in fact
the
natural structure for comparing collider events, which accounts for its recent success in understanding event and jet substructure. We then present a Shape Hunting Algorithm using Parameterized Energy Reconstruction (S
haper
), which is a general framework for defining and computing shape-based observables. S
haper
generalizes
N
-jettiness from point clusters to any extended, parametrizable shape. This is accomplished by efficiently minimizing the EMD between events and parameterized manifolds of energy flows representing idealized shapes, implemented using the dual-potential Sinkhorn approximation of the Wasserstein metric. We show how the geometric language of observables as manifolds can be used to define novel observables with built-in infrared-and-collinear safety. We demonstrate the efficacy of the S
haper
framework by performing empirical jet substructure studies using several examples of new shape-based observables.
Summary
Background
Four validated psoriatic arthritis (PsA) screening tools are used for diagnosing PsA in patients with psoriasis.
Objectives
To evaluate the sensitivity and specificity of the ...Toronto Psoriatic Arthritis Screen II (ToPAS II), the Psoriatic Arthritis Screening and Evaluation (PASE), the Psoriasis Epidemiology Screening Tool (PEST) and the Early Arthritis for Psoriatic Patients (EARP) questionnaires in diagnosing PsA in patients with psoriasis.
Methods
This was a noninterventional, cross‐sectional study. In total, 302 patients with psoriasis completed all the questionnaires prior to rheumatological evaluation. Patients diagnosed as having a rheumatological disease were excluded. Characteristics of joint involvement in PsA were noted, but details of non‐PsA rheumatological diseases were not captured.
Results
Of 302 patients with psoriasis, 45 (14·9%) had PsA, according to the Classification of Psoriatic Arthritis criteria; 27 (8·9%) had a ToPAS II score ≥ 8, suggestive of PsA; 36 (11·9%) had a PEST questionnaire score ≥ 3, suggestive of PsA; 50 (16·5%) had a PASE questionnaire score ≥ 44 (PASE 44), suggestive of PsA; 47 (15·5%) had a PASE score of 47 (PASE 47; used in development of the PASE questionnaire); and 72 (23·8%) patients had an EARP questionnaire score ≥ 3, suggestive of PsA. The sensitivities and specificities of EARP, PASE 44, PASE 47, PEST and ToPAS II were 91%, 80%, 76%, 53% and 44%, and 88%, 95%, 95%, 95% and 97%, respectively.
Conclusions
EARP was found to have the best sensitivity; ToPAS II had the highest specificity. A major limitation of the study design was the exclusion of pre‐existing rheumatological diseases.
What's already known about this topic?
Four screening tools for the diagnosis of psoriatic arthritis (PsA) in patients with psoriasis have been evaluated in different settings and populations, with different results.
What does this study add?
We have evaluated the sensitivity of four screening questionnaires used in the diagnosis of PsA in patients with psoriasis Toronto Psoriatic Arthritis Screen II, Psoriatic Arthritis Screening and Evaluation, Psoriasis Epidemiology Screening Tool and Early Arthritis for Psoriatic Patients (EARP) in a clinical setting and found that the newest tool (EARP) has the best sensitivity.
This is the first such evaluation to be carried out in real‐life clinical practice.
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Linked Comment: Coates. Br J Dermatol 2017; 176:574–575.
High-grade serous (HGS) ovarian cancer accounts for 90% of all ovarian cancer-related deaths. However, factors that drive HGS ovarian cancer tumor growth have not been fully elucidated. In ...particular, comprehensive analysis of the metabolic requirements of ovarian cancer tumor growth has not been performed. By analyzing The Cancer Genome Atlas mRNA expression data for HGS ovarian cancer patient samples, we observed that six enzymes of the folic acid metabolic pathway were overexpressed in HGS ovarian cancer samples compared with normal ovary samples. Systematic knockdown of all six genes using short hairpin RNAs (shRNAs) and follow-up functional studies demonstrated that serine hydroxymethyl transferase 1 (SHMT1) was necessary for ovarian cancer tumor growth and cell migration in culture and tumor formation in mice. SHMT1 promoter analysis identified transcription factor Wilms tumor 1 (WT1) binding sites, and WT1 knockdown resulted in reduced SHMT1 transcription in ovarian cancer cells. Unbiased large-scale metabolomic analysis and transcriptome-wide mRNA expression profiling identified reduced levels of several metabolites of the amino sugar and nucleotide sugar metabolic pathways, including sialic acid N-acetylneuraminic acid (Neu5Ac), and downregulation of pro-oncogenic cytokines interleukin-6 and 8 (IL-6 and IL-8) as unexpected outcomes of SHMT1 loss. Overexpression of either IL-6 or IL-8 partially rescued SHMT1 loss-induced tumor growth inhibition and migration. Supplementation of culture medium with Neu5Ac stimulated expression of IL-6 and IL-8 and rescued the tumor growth and migratory phenotypes of ovarian cancer cells expressing SHMT1 shRNAs. In agreement with the ovarian tumor-promoting role of Neu5Ac, treatment with Neu5Ac-targeting glycomimetic P-3Fax-Neu5Ac blocked ovarian cancer growth and migration. Collectively, these results demonstrate that SHMT1 controls the expression of pro-oncogenic inflammatory cytokines by regulating sialic acid Neu5Ac to promote ovarian cancer tumor growth and migration. Thus, targeting of SHMT1 and Neu5Ac represents a precision therapy opportunity for effective HGS ovarian cancer treatment.
Ovarian torsion is defined as partial or complete rotation of the ovarian vascular pedicle and causes obstruction to venous outflow and arterial inflow. Ovarian torsion is usually associated with a ...cyst or tumor, which is typically benign; the most common is mature cystic teratoma. Ultrasonography (US) is the primary imaging modality for evaluation of ovarian torsion. US features of ovarian torsion include a unilateral enlarged ovary, uniform peripheral cystic structures, a coexistent mass within the affected ovary, free pelvic fluid, lack of arterial or venous flow, and a twisted vascular pedicle. The presence of flow at color Doppler imaging does not allow exclusion of torsion but instead suggests that the ovary may be viable, especially if flow is present centrally. Absence of flow in the twisted vascular pedicle may indicate that the ovary is not viable. The role of computed tomography (CT) has expanded, and it is increasingly used in evaluation of abdominal pain. Common CT features of ovarian torsion include an enlarged ovary, uterine deviation to the twisted side, smooth wall thickening of the twisted adnexal cystic mass, fallopian tube thickening, peripheral cystic structures, and ascites. Understanding the imaging appearance of ovarian torsion will lead to conservative, ovary-sparing treatment.
The article presents a concise review of our investigations on the preferred transition paths followed as well as high-pressure-induced structural changes in nanocrystalline rare-earth sesquioxides ...that include Y2O3, Sm2O3, Gd2O3, Eu2O3, Dy2O3, Ho2O3, and Yb2O3. The starting phase in all samples was predominantly cubic, as characterized using X-ray diffraction and Raman spectroscopy. The pressure-induced structural changes were primarily tracked via changes in phonon modes in the Raman spectra. The structural transition sequences demonstrated behaviors differing from the polycrystalline trends usually observed; however, it was interesting to note that the onset pressures and subsequent shifts in the phonon modes followed a trend similar to the unpressurized samples when observed with respect to the f-electron number. The mode Grüneisen parameters were estimated from the high-pressure data, which indicated a swifter response to external stimuli as the particle size reduced below an average of 50 nm. It was also inferred that the presence of traces of disordered/nonstoichiometric material directly affected the structural transition sequence. A summary of the results and the mechanisms leading to such structural transitions is discussed.
Summary
Methotrexate (MTX) has remained the backbone of the treatment for moderate to severe psoriasis ever since its first use nearly half a century ago. Over the years, its high efficacy, low cost, ...relative ease of administration and usefulness in concomitant psoriatic arthritis have contributed in making MTX the drug of choice in managing severe psoriasis. Although the majority of patients achieve remission of disease activity with MTX, a significant proportion may experience mild and transient adverse effects. From time to time, various guidelines on the use of MTX have correctly and adequately stressed the need for strict monitoring of haematological and hepatic adverse events. Over the years, the safe total cumulative dose of MTX (above which the risk of developing liver fibrosis is significantly increased) has been raised. Simultaneously, there has been an increased emphasis on developing noninvasive tests such as scanning and serum biomarker assays for detecting early liver fibrosis, in order to obviate the need for liver biopsy. However, the recent discovery and subsequent proliferating use of biological response modifiers has gradually shifted the focus away from MTX, despite it still being the most commonly prescribed drug for psoriasis worldwide. The aim of this review is to present a detailed account of MTX therapy and its use in psoriasis, along with its current relevance in disease management in the evolving era of biological drugs.
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