bluuebunny/crossref_metadata_2025 huggingface dataset:
Peak Superstructure Responses of Single-Story Sliding Base Structures Under Earthquake Excitation
Authors: Hu Hong-Song
Published: August 2023

Compared to multistory sliding base (SB) structures, single-story SB structure is simple and suitable for acquiring the critical parameters influencing the structural response. For this reason, this chapter focuses on the peak superstructure responses of single-story SB structures subjected to three-component earthquake excitation. The influence of the vertical earthquake component and various structural and ground motion characteristics on the peak superstructure response are investigated, and simplified design equations are developed. The developed equations also lay a foundation for the design of multistory SB structures, which will be discussed in the next chapter.
Peak Sliding Displacements of Sliding Base Structures Under Earthquake Excitation
Authors: Hu Hong-Song
Published: August 2023

To ensure the safety of sliding base (SB) structures, the peak sliding displacement (PSD) should not exceed the predetermined sliding displacement threshold. Therefore, the PSD is an important response quantity that should be evaluated in design. In this chapter, the probability distribution of the PSD at a given level of ground motion intensity, and the influence of the vertical earthquake component and various structural and ground motion characteristics on the PSD are investigated. Simplified equations for estimating the PSD are also developed for design purposes.
Non-supersymmetric vacua and self-adjoint extensions
Authors: Mourad J. , Sagnotti A.
Published: August 2023

Abstract

Internal intervals spanned by finite ranges of a conformal coordinate z and terminating at a pair of singularities are a common feature of many string compactifications with broken supersymmetry. The squared masses emerging in lower-dimensional Minkowski spaces are then eigenvalues of Schrödinger-like operators, whose potentials have double poles at the ends of the intervals. For one-component systems, the possible self-adjoint extensions of Schrödinger operators are described by points in AdS3 × S1, and those corresponding to independent boundary conditions at the ends of the intervals by points on the boundary of AdS3. The perturbative stability of compactifications to Minkowski space time depends, in general, on these choices of self-adjoint extensions. We apply this setup to the orientifold vacua driven by the “tadpole potential” $$ V=T\ {e}^{\frac{3}{2}\phi } $$
V
=
T

e

3
2

ϕ

and find, in nine dimensions, a massive scalar spectrum, a unique choice of boundary conditions with stable tensor modes and a massless graviton, and a wide range of choices leading to massless and/or massive vector modes.
Tests of the Charge Convexity Conjecture in Caswell-Banks-Zaks theory
Authors: Aharony Ofer , Breitstein Yacov-Nir
Published: August 2023

Abstract

The Charge Convexity Conjecture (CCC) states that in a unitary conformal field theory in d ≥ 3 dimensions with a global symmetry, the minimal dimension of operators in certain representations of the symmetry, as a function of the charge q of the representation (or a generalized notion of it), should be convex. More precisely, this was conjectured to be true when q is restricted to positive integer multiples of some integer q0. The CCC was tested on a number of examples, most of which are in d < 4 dimensions, and its version in which q0 is taken to be the charge of the lowest-dimension positively-charged operator was shown to hold in all of them.

In this paper we test the conjecture in a non-trivial example of a d = 4 theory, which is the family of Caswell-Banks-Zaks IR fixed points of SU(Nc) gauge theory coupled to Nf massless fermions and Ns massless scalars. In these theories, the lowest-dimension gauge-invariant operators that transform non-trivially under the global symmetry are mesons. These may consist of two scalars, two fermions or one of each.

We find that the CCC holds in all applicable cases, providing significant new evidence for its validity, and suggesting a stronger version for non-simple global symmetry groups.
Vector Superstrata
Authors: Čeplak Nejc
Published: August 2023

Abstract

We present the construction of several microstate geometries of the supersymmetric D1-D5-P black hole in which, within six-dimensional supergravity, the momentum charge is carried by a vector field. The fully backreacted geometries are smooth and horizonless: they are asymptotically AdS3 × S3 with an AdS2 throat that smoothly caps off. We propose a holographic dual for these bulk solutions and discuss their extension to asymptotically flat space. In addition, we present several uplifts of the full six-dimensional supersymmetric ansatz to ten-dimensions. In particular, we show that there exists a frame in which geometries based on vector field momentum carriers are entirely in the NS-NS sector, making them possible starting points for the exploration of stringy black-hole microstates.
Patientenveranstaltungen in der deutschen Urologie: Trend zu Hybridformaten?
Authors: Karschuck Philipp , Müller Laura , Groeben Christer , Aksoy Cem , Flegar Luka , Zacharis Aristeidis , Baunacke Martin , Wülfing Christian , Huber Johannes
Published: August 2023

Hintergrund und Fragestellung

Patientenveranstaltungen sind ein wichtiges Instrument, um auf das steigende Bedürfnis der Öffentlichkeit nach Gesundheitsinformationen zu reagieren. Hierfür bietet die Deutsche Gesellschaft für Urologie e. V. (DGU) auf ihren Jahreskongressen das „Patientenforum“ an. Ziel der Arbeit war die Evaluation der Veranstaltungen in den Jahren 2017 bis 2019 und ein Vergleich mit dem ersten digitalen Patientenforum 2020.

Material und Methoden

Anhand eines zweiseitigen, standardisierten Fragebogens befragten wir die Besucher*innen der Präsenzpatientenforen (Präsenzgruppe = P) der drei Jahreskongresse der DGU 2017–2019 sowie die Nutzer*innen des digitalen Angebots 2020 (Onlinegruppe = O).

Ergebnisse

Für die Jahre 2017–2019 erhielten wir n = 71 und für 2020 n = 18 Datensätze. Das mediane Alter der Besucher*innen lag bei 64 (Spannweite 30–89) Jahren. Männlich waren 66 % (P) vs. 83 % (O) der Teilnehmer*innen (p = 0,005). Das Angebot wurde von beiden Gruppen gleichermaßen insgesamt als gut bis sehr gut bewertet, d. h. in Schulnoten 1,6 (P) vs. 1,6 (O; p = 0,7). Die Möglichkeit Fragen zu stellen wurde entsprechend der geringeren Interaktion im digitalen Format in Schulnoten mit 1,5 (P) vs. 2,8 (O) schlechter bewertet (p = 0,003). Auf die Frage nach dem zukünftig gewünschten Veranstaltungsformat sprachen sich die Nutzer des digitalen Patientenforums mit zwei Dritteln für eine Hybridveranstaltung vor Ort und online aus.

Schlussfolgerung

Patientenveranstaltungen eignen sich als Kommunikationsform für die Öffentlichkeit und werden von den Besucher*innen gut bewertet. Insbesondere die direkte Interaktion mit Expert*innen hat hier einen hohen Stellenwert. Präsenzformate sind mit einem hohen logistischen Aufwand sowie hohen Kosten verbunden und ihre Reichweite ist limitiert. Zukünftig können Hybridformate eine sinnvolle Alternative sein, da sie die Vorteile von Online- und Präsenzformaten kombinieren.
Preclinical and clinical pharmacology of brexanolone (allopregnanolone) for postpartum depression: a landmark journey from concept to clinic in neurosteroid replacement therapy
Authors: Reddy Doodipala Samba , Mbilinyi Robert H. , Estes Emily
Published: August 2023

This article describes the critical role of neurosteroids in postpartum depression (PPD) and outlines the landmark pharmacological journey of brexanolone as a first-in-class neurosteroid antidepressant with significant advantages over traditional antidepressants. PPD is a neuroendocrine disorder that affects about 20% of mothers after childbirth and is characterized by symptoms including persistent sadness, fatigue, dysphoria, as well as disturbances in cognition, emotion, appetite, and sleep. The main pathology behind PPD is the postpartum reduction of neurosteroids, referred to as neurosteroid withdrawal, a concept pioneered by our preclinical studies. We developed neurosteroid replacement therapy (NRT) as a rational approach for treating PPD and other conditions related to neurosteroid deficiency, unveiling the power of neurosteroids as novel anxiolytic-antidepressants. The neurosteroid, brexanolone (BX), is a progesterone-derived allopregnanolone that rapidly relieves anxiety and mood deficits by activating GABA-A receptors, making it a transformational treatment for PPD. In 2019, the FDA approved BX, an intravenous formulation of allopregnanolone, as an NRT to treat PPD. In clinical studies, BX significantly improved PPD symptoms within hours of administration, with tolerable side effects including headache, dizziness, and somnolence. We identified the molecular mechanism of BX in a neuronal PPD-like milieu. The mechanism of BX involves activation of both synaptic and extrasynaptic GABA-A receptors, which promote tonic inhibition and serve as a key target for PPD and related conditions. Neurosteroids offer several advantages over traditional antidepressants, including rapid onset, unique mechanism, and lack of tolerance upon repeated use. Some limitations of BX therapy include lack of aqueous solubility, limited accessibility, hospitalization for treatment, lack of oral product, and serious adverse events at high doses. However, the unmet need for synthetic neurosteroids to address this critical condition supersedes these limitations. Recently, we developed novel hydrophilic neurosteroids with a superior profile and improved drug delivery. Overall, approval of BX is a major milestone in the field of neurotherapeutics, paving the way for the development of novel synthetic neurosteroids to treat depression, epilepsy, and status epilepticus.

Graphical abstract
Limiting Behavior of Random Attractors of Stochastic Supercritical Wave Equations Driven by Multiplicative Noise
Authors: Chen Zhang , Wang Bixiang
Published: August 2023

This paper deals with the limiting behavior of random attractors of stochastic wave equations with supercritical drift driven by linear multiplicative white noise defined on unbounded domains. We first establish the uniform Strichartz estimates of the solutions with respect to noise intensity, and then prove the convergence of the solutions of the stochastic equations with respect to initial data as well as noise intensity. To overcome the non-compactness of Sobolev embeddings on unbounded domains, we first utilize the uniform tail-ends estimates to truncate the solutions in a bounded domain and then employ a spectral decomposition to establish the pre-compactness of the collection of all random attractors. We finally prove the upper semicontinuity of random attractor as noise intensity approaches zero.
Non-concave Expected Utility Optimization with Uncertain Time Horizon
Authors: Dehm Christian , Nguyen Thai , Stadje Mitja
Published: August 2023

We consider an expected utility maximization problem where the utility function is not necessarily concave and the time horizon is uncertain. We establish a necessary and sufficient condition for the optimality for general non-concave utility function in a complete financial market. We show that the general concavification approach of the utility function to deal with non-concavity, while being still applicable when the time horizon is a stopping time with respect to the financial market filtration, leads to sub-optimality when the time horizon is independent of the financial risk, and hence can not be directly applied. For the latter case, we suggest a recursive procedure which is based on the dynamic programming principle. We illustrate our findings by carrying out a multi-period numerical analysis for optimal investment problem under a convex option compensation scheme with random time horizon. We observe that the distribution of the non-concave portfolio in both certain and uncertain random time horizon is right-skewed with a long right tail, indicating that the investor expects frequent small losses and a few large gains from the investment. While the (certain) average time horizon portfolio at a premature stopping date is unimodal, the random time horizon portfolio is multimodal distributed which provides the investor a certain flexibility of switching between the local maximizers, depending on the market performance. The multimodal structure with multiple peaks of different heights can be explained by the concavification procedure, whereas the distribution of the time horizon has significant impact on the amplitude between the modes.
TIM-3 as a promising target for cancer immunotherapy in a wide range of tumors
Authors: Sauer Natalia , Janicka Natalia , Szlasa Wojciech , Skinderowicz Bartłomiej , Kołodzińska Katarzyna , Dwernicka Wioletta , Oślizło Małgorzata , Kulbacka Julita , Novickij Vitalij , Karłowicz-Bodalska Katarzyna
Published: August 2023

T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) expression has been a trending topic in recent years due to its differential expression in a wide range of neoplasms. TIM-3 is one of the key immune checkpoint receptors that interact with GAL-9, PtdSer, HMGB1 and CEACAM1. Initially identified on the surface of T helper 1 (Th1) lymphocytes and later on cytotoxic lymphocytes (CTLs), monocytes, macrophages, natural killer cells (NKs), and dendritic cells (DCs), TIM-3 plays a key role in immunoregulation. Recently, a growing body of evidence has shown that its differential expression in various tumor types indicates a specific prognosis for cancer patients. Here, we discuss which types of cancer TIM-3 can serve as a prognostic factor and the influence of coexpressed immune checkpoint inhibitors, such as LAG-3, PD-1, and CTLA-4 on patients' outcomes. Currently, experimental medicine involving TIM-3 has significantly enhanced the anti-tumor effect and improved patient survival. In this work, we summarized clinical trials incorporating TIM-3 targeting monoclonal and bispecific antibodies in monotherapy and combination therapy and highlighted the emerging role of cell-based therapies.
Outcome prediction by interim positron emission tomography and IgM monoclonal gammopathy in diffuse large B-cell lymphoma
Authors: Johansson Patricia , Alig Stefan , Richter Julia , Hanoun Christine , Rekowski Jan , Dürig Jan , Ylstra Bauke , de Jong Daphne , Klapper Wolfram , Alizadeh Ash A. , Dührsen Ulrich , Hüttmann Andreas
Published: August 2023

In diffuse large B-cell lymphoma (DLBCL), a positive interim positron emission tomography (PET) scan predicts treatment failure, but the proportion of high-risk patients thus identified is small. To improve prediction, we combined the interim PET result with the presence or absence of an associated IgM gammopathy. Of 108 DLBCL patients participating in a prospective trial, nine (8%) were interim PET positive and 19 (18%) had an IgM gammopathy. The monoclonal protein was not associated with distinguishing genetic features, and its light chain restriction was not always concordant with the light chain restriction of the lymphoma. The information provided by interim PET and IgM gammopathy was combined to dichotomize the population into sizeable high-risk (1–2 adverse factors) and low-risk groups (no adverse factor) with widely different outcomes (population size, 25% vs. 75%; 3-year risk of progression, 51% vs. 10%; 3-year overall survival, 64% vs. 95%). Multivariable analyses including established risk factors revealed the interim PET result and the IgM gammopathy status to be the only factors significantly associated with outcome. Information about interim PET response and IgM gammopathy may be useful in studies testing risk-adapted treatment strategies.
Multi-disciplinary community-based group intervention for fibromyalgia: a pilot randomized controlled trial
Authors: Turcotte Kara , Oelke Nelly D. , Whitaker Gina , Holtzman Susan , O’Connor Brian , Pearson Neil , Teo Michelle
Published: August 2023

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances, mood disturbances, and cognitive impairment. Most individuals with fibromyalgia experience poorly managed symptoms and increased healthcare service use. Multicomponent therapies, with a focus on nonpharmacological modalities, are increasingly supported in the literature. However, given the limited resources available, implementation in smaller communities remains a challenge. This research tested a community-based multidisciplinary group intervention for individuals diagnosed with FM living in a small urban centre. The primary outcome was perceptions of quality of care and secondary outcomes included disease-related functioning, anxious and depressive symptoms, pain beliefs, and health service utilization. A pilot randomized control trial was conducted in which 60 patients diagnosed with fibromyalgia were randomized into a 10-week community-based multidisciplinary group intervention program or usual care. Treatment components included twice-weekly exercise sessions and weekly education sessions (e.g., pain education, cognitive behavioral strategies for stress, nutrition, peer support). The trial (NCT03270449) was registered September 1 2017. Statistically significant post-intervention improvements were found in the primary outcome, perceived quality of care (Cohen’s d = 0.61, 0.66 for follow up care and goal setting, respectively). Secondary outcomes showing statistically significant improvements were disease-related daily functioning (Cohen’s d = 0.70), depressive symptoms (Cohen’s d = 0.87), and pain beliefs (Cohen’s d = 0.61, 0.67, 0.82 for harm, disability and control, respectively). No adverse events were reported. Community-based multidisciplinary group interventions for fibromyalgia show promise for improving satisfaction with quality of care, disease-related functioning, and depression, and fostering more adaptive pain beliefs.
Can vitamin D be an adjuvant therapy for juvenile rheumatic diseases?
Authors: Stawicki Maciej K. , Abramowicz Paweł , Sokolowska Gabriela , Wołejszo Sebastian , Grant William B. , Konstantynowicz Jerzy
Published: August 2023

Vitamin D, known for its essential role in calcium and bone homeostasis, has multiple effects beyond the skeleton, including regulation of immunity and modulation of autoimmune processes. Several reports have shown suboptimal serum 25 hydroxyvitamin D [25(OH)D] levels in people with different inflammatory and autoimmune rheumatic conditions, and an association between 25(OH)D levels, disease activity and outcomes. Although most available data pertain to adults, insights often are extended to children. Juvenile rheumatic diseases (JRDs) are a significant health problem during growth because of their complex pathogenesis, chronic nature, multisystemic involvement, and long-term consequences. So far, there is no definitive or clear evidence to confirm the preventive or therapeutic effect of vitamin D supplementation in JRDs, because results from randomized controlled trials (RCTs) have produced inconsistent outcomes. This review aims to explore and discuss the potential role of vitamin D in treating selected JRDs. Medline/PubMed, EMBASE, and Scopus were comprehensively searched in June 2023 for any study on vitamin D supplementary role in treating the most common JRDs. We used the following keywords: “vitamin D” combined with the terms “juvenile idiopathic arthritis”, “juvenile systemic scleroderma”, “juvenile systemic lupus erythematosus”, “juvenile inflammatory myopathies”, “Behcet disease”, “periodic fever syndromes” and “juvenile rheumatic diseases”. Observational studies have found that serum 25(OH)D concentrations are lower in juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile systemic scleroderma, Behcet disease and proinflammatory cytokine concentrations are higher. This suggests that vitamin D supplementation might be beneficial, however, current data are insufficient to confirm definitively the complementary role of vitamin D in the treatment of JRDs. Considering the high prevalence of vitamin D deficiency worldwide, children and adolescents should be encouraged to supplement vitamin D according to current recommendations. More interventional studies, especially well-designed RCTs, assessing the dose–response effect and adjuvant effect in specific diseases, are needed to determine the potential significance of vitamin D in JRDs treatment.
Effects of glutamine on plasma protein and inflammation in postoperative patients with colorectal cancer: a meta-analysis of randomized controlled trials
Authors: Xiong Kai , Li Guangsong , Zhang Yu , Bao Tiantian , Li Ping , Yang Xiangdong , Chen Jiang
Published: August 2023

Objective

To evaluate the effects of glutamine on the plasma protein and inflammatory responses in colorectal cancer (CRC) patients following radical surgery.

Methods

We thoroughly retrieved online databases (EMBASE, MEDLINE, PubMed, and others) and selected the randomized controlled trials (RCTs) with glutamine vs. conventional nutrition or blank treatment up until March 2023. The plasma protein associated markers indicators (consisting of albumin (ALB), prealbumin (PA), nitrogen balance (NB), total protein (TP)), inflammatory indicators (including TNF-α, CRP, infectious complications (ICs)), and matching 95% confidence intervals (CIs) were evaluated utilizing the pooled analysis. Subsequently, meta-regression analysis, contour-enhanced funnel plot, Egger’s test, and sensitivity analysis were carried out.

Results

We discovered 26 RCTs, included an aggregate of 1678 patients, out of which 844 were classified into the glutamine group whereas 834 were classified into the control group. The findings recorded from pooled analysis illustrated that glutamine substantially enhanced the plasma protein markers (ALB [SMD[random-effect] = 0.79, 95% CI: 0.55 to 1.03, I2 = 79.4%], PA [SMD[random-effect] = 0.94, 95% CI: 0.69 to 1.20, I2 = 75.1%], NB [SMD[random-effect] = 1.11, 95% CI: 0.46 to 1.75, I2 = 86.9%). However, the content of TP was subjected to comparison across the 2 groups, and no statistical significance was found (SMD[random-effect] = − 0.02, 95% CI: − 0.60 to 0.57, P = 0.959, I2 = 89.7%). Meanwhile, the inflammatory indicators (including TNF-α [SMD[random-effect] = − 1.86, 95% CI: − 2.21 to − 1.59, I2 = 56.7%], CRP [SMD[random-effect] = − 1.94, 95% CI: − 2.41 to − 1.48, I2 = 79.9%], ICs [RR[fixed-effect] = 0.31, 95% CI: 0.21 to 0.46, I2 = 0.00%]) were decreased significantly followed by the treatment of glutamine.

Conclusions

The current study’s findings illustrated that glutamine was an effective pharmaco-nutrient agent in treating CRC patients following a radical surgical operation.

PROSPERO registration number: CRD42021243327.
Associations of food motives with red meat and legume consumption in the population-based DILGOM study
Authors: Hentilä Annukka , Männistö Satu , Kaartinen Niina E. , Jousilahti Pekka , Konttinen Hanna
Published: August 2023

Purpose

To improve human health and environmental sustainability, red meat consumption should decrease and legume consumption increase in diets. More information on food motives, however, is required when developing more tailored and effective interventions targeting legume and meat consumption. We aimed to examine the associations between food motives and red meat and legume consumption, and whether these associations differ between different subgroups (gender, age groups, marital status, education, BMI).

Methods

Ten food motives (health, mood, convenience, sensory appeal, natural content, price-cheap, price-value, weight control, familiarity and ethical concern measured with Food Choice Questionnaire) were studied in 3079 Finnish adults in the population-based DILGOM study. Food consumption was assessed with Food Frequency Questionnaire. The adjusted estimates from multivariable regression models are reported.

Results

Higher relative importance of natural content (β = − 0.275, 95% CI − 0.388; − 0.162) and ethical concern (β = − 0.462, 95% CI − 0.620; − 0.305) were associated with lower red meat consumption, and higher appreciation of sensory appeal (β = 0.482, 95% CI 0.347; 0.616) and price-cheap (β = 0.190, 95% CI 0.099; 0.281) with higher red meat consumption. Higher importance of health (β = 0.608, 95% CI 0.390; 0.825) was associated with higher legume consumption, and higher appreciation of convenience (β = − 0.401, 95% CI − 0.522; − 0.279), price-value (β = − 0.257, 95% CI − 0.380; − 0.133) and familiarity (β = − 0.278, 95% CI − 0.393; − 0.164) with lower legume consumption. The associations of particularly ethical concern, weight control, sensory appeal and mood varied according to gender, age, marital status or BMI.

Conclusion

The development and implementation of actions to decrease red meat and increase legume consumption should focus on several food motives across different subgroups.
Comparison of cementless twin-peg, cemented twin-peg and cemented single-peg femoral component migration after medial unicompartmental knee replacement: a 5-year randomized RSA study
Authors: Mosegaard Sebastian Breddam , Odgaard Anders , Madsen Frank , Rømer Lone , Kristensen Per Wagner , Vind Tobias Dahl , Søballe Kjeld , Stilling Maiken
Published: August 2023

Background

The component design and fixation method of joint arthroplasty may affect component migration and survival. The aim of this study was to compare fixation of cementless twin-peg (CLTP), cemented twin-peg (CTP) and cemented single-peg (CSP) femoral components of medial unicompartmental knee replacement (UKR).

Methods

Eighty patients (mean age = 63 years, 48 males) with medial knee osteoarthritis were randomized in three ways to CLTP (n = 25), CTP (n = 26) or CSP (n = 29) femoral UKR components. The patients were followed 5 years postoperatively with RSA, bone mineral density (BMD), PROMs and radiological evaluation of radiolucent lines (RLL), femoral component flexion angle and complications.

Results

At the 5-year follow-up, femoral component total translation was comparable between the three groups (p = 0.60). Femoral component internal rotation was 0.50° (95% CI 0.3; 0.69) for the CLTP group, 0.58° (95% CI 0.38; 0.77) for the CTP group and 0.25° (95% CI 0.07; 0.43) for the CSP group (p = 0.01). BMD decreased peri-prosthetically (range − 11.5%; − 14.0%) until 6-month follow-up and increased toward the 5-year follow-up (range − 3.6%; − 5.8%). BMD change did not correlate with component migration. Lower flexion angle was correlated with higher 5-year subsidence, total translation, varus rotation and maximum total point motion (p = 0.01). Two patients (1 CLTP, 1 CTP) had RLL in the posterior zone. There were two revisions.

Conclusion

At 5-year follow-up, fixation of UKA femoral components with twin-peg was not superior to the single-peg design. Cementless and cemented twin-peg femoral components had similar fixation. A lower flexion angle was correlated with higher component migration.
Evolution of macular atrophy in eyes with neovascular age-related macular degeneration compared to fellow non-neovascular eyes
Authors: Blazaki Styliani , Blavakis Emmanouil , Chlouverakis Gregory , Bontzos Georgios , Chatziralli Irini , Smoustopoulos Georgios , Dimitriou Eleni , Stavrakakis Anastasios , Kabanarou Stamatina , Xirou Tina , Vavvas Demetrios G. , Tsilimbaris Miltiadis K.
Published: August 2023

Purpose

Τo evaluate the evolution of macular atrophy (MA) in patients with neovascular AMD (nAMD), compared with their fellow eyes exhibiting dry AMD (dAMD).

Methods

This retrospective study included 124 patients from three centers treated with anti-VEGF in their nAMD eye and having dAMD in the fellow eye. Patients without MA at baseline were analyzed to study the time to first MA development. Synchronous and unsynchronous time course of MA was also studied. MA was evaluated using near-infrared images, while all available optical coherence tomography (OCT) images were used to confirm the criteria proposed by the Classification of Atrophy Meetings group for complete MA.

Results

MA first detection in nAMD eyes increased significantly from year 2 to 6 compared to dAMD eyes. Over the study’s follow-up, 45.1% of nAMD-E developed MA, compared to 16.5% of fellow eyes (p < 0.001). When MA in the two eyes was compared in a synchronous paired manner over 4 years, nAMD eyes had an average MA progression rate of 0.275 mm/year versus 0.110 mm/year in their fellow dAMD eyes. Multivariate ANOVA revealed significant time (p < 0.001), eye (p = 0.003), and time-eye interaction (p < 0.001) effects. However, when MA did develop in dAMD eyes and was compared in an asynchronous manner to MA of nAMD eyes, it was found to progress faster in dAMD eyes (dAMD: 0.295 mm/year vs. nAMD: 0.176 mm/year) with a significant time-eye interaction (p = 0.015).

Conclusions

In this study, a significant difference in MA incidence and progression was documented in eyes with nAMD under treatment, compared to fellow eye exhibiting dAMD. Eyes with nAMD tended to develop more MA compared to fellow dAMD eyes. However, when atrophy did develop in the fellow dAMD eyes, it progressed faster over time compared to MA in nAMD eyes.
The late-evolving salmon and trout join the GnRH1 club
Authors: von Schalburg Kristian R. , Gowen Brent E. , Christensen Kris A. , Ignatz Eric H. , Hall Jennifer R. , Rise Matthew L.
Published: August 2023

Although it is known that the whitefish, an ancient salmonid, expresses three distinct gonadotropin-releasing hormone (GnRH) forms in the brain, it has been thought that the later-evolving salmonids (salmon and trout) had only two types of GnRH: GnRH2 and GnRH3. We now provide evidence for the expression of GnRH1 in the gonads of Atlantic salmon by rapid amplification of cDNA ends, real-time quantitative PCR and immunohistochemistry. We examined six different salmonid genomes and found that each assembly has one gene that likely encodes a viable GnRH1 prepropeptide. In contrast to both functional GnRH2 and GnRH3 paralogs, the GnRH1 homeolog can no longer express the hormone. Furthermore, the viable salmonid GnRH1 mRNA is composed of only three exons, rather than the four exons that build the GnRH2 and GnRH3 mRNAs. Transcribed gnrh1 is broadly expressed (in 17/18 tissues examined), with relative abundance highest in the ovaries. Expression of the gnrh2 and gnrh3 mRNAs is more restricted, primarily to the brain, and not in the gonads. The GnRH1 proximal promoter presents composite binding elements that predict interactions with complexes that contain diverse cell fate and differentiation transcription factors. We provide immunological evidence for GnRH1 peptide in the nucleus of 1-year-old type A spermatogonia and cortical alveoli oocytes. GnRH1 peptide was not detected during other germ cell or reproductive stages. GnRH1 activity in the salmonid gonad may occur only during early stages of development and play a key role in a regulatory network that controls mitotic and/or meiotic processes within the germ cell.
The context-dependent role of the Na+/Ca2+-exchanger (NCX) in pancreatic stellate cell migration
Authors: Loeck Thorsten , Rugi Micol , Todesca Luca Matteo , Kalinowska Paulina , Soret Benjamin , Neumann Ilka , Schimmelpfennig Sandra , Najder Karolina , Pethő Zoltán , Farfariello Valerio , Prevarskaya Natalia , Schwab Albrecht
Published: August 2023

Pancreatic stellate cells (PSCs) that can co-metastasize with cancer cells shape the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) by producing an excessive amount of extracellular matrix. This leads to a TME characterized by increased tissue pressure, hypoxia, and acidity. Moreover, cells within the tumor secrete growth factors. The stimuli of the TME trigger Ca2+ signaling and cellular Na+ loading. The Na+/Ca2+ exchanger (NCX) connects the cellular Ca2+ and Na+ homeostasis. The NCX is an electrogenic transporter, which shuffles 1 Ca2+ against 3 Na+ ions over the plasma membrane in a forward or reverse mode. Here, we studied how the impact of NCX activity on PSC migration is modulated by cues from the TME. NCX expression was revealed with qPCR and Western blot. [Ca2+]i, [Na+]i, and the cell membrane potential were determined with the fluorescent indicators Fura-2, Asante NaTRIUM Green-2, and DiBAC4(3), respectively. PSC migration was quantified with live-cell imaging. To mimic the TME, PSCs were exposed to hypoxia, pressure, acidic pH (pH 6.6), and PDGF. NCX-dependent signaling was determined with Western blot analyses. PSCs express NCX1.3 and NCX1.9. [Ca2+]i, [Na+]i, and the cell membrane potential are 94.4 nmol/l, 7.4 mmol/l, and − 39.8 mV, respectively. Thus, NCX1 usually operates in the forward (Ca2+ export) mode. NCX1 plays a differential role in translating cues from the TME into an altered migratory behavior. When NCX1 is operating in the forward mode, its inhibition accelerates PSC migration. Thus, NCX1-mediated extrusion of Ca2+ contributes to a slow mode of migration of PSCs.
A comprehensive analysis of Fanconi anemia genes in Chinese patients with high-risk hereditary breast cancer
Authors: Zhu Qiao-Yan , Li Pu-Chun , Zhu Yi-Fan , Pan Jia-Ni , Wang Rong , Li Xiao-Lin , Ye Wei-Wu , Ding Xiao-Wen , Wang Xiao-Jia , Cao Wen-Ming
Published: August 2023

Background

Four Fanconi anemia (FA) genes (BRCA1, BRCA2, PALB2 and RAD51C) are defined as breast cancer (BC) susceptibility genes. Other FA genes have been inconsistently associated with BC. Thus, the role of other FA genes in BC should be explored in specific populations.

Methods

Mutations in 16 FA genes were screened with a 98-gene panel sequencing assay in a cohort of 1481 Chinese patients with high-risk hereditary BC. The association between mutations and clinicopathological characteristics as well as prognosis was analyzed. The risk of BC in carriers of FA gene mutations was assessed in the Genome Aggregation Database and the Westlake Biobank for Chinese cohort.

Results

A total of 2.57% (38/1481) BC patients were identified who had 12 other FA gene germline mutations. Among them, the most frequently mutated gene was FANCA (8/1481, 0.54%). These 38 patients carried 35 distinct pathogenic/likely pathogenic variants, of which 21 were novel. We found one rare FANCB deleterious variant (c.1327-3dupT) in our cohort. There was a statistically significant difference in lymph node status between FA gene mutation carriers and non-carriers (p = 0.041). We observed a trend that mutation carriers had larger tumor sizes, lower estrogen receptor (ER) and progesterone receptor (PR) positivity rates, and lower 3.5-year invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS) rates than non-carriers (tumor size > 2 cm: 51.43% vs. 45.63%; ER positivity rates: 51.43% vs. 60.81%; PR positivity rates: 48.57% vs. 55.16%; 3.5-year iDFS rates: 58.8% vs. 66.7%; 3.5-year DRFS rates: 58.8% vs. 68.8%). The frequency of the mutations in FANCD2, FANCM and BRIP1 trended to be higher among BC cases than that in controls (p = 0.055, 0.08 and 0.08, respectively).

Conclusion

This study comprehensively estimated the prevalence, clinicopathological characteristics, prognosis and risk of BC associated with deleterious variants in FA genes in Chinese high-risk hereditary BC patients. It enriches our understanding of the role of FA genes with BC.
Wound reaction to trunk injection of oxytetracycline or water in huanglongbing-affected sweet orange (Citrus sinensis) trees
Authors: Archer Leigh , Albrecht Ute
Published: August 2023

Key message

Trunk injection causes injury to trees and best practices must be established for use of this technology to manage vascular diseases such as huanglongbing.

Trunk injection is a technique for applying plant protection compounds that has demonstrated efficacy for management of huanglongbing (HLB), a bacterial disease which has devastated the Florida citrus industry. Recently, the antibacterial oxytetracycline has been approved for trunk injection in citrus in Florida. Despite its potential for restoring health of HLB-affected trees, little information is available on the trees’ ability to heal and compartmentalize the wounds caused by trunk injection and the interaction with season and other factors. In this study, 5-year-old HLB-affected sweet orange (Citrus sinensis) trees were injected bi-monthly to measure seasonal differences in the rate of uptake of injected water and to compare the external and internal wound reaction in both scion and rootstock. Also investigated was the wound reaction after trunk injection of an injectable formulation of oxytetracycline. Injection during spring and summer promoted more rapid wound closure compared to injection in fall or winter, and injection into the scion was less damaging than injection into the rootstock. Although citrus trees effectively compartmentalized wounds inflicted by injection of water, injection of oxytetracycline impeded wound healing and increased internal damage. Application of a fungicide or pruning sealant increased the size of the wound internally and externally. For trunk injection to be adopted for use in commercial citrus orchards, the benefits of injection must outweigh the risks of wounding associated with the application method. This study provides first insight on some of the best practices for effectively utilizing trunk injection in citrus as a crop protection strategy.
Efficacy of ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam combinations against carbapenemase-producing Enterobacterales in Switzerland
Authors: Nordmann Patrice , Bouvier Maxime , Poirel Laurent
Published: August 2023

Carbapenemase-producing in Enterobacterales (CPE) represent a critical health concern worldwide, including in Switzerland, leading to very limited therapeutic options. Therefore, our aim was to evaluate the susceptibility to the novel ß-lactam/ß-lactamase inhibitor combinations ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam of CPE isolates recovered in Switzerland from 2018 to 2020. A total of 150 clinical CPE were studied including mainly Klebsiella pneumoniae (n = 61, 40.3%) and Escherichia coli (n = 53, 35.3%). The distribution of carbapenemases was as follows: KPC-like (32%), OXA-48-like (32%), NDM-like (24%), combinations of carbapenemases (10%), VIM-1 producers (n = 2), and a single IMI-1 producer. Overall, 77% of the strains were susceptible to meropenem-vaborbactam, 63% was susceptible to ceftazidime-avibactam, and 62% susceptible to imipenem-relebactam. Those data may contribute to optimize the choice of first line therapy for treating infections due to CPE.
A numerical study of the effect of thrombus breakdown on predicted thrombus formation and growth
Authors: Wang Kaihong , Armour Chlöe H. , Gibbs Richard G. J. , Xu Xiao Yun
Published: August 2023

Thrombosis is a complex biological process which involves many biochemical reactions and is influenced by blood flow. Various computational models have been developed to simulate natural thrombosis in diseases such as aortic dissection (AD), and device-induced thrombosis in blood-contacting biomedical devices. While most hemodynamics-based models consider the role of low shear stress in the initiation and growth of thrombus, they often ignore the effect of thrombus breakdown induced by elevated shear stress. In this study, a new shear stress-induced thrombus breakdown function is proposed and implemented in our previously published thrombosis model. The performance of the refined model is assessed by quantitative comparison with experimental data on thrombus formation in a backward-facing step geometry, and qualitative comparison with in vivo data obtained from an AD patient. Our results show that incorporating thrombus breakdown improves accuracy in predicted thrombus volume and captures the same pattern of thrombus evolution as measured experimentally and in vivo. In the backward-facing step geometry, thrombus breakdown impedes growth over the step and downstream, allowing a stable thrombus to be reached more quickly. Moreover, the predicted thrombus volume, height and length are in better agreement with the experimental measurements compared to the original model which does not consider thrombus breakdown. In the patient-specific AD, the refined model outperforms the original model in predicting the extent and location of thrombosis. In conclusion, the effect of thrombus breakdown is not negligible and should be included in computational models of thrombosis.
Diagnostic difficulties in pediatric annular dermatoses
Authors: Weiss Doris , Weber Philipp , Hampel Amélie , Tittes Julia , Weninger Wolfgang , Kinaciyan Tamar
Published: August 2023

The polymorphic presentation of annular dermatoses in the pediatric population renders them a diagnostic challenge to the clinician. They include various distinct disease entities that can be vaguely categorized according to the age of onset. Herein, we report on a young girl with clinical characteristics of Wells’ syndrome, while histological findings favored the diagnosis of annular erythema of infancy (AEI). Although morphological and histological similarities do exist, AEI and eosinophilic annular erythema (EAE) of childhood are considered as distinct entities in the literature. Wells’ syndrome (WS) is an eosinophilic dermatosis and histologically characterized by eosinophilic dermal infiltration with the hallmark feature of “flame figures.” Based on this case, we discuss and review the differential diagnoses of annular dermatoses in children.
Deep neural network-based clustering of deformation curves reveals novel disease features in PLN pathogenic variant carriers
Authors: Taha Karim , van de Leur Rutger R. , Vessies Melle , Mast Thomas P. , Cramer Maarten J. , Cauwenberghs Nicholas , Verstraelen Tom E. , de Brouwer Remco , Doevendans Pieter A. , Wilde Arthur , Asselbergs Folkert W. , van den Berg Maarten P. , D’hooge Jan , Kuznetsova Tatiana , Teske Arco J. , van Es René
Published: August 2023

Echocardiographic deformation curves provide detailed information on myocardial function. Deep neural networks (DNNs) may enable automated detection of disease features in deformation curves, and improve the clinical assessment of these curves. We aimed to investigate whether an explainable DNN-based pipeline can be used to detect and visualize disease features in echocardiographic deformation curves of phospholamban (PLN) p.Arg14del variant carriers. A DNN was trained to discriminate PLN variant carriers (n = 278) from control subjects (n = 621) using raw deformation curves obtained by 2D-speckle tracking in the longitudinal axis. A visualization technique was used to identify the parts of these curves that were used by the DNN for classification. The PLN variant carriers were clustered according to the output of the visualization technique. The DNN showed excellent discriminatory performance (C-statistic 0.93 [95% CI 0.87–0.97]). We identified four clusters with PLN-associated disease features in the deformation curves. Two clusters showed previously described features: apical post-systolic shortening and reduced systolic strain. The two other clusters revealed novel features, both reflecting delayed relaxation. Additionally, a fifth cluster was identified containing variant carriers without disease features in the deformation curves, who were classified as controls by the DNN. This latter cluster had a very benign disease course regarding development of ventricular arrhythmias. Applying an explainable DNN-based pipeline to myocardial deformation curves enables automated detection and visualization of disease features. In PLN variant carriers, we discovered novel disease features which may improve individual risk stratification. Applying this approach to other diseases will further expand our knowledge on disease-specific deformation patterns.

Graphical abstract

Overview of the deep neural network-based pipeline for feature detection in myocardial deformation curves. Firstly, phospholamban (PLN) p.Arg14del variant carriers and controls were selected and a deep neural network (DNN) was trained to detect the PLN variant carriers. Subsequently, a clustering-based approach was performed on the attention maps of the DNN, which revealed 4 distinct phenotypes of PLN variant carriers with different prognoses. Moreover, a cluster without features and a benign prognosis was detected.
Dissolution of viscose rayon multifilament yarn in the ionic liquid 1-ethyl-3-methylimidazolium acetate studied using time–temperature superposition
Authors: Alanazi Maer , Ries Michael E. , Hine Peter J.
Published: August 2023

Wide-angle X-ray diffraction (WAXS) and mechanical testing techniques are used to track the dissolution of a viscose rayon multifilament yarn in the ionic liquid 1-ethyl-3-methyl-imidazolium acetate [C2mim]+ [OAc]− for different times and temperatures. In the dissolution process, the oriented cellulose II crystals in the regenerated cellulose fibres dissolve and then reform into randomly oriented crystals to form a matrix phase, and this change in orientation enables us to follow the dissolution process using WAXS, and hence determine the dissolved matrix volume fraction $${v}_{m}$$

v
m

. The change in the average molecular orientation $${P}_{2}$$

P
2

determined from an azimuthal $$(\alpha$$

(
α

) X-ray scan, allows the growth of the matrix volume fraction $${v}_{m}$$

v
m

to be calculated with time and temperature. The growth of $${v}_{m}$$

v
m

was found to follow time temperature superposition, with an Arrhenius behaviour, giving a value for the activation energy of Ea = 149 ± 4 kJ/mol. Young’s modulus was measured on all the resulting processed composites. The fall of Young’s modulus with dissolution time and temperature was also found to follow time–temperature superposition, with an Arrhenius behaviour giving a value for Ea = 198 ± 29 kJ/mol. The Young’s Modulus results plotted against $${v}_{m}$$

v
m

determined from the WAXS measurements fitted well to the Voigt upper bound parallel Rule of Mixtures $$.$$
.
Care and academic work in a pandemic lockdown: a study of women academics in South Africa
Authors: Bam Armand , Walters Cyrill , Jansen Jonathan
Published: August 2023

The lack of women in leadership across higher education has been problematised in the literature. Often, contemporary discourses promote “fixing the women” as a solution. Consequently, interventions aimed at helping women break through “the glass ceiling” abound. We argue that the gendered power relations at play in universities cause entrenched inequalities to remain in place, regardless of measures implemented for and by women. This article reports on a study of the impact of COVID-19 on 2029 women academics in South Africa. We examine how academic women’s roles as nurturers at home are extended to their roles as carers at work, and how these impact their prospects for career progression. The article further shows how expectations placed on women academics as carers contribute to gendered dimensions of inequality that are detrimental to both their own well-being and careers. Finally, we call on higher education institutions to “fix themselves”, rather than “the women”, if they want to dismantle gender inequalities.
Clinical pregnancy in Turner syndrome following re-implantation of cryopreserved ovarian cortex
Authors: Dunlop CE , Jack SA , Telfer EE , Zahra S. , Anderson RA
Published: August 2023

Turner syndrome (TS) leads to a characteristic phenotype, including premature ovarian insufficiency and infertility. Ovarian tissue cryopreservation (OTC) is becoming an established fertility preservation strategy for both pre- and post-pubertal females and may offer the chance of having a biological family to selected patients with TS. To date, women with TS have had ovarian tissue cryopreserved but there are few reports of autologous re-implantation and none of pregnancy. We herein report, to our knowledge, the first clinical pregnancy in a patient with TS, conceived naturally following re-implantation of cryopreserved ovarian tissue which had been removed soon after spontaneous puberty. This provides proof of concept for OTC as a means of fertility preservation in TS.