bluuebunny/crossref_metadata_2025 huggingface dataset:
The Preparation of Iridium-Based Catalyst with Different Melting Point-Metal Nitrate and Its OER Performance in Acid Media
Authors: Deng Jiayao , Hu Xiao , Xu Guizhi , Deng Zhanfeng , Yang Lan , Chen Ding , Zhou Ming , Tian Boyuan
Published: January 2024

Oxygen evolution reaction (OER) is the main factor limiting the large-scale development of proton-exchange membrane (PEM) hydrogen production. It is urgent to develop catalysts with excellent OER catalytic performance and stability. Herein, several Iridium-based catalysts were prepared by simple mixing and calcination, the OER properties of catalysts with different melting points of nitrates as calcinating additives were investigated. The RbNO3 treated catalyst displayed a low overpotential(η) of 297.6 mV versus RHE, which is lower than the catalyst calcinated without nitrate (323.8 mV vs. RHE). Moreover, the RbNO3 treated catalyst displayed good acid stability over 20 h Chronopotentiometric test. The high OER catalytic activity and stability of RbNO3 treated catalyst may be attribute to the smaller nanoparticle morphology, pure IrO2 structure and high electrochemical surface area (ECSA), which increase the number of active sites and the intrinsic catalytic activity. This work indicated that the catalyst with excellent OER performance can be obtained by selecting nitrate with moderate melting point as the calcinating additive. Nitrates (like RbNO3) treated catalyst with excellent catalytic activity and stability has good application prospect in hydrogen production of PEM water splitting.
Holographic complexity of rotating quantum black holes
Authors: Chen Bin , Liu Yuefeng , Yu Boyang
Published: January 2024

Abstract

We study holographic complexity for the rotating quantum BTZ black holes (quBTZ), the BTZ black holes with corrections from bulk quantum fields. Using double holography, the combined system of backreacted rotating BTZ black holes with conformal matters, can be holographically described by the rotating AdS4 C-metric with the BTZ black hole living on a codimension-1 brane. We investigate both volume complexity and action complexity of rotating quBTZ, and pay special attention to their late-time behaviors. When the mass of BTZ black hole is not very small compared to $$ {g}_{\textrm{eff}}^{2/3}/{G}_3 $$

g
eff

2
/
3

/

G
3

and the rotation is not very slow compared to parameter ℓ, where geff as well as ℓ both characterize the backreaction of quantum fields and G3 is the 3D Newton constant, we show that the late-time rates of the volume complexity and the action complexity agree with each other up to a factor 2 and reduce to the ones of BTZ at the leading classical order, and they both receive subleading quantum corrections. For the volume complexity, the leading quantum correction comes from the backreaction of conformal matter on the geometry, similar to the static quBTZ case. For the action complexity, unlike the static case, the Wheeler-de Witt (WdW) patch in computing the action complexity for the rotating black hole does not touch the black hole singularity such that the leading order result is in good match with the one of classical BTZ. However, when the mass of BTZ black hole is small compared to $$ {g}_{\textrm{eff}}^{2/3}/{G}_3 $$

g
eff

2
/
3

/

G
3

or the rotation parameter a is small compared to ℓ, the quantum correction to the action complexity could be significant such that the late-time slope of the action complexity of quBTZ deviates very much from the one of classical BTZ. Remarkably, we notice that the nonrotating limit a → 0 is singular and the action complexity of the static quBTZ black holes cannot be reproduced by taking the nonrotating limit a → 0 on the one of the rotating black holes. This discontinuity also appears in higher dimensional rotating black holes, such as Kerr-AdS4 black hole and rotating AdS5 black hole.
Dark photon production via elastic proton bremsstrahlung with non-zero momentum transfer
Authors: Gorbunov D. , Kriukova E.
Published: January 2024

Abstract

We explore hypothetical vector particles, dark photons γ′, which mix with the Standard Model photons and thus mediate interactions with charged particles into the hidden sector. We study the elastic proton bremsstrahlung of dark photons with masses 0.4–1.8 GeV, relevant for direct searches with proton accelerators. A key feature of our calculation is that it explicitly considers the non-zero momentum transfer between protons in the process pp → ppγ′. We compare the obtained differential and full bremsstrahlung cross sections with the results of other authors. Our calculation agrees well (up to 3–9% corrections) with the Weizsacker-Williams approximation that confirms its applicability for proton beams. Then we refine predictions for the dark photon production with proton beams of energy 30 GeV, 70 GeV, 120 GeV and 400 GeV relevant for past, present and future experiments considered in literature.
Renormalization scheme factorization of one-loop Fierz identities
Authors: Aebischer Jason , Pesut Marko , Polonsky Zachary
Published: January 2024

Abstract

We present a proof of the factorization of renormalization scheme in one-loop-corrected Fierz identities. This scheme factorization facilitates the simultaneous transformation of operator basis and renormalization scheme using only relations between physical operators; the evanescent operators in the respective bases may be chosen entirely independently of each other. The relations between evanescent operators in the two bases is automatically accounted for by the corrected Fierz identities. We illustrate the utility of this result with a two-loop anomalous dimension matrix computation using the Naive-Dimensional Regularization scheme, which is then transformed via one-loop Fierz identities to the known result in the literature given in a different basis and calculated in the Larin scheme. Additionally, we reproduce results from the literature of basis transformations involving the rotation of evanescent operators into the physical basis using our method, without the need to explicitly compute one-loop matrix elements of evanescent operators.
Scattering of compact kinks
Authors: Hahne F. M. , Klimas P.
Published: January 2024

Abstract

We study the scattering processes of kink-antikink and kink-kink pairs in a field theory model with non-differentiable potential at its minima. The kink-antikink scattering includes cases of capture and escape of the soliton pair separated by a critical velocity, without windows of multi bounce followed by escape. Around the critical velocity, the behavior is fractal. The emission of radiation strongly influences the small velocity cases, with the most radiative cases being also the most chaotic. The radiation appears through the emission of compact oscillons and the formation of compact shockwaves. The kink-kink scattering happens elastically, with no emission of radiation. Some features of both the kink-antikink and the kink-kink scattering are explained using a collective coordinate model, even though the kink-kink case exhibits a null-vector problem.
Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution
Authors: Jeong Jaekwang , Lee Jongwon , Talaia Gabriel , Kim Wonnam , Song Junho , Hong Juhyeon , Yoo Kwangmin , Gonzalez David G. , Athonvarangkul Diana , Shin Jaehun , Dann Pamela , Haberman Ann M. , Kim Lark Kyun , Ferguson Shawn M. , Choi Jungmin , Wysolmerski John
Published: January 2024

Involution of the mammary gland after lactation is a dramatic example of coordinated cell death. Weaning causes distension of the alveolar structures due to the accumulation of milk, which, in turn, activates STAT3 and initiates a caspase-independent but lysosome-dependent cell death (LDCD) pathway. Although the importance of STAT3 and LDCD in early mammary involution is well established, it has not been entirely clear how milk stasis activates STAT3. In this report, we demonstrate that protein levels of the PMCA2 calcium pump are significantly downregulated within 2–4 h of experimental milk stasis. Reductions in PMCA2 expression correlate with an increase in cytoplasmic calcium in vivo as measured by multiphoton intravital imaging of GCaMP6f fluorescence. These events occur concomitant with the appearance of nuclear pSTAT3 expression but prior to significant activation of LDCD or its previously implicated mediators such as LIF, IL6, and TGFβ3, all of which appear to be upregulated by increased intracellular calcium. We further demonstrate that increased intracellular calcium activates STAT3 by inducing degradation of its negative regulator, SOCS3. We also observed that milk stasis, loss of PMCA2 expression and increased intracellular calcium levels activate TFEB, an important regulator of lysosome biogenesis through a process involving inhibition of CDK4/6 and cell cycle progression. In summary, these data suggest that intracellular calcium serves as an important proximal biochemical signal linking milk stasis to STAT3 activation, increased lysosomal biogenesis, and lysosome-mediated cell death.
Epigenetic repression of CHCHD2 enhances survival from single cell dissociation through attenuated Rho A kinase activity
Authors: Kim Jumee , Kwon Eun-Ji , Kim Yun-Jeong , Kim Dayeon , Shin Yoon-Ze , Gil Dayeon , Kim Jung-Hyun , Shin Hyoung Doo , Kim Lyoung Hyo , Lee Mi-Ok , Go Young-Hyun , Cha Hyuk-Jin
Published: January 2024

During in vitro culture, human pluripotent stem cells (hPSCs) often acquire survival advantages characterized by decreased susceptibility to mitochondrial cell death, known as “culture adaptation.” This adaptation is associated with genetic and epigenetic abnormalities, including TP53 mutations, copy number variations, trisomy, and methylation changes. Understanding the molecular mechanisms underlying this acquired survival advantage is crucial for safe hPSC-based cell therapies. Through transcriptome and methylome analysis, we discovered that the epigenetic repression of CHCHD2, a mitochondrial protein, is a common occurrence during in vitro culture using enzymatic dissociation. We confirmed this finding through genetic perturbation and reconstitution experiments in normal human embryonic stem cells (hESCs). Loss of CHCHD2 expression conferred resistance to single cell dissociation-induced cell death, a common stress encountered during in vitro culture. Importantly, we found that the downregulation of CHCHD2 significantly attenuates the activity of Rho-associated protein kinase (ROCK), which is responsible for inducing single cell death in hESCs. This suggests that hESCs may survive routine enzyme-based cell dissociation by downregulating CHCHD2 and thereby attenuating ROCK activity. These findings provide insights into the mechanisms by which hPSCs acquire survival advantages and adapt to in vitro culture conditions.
Die Anwendung von Real-world-Evidenz in Entscheidungsprozessen der Arzneimittelregulation
Authors: Wicherski Julia , Haenisch Britta
Published: January 2024

Die Arzneimittelregulation ist ein System zur Förderung und zum Schutz der öffentlichen Gesundheit. Auf dem Markt erhältliche Arzneimittel müssen wirksam, sicher und qualitativ hochwertig sein. Dafür werden von den zuständigen Behörden Entscheidungen auf wissenschaftlicher Basis getroffen. Real-world-Evidenz (RWE) aus Real-world-Daten (RWD) findet bisher überwiegend unterstützende Berücksichtigung bei den Entscheidungsfindungen hinsichtlich der Sicherheit des Arzneimittels nach der Zulassung. Das umfängliche Potenzial von RWE für regulatorische Entscheidungsprozesse entlang des gesamten Produktlebenszyklus wird seit wenigen Jahren zunehmend genutzt und weiter erforscht.

Dieser Beitrag bietet einen Überblick zu aktuellen Anwendungen von RWE in arzneimittelregulatorischen Entscheidungsprozessen. Die diesbezüglichen Potenziale von RWE entlang der zu adressierenden Hürden werden beschrieben sowie Beispiele für aktuelle Projekte zur RWE-Forschung für die Arzneimittelregulation gegeben. Die Arbeit basiert auf aktueller internationaler Literatur sowie Beispielen aus internationalen und europäischen Initiativen und der aktuellen regulatorischen Praxis, die die zunehmende Anwendung von RWD/RWE in regulatorischen Entscheidungsprozessen unterstützen sollen. Um das Potenzial von RWE zukünftig noch besser nutzen zu können, gilt es, durch Forschungsprojekte und Initiativen relevante RWD-Quellen besser verfügbar zu machen, auswertende Methoden weiterzuentwickeln und den Stellenwert von RWE zu etablieren.
Combination of nivolumab with standard induction chemotherapy in children and adults with EBV-positive nasopharyngeal carcinoma
Authors: Römer Tristan , Vokuhl Christian , Staatz Gundula , Mottaghy Felix M. , Christiansen Hans , Eble Michael J. , Timmermann Beate , Klussmann Jens Peter , Elbracht Miriam , Calaminus Gabriele , Zimmermann Martin , Brümmendorf Tim H. , Feuchtinger Tobias , Kerp Helena , Kontny Udo
Published: January 2024

Background

Treatment of Epstein-Barr virus(EBV)-positive nasopharyngeal carcinoma (NPC) with cisplatin/5-fluorouracil (5-FU) induction chemotherapy, followed by radiochemotherapy and subsequent interferon‑β, has yielded high survival rates in children, adolescents, and young adults. A previous study has shown that reduction of radiation dose from 59.4 to 54.0 Gy appears to be safe in patients with complete response (CR) to induction chemotherapy. As immune checkpoint-inhibitors have shown activity in NPC, we hypothesize that the addition of nivolumab to standard induction chemotherapy would increase the rate of complete tumor responses, thus allowing for a reduced radiation dose in a greater proportion of patients.

Methods

This is a prospective multicenter phase 2 clinical trial including pediatric and adult patients with their first diagnosis of EBV-positive NPC, scheduled to receive nivolumab in addition to standard induction chemotherapy. In cases of non-response to induction therapy (stable or progressive disease), and in patients with initial distant metastasis, treatment with nivolumab will be continued during radiochemotherapy. Primary endpoint is tumor response on magnetic resonance imaging (MRI) and positron emission tomography (PET) after three cycles of induction chemotherapy. Secondary endpoints are event-free (EFS) and overall survival (OS), safety, and correlation of tumor response with programmed cell death ligand 1 (PD-L1) expression.

Discussion

As cure rates in localized EBV-positive NPC today are high with standard multimodal treatment, the focus increasingly shifts toward prevention of late effects, the burden of which is exceptionally high, mainly due to intense radiotherapy. Furthermore, survival in patients with metastatic disease and resistant to conventional chemotherapy remains poor. Primary objective of this study is to investigate whether the addition of nivolumab to standard induction chemotherapy in children and adults with EBV-positive NPC is able to increase the rate of complete responses, thus enabling a reduction in radiation dose in more patients, but also offer patients with high risk of treatment failure the chance to benefit from the addition of nivolumab.

Trial registration

EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) No. 2021-006477-32.
Assessing the potential of genetic resource introduction into elite germplasm: a collaborative multiparental population for flint maize
Authors: Sanchez Dimitri , Allier Antoine , Ben Sadoun Sarah , Mary-Huard Tristan , Bauland Cyril , Palaffre Carine , Lagardère Bernard , Madur Delphine , Combes Valérie , Melkior Stéphane , Bettinger Laurent , Murigneux Alain , Moreau Laurence , Charcosset Alain
Published: January 2024

Key message

Implementing a collaborative pre-breeding multi-parental population efficiently identifies promising donor x elite pairs to enrich the flint maize elite germplasm.

Genetic diversity is crucial for maintaining genetic gains and ensuring breeding programs’ long-term success. In a closed breeding program, selection inevitably leads to a loss of genetic diversity. While managing diversity can delay this loss, introducing external sources of diversity is necessary to bring back favorable genetic variation. Genetic resources exhibit greater diversity than elite materials, but their lower performance levels hinder their use. This is the case for European flint maize, for which elite germplasm has incorporated only a limited portion of the diversity available in landraces. To enrich the diversity of this elite genetic pool, we established an original cooperative maize bridging population that involves crosses between private elite materials and diversity donors to create improved genotypes that will facilitate the incorporation of original favorable variations. Twenty donor × elite BC1S2 families were created and phenotyped for hybrid value for yield related traits. Crosses showed contrasted means and variances and therefore contrasted potential in terms of selection as measured by their usefulness criterion (UC). Average expected mean performance gain over the initial elite material was 5%. The most promising donor for each elite line was identified. Results also suggest that one more generation, i.e., 3 in total, of crossing to the elite is required to fully exploit the potential of a donor. Altogether, our results support the usefulness of incorporating genetic resources into elite flint maize. They call for further effort to create fixed diversity donors and identify those most suitable for each elite program.
Early-childhood body mass index and its association with the COVID-19 pandemic, containment measures and islet autoimmunity in children with increased risk for type 1 diabetes
Authors: Hummel Sandra , Rosenberger Sarah , von dem Berge Thekla , Besser Rachel E. J. , Casteels Kristina , Hommel Angela , Kordonouri Olga , Elding Larsson Helena , Lundgren Markus , Marcus Benjamin A. , Oltarzewski Mariusz , Rochtus Anne , Szypowska Agnieszka , Todd John A. , Weiss Andreas , Winkler Christiane , Bonifacio Ezio , Ziegler Anette-G. ,   for the GPPAD and POInT Study Group
Published: January 2024

Aims/hypothesis

The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for islet autoimmunity.

Methods

Between February 2018 and May 2023, data on BMI and islet autoimmunity were collected from 1050 children enrolled in the Primary Oral Insulin Trial, aged from 4.0 months to 5.5 years of age. The start of the COVID-19 pandemic was defined as 18 March 2020, and a stringency index was used to assess the stringency of containment measures. Islet autoimmunity was defined as either the development of persistent confirmed multiple islet autoantibodies, or the development of one or more islet autoantibodies and type 1 diabetes. Multivariate linear mixed-effect, linear and logistic regression methods were applied to assess the effect of the COVID-19 pandemic and the stringency index on early-childhood BMI measurements (BMI as a time-varying variable, BMI at 9 months of age and overweight risk at 9 months of age), and Cox proportional hazard models were used to assess the effect of BMI measurements on islet autoimmunity risk.

Results

The COVID-19 pandemic was associated with increased time-varying BMI (β = 0.39; 95% CI 0.30, 0.47) and overweight risk at 9 months (β = 0.44; 95% CI 0.03, 0.84). During the COVID-19 pandemic, a higher stringency index was positively associated with time-varying BMI (β = 0.02; 95% CI 0.00, 0.04 per 10 units increase), BMI at 9 months (β = 0.13; 95% CI 0.01, 0.25) and overweight risk at 9 months (β = 0.23; 95% CI 0.03, 0.43). A higher age-corrected BMI and overweight risk at 9 months were associated with increased risk for developing islet autoimmunity up to 5.5 years of age (HR 1.16; 95% CI 1.01, 1.32 and HR 1.68, 95% CI 1.00, 2.82, respectively).

Conclusions/interpretation

Early-childhood BMI increased during the COVID-19 pandemic, and was influenced by the level of restrictions during the pandemic. Controlling for the COVID-19 pandemic, elevated BMI during early childhood was associated with increased risk for childhood islet autoimmunity in children with genetic susceptibility to type 1 diabetes.

Graphical Abstract
Prediction of absorptivity in Multi-Jet Fusion manufactured polypropylene structures through laser flash and corrected porosity method
Authors: Kafi Abdullah , Khorasani Mahyar , Downing David , Rashed Kaifur , Leary Martin , Zhang Danielle , Bateman Stuart
Published: January 2024

For the first time in the literature, this study validates the absorption phenomena in Multi-Jet Fusion (MJF) printed polypropylene (PP) structures through Laser Flash (LFA) and Corrected Porosity (CP) methods. The influence of process parameters such as build height and build orientation was investigated on tensile properties, crystallinity, porosity and thermophysical attributes in MJF printed PP coupons. Results showed that both crystallinity and tensile performance did not significantly vary with either location or build orientation. Interestingly, samples printed in the Z orientation showed a 35% decrease in strain, indicating that Z-oriented MJF coupons were more brittle than the flat samples (XY). Samples printed in Z orientation also possessed higher porosity and relatively lower crystallinity than the XY orientation. However, large deviations within porosity values were an obstacle to determining a suitable build chamber location for manufacturing dense samples. Therefore, a detailed investigation on porosity of printed samples using micro-CT scans and CT image analysis was necessary. Initially, poor contrast was obvious when MJF printed samples were positioned vertically in the micro-CT chamber which was mainly due to high value of horizontal intensity profile (HIP ~ 70%). Contrast in MJF samples improved significantly in the horizontal orientation (HIP ~ 40%). In parallel, the half-time and heat loss were measured in LFA to understand changes in absorption phenomena with height and orientation of the build. A direct correlation was found between LFA half-time and porosity only when the porosity correction method was implemented. Corrected porosity value was found to be inversely proportional to the heat loss of printed PP samples which indicated higher absorption for samples printed in the bottom of build chamber, XY12, whereas lower absorption was observed for less dense Z samples. Finally, heat loss phenomenon was verified using dense reference Pyroceram samples as they possess high diffusivity and low half-time and porosity compared to MJF printed samples. There is a science behind understanding the absorptivity of the MJF process which is related to the complexity of the process and is challenging to address in MJF PP samples when mixed with carbon black. The study showed that accurately determining the level of porosity is the key to validate absorption phenomena within MJF printed coupons. The contributions of this work are the investigation of the light absorption phenomena in MJF printed PP structures, and the establishment of the absorption-porosity correlation. These contributions help to predict the mechanical properties and subsequently the overall quality of the produced parts which can save cost and time in effectively utilising the MJF process.
Optimization of an agent-based model for continuous trading energy market
Authors: Alberizzi A. , Di Barba P. , Mognaschi M. E. , Zani A.
Published: January 2024

The high penetration of intermittence resources in the energy market accelerates significantly the decarbonization process, but, on the other hand, the electrical system has to face the problem of unbalances. Renewable energies sources are hard to precisely forecast, and power plants are not able to predict the amount of energy that they can provide far from the real-time delivery. In this frame, the intraday market gets a fundamental role allowing agents to adjust their position close to the delivery time. In this work, we suggest an agent-based model of intraday market combined with genetics algorithms to understand what the best strategy could be adopted by players in order to optimize the market efficiency in terms of welfare and unsold quantity. In the first part, we show the effect on the market prices of different scenarios in which players aim at maximizing their revenues and selling/buying all their volumes. In the second part, we show the effect of a particular genetic algorithm on the model, focusing on how agents can adapt their strategy to enhance the market efficiency. Comparative analyses are also performed to investigate how the welfare of the system increases as well as the unsold quantity decrease when genetic algorithm is introduced.
LC-ESI-HRMS — lipidomics of phospholipids
Authors: Rund Katharina M. , Carpanedo Laura , Lauterbach Robin , Wermund Tim , West Annette L. , Wende Luca M. , Calder Philip C. , Schebb Nils Helge
Published: January 2024

Lipids are a diverse class of molecules involved in many biological functions including cell signaling or cell membrane assembly. Owing to this relevance, LC–MS/MS-based lipidomics emerged as a major field in modern analytical chemistry. Here, we thoroughly characterized the influence of MS and LC settings — of a Q Exactive HF operated in Full MS/data-dependent MS2 TOP N acquisition mode — in order to optimize the semi-quantification of polar lipids. Optimization of MS-source settings improved the signal intensity by factor 3 compared to default settings. Polar lipids were separated on an ACQUITY Premier CSH C18 reversed-phase column (100 × 2.1 mm, 1.7 µm, 130 Å) during an elution window of 28 min, leading to a sufficient number of both data points across the chromatographic peaks, as well as MS2 spectra. Analysis was carried out in positive and negative ionization mode enabling the detection of a broader spectrum of lipids and to support the structural characterization of lipids. Optimal sample preparation of biological samples was achieved by liquid–liquid extraction using MeOH/MTBE resulting in an excellent extraction recovery > 85% with an intra-day and inter-day variability < 15%. The optimized method was applied on the investigation of changes in the phospholipid pattern in plasma from human subjects supplemented with n3-PUFA (20:5 and 22:6). The strongest increase was observed for lipids bearing 20:5, while 22:4 bearing lipids were lowered. Specifically, LPC 20:5_0:0 and PC 16:0_20:5 were found to be strongest elevated, while PE 18:0_22:4 and PC 18:2_18:2 were decreased by n3-PUFA supplementation. These results were confirmed by targeted LC–MS/MS using commercially available phospholipids as standards.

Graphical abstract
Approximating subset sum ratio via partition computations
Authors: Alonistiotis Giannis , Antonopoulos Antonis , Melissinos Nikolaos , Pagourtzis Aris , Petsalakis Stavros , Vasilakis Manolis
Published: January 2024

We present a new FPTAS for the Subset Sum Ratio problem, which, given a set of integers, asks for two disjoint subsets such that the ratio of their sums is as close to 1 as possible. Our scheme makes use of exact and approximate algorithms for Partition, and clearly showcases the close relationship between the two algorithmic problems. Depending on the relationship between the size of the input set n and the error margin $$\varepsilon $$
ε
, we improve upon the best currently known algorithm of Melissinos and Pagourtzis [COCOON 2018] of complexity $$\mathcal {O} (n^4 / \varepsilon )$$

O
(

n
4

/
ε
)

. In particular, the exponent of n in our proposed scheme may decrease down to 2, depending on the Partition algorithm used.
Predictors of Good Clinical Outcome After Endovascular Treatment for Acute Ischemic Stroke due to Tandem Lesion in Anterior Circulation: Results from the ASCENT Study
Authors: Havlíček Roman , Šaňák Daniel , Černík David , Neradová Jarmila , Leško Norbert , Gdovinová Zuzana , Köcher Martin , Cihlář Filip , Malik Jozef , Fedorko Jakub , Pedowski Piotr , Zapletalová Jana
Published: January 2024

Purpose

Endovascular treatment (EVT) of tandem lesion (TL) in anterior circulation (AC) acute ischemic stroke (AIS) represents still a clinical challenge. We aimed to evaluate selected factors related to EVT and assess other possible predictors of good clinical outcome besides the generally known ones.

Methods

AIS patients with TL in AC treated with EVT were enrolled in the multicenter retrospective ASCENT study. A good three-month clinical outcome was scored as 0–2 points in modified Rankin Scale (mRS) and achieved recanalization using the TICI scale. Symptomatic intracerebral hemorrhage (SICH) was assessed using the SITS-MOST criteria. Logistic regression analysis was used for the assessment of possible predictors of mRS 0–2 with adjustment for potential confounders.

Results

In total, 300 (68.7% males, mean age 67.3 ± 10.2 years) patients with median of admission NIHSS 17 were analyzed. Recanalization (TICI 2b-3) was achieved in 290 (96.7%) patients and 176 (58.7%) had mRS 0–2. Besides the age, admission NIHSS and SICH, admission glycemia (p = 0.005, OR: 0.884) the stent patency within the first 30 days after EVT (p = 0.0003, OR: 0.219), dual antiplatelet therapy (DAPT) started within 12 h after EVT (p < 0.0001, OR: 5.006) and statin therapy started within 24 h after stenting (p < 0.0001, OR: 5.558) were found as other predictors.

Conclusion

Admission glycemia, start of DAPT within 12 h and statin therapy within 24 h after EVT, and stent patency within the first 30 days after EVT were found as other predictors of good three-month clinical outcome in AIS patients treated with EVT for TL.

Graphical Abstract
VEXAS syndrome: complete molecular remission after hypomethylating therapy
Authors: Sockel Katja , Götze Katharina , Ganster Christina , Bill Marius , Georgi Julia-Annabell , Balaian Ekaterina , Aringer Martin , Trautmann-Grill Karolin , Uhlig Maria , Bornhäuser Martin , Haase Detlef , Thiede Christian
Published: January 2024

The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial description in 2020. While various therapeutic strategies have been explored in case studies, the optimal treatment strategy is still under investigation and allogeneic cell transplantation is considered the only curative treatment. Here, we describe 2 patients who achieved complete molecular remission of the underlying UBA1 mutant clone outside the context of allogeneic HCT. Both patients received treatment with the hypomethylating agent azacitidine, and deep molecular remission triggered treatment de-escalation and even cessation with sustained molecular remission in one of them. Prospective studies are necessary to clarify which VEXAS patients will benefit most from hypomethylating therapy and to understand the variability in the response to different treatment strategies.
Customized GRASP for rehabilitation therapy scheduling with appointment priorities and accounting for therapist satisfaction
Authors: Kling Sebastian , Kraul Sebastian , Brunner Jens O.
Published: January 2024

Physical therapy in acute care hospitals plays an important role in the rehabilitation of patients. Nevertheless, the profession must deal with staff shortages caused by a lack of potential employees and absenteeism which are results of high physical and mental workloads. The therapist shortage negatively affects the total number of daily appointments the department can fulfill. For appointments that can be successfully scheduled, continuity of care with the same therapist cannot be guaranteed for individual patients. Lack of continuity of care negatively influences the therapist's satisfaction. Therapist preferences for individual appointments in general cannot always be guaranteed when designing schedules, which also hurts satisfaction. This paper develops a multi-criteria model for the daily therapy appointment-scheduling problem. The primary objective is to minimize the total sum of priority violations for unscheduled appointments. To improve therapist satisfaction, we consider therapist preferences including continuity of care as a secondary objective. Here, our integer programming formulation aims to minimize the total sum of preference violations for scheduled appointments. We are dealing with an operational planning problem with a daily planning horizon. The operational objective is to achieve therapist schedules in at most two hours. The therapists’ schedules together need to include several hundred appointments for a planning day. Due to intractability, the developed integer program cannot provide schedules for such problem sizes. Therefore, we develop a customized Greedy Randomized Adaptive Search Procedure (GRASP) with six innovative local search operations to improve an initially constructed solution. We test the heuristic algorithm on realistic data instances. The metaheuristic provides high-quality schedules for various problem sizes in short runtimes, i.e., within minutes. Comparisons with the optimal solutions for small problem instances show very good results of the GRASP with a similar number of scheduled appointments and good adherence to continuity of care and therapist preference requirements.
A stepwise strategy integrating dynamic stress CT myocardial perfusion and deep learning–based FFRCT in the work-up of stable coronary artery disease
Authors: Lyu Lijuan , Pan Jichen , Li Dumin , Yu Dexin , Li Xinhao , Yang Wei , Dong Mei , Han Yeming , Liang Yongfeng , Zhang Pengfei , Zhang Mei
Published: January 2024

Objectives

To validate a novel stepwise strategy in which computed tomography–derived fractional flow reserve (FFRCT) is restricted to intermediate stenosis on coronary computed tomography angiography (CCTA) and computed tomography myocardial perfusion imaging (CT-MPI) was reserved for vessels with gray zone FFRCT values.

Materials and methods

This retrospective study included 87 consecutive patients (age, 58 ± 10 years; 70% male) who underwent CCTA, dynamic CT-MPI, interventional coronary angiography (ICA), and fractional flow reserve (FFR) for suspected or known coronary artery disease. FFRCT was computed using a deep learning–based platform. Three stepwise strategies (CCTA + FFRCT + CT-MPI, CCTA + FFRCT, CCTA + CT-MPI) were constructed and their diagnostic performance was evaluated using ICA/FFR as the reference standard. The proportions of vessels requiring further ICA/FFR measurement based on different strategies were noted. Furthermore, the net reclassification index (NRI) was calculated to ascertain the superior model.

Results

The CCTA + FFRCT + CT-MPI strategy yielded the lowest proportion of vessels requiring additional ICA/FFR measurement when compared to the CCTA + FFRCT and CCTA + CT-MPI strategies (12%, 22%, and 24%). The CCTA + FFRCT + CT-MPI strategy exhibited the highest accuracy for ruling-out (91%, 84%, and 85%) and ruling-in (90%, 85%, and 85%) functionally significant lesions. All strategies exhibited comparable sensitivity for ruling-out functionally significant lesions and specificity for ruling-in functionally significant lesions (p > 0.05). The NRI indicated that the CCTA + FFRCT + CT-MPI strategy outperformed the CCTA + FFRCT strategy (NRI = 0.238, p < 0.001) and the CCTA + CT-MPI strategy (NRI = 0.233%, p < 0.001).

Conclusions

The CCTA + FFRCT + CT-MPI stepwise strategy was superior to the CCTA + FFRCT strategy and CCTA+ CT-MPI strategy by minimizing unnecessary invasive diagnostic catheterization without compromising the agreement rate with ICA/FFR.

Clinical relevance statement

Our novel stepwise strategy facilitates greater confidence and accuracy when clinicians need to decide on interventional coronary angiography referral or deferral, reducing the burden of invasive investigations on patients.

Key Points

• A stepwise CCTA + FFRCT + CT-MPI strategy holds promise as a viable method to reduce the need for invasive diagnostic catheterization, while maintaining a high level of agreement with ICA/FFR.

• The CCTA + FFRCT + CT-MPI strategy performed better than the CCTA + FFRCT and CCTA + CT-MPI strategies.

• A stepwise CCTA + FFRCT + CT-MPI strategy allows to minimize unnecessary invasive diagnostic catheterization and helps clinicians to referral or deferral for ICA/FFR with more confidence.
Iatrogene Netzhautdefekte nach intravitrealer operativer Medikamenteneingabe
Authors: Märker David A. , Radeck Viola , Lehmann Fabian , Barth Teresa , Helbig Horst , Eter Nicole , Alten Florian , Clemens Christoph R.
Published: January 2024

Hintergrund

Intravitreale operative Medikamenteneingaben (IVOM) stellen einen der häufigsten Eingriffe in der Medizin dar. Das Risikoprofil ist gering. Neben intraokularen Drucksteigerungen zählen insbesondere erregerbedingte Endophthalmitiden, Glaskörperblutungen und rhegmatogene Netzhautablösungen zu den gängigen Komplikationen. Darüber hinaus wurden auch einzelne Fälle von Linsenverletzungen sowie peripheren Netzhautdefekten und Makulaforamina in Assoziation mit vitreoretinalen Traktionen beschrieben. In der hier vorliegenden Fallserie berichten wir über scharfe iatrogene Netzhaut- bzw. Makulaverletzungen.

Methoden

Multizentrische Fallsammlung von IVOM-Patienten mit iatrogenen Netzhautdefekten, retrospektiv über den Zeitraum 2016 bis 2023.

Ergebnisse

Es konnten 9 Fälle (72 Jahre ± 8,1, 3 Augen pseudophak) mit einem iatrogenen retinalen Trauma nach IVOM zur Therapie einer neovaskulären altersbedingten Makuladegeneration (nAMD) dokumentiert werden. Während in 6 Fällen scharfe Verletzungen innerhalb der Makula vorlagen, waren die Läsionen in den anderen Fällen extramakulär lokalisiert.

Schlussfolgerungen

Iatrogene Netzhaut- und Makulaverletzungen sind seltene Komplikationen im Rahmen der IVOM und bei sachgemäßer Durchführung insbesondere mit Blick auf die Kanülenverwendung und die Wahl des Limbusabstands vermeidbar.
Complement and MHC patterns can provide the diagnostic framework for inflammatory neuromuscular diseases
Authors: Nelke Christopher , Schmid Simone , Kleefeld Felix , Schroeter Christina B. , Goebel Hans-Hilmar , Hoffmann Sarah , Preuße Corinna , Kölbel Heike , Meuth Sven G. , Ruck Tobias , Stenzel Werner
Published: January 2024

Histopathological analysis stands as the gold standard for the identification and differentiation of inflammatory neuromuscular diseases. These disorders continue to constitute a diagnostic challenge due to their clinical heterogeneity, rarity and overlapping features. To establish standardized protocols for the diagnosis of inflammatory neuromuscular diseases, the development of cost-effective and widely applicable tools is crucial, especially in settings constrained by limited resources. The focus of this review is to emphasize the diagnostic value of major histocompatibility complex (MHC) and complement patterns in the immunohistochemical analysis of these diseases. We explore the immunological background of MHC and complement signatures that characterize inflammatory features, with a specific focus on idiopathic inflammatory myopathies. With this approach, we aim to provide a diagnostic algorithm that may improve and simplify the diagnostic workup based on a limited panel of stainings. Our approach acknowledges the current limitations in the field of inflammatory neuromuscular diseases, particularly the scarcity of large-scale, prospective studies that validate the diagnostic potential of these markers. Further efforts are needed to establish a consensus on the diagnostic protocol to effectively distinguish these diseases.
The impact of PA/I38 substitutions and PA polymorphisms on the susceptibility of zoonotic influenza A viruses to baloxavir
Authors: Taniguchi Keiichi , Noshi Takeshi , Omoto Shinya , Sato Akihiko , Shishido Takao , Matsuno Keita , Okamatsu Masatoshi , Krauss Scott , Webby Richard J , Sakoda Yoshihiro , Kida Hiroshi
Published: January 2024

Genetic reassortment of avian, swine, and human influenza A viruses (IAVs) poses potential pandemic risks. Surveillance is important for influenza pandemic preparedness, but the susceptibility of zoonotic IAVs to the cap-dependent endonuclease inhibitor baloxavir acid (BXA) has not been thoroughly researched. Although an amino acid substitution at position 38 in the polymerase acidic protein (PA/I38) in seasonal IAVs reduces BXA susceptibility, PA polymorphisms at position 38 are rarely seen in zoonotic IAVs. Here, we examined the impact of PA/I38 substitutions on the BXA susceptibility of recombinant A(H5N1) viruses. PA mutants that harbored I38T, F, and M were 48.2-, 24.0-, and 15.5-fold less susceptible, respectively, to BXA than wild-type A(H5N1) but were susceptible to the neuraminidase inhibitor oseltamivir acid and the RNA polymerase inhibitor favipiravir. PA mutants exhibited significantly impaired replicative fitness in Madin-Darby canine kidney cells at 24 h postinfection. In addition, in order to investigate new genetic markers for BXA susceptibility, we screened geographically and temporally distinct IAVs isolated worldwide from birds and pigs. The results showed that BXA exhibited antiviral activity against avian and swine viruses with similar levels to seasonal isolates. All viruses tested in the study lacked the PA/I38 substitution and were susceptible to BXA. Isolates harboring amino acid polymorphisms at positions 20, 24, and 37, which have been implicated in the binding of BXA to the PA endonuclease domain, were also susceptible to BXA. These results suggest that monitoring of the PA/I38 substitution in animal-derived influenza viruses is important for preparedness against zoonotic influenza virus outbreaks.
A short review of the effect of external pressure on the batteries
Authors: Šedina Martin , Šimek Antonín , Báňa Jiří , Kazda Tomáš
Published: January 2024

The research of the batteries is still going forward and there are lots of challenges which should be solved. This text examines the effect of external pressure on different types of batteries and explores their potential for improving performance and lifetime. The studies reviewed in the text show interesting results where external pressure affects capacity, internal resistance, stability or other parameters of modern battery systems as Li-ion, solid-state, or Li–S batteries. Despite the challenges, the benefits for next-generation batteries seem promising and show its role in battery development and manufacturing.

Graphical abstract
Input/output-style approach to standardized traditional amortization plans
Authors: Pressacco Flavio , Ziani Laura
Published: January 2024

We apply an Input/Output approach to the analysis of the so-called traditional standardized amortization plans (STAP). The approach is based on a clear distinction between Input/trigger and Output of a STAP. The Output is a set of four vectors obtained by applying a set of transformation matrices to an appropriate Input/trigger vector. The main result of the paper is that, by this approach, any STAP reveals a dual nature through the introduction of the twin trigger theory.
Natural Language Processing Algorithm Used for Staging Pulmonary Oncology from Free-Text Radiological Reports: “Including PET-CT and Validation Towards Clinical Use”
Authors: Nobel J. Martijn , Puts Sander , Krdzalic Jasenko , Zegers Karen M. L. , Lobbes Marc B. I. , F. Robben Simon G. , Dekker André L. A. J.
Published: January 2024

Natural language processing (NLP) can be used to process and structure free text, such as (free text) radiological reports. In radiology, it is important that reports are complete and accurate for clinical staging of, for instance, pulmonary oncology. A computed tomography (CT) or positron emission tomography (PET)-CT scan is of great importance in tumor staging, and NLP may be of additional value to the radiological report when used in the staging process as it may be able to extract the T and N stage of the 8th tumor–node–metastasis (TNM) classification system. The purpose of this study is to evaluate a new TN algorithm (TN-PET-CT) by adding a layer of metabolic activity to an already existing rule-based NLP algorithm (TN-CT). This new TN-PET-CT algorithm is capable of staging chest CT examinations as well as PET-CT scans. The study design made it possible to perform a subgroup analysis to test the external validation of the prior TN-CT algorithm. For information extraction and matching, pyContextNLP, SpaCy, and regular expressions were used. Overall TN accuracy score of the TN-PET-CT algorithm was 0.73 and 0.62 in the training and validation set (N = 63, N = 100). The external validation of the TN-CT classifier (N = 65) was 0.72. Overall, it is possible to adjust the TN-CT algorithm into a TN-PET-CT algorithm. However, outcomes highly depend on the accuracy of the report, the used vocabulary, and its context to express, for example, uncertainty. This is true for both the adjusted PET-CT algorithm and for the CT algorithm when applied in another hospital.
Development of End-to-End AI–Based MRI Image Analysis System for Predicting IDH Mutation Status of Patients with Gliomas: Multicentric Validation
Authors: Santinha João , Katsaros Vasileios , Stranjalis George , Liouta Evangelia , Boskos Christos , Matos Celso , Viegas Catarina , Papanikolaou Nickolas
Published: January 2024

Radiogenomics has shown potential to predict genomic phenotypes from medical images. The development of models using standard-of-care pre-operative MRI images, as opposed to advanced MRI images, enables a broader reach of such models. In this work, a radiogenomics model for IDH mutation status prediction from standard-of-care MRIs in patients with glioma was developed and validated using multicentric data. A cohort of 142 (wild-type: 32.4%) patients with glioma retrieved from the TCIA/TCGA was used to train a logistic regression model to predict the IDH mutation status. The model was evaluated using retrospective data collected in two distinct hospitals, comprising 36 (wild-type: 63.9%) and 53 (wild-type: 75.5%) patients. Model development utilized ROC analysis. Model discrimination and calibration were used for validation. The model yielded an AUC of 0.741 vs. 0.716 vs. 0.938, a sensitivity of 0.784 vs. 0.739 vs. 0.875, and a specificity of 0.657 vs. 0.692 vs. 1.000 on the training, test cohort 1, and test cohort 2, respectively. The assessment of model fairness suggested an unbiased model for age and sex, and calibration tests showed a p < 0.05. These results indicate that the developed model allows the prediction of the IDH mutation status in gliomas using standard-of-care MRI images and does not appear to hold sex and age biases.
Hybrid Topological Data Analysis and Deep Learning for Basal Cell Carcinoma Diagnosis
Authors: Maurya Akanksha , Stanley R. Joe , Lama Norsang , Nambisan Anand K. , Patel Gehana , Saeed Daniyal , Swinfard Samantha , Smith Colin , Jagannathan Sadhika , Hagerty Jason R. , Stoecker William V.
Published: January 2024

A critical clinical indicator for basal cell carcinoma (BCC) is the presence of telangiectasia (narrow, arborizing blood vessels) within the skin lesions. Many skin cancer imaging processes today exploit deep learning (DL) models for diagnosis, segmentation of features, and feature analysis. To extend automated diagnosis, recent computational intelligence research has also explored the field of Topological Data Analysis (TDA), a branch of mathematics that uses topology to extract meaningful information from highly complex data. This study combines TDA and DL with ensemble learning to create a hybrid TDA-DL BCC diagnostic model. Persistence homology (a TDA technique) is implemented to extract topological features from automatically segmented telangiectasia as well as skin lesions, and DL features are generated by fine-tuning a pre-trained EfficientNet-B5 model. The final hybrid TDA-DL model achieves state-of-the-art accuracy of 97.4% and an AUC of 0.995 on a holdout test of 395 skin lesions for BCC diagnosis. This study demonstrates that telangiectasia features improve BCC diagnosis, and TDA techniques hold the potential to improve DL performance.