bluuebunny/crossref_metadata_2025 huggingface dataset:
A molecular basis for tetramer destabilization and aggregation of transthyretin Ala97Ser
Authors: Wang Yi‐Shiang , Huang Chun‐Hsiang , Liou Gunn‐Guang , Hsueh Hsueh‐Wen , Liang Chi‐Ting , Tseng Hsi‐Ching , Huang Shing‐Jong , Chao Chi‐Chao , Hsieh Sung‐Tsang , Tzeng Shiou‐Ru
Published: March 2023

Transthyretin (TTR)‐related amyloidosis (ATTR) is a syndrome of diseases characterized by the extracellular deposition of fibrillar materials containing TTR variants. Ala97Ser (A97S) is the major mutation reported in Taiwanese ATTR patients. Here, we combine atomic resolution structural information together with the biochemical data to demonstrate that substitution of polar Ser for a small hydrophobic side chain of Ala at residue 97 of TTR largely influences the local packing density of the FG‐loop, thus leading to the conformational instability of native tetramer, the increased monomeric species, and thus the enhanced amyloidogenicity of apo‐A97S. Based on calorimetric studies, the tetramer destabilization of A97S can be substantially altered by interacting with native stabilizers via similarly energetic patterns compared to that of wild‐type (WT) TTR; however, stabilizer binding partially rearranges the networks of hydrogen bonding in TTR variants while FG‐loops of tetrameric A97S still remain relatively flexible. Moreover, TTR in complexed with holo‐retinol binding protein 4 is slightly influenced by the structural and dynamic changes of FG‐loop caused by A97S substitution with an approximately five‐fold difference in binding affinity. Collectively, our findings suggest that the amyloidogenic A97S mutation destabilizes TTR by increasing the flexibility of the FG‐loop in the monomer, thus modulating the rate of amyloid fibrillization.
Mass spectrometry redefines optimal testosterone thresholds in prostate cancer patients undergoing androgen deprivation therapy
Authors: Beck Jérémie , Rouleau Mélanie , Lemire Francis , Neveu Bertrand , Déry Michel , Thériault Benoît , Dubois Gabriel , Guérette Dominique , Pouliot Frédéric
Published: March 2023

Background

Androgen deprivation therapy (ADT) is the standard of care for prostate cancer treatment. Studies suggest that patients with testosterone levels below 0.7 nM have a longer time to castration resistance. Using the most accurate testosterone measurement method, namely mass spectrometry (MS), we sought to determine if a lower testosterone level under ADT could be associated with longer time to castration resistance.

Methods

This retrospective study included 138 prostate cancer patients undergoing noncurative continuous ADT for which we had access to testosterone measurements assessed by MS. For 108 samples, paired immunoassays (IA) testosterone measurement was available. Primary outcome was time to castration‐resistant prostate cancer (CRPC). The Contal and O'Quigley method was used to determine the optimal testosterone castration cut‐off point considering the outcome and time‐to‐event variables. Relationship between testosterone levels assessed either by IA or MS and time to CRPC was evaluated using Cox regression.

Results

Mean testosterone level was 0.370 nM by IA and 0.275 nM as assessed by MS. The optimal testosterone cut‐off point identified to predict time to CRPC was of 0.705 nM for IA and of 0.270 nM for MS. While no significant difference for time to CRPC was found between patients showing IA testosterone level ≥0.705 nM versus <0.705 nM (hazard ratio [HR]: 1.579; 95% confidence interval [CI]: 0.908–2.745), patients with MS testosterone ≥0.270 nM had an increased risk of progression to CRPC compared to MS testosterone <0.270 nM in univariate (HR: 1.717; 95% CI: 1.160–2.541) and multivariate analysis (HR: 1.662; 95% CI: 1.043–2.648).

Conclusions

The higher sensitivity of MS testosterone measurement methods allows the identification of a lower castration threshold and leads to early identification of patients more likely to progress to CRPC. These patients would likely benefit from treatment intensification by androgen receptor axis‐targeted therapies to delay disease progression.
Population model‐based analysis of the memory B‐cell response following belimumab therapy in the treatment of systemic lupus erythematosus
Authors: Dimelow Richard , Gillespie William R. , van Maurik Andre
Published: March 2023

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B‐cell hyperactivity and breach of tolerance. Autoreactive memory B cells, which have a decreased activation threshold and the ability to survive in absence of antigen, are believed to contribute to chronicity in autoimmune diseases like SLE. Belimumab, the first approved biological treatment of active SLE and lupus nephritis, reduces B cells dependent on B‐lymphocyte stimulator protein (BLyS) for survival, whereas memory B cells are spared; several studies reported circulating memory B‐cell concentrations increase following BLyS neutralization. This analysis investigated the effect of dose, demographics, and disease status on memory B‐cell response after starting belimumab treatment. Population pharmacodynamic models were fitted to a pooled dataset from seven belimumab SLE trials. The optimal model was selected using maximum likelihood methods and was then refit to the data using Bayesian analysis and used to simulate memory B‐cell response by belimumab dose and covariate subgroups. At the belimumab approved doses (10 mg/kg intravenously every 4 weeks, 200 mg subcutaneously every week), circulatory memory B cells increase in the first 4–8 weeks after belimumab initiation, typically returning to baseline levels over 76 weeks. The model analysis suggested belimumab stimulates memory B‐cell transition from lymphoid and/or inflamed tissues into the circulation, rather than inhibiting trafficking in the reverse direction. Baseline BLyS and anti–double‐stranded deoxyribonucleic acid antibody concentrations were statistically identifiable covariates of memory B‐cell response, although their impact on predicting size and response duration was small.
Mechanistic modeling of ophthalmic, nasal, injectable, and implant generic drug products: A workshop summary report
Authors: Tan Ming‐Liang , Chandran Sajeev , Jereb Rebeka , Alam Khondoker , Bies Robert , Kozak Darby , Walenga Ross , Le Merdy Maxime , Babiskin Andrew
Published: March 2023

For approval, a proposed generic drug product must demonstrate it is bioequivalent (BE) to the reference listed drug product. For locally acting drug products, conventional BE approaches may not be feasible because measurements in local tissues at the sites of action are often impractical, unethical, or cost‐prohibitive. Mechanistic modeling approaches, such as physiologically‐based pharmacokinetic (PBPK) modeling, may integrate information from drug product properties and human physiology to predict drug concentrations in these local tissues. This may allow clinical relevance determination of critical drug product attributes for BE assessment during the development of generic drug products. In this regard, the Office of Generic Drugs of the US Food and Drug Administration has recently established scientific research programs to accelerate the development and assessment of generic products by utilizing model‐integrated alternative BE approaches. This report summarizes the presentations and panel discussion from a public workshop that provided research updates and information on the current state of the use of PBPK modeling approaches to support generic product development for ophthalmic, injectable, nasal, and implant drug products.
Risperidone dosing schedule
Authors: Lam Y. W. Francis
Published: March 2023

Medication adherence is an important determinant of treatment outcome and is especially pertinent in managing chronic disorders such as schizophrenia. Clinicians who work with patients with schizophrenia generally agree that non‐adherence with antipsychotics such as risperidone is associated with high rates of relapse and rehospitalization, with worsening symptoms that can include suicidality and violence.
A novel dynamic proteomics approach for the measurement of broiler chicken protein fractional synthesis rate
Authors: Peinado‐Izaguerri Jorge , Zarzuela Eduardo , McLaughlin Mark , Small Alexandra C. , Riva Francesca , McKeegan Dorothy E. F. , Bain Maureen , Muñoz Javier , Bhide Mangesh , Preston Tom
Published: March 2023

Rationale

The study of protein synthesis in farm animals is uncommon despite its potential to increase knowledge about metabolism and discover new biomarkers of health and growth status. The present study describes a novel dynamic proteomics approach for the measurement of protein fractional synthesis rate (FSR) in broiler chickens.

Methods

Chickens received a 10 g/kg oral dose of 2H2O at day 21 of their life. Body water 2H abundance was measured in plasma samples using a portable Fourier transform infrared spectrometer. Free and protein‐bound amino acids (AAs) were isolated and had their 2H enrichment measured by gas chromatography with mass spectrometry (GC/MS). Peptide 2H enrichment was measured by proteomics analysis of plasma and muscle samples. Albumin, fibrinogen and muscle protein FSR were calculated from GC/MS and proteomics data.

Results

Ala appeared to be more enriched at the site of protein synthesis than in the AA free pools. Glu was found to be the AA closest to isotopic equilibrium between the different AA pools. Glu was used as an anchor to calculate n(AA) values necessary for chicken protein FSR calculation in dynamic proteomics studies. FSR values calculated using proteomics data and GC/MS data showed good agreement as evidenced by a Bland–Altman residual plot.

Conclusions

A new dynamic proteomics approach for the measurement of broiler chicken individual protein FSR based on the administration of a single 2H2O oral bolus has been developed and validated. The proposed approach could facilitate new immunological and nutritional studies on free‐living animals.
Improving human development through urbanization, demographic dividend and biomass energy consumption
Authors: Nguea Stéphane Mbiankeu
Published: March 2023

The policy debate on the effects of urbanization, demographic dividend and biomass energy consumption on human development in Africa has long suffered from a scarcity of empirical evidence. This study, therefore, explores the relationship between urbanization, demographic dividend, biomass energy consumption and human development (measured by the human development index, human capital, life expectancy and infant mortality) in 33 African countries between 1990 and 2019. We employ Driscoll‐Kraay, instrumental variable and the panel quantile regression methods. We find that an increase in urbanization, demographic dividend and biomass energy consumption leads to a higher level of human development. Accounting for different facets of human development such as education (human capital) and health (life expectancy and infant mortality), the results show that urbanization and biomass energy consumption improve education and health. The results also show that while demographic dividend improves education and infant mortality, its effect on life expectancy is negative and significant. These findings are robust for reliable and consistent policy directives.
A Metabolic Driven Bio‐Responsive Hydrogel Loading Psoralen for Therapy of Rheumatoid Arthritis
Authors: Wang Kexin , Yin Chuanhui , Ye Xiangmin , Chen Quanlin , Wu Jie , Chen Yupeng , Li Yi , Wang Jun , Duan Chuanzhi , Lu Aiping , Guan Daogang
Published: March 2023

Overexpressed matrix metalloproteinases, hypoxia microenvironment, and metabolic abnormality are important pathological signs of rheumatoid arthritis (RA). Designing a delivery carrier according to the pathological characteristics of RA that can control drug release in response to disease severity may be a promising treatment strategy. Psoralen is the main active ingredient isolated from Psoralea corylifolia L. and possesses excellent anti‐inflammatory activities as well as improving bone homeostasis. However, the specific underlying mechanisms, particularly the possible relationships between the anti‐RA effects of psoralen and related metabolic network, remain largely unexplored. Furthermore, psoralen shows systemic side effects and has unsatisfactory solubility. Therefore, it is desirable to develop a novel delivery system to maximize psoralen's therapeutic effect. In this study, a self‐assembled degradable hydrogel platform is developed that delivers psoralen and calcium peroxide to arthritic joints and controls the release of psoralen and oxygen according to inflammatory stimulation, to regulate homeostasis and the metabolic disorder of the anoxic arthritic microenvironment. Therefore, the hydrogel drug delivery system based on the responsiveness of the inflammatory microenvironment and regulation of metabolism provides a new therapeutic strategy for RA treatment.
Bi‐Functional Co/Al Modified 1T‐MoS2/rGO Catalyst for Enhanced Uranium Extraction and Hydrogen Evolution Reaction in Seawater
Authors: Jian Jiahuang , Kang Hongjun , Yu Dongmei , Qiao Xianshu , Liu Yang , Li Yang , Qin Wei , Wu Xiaohong
Published: March 2023

Uranium is a key element in the preparation of nuclear fuel. An electrochemical uranium extraction technique is proposed to achieve high efficiency uranium extraction performance through HER catalyst. However, it is still a challenge to design and develop a high‐performance hydrogen evolution reaction (HER) catalyst for rapid extraction and recovery of uranium from seawater. Herein, a bi‐functional Co, Al modified 1T‐MoS2/reduced graphene oxide (CA‐1T‐MoS2/rGO) catalyst, showing a good HER performance with a HER overpotential of 466 mV at 10 mA cm−2 in simulated seawater, is first developed. Benefiting from the high HER performance of CA‐1T‐MoS2/rGO, efficient uranium extraction is achieved with a uranium extraction capacity of 1990 mg g−1 in simulated seawater without post‐treatment, exhibiting a good reusability. The results of experiments and density functional theory (DFT) show that a high uranium extraction and recovery capability is attributed to the synergy effect of the improved HER performance and the strong adsorption capacity between U and OH*. This work provides a new strategy for the design and preparation of bi‐functional catalysts with high HER performance and uranium extraction and recovery capabilities in seawater.
Double‐Shelled Porous g‐C3N4 Nanotubes Modified with Amorphous Cu‐Doped FeOOH Nanoclusters as 0D/3D Non‐Homogeneous Photo‐Fenton Catalysts for Effective Removal of Organic Dyes
Authors: Tang Jing , Xu Rongping , Sui Guozhe , Guo Dongxuan , Zhao Zhenlong , Fu Shanshan , Yang Xue , Li Yue , Li Jinlong
Published: March 2023

Graphite phased carbon nitride (g‐C3N4) has attracted extensive attention attributed to its non‐toxic nature, remarkable physical–chemical stability, and visible light response properties. Nevertheless, the pristine g‐C3N4 suffers from the rapid photogenerated carrier recombination and unfavorable specific surface area, which greatly limit its catalytic performance. Herein, 0D/3D Cu‐FeOOH/TCN composites are constructed as photo‐Fenton catalysts by assembling amorphous Cu‐FeOOH clusters on 3D double‐shelled porous tubular g‐C3N4 (TCN) fabricated through one‐step calcination. Combined density functional theory (DFT) calculations, the synergistic effect between Cu and Fe species could facilitate the adsorption and activation of H2O2, and the separation and transfer of photogenerated charges effectively. Thus, Cu‐FeOOH/TCN composites acquire a high removal efficiency of 97.8%, the mineralization rate of 85.5% and a first‐order rate constant k = 0.0507 min−1 for methyl orange (MO) (40 mg L−1) in photo‐Fenton reaction system, which is nearly 10 times and 21 times higher than those of FeOOH/TCN (k = 0.0047 min−1) and TCN (k = 0.0024 min−1), respectively, indicating its universal applicability and desirable cyclic stability. Overall, this work furnishes a novel strategy for developing heterogeneous photo‐Fenton catalysts based on g‐C3N4 nanotubes for practical wastewater treatment.
Improved Crystallization of Lead Halide Perovskite in Two‐Step Growth Method by Polymer‐Assisted “Slow‐Release Effect”
Authors: Lin Siyuan , Wu Shuyue , Guo De'en , Huang Han , Zhou Xuefan , Zhang Dou , Zhou Kechao , Zhang Wenhao , Hu Yue , Gao Yongli , Zhou Conghua
Published: March 2023

Fast reaction between organic salt and lead iodide always leads to small perovskite crystallites and concentrated defects. Here, polyacrylic acid is blended with organic salt, so as to regulate the crystallization in a two‐step growth method. It is observed that addition of polyacrylic acid retards aggregation and crystallization behavior of the organic salt, and slows down the reaction rate between organic salt and PbI2, by which “slow‐release effect” is defined. Such effect improves crystallization of perovskite. X‐ray diffraction study shows that, after addition of 2 mm polyacrylic acid, average crystallite size of perovskite increases from ≈40 to ≈90 nm, meanwhile, grain size increases. Thermal admittance spectroscopy study shows that trap density is reduced by nearly one order (especially for deep energy levels). Due to the improved crystallization and reduced trap density, charge recombination is obviously reduced, while lifetime of charge carriers in perovskite film and devices are prolonged, according to time‐resolved photoluminescence and transient photo‐voltage decay curve tests, respectively. Accordingly, power conversion efficiency of the device is promoted from 19.96 (±0.41)% to 21.84 (±0.25)% (with a champion efficiency of 22.31%), and further elevated to 24.19% after surface modification by octylammonium iodide.
Experimental and numerical study of recycled aggregate concrete column
Authors: Pradhan Subhasis , Nayak Tusar Kumar , Kumar Shailendra , Barai Sudhirkumar V.
Published: March 2023

The improved mechanical properties of recycled aggregate concrete (RAC) by employing the particle packing method (PPM) of the mix design approach encourages its application to study the performance of structural members. The experimental investigation is conducted on the axial compressive behavior of reinforced natural aggregate concrete (NAC) and RAC columns using two different tie spacing conditions. A reduction of 18% in the axial load of RAC columns is observed with respect to the NAC columns and only 2.7% improvement in axial load is recorded as the tie spacing reduces by 22.5%. Subsequently, the finite element (FE) analysis is conducted to investigate the axial compressive strength of both NAC and RAC columns using different tie spacing conditions. The FE analyses of RAC columns with different tie spacing support to modify the spacing of transverse reinforcement as half as that of the spacing specified in the prevailing design for NAC columns.
Scale effects in GFRP‐bar reinforced concrete beams
Authors: Accornero Federico , Cafarelli Renato , Carpinteri Alberto , Nanni Antonio
Published: March 2023

Glass fiber‐reinforced polymer (GFRP)‐reinforced concrete (RC) can be defined as a cementitious material in which the reinforcing secondary phase consists in corrosion‐resistant GFRP rebars. For this next‐generation structural material, experimental flexural tests highlight how the postcracking response is strongly affected by the amount of GFRP area together with the structural size‐scale. In this work, the cohesive/overlapping crack model (COCM) is adopted to describe the transition between cracking and crushing failures occurring in GFRP‐RC beams by increasing the beam depth, the reinforcement percentage, and/or the concrete compression strength. Within this nonlinear fracture mechanics model, the tensile and compression ultimate behaviors of the concrete matrix are modeled through two different process zones that advance independently one of another. Moreover, this model is able to investigate local mechanical instabilities occurring in the structural behavior of GFRP‐RC beams: tensile snap back and snap‐through, which are due to concrete cracking and reinforcement bridging action, and the compression snap‐back generated by the unstable growth of the crushing zone. In this context, the application of the COCM highlights that the ductility, which is represented by the plastic rotation capacity of the GFRP‐RC beam only when the reinforcement can slip, decreases as reinforcement percentage and/or beam depth increase. In this way, rational and quantitative definitions of hyperstrength and brittle compression crushing behaviors can be provided as a GFRP percentage depending on the beam depth.
State‐of‐the‐art review on the post‐fire assessment of concrete structures
Authors: Jovanović Balša , Caspeele Robby , Lombaert Geert , Reynders Edwin , Van Coile Ruben
Published: March 2023

Fires are rare events, but in the case of their occurrence, they can have a significant effect on the structure. Concrete is a durable noncombustible material but can be damaged by fire. This damage does not often lead to structural collapse, but can significantly hinder the structure's future performance. A thorough post‐fire assessment of concrete structures is essential to determine the condition of the structure and select the best course of action to take. This paper reviews the current state of knowledge on the post‐fire assessment of concrete structures. The techniques that are commonly used are presented and discussed, highlighting their advantages and disadvantages. Furthermore, based on the literature case studies, an overview of different approaches and techniques is presented. Finally, the framework and goals of the post‐fire assessment are investigated. The paper concludes with a summary of the current state of knowledge and a list of key research needs.
Leachate characteristics, dry matter yield of Urochloa decumbens and properties of two contrasting soils irrigated with sludgewater in columns
Authors: Dube Sinikiwe , Muchaonyerwa Pardon , Mapanda Farai , Hughes Jeffrey C.
Published: March 2023

Increasing demands on freshwater and challenges in disposal of wastewaters encourage their use for irrigation. The study evaluated the effects of irrigation of signal grass (Urochloa decumbens) with sludgewater on leaching, uptake and retention of a range of elements in two contrasting soils in columns. The grass was grown on a sandy loam and a clay soil packed in plastic columns and irrigated for 119 days with either undiluted, diluted sludgewater or tap water. The sludgewater had a pH of 6.9 and high aluminum (Al), manganese (Mn), iron (Fe), and boron (B). Analyses were conducted on leachates, above‐ground plant biomass (two harvests), and soils at the end of the experiment. Sludgewater treatments increased grass biomass yield and uptake of nitrogen (N), phosphorus (P), potassium (K), and magnesium (Mg) in both soils with a greater nutrient uptake from the clay than the sandy loam. The application of sludgewater increased Mn and reduced P (sandy loam only) in the leachate with no effects on Al, Fe, or B. Uptake of Al, Fe, and B was increased by sludgewater application. Even when diluted, the sludgewater increased extractable Mn, particularly in the clay soil. The findings showed that irrigation of the soils with sludgewater increased Mn and B concentrations and uptake by signal grass, with no negative effects on biomass production. Leaching and accumulation in the soils of toxic elements were minimal in the short term. Sludgewater can therefore be used to grow signal grass in both soils although these effects need to be evaluated under field conditions.
Well‐differentiated hepatic carcinoid in a dog: Long‐term survival following partial hepatectomy
Authors: Bellamy Edward , Bestwick Jason , Palma Stefano Di , Ressel Lorenzo , Verganti Sara
Published: March 2023

An 11‐year‐old, female, spayed Shetland sheepdog was referred for a 48‐hour onset of lethargy, inappetence, pigmenturia and intra‐abdominal mass of unknown origin. Laboratory sampling identified regenerative anaemia, hyperbilirubinemia, hypercholesterolemia and elevated alanine transaminase and alkaline phosphatase. Bilirubinuria and haematuria were noted on urinalysis. Thoracic radiographs were unremarkable. Ultrasonographic examination identified free abdominal fluid and a heterogeneous mass associated with a medial liver lobe. Haemoabdomen was confirmed, and partial hepatectomy was performed. Histopathology identified neoplastic cells arranged in nests and rosettes. On immunohistochemistry, neoplastic cells were positive for neuron‐specific enolase and synaptophysin and negative for S100, chromogranin A and cytokeratin. Transmission electron microscopy revealed small round electrodense granules consistent with neuroendocrine granules. A final diagnosis of hepatic carcinoid was made. The dog received no adjuvant treatment. Re‐staging with conventional imaging was performed every 3 months. No local recurrence or metastatic disease was identified within a 21‐month follow‐up period.
Candida parapsilosis cell wall proteins—CPAR2_404800 and CPAR2_404780—Are adhesins that bind to human epithelial and endothelial cells and extracellular matrix proteins
Authors: Satala Dorota , Karkowska‐Kuleta Justyna , Bras Grazyna , Rapala‐Kozik Maria , Kozik Andrzej
Published: March 2023

One of the initial steps necessary for the development of Candida infections is the adherence to the host tissues and cells. Recent transcriptomic studies suggest that, in Candida parapsilosis—a fungal infectious agent that causes systemic candidiasis in immunosuppressed individuals—the adhesion is mediated by pathogen cell‐exposed proteins belonging to the agglutinin‐like sequence (Als) family. However, to date, the actual interactions of individual members of this family with human cells and extracellular matrix (ECM) have not been characterized in detail. In the current study, we focused attention on two of these C. parapsilosis Als proteins—CPAR2_404800 and CPAR2_404780—that were proteomically identified in the fungal cell wall of yeasts grown in the media suitable for culturing human epithelial and endothelial cells. Both proteins were extracted from the cell wall and purified, and using a microplate binding assay and a fluorescence microscopic analysis were shown to adhere to human cells of A431 (epithelial) and HMEC‐1 (endothelial) lines. The human extracellular matrix components that are also plasma proteins—fibronectin and vitronectin—enhanced these interactions, and also could directly bind to CPAR2_404800 and CPAR2_404780 proteins, with a high affinity (KD in a range of 10−7 to 10−8 M) as determined by surface plasmon resonance measurements. Our findings highlight the role of proteins CPAR2_404800 and CPAR2_404780 in adhesion to host cells and proteins, contributing to the knowledge of the mechanisms of host‐pathogen interactions during C. parapsilosis‐caused infections.
Meromorphic cosets and the classification of three-character CFT
Authors: Das Arpit , Gowdigere Chethan N. , Mukhi Sunil
Published: March 2023

Abstract

We investigate the admissible vector-valued modular forms having three independent characters and vanishing Wronskian index and determine which ones correspond to genuine 2d conformal field theories. This is done by finding bilinear coset-type relations that pair them into meromorphic characters with central charges 8, 16, 24, 32 and 40. Such pairings allow us to identify some characters with definite CFTs and rule out others. As a key result we classify all unitary three-character CFT with vanishing Wronskian index, excluding c = 8, 16. The complete list has two infinite affine series Br,1, Dr,1 and 45 additional theories. As a by-product, at higher values of the total central charge we also find constraints on the existence or otherwise of meromorphic theories. We separately list several cases that potentially correspond to Intermediate Vertex Operator Algebras.
Flavor- and CP-safe explanation of gμ − 2 anomaly
Authors: Evans Jason L. , Yanagida Tsutomu T. , Yokozaki Norimi
Published: March 2023

Abstract

Supersymmetry is still a viable explanation for the muon g – 2 anomaly, if the sleptons and electroweak gauginos are $$ \mathcal{O}(100) $$
O

100

GeV. However, for supersymmetry breaking masses this light, the SUSY flavor and CP-problem are exacerbated. To address this issue, we consider a flavor-safe gauge mediated explanation of the muon g – 2 with additional Higgs soft supersymmetry breaking mass parameters. The setup provides a generic parameter space within minimal gauge mediation. Furthermore, we show that the problematic CP violating phase can be dynamically suppressed. We find that gauge mediation models have large portions of parameter space where the muon g – 2 can be explained at 1 σ level. The interplay between the slepton and the CP-odd Higgs masses also makes the majority of this model’s parameter space testable at the LHC through searches for sleptons or additional Higgs bosons.
Topological phenomena in honeycomb Floquet metamaterials
Authors: Ammari Habib , Kosche Thea
Published: March 2023

Being driven by the goal of finding edge modes and of explaining the occurrence of edge modes in the case of time-modulated metamaterials in the high-contrast and subwavelength regime, we analyse the topological properties of Floquet normal forms of periodically parameterized time-periodic linear ordinary differential equations $$\left\{ \frac{d}{dt}X = A_\alpha (t)X\right\} _{\alpha \in {\mathbb {T}}^d}$$

d

dt

X
=

A
α

(
t
)

X

α
∈

T

d

. In fact, our main goal being the question whether an analogous principle as the bulk-boundary correspondence of solid-state physics is possible in the case of Floquet metamaterials, i.e., subwavelength high-contrast time-modulated metamaterials. This paper is a first step in that direction. Since the bulk-boundary correspondence states that topological properties of the bulk materials characterize the occurrence of edge modes, we dedicate this paper to the topological analysis of subwavelength solutions in Floquet metamaterials. This work should thus be considered as a basis for further investigation on whether topological properties of the bulk materials are linked to the occurrence of edge modes. The subwavelength solutions being described by a periodically parameterized time-periodic linear ordinary differential equation $$\left\{ \frac{d}{dt}X = A_\alpha (t)X\right\} _{\alpha \in {\mathbb {T}}^d}$$

d

dt

X
=

A
α

(
t
)

X

α
∈

T

d

, we put ourselves in the general setting of periodically parameterized time-periodic linear ordinary differential equations and introduce a way to (topologically) classify a Floquet normal form F,  P of the associated fundamental solution $$\left\{ X_\alpha (t) = P(\alpha ,t)\exp (tF_\alpha )\right\} _{\alpha \in {\mathbb {T}}^d}$$

X
α

(
t
)

=
P

(
α
,
t
)

exp

(
t

F
α

)

α
∈

T

d

. This is achieved by analysing the topological properties of the eigenvalues and eigenvectors of the monodromy matrix $$X_\alpha (T)$$

X
α

(
T
)

and the Lyapunov transformation $$P(\alpha ,t)$$

P
(
α
,
t
)

. The corresponding topological invariants can then be applied to the setting of Floquet metamaterials. In this paper these general results are considered in the case of a hexagonal structure. We provide two interesting examples of topologically non-trivial time-modulated hexagonal structures.
Diurnal variation of cardiac autonomic activity in adolescent non-suicidal self-injury
Authors: Sigrist Christine , Jakob Hannah , Beeretz Christoph J. , Schmidt Stefanie J. , Kaess Michael , Koenig Julian
Published: March 2023

Heart rate (HR) and vagally mediated heart rate variability (HRV) are two distinct biomarkers of cardiac autonomic activity. Decreased cardiac vagal activity (or decreased HRV) in particular has been linked with impairments in the functional flexibility of the central autonomic network (CAN), resulting in impaired stress and emotion regulatory capacities. Decreased HRV is widely used as trait marker of psychopathology. Repetitive engagement in non-suicidal self-injury (NSSI) in adolescence correlates with both deficits in stress and emotion regulation, as well as decreased HRV. Existing research has, however, focused on short-term recordings of HR and HRV under resting and phasic conditions. In this study, we examined whether diurnal variation of cardiac autonomic activity, indexed by cosinor parameters of HR and HRV derived from 48 h of ambulatory ECG recording under natural conditions over a weekend, are altered in female adolescents with NSSI disorder compared to controls (HC; N = 30 per study group). Several important confounds, including physical activity, were controlled for. Female adolescents with NSSI show higher rhythm-adjusted 24 h mean levels and greater respective amplitude of HR, as well as lower rhythm-adjusted 24 h mean levels and smaller respective amplitude of HRV. Peak levels in both HR and HRV in the NSSI group were reached approximately 1 h later compared to HC. Severity of exposure to early life maltreatment might be linked with altered amplitudes of 24 h HR and HRV. Diurnal rhythms of cardiac autonomic activity might hold promise as objective indicators of disordered stress and emotion regulation in developmental psychopathology, and as such should be investigated in future studies with rigorous assessment and control of potential confounds.
Psychological impact of COVID-19 containment on CADASIL patients
Authors: Reyes S. , Jabouley A. , Alili N. , De Sanctis M. H. , Machado C. , Taleb A. , Herve D. , Dias-Gastellier N. , Chabriat H.
Published: March 2023

Introduction

COVID-19 restrictive containment was responsible for major psychological distress and alteration of quality of life (QoL) in the general population. Their impact in a group of patients having cerebral small vessel disease (SVD) and at high risk of stroke and disability was unknown.

Objective

We aimed to determine the potential psychological impact of strict containment during the COVID-19 pandemic in a sample of CADASIL patients, a rare SVD caused by NOTCH3 gene mutations.

Methods

Interviews of 135 CADASIL patients were obtained just after the end of the strict containment in France. Depression, QoL and negative subjective experience of the containment were analysed, as well as predictors of posttraumatic and stressor-related manifestations, defined as an Impact Event Scale-Revised score ≥ 24, using multivariable logistic analysis.

Results

Only 9% of patients showed a depressive episode. A similar proportion had significant posttraumatic and stressor-related disorder manifestations independently associated only with socio-environment factors, rather than clinical ones: living alone outside a couple (OR 7.86 (1.87–38.32), unemployment (OR 4.73 (1.17–18.70)) and the presence of 2 or more children at home (OR 6.34 (1.35–38.34).

Conclusion

Psychological impact of the containment was limited in CADASIL patients and did not appear related to the disease status. About 9% of patients presented with significant posttraumatic and stressor-related disorder manifestations which were predicted by living alone, unemployment, or exhaustion related to parental burden.
The outcomes of a low-cost, non-valved glaucoma drainage device using mitomycin-C: 1-year results
Authors: Awad-Allah Mo’mena Ahmad A. , Mousa Amr Saleh , Ashour Doaa Maamoun
Published: March 2023

Purpose

To evaluate the indications, outcomes, and complications of the usage of Aurolab Aqueous Drainage Implant (AADI) using mitomycin-C.

Methods

A retrospective case series of patients who underwent AADI placement using mitomycin-C between April 2018 and June 2020 at Ain Shams University Hospitals, Cairo, Egypt. The data was extracted from the records of the patients with a minimum of 1 year of follow-up. Complete success was defined as IOP ≥ 5 mmHg and ≤ 21 mmHg or reduction of IOP by ≥ 20% from baseline without antiglaucoma medications (AGMs). Qualified success was defined as reaching the same IOP range with the aid of AGM.

Results

A total of 50 eyes of 48 patients were included. Neovascular glaucoma represented the commonest indication (13 patients, 26%). The mean preoperative IOP was 34.0 ± 7.1 mmHg, with a median number of AGM of 3 (mean ± SD = 2.84 ± 1), while the mean IOP after 12 months was 14.3 ± 4 with a median number of AGM of 0. (mean ± SD = 0.52 ± 0.89) (p < 0.001). Complete success was achieved in 33 patients (66%). Qualified success was achieved in 14 patients (28%). Thirteen eyes (26%) had variable postoperative complications; none of them required explantation of the device or affected the visual acuity (except one patient).

Conclusion

AADI with using mitomycin-C and ripcord during the surgery is an effective and relatively safe method of control of IOP in refractory and advanced cases of glaucoma, with an overall success rate of 94%.
The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia
Authors: Deręgowska Anna , Pępek Monika , Solarska Iwona , Machnicki Marcin M. , Pruszczyk Katarzyna , Dudziński Marek , Niesiobędzka-Krężel Joanna , Seferyńska Ilona , Sawicki Waldemar , Wnuk Maciej , Stokłosa Tomasz
Published: March 2023

Purpose

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by recurrent genetic aberration in leukemic stem cells, namely Philadelphia chromosome caused by reciprocal translocation t(9;22)(q34;q11). In our study, we analyzed the telomeric complex expression and function in the molecular pathogenesis of CML.

Methods

We employed CD34+ primary leukemic cells, comprising both leukemic stem and progenitor cell populations, isolated from peripheral blood or bone marrow of CML patients in chronic and blastic phase to analyze the telomere length and telomeric-associated proteins.

Results

The reduction in telomere length during disease progression was correlated with increased expression of BCR::ABL1 transcript and the dynamic changes were neither associated with the enzymatic activity of telomerase nor with gene copy number and expression of telomerase subunits. Increased expression of BCR::ABL1 was positively correlated with expression of TRF2, RAP1, TPP1, DKC1, TNKS1, and TNKS2 genes.

Conclusions

The dynamics of telomere length changes in CD34+ CML cells is dependent on the expression level of BCR::ABL, which promotes the expression of certain shelterins including RAP1 and TRF2, as well as TNKS, and TNKS2, and results in telomere shortening regardless of telomerase activity. Our results may allow better understanding of the mechanisms responsible for the genomic instability of leukemic cells and CML progression.
An analysis of temperature anomalies in Chile using fractional integration
Authors: Gil-Alana Luis A. , Martin-Valmayor Miguel A. , Hube-Antoine Cristina
Published: March 2023

This paper deals with the study of stationarity and mean reversion in the temperature anomalies series in the southwestern American cone. In particular, monthly temperatures in 12 Chilean meteorological stations were studied (from the 1960’s to nowadays), examining if temperature shocks are expected to remain in the long term or if they are reversible. The results clearly show a significant relationship between the latitude, climate, and the order of integration of the temperatures. The orders of integration tend to be smaller in colder southern parts, therefore impacts of climate change are expected to be more reversible. However, in northern desert areas the orders of integration are larger than 0.5, thus impacts are expected to be maintained for a longer time.
Informing interventions to improve uptake of adjuvant endocrine therapy in women with breast cancer: a theoretical-based examination of modifiable influences on non-adherence
Authors: Cahir Caitriona , Bennett Kathleen , Dombrowski Stephan U. , Kelly Catherine M. , Wells Mary , Watson Eila , Sharp Linda
Published: March 2023

Purpose

To inform intervention development, we measured the modifiable determinants of endocrine therapy (ET) non-adherence in women with breast cancer, using the Theoretical Domains Framework (TDF) and examined inter-relationships between these determinants and non-adherence using the Perceptions and Practicalities Approach (PAPA).

Methods

Women with stages I–III breast cancer prescribed ET were identified from the National Cancer Registry Ireland (N = 2423) and invited to complete a questionnaire. A theoretically based model of non-adherence was developed using PAPA to examine inter-relationships between the 14 TDF domains of behaviour change and self-reported non-adherence. Structural equation modelling (SEM) was used to test the model.

Results

A total of 1606 women participated (response rate = 66%) of whom 395 (25%) were non-adherent. The final SEM with three mediating latent variables (LVs) (PAPA Perceptions: TDF domains, Beliefs about Capabilities,Beliefs about Consequences; PAPA Practicalities: TDF domain, Memory, Attention,Decision Processes and Environment) and four independent LVs (PAPA Perceptions: Illness intrusiveness; PAPA Practicalities: TDF domains, Knowledge,Behaviour Regulation; PAPA External Factors: TDF domain, Social Identity) explained 59% of the variance in non-adherence and had an acceptable fit (χ2(334) = 1002, p < 0.001; RMSEA = 0.03; CFI = 0.96 and SRMR = 0.07) Knowledge had a significant mediating effect on non-adherence through Beliefs about Consequences and Beliefs about Capabilities. Illness intrusiveness had a significant mediating effect on non-adherence through Beliefs about Consequences. Beliefsabout Consequences had a significant mediating effect on non-adherence through Memory, Attention, Decision Processesg and Environment.

Conclusions

By underpinning future interventions, this model has the potential to improve ET adherence and, hence, reduce recurrence and improve survival in breast cancer.
Combining variable neighborhood with gradient ascent for learning to rank problem
Authors: Ibrahim Osman Ali Sadek , Younis Eman M. G.
Published: March 2023

Metaheuristic applications for information retrieval research are limited in spite of the importance of this problem domain. Ranking the retrieved documents based on their importance is a vital issue for the scientific and industrial communities. This paper proposes a novel variable neighborhood search (VNS) algorithm with adaptation based on an objective function for the learning to rank (LTR) problem. VNS is a global optimum metaheuristic algorithm that has been engaged to evolve the optimal solutions for heuristic problems based on exploring better neighbor solutions from the current one. The changes from the current to the next optimal solution are made during the perturbation stage to identify the global optimal solutions. The exploration procedure has been made through various mutation step sizes, whereas the exploitation process has been done by checking the quality of the evolved solutions using the fitness function. This research proposes a novel version of VNS based on four random probability distributions with gradient ascent. In addition to using the traditional random generator with gradient ascent for modifying the mutated genes of the neighborhood candidate solution in the following evolving iteration. This novel method in LTR is called gradient variable neighborhood (GVN). In the experiments, we utilized Microsoft Bing search (MSLR-WEB30K), Yahoo, and TREC Million Queries Competitions in 2008 and 2007 (LETOR 4) datasets. From the findings of the results, we can deduce that the GVN method outperformed recent studies on LTR methods.
Metabolic control during the first two years of the COVID-19 pandemic in pediatric patients with type 1 diabetes: results from the German DPV initiative
Authors: Hammersen Johanna , Tittel Sascha R. , Khodaverdi Semik , Reschke Felix , Flury Monika , Menzel Ulrike , Mönkemöller Kirsten , Meissner Thomas , Karges Beate , Holl Reinhard W.
Published: March 2023

Aim

To assess effects of the SARS-CoV2 pandemic on metabolic control in youth with type 1 diabetes (T1D) in Germany in a population-based analysis.

Methods

Data from 33,372 pediatric T1D patients from the Diabetes Prospective Follow-up (DPV) registry, with face-to-face visits or telemedicine contacts in the years 2019–2021, were available. Datasets from eight time periods between March 15, 2020, and December 31, 2021, according to SARS-CoV2 incidence waves, were compared to those from five control time periods. Parameters of metabolic control were assessed with adjustment for sex, age, diabetes duration, and repeated measurements. Laboratory-measured HbA1c values and those estimated from CGM were aggregated into a combined glucose indicator (CGI).

Results

There was no clinically relevant difference in metabolic control between pandemic and control time periods with adjusted CGI values ranging from 7.61% [7.60–7.63] (mean [95% confidence interval (CI)]) in the third quarter of 2019 to 7.83% [7.82–7.85] in the time period from January 1 to March 15 2020, in the other control periods, and during the pandemic, CGI values lay between these values. BMI-SDS rose during the pandemic from 0.29 [0.28–0.30] (mean [95% CI]) in the third quarter of 2019 to 0.40 [0.39–0.41] during the fourth wave. Adjusted insulin dose rose during the pandemic. Event rates for hypoglycemic coma and diabetic ketoacidosis remained unchanged.

Conclusions

We found no clinically relevant change of glycemic control or incidence of acute diabetes complications during the pandemic. The observed BMI increase may represent an important health risk for youth with T1D.
Electrochemistry for non-electrochemists: a postgraduate formative project
Authors: Doménech-Carbó Antonio , Martini Mariele , Di Turo Francesca , de Silveira Géssica Domingos , Montoya Noemí
Published: March 2023

The essential guidelines are presented of a postgraduate course on electrochemistry for master studies at the University of Valencia (Spain). This course has been designed for students with a minimal knowledge of electrochemistry. It is based on laboratory experiments that, starting from an initial theoretical core, promotes the in-laboratory discussion of concepts, operations, functional relations, etc. The course, although focused on voltammetric techniques, covers the main concepts and experimental aspects of electrochemistry and particular attention is put to erroneous conceptions regarding fundamental physicochemical concepts and operations (misconceptions) as well as on general aspects of the scientific methodology (meta-conceptions) around this discipline.
The infinite Lanczos method for symmetric nonlinear eigenvalue problems
Authors: Mele Giampaolo
Published: March 2023

A new iterative method for solving large scale symmetric nonlinear eigenvalue problems is presented. We firstly derive an infinite dimensional symmetric linearization of the nonlinear eigenvalue problem, then we apply the indefinite Lanczos method to this specific linearization, resulting in a short-term recurrence. We show how, under specific assumption on the starting vector, this method can be carried out in finite arithmetic and how the exploitation of the problem structure leads to improvements in terms of computation time. The eigenpair approximations are extracted with the nonlinear Rayleigh-Ritz procedure combined with a specific choice of the projection space. We illustrate how this extraction technique resolves the instability issues that may occur due to the loss of orthogonality in many standard Lanczos-type methods.