bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Tempering Parameters on the Microstructure, Mechanical Property, and the Corresponding Strengthening Mechanism of Metastable 301 Austenitic Stainless Steel
Authors: Zhao Liyuan , Yang Jiawei , Tian Lei , Li Xiaolin , Lei Chengshuai , Wang Haifeng
Published: February 2024

Metastable austenitic stainless steels (MASS) are widely used in various industrial applications due to their exceptional mechanical properties. The microstructure of MASS can be regulated through severe plastic deformation, heat treatments, and surface treatments to achieve further improvement of mechanical properties. Herein, nanograin and quasiheterostructure are prepared by cold rolling and annealing process in Fe–17Cr–6Ni MASS. The mechanical response, deformation mechanism, and strengthening contribution of the two steels with representative microstructure are studied. The results indicate that nanograin austenitic steel (803 MPa, 22%) has superior yield strength and similar ductility compared with that of quasiheterostructure steel (600 MPa, 25%). In the nanograin steel, the deformation mechanism is mainly dislocation slip and deformation‐induced martensite transformation, while in quasiheterostructure steel, the deformation twinning is also included for the relative lower stacking fault energy in the coarse grain. The yield strength of nanograin structural steel is about 200 MPa higher than that of quasiheterostructure steel, which can be attributed to the differences in grain refinement strengthening, phase‐transformation strengthening, and precipitation strengthening of Cu particles. The findings presented in this study are informative for modulating MASS properties and ultimately improving the lifespan in a variety of industrial settings.
Chirality Regulates Macrophage Polarization for Tissue Regeneration Through Bidirectionally Modulating WTAP‐Mediated m6A Modification
Authors: Yang Yue , Guo Xinwei , Huang Chenyan , Chen Chen , Zhou Yingying , Gao Zhengrong , Feng Chuanliang , Jiang Shengjie , Deng Xuliang , Wei Yan
Published: February 2024

Chirality, a fundamental design feature at all levels of life organization, has shown great capability in guiding cell‐fate determination and tissue regeneration. Chirality‐directed differentiation programs involve remarkable changes in transcriptional networks, yet whether epigenetic regulatory events are also required is less well understood. Herein, by combining high‐throughput m6A MeRIP sequencing, RIP‐qPCR, and gene modulation techniques, it is demonstrated that biomimetic chiral nanofibrils can bidirectionally regulate wilms tumor 1 associated protein (WTAP)‐mediated m6A RNA methylation to guide macrophages polarization for tissue regeneration. The biomimic chiral nanofibril hydrogels are fabricated using a self‐assembly approach based on C2‐symmetric phenylalanine derivatives. In vitro and in vivo studies indicated that the L‐nanofibrils exhibit a greater propensity to promote M2‐macrophage polarization than D‐nanofibrils, thereby favoring osteogenesis. Then, m6A‐MeRIP sequencing revealed a unique chirality‐dependent m6A methylation level in macrophages, which was gated by a competitive pair of CCM3‐FAK through enantioselectively integrin recognition. L‐nanofibrils considerably suppressed WTAP‐mediated m6A methylation by promoting Itgα3‐FAK expression and paxillin‐driven mechanotransduction, whereas D‐nanofibrils induced WTAP‐mediated m6A methylation by favoring ItgαV‐CCM3 expression and suppressing mechanotransduction. Furthermore, the gain‐of‐function and loss‐of‐function experiments and RIP‐qPCR demonstrate that the WTAP expression could direct macrophage polarization via manipulating the functional molecule B7‐H3 (CD276). Thus, a mechano‐epigenetic mechanism of chirality‐mediated cell‐fate determination is unveiled, which holds remarkable promise in the realm of assisted regenerative material design.
α‐Boryl Carbanions: The Influence of Geminal Heteroatoms in C−C Bond Formation
Authors: Fernández Elena
Published: February 2024

The wide applications of alpha‐boryl carbanions in selective coupling with organohalides, imines/carbonyls and conjugated unsaturated substrates has become an interesting tool for organic synthesis. Strategically, the inclusion of heteroatoms, such as Si, S, N, F, Cl, Br and I in the alpha position opens a new venue towards multifunctionalities in molecular design. Here, a conceptual and practical view on powerful carbanions, containing α‐silicoboron, α‐thioboron, α‐haloboron and α‐aminoboron is given, as well as a prespective on their efficient application for selective electrophilic trapping.
How to perform standardized sonographic examination of Cesarean scar pregnancy in the first trimester
Authors: Verberkt C. , Jordans I. P. M. , van den Bosch T. , Timmerman D. , Bourne T. , de Leeuw R. A. , Huirne J. A. F.
Published: February 2024

Early diagnosis and appropriate management of Cesarean scar pregnancy (CSP) are crucial to prevent severe complications, such as uterine rupture, severe hemorrhage and placenta accreta spectrum disorders. In this article, we provide a step‐by‐step tutorial for the standardized sonographic evaluation of CSP in the first trimester. Practical steps for performing a standardized transvaginal ultrasound examination to diagnose CSP are outlined, focusing on criteria and techniques essential for accurate identification and classification. Key sonographic markers, including gestational sac location, cardiac activity, placental implantation and myometrial thickness, are detailed. The evaluation process is presented according to assessment of the uterine scar, differential diagnosis, detailed CSP evaluation and CSP classification. This step‐by‐step tutorial emphasizes the importance of scanning in two planes (sagittal and transverse), utilizing color or power Doppler and differentiating CSP from other low‐lying pregnancies. The CSP classification is described in detail and is based on the location of the largest part of the gestational sac relative to the uterine cavity and serosal lines. This descriptive classification is recommended for clinical use to stimulate uniform description and evaluation. Such a standardized sonographic evaluation of CSP in the first trimester is essential for early diagnosis and management, helping to prevent life‐threatening complications and to preserve fertility. Training sonographers in detailed evaluation techniques and promoting awareness of CSP are critical. The structured approach to CSP diagnosis presented herein is supported by a free e‐learning course available online. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
A cross‐sectional study on predictors of patients' tinnitus severity
Authors: Li Teng‐Fei , Cha Xu‐Dong , Wang Tian‐Yu , Liang Cai‐Quan , Li Feng‐Zhen , Wang Sheng‐Lei , Peng Hu , Ren Wen‐Wen , Deng Yue , Liu Huan‐Hai
Published: February 2024

Objective

To identify factors that influence the severity of tinnitus via a hierarchical multiple linear regression model.

Methods

The study was a retrospective cross‐sectional analysis. The study included 331 patients experiencing tinnitus as their primary concern, who visited Shanghai Changzheng Hospital of the Navy Medical University between 2019 and 2021. Data on general health status and disease characteristics were collected from all patients. With their consent, participants underwent audiological evaluatons and completed questionnaires to analyze the characteristics of their tinnitus and the factors influencing its severity.

Results

The correlation analysis showed a positive relationship between tinnitus frequency, tinnitus loudness, SAS scores, and PSQI scores with THI scores (P < 0.05) among nine examined variables (gender, handedness, employment status, age, BMI, tinnitus frequency, tinnitus loudness, SAS scores, and PSQI scores). The variables that were extracted from the multiple regression were; for the constant; β = −51.797, t = −4.484, P < 0.001, variable is significant; for the tinnitus loudness; β = 0.161, t = 2.604, P < 0.05, variable is significant; for the tinnitus frequency; β = 0.000, t = 1.269, P = 0.206, variable is not significant; for the SAS scores; β = 1.310, t = 7.685, P < 0.001, variable is significant; for the PSQI scores; β = 1.680, t = 5.433, P < 0.001, variable is significant. Therefore, the most accurate model for predicting severity in tinnitus patients is a linear combination of the constant, tinnitus loudness, SAS scores, and PSQI scores, Y(Tinnitus severity) = β0 + β1(Tinnitus loudness) + β2(SAS scores) + β3(PSQI scores). β0, β1, β2, and β3 are −51.797, 0.161, 1.310 and 1.680, respectively.

Conclusion

Tinnitus severity is positively associated with loudness, anxiety levels, and sleep quality. To effectively manage tinnitus in patients, it is essential to promptly identify and address these accompanying factors and related symptoms.
Understanding the Political Economy of Education: Exploring Debates in Central Asia
Authors: Sharimova Assel , Durrani Naureen , Thibault Hélène
Published: February 2024

As an introductory part, this chapter aims to set the scene for this book. The chapter starts with an understanding of the research on the Political Economy of Education, the variety of approaches within the field and the relevance of the book. The subsequent section provides reflections on some of the contentious issues concerning education and social cohesion in Kazakhstan, Tajikistan and Uzbekistan, the three countries covered in this book. The concluding part explains the collaborative initiative that united all authors of the book, and introduces the contributions included in this volume.
Equity in Assessment in Tajikistan: Language Minority Students and Students with Disabilities in Higher Education
Authors: Bozichaeva Vasila
Published: February 2024

The assessment system determines the learning achievements of students. A developed education system employs an assessment policy that benefits the most diverse groups of students. This chapter examines the perspective of faculty and students in three higher education institutions in Tajikistan regarding how students from minority languages and those with disabilities experience the assessment policy. Using ten semi-structured interviews with lecturers and 215 questionnaires completed by students, this study revealed that the assessment tools and forms do not recognize the needs of students from minority languages and students with disabilities. This is due to the limited implementation of inclusive education. Assessment policy developers should acknowledge these issues and adopt an equity-minded assessment policy.
Examination of the Financial Sustainability of NGOs’ Education Programmes: Kazakhstani Case Study
Authors: Hanley Natalya
Published: February 2024

This chapter analyses the financial sustainability of education programmes provided by NGOs in the conflict-affected Kazakhstani context. A multi-dimensional framework was used to investigate social-economic injustice (redistribution) through the lens of political injustice (representation). The study focuses on the historical development of NGOs, legislation development, and the current challenges with different types of funding, discussing the veiled injustices of fair access to funding, unequal distribution of funding, exclusion of NGOs from political participation, and unfair competition. Multiple approaches within and beyond the work of NGOs were offered towards transformative social-economic justice.
The Right to Education of Children Affected by Nuclear Tests in the Semipalatinsk Region, Kazakhstan (1991–2021)
Authors: Mussabalinova Aigerim
Published: February 2024

Respecting and protecting children’s rights is essential to children’s fulfillment, especially for children with special needs who depend on adults’ assistance and special services. This chapter presents the findings of a qualitative study that explored the provision of education to children affected by nuclear tests in the Semipalatinsk region in Kazakhstan, the primary testing site for the Soviet Union’s nuclear weapons during the Cold War. Thirty participants were interviewed, including teachers, medical professionals, social workers, and civil activists. The study finds an underestimation of the role of education in sustainable peacebuilding. The adverse aftermath of nuclear testing in the region on children’s access to education was not considered during and after the closure of the nuclear test site. Children affected by the radiation left by nuclear tests have special needs in access to education, which policymakers need to consider ensuring inclusive education in Kazakhstan.
Uncovering Gender, Language, and Intersected Asymmetries in History Textbooks
Authors: Bekzhanova Zhazira
Published: February 2024

The study employs multimodal critical discourse analysis (MCDA) and quantitative analysis to investigate the enactment of gender and intersected asymmetries in the Central Asian school curriculum, using the History of Kazakhstan, a compulsory subject taught across grades 5 and 11, as a case study. The analysis is based on the 4Rs framework of redistribution, representation, recognition, and reconciliation. The findings indicate that women, especially non-Kazakh ones, are marginalised; ideal femininity is associated with weakness, but at the same time, stereotypically masculine traits are praised in women; ideal masculinity is associated with violence, and it is also praised in textbooks. Additionally, Russian language textbooks exhibit more gender bias due to gender-discriminatory language, while Kazakh language textbooks often obscure non-Kazakh individuals. Thus, the analysis detects an ethnic bias. The study highlights the need to update textbook content, reducing gender, language, and ethnic disparities in the discourse.
Bilinear R-parity violating supersymmetry under the light of neutrino oscillation, Higgs and flavor data
Authors: Choudhury Arghya , Mitra Sourav , Mondal Arpita , Mondal Subhadeep
Published: February 2024

Abstract

In this work, we explore a well motivated beyond the Standard Model scenario, namely, R-parity violating Supersymmetry, in the context of light neutrino masses and mixing. We assume that the R-parity is only broken by the lepton number violating bilinear term. We try to fit two non-zero neutrino mass square differences and three mixing angle values obtained from the global χ2 analysis of neutrino oscillation data. We have also taken into account the updated data of the standard model (SM) Higgs mass and its coupling strengths with other SM particles from LHC Run-II along with low energy flavor violating constraints like rare b-hadron decays. We have used a Markov Chain Monte Carlo (MCMC) analysis to constrain the new physics parameter space. While doing so, we ensure that all the existing collider constraints are duly taken into account. Through our analysis, we have derived the most stringent constraints possible to date with existing data on the 9 bilinear R-parity violating parameters along with μ and tan β. We further explore the possibility of explaining the anomalous muon (g - 2) measurement staying within the parameter space allowed by neutrino, Higgs and flavor data while satisfying the collider constraints as well. We find that there still remains a small sub-TeV parameter space where the required excess can be obtained.
A POWHEG generator for deep inelastic scattering
Authors: Banfi Andrea , Ravasio Silvia Ferrario , Jäger Barbara , Karlberg Alexander , Reichenbach Felix , Zanderighi Giulia
Published: February 2024

Abstract

We present a new event generator for the simulation of both neutral- and charged-current deep inelastic scattering (DIS) at next-to-leading order in QCD matched to parton showers using the POWHEG method. Our implementation builds on the existing POWHEG BOX framework originally designed for hadron-hadron collisions, supplemented by considerable extensions to account for the genuinely different kinematics inherent to lepton-hadron collisions. In particular, we present new momentum mappings that conserve the special kinematics found in DIS, which we use to modify the POWHEG BOX implementation of the Frixione-Kunszt-Signer subtraction mechanism. We compare our predictions to fixed-order and resummed predictions, as well as to data from the HERA ep collider. Finally we study a few representative distributions for the upcoming Electron Ion Collider.
Intervertebral disc-intrinsic Hedgehog signaling maintains disc cell phenotypes and prevents disc degeneration through both cell autonomous and non-autonomous mechanisms
Authors: Zhang Lei , Hu Siyuan , Xiu Chunmei , Li Meng , Zheng Yixin , Zhang Rui , Li Bin , Chen Jianquan
Published: February 2024

Intervertebral disc degeneration is closely related to abnormal phenotypic changes in disc cells. However, the mechanism by which disc cell phenotypes are maintained remains poorly understood. Here, Hedgehog-responsive cells were found to be specifically localized in the inner annulus fibrosus and cartilaginous endplate of postnatal discs, likely activated by Indian Hedgehog. Global inhibition of Hedgehog signaling using a pharmacological inhibitor or Agc1-CreERT2-mediated deletion of Smo in disc cells of juvenile mice led to spontaneous degenerative changes in annulus fibrosus and cartilaginous endplate accompanied by aberrant disc cell differentiation in adult mice. In contrast, Krt19-CreER-mediated deletion of Smo specifically in nucleus pulposus cells led to healthy discs and normal disc cell phenotypes. Similarly, age-related degeneration of nucleus pulposus was accelerated by genetic inactivation of Hedgehog signaling in all disc cells, but not in nucleus pulposus cells. Furthermore, inactivation of Gli2 in disc cells resulted in partial loss of the vertebral growth plate but otherwise healthy discs, whereas deletion of Gli3 in disc cells largely corrected disc defects caused by Smo ablation in mice. Taken together, our findings not only revealed for the first time a direct role of Hedgehog-Gli3 signaling in maintaining homeostasis and cell phenotypes of annuls fibrosus and cartilaginous endplate, but also identified disc-intrinsic Hedgehog signaling as a novel non-cell-autonomous mechanism to regulate nucleus pulposus cell phenotype and protect mice from age-dependent nucleus pulposus degeneration. Thus, targeting Hedgehog signaling may represent a potential therapeutic strategy for the prevention and treatment of intervertebral disc degeneration.
Further investigations on the influence of protein phosphatases on the signaling of muscarinic receptors in the atria of mouse hearts
Authors: Gergs Ulrich , Wackerhagen Silke , Fuhrmann Tobias , Schäfer Inka , Neumann Joachim
Published: February 2024

The vagal regulation of cardiac function involves acetylcholine (ACh) receptor activation followed by negative chronotropic and negative as well as positive inotropic effects. The resulting signaling pathways may include Gi/o protein-coupled reduction in adenylyl cyclase (AC) activity, direct Gi/o protein-coupled activation of ACh-activated potassium current (IKACh), inhibition of L-type calcium ion channels, and/or the activation of protein phosphatases. Here, we studied the role of the protein phosphatases 1 (PP1) and 2A (PP2A) for muscarinic receptor signaling in isolated atrial preparations of transgenic mice with cardiomyocyte-specific overexpression of either the catalytic subunit of PP2A (PP2A-TG) or the inhibitor-2 (I2) of PP1 (I2-TG) or in double transgenic mice overexpressing both PP2A and I2 (DT). In mouse left atrial preparations, carbachol (CCh), cumulatively applied (1 nM–10 µM), exerted at low concentrations a negative inotropic effect followed by a positive inotropic effect at higher concentrations. This biphasic effect was noted with CCh alone as well as when CCh was added after β-adrenergic pre-stimulation with isoprenaline (1 µM). Whereas the response to stimulation of β-adrenoceptors or adenosine receptors (used as controls) was changed in PP2A-TG, the response to CCh was unaffected in atrial preparations from all transgenic models studied here. Therefore, the present data tentatively indicate that neither PP2A nor PP1, but possibly other protein phosphatases, is involved in the muscarinic receptor-induced inotropic and chronotropic effects in the mouse heart.
Diffractaic acid exerts anti-cancer effects on hepatocellular carcinoma HepG2 cells by inducing apoptosis and suppressing migration through targeting thioredoxin reductase 1
Authors: Sulukoğlu Emine Karaca , Günaydın Şükran , Kalın Şeyda Nur , Altay Ahmet , Budak Harun
Published: February 2024

Hepatocellular carcinoma (HCC) represents one of the most common malignant tumors worldwide. Due to the limited number of available drugs and their side effects, the development of new chemotherapeutic strategies for HCC treatment has become increasingly important. This study is aimed at investigating whether diffractaic acid (DA), one of the secondary metabolites of lichen, exhibits a potential anticancer effect on HepG2 cells and whether its anticancer effect is mediated by inhibition of thioredoxin reductase 1 (TRXR1), which is a target of chemotherapeutic strategies due to overexpression in tumor cells including HCC. XTT assay results showed that DA exhibited strong cytotoxicity on HepG2 cells with an IC50 value of 78.07 µg/mL at 48 h. Flow cytometric analysis results revealed that DA displayed late apoptotic and necrotic effects on HepG2 cells. Consistent with these findings, real-time PCR results showed that DA did not alter the BAX/BCL2 ratio in HepG2 cells but upregulated the P53 gene. Moreover, the wound healing assay results revealed a strong anti-migratory effect of DA in HepG2 cells. Real-time PCR and Western blot analyses demonstrated that DA increased TRXR1 gene and protein expression levels, whereas enzyme activity studies disclosed that DA inhibited TRXR1. These findings suggest that DA has an anticancer effect on HepG2 cells by targeting the enzymatic inhibition of TRXR1. In conclusion, DA as a TRXR1 inhibitor can be considered an effective chemotherapeutic agent which may be a useful lead compound for the treatment of HCC.
Evaluation of deep eutectic solvents in the synthesis of molecularly imprinted fibers for the solid-phase microextraction of triazines in soil samples
Authors: Monnier Alexia , Díaz-Álvarez Myriam , Turiel Esther , Martín-Esteban Antonio
Published: February 2024

Nowadays, molecularly imprinted polymers (MIPs) are well established and are considered excellent materials for performing selective extractions. However, with the progressive implementation of the principles of green chemistry, it is necessary to find greener alternatives for both the synthesis and further use of MIPs in sample preparation. Accordingly, in the present work, different deep eutectic solvents (DES, both hydrophilic and hydrophobic), as an alternative to conventional organic solvents (i.e., toluene), were evaluated as porogens for the synthesis of imprinted fibers (monoliths), using fused silica capillaries as molds, for solid-phase microextraction (SPME). From this study, the polymer prepared with propazine (dummy template), methacrylic acid (monomer), ethylene glycol dimethacrylate (cross-linker), and a formic acid:L-menthol (1:1) DES (porogen) showed the best performance for selective rebinding of triazines. After optimization of the different variables involved in SPME, the new imprinted fibers were successfully applied to the extraction of target analytes (desisopropylatrazine, desethylatrazine, simazine, and atrazine) from soil sample extracts, providing relative recoveries ranging from 75.7 to 120.1%, reaching limits of detection within the range of 6.2–15.7 ng g−1, depending upon the analyte.

Graphical Abstract
Optimizing gluteal augmentation with hyaluronic acid: a comprehensive anthropometric study
Authors: Fantozzi Fabio
Published: February 2024

The buttock, positioned between the trunk and lower limbs, plays a pivotal role in body contour aesthetics. Achieving the ideal combination of shape and volume is crucial for natural-looking gluteal augmentation, particularly when employing hyaluronic acid (HA). This study seeks to establish an anthropometrically informed protocol for optimal HA infiltration, aiming to avoid unnatural outcomes. The study utilized Genefill Contour Plus for buttock reshaping. An oval was delineated, strategically positioned in relation to anatomical landmarks, and HA was injected through an 18-gauge cannula on the suprafascial plane. The protocol involved meticulous considerations of gluteal geometry. Sixty participants (55 females, 5 males) with a mean age of 35.5 years underwent HA buttock augmentation. The HA quantities ranged from 30 to 50 ml per buttock to enhance gluteal projection. All participants attended follow-ups at 7 to 14 days and 3 to 6 months. Satisfaction evaluation, utilizing aesthetic improvement ratings, involved assessments from both patients and physicians. The complexity of infiltrating semi-dense material for buttock augmentation demands a meticulous protocol grounded in an understanding of gluteal geometry. Gluteal augmentation using HA, guided by anthropometric measures, emerges as a secure and effective approach, yielding optimal aesthetic results while minimizing complications. This study contributes to refining the protocol for HA infiltration, ensuring a natural and harmonious gluteal contour. All participants attended regular follow-ups at 7 to 14 days and 3 to 6 months post-injection for a comprehensive evaluation of aesthetic outcomes and patient well-being. This anthropometrically guided HA injection protocol ensures a meticulous and tailored approach to gluteal remodeling, emphasizing natural contours and aesthetic satisfaction while minimizing complications.

Level of evidence: Level IV, Therapeutic.
Extended parental care in the mass provisioning silk wasp, Microstigmus rosae
Authors: Bonifacii Rosa Leena , Field Jeremy
Published: February 2024

Insurance-based mechanisms, where surviving group-members can complete parental care after the death of a nestmate, are key to the origin of cooperative group formation in insects. Selection for group living via these models is proposed to be dependent on the life expectancy of adult carers relative to the duration of offspring dependency on parental care. Progressive provisioning, where adults feed offspring gradually as they grow, is thought to extend this period of dependency and is therefore suggested to be an important factor promoting the evolution of sociality. In contrast, mass-provisioning species provide offspring with all the food they need to reach maturity at the beginning of their development. Since offspring are then nutritionally independent, the applicability of insurance models is less clear. In this paper we experimentally demonstrate that adult presence on the nest, even after the end of provisioning, is critical for brood survival in the mass provisioning silk wasp Microstigmus rosae. After 10 days, experimentally orphaned nests contained 65% fewer healthy offspring than controls. Adult females were also recorded performing post-provisioning parental care behaviours including nest maintenance and repair, putative hygienic brood care and aggressive nest defence against both ants and parasitoid wasps. By demonstrating the potential applicability of insurance advantages our results highlight how, even in mass provisioners, insurance-based mechanisms may be part of what favours group living.

Significance statement

Extended parental care is an important precursor to the evolution of eusociality. In this context, group living can serve as a form of “life insurance”, ensuring that dependent offspring receive the care they need to reach maturity should the mother die. Such mechanisms are especially important to our understanding of social evolution as they are able to account for the origins of cooperative group formation, not just its maintenance. However, for mass-provisioning species, where all food items are provided upfront, the significance of insurance advantages remains unclear. In this study, we experimentally demonstrate that adult attendance is critical for brood survival in the mass provisioning wasp, Microstigmus rosae. Our results reveal the applicability of insurance advantages to M. rosae with important implications for our understanding of the potential adaptive value of group living in mass provisioning species.
Conditional survival to assess prognosis in patients with chronic lymphocytic leukemia
Authors: Schlosser Pascal , Schiwitza Annett , Klaus Jonas , Hieke-Schulz Stefanie , Szic Katarzyna Szarc vel , Duyster Justus , Trepel Martin , Zirlik Katja , Schumacher Martin , Claus Rainer
Published: February 2024

Biomarkers in chronic lymphocytic leukemia (CLL) allow assessment of prognosis. However, the validity of current prognostic biomarkers based on a single assessment point remains unclear for patients who have survived one or more years. Conditional survival (CS) studies that address how prognosis may change over time, especially in prognostic subgroups, are still rare. We performed CS analyses to estimate 5-year survival in 1-year increments, stratified by baseline disease characteristics and known risk factors in two community-based cohorts of CLL patients (Freiburg University Hospital (n = 316) and Augsburg University Hospital (n = 564)) diagnosed between 1984 and 2021. We demonstrate that 5-year CS probability is stable (app. 75%) for the entire CLL patient cohort over 10 years. While age, sex, and stage have no significant impact on CS, patients with high-risk disease features such as non-mutated IGHV, deletion 17p, and high-risk CLL-IPI have a significantly worse prognosis at diagnosis, and 5-year CS steadily decreases with each additional year survived. Our results confirm that CLL patients have a stable survival probability with excess mortality and that the prognosis of high-risk CLL patients declines over time. We infer that CS-based prognostic information is relevant for disease management and counseling of CLL patients.
Experimental modeling and optimization of pullulan production by Aureobasidium pullulans AZ-6
Authors: Mujdeci Gamze Nur , Bozdemir M. Tijen , Ozbas Z. Yesim
Published: February 2024

The objective of this study was to optimize the fermentation parameters by using response surface methodology for increasing pullulan production of Aureobasidium pullulans AZ-6 in synthetic fermentation medium. The optimum conditions were determined as follows: the initial sucrose concentration (X1): 100 g/L; the initial peptone concentration (X2): 11.31 g/L; the initial pH (X3): 6.48; and the temperature (X4): 24.2 °C. In the optimum conditions, the maximum exopolysaccharide (EPS) concentration (Y1), the maximum pullulan concentration (Y2), the specific growth rate (Y3), the maximum specific pullulan formation rate (Y4), and the pullulan yield (Y5) were expected to be obtained as 37.078 and 35.372 g/L, 0.062 h−1, 0.021 [g pullulan/(g mo.h)], and 53.681%, respectively. The observed values of Y1, Y2, Y3, Y4, and Y5 were 36.950 g/L, 35.470 g/L, 0.064 h−1, 0.036 [g pullulan/(g mo.sa)], and 54.480%, respectively, as a result of validation experiments. EPS samples were characterized by Fourier-transform infrared spectroscopy and scanning electron microscope analyses. The optimization process caused more than a 50% increase in EPS and pullulan concentrations. This study showed that the color-variant A. pullulans AZ-6 strain could become a significant industrial strain if it is explored further in the future to produce pullulan on a larger scale.
Bone tissue engineering for osteointegration: Where are we now?
Authors: Aykora Damla , Uzun Metehan
Published: February 2024

Bone fracture healing is a challenging process, due to insufficient and slow tissue repair. Sufferers from bone fractures struggle with one-third of nonunion, display graft rejection, high-costed implantation, or chronic pain. Novel advances in tissue engineering presented promising options for this strain. Biomaterials for bone repair allow accelerated regeneration, osteoblastic cell activation, and enhanced bone remodeling. There is a wide range of biomaterials that are biocompatible, bioresorbable, and biodegradable and used for bone tissue regeneration, promoting osteoconductive and osteoinductive properties. The main aim of bone tissue engineering is to generate rapid and optimal functional bone regeneration through a combination of biomaterials, growth factors, cells, and various agents. Recently bone tissue engineering has been attracted to the use of bioactive glass scaffolds incorporated with polymers and patient-specific fabrication of the bone healing material by 3D bioprinting. There are promising future outcomes that were reported by several research. The present review provides an outlook for recent most common biomaterials in bone tissue engineering suggesting bone tissue engineering practices should have been proceeded to clinical application.
Comparison of force measurement techniques in a short duration hypersonic facility
Authors: Hyslop Andrew , Doherty Luke J. , McGilvray Matthew
Published: February 2024

Force measurement experiments have been conducted within the University of Oxford’s High Density Tunnel with a $$7^{\circ }$$

7
∘

half-angle cone. The purpose of the study was to provide a direct comparison between two independent force techniques in the same facility at the same free-stream conditions to provide a quantitative and qualitative discussion of the advantages and disadvantages of both techniques. The first force measurement technique used a conventional 4-axis sting-mounted force balance which was calibrated both statically and through the stress wave deconvolution method, whilst the second technique used the less established static free-flight methodology. Experiments were conducted at a Mach 5 test condition which provided sufficient dynamic pressure to generate aerodynamic forces suitable for the measurement range of the force balance. Results for lift, drag and pitching moment coefficients were obtained over a range of angles of attack and compared with predictions from a hypersonic panel method code. Agreement between the independent force techniques and numerical data sets was good over the range of angles of attack. Maximum uncertainties were shown to be 38.46 ± 0.56 N and 22.52 ± 0.44 N for free-flight in lift and drag, respectively, and 38.74 ± 1.59 N and 22.13 ± 1.27 N for the dynamically calibrated force balance which demonstrates the superiority of free-flight.
Improved subseasonal-to-seasonal precipitation prediction of climate models with nudging approach for better initialization of Tibetan Plateau-Rocky Mountain Circumglobal wave train and land surface conditions
Authors: Qin Yi , Tang Qi , Xue Yongkang , Liu Ye , Lin Yanluan
Published: February 2024

Reliable subseasonal-to-seasonal (S2S) precipitation prediction is highly desired due to the great socioeconomical implications, yet it remains one of the most challenging topics in the weather/climate prediction research area. As part of the Impact of Initialized Land Temperature and Snowpack on Sub-seasonal to Seasonal Prediction (LS4P) project of the Global Energy and Water Exchanges (GEWEX) program, twenty-one climate models follow the LS4P protocol to quantify the impact of the Tibetan Plateau (TP) land surface temperature/subsurface temperature (LST/SUBT) springtime anomalies on the global summertime precipitation. We find that nudging towards reanalysis winds is crucial for climate models to generate atmosphere and land surface initial conditions close to observations, which is necessary for meaningful S2S applications. Simulations with nudged initial conditions can better capture the summer precipitation responses to the imposed TP LST/SUBT spring anomalies at hotspot regions all over the world. Further analyses show that the enhanced S2S prediction skill is largely attributable to the substantially improved initialization of the Tibetan Plateau-Rocky Mountain Circumglobal (TRC) wave train pattern in the atmosphere. This study highlights the important role that initial condition plays in the S2S prediction and suggests that data assimilation technique (e.g., nudging) should be adopted to initialize climate models to improve their S2S prediction.
New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis
Authors: Guo Yong , Endmayr Verena , Zekeridou Anastasia , McKeon Andrew , Leypoldt Frank , Hess Katharina , Kalinowska-Lyszczarz Alicja , Klang Andrea , Pakozdy Akos , Höftberger Elisabeth , Hametner Simon , Haider Carmen , De Simoni Désirée , Peters Sönke , Gelpi Ellen , Röcken Christoph , Oberndorfer Stefan , Lassmann Hans , Lucchinetti Claudia F. , Höftberger Romana
Published: February 2024

Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8+/perforin+/granzyme A/B+ cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.

Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.
Hair cortisol concentrations in pregnant women with bipolar, depressive, or schizophrenic spectrum disorders
Authors: Nyström-Hansen Maja , Andersen Marianne Skovsager , Davidsen Kirstine Agnete , Roehder Katrine , Trier Christopher , Nayberg Emilie , Lyons-Ruth Karlen , Harder Susanne
Published: February 2024

Purpose

Maternal cortisol levels in pregnancy may support the growth of or adversely affect fetal organs, including the brain. While moderate cortisol levels are essential for fetal development, excessive or prolonged elevations may have negative health consequences for both the mother and the offspring. Little is known about predictors of altered hypothalamic–pituitary–adrenal (HPA) axis activity during pregnancy. This study examined maternal hair cortisol concentration (HCC) in the 3rd trimester of pregnancy in relation to severe psychopathology.

Methods

Hair samples were collected from 69 women, 32 with a lifetime diagnosis of severe mental disorders (bipolar I or II disorder, moderate or severe depressive disorder, schizophrenic spectrum disorder), and 37 non-clinical controls. Hair samples were collected during the 3rd trimester, and liquid chromatography tandem mass spectrometry was used for cortisol assessment. Psychiatric diagnosis and current level of symptomatic functioning were assessed using the structured clinical interview from the DSM-5 and the global assessment of functioning scale.

Results

Women with a lifetime diagnosis of severe mental illness had significantly elevated HCC compared to controls. Poorer current symptomatic functioning was also significantly associated with elevated HCC in pregnancy.

Conclusions

The implications of alterations in HCC on both maternal and infant health need further study.
Advances in automated support for requirements engineering: a systematic literature review
Authors: Umar Muhammad Aminu , Lano Kevin
Published: February 2024

Requirements Engineering (RE) has undergone several transitions over the years, from traditional methods to agile approaches emphasising increased automation. In many software development projects, requirements are expressed in natural language and embedded within large volumes of text documents. At the same time, RE activities aim to define software systems' functionalities and constraints. However, manually executing these tasks is time-consuming and prone to errors. Numerous research efforts have proposed tools and technologies for automating RE activities to address this challenge, which are documented in published works. This review aims to examine empirical evidence on automated RE and analyse its impact on the RE sub-domain and software development. To achieve our goal, we conducted a Systematic Literature Review (SLR) following established guidelines for conducting SLRs. We aimed to identify, aggregate, and analyse papers on automated RE published between 1996 and 2022. We outlined the output of the support tool, the RE phase covered, levels of automation, development approach, and evaluation approaches. We identified 85 papers that discussed automated RE from various perspectives and methodologies. The results of this review demonstrate the significance of automated RE for the software development community, which has the potential to shorten development cycles and reduce associated costs. The support tools primarily assist in generating UML models (44.7%) and other activities such as omission of steps, consistency checking, and requirement validation. The analysis phase of RE is the most widely automated phase, with 49.53% of automated tools developed for this purpose. Natural language processing technologies, particularly POS tagging and Parser, are widely employed in developing these support tools. Controlled experimental methods are the most frequently used (48.2%) for evaluating automated RE tools, while user studies are the least employed evaluation method (8.2%). This paper contributes to the existing body of knowledge by providing an updated overview of the research literature, enabling a better understanding of trends and state-of-the-art practices in automated RE for researchers and practitioners. It also paves the way for future research directions in automated requirements engineering.
Ablative fractional laser treatment reduces hedgehog pathway gene expression in murine basal cell carcinomas
Authors: Pedersen Kristian Kåber , Granborg Jonatan Riber , Lerche Catharina Margrethe , Litman Thomas , Olesen Uffe Høgh , Hædersdal Merete
Published: February 2024

This study aimed to investigate the impact of ablative fractional laser (AFL) on hedgehog pathway gene expression in murine microscopic basal cell carcinomas (BCCs) and compare these results to the effect of topical treatment with vismodegib, an FDA-approved hedgehog inhibitor. In 25 mice, 1 cm2 skin test sites (n = 44) containing microscopic BCCs were exposed to one of three interventions: a single CO2 AFL treatment (1 pulse, 40 mJ/microbeam, wavelength 10.6 μm, 5% density, pulse rate 250 Hz, n = 12), eight topical vismodegib treatments (3.8 mg/mL, n = 8), or combination of AFL and vismodegib treatments (n = 9). Untreated controls were included for comparison (n = 15). After 4 days, skin samples were analyzed for hedgehog gene expression (Gli1, Gli2, and Ptch1) by qPCR and vismodegib concentrations by liquid chromatography mass spectrometry (data analyzed with two-tailed t-tests and linear regression). A single treatment with AFL monotherapy significantly reduced hedgehog gene expression compared to untreated controls (Gli1 72.4% reduction, p = 0.003; Gli2 55.2%, p = 0.010; Ptch1 70.9%, p < 0.001). Vismodegib treatment also reduced hedgehog gene expression (Gli1 91.6%; Gli2 83.3%; Ptch1 83.0%), significantly surpassing AFL monotherapy for two out of three genes (Gli1, p = 0.017; Gli2, p = 0.007; Ptch1, p = 0.15). AFL and vismodegib combination mirrored the effects of vismodegib monotherapy (Gli1, p = 0.424; Gli2, p = 0.289; Ptch1, p = 0.593), possibly due to comparable cutaneous vismodegib concentrations (mean ± SD, vismodegib monotherapy 850 ± 475 µmol/L; combination 1036 ± 824 µmol/L; p = 0.573). In conclusion, a single AFL treatment significantly reduced hedgehog gene expression in murine BCCs mimicking the effects of eight topical applications of vismodegib. Further studies are needed to assess whether AFL can be utilized for BCC treatment, either as monotherapy or in combination with other drugs.
Comparing heuristic valuation processes between health state valuation from child and adult perspectives
Authors: Lipman Stefan A. , Reckers-Droog Vivian T.
Published: February 2024

Objectives

Health state valuation assumes that respondents trade off between all aspects of choice tasks and maximize their utility. Yet, respondents may use heuristic valuation processes, i.e., strategies to simplify or avoid the trade-offs that are core to health state valuation. The objective of this study is to explore if heuristic valuation processes are more prevalent for valuation from a 10-year-old child’s perspective compared to the use of an adult perspective.

Methods

We reused existing data in which EQ-5D health states were valued from adult and child perspectives with composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks. Our analyses focused on comparing completion time and responding patterns across both perspectives. We also explored how reflective of a set of heuristic strategies respondents’ choices were in both perspectives.

Results

We found no evidence for systematic differences in completion time across perspectives. Generally, we find different responding patterns in child perspectives, e.g., more speeding, dominance violations, and clustering of utilities at 1.0, 0.8, and 0. Very few heuristic strategies provide a coherent explanation for the observed DCE responses.

Conclusion

Our results provide some, albeit indirect, evidence for differences in heuristic valuation processes between perspectives, although not across all data sources. Potential effects of heuristic valuation processes, such as transfer of responsibility, may be identified through studying responding patterns in cTTO and DCE responses.