bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized phase 1 study of safety, tolerability, and pharmacokinetics of MK-1088, a novel dual adenosine receptor antagonist, in healthy adult participants
Authors: Gupta Pranav , Chatterjee Manash , Kim Yeonil , Deschamps Kathleen , Lemoine Lieselotte , Van Dyck Kristien , Matthews Catherine Zhou , Rottey Sylvie , Stoch Aubrey , Lai Eseng
Published: August 2024

This phase 1 first-in-human study evaluated the safety, tolerability, and pharmacokinetics of MK-1088, a novel, small-molecule dual inhibitor of adenosine A2A and A2B receptors. Healthy adult participants were enrolled in two panels (n = 8 each) and randomly assigned to receive MK-1088 (n = 6) or placebo (n = 2) orally in each of five treatment periods. Participants in panel A received single ascending doses of MK-1088 at 1, 10, 50, and 150 mg or placebo in a fasted or fed (50 mg only) state. Participants in panel B received MK-1088 at 3, 25, 100, and 224 mg or placebo in a fasted state. Primary objectives were to evaluate safety, tolerability, and plasma pharmacokinetics following a single dose of MK-1088. The secondary objective was to evaluate the effects of a high-fat meal on pharmacokinetics. All participants (n = 16) completed the study (median age: 33 years [range: 20–43]; all were male). Treatment-related adverse events (AEs) occurred in 1 of 6 (17%), 4 of 6 (67%), 4 of 6 (67%), and 2 of 6 (33%) participants after receiving MK-1088 at 3, 25, 100, and 224 mg, respectively. No serious AEs or deaths due to any cause occurred. MK-1088 was rapidly absorbed after a single dose; half-life was ~ 11 h in the 100–224 mg dose range. The target concentration at 12 h (> 0.3 µM) was exceeded at the 50-mg dose level. MK-1088 plasma pharmacokinetics increased dose proportionately. A high-fat meal did not significantly affect pharmacokinetics at the 50-mg dose. MK-1088 was well tolerated and demonstrated dose-proportional pharmacokinetic properties that were not affected by a high-fat meal.
Impactful Conceptual Engineering: Designing Technological Artefacts Ethically
Authors: Veluwenkamp Herman
Published: August 2024

Conceptual engineering is the design, evaluation and implementation of concepts. Despite its popularity, some have argued that the methodology is not worthwhile, because the implementation of new concepts is both inscrutable and beyond our control. In the recent literature we see different responses to this worry. Some have argued that it is for political reasons just as well that implementation is such a difficult task, while others have challenged the metasemantic and social assumptions that underlie this skepticism about implementation. In this paper, I argue that even if implementation is as difficult as critics maintain, there is at least one context in which conceptual engineering is extremely impactful and demonstrably so: the design of new technology. Different conceptions of control, freedom, trust, etc. lead to different designs and implementations of systems that are built to embed those concepts. This means that if we want to design for control, freedom, trust, etc., we have to decide which conception we ought to use. When we determine what the appropriate conception of a concept is in a technological context and use this conception to operationalize a norm or value, we generate requirements which have real-world effects. This not only shows that conceptual engineering can be extremely impactful, the fact that it leads to different design requirements means that we have a way to evaluate our conceptual choices and that we can use this feedback loop to improve upon our conceptual work By illustrating the direct impacts of different conceptions on technology design, this paper underscores the practical applicability and value of conceptual engineering, demonstrating how it serves as a crucial bridge between abstract philosophical analysis and concrete technological innovation.
Real Talk: Conversations on HIV with Black Heterosexual Men in Healthcare Settings
Authors: Urquhart Rakira , Adams Mackenzie , Chakraborty Shawtaabdee , Burns Jade C.
Published: August 2024

Nearly half of heterosexually transmitted human immunodeficiency virus (HIV) infections occur among Black men in the United States. Yet Black heterosexual men (BHM) are largely ignored in HIV programming, policy implementation, and research. This study explores how masculinity, mental health, and socioeconomic factors such as income, education, and insurance (e.g., enrollment and coverage) correlate with the likelihood of BHM having important conversations surrounding HIV with their healthcare providers and family members. Conversations among social networks (e.g., peers, family, and neighbors) create an opportunity to increase comfortability while discussing HIV-related topics around condom use and testing. This study used a cross-sectional survey design and convenience sampling (N = 279) to recruit participants from a community-academic partnership involving a Federally Qualified Health Center (FQHC) in Detroit between June 1, 2020, and July 31, 2020. Descriptive statistics were used to report demographics, socioeconomic information, and sexual health-related behavior variables. Spearman’s correlation test was used to report bivariate correlations between predictor and outcome variables. 49.3% of the study participants disclosed having ever talked to a healthcare provider about HIV/acquired immune deficiency syndrome (AIDS), and 40.9% disclosed having ever talked to a family member about HIV/AIDS and sexually transmitted infections (STIs). The results from this article highlight potential barriers that may inhibit BHM from engaging in conversations about HIV with their healthcare providers and family members. It is important to include BHM in future research that focuses on HIV prevention and education to support community leaders and clinicians who work to address these disparities.
Soft power in complicated and complex education systems: Gender, education and global governance in organisational responses to SDG 4
Authors: Unterhalter Elaine
Published: August 2024

This article examines how the distinction between complicated and complex education systems contributes to our understanding of global governance and how “soft power” concerned with gender is used in international development organisations’ responses to Sustainable Development Goal (SDG) 4, the global goal for education. Four global governance approaches which shape these organisations are distinguished: partnership building, gender mainstreaming, gender activism and contestation by global feminist movements. These strands of soft power have implications for how meanings of gender, education, power and accountability are interpreted. The work of three organisations – the Global Partnership for Education (GPE), the Gender at the Centre Initiative (GCI) and the Malala Fund – are reviewed to exemplify these global governance approaches. The analysis draws on a close reading of the organisations’ published documents to build a history of how the gender concerns of SDG 4 came to be interpreted, negotiated, contested or ignored. The activities of the three organisations show considerable interplay between concepts of complicated and complex education systems. The discussion raises questions regarding what kind of work soft power in gender and education does in a context of huge and growing global inequalities and insecurities. In addition, the question is posed why there is still no institutional base to articulate a global feminist politics which confronts and seeks to dismantle unjust structures of power.
Bayesian Adaptive Lasso for Detecting Item–Trait Relationship and Differential Item Functioning in Multidimensional Item Response Theory Models
Authors: Shan Na , Xu Ping-Feng
Published: August 2024

In multidimensional tests, the identification of latent traits measured by each item is crucial. In addition to item–trait relationship, differential item functioning (DIF) is routinely evaluated to ensure valid comparison among different groups. The two problems are investigated separately in the literature. This paper uses a unified framework for detecting item–trait relationship and DIF in multidimensional item response theory (MIRT) models. By incorporating DIF effects in MIRT models, these problems can be considered as variable selection for latent/observed variables and their interactions. A Bayesian adaptive Lasso procedure is developed for variable selection, in which item–trait relationship and DIF effects can be obtained simultaneously. Simulation studies show the performance of our method for parameter estimation, the recovery of item–trait relationship and the detection of DIF effects. An application is presented using data from the Eysenck Personality Questionnaire.
Analysis of microplastics in the reuse of compost in three agricultural sites (Cádiz, Spain) as a circular economy strategy: detection of micropollutants and incidence of plastic ingestion levels by annelids
Authors: Sakali Ayda , Egea-Corbacho Agata , Coello Dolores , Albendín Gemma , Arellano Juana , Rodríguez-Barroso Rocío
Published: August 2024

The system of fertilizing agricultural soils with sludge or compost from wastewater treatment processes, as one of the principles of the circular economy, can lead to microplastic (MP) contamination. The existing technical standards for fertilization are very recent and do not consider this problem, although there is scientific evidence of their existence. Therefore, this study, on the one hand, evaluates the presence of MPs in agricultural soils, previously treated with sludge or compost from wastewater treatment plants for fertilization, and on the second hand, it studies the effect of these MPs on earthworms in three different locations in the south of Spain. For the study, selected composts deriving from the different stages of the composting process and three fertilized soils with increasing MP doses were followed. Samples were taken from different sections in depth (0–5, 5–10, and 10–20 cm) to study the shape, size, type, and abundance of MPs using infrared spectroscopy (FTIR). The results showed that the most abundant shape was fiber, followed by fragment and finally bulk, for both composts and soils. Regarding size distribution, 100 µm was the predominant size in composts (64.3% ± 9.8), while in the case of soils, the predominant range was from 100 to 500 µm. The prevalent polymers in both, composts and soils, were PTFE, TPE, PP, and PET, with four times higher amounts in composts than in soils. Ingestion of common MPs were also verified in two earthworm species, which ingested concentrations higher than 2.1% w/w. PP was the most ingested MP and Eisenia fetida was more voracious compared with Lumbricus terrestris. Therefore, it can be considered a suitable bioindicator for monitoring microplastic contamination in agricultural soil.

Graphical Abstract
Comparative study of polyphenol extraction using physical techniques and water as a solvent: a sustainable approach for the valorization of apple pomace
Authors: Fraterrigo Garofalo Silvia , Demichelis Francesca , Peletti Veronica , Picco Lorenzo , Tommasi Tonia , Fino Debora
Published: August 2024

Apples are among the most commonly cultivated fruits globally. Approximately 65% of annual apple production is transformed into apple juice concentrate generating a large amount of waste material named apple pomace, which includes seeds, skin, and other components. Disposing of apple by-products directly into the environment constitutes a source of environmental pollution due to its high-water content and easily fermentable nature. Apple pomace is rich in polyphenols that can be utilized as active components in cosmetic, nutraceutical, or pharmaceutical products. The present study aims to describe and compare different physical methods for the extraction of polyphenols from apple pomace. Water was used as the extraction solvent in thermal-stirred extraction (TSE), ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE). The best extraction conditions were identified in terms of solid to solvent ratio, temperature, power, and time through a kinetic study. The best extraction parameters were compared environmentally on a pilot scale through a life cycle assessment (LCA). All the results demonstrated the MAE is the best technique to extract polyphenol from apple pomace in terms yield and environmental impact proving that it is possible to transform waste into a sustainable source of bioactive ingredients.
Educational heterogeneity of the founding team of innovative start-ups: confirmations and denials
Authors: Fiorentino Raffaele , Longobardi Sergio , Morrone Carla , Scaletti Alessandro
Published: August 2024

This paper focuses on the value drivers of innovative start-ups (ISUs). Few companies can overcome the start-up stage; often, the early performance is insufficient, and the potential contribution of innovation to economic development is very poor. Studies based on a firm-level perspective show mixed results on the factors affecting the growth of ISUs. Most studies emphasize the role of “external” drivers of ISUs growth, while more knowledge is required of “internal” drivers. Consequently, this research focuses on the relationship between the features of the founding teams and the early performance of ISUs. Specifically, it concentrates on education heterogeneity and analyzes whether the heterogeneity of the founding team in terms of educational level (vertical heterogeneity) and field of studies (horizontal heterogeneity) affects the Italian ISUs performance. Growth regression and unconditional quantile regression models confirm the prior literature: the educational level affects the performance and the vertical heterogeneity in the composition of the founding team is relevant for ISUs performance. However, the results also suggest interesting denials: horizontal heterogeneity does not play any role, and no moderating effect of heterogeneity is shown. These findings are strongly attractive for new ventures and policymakers.
Effect of stress conditions on concentrated leak erosion resistant of fine-grained soils with different characteristics
Authors: Topçu Sadettin , Savaş Hasan , Tosun Hasan
Published: August 2024

Internal erosion is one of the most important factors that cause earth structures that retain water, such as embankment dams, to collapse. Concentrated leak erosion, one of the forms of internal erosion, occurs in cracked fine-grained soils and pressurized flow conditions. To evaluate the concentrated leak erosion risk of cracks/voids, it is necessary to ascertain the erosion resistance of these materials. The erosion rate and critical shear stresses determine internal erosion resistance in concentrated leak erosion. This study determined soil’s concentrated leak erosion resistance using test equipment that allowed the flow to pass through a hole with stress-free (no loading), anisotropic-compression stress, anisotropic-expansion stress, and isotropic stress conditions. The stresses that developed in the samples’ hole wall where erosion occurred were determined with numerical modeling as pre-experimental stress conditions. The experiments were performed under a single hydraulic head on four selected cohesive soils with different erosion sensitivity. Time-dependent flow rates obtained from the test system can be used to determine hydraulic parameters, such as energy grade lines, with the help of basic theorems of pipe hydraulics in theoretical hydraulic models. Moreover, the erosion rates were quantitatively determined using the continuity equation, while critical shear stresses were qualitatively compared for concentrated leak erosion developed by the dispersion mechanism. As a result of the experiments, stress conditions influence the concentrated leak erosion resistance in the soil samples with dispersive erosion. Moreover, the shear strength in the Mohr–Coulomb hypothesis can explain the erosion resistance in these soils under stress conditions depending on the sand/clay ratio.
Development of a human machine interface for robotically assisted surgery optimized for laparoscopic workflows
Authors: Wegener Luca , Wilhelm Dirk , Berlet Maximilian , Fuchtmann Jonas
Published: August 2024

Introduction

In robotic-assisted surgery (RAS), the input device is the primary site for the flow of information between the user and the robot. Most RAS systems remove the surgeon’s console from the sterile surgical site. Beneficial for performing lengthy procedures with complex systems, this ultimately lacks the flexibility that comes with the surgeon being able to remain at the sterile site.

Methods

A prototype of an input device for RAS is constructed. The focus lies on intuitive control for surgeons and a seamless integration into the surgical workflow within the sterile environment. The kinematic design is translated from the kinematics of laparoscopic surgery. The input device uses three degrees of freedom from a flexible instrument as input. The prototype’s performance is compared to that of a commercially available device in an evaluation. Metrics are used to evaluate the surgeons’ performance with the respective input device in a virtual environment implemented for the evaluation.

Results

The evaluation of the two input devices shows statistically significant differences in the performance metrics. With the proposed prototype, the surgeons perform the tasks faster, more precisely, and with fewer errors.

Conclusion

The prototype is an efficient and intuitive input device for surgeons with laparoscopic experience. The placement in the sterile working area allows for seamless integration into the surgical workflow and can potentially enable new robotic approaches.
Exploring Microstructure and Magnetic Domain Evolution in the As-cast Soft Magnetic Fe74B20Nb2Hf2Si2 Alloy: A Comprehensive Study Using STEM, Lorentz TEM, and LM-STEM DPC Microscopy
Authors: Czaja Pawel , Rezaei-Shahreza Parisa , Hasani Saeed , Seifoddini Amir , ´Sliwa Agata , Nabiałek Marcin
Published: August 2024

This study delves into subtle changes in the microstructure and domain arrangement of a Fe74B20Nb2Hf2Si2 soft magnetic amorphous alloy. Utilizing transmission electron microscopy in Lorentz mode, low-magnification STEM, and differential phase contrast analysis (DPC), the research explores both the as-cast state and annealed samples. The results confirmed the formation of α-Fe, Fe23B6, Fe2(Hf, Nb), and Fe2B crystalline phases with increasing annealing temperature. Consequently, these crystallization stages induce significant alterations in magnetic domain size and spatial distribution due to microstructural changes. As the crystallization temperature rises, the volume fraction of crystalline phases increases, leading to modifications in the arrangement and size of magnetic domains. The decrease in magnetic domain size, associated with the formation of pinning sites during heat treatment, leads to alterations in soft magnetic properties. This includes an increase in coercivity (Hc) up to 40 A/m in the sample annealed at the temperature range of the third crystallization stage compared to the as-cast sample (1.5 A/m). Furthermore, as the annealing temperature rises, there is a corresponding increase in saturation magnetization (Ms), which reached to 1.71 T in the sample annealed within the temperature range of the third crystallization stage. These findings hold substantial implications for the practical applications of the Fe-based soft bulk metallic glasses (BMGs) alloy across various industries.
A simple and effective method coupling coagulation and UV/TiO2 photocatalysis for treating real-produced wastewater from oil processing
Authors: Rosa Domenico , Hasanova Seynura , Abbasova Nigar , Nacer Hamza , Aliyev Fegan , Di Palma Luca
Published: August 2024

The complex composition of real-produced wastewater from oil processing poses significant challenges for wastewater treatment. The employed conventional methods have disadvantages such as low efficiency, high-cost demand, secondary waste, adverse effects on the environment and need to be intensified. The combined treatment of coagulation (carried out with Al2(SO4)3) and photocatalysis (UV/TiO2) was studied on wastewater produced from a SOCAR (Pirallahi dry well) oil extraction plant and synthetic paracetamol-based wastewater. Two different dosages of Degussa P25 catalyst at different pH conditions and ion presence were studied. Characterization of the produced wastewater showed the complexity of the treated matrix given the presence of inorganic ions and aromatic and aliphatic contaminants, and an important parameter that was reduced through coagulation was turbidity. The initial concentration expressed as THC was 714 mg/L. At the end of the treatment, a THC value of 210 mg/L was reached.
The Composition of Graded Dental Zirconias
Authors: Maharishi Anvita , Horkley Kenny , Unruh Daniel K. , McLaren Edward A. , White Shane N.
Published: August 2024

Zirconia dental ceramics have evolved from uniform blocks of 3 mol.% yttria (3Y) to strength- and color-graded blocks containing 3 mol.% and 5 mol.% components. Relatively little is known about the graded materials’ compositions and microstructures. Concerns have been raised about aging and degradation. This study investigated the microstructure, elemental composition, and phase content of different zones of strength- and color-graded zirconia blocks using scanning electron microscopy, x-ray fluorescence, and x-ray diffraction. Specimens were made from green-state blocks using CAD/CAM machining and sintering. Two strength- and color-graded zirconia materials had different grain sizes, elemental compositions, and phase contents between their top and bottom zones, these data being internally consistent as well as being broadly consistent with prior compositional physical property data. A color-graded zirconia material did not exhibit substantial differences between its top and bottom zones, consistent with expectations and previously published data. Modeling phase content for complex yttria-doped zirconia crystal systems with multiple heterogeneous crystal lattices from XRD data was inherently difficult, which may account for the ranges among previously published data; authors should describe detailed methodologies. Detailed compositional data at the scale of the microstructure is needed to relate composition to phase content, physical behavior, including crack evolution.
Native nephrectomies in patients with autosomal dominant polycystic kidney disease: retrospective cohort study
Authors: Hogan Richard Edmund , McHale Barry , Dowling Gavin Paul , Elhassan Elhussein , Kilkenny Conor James , Mohan Ponnusamy , Conlon Peter
Published: August 2024

Background

Approximately 1 in 5 patients with autosomal dominant polycystic kidney disease (ADPKD) will undergo a native nephrectomy in their lifetime. These can be emergent or planned and the indications can range from space for kidney transplant, pain, hematuria and frequent urinary tract infections (UTIs). Due to the diverse nature of presentations, there is a lack of certainty about outcomes and optimal management.

Aims

This study aimed to evaluate preoperative indications and perioperative/postoperative complications in this patient cohort.

Methods

This retrospective review included 41 patients with ADPKD who underwent unilateral or bilateral nephrectomy in a single hospital between 2010 and 2020. We collected data on patient demographics, surgical indications, histological results and postoperative complications. We sourced this information using the hospital’s patient medical records.

Results

The main indications for nephrectomy were pain (39.5%) and bleeding (41.8%). Further indications included recurrent UTIs (16.3%), space for transplantation (27.9%), query malignancy (4.7%) and compressive gastropathy (2.3%). With regard to side, 55.8% were right-sided, 23.3% were left-sided, and 20.9% were bilateral. Seven percent of nephrectomy specimens demonstrated malignancy. Postoperative morbidity included requiring blood transfusion and long hospital stay. Thirty-seven percent of patients received a postoperative blood transfusion. There was no immediate or postoperative mortality associated with any of the cases reviewed.

Conclusions

In conclusion, this study demonstrates that native nephrectomy remains a safe operation for patients with ADPKD. Although further research is needed into, transfusion protocols, adjunctive therapies, such as TAE and research into timing of nephrectomy are still needed.
A Methodological Benchmark in Determining the Urban Growth: Spatiotemporal Projections for Eskişehir, Türkiye
Authors: Isinkaralar Oznur
Published: August 2024

Urban growth changes spatial uses over time due to different dynamics. These processes cause many physical, environmental, and socioeconomic problems, such as climate change, pollution, and population-related events. Therefore, it is essential to predict future urban expansion to produce effective policies in sustainable urban planning and make long-term plans. Many models, such as dynamic, statistical, and Cellular Automata and Markov Chain (CA-MC) models, are used in geographic information system (GIS) environments to meet the high-performance requirements of land use modeling. This study estimated the growth of settled areas in Eskişehir city center using models developed using two different methods. In this context, settled areas in the city center were examined within the scope of 1990–2018, and the growth areas of settled areas in 2046 were predicted using the CA-Markov method in Model 1: Quantum GIS (QGIS) MOLUSCE plugin and Model 2: IDRISI Selva. While settled areas are continuously increasing, other urban areas are decreasing. Model 1 predicts an increase of 1195 ha in settled areas by 2046, while Model 2 predicts an increase of 45,022 ha. At the same time, it is concluded that settled areas will grow in a central location in Model 1, while they will spread in an east-west extension in Model 2. The study results show that QGIS-based modeling predicts more limited spatial growth than IDRISI Selva. The research interprets growth in terms of the staging of urban services, the population size of neighboring cities, distances, and income levels based on the internal and external dynamics of the city.
Tumor-exosomal miR-205-5p as a diagnostic biomarker for colorectal cancer
Authors: Zhao Yajing , Zhao Yapeng , Liu Lisheng , Li Guanghao , Wu Yawen , Cui Yanan , Xie Li
Published: August 2024

Background

Tumor-derived exosomal miRNAs play crucial roles in cancer diagnosis. Current studies aim to identify exosomal miRNAs associated with colorectal cancer (CRC) that are noninvasive, sensitive, and specific.

Patients and methods

Exosomes were extracted from CRC patients and healthy donors via ultracentrifugation, followed by verification via transmission electron microscopy (TEM), qNano, and Western blot analysis. The differential expression levels and clinical characteristics of miR-205-5p were analyzed in CRC via data from The Cancer Genome Atlas (TCGA). Real-time quantitative PCR was used to assess the expression levels of exosomal miRNAs in 157 primary CRC patients, 20 patients with benign diseases, and 135 healthy donors. Predictions regarding target genes were made to guide further exploration of the disease’s etiopathogenesis through bioinformatics.

Results

Compared with that in healthy donors, the expression of miR-205-5p in colorectal cancer (CRC) patients was significantly lower, as determined through analysis of the TCGA database. We conducted a prediction and analysis of the functional enrichment of downstream target genes regulated by miR-205-5p. A lower level of exosomal miR-205-5p in the serum of CRC patients than in that of healthy controls (p < 0.0001) and patients with benign disease (p < 0.0001) was observed. Furthermore, the expression levels of exosomal miR-205-5p were significantly lower in early-stage CRC patients than in the comparison groups (p<0.001 and p < 0.0001). Notably, the expression levels of exosomal miR-205-5p significantly increased postoperatively (p = 0.0053).

Conclusions

The present study demonstrated that serum exosomal miR-205-5p may be a diagnostic biomarker for CRC.
Importance of allogeneic stem cell transplantation in myelofibrosis
Authors: Hirschbühl Klaus , Schmid Christoph
Published: August 2024

Allogeneic stem cell transplantation (alloSCT) is the only curative treatment option for patients with high-risk myelofibrosis (MF). However, it is important to bear in mind that alloSCT in MF is associated with a nonrelapse mortality that should not be underestimated. Therefore, both exact disease risk categorization and thorough evaluation of the individual transplant-related risk are mandatory to identify those patients to whom alloSCT should be offered. This short review is intended to provide a concise overview on relevant aspects to be considered for patient selection, planning, and performing alloSCT.
Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM)
Authors: Nakayama Takahiro , Niikura Naoki , Yamanaka Takashi , Yamamoto Mitsugu , Matsuura Kazuo , Inoue Kenichi , Takahara Sachiko , Nomura Hironori , Kita Shosuke , Yamaguchi Miki , Aruga Tomoyuki , Shibata Nobuhiro , Shimomura Akihiko , Ozaki Yuri , Sakai Shuji , Takiguchi Daisuke , Takata Takehiko , Bastanfard Armin , Shiosakai Kazuhito , Tsurutani Junji
Published: August 2024

We provide updated results (median follow-up duration: 20.4 months) of a retrospective study on the effectiveness of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer with brain metastases (BM) and/or leptomeningeal disease (ROSET-BM). Median progression-free survival (PFS) was 14.6 months. Median overall survival (OS) was not reached (NR); 24-month OS rate was 56.0%. Subgroup analysis showed that median PFS was 13.2 months in patients with analytical active BM, 17.5 months in patients with leptomeningeal carcinomatosis (LMC), and NR in patients with analytical stable BM (24-month PFS rates in patients with analytical active BM, LMC, and analytical stable BM were 32.7%, 25.1%, and 60.8%, respectively). Median OS was 27.0 months in patients with analytical active BM and NR in patients with LMC or analytical stable BM (24-month OS rates in patients with analytical active BM, LMC, and analytical stable BM were 52.0%, 61.6%, and 71.6%, respectively). The most common adverse event leading to discontinuation of T-DXd was interstitial lung disease (ILD; 23.1%); median ILD onset time among patients who discontinued T-DXd treatment due to ILD was 5.3 months. T-DXd has promising effectiveness in heavily pre-treated HER2+ metastatic breast cancer patients with BM and LMC. The incidence and median onset time of ILD were similar to those of Japanese subgroups in previous studies.
Demokratische Teilhabe in der Grundschule – Welche Mitbestimmungsmöglichkeiten nehmen Kinder im Klassenkontext wahr?
Authors: Gerbeshi Leonora , Ertl Sonja , Torrau Sören
Published: August 2024

Die UN-Kinderrechtskonvention gilt als Leitprinzip demokratischer Teilhabe, wodurch die Forderung nach Mitbestimmungsmöglichkeiten für Kinder begründet wird. Inwiefern Kinder im Grundschulalter in Unterricht und Schulleben mitbestimmen können und welche Rolle dabei personenbezogene und andere unterrichtsbezogene Merkmale spielen, ist bislang noch unzureichend erforscht. Der Beitrag stellt Ergebnisse einer querschnittlichen Fragebogenstudie mit Drittklässler*innen (N = 543) zur Mitbestimmung im Klassenkontext dar. Die Ergebnisse multipler Regressionsmodelle unter Berücksichtigung der Klassenstruktur zeigen, dass die Schüler*innen Mitbestimmung vorrangig bezüglich organisatorischer Aspekte und weniger bezüglich des konkreten Unterrichts wahrnehmen: Sie fühlen sich informiert und gehört, erleben jedoch wenig Austausch- und Abstimmungsprozesse. Sowohl die Migrationsgeschichte als auch die wahrgenommene Selbstbestimmung im Unterricht stellen dabei bedeutsame Prädiktoren für die wahrgenommene Mitbestimmung der Kinder im Klassenkontext dar. Die Ergebnisse werden diskutiert und weitere Forschungsdesiderata aufgezeigt. Abschließend werden Implikationen für die demokratische Teilhabe von Grundschulkindern im Klassenkontext abgeleitet.
Direct and some inverse problems for a generalized diffusion equation with variable coefficients
Authors: Ilyas Asim , Malik Salman A.
Published: August 2024

Direct and two inverse problems for a Legendre equation involving integral convolution in time are studied. The inverse problems are ill-posed in the sense of Hadamard. The analytical series solutions of the problems are constructed by using method of variable separation. The determination of only u(x, y) is studied in the direct problem, the recovery of a pair of functions, i.e., $$\{u(x,y), f(x)\}$$

{
u
(
x
,
y
)
,
f
(
x
)
}

with appropriate addition data at some T is investigated in the 1st inverse problem while the identification of a pair of functions, i.e., $$\{u(x,y), q(y)\}$$

{
u
(
x
,
y
)
,
q
(
y
)
}

with an integral type data is considered in the 2nd inverse problem. By imposing certain regularity conditions, the unique existence of series solutions is developed. We provided some numerical examples to illustrate our results for the inverse problems.
Esercizio fisico nel diabete mellito di tipo 1
Authors: Haxhi Jonida , Bellini Alessio
Published: August 2024

Sommario

L’esercizio fisico migliora il controllo glicemico e la salute generale nelle persone con diabete. Tuttavia, nel diabete di tipo 1 esiste un aumento del rischio di ipoglicemia durante e dopo l’esercizio, che si traduce in contromisure inappropriate quali il consumo non necessario di carboidrati, o anche l’omissione dell’insulina o, addirittura, nell’astenersi dall’esercizio, tutte contromisure che incidono sul controllo glicemico e sul rischio cardio-metabolico. Il buon controllo glicemico durante l’esercizio fisico, implica però un’adeguata formazione dei pazienti oltre che di chi se ne prende cura. È importante un’adeguata pianificazione finalizzata a ottenere un buon controllo glicemico e ridurre il rischio di ipoglicemia durante e dopo l’allenamento, e ancora più importante durante le competizioni sportive. Questa Rassegna analizza e discute i fattori e le strategie utili a gestire la glicemia durante e dopo l’esercizio fisico, con l’obiettivo di migliorare il controllo glicemico, ridurre l’ipoglicemia e migliorare le prestazioni fisiche.
Controls on the terrigenous fractions in Early Kimmeridgian shallow-water carbonate deposits in Southern Iberia
Authors: Coimbra Rute , Olóriz Federico , Rocha Fernando
Published: August 2024

Two Kimmeridgian shallow-marine carbonate successions (mid-shelf), sharing a similar paleoclimatic framework (climatic zone), were previously explored using carbonate chemostratigraphy. Before, the goal was to detect signals related to paleoplatform bottom physiography, degree of connection with oceanic waters and overall circulation patterns. In this contribution, complementary bulk mineralogical composition and clay mineral fractions are investigated to contrast and complement previous information, aiming for a more complete overview of continent-ocean dynamics along shallow-carbonate platforms of southern Iberia. The goal is now to explore complex patterns of continental influence along proximal settings and their relative spatial distribution across differentiated settings without relevant difference in paleolatitude. The choice of both stratigraphic sections is based on this distinctness: Rocha Poço (Algarve Basin, Portugal) represents a more restricted and relatively proximal setting, in contrast to Puerto Lorente (South Iberian Paleomargin, S Spain) placed at a relatively more open and probably distal shallow-water context. Accordingly, quartz content was higher at Rocha Poço, especially at the lower siliciclastic interval of this section. Quartz contribution fades out at Puerto Lorente, where it was mainly controlled by short-lived terrigenous pulses. Clay mineral assemblages also differed, being more varied (smectite, illite and traces of kaolinite) and abundant at Rocha Poço, and generally leaner at Puerto Lorente. At the latter site, terrigenous pulses do not contribute to clay mineral abundance, only showing abundant illite at the topmost horizons. New information retrieved from mineralogical data provided evidence on depositional contrasts resulting from local differences in platform configuration, allowing a better understanding of mechanisms controlling the terrigenous fraction in the shallow-water carbonates analyzed.
Assessment of the urban pollution island intensity in Rome (Italy) from in-situ PM measurements
Authors: Di Bernardino Annalisa , Erriu Margherita , Argentini Stefania , Campanelli Monica , Casasanta Giampietro , Cecilia Andrea , Falasca Serena , Siani Anna Maria
Published: August 2024

The Urban Pollution Island (UPI), describing the temporal and spatial distribution of pollutants’ concentration attributed to the presence of urban features and activities, is one of the major problems affecting urban areas and has become more severe with rapid urbanization. To correctly evaluate the UPI Intensity (UPII), i.e., the difference in pollution concentration between the urban agglomeration and its rural surroundings, it is crucial to carefully select rural and, above all, urban reference stations, as local factors such as orography, location of the air quality monitoring stations, and street orientation can significantly impact UPII values. In this work, the UPII in Rome (Italy) is determined using daily-averaged concentrations of PM10 and PM2.5 collected by in-situ stations over the period 2018–2023. Three different methods for the assessment of UPII are tested and compared by varying the sub-set of selected urban stations, according to their environmental classification. The approach proposed will have significant implications on the management of urban environment and on the tailored design of urban air quality improvement strategies.

Results show slight differences in the monthly-averaged concentrations of both PM10 and PM2.5 between the “urban traffic” and “urban background” stations, suggesting that the proximity of the emission sources to the monitoring stations moderately influences the concentrations, potentially due to limited ventilation within street canyons, which can inhibit mixing processes. The annual variation of UPII reveals that PM10 is more sensitive to the selection of the stations particularly during winter, when the differences between the three assessment methods reach 100%. Our findings also indicate that, in the case of Rome, using the largest number of stations available in the urban area could enhance the UPII evaluation, taking into consideration the urban structure and the specific characteristics of local emission sources. The results presented here, although related to a single city, demonstrate that the selection of urban stations for the evaluation of UPII is not straightforward and requires further investigation.
Trolley Optimisation for Loading Printed Circuit Board Components
Authors: Chauhan Vinod Kumar , Bass Mark , Parlikad Ajith Kumar , Brintrup Alexandra
Published: August 2024

A trolley is a container for loading printed circuit board (PCB) components, and a trolley optimisation problem (TOP) is an assignment of PCB components to trolleys for use in the production of a set of PCBs in an assembly line. In this paper, we introduce the TOP, a novel operation research application. To formulate the TOP, we derive a novel extension of the bin packing problem. We exploit the problem structure to decompose the TOP into two smaller, identical, and independent problems. Further, we develop a mixed integer linear programming model to solve the TOP and prove that the TOP is an NP-complete problem. A case study of an aerospace manufacturing company is used to illustrate the TOP which successfully automated the manual process in the company and resulted in significant cost reductions and flexibility in the building process.
Paecilomyces variotii extracts promote growth and alleviate nutrient deficiency symptoms in apple
Authors: Zhang Yali , Lv Huimin , Man Yaoyang , Sun Wei , Cui Jianying , Wang Tao , Lv Yanhui , Li Yuanyuan
Published: August 2024

It is essential to find environment-friendly agrochemicals to cope with the problems of nutrient imbalance, fruit quality decline, and physiological disorders during apple fruit production, which is beneficial for improving the quality and yield of apple. A natural extract from Paecilomyces variotii (ZNC), an endophytic fungus, has been used widely to enhance crop performance. However, an understanding of the mechanism underlying ZNC-triggered growth and alleviation of nutrient deficiency-associated symptoms in apples remains elusive. Here, the photosynthesis, leaf growth, and fruit quality were enhanced by adding ZNC. In addition, ZNC relieved nutrient deficiency-related symptoms promoted the differentiation of root morphology and vitality, and reduced the accumulation of osmoprotectants and reactive oxygen species, thereby promoting growth under normal and nutrient-deficient conditions. Finally, genome-wide RNA sequencing reveals the ZNC-regulated mechanisms involved in hormone and metal ion pathways. Our study reveals the role of ZNC in promoting growth and improving the quality of apple, providing a new direction for reducing the use of chemical fertilizers and pesticides.
Pore-scale study of CO2 desublimation and sublimation in a packed bed during cryogenic carbon capture
Authors: Lei Timan , Luo Kai H. , Hernández Pérez Francisco E. , Wang Geng , Yang Junyu , Restrepo Cano Juan , Im Hong G.
Published: August 2024

Cryogenic carbon capture (CCC) is an innovative technology to desublimate

$\text {CO}_2$

out of industrial flue gases. A comprehensive understanding of

$\text {CO}_2$

desublimation and sublimation is essential for widespread application of CCC, which is highly challenging due to the complex physics behind. In this work, a lattice Boltzmann (LB) model is proposed to study

$\text {CO}_2$

desublimation and sublimation for different operating conditions, including the bed temperature (subcooling degree

$\Delta T_s$

), gas feed rate (Péclet number

$Pe $

) and bed porosity (

$\psi$

). The

$\text {CO}_2$

desublimation and sublimation properties are reproduced. Interactions between convective

$\text {CO}_2$

supply and desublimation/sublimation intensity are analysed. In the single-grain case,

$Pe $

is suggested to exceed a critical value

$Pe _c$

at each

$\Delta T_s$

to avoid the convection-limited regime. Beyond

$Pe _c$

, the

$\text {CO}_2$

capture rate (

$v_c$

) grows monotonically with

$\Delta T_s$

, indicating a desublimation-limited regime. In the packed bed case, multiple grains render the convective

$\text {CO}_2$

supply insufficient and make CCC operate under the convection-limited mechanism. Besides, in small-

$\Delta T_s$

and high-

$Pe $

tests,

$\text {CO}_2$

desublimation becomes insufficient compared with convective

$\text {CO}_2$

supply, thus introducing the desublimation-limited regime with severe

$\text {CO}_2$

capture capacity loss (

$\eta _d$

). Moreover, large

$\psi$

enhances gas mobility while decreasing cold grain volume. A moderate porosity

$\psi _c$

is recommended for improving the

$\text {CO}_2$

capture performance. By analysing

$v_c$

and

$\eta _d$

, regime diagrams are proposed in

$\Delta T_s$

–

$Pe $

space to show distributions of convection-limited and desublimation-limited regimes, thus suggesting optimal conditions for efficient

$\text {CO}_2$

capture. This work develops a viable LB model to examine CCC under extensive operating conditions, contributing to facilitating its application.
Lagrangian-based simulation method using constrained Stokesian dynamics for particulate flows in microchannel
Authors: Lee Young Jin , Jin Howon , Kim Dae Yeon , Kang Seunghoon , Ahn Kyung Hyun
Published: August 2024

A simulation method has been developed to efficiently evaluate the motion of colloidal particles in a low-Reynolds-number confined microchannel flow using a Lagrangian-based approach. In this method, the background velocity within the channel, in the absence of suspended particles, is obtained from a fluid dynamics solver and is used to update the velocity at the particle centres using the Stokesian dynamics (SD) method, which incorporates multi-body hydrodynamic interactions. As a result, instead of computing the momentum of both the fluid and particles throughout the entire computational domain, the microscopic balance equation is solved only at the particle centres, increasing the computational efficiency. To accommodate complex boundary conditions within the SD framework, imaginary particles are placed on the channel walls, allowing the mobility relation to be reformulated to apply velocity constraints to immobilized wall particles. By employing this constrained SD approach, global mobility interactions that need to be computed at each time step are limited to the interior particles, resulting in a significant reduction in computational cost. The efficiency of this study is demonstrated through case studies on particulate flows in contraction and cross-flow microchannels. By using colloidal particles that incorporate Brownian motion and inter-particle attraction, observations through the entire stages of fouling dynamics are possible, from particle inflow to channel blockage. The fouling patterns observed in the simulations are consistent with experiments conducted under the same flow conditions. This study provides an efficient approach for analysing the effect of hydrodynamic interactions on particle dynamics in microfluidics and materials processing fields while allowing for predictions about structural changes over long-time scales, including complex phenomena such as clogging.
The impact of non-frozen turbulence on the modelling of the noise from serrated trailing edges
Authors: Tian H. , Lyu B.
Published: August 2024

Serrations are commonly employed to mitigate the turbulent boundary layer trailing-edge noise. However, significant discrepancies persist between model predictions and experimental observations. In this paper, we show that this results from the frozen turbulence assumption. A fully developed turbulent boundary layer over a flat plate is first simulated using the large-eddy simulation method, with the turbulence at the inlet generated using the digital filter method. The space–time correlations and spectral characteristics of wall pressure fluctuations are examined. The simulation results demonstrate that the coherence function decays in the streamwise direction, deviating from the constant value of unity assumed in the frozen turbulence assumption. By considering an exponential decay function, we relax the frozen turbulence assumption and develop a prediction model that accounts for the intrinsic non-frozen nature of turbulent boundary layers. To facilitate a direct comparison with frozen models, a correction coefficient is introduced to account for the influence of non-frozen turbulence. The comparison between the new and original models demonstrates that the new model predicts lower noise reductions, aligning more closely with the experimental observations. The physical mechanism underlying the overprediction of the noise model assuming frozen turbulence is discussed. The overprediction is due to the decoherence of the phase variation along the serrated trailing edge. Consequently, the ratio of the serration amplitude to the streamwise frequency-dependent correlation length is identified as a crucial parameter in determining the correct prediction of far-field noise.