bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of PD‐1/PD‐L1 immune checkpoint inhibitor in squamous and nonsquamous non‐small cell lung cancer: A systematic review and meta‐analysis
Authors: Dai Zhenjie , Chen Jing , Wang Yong
Published: July 2024

Background

The effects of programmed cell death protein 1/programmed cell death ligand 1 (PD‐1/PD‐L1) immune checkpoint inhibitors (ICIs) in patients with squamous and nonsquamous non‐small cell lung cancer (NSCLC) remain controversial. We conducted a meta‐analysis to summarize the existing evidence on this topic.

Methods

We searched PubMed, Medline, and Embase for studies published before December 1, 2022, comparing PD‐1/PD‐L1 ICIs with docetaxel in squamous and nonsquamous NSCLC patients in any language. The different hazard ratio (HR) values for overall survival (OS) and progression‐free survival (PFS) were calculated in this study.

Results

A total of seven studies were identified. In a summary analysis of all studies, the HR values of OS in patients with nonsquamous and squamous NSCLC were 0.73, 95% confidence interval (CI): 0.67–0.79 and 0.70, 95% CI: 0.62–0.79, respectively. In patients with PD‐L1 expression levels of 1% or higher, the HR values of OS in nonsquamous and squamous NSCLC patients were 0.60, 95% CI: 0.49–0.74 and 0.72, 95% CI: 0.54–0.96, respectively. The HR values of OS in nonsquamous and squamous NSCLC patients with PD‐L1 expression levels of 5% or higher were 0.46, 95% CI: 0.35–0.59 and 0.55, 95% CI: 0.39–0.79, respectively. In nonsquamous and squamous NSCLC patients with PD‐L1 expression levels of 10% or higher, the HR values of OS were 0.42, 95% CI: 0.32–0.54, and 0.53, 95% CI: 0.36–0.78, respectively.

Conclusion

The meta‐analysis demonstrated possible evidence that there was different efficacy of PD‐1/PD‐L1 ICIs on OS in squamous and nonsquamous NSCLC patients with different PD‐L1 expression levels. Subgroup analysis showed that there was a greater OS benefit in patients with nonsquamous NSCLC.
Time‐restricted eating affects human adipose tissue fat mobilization
Authors: Zambrano Carolina , González‐Alvarado Elena , Salmerón Diego , Ruiz‐Ojeda Francisco Javier , Luján Juan , Scheer Frank A. J. L. , Garaulet Marta
Published: July 2024

Objective

Time‐restricted eating (TRE), a dietary approach that confines food intake to specific time windows, has shown metabolic benefits. However, its impact on body weight loss remains inconclusive. The objective of this study was to investigate the influence of early TRE (eTRE) and delayed TRE (dTRE) on fat mobilization using human adipose tissue (AT) cultures.

Methods

Subcutaneous AT was collected from 21 participants with severe obesity. We assessed fat mobilization by measuring glycerol release in AT culture across four treatment conditions: control, eTRE, dTRE, and 24‐h fasting.

Results

TRE had a significant impact on lipolysis (glycerol release [mean (SD)] in micromoles per hour per gram: control, 0.05 [0.003]; eTRE, 0.10 [0.006]; dTRE, 0.08 [0.005]; and fasting, 0.17 [0.008]; p < 0.0001). Both eTRE and dTRE increased lipolysis compared with the control group, with eTRE showing higher glycerol mobilization than dTRE during the overall 24‐h time window, especially at the nighttime/habitual sleep episode (p < 0.0001). Further analysis of TRE based on fasting duration revealed that, independently of the time window, glycerol release increased with fasting duration (in micromoles per hour per gram: 8 h = 0.08 [0.001]; 12 h = 0.09 [0.008]; and 16 h of fasting = 0.12 [0.011]; p < 0.0001).

Conclusions

This study provides insights into the potential benefits of TRE on fat mobilization and may guide the design of future dietary strategies for weight management and metabolic health.

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Nerve growth factor inducible (VGF) is a secreted mediator for metastatic breast cancer tropism to the brain
Authors: Carvalho Rita , Santos Liliana , Conde Inês , Leitão Ricardo , Ferreira Hugo RS , Gomes Célia , Silva Ana Paula , Schmitt Fernando , Carvalho‐Maia Carina , Lobo João , Jerónimo Carmen , Paredes Joana , Ribeiro Ana Sofia
Published: July 2024

Brain metastases are one of the most serious clinical problems in breast cancer (BC) progression, associated with lower survival rates and a lack of effective therapies. Thus, to dissect the early stages of the brain metastatic process, we studied the impact of brain organotropic BC cells’ secretomes on the establishment of the brain pre‐metastatic niche (PMN). We found that BC cells with specific tropism to the brain caused significant blood–brain barrier (BBB) disruption, as well as microglial activation, in both in vitro and in vivo models. Further, we searched for a brain‐organotropic metastatic signature, as a promising source for the discovery of new biomarkers involved in brain metastatic progression. Of relevance, we identified VGF (nerve growth factor inducible) as a key mediator in this process, also impacting the BBB and microglial functions both in vitro and in vivo. In a series of human breast tumors, VGF was found to be expressed in both cancer cells and the adjacent stroma. Importantly, VGF‐positive tumors showed a significantly worse prognosis and were associated with HER2 (human epidermal growth factor receptor 2) overexpression and triple‐negative molecular signatures. Further clinical validation in primary tumors from metastatic BC cases showed a significant association between VGF and the brain metastatic location, clearly and significantly impacting on the prognosis of BC patients with brain metastasis. In conclusion, our study reveals a unique secretome signature for BC with a tropism for the brain, highlighting VGF as a crucial mediator in this process. Furthermore, its specific impact as a poor prognostic predictor for BC patients with brain metastasis opens new avenues to target VGF to control the progression of brain metastatic disease. © 2024 The Pathological Society of Great Britain and Ireland.
Pan‐cancer evaluation of tumor‐infiltrating lymphocytes and programmed cell death protein ligand‐1 in metastatic biopsies and matched primary tumors
Authors: El Beaino Zakhia , Dupain Célia , Marret Grégoire , Paoletti Xavier , Fuhrmann Laëtitia , Martinat Charlotte , Allory Yves , Halladjian Maral , Bièche Ivan , Le Tourneau Christophe , Kamal Maud , Vincent‐Salomon Anne
Published: July 2024

Tumor immunological characterization includes evaluation of tumor‐infiltrating lymphocytes (TILs) and programmed cell death protein ligand‐1 (PD‐L1) expression. This study investigated TIL distribution, its prognostic value, and PD‐L1 expression in metastatic and matched primary tumors (PTs). Specimens from 550 pan‐cancer patients of the SHIVA01 trial (NCT01771458) with available metastatic biopsy and 111 matched PTs were evaluated for TILs and PD‐L1. Combined positive score (CPS), tumor proportion score (TPS), and immune cell (IC) score were determined. TILs and PD‐L1 were assessed according to PT organ of origin, histological subtype, and metastatic biopsy site. We found that TIL distribution in metastases did not vary according to PT organ of origin, histological subtype, or metastatic biopsy site, with a median of 10% (range: 0–70). TILs were decreased in metastases compared to PT (20% [5–60] versus 10% [0–40], p < 0.0001). CPS varied according to histological subtype (p = 0.02) and biopsy site (p < 0.02). TPS varied according to PT organ of origin (p = 0.003), histological subtype (p = 0.0004), and metastatic biopsy site (p = 0.00004). TPS was higher in metastases than in PT (p < 0.0001). TILs in metastases did not correlate with overall survival. In conclusion, metastases harbored fewer TILs than matched PT, regardless of PT organ of origin, histological subtype, and metastatic biopsy site. PD‐L1 expression increased with disease progression. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
TRKing down drug resistance in NTRK fusion‐positive cancers†
Authors: Parrish Abigail G , Szulzewsky Frank
Published: July 2024

In a recent issue of The Journal of Pathology, Chen and colleagues established novel patient‐derived ex vivo models of NTRK fusion‐positive soft tissue sarcoma to characterize resistance mechanisms against targeted therapy with tyrosine kinase inhibitors. Prolonged exposure to escalating concentrations of the tyrosine kinase inhibitor, entrectinib, ultimately led to the occurrence of resistant clones that harbored an inactivating mutation in the NF2 gene, not previously described in this context, accompanied by increased PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling. Finally, an inhibitor screen identified, among others, MEK and mTOR inhibitors as potential combination agents. © 2024 The Pathological Society of Great Britain and Ireland.
Pediatric asthma knowledge: Insights from a Portuguese central hospital study
Authors: Coelho Cristina , Pinho Joana , Pinto Mariana , Pedrosa Cláudia , Costa Herculano , Romariz Jorge , Carvalho Maria I.
Published: July 2024

Background

Asthma is a common chronic condition in children, with parental and child health literacy affecting health outcomes and asthma control. This study examined pediatric asthma knowledge at a Portuguese central hospital and its determinants.

Methods

We conducted a comparative cross‐sectional study, applying the Asthma Knowledge Questionnaire (QCSA), answered by adolescents and/or caregivers. The sample was categorized into two groups based on the presence or absence of respiratory conditions, such as asthma or recurrent wheezing, in children. Those with such conditions (Group A) were further divided into two subgroups: those receiving general pediatric care (Group A2) and those receiving specialized care, followed in pulmonology or allergology consultations (Group A1).

Results

The study involved 154 participants, predominantly female (74%) with an average age of 31.2 years ( ± 13.4). The average QCSA score was 14.8 ( ± 3.2), and Group A exhibited a statistically higher score, 15.5 points ±3.2 versus Group B, 14.2 points ± 3.2, p = .034. Group A1 achieved significantly better scores (16 points: range 4–21) than Group A2 (14 points: range 9–21) (p = .029). Scores were correlated positively with the duration of specialized follow‐up (ρ = .326; p = .027). Asthma knowledge was correlated with the level of education (r = .468; p < .001). The number of wheezing episodes (r = −.466; p < .001) within the past year were associated to QCSA scores.

Conclusion

In summary, the presence of respiratory condition, the follow‐up in specialized appointments and higher levels of education were associated with greater asthma knowledge.
Students' well‐being and school climate: A bibliometric analysis
Authors: Obeidat Bilal Fayiz , Haimed Saber , AlKhaza'leh Mohammad Salman
Published: July 2024

Schools are significant settings for the development of young people, yet few studies have investigated the multiple facets of school climate and students' well‐being. This research aims to map the literature production in the two intertwined concepts: students' well‐being, and school climate. The study applied bibliometric analysis to map the research status of school climate and students' well‐being using metadata extracted from over a period of 33 years. The analysis presents a detailed overview of school climate and students’ well‐being in terms of scientific production, citations, authorship, countries' production, and institutions' outputs. Results highlighted the recent developmental trends of publications on students' well‐being and school climate and outlined the precursors for triggering this combination. With reference to students' overall well‐being, analysing the results shows that research on school climate increased markedly in different parts of the world. However, when compared to Arab countries, rare studies were conducted.

Context and implications

Rationale: Mapping the exponentially growing research on school climate and student well‐being can guide stakeholders in understanding research, gaps and priorities. Using bibliometric analysis here is necessary to evaluate the growing literature.

Why the new findings matter: By elucidating exponential output, conceptual evolution and geographical imbalances, the analysis reveals a maturing yet decentralised field awaiting integration and high‐impact studies to inspire real‐world progress.

Implications for practitioners, policy makers, and researchers: Findings guide strategic investments in rigorous intervention trials, student‐centred methodologies, cross‐national collaborative networks, and pathways translating evidence to school policies/practices. This analysis equips stakeholders to cultivate coordinated, culturally responsive research ecosystems providing actionable insights to create nurturing climates enabling all students to thrive.
Pregaming normalizes culture of drinking, drug use
Authors: Sutton Halley
Published: July 2024

Pregaming, tailgating, or other party activities revolving around alcohol before athletics events on college campuses can have dire and long‐lasting effects on students, according to a recent study from Texas A&M University. The study found that those who engaged in pregaming and tailgating were at higher risks for engaging in alcohol and substance abuse, as well as for engaging in other risky behavior with potentially harmful consequences. The study was published in Substance Use and Misuse, a journal published by Taylor & Francis.
Gelatin Assisted Cerium–Copper Sulfide Nanoparticles as Efficient Catalysts for the Photocatalytic Degradation of Malachite Green Oxalate Dye Under UV‐A Light
Authors: Meena Kannaiyan , Kumaravel Sakthivel , Durai Mani , Hasan Imran , Gunamalai Lavanya , Ahn Young‐Ho , Shanthi Manohar
Published: July 2024

Chemical, petroleum, and dyeing industries generate a wide variety of highly toxic organic wastes. The discharge of this wastewater into the river without treatment will spoil the entire aquatic system. The photocatalytic degradation of dyes/toxic chemicals is considered a favorable technology for industrial wastewater treatment. For this purpose, we have prepared an efficient nanocomposite material. The Gelatin assisted Cerium loaded CuS (Ge−Ce−CuS) nanocomposite was successfully synthesized by a simple hydrothermal method and characterized by BET, UV‐DRS, and PL measurements. The BET surface area of Ge−Ce−CuS (88.6 m2 g−1) is higher than bare CuS (66.0 m2 g‐1). DRS Confirms that the photo‐absorption of Ge−Ce−CuS nanocomposite significantly increases from the 570 nm range to the whole visible region. PL measurements confirm that the CuS loading suppresses electron‐hole recombination of Ge−Ce−CuS. The photocatalytic activity of Ge−Ce−CuS was investigated for the degradation of malachite green oxalate dye (MGO) in an aqueous solution using UV light. The influence of operational parameters such as the amount of photocatalyst, dye concentration, and initial pH on the photo mineralization of MGO dye has been analyzed and discussed. Slightly basic pH enhances the degradation. The mineralization of MGO dye has been confirmed by COD measurements. The intermediates formed during degradations were analyzed by GC‐MS, and a suitable degradation pathway was proposed. The catalyst is found to be reusable. The mechanism of degradation of MGO dye by Ge−Ce−CuS is also proposed.
From Alkenes to Cyclic Carbonates with a Stable Iron‐Cross‐Bridged Cyclam Catalyst
Authors: Yeamin Md Bin , Annunziata Alfonso , Ruffo Francesco , Masdeu‐Bultó Anna M.
Published: July 2024

A stable iron(III) complex with the cross‐bridged cyclam 4,11‐dimethyl‐1,4,8,11‐tetraazabicyclo[6.6.2]hexadecane catalyzes the epoxidation of aromatic alkenes and the fixation of CO2 into cyclic carbonates. Best results were obtained for styrene conversion to styrene carbonate.
Surface‐Modified Mesoporous V2‐xSb2xO5‐δ Ceramics for Improving the Electrostatic Chemisorption of Methylene Blue
Authors: Sabna Melethil , Safna K. , C P Sona , Jayaram Peediyekkal
Published: July 2024

Herein, mesoporous V2‐xSb2xO5‐δ (Sb−V−O) compounds, encompassing a compositional range of x varying between, 0.05≤x≤0.08, with orthorhombic Pmmn space group symmetry, are synthesized by high‐temperature solid‐state reaction method. Scanning electron microscopy indicated the formation of microscale rods and flakes and EDS spectra affirmed the stoichiometric precision of their composition adhering to the formulated chemical formula. Nitrogen adsorption isotherms exhibited the distinctive type IV pattern, accompanied by an H3 hysteresis loop, signifying the formation of mesoporous micro rods and flakes. Brunauer‐Emmett‐Teller measurements demonstrated an augmented surface area, ranging from 16.67–28.74 m2/g, mirroring the effect of the increase in the concentration of Sb cations. The study demonstrated complete Methylene Blue dye removal within a brief 90 minute period, highlighting its efficacy in water remediation. The adsorption kinetics was aptly described by the pseudo‐second‐order model which exhibited a high degree of fit (R2=0.99). Freundlich adsorption isotherm was used to describe the multilayer adsorption of MB dye on the Sb−V−O surface indicating an exponential increase in adsorption active sites. Enhanced cationic MB dye adsorption on negative Sb−V−O surface is attributed to the electrostatic chemisorption by the interaction of NMe2+ on the negative surface modified Sb−V−O compounds.
Preparation and Properties of Multiple Dynamic Crosslinked Poly(siloxane‐urethane)
Authors: Liu Yujie , Zhang Xiaoyu , Yan Xixian , Zhang Chi , Li Ning , Zeng Fanglei , Jiang Shengling , Ding Jianning
Published: July 2024

Self‐healing poly(siloxane‐urethane) materials have garnered significant interest among researchers, owing to their superior resistance to high and low temperatures, solvents, corrosion, and biocompatibility. Nevertheless, most existing self‐healing poly(siloxane‐urethane) materials face challenges, including limited repair conditions and the challenge of balancing mechanical properties with repair efficiency. In this research, we introduced hydrogen bonds, metal coordination bonds, π–π bonds, and reversible ring structures into the poly(siloxane‐urethane) system through molecular chain structure design, successfully developing a multi‐dynamic cross‐linked poly(siloxane‐urethane) (PU‐Si), a development rarely reported in prior studies. This study examines the impact of varying amounts of hydroxyl‐terminated polydimethylsiloxane (PDMS‐OH) on the properties of PU‐Si. The results indicate that PU‐Si, regardless of the amount of PDMS‐OH added, can self‐healing under conditions of heating at 60 °C, and exposure to ultraviolet and infrared radiation. Specifically, when the PDMS‐OH addition reaches 1.0 g, the material exhibits superior mechanical properties and self‐healing efficiency, achieving a mechanical strength of 9.68 MPa and a self‐healing efficiency of 86.6 %. This material shows significant application potential in areas such as electronic skins, flexible sensors, and brain‐computer interfaces.
Structural Disorder by Octahedral Tilting in Inorganic Halide Perovskites: New Insight with Bayesian Optimization
Authors: Li Jingrui , Pan Fang , Zhang Guo‐Xu , Liu Zenghui , Dong Hua , Wang Dawei , Jiang Zhuangde , Ren Wei , Ye Zuo‐Guang , Todorović Milica , Rinke Patrick
Published: July 2024

Structural disorder is common in metal‐halide perovskites and important for understanding the functional properties of these materials. First‐principles methods can address structure variation on the atomistic scale, but they are often limited by the lack of structure‐sampling schemes required to characterize the disorder. Herein, structural disorder in the benchmark inorganic halide perovskites CsPbI3 and CsPbBr3 is computationally studied in terms of the three octahedral‐tilting angles. The subsequent variations in energetics and properties are described by 3D potential‐energy surfaces (PESs) and property landscapes, delivered by Bayesian optimization as implemented in the Bayesian optimization structure search code sampling density functional theory (DFT) calculations. The rapid convergence of the PES with about 200 DFT data points in 3D searches demonstrates the power of active learning and strategic sampling with Bayesian optimization. Further analysis indicates that disorder grows with increasing temperature and reveals that the material bandgap at finite temperatures is a statistical mean over disordered structures.
Defining and characterizing the operational context for human systems integration
Authors: Disdier Alexandre , Masson Dimitri , Jankovic Marija , Boy Guy‐André
Published: July 2024

Many efforts from multiple academic and industrial disciplines have studied the notion of context. The systems engineering and human systems integration fields, however, lack a generalized definition and characterization of context, in particular the operational context of complex sociotechnical systems. This paper reviews context definitions and builds a generalized definition of the operational context of complex sociotechnical systems. The objective is then to identify and extract context properties which are often implicit in the literature and do not necessarily appear in the definitions. However, eliciting them is helpful for understanding what context is made of, how it relates to complex sociotechnical systems comprising human and non‐human agents, and how an early understanding of the operational context can prove valuable to designing efficient and robust systems. Our analysis is followed by an example of how our definition and derived properties apply to the case study of the design of a remote and virtual air traffic control center.
Photoswitchable Surfactants–Are there Alternatives to Azobenzene‐Based Systems?
Authors: Bekir Marek , Gurke Johannes , Reifarth Martin
Published: July 2024

Owing to their property to alter their surface‐activity upon the irradiation with light, photoswitchable surfactants have gained tremendous interest in colloidal science. Their mere addition to a colloidal system allows, e. g., to obtain control over polyelectrolytes, micro‐ and nanoscale particles or emulsions. Most literature examples focus on azobenzene‐based, or related, systems, which employ a photoisomerization reaction for switching. Other structures, such as spiropyrans, play a subordinate role, although they have gained increasing attention over the past few years. In this perspective article, we want to provide an overview about existing systems of photoswitchable surfactants. We address the issue that alternative photoswitches are given less attention, and what benefits surfactants could possess that are based on said switchable units. With our contribution, we want to broaden the view on stimuli‐responsive surfactants – and to provide a guideline for the design of novel structures.
Polydactyl canine case: Exploring possible linkage between anomalies, secondary infertility and SHH/ALX4 mutations
Authors: Ogundipe Tolulope G. , Ameh Matthew P. , Bamikole Jeremiah O.
Published: July 2024

This case report details an unusual manifestation of polydactyly in a litter of purebred Caucasian puppies, where the dam exhibited polydactyl traits while the sire is suspected to have an incomplete penetrance of the trait. All littermates, except one, manifest severe postnatal mortality and displayed polydactyl at birth. Out of a litter of six puppies, only Luna survived, resulting in a mortality rate of approximately 83.33%. Luna, the surviving pup, presented with anomalies including polydactyly on both pelvic limbs, short limb development, double row teeth, thoracolumbar tenderness, anaemia and babesiosis. Furthermore, the dam also exhibited secondary infertility, which prompted a literature review on probable genetic influences. However, we suspect SHH and ALX4 mutations due to their possible interference with sonic hedgehog and Wnt/beta‐catenin signalling pathways as being causal for the observed clinical signs, particularly the role of Wnt/beta‐catenin signalling, which is crucial for reproductive organ development.
COVID-19, Anti-Asian Racism, and U.S.-China Relations
Authors: Kim D.G.
Published: July 2024

What role do race and racism play in shaping mutual perceptions and foreign policy views between the United States and China today? In this chapter, I analyze cross-national public opinion surveys and foreign policy discourses to examine the link between COVID-19, anti-Asian racism, and policy views and discuss implications of this behavioral feedback loop for contemporary Sino-American relations. I first find with American public opinion during the pandemic how heightened concern about the virus significantly correlated with both anti-Asian sentiment and support for hawkish China policy. I then examine the far-reaching effects of the growing visibility and politicization of anti-Asian racism in America on Chinese foreign policy discourses and mass opinion, highlighting the growing political salience of racialized resentment, identity, and worldviews in China. Based on the findings, I suggest that American and Chinese leaders should refrain from using strategic appeals to the sense of identity difference and exceptionalism that bring the risk of encouraging domestic racism, emboldening the other country’s own exclusionary identity and worldview, and fueling U.S.-China security dilemmas.
Introduction
Authors: Salehin Mohammad Musfequs
Published: July 2024

Gendered vulnerabilities and violence are intrinsically linked with forced migration. This chapter introduces the book’s main aim, which is to examine the gendered dynamics of violence experienced by the Rohingya people, first during the conflict in the Rakhine State of Myanmar, then after their forced migration to Bangladesh. It provides a brief overview of the context and the imperative to investigate the gendered dimension of Rohingya forced migration, emphasising the nature and extent of gendered vulnerabilities and violence, both in the country of origin and in the country of destination, as a continuous process. Additionally, it delineates the methodology employed in the research conducted for this book.
Gender, Violence, and Vulnerabilities in Forced Migration: A Multi-dimensional Approach
Authors: Salehin Mohammad Musfequs
Published: July 2024

Violence is intertwined with a gendered logic, encompassing physical, sexual, structural, cultural, and symbolic dimensions. However, this association becomes even more complex within the context of refugees and forced migration. This chapter delves into the conceptual and theoretical framework surrounding multidimensional gendered vulnerabilities and violence in the context of forced migration. It explores key concepts integral to my discussion, including Galtung’s conceptualisations of violence (direct, structural, and cultural violence), Bourdieu’s theory of symbolic violence, and sexual and gender-based violence (SGBV) and vulnerabilities. Additionally, this chapter examines intersectionality and the continuum of violence framework to deepen our understanding of gendered vulnerabilities and violence in forced migration contexts.
Sequence-based Learning
Authors: Loeffler Christoffer , Ott Felix , Ott Jonathan , Oppelt Maximilian P. , Feigl Tobias
Published: July 2024

Learning from time series data is an essential component in the AI landscape given the ubiquitous time-dependent data in real-world applications. To motivate the necessity of learning from time series data, we first introduce different applications, data sources, and properties. These can be as diverse as irregular and (non-)continuous time series data as well as streaming and spatio-temporal data. To introduce the mechanics of learning from time series data, we elaborate on the most renowned convolutional, recurrent and transformer architectures for learning from time series. Then, we discuss essential characteristics of learning with time series. Therefore, we explain deep metric learning, which learns feature representations that capture the similarity between time series data.We further describe time series similarity learning to extract representations that allow comparison between sequences of spatio-temporal data. In addition, we discuss the interpretability of learning methods on time series data that target safety, non-discrimination, and fairness.
Learning from Experience
Authors: Mutschler Christopher , Kontes Georgios , Rietsch Sebastian
Published: July 2024

Reinforcement Learning (RL) is one of the branches of Machine Learning (ML) that aims to learn from the interaction with an environment. In contrast to approaches such as supervised or unsupervised learning, where data samples usually are assigned to a ground truth label (supervised learning) or where they follow some stationary distribution (unsupervised learning), in RL, the agent is learning in direct interaction with the environment. This also defines what data is being collected as a result of which actions are being executed. The agent is hence learning from experience. While more traditionally, RL was focused purely on continuously arriving data, lately also approaches that resort to a given data pool of past environment interactions have gained more and more interest. This chapter covers the basics of RL and discusses the latest research in interactive environments, learning with available data or knowledge, and challenges that arise from the actual deployment of agents to the real world.
Acquisition of Semantics for Machine-Learning and Deep-Learning based Applications
Authors: Wittenberg Thomas , Lang Thomas , Eixelberger Thomas , Gruber Roland
Published: July 2024

For the development, training, and validation of machine learning (ML) and deep learning (DL) based methods, such as, e.g., image analysis, prediction of critical events, extraction or reconstruction of information from disrupted data streams, searching similarities in data collections, or planning of procedures, a lot of data is needed. Additionally to this data (images, bio-signals, vital-signs, text records, machine states, trajectories, antenna data, ...) adequate supplementary information about the meaning encoded in the data is required. Only with this additional information – the meaning or knowledge – a tight relation between the raw data and the human-understandable concepts – the semantics – from the real world can be established. Nevertheless, as the amount of data needed to develop robust ML or DL methods is strongly increasing, the assessment and acquisition of the related knowledge becomes more and more challenging. Within this chapter, an overview of concepts of knowledge acquisition applied to the different examples of applications is described and evaluated. Six main groups of knowledge acquisition related to AI-based technologies have been identified, namely (1) manual annotation methods, (2) data augmentation, (3) generative networks or simulation techniques, (4) synchronized sensors, (5)Active Learning approaches, and (6) explicit knowledge modeling using semantic networks.
Das Mathematische Forschungsinstitut Oberwolfach: Vom „Reichsinstitut für Mathematik“ zur internationalen „sozialen Forschungsinfrastruktur“ (1944–1960er Jahre)
Authors: Remmert Volker
Published: July 2024

Das Mathematische Forschungsinstitut Oberwolfach (MFO) ist seit 2005 Mitglied der Leibniz-Gemeinschaft und genießt international höchstes Ansehen. Es wurde im Herbst 1944 gegründet als „Reichsinstitut für Mathematik“, dessen Aufgaben sehr umfassend waren, aber völlig im zeitgenössischen institutionellen Rahmen blieben. In den 1950er und 1960er Jahren entwickelte das MFO sich zu einem Tagungszentrum, das zunehmend auch international ausstrahlte, d. h. hin zu einer „sozialen Forschungsinfrastruktur“ wie sie in der deutschen Forschungslandschaft der 1950er und 1960er Jahre völlig neu war. Dieser Wandel der institutionellen Identität des MFO zwischen 1944 und dem Beginn der 1960er Jahre lässt sich an den neuen Organisationsformen des Forschungsbetriebs am MFO ablesen, d. h. insbesondere an der Entwicklung und Bedeutung des wissenschaftlichen Programms des MFO und der verwendeten Forschungsinstrumente. Die neuen Formen des Forschungsbetriebs gingen einher mit einer komplexen Finanzierungsproblematik: einerseits bedingt durch die wegfallende Finanzierung bei Kriegsende, andererseits dadurch befördert, dass das MFO keinen kanonischen Platz in der gängigen Praxis der Forschungsförderung hatte. Im Fokus des Beitrags stehen die Strategien, die bis Mitte der 1960er Jahre entwickelt wurden, um die materielle Existenz des MFO zu sichern (frz. Militärregierung, Landesministerien, Bundesministerien, DFG und MPG, Thyssen und Volkswagen Stiftung). Im Jahr 1963 war die institutionelle Sicherung des MFO schließlich weitgehend abgeschlossen.
Modelling green knowledge production and environmental policies with semiparametric panel data regression models
Authors: Musolesi Antonio , Golinelli Davide , Mazzanti Massimiliano
Published: July 2024

This paper introduces a novel semiparametric econometric framework for policy evaluation and estimates a green knowledge production function for a large, 30-year panel dataset of high-income countries. Due to the substantial uncertainty in the data-generating process and the potential presence of nonlinearities and latent common factors, the paper explores semiparametric panel specifications that go beyond interactive fixed effects fully parametric models. The findings suggest that (i) the semiparametric additive specification with individual time trends is the preferred model, (ii) threshold effects and nonlinearities are salient features of the data that parametric specifications fail to capture, and (iii) the impact of environmental policy is noteworthy and exhibits clear heterogeneity when modelled as a nonparametric function of specific knowledge inputs. The evidence reveals a significant nonlinear policy inducement effect stemming from R&D investments.
An approximation algorithm for multiobjective mixed-integer convex optimization
Authors: Lammel Ina , Küfer Karl-Heinz , Süss Philipp
Published: July 2024

In this article we introduce an algorithm that approximates the nondominated sets of multiobjective mixed-integer convex optimization problems. The algorithm constructs an inner and outer approximation of the front exploiting the convexity of the patches for problems with an arbitrary number of criteria. In the algorithm, the problem is decomposed into patches, which are multiobjective convex problems, by fixing the integer assignments. The patch problems are solved using (simplicial) Sandwiching. We identify parts of patches that are dominated by other patches and ensure that these patch parts are not refined further. We prove that the algorithm converges and show a bound on the reduction of the approximation error in the course of the algorithm. We illustrate the behaviour of our algorithm using some numerical examples and compare its performance to an algorithm from literature.
Chronobiological variables predict non-response to serotonin and noradrenaline reuptake inhibitors in fibromyalgia: a cross-sectional study
Authors: Krupa Anna J. , Chrobak Adrian A. , Sołtys Zbigniew , Korkosz Mariusz , Nowakowski Jarosław , Dudek Dominika , Siwek Marcin
Published: July 2024

Available data shows associations between chronotype, circadian rhythms, sleep quality and fibromyalgia (FM) presentation. However, no studies have explored links between the chronobiological variables and effectiveness of pharmacotherapy. We aimed to assess the chronotypes, circadian rhythms, sleep-wake cycle and sleep quality in FM and their links to treatment response to serotonin and noradrenalin reuptake inhibitors (SNRI). 60 FM patients: 30 responsive to SNRI (FM T[+]), 30 non-responsive to SNRI (FM T[-]) and 30 healthy controls participated. Subjects were assessed by physician and with questionnaire tools: Composite Scale of Morningness, Biological Rhythms Interview of Assessment in Neuropsychiatry, Sleep-Wake Pattern Assessment Questionnaire, Pittsburgh Sleep Quality Index and Fibromyalgia Impact Questionnaire. ANOVA analysis and simple logistic regressions were used to examine the relationships between chronological variables and response to SNRI. FM T[-] vs. FM T[+] presented lower morning affect (11.50[95%CI 9.96-13.04] vs. 14.00[95%CI 12.42-15.57];p=0.04), anytime wakeability (2.27[95%CI 1.4-3.13] vs. 4.03[95%CI 2.99-5.08];p=0.013) worse overall (11.40[95%CI 9.92-12.88] vs. 7.97[95%CI 6.75-9.19];p=0.002) and subjective (1.70[95%CI 1.30-2.01] vs. 1.17[95%CI 0.94-1.39];p=0.008) sleep quality, higher circadian rhythm disruptions (55.47[95%CI 52.32-58.62] vs. 44.97[95%CI 41.31-48.62];p<0.001), sleep disturbances (1.63[95%CI 1.38-1.68] vs. 1.30[95%CI 1.1-1.5];p=0.04), sleeping-medication use (1.80[95%CI 1.27-2.32] vs. 0.70[95%CI 0.28-1.12];p=0.003). Levels of morningness (AIC=82.91,OR=0.93,p=0.05), morning affect (AIC=81.901,OR=0.86,p=0.03) diurnal dysrhythmia (AIC=69.566,OR=1.14,p<0.001), anytime wakeability (AIC=80.307,OR=0.76,p=0.015), overall sleep quality (AIC=74.665, OR=1.31,p=0.002) subjective sleep quality (AIC=79.353, OR=2.832,p=0.01) and disturbances (AIC=82.669,OR=2.54,p=0.043), sleep medication use (AIC=77.017, OR=1.9,p=0.003) and daytime disfunction (AIC=82.908, OR=1.971,p=0.049) were predictors of non-response to SNRI. Chronobiological variables vary between FM T[+] and FM T[-] and are predictors of non-response to SNRI.
Diverse and ecologically unique mesophotic coral ecosystems in the central Indian Ocean
Authors: Diaz C. , Howell K. L. , Hosegood P. , Bolton A. , Foster N. L.
Published: July 2024

Research on Mesophotic Coral Ecosystems (MCEs; 30–150 m) has grown exponentially in the last few decades, highlighting their rich diversity and extensive distribution. However, they are still largely underexplored compared to shallow-water coral reefs and frequently remain under-protected and under-represented in marine spatial planning. One reason for the imbalance between the high ecological value of MCEs and the limited levels of protection may be that baseline data on MCEs are largely missing to date, yet are crucial to provide evidence-based information for management actions. Here, we present data on the alpha and beta diversity of the benthic communities within MCEs in the Chagos Archipelago, Indian Ocean. Using imagery collected from Remotely Operated Vehicle surveys, benthic invertebrate megafauna were surveyed along the entire depth gradient from shallow to lower mesophotic depths (15–160 m). The diversity of the benthic communities decreased with increasing depth, from shallow water to the lower mesophotic zone. Nevertheless, the deepest parts of MCEs in the Archipelago displayed higher species richness values than several other shallow subtropical regions. In addition, the benthic communities showed high dissimilarity along the depth gradient, indicating that the key driver of community composition change with depth is species turnover (species replacement), revealing the uniqueness of MCEs. This study presents novel findings on MCEs in the central Indian Ocean, demonstrating that they host a high and unique benthic diversity, and highlighting the need to protect these ecosystems to preserve the overall biodiversity of coral reefs.
Comparison of outcomes in small bowel surgery for Crohn’s disease: a retrospective NSQIP review
Authors: Aras Oguz AZ. , Patel Apar S. , Satchell Emma K. , Serniak Nicholas J. , Byrne Raphael M. , Cagir Burt
Published: July 2024

Introduction

Despite advances in medical therapy, approximately 33% of Crohn’s disease (CD) patients will need surgery within 5 years after initial diagnosis. Several surgical approaches to CD have been proposed including small bowel resection, strictureplasty, and combined surgery with resection plus strictureplasty. Here, we utilize the American College of Surgeons (ACS) national surgical quality registry (NSQIP) to perform a comprehensive analysis of 30-day outcomes between these three surgical approaches for CD.

Methods

The authors queried the ACS-NSQIP database between 2015 and 2020 for all patients undergoing open or laparoscopic resection of small bowel or strictureplasty for CD using CPT and IC-CM 10. Outcomes of interest included length of stay, discharge disposition, wound complications, 30-day related readmission, and reoperation.

Results

A total of 2578 patients were identified; 87% of patients underwent small bowel resection, 5% resection with strictureplasty, and 8% strictureplasty alone. Resection plus strictureplasty (combined surgery) was associated with the longest operative time (p = 0.002). Patients undergoing small bowel resection had the longest length of hospital stay (p = 0.030) and the highest incidence of superficial/deep wound infection (44%, p = 0.003) as well as the highest incidence of sepsis (3.5%, p = 0.03). Small bowel resection was found to be associated with higher odds of wound complication compared to combined surgery (OR 2.09, p = 0.024) and strictureplasty (1.9, p = 0.005).

Conclusion

Our study shows that various surgical approaches for CD are associated with comparable outcomes in 30-day related reoperation and readmission, or disposition following surgery between all three surgical approaches. However, small bowel resection displayed higher odds of developing post-operative wound complications.
Regulatory T cells inhibit FoxP3 to increase the population of tumor initiating cells in hepatocellular carcinoma
Authors: Liu Chang , Tu Yi-jun , Cai Hong-Yang , Pan Yan-yan , Wu Yuan-yuan , Zhang Li
Published: July 2024

Purpose

Tumor initiating cells (TICs) or cancer stem cells (CSCs) are considered to be the main culprit of hepatocellular carcinoma (HCC) initiation and progression, nevertheless the mechanism by which tumor microenvironment maintains the HCC ‘stemness’ is not fully understood. This study aims to investigate the effect of regulatory T cells (Tregs) on the TICs characteristics of HCC.

Methods

Immunocytochemistry, flow cytometry, real-time PCR, western blot, in vitro sphere-formation, and in vivo tumorigenesis assay were used to detect HCC ‘stemness’. Additionally, after forced expression or inhibition of FoxP3, β-catenin expression and HCC ‘stemness’ were investigated.

Results

Tregs enhanced the ‘stemness’ of HCC cells by upregulating TIC-related markers CD133, Oct3/4, Sox2, c-Myc, Klf4, Nanog, CD13, EpCAM, and inducting epithelial to mesenchymal transition (EMT), increasing TICs ratio, as well as promoting tumorigenic ability. Moreover, β-catenin and c-Myc were upregulated in HCC cells after co-cultured with Tregs. HCC ‘stemness’ was inhibited after treatment with Wnt/β-catenin pathway inhibitor. Furthermore, forced expression of FoxP3 resulted in increased GSK3β, decreased β-catenin and TIC ratio in HCC. In contrast, FoxP3 interference reduced GSK3β, enhanced β-catenin and TIC ratio of HCC.

Conclusion

This study, for the first time, demonstrated that Tregs increased the population of TICs in HCC by inhibiting FoxP3 as well as promoting β-catenin expression.
„Diagnostics beyond bacteria“ – Wundabstriche zur Analyse biomolekularer Krankheitsmuster in chronischen Wunden
Authors: Rembe Julian-Dario , Garabet Waseem , Lackmann Jan-Wilm , Augustin Matthias , Dissemond Joachim , Scharf Sebastian Alexander , Rommerskirchen Anna , Wienemann Tobias , Ibing Wiebke , Schelzig Hubert , Stuermer Ewa K.
Published: July 2024

Hintergrund

Patientenindividuelle Therapieansätze sind in der Versorgung von Menschen mit chronischen Wunden wichtig. Die Heterogenität zugrunde liegender Krankheitsprofile ebenso wie die Diversität des Wundmilieus erschweren generalisierbare Ansätze. Während molekulare Analyseverfahren wie Hochdurchsatzverfahren (OMICS) zunehmend verbreiteter und besser verfügbar sind, hat die Analyse von objektiven biomolekularen Krankheitsmustern weitestgehend keinen Eingang in die alltägliche Diagnostik und Therapiesteuerung gefunden.

Fragestellung

Die Nutzung von Wundabstrichen für die Analyse von Biomarkern und Krankheitsmustern in kutanen Wunden wurde evaluiert.

Material und Methoden

Es erfolgte die Analyse einer Probekohorte aus dem multizentrischen „Wound-BIOME“-Projekt. Das Projekt zielt auf die Erforschung des lokalen Wundmilieus verschiedener Entitäten, Heilungstendenzen und Regenerationsstadien auf biomolekularer Ebene ab. Hierzu wurde ein alltagstaugliches Protokoll zur Probengewinnung und -handhabung entwickelt und erprobt. Des Weiteren wurden Machbarkeitsanalysen für Multiplex-Immunoassays, Proteomics und Metagenomanalysen (Mikrobiom) durchgeführt.

Ergebnisse

Trotz Heterogenität zwischen den Proben konnten ausreichende Mengen Protein und mikrobielle DNA mit adäquater Qualität extrahiert werden, um biomolekulare Muster zu analysieren. Erste Analysen von deskriptiven Proteinsignaturen und mikrobiellen Taxonomie zeigen vielversprechende Ansätze für zukünftige individuelle, objektive Diagnostik und gezielte therapeutische Interventionen.

Schlussfolgerung

Standardisierte Wundabstriche zeigen sich insgesamt gut geeignet, um Probenmaterial für die Analyse des komplexen Wundmilieus mittels verschiedener Hochdurchsatzverfahren zu gewinnen.
Peer victimization in early adolescence and maladjustment in adulthood
Authors: Kretschmer Tina , van der Ploeg Rozemarijn , Kaufman Tessa
Published: July 2024

Studies report different effect sizes for associations between peer victimization and later maladjustment. A possible origin of this heterogeneity is the length of the interval between victimization and maladjustment assessments. Effect sizes might also vary as a function of reporter. Longitudinal data from TRAILS, a study of adolescents followed from age 11 to 29 (baseline n = 2229) were used to test whether peer victimization assessed from adolescents themselves, their parents, teachers, and peers predicted internalizing symptoms, thought problems, and somatic complaints at six follow-ups with a temporal distance of up to 19 years. Neither self- nor peer-reported victimization predicted later maladjustment. In contrast, parent-reported victimization stably predicted adult maladjustment. Teacher-reported victimization also predicted maladjustment but associations were weaker and largely non-significant when parent reports were accounted for simultaneously. Parent-reported peer victimization has traditionally played a minor role in bullying research as parents are usually not present when victimization occurs. The results of this study however suggest that parents should be listened to when talking about their offspring being victimized.