bluuebunny/crossref_metadata_2025 huggingface dataset:
54 Identifying Geographic Clusters of H. pylori Associated Metastatic Early-Onset Gastric Cancer: A case-control study in Los Angeles
Authors: Bhutada Jessica Sheth , Iqbal Syma , Cockburn Myles , Halbert Chanita Hughes , Freyer David
Published: April 2024

OBJECTIVES/GOALS: More young adults (age <50 years) are diagnosed with metastatic gastric cancer (mGC) every year. We will evaluate the association between environmental risk factors (including historical racial residential segregation) clinical, pathologic, molecular features and H.pylori associated early-onset mGC (mE-GC). METHODS/STUDY POPULATION: This retrospective matched case-control study of patients (1:2 by diagnosis year) with mGC (early-onset [E-GC; <50 years]; vs older-onset [O-GC; >50 years]) from 2000-2022 from the Los Angeles Cancer Surveillance Program (LA-CSP) will be enriched by a chart-abstracted cohort from USC Norris Comprehensive Cancer (NCCC). This annotated database captures sociodemographic, medical, and pathologic features of patients treated for mGC at NCCC. It will link to LA-CSP data exploring neighborhood features (obesity rate, poverty, insurance, access to care, ethnic enclave, historical segregation, etc.) of cases and controls to identify, characterize, and compare geographic “hotspot” neighborhoods of mE-GC. We hypothesize younger Hispanic and Asian patients are at higher risk of H.pylori associated mGC. RESULTS/ANTICIPATED RESULTS: From 2000-2022, 339 patients (mE-GC n = 113; mO-GC n=226) were treated at NCCC. We will have characterized clinical and pathological features of mE-GC vs mO-GC. We determined the proportion of H. pylori associated mE-GC vs mO-GC. We will have established the geographical distribution of patients with mE-GC vs mO-GC to identify high-risk neighborhoods. We will link neighborhood risk factors such as food scarcity, poverty, health care access, ethnic enclaves, to the distinct clinical and pathological features of mE-GC, including H. pylori status. Descriptive statistics, chi-square, t-tests, and multivariable regression will be used to compare mE-GC to mO-GC. After controlling for underlying demographics and tumor features, we anticipate clusters of mE-GC and mO-GC in areas of historical racial segregation. DISCUSSION/SIGNIFICANCE: Linking neighborhood and individual risk factors for mE-GC will inform early detection and prevention efforts for vulnerable individuals in high-risk neighborhoods. Building community partnerships within these neighborhoods is essential for developing interventions targeting H. pylori treatment to reduce health disparities in mE-GC.
62 Unraveling the role of placental trophoblast cells in preeclampsia
Authors: Vadakke-Madathil Sangeetha , Wang Bingyan , Oniskey Micayla , Dekio Fumiko , Brody Rachel , Gelber Shari , Sperling Rhoda , Chaudhry Hina
Published: April 2024

OBJECTIVES/GOALS: Changes associated with placental vasculature contribute to the progression of gestational hypertensive disease preeclampsia. Caudal-type homeobox-2 (CDX2) regulates trophoblast stem cell differentiation. In this study, we investigate the role of placental CDX2 cells in healthy pregnancy and in conditions of preeclampsia. METHODS/STUDY POPULATION: To understand the role of CDX2 cells, here we collected human placenta samples from the prospectively enrolled cohort and also the de-identified cohort (n=84). We studied CDX2 distribution, and function using a lentivirus-based approach. We studied the CDX2 expression and functional differences using transcriptomics and examined the function in invasion and vasculogenesis in the presence and absence of the new target genes we have discovered in our study. RESULTS/ANTICIPATED RESULTS: Analysis of healthy human placenta samples showed that CDX2-expressing cells were present in fetal chorionic regions and are associated with HLA-G and cytokeratin-7 confirming their trophoblast identity. CDX2 cells demonstrated the potential to form a capillary network akin to endothelial cells. Placental samples from healthy (n=6) and preeclampsia (n=8) patients revealed higher levels of CDX2 expression in preeclampsia. Within preeclampsia CDX2 cells, Natriuretic peptide receptor 1 (NPR1), RET oncogene, and Homeobox D10 (HOXD10) were significantly differentially regulated, including a unique long-non-coding anti-sense RNA (KANSL1-AS1) that affected the function of CDX2 and trophoblast cells in invasion and normal vasculogenesis. DISCUSSION/SIGNIFICANCE: In sum, based on these observations, the present study postulates that CDX2 cells present in a healthy human placenta may serve as a prospective cellular reservoir for angiogenesis. Conversely, altered gene programs within CDX2 cells cause aberrant vascular function that could contribute to the progression of preeclampsia.
63 Allogeneic Recellularized Lung Orthotopic (ARLO) Transplant Research
Authors: Tran Douglas , Tran Douglas , Griffith Bartley , Wu Zhongjun
Published: April 2024

OBJECTIVES/GOALS: As of 2021, the lung transplantation waiting list has a mortality rate of 7.6 deaths per 100 patient-years. Bioengineered human organs is an emerging field of tissue engineering with a goal of developing suitable organs for transplantation. The focus of the project is to evaluate the efficacy of bioengineered lungs using a human-to-swine model. METHODS/STUDY POPULATION: This project will involve designing and assessing the bioengineered lung by establishing a human-to-pig xenotransplantation survival model. The project aims to evaluate how well the bioengineered lung functions within a living model. The bioengineered lung is constructed using swine connective tissue scaffolding, which has been recellularized with human cells. Anatomically, the lung will resemble a swine lung but will possess the immunological and cellular markers of human tissue. The proposed model will initially assess the immunological response of swine to human lung tissue. Lung function will be assessed during surgery using pulmonary vein gas samples and tissue sampling. Following the end of the study, additional tissues samples will be taken to evaluate the immunological response to the tissue. RESULTS/ANTICIPATED RESULTS: Xenotransplantation and bioengineered organs are two new emerging fields of research that have just begun to enter the large animal testing phase. This model will provide a novel human-to-pig xenotransplant survival model that will be used to test the efficacy of bioengineered lungs function in a dynamic living organism. The design has taken the principles of immunology learned from the current clinical and xenotransplant research and has incorporated this knowledge into the known pig-to-pig transplant models. We anticipate that this model design will be easily reproducible and can be expanded to other bioengineered organs as an effective means to test functionality. DISCUSSION/SIGNIFICANCE: The COVID-19 pandemic’s aftermath may lead to an increased demand for lung transplants. Bioengineered lungs could provide an additional source of organs to supplement current availability. This novel approach has the potential to offer a means to test several different types of bioengineered organs in the future.
72 Participant Recruitment at OHSU: Equipping Researchers to Overcome Recruitment Challenges
Authors: Zauflik Meredith , Swartz Kitt , Morris Cynthia D. , Ellison David H.
Published: April 2024

OBJECTIVES/GOALS: Under enrollment of trials is a continued challenge in clinical research. In response, the Oregon Clinical and Translational Research Institute (OCTRI), the CTSA at Oregon Health & Science University (OHSU), launched a central resource, OCTRI Recruitment, to equip researchers with the knowledge and tools needed for recruitment success. METHODS/STUDY POPULATION: OCTRI Recruitment focused programmatic development in response to the voice of OHSU researchers. In 2018, a qualitative assessment project, “Clinical Research Recruitment Methods at OHSU”, was launched, which included a survey (N=100) and optional interview (N=24), to determine recruitment method utilization and experience, along with opinions on the needs and culture of recruitment at OHSU. In 2022, as part of the same protocol project, a second survey was deployed (N=31), to determine changes in recruitment method use and to identify further recruitment challenges. OCTRI Recruitment also obtains continual informal input on perceived recruitment challenges and opportunities through engagement within the OHSU research team community. RESULTS/ANTICIPATED RESULTS: 2018 survey and interviews showed: many researchers relied on their clinic’s patient population for recruitment (74%); were unaware of available tools to recruit OHSU patients, especially informatics tools (5-22%); and were not aware of and minimally use methods to recruit outside OHSU (<40%). In response, OCTRI Recruitment developed and began recruitment consultations, guidance materials, and educational seminars. In 2022, survey results showed an increase in the use of informatics-based recruitment tools (2-14%+) and increased use of methods focused on individuals outside of OHSU (1-7%+). Additionally, a review of studies post OCTRI Recruitment consultation over three years (N=51) showed that of those studies, 40% increased enrollment numbers and 61% increased team’s confidence level post consult. DISCUSSION/SIGNIFICANCE: This approach to program creation allowed for a uniquely targeted development of services in response to the voice of OHSU researchers and recruitment challenges. Based on additional data, efforts have begun to address the recruitment challenges of a study opportunity website, participant compensation methods, and community-based recruitment.
79 Flexible Support Materials Maintain Disc Height and Support the Formation of Hydrated Tissue Engineered Intervertebral Discs in Vivo
Authors: Fidai Alikhan , Kim Byumsu , Lintz Marianne , Gadjradj Pravesh , Kirnaz Sertac , Boadi Blake , Hussain Ibrahim , Hartl Roger
Published: April 2024

OBJECTIVES/GOALS: We evaluated the long-term success of tissue engineered intervertebral discs (TE-IVDs) cultured in flexible (FPLA) or stiff (PLA) support materials, hypothesizing that FPLA would maintain disc height and tissue hydration in the minipig spine. METHODS/STUDY POPULATION: TE-IVD: NP cells were encapsulated in alginate and NP plugs were placed in the center of FPLA cages. AF cells were encapsulated in type I collagen and pipetted around NP plugs. Implantation: Empty FPLA cages (n=4), and TE-IVDs cultured in FPLA (n=4) were implanted at C3-4 or C5-6 following complete discectomy (DX) in skeletally mature minipigs (n=4). Imaging and Quantification: Terminal disc height indices (DHI) were calculated from weekly x-rays using a previously described method, and results were compared to the PLA pilot study. T2 MRI scans were taken of levels treated with TE-IVDs to quantify disc hydration as previously described. RESULTS/ANTICIPATED RESULTS: FPLA cages restored DHIs to native levels until endpoint. In contrast, PLA cages fractured, and terminal DHIs were statistically similar to DX levels. Of the four levels treated with TE-IVDs, 2 were displaced from the disc space. Stabilized levels yielded DHIs which were statistically similar to native IVD and greater than displaced and DX levels. Displaced levels yielded DHIs which were significantly lower than native and stabilized levels, but greater than DX levels (P<0.05). T2 MRIs of stabilized TEIVDs revealed that levels treated with a construct maintained tissue hydration which was significantly greater than levels treated with an empty cage or DX levels (P<0.0001), but which was about half the hydration of native disc tissue. DISCUSSION/SIGNIFICANCE: Implanting TE-IVDs with FPLA support cages leads to disc height maintenance and the stabilization of hydrated tissues in the spine, enhancing the long term success of TE-IVD implants and providing a basis for clinical translation.
84 Using Opportunistic Sampling and Remnant Blood Samples to Develop Pediatric Pharmacokinetic Models to Inform Antidepressant Dosing
Authors: Strawn Jeffrey R. , Poweleit Ethan A. , Taylor Zachary L. , Mizuno Tomoyuki , Vaughn Samuel , Desta Zeruesenay , Stancil Stephani , Ramsey Laura B.
Published: April 2024

OBJECTIVES/GOALS: Developing pharmacokinetic (PK) models to guide selective serotonin reuptake inhibitor (SSRI) dosing in youth is costly, time-intensive, and requires large numbers of participants. We evaluated the use of remnant blood samples from SSRI-treated youth and developed precision PK dosing strategies. METHODS/STUDY POPULATION: Following IRB approval, we used a clinical surveillance platform to identify patients with routine phlebotomy within 24 hours of escitalopram or sertraline dosing. Remnant blood samples were obtained from youth aged 5–18 years, escitalopram and sertraline concentrations were determined, and clinical characteristics (e.g., age, sex, weight, concomitant medications that inhibit sertraline or escitalopram metabolism) and phenotypes for CYP2C19, the predominant enzyme that metabolizes these SSRIs, were extracted from the electronic medical record (EMR). A population PK analysis of escitalopram and sertraline was performed using NONMEM. The influence of clinical variables, CYP2C19, and dosing was evaluated from simulated concentration-time curves. RESULTS/ANTICIPATED RESULTS: Over 21 months, we collected315 samples from escitalopram-treated patients (N=288) and 265 samples from sertraline-treated patients (N=255). In youth, escitalopram and sertraline exposure (concentrations over time) and specific pharmacokinetic parameters (e.g., clearance) were influenced by CYP2C19 phenotype, concomitant CYP2C19 inhibitors, and patient-specific characteristics. Escitalopram and sertraline concentrations from remnant blood samples were 3.98-fold higher and 3.23-fold higher, respectively, in poor metabolizers compared to normal metabolizers (escitalopram, p<0.001) and compared to normal, rapid, and ultrarapid metabolizers combined (sertraline, p<0.001). DISCUSSION/SIGNIFICANCE: Combining remnant blood sampling with pharmacogenetic-integrated EMR data can facilitate large-scale population PK analyses of escitalopram and sertraline in youth. This real-world approach can be used to rapidly develop precision SSRI dosing strategies, including slower titration and reduced target doses in CYP2C19 poor metabolizers.
88 Feasibility of a Home-based Physiotherapy Program to Increase Physical Activity Levels in Older Adults with Diabetes Mellitus
Authors: Rivera Wilitza Martínez , Ortiz Alexis , Orellano Elsa M. , Amaya-Ardila Claudia P. , Frontera-Roura Walter R.
Published: April 2024

OBJECTIVES/GOALS: The objective of this study is to assess the feasibility and preliminary impact of a physiotherapy protocol for developing an individualized home-based physical activity program to increase physical activity (PA) levels in sedentary older adults with Type II Diabetes Mellitus (T2DM) living in Puerto Rico (PR). METHODS/STUDY POPULATION: This will be a pilot study with two phases. In phase 1, we will design a novel patient-centered home-based PA program protocol for adults ≥65 years with T2DM based on the Information-Motivation-Behavioral Skills model. Its content validity will be assessed through focus groups with 10 experts and 10 older adults and analyzed using a directed content analysis. Phase 2 we will be program implementation using a one-group, repeated measures design with 12 adults ≥65 years with T2DM. PA levels will be assessed by recording active minutes with a Fitbit. Risk of falls, balance, strength, and physical function will be assessed through standardized tests validated for this population. Statistical analysis will include descriptive statistics, comparisons via chi-square/Fisher’s exact test, and non-parametric tests. RESULTS/ANTICIPATED RESULTS: We expect to recruit a minimum of 12 participants and to administer the program for 12 weeks at a frequency of two visits per week. We anticipate that implementing and supervising the home-based PA protocol will be feasible as determined by recruitment and retention rates, patients’ satisfaction, and compliance with the program. We also expect that this protocol will increase physical activity levels, improve general strength, balance, physical function, and reduce the risk of falls in sedentary older adults with T2DM. DISCUSSION/SIGNIFICANCE: As the third cause of death in PR, T2DM represents a public health challenge. An effective home-based PA program may decrease morbidity and mortality rates in older adults by increasing PA and functional health. This study will provide data for planning a randomized controlled trial to assess its effectiveness in the outcomes of interest.
89 Two Newly Developed Frontiers CTSI Applications to Support Recruitment and Trial Management: The Frontiers Trial Finder Mobile App and a Predictive Accrual Web-based App
Authors: Kuo Hanluen , Murakonda Vinay , Hines Hunter , Mudaranthakam Dinesh Pal , Monaghan-Nichols Paula , Rush Eric , Statland Jeffrey
Published: April 2024

OBJECTIVES/GOALS: Frontiers CTSI developed applications to ensure its science teams have technological tools to advance their community engagement and trial management. The Trial Finder app is a mobile application that allows users to navigate available trials. The Accrual app will help study teams monitor their recruitment performances in real time. METHODS/STUDY POPULATION: The Data Science team at the University of Kansas Medical Center (KUMC) had previously developed similar applications for The University of Kansas Cancer Center. Both retrieve information from KUMC’s clinical trial management system and ClinicalTrials.gov. This was replicated to include KUMC Pulmonary Critical Care (PCC) and KUMC Neuromuscular (NM) trials. Frontiers CTSI is working with both groups for piloting and feedback. Recruiting and marketing strategies for investigators to add their trials to both apps will be done through existing communication channels and be highlighted on Frontiers trial resource website. Recruiting and marketing strategies of the Frontiers Trial Finder app to the external community will have a focus on, but not limited to, paid social media advertising. RESULTS/ANTICIPATED RESULTS: The Trial Finder app can help providers search for trials their patient may be eligible for during clinic visits and to engage with the community by allowing anyone to download and browse on their Android/iOS device. Built in REDCap forms are used to capture contact information. The Accrual app is a web-based application that helps study teams monitor their recruitment performances in real time and provide an opportunity to adjust strategies. It uses an in-house algorithm to predict if trials will meet timeline goals. This data is conveniently laid out on a single web page so that science teams can overview all their trials’ recruitment performances simultaneously. The next phase of developing these applications is to market their use within Frontiers CTSI and its community catchment area. DISCUSSION/SIGNIFICANCE: Through collaboration, Frontiers CTSI is developing resources to support community engagement and trial management. New innovative applications like these ensure all the main stakeholders involved with clinical trial execution are always engaged and have access to iterative contemporary technologies that support their research.
90 Novel approach for childhood Sjögren’s Disease therapies: multistakeholder design of a series of N-of-1 trials
Authors: Singer Nora G. , Stern Sara M , Palm Marisha E , Selker Harry , Trinquart Ludovic
Published: April 2024

OBJECTIVES/GOALS: Childhood Sjögren’s disease (cSD) is a rare autoimmune disease. Despite the profound impact on children and their families, pediatric-specific clinical trials to inform therapeutic strategies in cSD are lacking. In 2022 we participated in the Trial Innovation Network (TIN) Design Lab with the purpose of designing a series of N-of-1 trials for cSD. METHODS/STUDY POPULATION: New medications have the potential to be safe/effective treatments for cSD but must be evaluated in randomized trials. To overcome limitations of traditional parallel-group designs given the rarity of cSD, we developed an N-of-1 trial approach. Our proposal was selected by the Tufts TIN Design Lab. The Design Lab multi-stakeholder process involved parents of and patients with cSD, pediatric and adult rheumatologists, and experts in clinical trial design and outcomes. We engaged all stakeholders in protocol development to maximize the impact of the proposed approach on clinical care, ensure a successful recruitment plan, and inform the choice of endpoints as there are no widely accepted cSD outcome measures to determine treatment efficacy. RESULTS/ANTICIPATED RESULTS: Using the Design Lab methodology, we clarified the N-of-1 study goals and engaged in an iterative process to develop a “briefing book” that ensured a sound premise for our study. We reviewed and accumulated published literature to support our focus on mucosal/glandular manifestations, identified potential interventions to be used in the N-of-1 trials, and enumerated possible outcomes, including outcomes important to patient/parents. This work culminated in a full-day Design Lab event that included multiple stakeholders who provided expertise from different perspectives on the full drug development pathway. Study design feedback focused on three specific areas. 1) Inclusion and exclusion criteria; 2) Identification of outcome measures; 3) Treatment and washout periods. DISCUSSION/SIGNIFICANCE: To address the critical need and move treatment of cSD forward, we are designing a prototype N-of-1 trial in children with rheumatic disease. We will continue to engage stakeholders by using a series of Delphi surveys and an in-person meeting to create composite outcome measures to test cSD therapies in personalized trials.
92 Honest Broker Tool to Automate Data Extraction from Clinical Research Data Warehouse
Authors: Amankwah Ernest K. , Taylor Bradley
Published: April 2024

OBJECTIVES/GOALS: To describe an Honest Broker (HB) tool and workflow integrated with the Institutional Review Board (IRB) to automate requests, approvals and delivery of both de-identified and identified data extractions from a clinical research data warehouse (CRDW). METHODS/STUDY POPULATION: The HB tool has predefined domain tables and is closely integrated IRB for quick and easy review and approval. Investigators can access patient data using query tools, barcodes from biospecimens or build a query in TriNetX and provide the patient list as an input for the HB tool. For de-identified data extraction, the required data domain tables and date ranges can be selected and submitted in the HB tool. For identified data extractions, investigators with an approved IRB protocol can enter the protocol number and the approved date range in the HB tool. This request is automatically forwarded to the IRB for review. RESULTS/ANTICIPATED RESULTS: For de-identified data extraction, an email alert is automatically sent to the investigator once the data extract is completed. For identified data extraction, if IRB approves the request, an HB is immediately notified to release the data. Data release triggers two emails to the investigator: (1) a link to an encrypted zipped file with the requested data, and (2) a password to unlock the encrypted file. If the request is denied, the IRB sends an email to the investigator with the reason for denial and options for remediation. The entire HB workflow is accomplished in a secure environment with an audit trail from the initial data request to data download by the investigator. Since the launch of the HB tool, the time from data request to delivery is approximately an hour for deidentified data and 24 hrs for identified data. DISCUSSION/SIGNIFICANCE: The HB tool has increased successful data delivery in support of publications, grant submissions, and clinical trial recruitment. Optimization of data extraction from the CRDW through automation and integration with the IRB can minimize interaction with data analysts and IRB staff, thus accelerating the conduct of clinical research.
A 301 W narrow-linewidth in-band pumped Er:Yb co-doped fiber amplifier at 1585 nm and related modeling for dynamics study and optimization
Authors: Fu Guohao , Li Guanzhong , Yu Weilong , Li Pei , Li Dan , Xiao Qirong , Gong Mali , Yan Ping
Published: April 2024

To overcome Yb lasing, a kilowatt-level 1535 nm fiber laser is utilized to in-band pump an Er:Yb co-doped fiber (EYDF) amplifier. The output power of a 301 W narrow-linewidth EYDF amplifier operating at 1585 nm, with 3 dB bandwidth of 150 pm and

${M}^2$

< 1.4, is experimentally demonstrated. To the best of our knowledge, it is the highest output power achieved in L-band narrow-linewidth fiber amplifiers with good beam quality. Theoretically, a new ion transition behavior among energy levels for in-band pumping EYDF is uncovered, and a spatial-mode-resolved nonlinearity-assisted theoretical model is developed to understand its internal dynamics. Numerical simulations reveal that the reduction in slope efficiency is significantly related to excited-state absorption (ESA). ESA has a nonlinear hindering effect on power scaling. It can drastically lower the pump absorption and slope efficiency with increasing pump power for in-band pumped EYDF amplifiers. Meanwhile, optimized approaches are proposed to improve its power to the kilowatt level via in-band pumping.
Modern trends in labor law: a comparative analysis of the EU and Ukraine
Authors: Yaroshenko Oleg M. , Lutsenko Оlena Yе. , Karaulna Nataliia V. , Sokolov Volodymyr M. , Zubrytskyy Mykola I.
Published: April 2024

The norms of labor law that regulate the relevant relationship between the employee and the employer are constantly evolving under the influence of various factors, including society and the State. Labor law trends have become especially prominent over the past several years, particularly during the COVID-19 pandemic. Lockdown restrictions have dealt a serious blow to the labor field and have required urgent action from both companies and governments. In view of this, a number of relevant subtopics have been formed in labor relations, the study of which is of interest to the entire scientific community. The purpose of the research paper is to study the main trends that have emerged in modern labor law and their impact on the formation of the labor legislation system in Ukraine and the European Union (EU) from a comparative perspective. The article analyzes the main directions that the authors have identified as especially relevant in the development of labor relations and the legal regulation of such issues. Considering that some trends have arisen spontaneously under the influence of the COVID-19 pandemic, and many States were not ready for them, we have analyzed how the legislator settled such issues. The laws of Ukraine, the EU, and individual EU member States are examined here in a comparative perspective to draw upon and understand a complete picture of the modern development of labor relations in Europe and to identify the most beneficial approaches to regulating topical issues of labor law. The information obtained as a result of the study can be used to improve Ukraine's national legislation, bring it in line with European standards, further study the issue of the modern development of labor relations, and teach and develop methodological support for educational disciplines related to labor law and social security law.
The Late Miocene Talpidae (Eulipotyphla, Mammalia) from the Pannonian Region, Slovakia
Authors: Cailleux Florentin , van den Hoek Ostende Lars W. , Joniak Peter
Published: April 2024

Central Europe is an area of high diversity for the Talpidae (Eulipotyphla, Mammalia) during the Late Miocene. The assemblages from Slovakia (Borský Svätý Jur, Krásno, Pezinok, Šalgovce, Studienka, Triblavina) are no exception with their abundant material representing eleven species. The uropsiline Desmanella is represented by D. rietscheli and D. dubia. Desmanini fossils are attributed to Archaeodesmana vinea, Archaeodesmana dissona new species, Gerhardstorchia biradicata, and Gerhardstorchia sp. The scalopines Proscapanus minor and P. austriacus are well recorded in the Vallesian localities and support the emergence of P. austriacus before the MN9/10 transition. Talpini and Urotrichini are especially rare and only represented by Talpa cf. T. minuta and Urotrichini gen. sp. indet. Finally, we identified the youngest occurrence of Desmanodon in Europe, D. cf. D. fluegeli, at the MN9 locality of Borský Svätý Jur. The high diversity in the Late Miocene Central European is partly explained by the co-occurrence of the competing Scalopini and Talpini during the Vallesian, indicating high resource environments. The decline of these tribes, followed by the success of the desmans during the Turolian, appears as a consequence of regional environmental changes.

UUID: http://zoobank.org/a3eb532b-c341-489a-b0ff-ecf3f9466a76
CANTOR’S THEOREM MAY FAIL FOR FINITARY PARTITIONS
Authors: SHEN GUOZHEN
Published: April 2024

A partition is finitary if all its members are finite. For a set A,

$\mathscr {B}(A)$

denotes the set of all finitary partitions of A. It is shown consistent with

$\mathsf {ZF}$

(without the axiom of choice) that there exist an infinite set A and a surjection from A onto

$\mathscr {B}(A)$

. On the other hand, we prove in

$\mathsf {ZF}$

some theorems concerning

$\mathscr {B}(A)$

for infinite sets A, among which are the following:

(1)

If there is a finitary partition of A without singleton blocks, then there are no surjections from A onto

$\mathscr {B}(A)$

and no finite-to-one functions from

$\mathscr {B}(A)$

to A.

(2)

For all

$n\in \omega $

,

$|A^n|<|\mathscr {B}(A)|$

.

(3)

$|\mathscr {B}(A)|\neq |\mathrm {seq}(A)|$

, where

$\mathrm {seq}(A)$

is the set of all finite sequences of elements of A.
Ray Kea and the Historians of the Gold Coast: Debates Over Continuity and Rupture in African and African Diaspora Atlantic Histories
Authors: Odamtten Harry N. K.
Published: April 2024

The central role of Gold Coast societies, ports, and cities in the emerging Atlantic circuit is critical to understanding the history of the Atlantic world. The study of the causes and effects of Gold Coast societies’ transition from African polities and economies to transatlantic entrepots and trading emporiums and their subsequent impact on the Americas has been the hallmark of Ray Kea's scholarship. Since the beginning of his career, Kea has been a significant contributor to the study of the African Atlantic, and the field's various debates and disciplinary evolutions. While many scholars of the Gold Coast recognize Kea's work as foundational to scholarship on the Gold Coast, engagement with his work has not been rigorous. Kea is often cited in bibliographies and aspects of his work have served as benchmarks for other forays into Gold Coast histories. However, there is a need to go beyond an appreciation for Kea as a trailblazer, passing reference of his scholarship, and bibliographic citation of his work to a more thorough and consistent discourse with his major ideas and propositions. Kea has been, for example, adept at integrating innovations and ideas in various disciplinary arenas. He dexterously applies Marxist and postmodernist theories, diverse historiographies of the Atlantic world, and conceptual tools to traditional archival and oral historical data in his analyses of Gold Coast and diasporic societies. This review essay argues for Kea's importance and the need for a deeper engagement with his work in the field by putting his work into conversation with both classic Atlantic historiographies and recent scholarship that has built off Kea's.
Language assessment literacy
Authors: Vogt Karin , Bøhn Henrik , Tsagari Dina
Published: April 2024

Numerous references to ‘new’ literacies have been added to the discourse of various academic and public domains, resulting in a multiplication of literacies. Among them is the term ‘language assessment literacy’ (LAL), which has been used as a subset of Assessment Literacy (AL) (Gan & Lam, 2022) in the field of language testing and assessment and has not been uncontested. LAL refers to the skills, knowledge, methods, techniques and principles needed by various stakeholders in language assessment to design and carry out effective assessment tasks and to make informed decisions based on assessment data (e.g., Fulcher, 2012*; Inbar-Lourie, 2008*[1]; 2013; Taylor, 2009*, 2013*).
Five years in: a case study of an Australian early-career secondary school music teacher
Authors: Robinson Jennifer Anne
Published: April 2024

Early-career secondary school music teachers navigate many challenges as they settle into the profession. These include consolidating their knowledge of subject content, gaining classroom confidence and honing skills in classroom management. In addition, their sense of belonging can be enhanced by working at collegial relationships within their faculty, across the school and feeling a part of the wider school community. These factors can elicit a ‘make or break’ response for continuing in the profession.

This paper reports on a case study of an Australian early-career secondary school music teacher, in her fifth year in the profession. The case study, as a part of a larger study, sequenced quantitative and qualitative research methods, allowing insight into the music teacher’s working life and enabled the researcher to understand factors that impact daily practice. Themes explored in the study include motivation, perception of value, stress and the difficulties of securing permanent employment. The music teacher presented a positive approach to her work through her development of resilience and shared her future goals and dreams.

This research offers suggestions on how schools and education authorities can best support early-career secondary school music teachers to enable them to become resilient, confident and valued practitioners for the future.
Digitalisierung der Arbeit und Eigeninitiative – die Rolle der organisationalen Fehlerkultur
Authors: Traum Anne , Görs Philipp K. , Nerdinger Friedemann W.
Published: April 2024

Zusammenfassung: Die Digitalisierung der Arbeit eröffnet Freiräume für mehr Eigeninitiative (EI) der Beschäftigten und birgt das Risiko von Fehlern. Die Einführung neuer Technologien berührt deshalb auch stets die organisationale Fehlerkultur (FK). Besonders relevant ist dies bei wissensintensiven Dienstleistungen. Untersucht wird der Einfluss des arbeitsplatzbezogenen Digitalisierungsgrades (ADG) auf die Eigeninitiative von Beschäftigten ( N = 457) in Steuerberatungskanzleien unter Berücksichtigung von organisationaler Fehlerkultur und Betriebs- bzw. Kanzleigröße. Die Prüfung erfolgt über ein moderiertes Mediationsmodell. (Angestellte) Angehörige freier Berufe (z. B. Steuerberaterinnen und –berater) zeigen grundsätzlich mehr Eigeninitiative als Nicht-Angehörige freier Berufe (NFB) (z. B. Steuerfachangestellte). Der Zusammenhang zwischen ADG und EI wird partiell von FK mediiert. Der Einfluss von FK auf EI ist stärker bei NFB. Theoretische wie praktische Implikationen sowie die Übertragbarkeit auf andere wissensintensive Dienstleistungstätigkeiten werden u. a. mit Blick auf die Arbeitsgestaltung diskutiert. Hierbei wird auch auf die Ergebnisse objektiv-bedingungsbezogener Tätigkeitsanalysen Bezug genommen.
Centripetal integration of past events in hippocampal astrocytes regulated by locus coeruleus
Authors: Rupprecht Peter , Duss Sian N. , Becker Denise , Lewis Christopher M. , Bohacek Johannes , Helmchen Fritjof
Published: April 2024

An essential feature of neurons is their ability to centrally integrate information from their dendrites. The activity of astrocytes, in contrast, has been described as mostly uncoordinated across cellular compartments without clear central integration. Here we report conditional integration of calcium signals in astrocytic distal processes at their soma. In the hippocampus of adult mice of both sexes, we found that global astrocytic activity, as recorded with population calcium imaging, reflected past neuronal and behavioral events on a timescale of seconds. Salient past events, indicated by pupil dilations, facilitated the propagation of calcium signals from distal processes to the soma. Centripetal propagation to the soma was reproduced by optogenetic activation of the locus coeruleus, a key regulator of arousal, and reduced by pharmacological inhibition of α1-adrenergic receptors. Together, our results suggest that astrocytes are computational units of the brain that slowly and conditionally integrate calcium signals upon behaviorally relevant events.
In-vitro dehydration kinetics coefficient of Kalifilcon A and other contact lens materials
Authors: Ponzini Erika , Maspero Francesco , Galli Anna , Tavazzi Silvia
Published: April 2024

In contact lens (CL) wear, dehydration needs to be tailored to avoid dryness and related symptoms. In this view, this work aims to assess and compare the in-vitro dehydration kinetics of five CL materials, including the newly developed Kalifilcon A CL. At 36 °C and 60% relative humidity, the in-vitro dehydration kinetics of the different CLs were compared using a gravimetric method. CLs were analyzed either after a rinse of a few seconds in preservative-free saline solution or after a 24-h incubation in the same solution. A model based on the Fick diffusion equation was employed to deduce a water kinetics coefficient, providing insights into water diffusion within the polymeric matrix. The study reveals that all materials exhibit a non-Fickian dehydration behavior, with significant differences in dehydration kinetics coefficients and dehydration rate slopes. Etafilcon A and Omafilcon A, both hydrogel CLs, exhibit a similar behavior, different compared to the pattern shown by Senofilcon A and Delefilcon A, silicone-hydrogel CLs. Notably, Kalifilcon A, despite being a silicone-hydrogel, displays a hydration behavior reminiscent of hydrogel CLs.
Secure malicious node detection in flying ad-hoc networks using enhanced AODV algorithm
Authors: Chandrasekar V. , Shanmugavalli V. , Mahesh T. R. , Shashikumar R. , Borah Naiwrita , Kumar V. Vinoth , Guluwadi Suresh
Published: April 2024

In wireless networking, the security of flying ad hoc networks (FANETs) is a major issue, and the use of drones is growing every day. A distributed network is created by a drone network in which nodes can enter and exit the network at any time. Because malicious nodes generate bogus identifiers, FANET is unstable. In this research study, we proposed a threat detection method for detecting malicious nodes in the network. The proposed method is found to be most effective compared to other methods. Malicious nodes fill the network with false information, thereby reducing network performance. The secure ad hoc on-demand distance vector (AODV) that has been suggested algorithm is used for detecting and isolating a malicious node in FANET. In addition, because temporary flying nodes are vulnerable to attacks, trust models based on direct or indirect reliability similar to trusted neighbors have been incorporated to overcome the vulnerability of malicious/selfish harassment. A node belonging to the malicious node class is disconnected from the network and is not used to forward or forward another message. The FANET security performance is measured by throughput, packet loss and routing overhead with the conventional algorithms of AODV (TAODV) and reliable AODV secure AODV power consumption decreased by 16.5%, efficiency increased by 7.4%, and packet delivery rate decreased by 9.1% when compared to the second ranking method. Reduced packet losses and routing expenses by 9.4%. In general, the results demonstrate that, in terms of energy consumption, throughput, delivered packet rate, the number of lost packets, and routing overhead, the proposed secure AODV algorithm performs better than the most recent, cutting-edge algorithms.
Minimization of a ship's magnetic signature under external field conditions using a multi-dipole model
Authors: Woloszyn Miroslaw , Tarnawski Jarosław
Published: April 2024

The paper addresses the innovative issue of minimizing the ship's magnetic signature under any external field conditions, i.e., for arbitrary values of ambient field modulus and magnetic inclination. Varying values of the external field, depending on the current geographical location, affect only the induced part of ship's magnetization. A practical problem in minimizing the ship signature is separating permanent magnetization from induced magnetization. When the ship position changes, a signature measurement has to be made under new magnetic field conditions to update the currents in the coils. This is impractical or even difficult to do (due to the need for a measuring ground), so there is a need to predict the ship's magnetization value in arbitrary geographical location conditions based on the reference signature determined on the measuring ground. In particular, the model predicting the signatures at a new geographical location must be able to separate the two types of magnetization, as permanent magnetization is independent of external conditions. In this paper, a FEM model of the vessel is first embedded in an external field and permanent magnetization is simulated using DC coils placed inside the model. Then, using the previously developed rules for data acquisition and determination of model parameters, a multi-dipole model is synthesized in which the induced and permanent parts are separated. The multi-dipole model thus developed has been successfully confronted with the initial model in FEM environment. The separation of permanent and induced magnetization allows the latter to be scaled according to new values of the external field. In the paper, the situation of determining a signature at one geographical position and its projection onto two other positions is analyzed. Having determined the signature with a high degree of accuracy anywhere in the world, it is possible to perform classical signature minimization by determining DC currents in coils placed inside the ship's hull. The paper also analyzes the effectiveness of ship's signature minimization and the influence of ship's course on the signature value. The advantage of the method presented in this paper is an integrated approach to the issue of scaling and minimization of ship magnetic signature, which has not been presented in the literature on such a scale before.
Investigating child sexual abuse material availability, searches, and users on the anonymous Tor network for a public health intervention strategy
Authors: Nurmi Juha , Paju Arttu , Brumley Billy Bob , Insoll Tegan , Ovaska Anna K. , Soloveva Valeriia , Vaaranen-Valkonen Nina , Aaltonen Mikko , Arroyo David
Published: April 2024

Tor is widely used for staying anonymous online and accessing onion websites; unfortunately, Tor is popular for distributing and viewing illicit child sexual abuse material (CSAM). From 2018 to 2023, we analyse 176,683 onion domains and find that one-fifth share CSAM. We find that CSAM is easily available using 21 out of the 26 most-used Tor search engines. We analyse 110,133,715 search sessions from the Ahmia.fi search engine and discover that 11.1% seek CSAM. When searching CSAM by age, 40.5% search for 11-year-olds and younger; 11.0% for 12-year-olds; 8.2% for 13-year-olds; 11.6% for 14-year-olds; 10.9% for 15-year-olds; and 12.7% for 16-year-olds. We demonstrate accurate filtering for search engines, introduce intervention, show a questionnaire for CSAM users, and analyse 11,470 responses. 65.3% of CSAM users first saw the material when they were children themselves, and half of the respondents first saw the material accidentally, demonstrating the availability of CSAM. 48.1% want to stop using CSAM. Some seek help through Tor, and self-help websites are popular. Our survey finds commonalities between CSAM use and addiction. Help-seeking correlates with increasing viewing duration and frequency, depression, anxiety, self-harming thoughts, guilt, and shame. Yet, 73.9% of help seekers have not been able to receive it.
Interplay between tie strength and neighbourhood topology in complex networks
Authors: Mrowinski Maciej J. , Orzechowski Kamil P. , Fronczak Agata , Fronczak Piotr
Published: April 2024

Granovetter’s weak ties theory is a very important sociological theory according to which a correlation between edge weight and the network’s topology should exist. More specifically, the neighbourhood overlap of two nodes connected by an edge should be positively correlated with edge weight (tie strength). However, some real social networks exhibit a negative correlation—the most prominent example is the scientific collaboration network, for which overlap decreases with edge weight. It has been demonstrated that the aforementioned inconsistency with Granovetter’s theory can be alleviated in the scientific collaboration network through the use of asymmetric measures. In this paper, we explain that while asymmetric measures are often necessary to describe complex networks and to confirm Granovetter’s theory, their interpretation is not simple, and there are pitfalls that one must be wary of. The definitions of asymmetric weights and overlaps introduce structural correlations that must be filtered out. We show that correlation profiles can be used to overcome this problem. Using this technique, not only do we confirm Granovetter’s theory in various real and artificial social networks, but we also show that Granovetter-like weight-topology correlations are present in other complex networks (e.g. metabolic and neural networks). Our results suggest that Granovetter’s theory is a sociological manifestation of more general principles governing various types of complex networks.
High-dose short-term osimertinib treatment is effective in patient-derived metastatic colorectal cancer organoids
Authors: Iyer Kirti K. , Poel Dennis , Miggelenbrink Anne , Kerkhof Wouter , Janssen Jorien , Bakkerus Lotte , de Jong Loek , van den Hombergh Erik , Nagtegaal Iris D. , Tauriello Daniele V. F. , van Erp Nielka P. , Verheul Henk M. W.
Published: April 2024

Background

Most tyrosine kinase inhibitors (TKIs) have failed in clinical trials for metastatic colorectal cancer (mCRC). To leverage the additional lower-affinity targets that most TKIs have, high-dose regimens that trigger efficacy are explored. Here, we studied unprecedented drug exposure–response relationships in vitro using mCRC patient-derived tumour organoids (PDTOs).

Methods

We investigated the cytotoxic anti-tumour effect of high-dose, short-term (HDST) TKI treatment on 5 PDTOs. Sunitinib, cediranib and osimertinib were selected based on favourable physicochemical and pharmacokinetic properties. Intra-tumoroid TKI concentrations were measured using a clinically validated LC/MS-MS method. Cell death was determined using an enzyme activity assay, immunofluorescent staining and western blotting.

Results

Most PDTOs tested were sensitive to sunitinib and cediranib, but all to osimertinib. Furthermore, HDST osimertinib treatment effectively blocks organoid growth. This treatment led to markedly elevated intra-tumoroid TKI concentrations, which correlated with PDTO sensitivity. Mechanistically, HDST osimertinib treatment induced apoptosis in treated PDTOs.

Conclusion

Our work provides a better understanding of TKI exposure vs response and can be used to determine patient-specific sensitivity. Additionally, these results may guide both mechanistic elucidation in organotypic translational models and the translation of target drug exposure to clinical dosing strategies. Moreover, HDST osimertinib treatment warrants clinical exploration for mCRC.
Prediction of induced magnetism in 2D Ti2C based MXenes by manipulating the mixed surface functionalization and metal substitution computed by xTB model Hamiltonian of the DFTB method
Authors: Sakhraoui Taoufik , Karlický František
Published: April 2024

We employed the recently developed density functional tight binding (DFTB) method's Hamiltonian, GFN1-xTB, for modeling the mixed termination in Ti2C MXenes, namely three types of termination by combining –O and –OH, –O and –F, and –F and –OH.