Real World Research Articles

Basic research on the development of mathematics utilisation skills that contribute to problem solving in real-life situations

In today’s modern world, in which technology is everywhere, there is a new focus on the importance of mathematics, technology and data science. There is a need for appropriate education to ensure literacy in these skills and the equivocality of mathematical literacy is an important factor. As someone who is in charge of classes in mathematical literacy, information literacy and data science literacy, Associate Professor Joji Goto sees first hand the challenges facing the education industry in these areas and wants to help solve them. He has a background in mathematics and education and is passionate about the impact knowledge of maths can have in people’s daily lives. In his latest project, Goto, who is based in the Institute of Education and Student Affairs at Niigata University in Japan, is developing mathematics utilisation skills that contribute to problem solving in real-life situations. He is considering the kinds of problems that could use mathematics and believes this awareness of the relationship between mathematics and real-world situations will enhance the application of mathematics in the real world. Studies have found students’ to have negative views on mathematics and also the narrow view that they are studying the topic only to pass exams. Students may avoid learning mathematics as they don’t believe it is useful or applicable to daily life. Goto wants to change this perception of the subject and, in doing so, expand students’ possibilities and enrich their learning.

Real world study on combining local interventions with systemic therapy in unresectable hepatocellular carcinoma

Real world study on combining local interventions with systemic therapy in unresectable hepatocellular carcinoma

Large Bias in Matching Small Horizontal and Vertical Extents Separated in Depth in the Real World Is Similar for Upright and Supine Observers

The apparent sizes of horizontal and vertical lines show an anisotropy known as the horizontal vertical illusion (HVI) wherein vertical lines appear to be longer than their horizontal counterparts. Whereas a typical HVI comparing vertical and horizontal lines in a plane produces a 5–10% illusion, a much larger-scale illusion (15–25%) is often found for large objects in the real world, and this has been related to differential angular exaggerations in perceived elevation (vertical) and azimuthal (horizontal) direction. Recently supine observers in virtual environments were found to show larger exaggerations in perceived azimuth than upright observers. Here, 48 participants were tested in both supine and upright postures in an outdoor environment while matching fairly small physical extents in the real world. They adjusted the magnitude of the horizontal extent to perceptually match fairly small vertical poles (0.7–1.3 m tall) that were either presented at the same viewing distance as the matching extent or in a different depth plane, so that size at a distance had to be compared. Supine observers viewed the scene, as though upright, through a large mirror mounted overhead at 45° that was adjusted to approximate their normal eye height. When the matcher extent was at a different distance than the pole, horizontal extent matches typically exceeded the actual pole height by about 15% or more, whether the viewer was upright or supine. The average overestimation was only about 10% when the matching extent was at the same distance. Despite the similarity in performance across different postures for spatial matching, supine observers gave much higher explicit estimates of azimuthal direction than upright observers. However, although the observation of exaggeration in perceived azimuth for supine observers was replicated in a second study with 24 additional participants using a mirror with a smaller (more normal) aspect ratio, the magnitude of the exaggeration seemed to be greatly reduced when the field of view of the apparatus had a more typical aspect ratio. This suggests that the unusually large exaggeration of azimuth found in a previous report with supine observers may have been caused by the unusually large aspect ratio of the viewing apparatus used.

Clinical and economic assessment of nosocomial pneumonia antibacterial therapy in Moscow hospital

Objective: to conduct clinical and economic analysis of nosocomial pneumonia antibacterial therapy in a multidisciplinary hospital in Moscow.Material and methods. The medical records of patients admitted to Yudin City Clinical Hospital in Moscow in 2019–2021 were analyzed retrospectively. Pharmacoepidemiological analysis included the structure of prescriptions of antibacterial drugs (ABDs), features of empirical and etiotropic therapy, duration of using ABDa and other parameters. In total, 110 cases of severe nosocomial pneumonia caused by ESKAPE pathogens were selected for analysis. Direct medical costs and cost-effectiveness coefficients were calculated based on real world data.Results. It was established that nosocomial pneumonia is the most common complication among hospitalized patients in the intensive care unit (ICU). The etiology of nosocomial pneumonia was mostly presented by K. pneumoniae, A. Baumanii, and P. aeruginosa. The administered ABDs included 31 international nonproprietary names of the group J01 Systemic antibacterial drugs. The direct medical costs of empirical antibacterial therapy averaged for 9367 rubles (2118 rubles [1462; 3525]). Comparative cost-effectiveness analysis was performed based on surrogate and endpoints. It was found that direct medical costs associated with ESKAPE pathogens spend about 70% of the budget of established tariff to pay for medical care of the compulsory health insurance program for the patient's stay in the ICU.Conclusion. Antibacterial therapy costs for nosocomial pneumonia significantly increase the total cost of a patient's hospital stay. Сlinical and economic assessment of drug use help optimize therapy costs and develop a hospital formulary of antimicrobial drugs.

How to Teach Literacy to Artificial Neural Networks Making AI intelligent by Learning from other Disciplines

What does literacy mean in AI? Generative AI, especially Large Language Models (LLM), use statistical relevance to build responses to prompts. Literacy in education means understanding cause and effect from a text and why one observation follows another. It has to do with the real world and some understanding of how the grounding behaves and works. This kind of learning can be achieved with intelligent systems that combine AI engines with traditional programming, or in terms of the Graph Model of Combinatorial Logic: Observations and Concepts with Lambda Concepts. In conclusion, it is very helpful to listen to other disciplines for making AI intelligent. The respective task list for AI engineers includes, but is not limited to, education and teaching to children and humans. Keywords: artificial intelligence, generative pretrained translators, knowledge acquisition transformation, intelligent systems

Barriers to the Adoption of Augmented Reality Technologies for Education and Training in the Built Environment: A Developing Country Context

The construction industry has been tasked to adapt to technological advancements that other industries have implemented to grow and remain relevant. One of these technological advancements is augmented reality technologies. ART combines real and virtual worlds without completely immersing the individual in a virtual simulation. The use of ART can significantly improve education and training, especially in the construction industry, by analysing real-world environments while training in a controlled setting. This study, therefore, sets out to identify the factors that hinder the use of ART in the built environment. To achieve this, a quantitative research approach was adopted, and questionnaires were distributed to professionals in the built environment using South Africa as the research location. Retrieved data were analysed using both descriptive and inferential statistics. Findings revealed that investment cost is the major hindrance stakeholders face in implementing ART for education and training in the built environment. The exploratory factor analysis result clustered the identified barriers as internal organisation-related, culture-related, knowledge-related, and educator-related barriers. The study concluded that stakeholders in the built environment still have major responsibilities to ensure there is proper awareness of the benefits of adopting ART for education and training.

Hardware-in-the-Loop testing for low-inertia grids

Abstract Extensive testing of various control algorithms using comprehensive testing frameworks enables us to assess their effectiveness in managing system dynamics and maintaining grid stability. In order to validate the algorithms in the real world, testing of the developed applications in an empirical laboratory environment is essential and the testing parameters in the laboratory have to closely resemble real-world conditions. The fundamental aspect of such testing is to monitor and analyze the dynamics and interaction between the various components in synchronous mode, thereby assessing the system’s ability to operate the grid without violations. The experimental test setup and script-based testing explained in this paper helps to develop innovative control algorithms, with a key focus on medium voltage and low voltage grids with low rotating masses. The test platform makes extended use of a Typhoon Real-Time Simulator (RTS). Firstly, it is used for the simulation of the distributed energy resources and the overlying distribution grid as well as the implementation of control algorithms. Secondly, the RTS acts as a control and SCADA system for the whole testing platform. While the physical components provide measurements in regular intervals, the control algorithms and the energy management system are implemented directly in the Typhoon platform. The data acquisition is performed either via programmable logic controllers for the nodal measurements or through faster measurements such as current transformers. This ensures that the developed algorithms are empirically tested and optimized in close to real-world conditions. The control algorithms provide the set points for the individual components, and the results show the advantages of script-based testing in HIL testing to ensure deterministic and reliable operation of innovative grid components.

Features of Medan's Millennials and Z-Gens as Social Media Users

Objectives: The study aimed at examining two generations behavior (Generation Y and Generation Z), especially on social media. The respondents are Gen Y and Gen Z in Medan City, North Sumatra Province, Indonesia. The study focuses on similarities and differences in digital communication behavior between these two generations on social media. Stakeholders such as the government that formulates public policies, industry, politicians, and so on, need to map and understand what the characteristics of social media users are their citizens. Methods: The researchers used quantitative methods with descriptive statistical analysis techniques with a total of 400 respondents. Data was collected using questionnaires and analyzed using the statistical utility SPSS. Results: Research has shown that Generation Y prefers Facebook, while Generation Z prefers Instagram and YouTube. Both generations spend 30–60 minutes on social media, especially at night. While the level of caution on social media tends to appear in Gen Z. A significant difference between the two generations can be seen in the topics they post on social media, Gen Y posts topics about family more often. Meanwhile, Gen Z posts more about achievements. But in terms of how to communicate with each other, these two generations are no different. The majority of these two generations interact online every day with their friends, be it through social media, chat applications, or gaming. Conclusions: Social media interaction has replaced interaction in the real world. Generation Y and Generation Z, as social media users, develop different communication behaviors compared to the other older generations.

Characterization of the real-world first line (1L) use of single dose tremelimumab regular interval durvalumab (STRIDE), for treatment of unresectable hepatocellular carcinoma (uHCC), using two electronic medical record (EMR) databases.

534 Background: In October 2022, the US FDA approved the STRIDE (Single Dose Tremelimumab Regular Interval Durvalumab) regimen, comprising tremelimumab 300 mg for 1 dose plus durvalumab 1500 mg every 4 weeks, for the 1L treatment of uHCC in adults aged ≥18 years. Thus far there is limited data characterizing STRIDE's 1L use in the real world. This observational study aims to describe patient characteristics, and clinical profiles of a 1L STRIDE cohort. Methods: A retrospective cohort study was conducted using EMR data from two community oncology practice networks, Florida Cancer Specialists and American Oncology Network, from January 1, 2018, to March 31, 2024. Adults with HCC who received ≥1 administration of the STRIDE regimen as 1L treatment following diagnosis were included. Patients with evidence of other cancers or systemic therapies pre-index date were excluded, to establish a cancer-naïve cohort at index. Index date was first administration of STRIDE. The analysis described the patient characteristics and clinical profile at index date. Patient demographics, severity indicators (cancer stage, albumin-bilirubin index (ALBI), alpha fetoprotein (AFP), Eastern Cooperative Oncology Group (ECOG)) and lab data were assessed on or closest to index date. Results: 79 patients initiated the 1L STRIDE regimen. The median (P25, P75) age at index was 70 (63.2-76.4) years. 72.2% were males, 64.6% were white, and 69.6% were overweight or obese patients. 95% had their first HCC diagnosis between 2022-2024 and the mean time from diagnosis to index date was 3.8 months (SD: 10.2). Among patients with reported cancer stage (n=57), most (82.5%, n=47) were diagnosed with stages IIIA to IVB. 18% had ECOG scores ≥2. 86% had ALBI grades between 2-3; 42.1% had AFP level ≥400 ng/ml; 30.4% had cirrhosis (among those that reported comorbidities) and 24.1% received any loco-regional therapy. Conclusions: Our study provides a real-world profile of patients on 1L STRIDE. Compared to the HIMALAYA trial, these findings suggest that patients in this real-world study tend to be older, diagnosed at late-stage, have a poor liver profile, and potentially worse prognosis over time. Further research is required to explore treatment pathways after index date, over a long follow-up, which may provide more insight into the continuity and effectiveness of IL STRIDE in the real-world.

Effects of disease aetiology on outcomes for unresectable HCC treated with lenvatanib or atezobev: A real world retrospective study.

554 Background: Hepatocellular Carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-death worldwide. 1 Standard of care first line treatment for unresectable HCC is Atezolizumab plus Bevacizumab (AtezoBev) 1 while the multi-kinase inhibitor Lenvatinib 2 is also available in the first line setting. No randomised studies have compared these treatments directly. Real world data suggests similar overall survival (OS) with AtezoBev possibly superior in patients with a viral hepatitis aetiology and Lenvatinib superior in NAFLD. 3,4,5,6,7 Methods: We evaluated patients treated with Lenvatinib or AtezoBev in a retrospective cohort of patients who commenced first-line treatment in the West of Scotland from 04/12/2015 to 28/11/2023. 102 received Lenvatinib and 52 AtezoBev. We collected data on progression free survival (PFS), OS, demographics and disease aetiology- classified primarily as viral hepatitis, acholic liver disease (ALD) or NAFLD. Results: AtezoBev patients had improved mOS compared with Lenvatinib (13.8 vs 9. 1 months, p = 0.04). No statistically significant differences were observed in mPFS (5.5 vs 3.5 months, p = 0.31). Of the three aetiologies considered, the only statistically significant (p<0.05) difference between the treatments was OS in the NAFLD group (24.1 vs 9.1 months, p = 0.04). When considering patient demographic and disease factors, Child-Pugh score was most significant. Patients with Childs=5 liver disease had much longer OS and PFS compared with Childs≥6 disease. Similarly, patients with ECOG PS=0 had improved survival than PS≥1. There were no statistically significant (p<0.05) differences between AtezoBev and Lenvatinib. Age, sex and social deprivation (SIMD) score had minimal effects on survival although high levels of social deprivation and male sex were over-represented in our population. Conclusions: In contrast to other real world analyses, our patients demonstrated improved mOS with Atezo/Bev vs Lenvatinib. 3 However, mPFS was similar for the two regimes. The difference in OS may be explained by differences in patient selection, with the Lenvatinib group disproportionately representing patients with a poorer performance status (PS>0) and higher Childs-Pugh scores (CP>5). Furthermore, patients in the AtezoBev group who progressed were often offered Lenvatinib second-line, possibly improving mOS, whereas Lenvatinib patients who progressed were offered either Sorafenib, a clinical trial or best supportive care. However, we cannot rule out a direct survival benefit from the use of AtezoBev vs Lenvatinib in the first line setting. The choice of first line therapy for HCC remains complex and must account for patient preferences such as convenience and side effect profile in addition to observed trial outcomes and the increasing body of real world evidence. 1. Finn RS et. al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N. Engl. J. Med. 2020 May 14;382(20):1894-1905. 2. Kudo, Masatoshi et. al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018. Volume 391, Issue 10126, 1163 – 1173. 3. Wang, BC. et. al. Lenvatinib Versus Atezolizumab Plus Bevacizumab in the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis of Real-World Studies. Targ. Oncol. 2024. 19, 203–212. 4. Casadei-Gardini A et. al. Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Eur. J. Cancer. 2023; 180:9-20. 5. Rimini M et. al. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis. ESMO Open. 2022 Dec;7(6):100591. 6. Su CW et. al. Similar efficacy and safety between lenvatinib versus atezolizumab plus bevacizumab as the first-line treatment for unresectable hepatocellular carcinoma. Cancer Med. 2023. 12(6):7077-7089. 7. Rimini, M., et al. Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients. J. Cancer. Res. Clin. Oncol. 2023. 149, 7565–7577.

A cross-sectional analysis from a real-world cohort of patients with microsatellite instability colorectal cancer (MSI-CRC) with localized disease from the Spanish RETUD registry.

173 Background: Microsatellite instability (MSI) localized colorectal cancer (CRC) constitutes a subgroup of patients (pts) with different clinical and molecular characteristics and prognosis compared to microsatellite stable (MSS) disease. Here, we present our real world data regarding the management and clinical outcomes of a cohort of MSI-h localized CRC patients included in the Spanish Group of Treatment of Digestive Tumors (TTD) Registry (RETUD). Methods: RETUD is a national, multicenter registry for gastrointestinal tumors from the Spanish TTD Group. In this cross-sectional analysis we evaluated a real-world cohort of MSI-h localized CRC pts diagnosed from 1 st January 2017 to 29 th April 2024. Baseline characteristics and neo/adjuvant treatments are descriptively presented. Disease-free survival (DFS) and overall survival (OS) analyzed by Kaplan-Meier method are presented along with 95% confidence intervals (CI). Results: Five hundred and sixty-one (561) evaluable pts out of 679 MSI-CRC included in RETUD had a localized disease as initial diagnosis. Pts had a median age of 73.1 years and were predominantly Caucasian (97.7%) and female (52.6%). Fifty (12.4%) pts had Lynch Syndrome. Main tumor baseline characteristics are described (Table). Local-locoregional therapeutic procedures were: primary tumor resection in 531 (99.1%) pts and radiotherapy in 18 (3.2%) pts. A total of 198 (35.3%) pts received systemic therapy, mostly chemotherapy (n=165 83.3%) but 18 (9.1%) were treated with pembrolizumab due to unresectable disease. At database cut-off, 123 (21.9%) patients died, mostly due to not related intercurrent illness, and 96 (17.1%) pts developed metastasis. After a median follow up period of 28.5 months, the median (95% CI) OS was not reached and DFS was 78.2 (55.4-NA) months. The impact of adjuvant systemic therapy (chemotherapy vs. non-chemotherapy) for both stage II and stage III pts is under evaluation. Conclusions: Our work provides valuable real-world data from a cohort of MSI-h localized CRC pts treated under clinical practice conditions in Spain, reiterating the good disease prognosis exhibited by this subset of pts in contrast to MSS pts. Main tumor characteristics. Stage at initial diagnosis, n (%) I/II n (%) 55 (9.8) / 258 (46.0) III, n (%) 248 (44.2) Location of primary tumor a , n (%) right colon /left colon /rectum 447 (78.4) / 82 (14.4) / 41 (7.2) Type histological b , n (%) Intestinal 271 (48.9) Mucinous (colloid) adenocarcinoma (>50% mucinous) 115 (20.8) Signet ring cell carcinoma (>50% signet ring) 14 (2.5) Medullary carcinoma 18 (3.2) a Pts with more than 1 primary tumor; the percentage may be over 100%. b Unknown histology in 132 (23.8%) pts and missing data in 7 pts.

Efficacy and safety of durvalumab plus tremelimumab for unresectable hepatocellular carcinoma in Thailand: A real-world multicenter observational study.

539 Background: Durvalumab plus tremelimumab (Durva/Treme) andatezolizumab plus bevacizumab are preferable first-line therapy for unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of Durva/Treme in real world setting. Methods: Fifty patients with uHCC who enrolled in the expanded access program (EAP) for Durva/Treme as the first-line treatment from 12 centers in Thailand were included. Analysis was assessed for objective response rate (ORR), survival, and adverse events. We also compared data with the HIMALAYA study. Results: Median follow-up time was 9.8 months. There were 24 patients alive and 26 patients deceased. The median age was 62 years. Majority of the patients were male (80%). Hepatitis B, C and non-viral cause were identified in 44%, 30%, and 26%, respectively. Ninety-two percent of patients had Child-Pugh A, while 8% had Child-Pugh B(7). Macrovascular invasion was found in 24% of cases. The full data on efficacy and safety were summarized in table below. Conclusions: To date,this is the largest real-world data of Durva/Treme in the first-line treatment of uHCC. Our study demonstrated that Durva/Treme was effective but had lower ORR and higher liver toxicities than what reported in the HIMALAYA study. EAP (N=50) HIMALAYA (N=393) Response by RECIST1.1, n (%) CR PR SD PD Not evaluable 2(4)4(8)24(48)18(36)2(4) 12(3.1)67(17)157(39.9)157(39.9) - ORR (%) 12 20.1 DCR (%) 60 60.1 mPFS (range), mo 5.36(0.2-12.5) 3.78(3.7-5.3) mOS (range), mo NA 16.4 (14.2-19.6) Adverse events, n (%) A ny grade G rade > 3 A ny grade G rade > 3 Any AE Diarrhea Rash AST elevation ALT elevation Increase bilirubin Hypothyroidism Myocarditis Myositis 37(74) 3(6) 12(24) 23(46) 21(42) 8(16) 7(14) 1(2) 1(2) 12(24) 1(2) 0 6(12) 7(14) 4(8) 01(2) 1(2) 378(97.4)103(26.5) 87(22.4) 48(12.4) 36(9.3) 20(5.2) 47(12.1) -- 196(50.5)17(4.4) 6(1.5) 20(5.2) 10(2.6) 3(0.8) 02(0.5) 3(0.8)

Real-world biomarker testing patterns, first line treatment and drivers of treatment choice in patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma in the United States and Europe.

353 Background: For first line (1L) treatment (tx) in HER2- gastric/gastroesophageal junction (G/GEJ) adenocarcinoma (AC), clinical guidelines recommended platinum-fluoropyrimidine (PF) chemotherapy (CT) in patients (pts) with a PD-L1 combined positive score (CPS) <5 and PF CT in combination with immunotherapy (IO) for CPS ≥5. There is little contemporary evidence into IO tx uptake in the real world. This real world study examined biomarker testing, 1L tx characteristics, and reasons for 1L tx choice in pts with HER2- G/GEJ AC to identify unmet needs and opportunities for optimal clinical practice. Methods: Data were derived from the Adelphi G/GEJ Cancer Disease Specific Programme: a systematic approach involving multi-national, multi-faceted data sources including cross-sectional surveys capturing data from physicians and their consulting pts. Physicians reported pt demographics, clinical characteristics, tx received and reasons for tx decisions, via chart review. Data were collected across US and Europe (EU: France, Germany, Spain, the UK) between Oct 2022 to Apr 2023. All pts were alive at data collection and analyses were descriptive. Results: Overall, 243 treating physicians (US n=60/EU n=183) provided data on 642 HER2- pts (US n=83/EU n=559) receiving 1L tx at data collection. For pts from US/EU, median age was 66/67 years, 84%/79% had an ECOG of 0-1 and 52%/75% had metastatic disease at data collection. In the US/EU, 87%/80% of pts were tested for PD-L1 status respectively, of which 63%/69% had a known CPS. For US/EU, 67%/45% of pts (n=30/n=139) had a CPS ≥5. Differences in biomarker testing rates were observed in US v EU pts respectively for MSI/dMMR (66% v 58%), NTRK-gene fusion (31% v 4%) and FGFR2 (27% v 3%). Of US/EU physicians, 70%/85% (n=60/n=183), reported the main reason for conducting biomarker testing was ‘to inform tx decisions’. Cost related concern (50%/39%) and time constraints (23%/15%) were the main perceived barriers to testing. Among pts with PD-L1 CPS <5, 27% of US pts and 2% of EU pts received IO + CT; in pts with CPS ≥5, 63% of US pts and 76% of EU pts received IO + CT. Whilst progression free survival/overall survival benefit were the most common reasons selected by physicians for 1L tx choice across the US/EU (75%/74% and 60%/61%), differences across regions were reported for tx choice based on maintaining and improving pt’s QoL (4%/28%) and pt’s performance status (2%/24%). Conclusions: PD-L1 testing was not performed by 19% of physicians and approximately one third of pts with CPS ≥5 across the US/EU were not receiving IO + CT in 1L. As informing 1L tx choice was a key driver for biomarker testing, there may be scope for improvement in 1L tx by increasing testing rates. Further studies are needed to address barriers to biomarker testing and uptake of IO in pts who can benefit from 1L IO tx.

Genomic Testing in Adults With Undiagnosed Rare Conditions: Improvement of Diagnosis Using Clinical Exome Sequencing as a First-Tier Approach.

Adult patients with undiagnosed genetic disorders suffer most from diagnostic delay and seldom appear in cohort studies investigating the diagnostic yield in medical genetic clinical practice. Here we present the results of the diagnostic activity performed in a referral center on 654 consecutive, unselected adult subjects presenting with molecularly unsolved conditions. More than 50% of the referred individuals were affected by syndromic or isolated intellectual disability. Different molecular approaches, including clinical/whole exome sequencing (CES/WES), chromosomal microarray analysis (CMA), and/or targeted gene or gene panel sequencing were used to analyze patients' DNA. Definitive diagnosis was obtained in over 30% of individuals. The most sensitive methodology was CES/WES, which allowed us to reach a diagnosis in over 50% of the 162 solved cases. Despite the great variety of clinical presentations, our results represent a reliable picture of the "real world" daily routine in an outpatient medical genetics clinic dedicated to diagnostic activity, and contribute to better understand the great value of a definitive molecular diagnosis in adults, either for the affected individuals and their families. This retrospective analysis demonstrates the importance of adopting a genomic-first approach within the diagnostic process for adults affected with unsolved rare conditions.

Bridging the gap: using communicative language testing to assess real-world language skills

Communicative Language Testing has to be applicable for four language skills: listening, reading, speaking and writing. Language assessment has an important role in monitoring the progress of language learning. Assessment of productive skills that occurs in the classroom is to be considered specific language skills in real world contact. Language assessment is not only to measure its performance and the language skills of the students and to monitor the progress of the students, but also to identify the difficulties of the students in learning the target language. This observation is focusing on the assessment of students' communicative competence, since hospitality students learn English for Specific Purposes (ESP). The objective of hospitality students learns English is to be able to apply their knowledge to meaningful communicative situations based on the students demand and their real world required.

Real-world (RW) experience with atezolizumab + bevacizumab (A+B) for the treatment of unresectable HCC (uHCC): A multicenter study.

537 Background: A+B is the preferred first-line (1L) standard of care for uHCC, with emerging RW evidence supporting its use in a broad patient (pt) cohort. We evaluated pt characteristics, clinical and treatment outcomes in pts treated at five U.S. institutions: Mayo Clinic, Houston Methodist, Moffitt Cancer Center, Mays Cancer Center, and University of Arizona. Methods: This is a retrospective study of uHCC pts who initiated A+B after January 1, 2019. De-identified pt data were extracted by treating oncologists. Overall survival (OS) and real-world progression-free survival (rwPFS) were assessed using Kaplan-Meier methods for all pts and for a “trial-like” subgroup with characteristics similar to those in the IMbrave150 trial (ECOG performance status [PS] 0-1, Child-Pugh [CP] class A, albumin-bilirubin [ALBI] grade 1-2). HCC-related hospitalizations were evaluated within 1 year of A+B initiation. Results: A total of 300 eligible pts were treated with 1L A+B (median age 68 years, 79% male, 79% White, 82% BCLC C, 44% viral etiology,12% ECOG PS >1). Liver function was CP A in 73% (36% A5, 31% A6, 6% not reported), CP B in 26% pts (15% B7, 7% B8, 5% B9), and CP C in 2 (<1%) pts. Compared with CP A, more CP B pts had characteristics of compromised liver function (CP A vs B: cirrhosis: 61% vs 91%; ascites: 7% vs 46%; encephalopathy: 4% vs 17%; esophageal varices: 14% vs 32%), bile duct invasion (2% vs 11%), and ECOG PS>1 (8% vs 22%), all Ps<0.001. Over a median follow-up of 8.7 mos, 244 (81%) pts discontinued A+B, primarily due to disease progression. Toxicity-related treatment discontinuation and hospitalizations due to treatment-related adverse events (TRAE) were similar between the two groups (Table). Median OS (mOS) was 14.4 mos (95% CI: 12.3, 18.2) and median rwPFS was 6.8 mos (95% CI: 5.8, 8.4). In the trial-like subgroup (n=194), mOS was 19.5 mos (95%CI: 14.6, 24.7) and median rwPFS was 8.8 mos (95% CI: 7.6, 12.1). In the CP B subgroup, mOS was 5.6 mos (95% CI: 4.6, 11.3) and median rwPFS was 3.1 mos (95% CI: 2.4, 5.8). Conclusions: This study demonstrates the RW outcomes of 1L A+B in a diverse pt cohort. Results from the “trial-like” pts further confirm the reproducible efficacy of A+B in clinical practice. Although pts with CP-B had higher hospitalization rates due to disease progression or symptoms, consistent with their underlying liver complications, they had similar rates of toxicity-related treatment discontinuation and TRAE-related hospitalizations compared to CP-A. Further characterization of safety for A+B in CP B pts within a prospective, controlled trial is warranted. N (%) CP A (n=219) CP B (n=79) Treatment discontinuation* 167 (76) 75 (95) Atezolizumab-related toxicity 20 (12) 13 (17) Bevacizumab-related toxicity 26 (16) 16 (21) Hospitalization* 87 (40) 58 (73) Symptom-related 42 (48) 35 (60) Progression 8 (9) 11 (19) TRAE 7 (8) 6 (10) *P-value comparing CP A vs CP B <0.001.

Efficacy and safety of durvalumab and gemcitabine-based chemotherapy combined with or without lenvatinib in advanced biliary tract cancer.

595 Background: Immunotherapy in combination with gemcitabine-based chemotherapy, has now become the standard first-line treatment for advanced biliary tract cancer (BTC). Some small-sample studies have shown that immune checkpoint inhibitors (ICIs), when used in combination with lenvatinib and chemotherapy as first-line therapy, exhibit high anti-tumor activity in BTC. Therefore, we conducted a retrospective study to assess the efficacy and safety of durvalumab and gemcitabine-based chemotherapy with or without lenvatinib, in combination for advanced BTC in the real world. Methods: Between January 2021 and September 2024, patients with advanced BTC who received either durvalumab combined with or without lenvatinib, along with gemcitabine-based chemotherapy, were enrolled in this study. The study endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Thirty patients with advanced BTC were included in this study. Fourteen (46.7%) patients had received durvalumab combined with lenvatinib plus chemotherapy. For all the patients, the median OS was 9.5 months(95% CI: 4.98-14.02), and the median PFS was 5.9 months(95% CI: 4.56-7.24). ORR was 43.4% and DCR was 76.7%. Patients with lenvatinib treatment had a longer median PFS (7.1 vs. 4.6 months, P = 0.06) compared with the non-lenvatinib treatment group. However, the median OS was shorter in patients with lenvatinib treatment group (9.0 vs. 9.5 months, P = 0.915). ORR and DCR in patients with lenvatinib were 57.1% and 92.9%, respectively. However, in patients without lenvatinib treatment group, ORR and DCR were only 31.2% and 62.5%, respectively. All patients experienced adverse events (AEs), addition of lenvatinib does not increase the risk of AEs. The data is still being updated. Conclusions: Durvalumab and gemcitabine-based chemotherapy combined with or without lenvatinib has shown to be effective and safe in routine practice. Regarding lenvatinib, its addition has only improved the DCR, ORR, and PFS, but has not been able to prolong OS.

Age differences in pedestrian navigational skills and performance: A systemic review and meta-analysis.

This study summarized current findings on age differences (young vs. older adults) in pedestrian navigational performance, spatial learning, and examined moderating effects of experimental environment (e.g., real-world vs. virtual environments). Two reviewers independently screened studies from PubMed, Web of Science, PsychInfo, and AgeLine until December 2022. (1) empirical navigational study; (2) healthy older adults (mean age above 60); (3) age as a categorical variable; (4) peer-reviewed paper in English. (1) overly simplified environments; (2) tasks performed with transportation; (3) small sample size (n < 10). 5981 studies were screened, 18 were eligible with 406 total participants. Three-level meta-analysis estimated standardized mean age difference of 1.15 (95 % CI: [0.64, 1.65]) in navigational performance, and 0.97 (95 % CI: [0.81, 1.13]) in spatial learning. Study environments were found to marginally moderate age differences in navigational performance, but not in spatial learning. Older adults have poorer navigational performance and spatial learning outcomes compared to their younger counterparts, with marginally greater performance differences in virtual environments than in the real world. Findings were limited by low number eligible studies, especially real-world experiments. Future studies should continue to test generalizability of high-fidelity VR and identify spatial design elements that can mitigate age differences.

Global Projection of Terrestrial Vertebrate Food Webs Under Future Climate and Land-Use Changes.

Food webs represent an important nexus between biodiversity and ecosystem functioning, yet considering changes in food webs around the world has been limited by data availability. Previous studies have predicted food web collapses and coextinction, but changes in food web structure have been less investigated under climate warming and anthropogenic pressures on a global scale. We systematically amassed information about species' diets, traits, distributions, habitat use, and phylogenetics in the real world and used machine learning to predict changes in global meta-food webs of terrestrial vertebrates under climate and land-use changes. By year 2100, terrestrial vertebrate food webs are expected to decrease in web size by 32% and trophic links by 49%. Projections predict declines of over 25% in modularity, predator generality, and diversity of trophic groups. Increased species' dispersal could ameliorate these trends but indicate disproportionate vulnerability of regional food webs. Unlike many previous studies, this work combines extensive empirical data with advanced modeling techniques, providing a more detailed and spatially explicit prediction of how global food webs will respond to climate and land-use changes. Overall, our study predicts terrestrial vertebrate food webs will undergo drastic and spatially heterogeneous structural changes.

FOLFIRI-ramucirumab (FOLFIRI-Ram) versus ramucirumab-paclitaxel (Ram-Pac) in the second line (2L) for patients with advanced upper gastrointestinal (UGI) cancer: A real-world propensity-score matched analysis of survival.

377 Background: The approach to 2L treatment of advanced UGI (gastric, esophageal, and gastroesophageal junction) cancers is guided primarily by the results of the RAINBOW trial, a global randomized phase III trial that demonstrated the benefit of Ram-Pac over paclitaxel. However, the onset of peripheral neuropathy limits its use in the palliative-intent setting. The RAMIRIS trial demonstrated the feasibility of 2L FOLFIRI-Ram compared to Ram-Pac, however it failed to meet the prespecified endpoint of ≥ 65% 6-month overall survival (OS). Despite this, FOLFIRI-Ram has emerged as an alternative 2L regimen and now endorsed in major society guidelines. Yet, comparative outcomes between FOLFIRI-Ram and Ram-Pac therapy in the real world are lacking. Methods: This study used the nationwide Flatiron Health electronic health record-derived deidentified database. During the study period (January 2011-June 2024), longitudinal patient-level data were derived from approximately 280 cancer clinics. Patients were eligible for inclusion if they had advanced unresectable or metastatic UGI cancer and received 2L treatment with either FOLFIRI-Ram or Ram-Pac. Demographics and lab values at the time of 2L initiation were extracted. Given anticipated imbalances in sample size, patients were matched 1:6 (FOLFIRI-Ram:Ram-Pac) for inclusion into the analytic dataset using a greedy match based on a logit model to predict propensity scores from key clinical and laboratory characteristics. The primary endpoint was OS from the start of 2L therapy, analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. A hybrid approach was used to construct a multivariate Cox model. Results: A total of 15,908 patients were included in the database, of whom 5189 received a 2L treatment. Of these, 631 patients received 2L Ram-Pac and 40 received 2L FOLFIRI-Ram. After matching, the final sample size was 240 patients who received Ram-Pac and 40 who received FOLFIRI-Ram. Baseline clinical and laboratory characteristics were well-balanced. The median OS from initiation of 2L FOLFIRI-Ram was 9.7 months (95% CI 6.9-12.3) and 7.6 months with 2L Ram-Pac (95% CI 6.3-9.2 months). The hazard ratio (HR) for death with FOLFIRI-Ram was 0.77 (95% CI 0.52-1.15, log-rank P=0.20) in reference to Ram-Pac. The adjusted HR death for FOLFIRI-Ram after adjustment for baseline albumin and white blood cell count was 0.87 (95% CI 0.58-1.30, p=0.49) in the final multivariate model. Conclusions: This real-world propensity-score matched analysis of patients with advanced UGI cancers receiving FOLFIRI-Ram or Ram-Pac supports the ongoing use of FOLFIRI-Ram in the 2L as an alternative to Ram-Pac. These data are consistent with results from the RAMIRIS study, however further prospective study is needed.