bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 3, randomized study of adjuvant rilvegostomig plus chemotherapy in resected biliary tract cancer: ARTEMIDE-Biliary01.
Authors: Fan Jia , Bekaii-Saab Tanios S. , Aldrighetti Luca A. , Bridgewater John A , Ferrone Cristina R. , Harding James J. , Ikeda Masafumi , Knox Jennifer J. , Wang Julie , Kayhanian Hamzeh , Chen Xin , Bai Sally Yan , Drachsler Moritz Wolfgang , Oh Do-Youn 
Published: July 2024

TPS4199 Background: Biliary tract cancer (BTC) is a rare but aggressive heterogenous group of gastrointestinal cancers that arise from the intra- or extrahepatic bile ducts (cholangiocarcinoma [CCA]) or the gallbladder (GBC). In early-stage disease following curative resection, adjuvant chemotherapy with a fluoropyrimidine- or gemcitabine-based regimen is usually recommended, however, recurrence rates remain high (e.g. in the BILCAP study, 5-year recurrence-free survival with adjuvant capecitabine was 34%). Immunotherapy is efficacious as adjuvant therapy in other cancer types. Results from the TOPAZ-1 and KEYNOTE-966 studies support combining immunotherapy and chemotherapy in advanced BTC, including in locally advanced non-metastatic disease. Furthermore, dual inhibition of programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) and the novel immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), has shown promising results across multiple tumor types without major increases in high-grade toxicity compared with PD-1 or PD-L1 inhibition alone. Rilvegostomig is an anti-PD-1/-TIGIT bi-specific monoclonal antibody that appears active and well tolerated in non-small-cell lung cancer. ARTEMIDE-Biliary01 will investigate the efficacy of rilvegostomig plus standard of care adjuvant chemotherapy in patients with BTC after curative intent resection. Methods: ARTEMIDE-Biliary01 (NCT06109779) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, global study to assess the efficacy and tolerability of rilvegostomig IV every three weeks versus placebo in combination with investigator's choice of chemotherapy (capecitabine, S-1 [tegafur/gimeracil/oteracil] or gemcitabine/cisplatin) as adjuvant treatment in patients with BTC after curative intent resection. This study will enroll approximately 750 adults with histologically confirmed adenocarcinoma of the biliary tract (intrahepatic or extrahepatic CCA or muscle-invasive GBC) after macroscopically complete resection (R0 or R1) and an ECOG PS of 0–1. Key exclusion criteria include locally advanced, unresectable, or metastatic disease at initial diagnosis and any anti-cancer therapy for BTC prior to surgery. The primary endpoint is recurrence-free survival, and the key secondary endpoint is overall survival. Additional endpoints include progression-free survival following recurrence, patient-reported tolerability, and safety. Enrollment has begun, and approximately 200 sites will be recruiting globally across Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT06109779 .
Xevinapant with radiation and concurrent carboplatin and paclitaxel in patients ineligible for cisplatin with locoregionally advanced squamous cell carcinoma of the head and neck (EXtRaCT study).
Authors: Mir Nabiel Ali , Juloori Aditya , Swiecicki Paul , Katipally Rohan Reddy , Agrawal Nishant , Blair Elizabeth A. , Haraf Daniel J. , Pearson Alexander T. , Vokes Everett E. , Rosenberg Ari Joseph 
Published: July 2024

TPS6126 Background: Locoregionally advanced (LA) head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT) who are ineligible for cisplatin have comparatively poor outcomes, with only ~40% alive at 5 years. There is an urgent unmet need to improve survival in these vulnerable patients with no standard therapeutic approach. Xevinapant, an oral inhibitor of XIAP and cIAP1/2, sensitizes cancer cells to apoptosis. Randomized phase II results in patients eligible for cisplatin combining xevinapant with CRT showed improved locoregional control, manageable toxicity, and promising survival outcomes. (Sun et al. Lancet Oncol. 2020) The current trial aims to extend these benefits to patients ineligible for cisplatin using xevinapant with carboplatin-paclitaxel-based CRT, hypothesizing safety and tolerability in this high-risk group. Methods: This phase I dose escalation/expansion study investigates xevinapant combined with carboplatin and paclitaxel to treat LA HNC in patients ineligible for cisplatin. Key eligibility includes previously untreated LA HNC and specific cisplatin ineligibility criteria, including >=70yo with moderate to severe comorbidity or vulnerability (Geriatric-8 score ≤ 14 and/or CARG score ≥ 30%) or <70yo with severe comorbidity and/or vulnerability, or >=18yo with an absolute contraindication to cisplatin. The treatment regimen comprises escalating doses of oral xevinapant (50-200 mg daily) on days 1-14 of a 21-day cycle for 3 cycles concurrent with CRT and 3 cycles adjuvant, weekly carboplatin AUC 1.5 IV, and paclitaxel 30 mg/m2 IV for 7 doses, and radiotherapy to 70 Gy in standard 2Gy fractions over 7 weeks with primary endpoint of tolerability and recommended phase 2 dose. A Bayesian-modified toxicity probability interval design will identify the maximum tolerated dose (MTD), targeting a 25% dose-limiting toxicity rate, with a sample size of 24 patients in dose-finding. 18 additional patients will be enrolled in the dose-expansion cohort at the MTD, totaling 42 patients. Secondary objectives include safety, response, progression-free, overall survival, and locoregional and distant control. Exploratory aims: in-clinic geriatric evaluations (Katz ADL, Lawton iADL, MMSE), QoL surveys, symptom tracking via smartphone, and wearable-derived steps and sarcopenia assessment. Recruitment began 02/2024. Clinicaltrials.gov ID: NCT06110195. Clinical trial information: NCT06110195 .
Fetal/Maternal-Determined Birth Weight and Adulthood Type 2 Diabetes and Its Subtypes: A Mendelian Randomization Study
Authors: Wang Wenxiu , Xiao Wendi , Song Zimin , Zhuang Zhenhuang , Huang Ninghao , Zhao Yimin , Huang Tao 
Published: July 2024

Abstract

Background
Lower birth weight (BW) might increase the risk of adulthood type 2 diabetes, but its associations with the highly heterogeneous type 2 diabetes subtypes remain to be studied. In addition, whether the associations between lower BW and adulthood type 2 diabetes risks depend on fetal or maternal effect is largely unknown.

Methods
In this study, we performed a two-sample Mendelian randomization analysis to study the associations between overall, fetal-determined, and maternal-determined BW and the risks of type 2 diabetes and its subtypes, namely mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), and severe insulin-resistant diabetes (SIRD).

Results
Lower BW was genetically associated with increased risks of type 2 diabetes (odds ratio [OR]: 1.86; 95% CI: 1.53, 2.26), MARD (OR: 2.15; 95% CI: 1.43, 3.23), MOD (OR: 1.75; 95% CI: 1.10, 2.77), SIDD (OR: 1.86; 95% CI: 1.11, 3.10), and SIRD (OR: 1.66; 95% CI: 1.06, 2.60). When examining the fetal-determined genetic effects independently, lower BW remained associated with type 2 diabetes and its subtypes, except for MOD. Using maternal-determined BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it raised offspring risks of type 2 diabetes.

Conclusion
Fetal-determined but not maternal-determined lower BW were associated with increased risks of adulthood type 2 diabetes and its subtypes. Our results underscored the importance of early targeted management among people with a low BW in the prevention of type 2 diabetes.
Mechanisms underlying the direct programming of mouse embryonic fibroblasts to thymic epithelial cells by FOXN1
Authors: Ma Zhongyao , Kang Seung Woo , Condie Brian G. , Manley Nancy R. 
Published: July 2024

ABSTRACT
Thymic epithelial cells (TECs) are crucial to the ability of the thymus to generate T cells for the adaptive immune system in vertebrates. However, no in vitro system for studying TEC function exists. Overexpressing the transcription factor FOXN1 initiates transdifferentiation of fibroblasts into TEC-like cells (iTECs) that support T-cell differentiation in culture or after transplant. In this study, we have characterized iTEC programming at the cellular and molecular level in mouse to determine how it proceeds, and have identified mechanisms that can be targeted for improving this process. These data show that iTEC programming consists of discrete gene expression changes that differ early and late in the process, and that iTECs upregulate markers of both cortical and medullary TEC (cTEC and mTEC) lineages. We demonstrate that promoting proliferation enhances iTEC generation, and that Notch inhibition allows the induction of mTEC differentiation. Finally, we show that MHCII expression is the major difference between iTECs and fetal TECs. MHCII expression was improved by co-culturing iTECs with fetal double-positive T-cells. This study supports future efforts to improve iTEC generation for both research and translational uses.
Comparison of different types of ultrasound probes for lung ultrasound in neonates—A prospective randomized comparison study
Authors: Aichhorn Lukas , Habrina Lisa , Werther Tobias , Berger Angelika , Küng Erik 
Published: July 2024

Objective
To determine the effect of different types of probes for lung ultrasound in neonates.

Design
Prospective, blinded, randomized, comparative study between 2020 and 2022.

Setting
Single-center study at a third level neonatal unit.

Patients
Hemodynamically stable infants with either nasal continuous positive airway pressure, high flow nasal cannula or without respiratory support.

Intervention
Lung ultrasound using either an echo or microconvex probe. As control, the linear probe was used.

Main outcome measures
Primary outcome measure was neonatologist performed lung ultrasound (NPLUS) score. Secondary outcome measures were number of B-Lines, thickness of the pleural line and subjective image quality. Furthermore, correlation between NPLUS results and clinical data was assessed.

Results
A total of 1584 video loops from 66 patients, with a mean corrected gestational age of 33.8 weeks (SD 4.23) and weight of 1950g (SD 910), respectively, were analyzed. NPLUS score was estimated lower with the echo- and microconvex probe compared to the linear probe, with a coefficient of -2.95 (p < 0.001) and -1.09 (p = 0.19), respectively. Correlation between the pulse oximetric saturation/fraction of inspired oxygen ratio and NPLUS score was moderately strong and best using the microconvex probe (Spearman’s rho = -0.63, p<0.001).

Conclusion
Our results not only confirm the current recommendations, but also demonstrate the extent of the varying results when different probes are used. The differences we discovered call for caution in interpreting scores, especially in the context of guiding therapies and communicating prognoses. Finally, the correlation between NPLUS score and clinical parameters contributes to validating the use of this diagnostic tool.
Building Successful Communication in EMI Contexts: A Multimodal Approach to Organizational Metadiscourse in Intercultural Lectures
Authors: Bernad-Mechó Edgar 
Published: July 2024

Abstract
Higher education (HE) has experienced a swift internationalization process in the last decade, introducing English as a Medium of Instruction (EMI) in many universities. This new reality brings about novel challenges for content lecturers as they adapt to a new way of teaching in English for intercultural audiences. Following Ädel’s (2010) taxonomy of metadiscourse, this paper aims to explore the use of organizational metadiscourse in EMI lectures to foster successful communicative interaction and engagement. Assuming that all communication is multimodal, i.e., meaning is conveyed through the combination of several semiotic resources, this paper sets out to go beyond traditional linguistic studies in order to examine the multimodal use of organizational metadiscourse in lectures. To carry out this analysis, three 90-minute-long videorecorded EMI lectures taught at Universitat Jaume I (Spain) were selected, transcribed and manually inspected to account for all instances of organizational metadiscourse. Next, six structuring segments were chosen, i. e. sections within the lectures in which the contents are being organized. Using the software Multimodal Analysis Video, interactions between speech (organizational metadiscourse) and paralanguage, gestures, gaze, proxemics, head movement and facial expression were examined. Finally, the findings were presented to the lecturers in the recordings to obtain an insight perspective. Results show the active utilization of complex multimodal ensembles co-occurring with organizational metadiscourse. These ensembles reveal an underlying aim of achieving successful communication, by accommodating language to a non-native intercultural audience, and engaging the audience. Lastly, these results are interpreted and pedagogical implications for teacher training are put forward.
Metadiscursive Features in Interdisciplinary Lectures: Implications for EAP Notetaking
Authors: Sezgin Hatice , Topkaya Ece Zehir 
Published: July 2024

Abstract
Academic lectures are among the primary resources of knowledge for higher education students, which makes notetaking a requirement during lectures. The ability to take good notes and the quality of notes taken during lectures are associated with academic achievement; therefore, notetaking instruction is an important aspect of EAP courses. To this end, the present study aims at offering a genre-based instruction framework for notetaking instruction. In accordance with this purpose, eight interdisciplinary lectures were analysed. First, rhetorical functions were identified using the framework developed by Bouziri (2020). Then, metadiscursive elements signalling the organisational structure were identified using the metadiscourse frameworks developed by Ädel (2010) and Hyland (2005). Major findings indicate a relationship between rhetorical functions and metadiscursive elements. Namely, certain metadiscourse items can signal the use of certain rhetorical functions. Thus, the GBI framework for notetaking was structured focusing on the associations that can be established between the rhetorical functions and metadiscursive elements.
Numerical investigation of discharge pressure effect on steam ejector performance in renewable refrigeration cycle by considering wet steam model and dry gas model
Authors: Lin Yongman , Xie Zaijin , Guan Weihua , Gan Lili 
Published: July 2024

Abstract
In recent times, steam ejectors have garnered significant interest among researchers due to their environmental friendliness and the utilization of low-grade energy sources. However, a key drawback of the ejector refrigeration cycle (ERC) is its relatively low coefficient of performance (COP). Understanding the behavior of ejectors under various operating conditions is crucial for addressing this concern. This study specifically focuses on investigating the flow characteristics of ejectors in the single-choking mode. Both dry steam model (DSM) and wet steam model (WSM) are employed to analyze and evaluate the performance in this study. Based on the findings, it is evident that the discharge pressure (DP) significantly influences the flow characteristics. With increasing DP, there is a decrease in the Mach number and liquid mass fraction (LMF) within the ejector, while the temperature distribution shows an upward trend. Additionally, as the DP increases, there is a notable decline in the entrainment ratio (ER) and production entropy. With an increase in the DP, both the DSM and WSM exhibit similar trends. However, in the DSM, the ER reaches zero at an earlier stage compared to the WSM. Specifically, when the DP rises from 5000 Pa to 5600 Pa, there is a 12.6 % increase in the production entropy in the WSM, while the DSM experiences a slightly higher increase of 12.9 %.
Behavioral responses of Ixodiphagus hookeri (Hymenoptera; Encyrtidae) to Rhipicephalus sanguineus nymphs (Ixodida: Ixodidae) and dog hair volatiles
Authors: López-López Noe , Rojas Julio C. , Cruz-López Leopoldo , Malo Edi A. 
Published: July 2024

Abstract
The wasp Ixodiphagus hookeri (Howard; Hymenoptera: Encyrtidae) parasitizes the larvae and nymphs of several tick species worldwide. In this study, we investigated whether I. hookeri females are attracted to Rhipicephalus sanguineus Latreille (Ixodida: Ixodidae) nymphs, hair samples from non-infested and infested Schnauzer dog volatiles, and a synthetic blend of compounds isolated from dog hair in a Y-tube glass olfactometer. We also studied the acceptance of fed and unfed R. sanguineus nymphs by female wasps. Our results showed that I. hookeri females were not attracted to R. sanguineus nymphs. In contrast, they were attracted to dog hair samples and extracts from non-infested and R. sanguineus-infested Schnauzer dog hair. Wasps were more attracted to hair samples from R. sanguineus-infested dogs than to those from non-infested dogs. In addition, I. hookeri females were attracted to a synthetic blend composed of hexanal, heptanal, and isovaleric acid, compounds previously isolated from dog hair. In contrast, I. hookeri females were not attracted to binary blends or individual compounds. Female wasps showed a higher acceptance of live-fed and live-unfed R. sanguineus nymphs than of dead fed nymphs washed with dichloromethane. Our results suggests that the host seeking behavior of I. hookeri females is attributable to a blend of volatiles from infested and non-infested schnauzer dogs, used to attack R. sanguineus nymphs.
Empirische Erkenntnisse zur didaktischen Diagnostik – Implikationen für potenzialorientierten Fachunterricht
Authors: Milius Frauke , Veber Marcel 
Published: July 2024

Zusammenfassung
Ziel des Beitrags ist es, die Relevanz didaktischer Diagnostik für potenzialorientiert-inklusiven Unterricht herauszuarbeiten, bedingt durch die lehrseitige Wahrnehmung von Heterogenität wie auch durch die systemische Rahmung. Zunächst wird der Zusammenhang zwischen Potenzialorientierung und didaktischer Diagnostik theoretisch gerahmt; anschließend werden empirische Erkenntnisse des BMBF-geförderten DiaGU-Projekts anhand ausgewählter Schwerpunkte dargestellt und diskutiert.
A three-way distinction in definiteness: sortal, individual, and functional concepts in Réyoné
Authors: Albers Ulrike 
Published: July 2024

Abstract
This article offers a case study of a definiteness split in a language in which three different types of nominal expressions are available for definite descriptions. The article contributes ample empirical data and comprises a close investigation of the patterns found in Reunion Creole (Réyoné), the language under study. Réyoné displays one kind of contrast also found in other languages which is frequently analyzed in terms of semantic versus pragmatic definiteness (following Löbner) or uniqueness versus familiarity (following Schwarz). What sets Réyoné apart from other languages though, is that it features a determiner that is dedicated to functional concepts. The language thereby distinguishes individual from functional concepts: the former type (the sun; the News) is exclusively expressed by bare noun phrases, while functional concepts – definite descriptions with functional head nouns (prefect of y; head of y), including a subtype of bridging reference, as well as compositionally created functional relations such as superlatives – are realized by lo-marked noun phrases. These facts offer strong support for Löbner’s theory. The article also discusses demonstrative descriptions, which have already been reported to play a role in certain definiteness splits, and which are obligatory with sortal concepts in Réyoné. It is argued that demonstratives are pragmatic definites.
Noninvasive transcranial brain stimulation in central post-stroke pain: A systematic review
Authors: Mayor Rita Sotto , Ferreira Natália R. , Lanzaro Camile , Castelo-Branco Miguel , Valentim Ana , Donato Helena , Lapa Teresa 
Published: July 2024

Abstract

Background
The aim of this systematic review is to analyze the efficacy of noninvasive brain stimulation (NBS) in the treatment of central post-stroke pain (CPSP).

Methods
We included randomized controlled trials testing the efficacy of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation versus placebo or other usual therapy in patients with CPSP. Articles in English, Portuguese, Spanish, Italian, and French were included. A bibliographic search was independently conducted on June 1, 2022, by two authors, using the databases MEDLINE (PubMed), Embase (Elsevier), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science Core Collection. The risk of bias was assessed using the second version of the Cochrane risk of bias (RoB 2) tool and the certainty of the evidence was evaluated through Grading of Recommendations Assessment, Development and Evaluation.

Results
A total of 2,674 records were identified after removing duplicates, of which 5 eligible studies were included, involving a total of 119 patients. All five studies evaluated repetitive TMS, four of which stimulated the primary motor cortex (M1) and one stimulated the premotor/dorsolateral prefrontal cortex. Only the former one reported a significant pain reduction in the short term, while the latter one was interrupted due to a consistent lack of analgesic effect.

Conclusion
NBS in the M1 area seems to be effective in reducing short-term pain; however, more high-quality homogeneous studies, with long-term follow-up, are required to determine the efficacy of this treatment in CSPS.
Structural influences of the substituents of tridentate triazole-based ligands – more than just a minor role in the solid-state structure
Authors: Kroos Simon , Hebenbrock Marian 
Published: July 2024

Abstract
New triazole-based tridentate ligands were synthesized, and their crystal structures determined. Through comparison with the crystal structures of the starting materials and related published ligands, dependencies of intermolecular interactions based on the substitution patterns of the triazole motif were identified. In addition to π-stacking interactions, hydrogen bonding, and C–H···π interactions emerged as key players in intermolecular interactions. The observed variations in these interactions will aid in the design of platinum(II) complexes with specific properties.