bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and anti-tumor activity of a novel aCD25 Treg depleter RG6292 as a single agent and in combination with atezolizumab in patients with solid tumors
Authors: Gambardella Valentina , Ong Michael , Rodriguez-Ruiz Maria E. , Machiels Jean-Pascal , Sanmamed Miguel F. , Galvao Vladimir , Spreafico Anna , Renouf Daniel J. , Luen Stephen J. , Galot Rachel , Doger de Speville Bernard , Calvo Emiliano , Naing Aung , Curdt Samira , Kolben Theresa Maria. , Rossmann Eva , Tanos Tamara , Smart Kevin , Amann Maria , Xie Yuying , Xu Linxinyu , Gomez Alcaide Enrique , Städler Nicolas , Justies Nicole , Boetsch Christophe , Karanikas Vaios , Schnetzler Gabriel , Rohrberg Kristoffer S. 
Published: February 2025

Abstract
Purpose: Therapeutic depletion of immunosuppressive regulatory T cells (Tregs) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector T cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and anti-tumor efficacy of selective Treg depletion by RG6292 administered as monotherapy or in combination with atezolizumab was evaluated in two Phase I studies. Materials and Methods: Adult patients with advanced solid tumors were administered intravenous RG6292 given every 3 weeks (Q3W) alone (Study 1: NCT04158583, N=76) or with 1200 mg atezolizumab Q3W (Study 2: NCT04642365, N=49). Both studies included dose escalation and expansion parts to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (R2PD). Results: RG6292 was well-tolerated. Pruritus and rash were most frequent AEs and were manageable with supportive treatment. Serum RG6292 levels increased dose-proportionally, independent of atezolizumab combination. RG6292 induced a sustained dose-dependent depletion of peripheral Tregs with no apparent effect on other immune cells. Evidence of intratumoral Treg cell reduction (≥50% vs baseline) was observed at RG6292 doses of 35 to 100 mg. The MTD was 165 mg Q3W and the RP2D was proposed as 70 mg Q3W. Objective responses were limited to three partial responses in patients receiving RG6292 combined with atezolizumab. Conclusions: RG6292 induced a dose-dependent peripheral blood and measurable intratumoral Treg depletion in concordance with the proposed mode of action; however, clinical efficacy as single agent or combined with atezolizumab was insufficient to warrant further exploration in this population.
Postural behavior of wild aye-ayes in Madagascar’s Ihofa Forest
Authors: Sefczek Timothy M. , Louis Edward E. , McGraw W. Scott 
Published: February 2025

Abstract
We studied an adult female and a juvenile male aye-aye (Daubentonia madagascariensis) in Madagascar’s Ihofa forest from May to December 2017 to investigate whether the postural diversity of this lemur varied with age, maintenance activity, and habitat use. We used bout sampling (female N = 488, male N = 355) to record postures during feeding and resting and tested for differences using . For both individuals, bimanual and unimanual cling were the most common postures used during feeding (78.4% and 82.9%) and these behaviors were strongly associated with the use of vertical supports – trunks and bamboo – in the main canopy. When feeding on branches and boughs, pronograde postures such as tri-pedal crouch and crouch were most common. Most rest occurred on horizontal branches using primarily pronograde postures. Our data indicate that although aye-ayes exploit multiple forest strata, the great majority of feeding is accomplished using orthograde postures from vertical supports, even in forest strata dominated by horizontal supports. These findings support recent arguments about the significance of vertically oriented behaviors in the evolution of early mammalian arboreal quadrupeds.
Can Plurilaterals Solve the WTO’s National Security Crisis?
Authors: Pahis Stratos 
Published: February 2025

Abstract
National security poses an existential threat to the WTO and trade multilateralism. The accommodation reached between trade and security under the GATT is no longer sufficient, and the United States has taken the WTO hostage until a new accommodation is reached. This article explores whether plurilateral agreements between a subset of WTO members can help resolve the crisis. It begins by explaining why national security poses such a challenge to multilateral trade. It analyzes how the prevailing interpretation of the existing GATT security exception addresses some but not all dimensions of the challenge. And it proposes how plurilateral agreements may do so instead, including by supporting a multilateral agreement to broaden the current GATT security exception or by creating a parallel dispute settlement mechanism for disputes not involving national security. It suggests that such agreements should be encouraged within the WTO to preserve the institution’s relevance in this new geopolitical era.
What and Where on Earth Is Waqwaq?
Authors: Toorawa Shawkat M. 
Published: February 2025

Abstract
For well over a century, Indian Ocean Arabists, using primarily linguistic (and biological) arguments, have posited that Waqwaq is one place or another, one life-form or another. It is now Madagascar, now Sumatra; now a milkweed, now a pandanus; now a bird, now a woman-fruit. It is now a tree, now an island … I myself have not been immune to this need to identify, categorize, classify, locate, and domesticate Waqwaq. The impulse is a dangerous one: it arises out of a notion implicit in the colonial and philological enterprise that to be able to name something, to know how it got its name, and to put it on one’s map, is the better to be able to control it. Recent scholarship has been less constrained by potential philological and interpretive tyrannies and Waqwaq has accordingly benefited from re-sitings and re-readings. In this paper, I ask: What are the roots of Waqwaq and what routes has it taken as it traveled from the Abbasid court to China, from Japan to the Mascarenes, from India to the Philippines, from Istanbul to the New World, and even to Hell (and back).
Scribal Habits of the Aramaic Qumran Texts
Authors: Tov Emanuel 
Published: February 2025

Abstract
In the description of the scribal habits of the Qumran corpus, usually no distinction is made between its constituent groups. Indeed, the Aramaic corpus shares the major scribal practices with the Hebrew corpus (Table 1) as well as some specific ones (Table 2). The two corpora reflect the same systems that were practiced in the last three pre-Christian centuries and the first century CE in Palestine. Further, quite unexpectedly from the angle of the scribal practices, the scribes of two scrolls may be linked to Qumran sectarian scrolls, 4QpapToba ar (4Q196) and 4QPsDana ar (4Q243).
Solomon b. Buyāʿā (Scribe of the Aleppo Codex) and St. Petersburg EVR II B 61+
Authors: Beiler Vincent D. 
Published: February 2025

Abstract
The article provides an introduction to RNL St. Petersburg Ms. EVR II B 61+, a 10th century Masoretic codex containing the Latter Prophets that is nearly entirely extant. There is considerable evidence that Solomon b. Buyāʿā, the scribe of the Aleppo Codex and RNL St. Petersburg Ms. EVR II B 17, wrote the consonantal text and most of the Masorah magna of Ms. EVR II B 61+. The identity of the scribe that provided the Masorah parva, vocalisation, and cantillation is also considered. Cantillation symbol and Masorah parva similarity between II B 17/L1 and the present codex suggest that these were added by Solomon’s brother Ephraim, the masran and naqdan of L1.
Sexual Functioning Among Drug-Naive Females with Depression at Tertiary Care Unit of North India: A Cross-Sectional Study
Authors: Prabhu Pooja Gloria , Devi Shyama , Kar Sujita Kumar , Mishra Sudha 
Published: February 2025

Introduction: Depression is a widespread issue among women in India, affecting all age groups. It can lead to sexual dysfunction, which is more commonly found in females than males, but often goes unreported. The purpose of the study was to evaluate the sexual functioning of females with depression. Methods: The study utilized a cross-sectional research approach to assess 60 females who were diagnosed with depression according to International Statistical Classification of Diseases, Tenth revision (ICD-10) in a psychiatric outpatient department (OPD). The assessment included the use of Mini International Neuropsychiatry Interview (MINI) 6.0.0 screener, sociodemographic and clinical variables, Hamilton Depression Rating Scale (HAM-D) scale, and Female Sexual Functioning Index (FSFI). The study sample only included married females who were drug-naive for the last three months, stayed with their husband for the majority of the time, and were willing to participate in the study. Results: The FSFI test revealed that 61.67% of the participants experienced sexual dysfunction across all domains, with the greatest impact observed in the desire, arousal, and orgasm domains. Lower mean percentages were indicative of more severe sexual dysfunction. Correlation analysis revealed a weak negative relationship between age, the severity of depression, and the duration of the current episode with sexual functioning; however, the results were not statistically significant. Conclusion: According to this study, depressed females experience sexual dysfunctions. Therefore, healthcare providers should ask and consider the sexual aspect while treating patients with depression. Identifying, discussing, and managing problems related to sexual health at an early stage are crucial.
Quality of guidelines for infection management in sepsis: a critical appraisal using the AGREE II instrument
Authors: Yang Guo-Xun , Que Ting , Wang Yi-fei , Liu Xiao-Bo , Dou Shu-Qian , Pu Shi-Ling , Wang Xin , Wu Kong-Jia , Wang Yuan , Wang Qi , Liu Wen-Jun 
Published: February 2025

Abstract

Objectives
The aim of this study was to systematically assess the methodological quality of current sepsis infection management guidelines and identify gaps in knowledge that limit evidence-based practice.

Methods
A systematic search was conducted to obtain guidelines for the management of sepsis infections (2012–2021), and three reviewers independently assessed the quality of eligible guidelines using Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. The intraclass correlation coefficients (ICCs) were used to measure the agreement between reviewers. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to analyze the strength of recommendation and level of evidence of the guideline, and the number of recommendations, strength of recommendation, and level of evidence were determined.

Results
Eleven guidelines for the management of sepsis infection were identified. An overall high agreement among the evaluators for each domain was observed (ICC ranged from 0.850 to 0.959). The overall scores of the included guidelines were all over 60% (range, 62.3-89.90%), which were worthy of recommendation for clinical use; among them, 4 guidelines had an overall score of over 80%, which were high-quality guideline articles. In terms of the quality domains of the guidelines, the scope and purpose domain and the clarity of expression domain had the highest average scores, which were 93.6% (range, 79.6–98.1%) and 91.4% (range, 64.8–98.1%), respectively, while the applicability domain had the lowest average score, which was 64.8% (range, 51.4–76.4%). The strength of the recommendations of the guideline recommendations was mainly weak, accounting for 73.4%; the level of evidence cited was mainly very low quality (60.2%) and low quality (28.1%).

Conclusions
The quality of sepsis infection management guidelines varies, but the overall quality level is satisfactory. Improving the low-quality areas of sepsis guidelines, attempting to resolve existing problems and controversies, and improving the quality of research evidence will be effective ways for developers to upgrade sepsis guidelines.
Role and competency model for coordination tasks in municipal health promotion: findings from an integrative review
Authors: Tollmann Patricia , Dieterich Sven , Kuchler Maja , Leimann Janna , Lubosch Laura , Mielenbrink Vivien , Rangnow Pia , Terhorst Stefanie , Quilling Eike 
Published: February 2025

Abstract

Background
Integrated municipal health promotion is becoming increasingly important in promoting health equity. Successful implementation of integrated municipal health promotion processes requires a central coordinator. Therefore, this study investigates which competencies are necessary to successfully manage the extensive coordination tasks. The aim is to present the necessary roles and competencies in a way that can be applied in practice.

Methods
An integrative review was conducted. As a first step, a systematic search was carried out in the databases LIVIVO, Web of Science and via the EBSCOhost platform (including APA PsycInfo, ERIC, MEDLINE, CINAHL, APA PsycArticles, SocINDEX) using various inclusion and exclusion criteria (e.g. English and German language). The steps of systematic data extraction, data evaluation and data analysis were subsequently carried out. In accordance with the integrative review method, the data were then iteratively compared and synthesised, followed by the final step of presentation and integration in the form of a new model.

Results
According to the pre-defined inclusion and exclusion criteria, 12 hits were included. The results identified were combined into a concept for a role and competency model. Central competencies for the coordination of municipal health promotion are e.g., public health expertise, interprofessional competencies as well as coordination, communication, and management competencies.

Conclusions
The role and competency model presents the roles and competencies needed to coordinate integrated municipal health promotion processes and emphasises the need to work intersectorally. The model provides a guide for practical application and can contribute to the selection of qualified staff, professionalisation, training and curriculum development. It can make a quality-assured contribution to the structural development of integrated health promotion at local level. Further research is needed to validate the model in practice.

Trial registration
This integrative review was not registered beforehand.
Exploring the therapeutic potential of marjoram (Origanum majorana L.) in polycystic ovary syndrome: insights from serum metabolomics, network pharmacology and experimental validation
Authors: Elfiky Aliaa M. , Ibrahim Reham S. , Khattab Amira R. , Kadry Mai O. , Ammar Naglaa M. , Shawky Eman 
Published: February 2025

Abstract

Background
Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with significant metabolic and hormonal dysregulation. Marjoram (Origanum majorana L.), known for its medicinal properties, has potential in managing PCOS through various bioactive compounds.

Objective
This study aims to evaluate the effects of marjoram on PCOS symptoms using serum pharmacochemistry, network pharmacology, and molecular docking in a DHEA-induced rat model.

Methods
Polycystic Ovary Syndrome (PCOS) was induced in rats using dehydroepiandrosterone (DHEA). Marjoram’s therapeutic effects were evaluated by analyzing oxidative stress biomarkers, hormone levels, and ovarian histopathology. Untargeted serum metabolomics, conducted with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC TQD-MS/MS), identified key bioactive compounds. These compounds were then examined through network pharmacology to map their interactions with PCOS-related pathways, with findings validated via molecular docking.

Results
Marjoram treatment significantly reduced oxidative stress by decreasing nitric oxide (NO) and increasing total antioxidant capacity (TAC). Hormonal analysis revealed that high-dose marjoram (100 mg/kg) normalized progesterone, estradiol, testosterone and FSH levels. Body weight gain was also reduced with marjoram treatment, especially at the higher dose. Histopathological evaluation showed fewer ovarian cysts and improved follicular structure with marjoram administration. Network pharmacology analysis highlighted the steroid hormone biosynthesis and estrogen signaling pathways as critical targets, with apigenin and oleic acid identified as active compounds. Molecular docking confirmed strong interactions of these compounds with core PCOS-associated proteins, further supporting marjoram’s potential in modulating PCOS symptoms.

Conclusion
This study reveals that marjoram contains a diverse range of active compounds that can modulate crucial biochemical and histological markers related to PCOS. By combining serum pharmacochemistry with network pharmacology, the research highlights marjoram’s potential as a natural supplement to help alleviate PCOS symptoms and slow the syndrome’s progression. These findings support further investigation into marjoram’s role as a complementary therapy for managing PCOS.
Proteomics revealed novel functions and drought tolerance of Arabidopsis thaliana protein kinase ATG1
Authors: Cheng Shan , Fan Siqi , Yang Chao , Hu Weiming , Liu Fen 
Published: February 2025

Abstract
ATG1 stimulates autophagy biogenesis and serves as a gatekeeper for classical autophagy. To obtain insight into the control of autophagy by ATG1 and determine whether ATG1 has broader processes, we performed a thorough proteomics analysis on the Col-0 wild-type and atg1abct mutant in Arabidopsis thaliana. Proteomic data analysis pointed out that ATG1 has an unidentified function within the inositol trisphosphate and fatty acid metabolism. We also discovered ATG1-dependent autophagy has an emerging connection with ER homeostasis and ABA biosynthesis. Moreover, Gene Ontology terms for abiotic and biotic stress were strongly enriched in differentially abundant proteins, consistent with the reported role of canonical autophagy in these processes. Additional physiological and biochemical analysis revealed that atg1abct exhibited stronger drought resistance under both PEG-simulated drought treatment and natural drought stress. Results from DAB staining also indicated that atg1abct accumulation fewer ROS than Col-0 following drought treatment. As a result, these results illuminate previously unknown functions for ATG1 and offers novel perspectives into the underlying processes of autophagy function.
Functional characterization and evolution of olfactory responses in coeloconic sensilla of the global fruit pest Drosophila suzukii
Authors: Xue Qi , Hasan Kazi Sifat , Dweck Omar , Ebrahim Shimaa A. M. , Dweck Hany K. M. 
Published: February 2025

Abstract

Background
When a species changes its host preference, it often requires modifications in its sensory systems. Many of these changes remain largely uninvestigated in the global fruit pest Drosophila suzukii (also known as spotted wing Drosophila, SWD). This species, which shares a last common ancestor with the model organism D. melanogaster—a species that prefers overripe fruits— ~ 15 million years ago, has shifted its preference from overripe to ripe, soft-skinned fruits, causing significant damage to fruit industries worldwide.

Results
Here, we functionally characterized the coeloconic sensilla in D. suzukii and compared their responses to those of its close relatives, D. biarmipes and D. melanogaster. We find that D. suzukii’s responses are grouped into four functional types. These responses are consistent across sexes and reproductive status. The odorant receptor co-receptor Orco is required for certain responses. Comparative analysis across these species revealed evolutionary changes in physiological and behavioral responses to specific odorants, such as acetic acid, a key indicator of microbial fermentation, and phenylacetaldehyde, an aromatic compound found in a diverse range of fruits. Phenylacetaldehyde produced lower electrophysiological responses in D. suzukii compared to D. melanogaster and elicited strong attraction in D. suzukii but not in any of the other tested species.

Conclusions
The olfactory changes identified in this study likely play a significant role in the novel behavior of D. suzukii. This work also identifies phenylacetaldehyde as a potent attractant for D. suzukii, which can be used to develop targeted management strategies to mitigate the serious impact of this pest.
Impacts of vaping and marijuana use on airway health as determined by exhaled breath condensate (EBC)
Authors: Rojas Dante E. , McCartney Mitchell M. , Borras Eva , Hicks Tristan L. , Lam Tiffany T. , Kenyon Nicholas J. , Davis Cristina E. 
Published: February 2025

Abstract
Across the United States, there is increased use of cannabis products and electronic delivery systems for cannabis products and nicotine, yet little is known about their impacts on lung health. We analyzed exhaled breath condensate of 254 participants who were non-users and users who used cannabis and tobacco products. The 132 participants reported using a product (“users”) were distributed into cohorts of tobacco products and cannabis products, with some participants following into multiple cohorts. Targeted analysis of inflammatory oxylipins found up-regulation among persons using tobacco products, while cannabis users had concentrations closer to nonusers, and often down-regulated. Untargeted screening of 403 significant metabolites found tobacco users had similar breath profiles, and that cannabis users had a similar profile that was closer to the profile of nonusers. Metabolites were significantly higher in breath of people using combustion products (tobacco and cannabis) relative to nonusers, and significantly lower in e-device users (nicotine and THC). Our work demonstrates the relative impact of e-delivery systems and cannabis products compared to traditional cigarette smoking on lung metabolic profiles.