bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging long-acting IL-15 agonists for intratumoral delivery and enhanced antimetastatic activity
Authors: Hangasky John A. , Fernández Rocío del Valle , Stellas Dimitris , Hails Guillermo , Karaliota Sevasti , Ashley Gary W. , Felber Barbara K. , Pavlakis George N. , Santi Daniel V. 
Published: November 2024

IntroductionIL-15 agonists hold promise as immunotherapeutics due to their ability to induce the proliferation and expansion of cytotoxic immune cells including natural killer (NK) and CD8+ T cells. However, they generally have short half-lives that necessitate frequent administration to achieve efficacy. To address this limitation, we have developed a half-life extension technology using hydrogel microspheres (MS). Here, the therapeutic is tethered to MSs by a releasable linker with pre-programed cleavage rates. We previously showed the MS conjugate of single-chain IL-15, MS~IL-15, effectively increased the half-life of IL-15 to approximately 1 week and enhanced the pharmacodynamics. We sought to determine whether the same would be true with a MS conjugate of the IL-15 agonist, receptor-linker IL-15 (RLI).MethodsWe prepared a long acting MS conjugate of RLI, MS~RLI. The pharmacokinetics and pharmacodynamics of MS~RLI were measured in C57BL/6J mice and compared to MS~IL-15. The antitumor efficacy of MS~RLI was measured when delivered subcutaneously or intratumorally in the CT26 tumor model and intratumorally in the orthotopic EO771 tumor model.ResultsMS~RLI exhibited a half-life of 30 h, longer than most IL-15 agonists but shorter than MS~IL-15. The shorter than expected half-life of MS~RLI was shown to be due to target-mediated-disposition caused by an IL-15 induced cytokine sink. MS~RLI resulted in very potent stimulation of NK and CD44hiCD8+ T cells, but also caused significant injection-site toxicity that may preclude subcutaneous administration. We thus pivoted our efforts toward studying the MS~RLI for long-acting intra-tumoral therapy, where some degree of necrosis might be beneficial. When delivered intra- tumorally, both MS~IL-15 and MS~RLI had modest anti-tumor efficacy, but high anti- metastatic activity.ConclusionIntra-tumoral MS~RLI and MS~RLI combined with systemic treatment with other agents could provide beneficial antitumor and anti-metastatic effects without the toxic effects of systemic IL-15 agonists. Our findings demonstrate that intra-tumorally administered long-acting IL-15 agonists counter two criticisms of loco-regional therapy: the necessity for frequent injections and the challenge of managing metastases.
Dynamics trajectory of patient-reported quality of life and its associated risk factors among hepatocellular carcinoma patients receiving immune checkpoint inhibitors: a prospective cohort study
Authors: You Xue-Mei , Lu Fei-Chen , Li Fan-Rong , Zhao Feng-Juan , Huo Rong-Rui 
Published: November 2024

ObjectiveWe aimed to characterize quality of life (QOL) trajectories among patients
with intermediate and advanced hepatocellular carcinoma patients treated with immunotherapy.MethodsBarcelona Clinic Liver Cancer (BCLC) stage B-C HCC patients receiving
immunotherapy at Guangxi Medical University Cancer Hospital were included. Trajectories of QOL,
assessed using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire,
were identified through iterative estimations of group-based trajectory models. Associations with trajectory group membership were analyzed using multivariable multinomial logistic regression.ResultsThree trajectory groups were identified (n=156): excellent (35.3%), poor
(43.6%), and deteriorating (21.1%) QOL. The deteriorating trajectory group reported a mean QOL score
of 124.79 (95% CI, 116.58–133.00), but then declined significantly at month-2 (estimated QOL
score 98.67 [95% CI, 84.33–113.00]), and the lowest mean score is reached at month-6 (estimated QOL score 16.58 [95% CI, 0–46.07]). Factors associated with membership to the deteriorating group included no drinking (odds ratio [OR] vs yes [95% CI], 3.70 [1.28–11.11]), no received radiotherapy (OR vs yes [95% CI], 8.33 [1.41–50.00]), diabetes (OR vs no [95% CI], 6.83 [1.57–29.73]), and extrahepatic metastasis (OR vs no [95% CI], 3.08 [1.07–8.87]). Factors associated with membership to the poor group also included body mass index ≤24.0 kg/m2 (OR vs no [95% CI], 4.49 [1.65–12.22]).ConclusionsThis latent-class analysis identified a high-risk cluster of patients with
severe, persistent post-immunotherapy QOL deterioration. Screening relevant patient-level
characteristics may inform tailored interventions to mitigate the detrimental impact of
immunotherapy and preserve QOL.
Overcoming drug resistance of cancer cells by targeting the FGF1/FGFR1 axis with honokiol or FGF ligand trap
Authors: Szymczyk Jakub , Sochacka Martyna , Biadun Martyna , Sluzalska Katarzyna Dominika , Witkowska Danuta , Zakrzewska Malgorzata 
Published: November 2024

BackgroundChemoresistance of cancer cells, resulting from various mechanisms, is a significant obstacle to the effectiveness of modern cancer therapies. Targeting fibroblast growth factors (FGFs) and their receptors (FGFRs) is becoming crucial, as their high activity significantly contributes to cancer development and progression by driving cell proliferation and activating signaling pathways that enhance drug resistance.MethodsWe investigated the potential of honokiol and FGF ligand trap in blocking the FGF1/FGFR1 axis to counteract drug resistance. Using PEAQ-ITC, we verified direct interaction of honokiol with the FGFR1 kinase domain. We then demonstrated the effect of FGF1/FGFR1 inhibition on taltobulin resistance in cells expressing FGFR1. Finally, we generated drug-resistant clones by prolonged exposure of cells with negligible FGFR levels to taltobulin alone, taltobulin and honokiol, or taltobulin and FGF ligand trap.ResultsWe demonstrated for the first time a direct interaction of honokiol with the FGFR1 kinase domain, resulting in inhibition of downstream signaling pathways. We revealed that both honokiol and FGF ligand trap prevent FGF1-dependent protection against taltobulin in cancer cells expressing FGFR1. In addition, we showed that cells obtained by long-term exposure to taltobulin are resistant to both taltobulin and other microtubule-targeting drugs, and exhibit elevated levels of FGFR1 and cyclin D. We also found that the presence of FGF-ligand trap prevents the development of long-term resistance to taltobulin.ConclusionOur results shed light on how blocking the FGF1/FGFR1 axis by honokiol and FGF ligand trap could help develop more effective cancer therapies, potentially preventing the emergence of drug-resistant relapses.
The Evolving Applications of Laparoscopic Intracorporeal Rectus Aponeuroplasty (LIRA) in Ventral Hernia Repair—A Systematic Review
Authors: Balthazar da Silveira Carlos A. , Rasador Ana C. D. , Marcolin Patrícia , Kasakewitch João P. G. , Lima Diego L. , Morales-Conde Salvador , Malcher Flavio 
Published: November 2024

PurposeLaparoscopic intracorporeal rectus aponeuroplasty (LIRA), emerged as a method that combines benefits from minimally invasive and abdominal wall reconstruction with defect closure, restoring the midline without tension by folding the posterior aponeurosis of both abdominal rectus muscles and using intraperitoneal mesh repair. We aimed to perform a systematic review of the existing evidence on LIRA results and potential applications.SourceA thorough search of Cochrane Central, Scopus, SciELO, LILACS, and PubMed/MEDLINE, focusing on studies that explored LIRA’s possible applications and results was performed. Key outcomes evaluated included recurrence, seroma, hematoma, surgical site infection (SSI), and length of hospital stay. We included both analytic data and descriptive studies.Principal FindingsOut of 128 screened studies, three met the inclusion criteria and comprised 113 patients, of which 69 (61.1%) were operated using LIRA. Three studies comprised two case series of conventional and robotic LIRA repair, and one comparative study of LIRA versus intraperitoneal underlay mesh repair (IPUM plus). No surgical site infections were reported. Seroma rates ranged between 11.1% and 50%, while no bleeding or hematoma was noted. There were no patients presenting recurrence in a median follow-up ranging from 12 to 15 months, despite the comparative study reporting a 4.4% rate of bulging without clinical recurrence. The mean length of hospital stay ranged from 12 to 36 h. LIRA presented no differences in postoperative complications compared to the IPUM plus technique.ConclusionLIRA is linked to low recurrence and postoperative complications. It is a novel approach with potential applications in various types of primary and incisional ventral hernias.
Assessing the Risk of Spreading Clostridioides difficile and Its Toxins Within the Dairy Farm
Authors: Filippova Valentina A. , Ilina Larisa A. , Yildirim Elena A. , Ponomareva Ekaterina S. , Kluchnikova Irina A. , Dubrovin Andrey V. , Kalitkina Ksenia A. , Zaikin Vasiliy A. , Laptev Georgy Y. 
Published: November 2024

Clostridioides difficile currently constitutes a major pathogen of the gastrointestinal tract, which poses a significant growing burden on medicine and veterinary medicine in many regions. A farm was assessed (feed table, silage pit, and feces (healthy animals, emaciated animals, and animals with mastitis)) for the presence of C. difficile toxins using the PCR method and for the microbiome in cow feed and feces using NGS technology, one month apart. C. difficile toxin A and binary toxin were detected in feed samples. C. difficile toxin genes were found in the feces of sick animals two to three times more often than in healthy animals. Analysis of the microbial community of cow feces revealed that, during the month, the animals experienced major changes in the community structure associated with the accumulation of pathogenic bacteria, in particular Paeniclostridium sp., as well as with the development of methanogenic archaea of the Methanobacteriaceae and associated microorganisms (Lachnospiraceae and Anaerovoracaceae), which may speak of a decrease in feed efficiency and, subsequently, animal productivity. Thus, it seems likely that C. difficile enters the gastrointestinal tract of animals through feed, while animals weakened by diseases are more sensitive to the reproduction of pathogens in the GIT due to a weakened organism.
Порівняльний аналіз класифікації ДНК з використанням методу випадкового лісу і згорткових нейронних мереж
Authors: Терпіловський Єгор Олександрович 
Published: November 2024

У статті представлено комплексне порівняльне дослідження двох різних методологій класифікації послідовностей ДНК як у здорових людей, так і у хворих, описано переваги та обмеження їхнього застосування. Перший підхід передбачає представлення k-mer, де кожен можливий k-мер — підрядок довжини k в послідовності ДНК — кодується як двійкова характеристика. Потім ці функції класифікуються за допомогою алгоритму випадкового лісу (random forest — RF), потужної методики ансамблевого навчання, відомої своєю надійністю, здатністю обробляти дані великої розмірності та можливістю інтерпретації. Цей алгоритм створює кілька дерев рішень під час навчання та агрегує їхні прогнози, забезпечуючи надійну структуру класифікації в управлінні різноманітними та зашумленими даними. Другий підхід використовує згорткові нейронні мережі (convolutional neural networks — CNN), які безпосередньо навчаються на необроблених послідовностях ДНК, наданих у форматі FASTA. CNN розроблені для автоматичного вибору ієрархічних характеристик з вхідних даних за допомогою кількох рівнів згортання та об’єднання, що дозволяє їм розпізнавати складні моделі та тонкі варіації в послідовностях ДНК, які можуть вказувати на здоровий стан людини чи хворобу. В процесі навчання CNN використовується зворотне поширення — алгоритм, що широко застосовується для оптимізації нейронних мереж та ітеративно регулює ваги мережі, щоб мінімізувати помилку класифікації та підвищити точність прогнозування. Результати дослідження показують, що CNN, незважаючи на високу точність у визначенні складних шаблонів послідовності, вимагають значно більше обчислювальних ресурсів і гірше інтерпретуються порівняно з RF. Особливо ефективні CNN при виборі нелінійних зв’язків у даних, що робить їх придатними для завдань, де потрібна висока точність. Однак підхід RF пропонує більш ефективне, з погляду обчислень, рішення зі швидшим навчанням і прогнозуванням, а також забезпечує вищий ступінь інтерпретації. Це робить RF особливо цінним у контекстах, де важлива прозорість моделі, наприклад у нормативному середовищі або коли результати потрібно повідомляти зацікавленим сторонам без глибокої технічної експертизи.
IMPLEMENTASI PERAMALAN HARGA BAHAN BAKU MENGGUNAKAN METODE TREND MOMENT BERBASIS WEBSITE
Authors: Robby Mohammad , Fahrudi Setiawan Ahmad , Auliasari Karina 
Published: November 2024

Salama Meat Shop adalah sebuah toko yang menghasilkan berbagai macam jenis daging beku baik itu daging lokal ataupun import. Dengan permintaan yang terus meningkat dari pelanggan, Salama Meat Shop telah mengalami pertumbuhan yang pesat sejak awal pendiriannya. Namun, meskipun demikian, mereka belum mengadopsi sistem peramalan. hal ini mengakibatkan kesulitan bagi pemilik dalam meramalkan harga bahan baku dan sering kali menyebabkan kesalahan dalam menentukan harga produk yang tersedia untuk dijual. Guna mengatasi hal itu metode peramalan trend moment dibutuhkan untuk mengidentifikasi permasalahan yang dihadapi oleh Salama Meat Shop dalam manajemen persediaan dan peramalan harga bahan baku berdasarkan kondisi saat ini. Penelitian ini menggunakan nilai data asli, yaitu data pembelian bahan baku dari Desember 2022 hingga Maret 2024.. Pengujian yang dilakukan menghasilkan nilai akurasi MAPE rata rata sebesar 14,87%.
PENCEGAHAN HAMA PADA TANAMAN PADI MENGGUNAKAN INTERNET OF THINGS (IOT) MENGGUNAKAN RIDDEX ULTRASONIC
Authors: Ucik Ning , Zainul Abidin Rahmad 
Published: November 2024

Pentingnya pencegahan hama pada tanaman padi bagi seorang petani untuk menjaga padi tidak terkena serangan hama, agar memaksimalkan padi ketika panen. Maka peneliti perlu membangun sebuah alat yang mampu memonitoring dan mencegah hama pada tanaman padi secara otomatis. Sensor yang dibuat memanfaatkan sensor Riddex Ultrasonic untuk mendeteksi datangnya hama. Mikrokontrollernya menggunakan Arduino wemo D1mini, karena sudah support networking Wi-Fi. Jika hama mendekat kea rah sensor sekitar 20 meter, maka secara otomatis sensor akan berbunyi dengan maksimal, sehingga membuat hama keluar dari area padi. Kemudian actor akan mendapatkan notifikasi melalui smartphone dengan menggunakan App Inventor yang sudah terkoneksi dengan internet. Metode yang di gunakan adalah sensor riddex ultrasonic yang berbasis iot agar memudahkan petanimendeteksi hama dari jarak jauh dan bisa memantau dari rumah dengan tenang dan damai. Maka, karena efek sistem navigasi sangat berpengaruh pada terganggunya komunikasi hama pada padi. Hasil dari penelitian ini adalah alat ini dapat mendeteksi keberadaan hama secara otomatis. Alat ini bekerja dengan menggunakan sensor riddex ultrasonic yang dapat mendeteksi keberadaan hama dan mengirimkan perintah kepada mikrokontroller ketika hama mendekati sensor.
Visual statistical learning requires attention
Authors: Duncan Dock H. , van Moorselaar Dirk , Theeuwes Jan 
Published: November 2024

AbstractStatistical learning is a person’s ability to automatically learn environmental regularities through passive exposure. Since the earliest studies of statistical learning in infants, it has been debated exactly how “passive” this learning can be (i.e., whether attention is needed for learning to occur). In Experiment 1 of the current study, participants performed a serial feature search task where they searched for a target shape among heterogenous nontarget shapes. Unbeknownst to the participants, one of these nontarget shapes was presented much more often in location. Even though the regularity concerned a nonsalient, nontarget item that did not receive any attentional priority during search, participants still learned its regularity (responding faster when it was presented at this high-probability location). While this may suggest that not much, if any, attention is needed for learning to occur, follow-up experiments showed that if an attentional strategy (i.e., color subset search or exogenous cueing) effectively prevents attention from being directed to this critical regularity, incidental learning is no longer observed. We conclude that some degree of attention to a regularity is needed for visual statistical learning to occur.
An X-Ray Shell Reveals the Supernova Explosion for Galactic Microquasar SS 433
Authors: Chi 池 Yi-Heng 奕恒 , Huang 黄 Jiahui 佳辉 , Zhou 周 Ping 平 , Feng 冯 Hua 骅 , Li 李 Xiang-Dong 向东 , Markoff Sera B. , Safi-Harb Samar , Olivera-Nieto Laura 
Published: November 2024

Abstract
How black holes are formed remains an open and fundamental question in astrophysics. Despite theoretical predictions, it lacks observations to understand whether the black hole formation experiences a supernova explosion. Here we report the discovery of an X-ray shell north of the Galactic microquasar SS 433 harboring a stellar-mass black hole spatially associated with radio continuum and polarization emissions and an H i cloud. Its spectrum can be reproduced by a 1 keV underionized plasma, from which the shell is inferred to have been created by a supernova explosion 20–30 kyr ago, and its properties constitute evidence for canonical supernova explosions to create some black holes. Our analysis precludes other possible origins including heated by jets or blown by disk winds. According to the lower mass limit of the compact object in SS 433, we roughly deduced that the progenitor should be more massive than 25 M
⊙. The existence of such a young remnant in SS 433 can also lead to new insights into the supercritical accretion in young microquasars and the γ-ray emission of this system. The fallback ejecta may provide accretion materials within tens of thousands of years, while the shock of the supernova remnant may play a crucial role in the cosmic-ray (re)acceleration.
Unified Theory of Negative and Positive Spectral Lags in the Gamma-Ray Burst Prompt Phase due to Shear Comptonization from a Structured Jet
Authors: Vyas Mukesh Kumar , Pe’er Asaf , Iyyani Shabnam 
Published: November 2024

Abstract
Positive spectral lags are commonly observed in gamma-ray burst (GRB) prompt phase where soft photons lag behind hard ones in their spectral studies. In contrast to this pattern, a fraction of GRBs show a negative spectral lag where hard photons arrive later compared to soft photons. Similarly, recent Fermi-Large Area Telescope observations show a late onset of high-energy photons in most GRB observations. A fraction of GRBs show a transition from positive to negative lags. Such negative lags and the spectral lag transition have no convincing explanation. We show that a structured GRB jet with velocity shear naturally produces both positive and negative spectral lags. The high-energy photons gain energy from repeated scattering with shearing layers and subsequently escape from higher altitudes. Hence, these photons are delayed compared to soft photons producing a negative spectral lag. The inner jet has no shear, and a positive lag appears to provide a unified picture of spectral lags in GRBs. The theory predicts a flip in spectral lag from positive to negative within the evolution of the prompt phase. Comparison of the observed lags with the prediction of the theory limits the possible range of GRB jet Lorentz factors to a few tens.
Le « grand remplacement » lexical : enjeux sémantiques, performatifs et démocratiques de « la bataille des mots » à l’extrême droite, du Front national à Éric Zemmour
Authors: Alduy Cécile 
Published: November 2024

L’article étudie comment les dirigeants des principaux partis d’extrême droite française (FN-RN, Reconquête !) se sont emparés depuis les années 1990 du thème de la « bataille culturelle » pour construire un récit performatif de conquête du pouvoir par les idées et les mots. Il analyse à partir d’un corpus de textes de Jean-Marie Le Pen, Marine Le Pen et Éric Zemmour diffusés entre 1987 et 2022 les modalités de mise en discours et en récit de la métaphore filée de la « bataille culturelle », son fonctionnement comme lieu commun et ses effets argumentatifs. Il montre que les divers procédés rhétoriques, stylistiques et lexicaux utilisés pour cadrer les débats et transformer le langage politique convergent dans un processus systématique de remplacement lexical et une altération sémantique du vocabulaire républicain. L’article interroge enfin le statut métaphorique ambigu de l’item « bataille culturelle », dont les implicites idéologiques en discours participent d’une valorisation de la violence comme mode d’action et construisent un espace politique et géographique où seul l’affrontement, voire la guerre – et non le débat démocratique – peuvent résoudre les conflictualités.
Quand Bolsonaro part en guerre : mobilisation des enjeux de genre et polarisation dans le Brésil contemporain
Authors: Athayde Sauandaj Antonio 
Published: November 2024

En profitant de l’essor aux années 2010 de la campagne brésilienne contre le « genre », Jair Bolsonaro s’impose comme leader hégémonique de l’opposition, et passe du statut de député à celui de président de la République en l’espace de huit ans. À partir de l’étude de sa stratégie de communication politique, cet article interroge la mise en ressource électorale des enjeux de genre et ses effets de polarisation dans le Brésil contemporain.
L’accueil humanitaire d’urgence aux Îles Canaries : encampement et pandémie aux frontières de l’Europe
Authors: Gallinal Arias Andrea 
Published: November 2024

La route migratoire des Îles Canaries est redevenue scène d’une nouvelle « crise migratoire » en 2020. Cette situation a été conçue et traitée comme une urgence dans le contexte de pandémie de la Covid-19. Cet article examine comment cette crise a conduit à des pratiques de confinement et d’isolement des personnes exilées justifiées par l’urgence humanitaire. Le nouveau modèle d’accueil mis en place par le gouvernement sera analysé pour mettre en avant ces pratiques de contrôle d’une population conçue comme vulnérable.
Confinement et mise en dépendance des refugié·es syrien·nes : le camp de Zaatari en Jordanie
Authors: Khaleefa Amal , Napolitano Valentina 
Published: November 2024

Cet article analyse les logiques humanitaires et sécuritaires qui font du camp de Zaatari en Jordanie un dispositif de confinement et de mise en dépendance des réfugié·es syrien·nes qui y sont installé·es depuis 2012. Il montre comment cet espace, initialement conçu pour faciliter leur accueil, devient un lieu de contrôle et d’isolement, dans un contexte marqué par les pressions des bailleurs de fonds internationaux visant l’endiguement des flux migratoires. Il illustre également comment le confinement dans ses dimensions politiques, juridiques, spatiales et symboliques, engendre une mise en dépendance des réfugié·es et entrave leur projection dans le futur. En s’appuyant sur des enquêtes ethnographiques, cet article place au cœur de l’analyse les représentations des réfugié·es et leurs stratégies de résistance face aux entraves des mobilités et aux difficultés d’accès aux ressources.