bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single‐cell dissection of cervical cancer reveals key subsets of the tumor immune microenvironment
Authors: Cao Guangxu , Yue Jiali , Ruan Yetian , Han Ya , Zhi Yong , Lu Jianqiao , Liu Min , Xu Xinxin , Wang Jin , Gu Quan , Wen Xuejun , Gao Jinli , Zhang Qingfeng , Kang Jiuhong , Wang Chenfei , Li Fang 
Published: July 2023

AbstractThe tumor microenvironment (TME) directly determines patients' outcomes and therapeutic efficiencies. An in‐depth understanding of the TME is required to improve the prognosis of patients with cervical cancer (CC). This study conducted single‐cell RNA and TCR sequencing of six‐paired tumors and adjacent normal tissues to map the CC immune landscape. T and NK cells were highly enriched in the tumor area and transitioned from cytotoxic to exhaustion phenotypes. Our analyses suggest that cytotoxic large‐clone T cells are critical effectors in the antitumor response. This study also revealed tumor‐specific germinal center B cells associated with tertiary lymphoid structures. A high‐germinal center B cell proportion in patients with CC is predictive of improved clinical outcomes and is associated with elevated hormonal immune responses. We depicted an immune‐excluded stromal landscape and established a joint model of tumor and stromal cells to predict CC patients' prognosis. The study revealed tumor ecosystem subsets linked to antitumor response or prognosis in the TME and provides information for future combinational immunotherapy.
Use of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer: a multidisciplinary perspective for daily practice
Authors: Capdevila Jaume , Deandreis Desiree’ , Durante Cosimo , Leboulleux Sophie , Luster Markus , Netea-Maier Romana , Newbold Kate , Singer Susanne , Sykiotis Gerasimos P , Bartes Beate , Farnell Kate , Locati Laura Deborah 
Published: July 2023

Background
Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers.

Methods
With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events.

Conclusions
It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.
ФОРМУВАННЯ ЕКОЛОГІЧНИХ КОМПЕТЕНТНОСТЕЙ ФАХІВЦІВ З МІЖНАРОДНОГО ГОТЕЛЬНО-ТУРИСТИЧНОГО БІЗНЕСУ
Authors: Semyrga L.I. , Khomyn V.R. , Kaziuka N.P. , Humeniuk V.V. 
Published: July 2023

У статті здійснено дослідження елементів екологічних компетентностей, які можливо сформувати у фахівців з міжнародного готельно-туристичного бізнесу з використанням міждисциплінарного підходу. Обґрунтовано необхідність оцінки знань, умінь, навичок, які є необхідними для успішної роботи у сфері готельно-туристичного бізнесу з точки зору екологічної відповідальності. Проаналізовано нормативні акти, інституційні норми та правила, які регулюють діяльність готельно-туристичних підприємств в екологічній сфері, що дало змогу з'ясувати понятійні конструкції, які пов’язані з екологічною відповідальністю в готельно-туристичному бізнесі.
На основі опитувань фахівців-практиків з’ясовано рівень обізнаності представників готельно-туристичного бізнесу з проблематикою екологічної відповідальності, застосування екологічних практик у готельній справі; завдяки спостереженням за роботою готелів та функціонуванням курортів виявлено питання відповідального поводження з відходами, енергетичними та водними ресурсами, природними територіями.
Обґрунтовано формування професійних компетентностей у фахівців за бакалаврською освітньою програмою «Міжнародний готельно-туристичний бізнес» Івано-Франківського національного технічного університету нафти і газу з екологічної відповідальності готельного бізнесу, що полягає у здатності готелів та інших закладів гостинності дбати про навколишнє середовище, зменшувати вплив своєї діяльності на природу та ресурси, регламентувати процес забезпечення збалансованого розвитку готельно-туристичної індустрії, забезпечувати економічний, соціальний і екологічний розвиток територій.
Розроблено структурно-логічну схему формування компетентностей майбутніх фахівців з міжнародного готельно-туристичного бізнесу; розглянуто асиметрію готельної індустрії Green Key на карті Європи; описано проблеми, що стримують подальший розвиток екологічного туризму; виокремлено фактори досягнення сталого розвитку готельно-туристичного бізнесу; ідентифіковано заходи, які можуть допомогти готелю зменшити свій вплив на навколишнє середовище та створити більш конкурентоспроможні послуги харчування за рахунок екологічного фактору.
На основі вивчення міжнародного досвіду доведено, що наявність сталих практик у готелях не лише приносить користь навколишньому середовищу, але й покращує економічну і соціальну поведінку туристів, підвищує моральний дух персоналу та сприяє довгостроковому успіху готелю.
Intensivists’ Reported Management of Critical Bronchiolitis: More Data and New Guidelines Needed
Authors: Zurca Adrian D. , González-Dambrauskas Sebastián , Colleti Jose , Vasquez-Hoyos Pablo , Prata-Barbosa Arnaldo , Boothe David , Combs Bryan E. , Lee Jan Hau , Franklin Donna , Pon Steven , Karsies Todd , Shein Steven L. 
Published: July 2023

OBJECTIVES
Existing bronchiolitis guidelines do not reflect the needs of infants admitted to the PICU. This study aimed to identify PICU providers’ reported practice variations and explore the need for critical bronchiolitis clinical guidelines.

METHODS
Cross-sectional electronic survey available in English, Spanish, and Portuguese between November 2020 and March 2021, distributed via research networks from North and Latin America, Asia, and Australia/New Zealand.

RESULTS
A total of 657 PICU providers responded, including 344 English, 204 Spanish, and 109 Portuguese. PICU providers indicated frequently using (≥25% of time) diagnostic modalities for nonintubated and intubated patients on PICU admission (complete blood count [75%–97%], basic metabolic panel [64%–92%], respiratory viral panel [90%–95%], chest x-ray [83%–98%]). Respondents also reported regularly (≥25% of time) prescribing β-2 agonists (43%–50%), systemic corticosteroids (23%–33%), antibiotics (24%–41%), and diuretics (13%–41%). Although work of breathing was the most common variable affecting providers’ decision to initiate enteral feeds for nonintubated infants, hemodynamic status was the most common variable for intubated infants (82% of providers). Most respondents agreed it would be beneficial to have specific guidelines for infants with critical bronchiolitis who are requiring both noninvasive (91% agreement) and invasive (89% agreement) respiratory support.

CONCLUSIONS
PICU providers report performing diagnostic and therapeutic interventions for infants with bronchiolitis more frequently than recommended by current clinical guidelines, with interventions occurring more frequently for infants requiring invasive support. More clinical research is needed to inform the creation of evidence-based guidelines specifically for infants with critical bronchiolitis.
educación online en los museos. El caso del Museo de la Evolución humana (Burgos, Castilla y León)
Authors: Alonso Alcalde Rodrigo , Juez Aparicio Laura , Abajo González Andrés 
Published: July 2023

La irrupción de la pandemia por COVID-19 paralizó de manera radical el funcionamiento normalizado de los museos. Ante esta situación, el Museo de la Evolución Humana (MEH), situado en Burgos y dependiente de la Junta de Castilla y León, desarrolló un programa educativo que le permitió estar conectado en tiempo real con los centros escolares. Las actividades diseñadas, basadas en la utilización de las nuevas tecnologías de la información y comunicación, han permitido diseñar una serie de visitas online y conexiones en directo a través de redes sociales que han acercado los contenidos del MEH a 100.000 escolares. De esta manera, el MEH se ha convertido en un paradigma que nos permite comprobar cómo la irrupción de la COVID-19 ha servido para consolidar las TIC en el ámbito educativo de los museos.
Blood metabolites profile and Growth Hormone mRNA expression of Peranakan Ongole cattle fed with finishing ration containing Vinasse-molasses
Authors: Fassah Dilla Mareistia , Nuraini Nanda Nadhifa , Khotijah Lilis , Komalasari Kokom , Suharti Sri , Astuti Dewi Apri , Wiryawan I Komang Gede , Sudarman Asep , Diapari Didid 
Published: July 2023

<p class="MDPI17abstract"><strong>Objective: </strong>This study aimed to investigate effects of Molasses replacement with Vinasse-molasses in ration on the blood metabolite profiles and mRNA expression of <em>Growth Hormone 1</em> (<em>GH1)</em> of finishing Peranakan Ongole (PO) Cattle.</p><p class="MDPI17abstract"><strong>Methods: </strong>Ten male PO cattle in averaged 209 ± 21 kg of body weight were equally allocated to receive either molasses or Vinasse-molasses dietary treatments. The concentrate diet was contained of either 15% of molasses (control) or Vinasse-molasses. This study observed the nutrient intake, percentage of weight gain, blood metabolite profiles and <em>GH1</em> mRNA expression of PO cattle.<strong></strong></p><p class="MDPI17abstract"><strong>Results: </strong>The result showed that replacing molasses with vinasse-molasses reduced (P&lt;0.05) dry matter intake (DMI) and intakes of crude protein (CP), ether extract (EE), crude fiber (CF), and total digestible nutrient (TDN). Nevertheless, Vinasse-molasses inclusion did not change (P&gt;0.05) percentage of weight gain. Vinasse-molasses increased (P&lt;0.05) the blood urea nitrogen level, while it did not affect (P&gt;0.05) the <em>GH1 </em>mRNA levels.</p><p class="MDPI17abstract"><strong>Conclusions:</strong> It can be concluded that replacing molasses with vinasse-molasses does not change blood metabolite profile, <em>GH1</em> mRNA expression and performance of PO cattle. Vinasse-molasses could be applied as energy sources ingredient to replace molasses in finishing cattle feed.<strong></strong></p>
Convict cichlid parental defense behavior towards conspecific and heterospecific parental pairs influences natural pair distribution
Authors: Santangelo Nicholas , Lane Morgan Rose , Breukelen Natalie April van 
Published: July 2023

Abstract
Parental defense is risky, so parents balance the costs and benefits to make context-dependent decisions based on the type of threat which may impact pair distribution. Our previous field studies in convict cichlids, Amatitlania nigrofasciata, showed that the risk of brood mixing impacts aggression towards conspecific intruders. We also observed that parental pairs seem to distribute differently in relation to conspecifics versus heterospecific pairs. Parental aggression appeared to vary depending on species, with more aggression towards conspecifics than heterospecifics at closer distances. Here, we mapped pair distribution identifying pairs with neighbors within 3m. We found that more convict cichlid pairs had neighbors than did not and those with neighbors tended to be closer to heterospecifics than conspecifics. We then presented pairs of parental convict cichlids with stimuli consisting of other parental convict cichlid pairs or parental Hypsophrys nematopus pairs. Each focal pair was exposed to each species separately and then simultaneously at both near (20cm) and far (60cm) distances. During separate presentations, focal parents were more aggressive at near distances versus far distances for both conspecifics and heterospecifics, though the aggression towards heterospecifics was always less than that toward conspecifics at each distance. In the simultaneous presentations the focal parents were always more aggressive toward conspecific stimuli. These results support the idea that each species represent separate risks (such as conspecific brood mixing or predation) and benefits (such as shared offspring or territory defense) to reproductive fitness, which help shape the observed natural distribution of pairs.
Two Novel Approaches for the Implementation and Assessment of Self-Directed Learning in the Pre-Clinical Medical School Curriculum
Authors: Menon Bindu , Matus Coral D. , Laukka Jeremy J. 
Published: July 2023

Abstract
Introduction:
Self-directed learning (SDL) is a process in which learners diagnose their learning needs, formulate learning goals, and identify appropriate resources to close the knowledge gap. While there has been a growing emphasis on medical schools incorporating SDL into their curriculum, implementation can bring challenges. The objective of this study was to assess student satisfaction as well as content mastery after implementing two novel models of SDL into our pre-clinical curriculum.
Methods
In the first model instructors provided a detailed clinical vignette (topic: anticoagulants; Cardio-Renal system) to the students, who were then instructed to identify a learning objective, identify appropriate resources, and submit their findings on the learning management software. Instructors provided individual narrative feedback to the students based on a well-defined rubric. In the second model, the faculty designed a series of questions/learning objectives based on a chosen topic (COVID-19). The students were divided into small groups of 5–6. Each group chose a clinical question, found original research papers that addressed their learning objective, and then presented the findings to their peers. The faculty provided narrative feedback based on their presentation guided by a rubric. The authors conducted a cross-sectional survey of the second-year students who participated in the program (n = 158/175; 90%). Survey items measured students' approach towards SDL, thoughts on the role of SDL in their learning process, and factors influencing their engagement and satisfaction. Finally, we analyzed students’ content mastery on the topic covered by SDL in the internal assessments using a cognitively diagnostic assessment called the Deterministic Input, Noisy “And” Gate (DINA) model.
Results
Students reacted positively in the survey with 69% percent of the respondents reporting that SDL reinforced their learning and 66% agreeing that it helped their development as lifelong learners. DINA model analysis showed that 91% of the students attained the skills necessary to answer questions on “COVID-19”.
Conclusions
Other medical schools can easily adapt the two innovative approaches described here. In the next phase, the methods will be further refined and elaborated into other systems based on student feedback.
Multiomics analysis reveals a Type III driven immune response in immunotherapy-induced toxicity in melanoma and identifies potential new therapeutic targets
Authors: Levesque Mitchell , Dimitriou Florentia , Cheng Phil , Saltari Annalisa , Schaper-Gerhardt Katrin , Staeger Ramon , Haunerdinger Veronika , Sella Federica , Tastanova Aizhan , Urban Christian , Dettwiler Susanne , Mihic-Probst Daniela , Michielin Olivier , Gutzmer Ralf , Long Georgina , Becher Burkhard , Dummer Reinhard 
Published: July 2023

Abstract

Immune checkpoint inhibitors (ICIs) are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events (irAEs). Proteomic analysis and multiplex cytokine/chemokine assay from serum at baseline and at irAEs onset in 82 patients indicated aberrant T-cell activity with differential expression of Type I and III immune signatures. This was in line with an increase in the proportions of monocytes and decrease of IL-17A producing CD4+ T-cells in the peripheral blood in single cell RNA sequencing. Multiplex immunohistochemistry and spatial transcriptomics on ICI-induced skin rash and colitis showed increase in the proportion of CD4+ T-cells with IL-17A expression. Anti-IL17A mAbs were administered in two patients with myocarditis, colitis and skin rash with resolution of the irAE. This study demonstrates the potential role of Type III CD4+ T-cells in the irAEs development and provides proof-of-principle evidence to support a clinical trial examining anti-IL17A in their management.
Upscaling modeling of effective elastic properties and anisotropic damage propagation in fractured materials regarded as homogenized media
Authors: Guimarães Marcos Bressan , de Aguiar Cássio Barros , Maghous Samir 
Published: July 2023

Abstract
A model combining the micromechanical reasoning with macroscopic thermodynamic concepts is formulated in this paper for damage evolution in microfractured materials. Fractures correspond to a region of small thickness, along which mechanical and physical properties of the material are degraded. Unlike cracks, fractures are discontinuities able to transfer stress and, therefore, can be regarded from a mechanical viewpoint as interfaces endowed with a specific behavior under normal and shear loading. The present paper consists of employing a micromechanical approach to formulate the homogenized elastic behavior of fractured media. In the context of Eshelby’s equivalent inclusion theory, the approach employs the Mori-Tanaka scheme to estimate the homogenized elastic moduli of materials with multiple fracture families. According to classical references, fractures are geometrically modeled as oblate spheroids endowed with appropriate elastic properties. In order to evaluate the damage evolution in materials with several families of microfractures, a damage model is formulated by combining the above results with a classical thermodynamics approach. Particular emphasis is dedicated to the representation of anisotropic damage, induced by a load applied in a specific direction to a material with an isotropic fracture distribution. The ability of the damage model to describe the response of a material under any loading is demonstrated through a comparison with available experimental data for a ceramic matrix composite silicon carbide reinforced with silicon carbide fibers (SiC-SiC).
Biostratigraphy and paleoecology of the upper Badenian carbonate and siliciclastic nearshore facies in the Vienna Basin
Authors: Jamrich Michal , Rybár Samuel , Ruman Andrej , Kováčová Marianna , Hudáčková Natália 
Published: July 2023

Abstract

This study provides a comprehensive examination of algal bioherm structures, including reefs and carpets that contain nannoplankton and foraminifera, originating from the upper Badenian (Middle Miocene) strata of the Vienna Basin in the Central Paratethys. These lithofacies primarily consist of calcareous red seaweeds from the Lithothamnion genus. Through an integrated approach that combines calcareous nannoplankton, foraminifera, sedimentology, and palynology, the study explores the Serravallian (upper Badenian) sediments from the Paratethys Sea shelf. The biostratigraphic age, consistent with the NN6 and CPN9 zones, is further corroborated by 87Sr/86Sr dating. Our research highlights the importance of taphonomic processes and paleoecological proxies in small-scale characterization and detecting short-term shifts within paleoenvironmental conditions. These unique bioherm structures contribute to recognizing a novel limestone formation within the Vienna Basin (The Sandberg Formation), which seems pervasive across the Central Paratethys region. The findings uphold the hypothesis of a profound connection between the Mediterranean and Central Paratethys via the Trans Tethyan Trench Corridor, bolstered by upwelling conditions observed in the eastern perimeter of the Vienna Basin. We confirm two main inhibitory mechanisms for carbonate growth in the upper Badenian epoch within the Central Paratethys area: the first is a substantial siliciclastic influx from the Alps and Carpathians, supported by the ongoing rifting of the Vienna and Danube basins; the second is the propagation of evaporites in the Transcarpathian and Transylvanian basins leading to precipitation, which disrupts carbonate growth. This investigation underlines the intertwined relationship between regional geodynamics and carbonate sedimentation processes during the Miocene era.
3d Pharamacophore Model, Virtual Screening, Binding Affinity and Molecular Dynamics Studies of Potential Anticancerous Compounds Against Mammalian Target Rapamycin
Authors: Aarthi S , Keerthana T , Puniethaa Prabhu 
Published: July 2023

Abstract
Breast cancer is a genetically-based public health issue that affects people worldwide. The advancement of the FKBP12-rapamycin complex of the mammalian target (mTOR), the protein that is dysregulated in breast cancer, is essentially concerned with a hormone receptor. The mTORC1 and mTORC2 multiprotein complexes may be cleaved by mTOR, a serine/threonine kinase. mTOR's fap receptor movement is deregulated, which plays a part in cancer, weight, and maturing. The current study aims to acquire anti-cancer compounds from Naturally occurring Plant-based Anti-cancer Compounds (NPACT) as ligands against the target proteins of human breast cancer and identify promising hits against each target protein by analyzing ADME/T (Absorption, Distribution, Metabolism, and Excretion) properties for the chosen ligands and biomolecular interactions. Analyzing the biomolecular interactions, a pharmacophore model with a structure-based was created. and validated using Maestro 11.1. The best three compounds obtained after high-throughput screening are fap-363127 (taiwanin C), 5490349 (20-hydroxyresiniferol 9,13,14-orthophenylacetate), and 493164 (taiwanin E). The pharmacophore model displayed three main features: ARRR, Hydrogen bond acceptor, donor, and aromatic rings. Molecular Dynamics (MD) is a computer simulation technique for examining the physical fluctuations of molecular complexes using GROMACS (GROningen MAchine for Chemical Simulations). The explicit solvent model simulated the protein-ligand complexes for 100 ns. The RMSD (Root Mean Square Deviation) value of the mTOR-Benzothiazol complex ranges between 0.2 nm and 3 nm. The RMSF (Root Mean Square Fluctuation) and Rg (Radiation of gyration) are done by the highest binding compounds. This study suggests that the selected chemicals should be researched and analyzed further for breast tumor treatment and care strategies.