bluuebunny/crossref_metadata_2025_split huggingface dataset:
Looking at Monarchy Askance: Royal Brand Names and Trademark Law in the German Empire
Authors: Giloi Eva 
Published: December 2023

AbstractThis article uses the example of Manoli Cigarettes and its product line, The Kaiser Cigarettes, to examine the concept of co-branding as applied to royal brand names in the German Empire. It reviews the broader networks of circulation that determined the production of royal brand names: commercial laws, business ties, advances in technology, advertising structures, tourism, and other sectors of the consumer economy. The article delves into how trademark law, the Imperial Patent Office's role in approving brand names, and case law contributed to the choice of royal brand names. The article also illuminates how manufacturers used royal brands to implement business strategies along a horizontal plane of market competition. The production of the monarchy as a cultural object was thus activated through a process of triangulation: not only through the bilateral relationship between monarch and subjects, but also lateral relations between producers who were concerned about their professional networks.
An investigation into the factors influencing teachers’ inclusion of improvisation in piano lessons
Authors: Cossey Catherine 
Published: December 2023

AbstractDespite the evidence of the benefits of improvisation in instrumental teaching, research indicates that many piano teachers do not include it in their lessons. The purpose of this study was to investigate the influences on piano teachers’ pedagogy to determine what factors impacted the teaching of improvisation. A total of 117 UK-based piano teachers participated in the survey. The data obtained indicates that an understanding of how to teach improvisation is a significant influence on teachers’ pedagogy. The conclusion argues that there is a need for piano teachers to have greater access to instrumental teaching courses to encourage them to reflect on their teaching practice.
Real-world evidence: experiences and challenges for decision making in Latin America
Authors: García Martí Sebastián , Pichón-Riviere Andrés , Augustovski Federico , Espinoza Manuel 
Published: December 2023

Abstract

Objective
The Health Technology Assessment (HTA) process aims to optimize health system funding of technologies. In recent years there has been an increase in what is known as Real-World Evidence (RWE) as a complement to clinical trials. The objective of Health Technology Assessment International’s Latin American Policy Forum 2022 was to explore the utility of incorporating RWE into HTA and decision-making processes in the region.

Methods
This article is based on a background document, survey, and the deliberative work of the country representatives who participated in the Forum.

Results
There is a growing interest in the use of Real-World Data / Real-World Evidence in HTA processes in Latin America, although currently there are no specific local guidelines for RWE use by HTA agencies. At present, its use is limited to certain areas such as adding context to HTA reports, the evaluation of adverse events, or cost estimation.
Potential future uses of RWE were identified, including the creation of risk-sharing agreements, the assessment of technology performance in routine practice, providing information on outcomes that are not so easily evaluated in clinical trials (e.g., the identification of specific subpopulations or quality of life), and the estimation of input parameters for economic evaluations.

Conclusions
The participants agreed that there are several areas presenting significant potential to expand the application of RWD/RWE and that the development of normative frameworks for its use could be helpful.
High-Flow Nasal Cannula versus Bag Valve Mask for Preoxygenation during Rapid Sequence Intubation in the Emergency Department: A Single-Center, Prospective, Randomized Controlled Trial
Authors: Cırıl Muhammed Fatih , Akarca Mustafa , Unal Akoglu Ebru , Cimilli Ozturk Tuba , Onur Özge 
Published: December 2023

AbstractObjective:Hypoxia is a frequently reported complication during the intubation procedure in the emergency department (ED) and may cause bad outcomes. Therefore, oxygenation plays an important role in emergency airway management. The efficacy of oxygenation with high-flow nasal cannula (HFNC) in the ED has been studied, though the evidence is limited. The study aim was to compare two methods of preoxygenation in patients undergoing rapid sequence intubation (RSI) in the ED: (1) HFNC and (2) bag-valve mask (BVM) oxygenation.Methods:This is a single-center, prospective, randomized controlled trial (RCT) in adult ED patients requiring RSI. Patients were randomized to receive preoxygenation with either HFNC or BVM. While HFNC therapy was continued during the intubation procedure, BVM oxygenation was interrupted for laryngoscopy. The primary outcome was the lowest peripheral oxygen saturation (SpO2) level during intubation. Secondary outcomes were incidence of desaturation (SpO2<90%) and severe hypoxemia (SpO2<80%) throughout the procedure, intubation time, rate of failed intubation, and 30-day survival rates.Results:A total of 135 patients were randomized into two groups (HFNC n = 68; BVM n = 67). The median lowest SpO2 value measured during intubation was 96% (88.8%-99.0%) in the HFNC group and 92% (86.0%-97.5%) in the BVM group (P = .161). During the intubation procedure, severe hypoxemia occurred in 13.2% (n = 9) of patients in the HFNC group and 8.9% (n = 6) in the BVM group, while mild hypoxemia was observed in 35.8% (n = 24) of the BVM group and 26.5% (n = 18) of the HFNC group. However, there was no statistically significant difference between the groups in terms of hypoxemia development (P = .429 and P = .241, respectively). No significant difference was reported in the rate of failed intubation between the groups. Thirty-day mortality was observed in 73.1% of the BVM group and 57.4% of the HFNC group, with a borderline statistically significant difference (difference 15.7; 95% CI of the difference: −0.4 to 30.7; P = .054).Conclusion:The use of HFNC for preoxygenation, when compared to standard care with BVM oxygenation, did not improve the lowest SpO2 levels during intubation. Also, the use of HFNC during intubation did not provide benefits in reducing the incidence of severe hypoxemia. However, the 30-day survival rates were slightly better in the HFNC group compared to the BVM group.
NORMAL SUBMONOIDS AND CONGRUENCES ON A MONOID
Authors: ELGUETA JOSEP 
Published: December 2023

AbstractA notion of normal submonoid of a monoid M is introduced that generalizes the normal subgroups of a group. When ordered by inclusion, the set
$\mathsf {NorSub}(M)$
of normal submonoids of M is a complete lattice. Joins are explicitly described and the lattice is computed for the finite full transformation monoids
$T_n$
,
$n\geq ~1$
. It is also shown that
$\mathsf {NorSub}(M)$
is modular for a specific family of commutative monoids, including all Krull monoids, and that it, as a join semilattice, embeds isomorphically onto a join subsemilattice of the lattice
$\mathsf {Cong}(M)$
of congruences on M. This leads to a new strategy for computing
$\mathsf {Cong}(M)$
consisting of computing
$\mathsf {NorSub}(M)$
and the so-called unital congruences on the quotients of M modulo its normal submonoids. This provides a new perspective on Malcev’s computation of the congruences on
$T_n$
.
Albedo as a Competing Warming Effect of Urban Greening
Authors: Schlaerth Hannah L. , Silva Sam J. , Li Yun , Li Dan 
Published: December 2023

AbstractUrban greening is often proposed for urban heat island (UHI) mitigation because vegetation provides shade and increases evapotranspiration. However, vegetation has lower albedo and higher emissivity than the bare soil it often replaces, which increases incoming energy fluxes. Here, we use the Weather Research and Forecasting model to quantify and compare the albedo and non‐albedo effects (i.e., changes in emissivity, surface roughness, and evaporative fluxes) of urban greening in the Los Angeles Basin under policy relevant urban greening scenarios. When albedo‐induced effects were included in the model, daytime surface temperatures in urban areas warmed by 0.70 ± 0.89°C with increases in the sensible heat flux outweighing increases in the latent heat flux from increased evapotranspiration. In contrast, daytime surface temperatures cooled by 0.27 ± 0.72°C when the albedo‐induced effects were ignored. At night, including albedo‐induced effects of urban greening resulted in only half the cooling modeled in the non‐albedo simulations. Near surface air temperatures also had contrasting model results, with nighttime cooling of 0.21 ± 0.47°C outweighing slight daytime warming of 0.04 ± 0.32°C in the non‐albedo simulations and daytime warming of 0.33 ± 0.41°C outweighing slight nighttime cooling of 0.05 ± 0.46°C in the albedo simulations. Our results reveal the critical role that albedo plays in determining the net surface climate effects of urban greening. Reductions in albedo from urban greening should be carefully considered by policy makers and urban planners, especially as high albedo roofs and pavements are simultaneously being deployed for UHI mitigation in many cities.
Clinical and Ethical Considerations of Maladaptive Social Media Use in Pediatric Patients With Disorders of Gut–Brain Interaction
Authors: David Jennie G. , Kroon Van Diest Ashley , Hatley-Cotter Allison , Sanchez Raul , McKillop Hannah N. 
Published: December 2023

Objective: Social media (SM) use among adolescents is commonplace and an extension of their daily lives, with emerging attention to how SM can impact healthcare behaviors. In particular, the clinical and ethical nuance of maladaptive SM use among adolescents with disorders of gut–brain interaction (DGBI) diagnoses remains unclear and pressing to consider. Method: This article presents case examples of maladaptive SM use in (a) a pediatric patient with DGBI and (b) a caregiver of a pediatric patient with a DGBI. We then contextualize these case examples in existing ethical frameworks (e.g., the American Psychological Association Ethics Code) and the extant literature. Results: SM use in pediatrics can negatively impact healthcare behaviors and can lead to consumption of medical misinformation; this impact is particularly significant in pediatric DGBI and merits clinical assessment of maladaptive SM use in this population. Conclusions: SM use can be adaptive or maladaptive for adolescents with DGBIs and caregivers, with maladaptive SM use presenting significant clinical and ethical considerations. In addition to discussing ethical considerations, recommendations, and resources, we also provide clinical questions and takeaways for healthcare professionals to implement in pediatric DGBI care. Implications for Impact Statement Adolescents commonly use social media (SM), with growing attention to how SM can negatively impact health. Adolescents with disorders of gut–brain interaction may be particularly sensitive to this, and healthcare professionals working with this population should consider the ethical and clinical implications of maladaptive SM use.
PAK inhibitor FRAX486 decreases the metastatic potential of triple-negative breast cancer cells by blocking autophagy
Authors: Lyu Liang , Li Haiyan , Lu Kefeng , Jiang Shu , Li Huihui 
Published: December 2023

Abstract
Background
Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with a high risk of metastasis and recurrence and a poor prognosis. Epithelial-mesenchymal transition (EMT) endows epithelial cells with the ability to move to distant sites, which is essential for the metastasis of TNBC to organs, including the lung. Autophagy, an intracellular degradation process that involves formation of double-layered lipid autophagosomes that transport cytosolic cargoes into lysosomes via autophagosome–lysosome fusion, is involved in various diseases, including cancer and neurodegenerative, metabolic, cardiovascular, and infectious diseases. The relationship between autophagy and cancer has become relatively clear. However, research on pharmacological drugs that block cancer EMT by targeting autophagy is still in the initial stages. Therefore, the re-evaluation of old drugs for their potential in blocking both autophagy and EMT was conducted.

Methods
More than 2000 small molecule chemicals were screened for dual autophagy/EMT inhibitors, and FRAX486 was identified as the best candidate inhibitor of autophagy/EMT. The functions of FRAX486 in TNBC metastasis were detected by CCK-8, migration and wound healing assays. The effects of FRAX486 on autophagy and its target PAK2 were determined by immunoblotting, immunofluorescence, immunoprecipitation analysis and transmission electron microscopy. The findings were validated in mouse models.

Results
Here, we report that FRAX486, a potent P21-activated kinase 2 (PAK2) inhibitor, facilitates TNBC suppression both in vitro and in vivo by blocking autophagy. Mechanistically, FRAX486 inhibits autophagy in TNBC cells by targeting PAK2, leading to the ubiquitination and proteasomal degradation of STX17, which mediates autophagosome–lysosome fusion. The inhibition of autophagy by FRAX486 causes upregulation of the epithelial marker protein E-cadherin and thus suppresses the migration and metastasis of TNBC cells.

Conclusions
The effects of FRAX486 on TNBC metastasis suppression were verified to be dependent on PAK2 and autophagy inhibition. Together, our results provide a molecular basis for the application of FRAX486 as a potential treatment for inhibiting the metastasis of TNBC.
Bacteroides is increased in an autism cohort and induces autism-relevant behavioral changes in mice in a sex-dependent manner
Authors: Carmel Julie , Ghanayem Nasreen , Mayouf Rasha , Saleev Natalia , Chaterjee Ipsita , Getselter Dmitriy , Tikhonov Evgeny , Turjeman Sondra , Shaalan Monia , Khateeb Saleh , Kuzminsky Alla , Kvetniy-Ferdman Netta , Kronos Tanya , Bretler-Zager Tali , Koren Omry , Elliott Evan 
Published: December 2023

AbstractAutism Spectrum Disorder (ASD) is a neurodevelopmental condition which is defined by decreased social communication and the presence of repetitive or stereotypic behaviors. Recent evidence has suggested that the gut-brain axis may be important in neurodevelopment in general and may play a role in ASD in particular. Here, we present a study of the gut microbiome in 96 individuals diagnosed with ASD in Israel, compared to 42 neurotypical individuals. We determined differences in alpha and beta diversity in the microbiome of individuals with ASD and demonstrated that the phylum Bacteroidetes and genus Bacteroides were the most significantly over-represented in individuals with ASD. To understand the possible functional significance of these changes, we treated newborn mice with Bacteroides fragilis at birth. B. fragilis-treated male mice displayed social behavior dysfunction, increased repetitive behaviors, and gene expression dysregulation in the prefrontal cortex, while female mice did not display behavioral deficits. These findings suggest that overabundance of Bacteroides, particularly in early life, may have functional consequences for individuals with ASD.
Impaired neuron differentiation in GBA-associated Parkinson’s disease is linked to cell cycle defects in organoids
Authors: Rosety Isabel , Zagare Alise , Saraiva Claudia , Nickels Sarah , Antony Paul , Almeida Catarina , Glaab Enrico , Halder Rashi , Velychko Sergiy , Rauen Thomas , Schöler Hans R. , Bolognin Silvia , Sauter Thomas , Jarazo Javier , Krüger Rejko , Schwamborn Jens C. 
Published: December 2023

AbstractThe mechanisms underlying Parkinson’s disease (PD) etiology are only partially understood despite intensive research conducted in the field. Recent evidence suggests that early neurodevelopmental defects might play a role in cellular susceptibility to neurodegeneration. To study the early developmental contribution of GBA mutations in PD we used patient-derived iPSCs carrying a heterozygous N370S mutation in the GBA gene. Patient-specific midbrain organoids displayed GBA-PD relevant phenotypes such as reduction of GCase activity, autophagy impairment, and mitochondrial dysfunction. Genome-scale metabolic (GEM) modeling predicted changes in lipid metabolism which were validated with lipidomics analysis, showing significant differences in the lipidome of GBA-PD. In addition, patient-specific midbrain organoids exhibited a decrease in the number and complexity of dopaminergic neurons. This was accompanied by an increase in the neural progenitor population showing signs of oxidative stress-induced damage and premature cellular senescence. These results provide insights into how GBA mutations may lead to neurodevelopmental defects thereby predisposing to PD pathology.
De novo design of high-affinity binders of bioactive helical peptides
Authors: Vázquez Torres Susana , Leung Philip J. Y. , Venkatesh Preetham , Lutz Isaac D. , Hink Fabian , Huynh Huu-Hien , Becker Jessica , Yeh Andy Hsien-Wei , Juergens David , Bennett Nathaniel R. , Hoofnagle Andrew N. , Huang Eric , MacCoss Michael J. , Expòsit Marc , Lee Gyu Rie , Bera Asim K. , Kang Alex , De La Cruz Joshmyn , Levine Paul M. , Li Xinting , Lamb Mila , Gerben Stacey R. , Murray Analisa , Heine Piper , Korkmaz Elif Nihal , Nivala Jeff , Stewart Lance , Watson Joseph L. , Rogers Joseph M. , Baker David 
Published: December 2023

AbstractMany peptide hormones form an α-helix on binding their receptors1–4, and sensitive methods for their detection could contribute to better clinical management of disease5. De novo protein design can now generate binders with high affinity and specificity to structured proteins6,7. However, the design of interactions between proteins and short peptides with helical propensity is an unmet challenge. Here we describe parametric generation and deep learning-based methods for designing proteins to address this challenge. We show that by extending RFdiffusion8 to enable binder design to flexible targets, and to refining input structure models by successive noising and denoising (partial diffusion), picomolar-affinity binders can be generated to helical peptide targets by either refining designs generated with other methods, or completely de novo starting from random noise distributions without any subsequent experimental optimization. The RFdiffusion designs enable the enrichment and subsequent detection of parathyroid hormone and glucagon by mass spectrometry, and the construction of bioluminescence-based protein biosensors. The ability to design binders to conformationally variable targets, and to optimize by partial diffusion both natural and designed proteins, should be broadly useful.
The energetic and allosteric landscape for KRAS inhibition
Authors: Weng Chenchun , Faure Andre J. , Escobedo Albert , Lehner Ben 
Published: December 2023

AbstractThousands of proteins have been validated genetically as therapeutic targets for human diseases1. However, very few have been successfully targeted, and many are considered ‘undruggable’. This is particularly true for proteins that function via protein–protein interactions—direct inhibition of binding interfaces is difficult and requires the identification of allosteric sites. However, most proteins have no known allosteric sites, and a comprehensive allosteric map does not exist for any protein. Here we address this shortcoming by charting multiple global atlases of inhibitory allosteric communication in KRAS. We quantified the effects of more than 26,000 mutations on the folding of KRAS and its binding to six interaction partners. Genetic interactions in double mutants enabled us to perform biophysical measurements at scale, inferring more than 22,000 causal free energy changes. These energy landscapes quantify how mutations tune the binding specificity of a signalling protein and map the inhibitory allosteric sites for an important therapeutic target. Allosteric propagation is particularly effective across the central β-sheet of KRAS, and multiple surface pockets are genetically validated as allosterically active, including a distal pocket in the C-terminal lobe of the protein. Allosteric mutations typically inhibit binding to all tested effectors, but they can also change the binding specificity, revealing the regulatory, evolutionary and therapeutic potential to tune pathway activation. Using the approach described here, it should be possible to rapidly and comprehensively identify allosteric target sites in many proteins.
Serial Lift-Out: sampling the molecular anatomy of whole organisms
Authors: Schiøtz Oda Helene , Kaiser Christoph J. O. , Klumpe Sven , Morado Dustin R. , Poege Matthias , Schneider Jonathan , Beck Florian , Klebl David P. , Thompson Christopher , Plitzko Jürgen M. 
Published: December 2023

AbstractCryo-focused ion beam milling of frozen-hydrated cells and subsequent cryo-electron tomography (cryo-ET) has enabled the structural elucidation of macromolecular complexes directly inside cells. Application of the technique to multicellular organisms and tissues, however, is still limited by sample preparation. While high-pressure freezing enables the vitrification of thicker samples, it prolongs subsequent preparation due to increased thinning times and the need for extraction procedures. Additionally, thinning removes large portions of the specimen, restricting the imageable volume to the thickness of the final lamella, typically <300 nm. Here we introduce Serial Lift-Out, an enhanced lift-out technique that increases throughput and obtainable contextual information by preparing multiple sections from single transfers. We apply Serial Lift-Out to Caenorhabditis elegans L1 larvae, yielding a cryo-ET dataset sampling the worm’s anterior–posterior axis, and resolve its ribosome structure to 7 Å and a subregion of the 11-protofilament microtubule to 13 Å, illustrating how Serial Lift-Out enables the study of multicellular molecular anatomy.
Transcriptional profiles of pulmonary artery endothelial cells in pulmonary hypertension
Authors: Singh Navneet , Eickhoff Carsten , Garcia-Agundez Augusto , Bertone Paul , Paudel Sunita S. , Tambe Dhananjay T. , Litzky Leslie A. , Cox-Flaherty Katherine , Klinger James R. , Monaghan Sean F. , Mullin Christopher J. , Pereira Mandy , Walsh Thomas , Whittenhall Mary , Stevens Troy , Harrington Elizabeth O. , Ventetuolo Corey E. 
Published: December 2023

AbstractPulmonary arterial hypertension (PAH) is characterized by endothelial cell (EC) dysfunction. There are no data from living patients to inform whether differential gene expression of pulmonary artery ECs (PAECs) can discern disease subtypes, progression and pathogenesis. We aimed to further validate our previously described method to propagate ECs from right heart catheter (RHC) balloon tips and to perform additional PAEC phenotyping. We performed bulk RNA sequencing of PAECs from RHC balloons. Using unsupervised dimensionality reduction and clustering we compared transcriptional signatures from PAH to controls and other forms of pulmonary hypertension. Select PAEC samples underwent single cell and population growth characterization and anoikis quantification. Fifty-four specimens were analyzed from 49 subjects. The transcriptome appeared stable over limited passages. Six genes involved in sex steroid signaling, metabolism, and oncogenesis were significantly upregulated in PAH subjects as compared to controls. Genes regulating BMP and Wnt signaling, oxidative stress and cellular metabolism were differentially expressed in PAH subjects. Changes in gene expression tracked with clinical events in PAH subjects with serial samples over time. Functional assays demonstrated enhanced replication competency and anoikis resistance. Our findings recapitulate fundamental biological processes of PAH and provide new evidence of a cancer-like phenotype in ECs from the central vasculature of PAH patients. This “cell biopsy” method may provide insight into patient and lung EC heterogeneity to advance precision medicine approaches in PAH.