bluuebunny/crossref_metadata_2025 huggingface dataset:
Johann Wenzel Kalliwoda, Morceau de salon, Op. 228 (1859)
Authors: Lewis Nora Anderson
Published: January 2025

This chapter offers commentary on Johann Wenzel Kalliwoda’s, Morceau de salon, Op. 228, composed in 1859. Kalliwoda, a Bohemian composer and violinist, lived at a time when musical style was transitioning from the Classical to the Romantic era. This chapter discusses Kalliwoda’s background, his position as Kapellmeister at Donaueschingen, and his interactions with prominent musicians like Clara and Robert Schumann and Franz Liszt. Despite his formal clarity and beautiful melodic gestures, Kalliwoda had mixed critical reception from Schumann. The work’s historical significance is discussed, as it showcases the early use of the Classical oboe’s virtuosic potential. The musical analysis highlights its compound ternary form with variations and its emotional depth, featuring passionate themes, capricious playfulness, tender lyricism, and virtuosic passages. This piece, though not part of the Paris Conservatory Concours repertoire, exemplifies the Romantic style and fills a gap in oboe repertoire from that period.
Antonio Pasculli, Concerto on Themes from Donizetti’s “La Favorita” (1840)
Authors: Lewis Nora Anderson
Published: January 2025

This chapter offers historical context and musical analysis of Antonio Pasculli’s Concerto on Themes from Donizetti’s “La Favorita.” The term “virtuoso” emerged in the late eighteenth century to describe eminent musicians with dazzling soloistic capabilities, and Pasculli, known as the “Paganini of the oboe,” was among the most prominent virtuoso oboists. His compositions were phenomenally demanding yet avoided awkward note combinations, and he drew on familiar operatic themes from Donizetti, Verdi, and Rossini for his performances. This chapter discusses the background of Donizetti’s opera La Favorite and its complicated history before its premiere at the Paris Opéra. Pasculli’s “La Favorita” starts with an introduction drawn from the accompaniment of Act I Scene I of Donizetti’s opera and features technically demanding variations and lightning-fast cadenzas that showcase the oboist’s virtuosity. The piece’s structure, key choices, and stylistic contrasts are explored, highlighting Pasculli’s brilliance as both a performer and composer.
Wolfgang Amadeus Mozart, Oboe Concerto, K. 314 (1777)
Authors: Lewis Nora Anderson
Published: January 2025

This chapter examines Mozart’s sole Oboe Concerto, K. 314, within a historical and analytical context. Mozart was exceptionally musically precocious, and his father, Leopold, played an instrumental role in developing Mozart’s innate musical abilities. Discussing Mozart’s development and early influences, this chapter traces the composition’s genesis, drawing on primary source letters. The concerto, written in 1777 for oboist Giuseppe Ferlendis, and championed by oboist Friedrich Ramm, disappeared for over a century until its rediscovery by Bernhard Paumgartner when he was director of the Mozarteum at Salzburg. Musically, the piece reflects both the galant style and the evolving Mannheim tradition. Furthermore, this chapter explores stylistic nuances of the concerto to convey the piece’s operatic characteristics, the handling of formal conventions, and the contrast between technical virtuosity and lyricism. It establishes the Allegro aperto, Adagio non troppo, and Allegretto movements within the broader Classical concerto format and discusses technical and interpretive decisions faced by performers.
Paul Hindemith, Sonata for Oboe and Piano (1938)
Authors: Lewis Nora Anderson
Published: January 2025

This chapter explores Paul Hindemith’s Sonata for Oboe and Piano (1938) in a historical and analytical context. The narrative traces Hindemith’s development as an artist against the backdrop of sociopolitical upheavals in Germany. His performance experience, interest in expanding the audience for contemporary music, role as an influential educator, commitment to early music performance, desire to compose practical music for nonprofessionals, and move to the United States are highlighted as defining traits. Discussion of his sonatas reveals stylistic transformation across two compositional periods. This chapter discusses Hindemith’s concept of “harmonic fluctuation” and shows how it is applied in the two-movement Sonata for Oboe and Piano. His innovative approach to composition offers an exciting confluence of the traditional and modern elements, where familiar formal devices meld with Hindemith’s unique harmonic and tonal languages.
William Grant Still, Incantation and Dance (1941)
Authors: Lewis Nora Anderson
Published: January 2025

This chapter explores the musical work of William Grant Still (1895–1978), with a focus on his composition, Incantation and Dance for oboe and piano (1941). Positioned within the nexus of American Modernism, American Nationalism, and the Harlem Renaissance, Still drew on his multicultural background and experiences of racial segregation to shape his notion of a “universal idiom.” The chapter discusses the cultural and historical factors that influenced Still’s work, revealing a sophisticated blend of various cultural traditions. The analysis of Incantation and Dance demonstrates Still’s innovative use of harmonic and rhythmic elements, notably his incorporation of the blues scale, call-and-response structures, and avant-garde dissonance. Additionally, this chapter considers how Still drew on his “universal idiom” to contribute to the development of “authentic American voices,” within the modernist movement, and highlights Still’s contributions to American music and broader cultural discourse.
Benjamin Britten, Six Metamorphoses after Ovid, Op. 49 (1951)
Authors: Lewis Nora Anderson
Published: January 2025

This chapter examines Benjamin Britten’s pivotal work, Six Metamorphoses after Ovid, Op. 49, its genesis, and its historical importance in the repertoire for solo oboe. Born into a middle-class family in England, Britten emerged as a dominant force in English art music, navigating the tensions between modernity and tradition in his compositions. His approach to modernism diverged from typical norms, which presents a challenge for scholars to historically situate his works. In his Six Metamorphoses, Britten explores his deep interest in Classical mythology and innovatively portrays six characters from Ovid’s Metamorphoses, using the oboe’s expressive range to depict transformations, while maintaining a predominantly tonal aesthetic. This chapter also discusses the work’s premiere, Britten’s working methods, and possible connections with other composers’ interpretations of the same myths. This chapter addresses the debates surrounding the interpretation of the tempo markings and the ways performance practices have developed through time.
Alyssa Morris, Four Personalities (2007)
Authors: Lewis Nora Anderson
Published: January 2025

This chapter offers an overview of the life and musical journey of Alyssa Morris, a renowned American composer, oboist, and pianist, and features her piece Four Personalities (2007). Born in Texas in 1984 and raised in Utah, Morris’s childhood affinity for the piano and oboe led to a lifelong pursuit of musical composition and performance, influenced by classical composers like Chopin and Liszt, and jazz artists such as John Coltrane. The chapter also discusses her professional journey and her significant contributions to expanding the oboe repertoire. Four Personalities reflects Morris’s love of jazz and features the distinct characteristics of the Hartman personality test’s color representations. Morris’s depictions of the personality types are subtle yet complex, as the contrast of character from movement to movement effectively reveals the distinctions between them. The pieces are cleverly programmatic, reflecting her interest in conveying the human experience through music.
Jenni Brandon, Wood Song for Solo Oboe (2019)
Authors: Lewis Nora Anderson
Published: January 2025

This chapter offers musicological context and analysis of Wood Song (2019), a composition for solo oboe by American composer Jenni Brandon. This chapter situates Brandon’s work within the broader historical context of contemporary classical music and examines the musical techniques employed in Wood Song. Born in Hershey, Pennsylvania, in 1977, Brandon’s composition reflects her various musical experiences, including singing, songwriting, choir conducting, and yoga teaching and practice, among others. Wood Song exemplifies Brandon’s lyrically driven style, her affinity for nature, and her collaborative compositional approach. The chapter provides an analysis of the piece’s musical structure, thematic development, and Brandon’s innovative use of the oboe to mimic the wood thrush. The analysis highlights Brandon’s use of a loose rondo form, tonal modulations, rhythmic variations, and her ability to create a rich soundscape that crosses between natural and musical worlds.
The Role of Fractional Radiofrequency in Long-term Acne Remission and Reduction of Acne Scar Load
Authors: Hamadani Fadi , Vranis Neil M
Published: January 2025

Background

Acne is an inflammatory skin disease afflicting the majority of the world's population at some point in their lifetime, and is seen to be chronic in about 50% of cases. Acne leads to significant social withdrawal, depression, and disfiguring scars in many cases. Available treatments are characterized by high rates of relapse, dangerous side effects, and social stigma, which often leads to poor patient compliance and treatment failure.

Objectives

The aim of this article was to discuss and share the authors’ experiences utilizing fractional radiofrequency (RF) (Morpheus8; InMode Ltd., Lake Forest, CA) in the treatment of both active acne and acne scars.

Methods

A retrospective review was conducted comparing 3 treatment modalities. In total, 356 patients received acne scar treatments. The cohort comprised a high-dose isotretinoin topical therapy series (n = 128, 36%), a 6-session ablative laser series (n = 89, 25%), and a 3-session fractional RF microneedling series (n = 139, 44).

Results

Of the patients with extended 3-year follow-up, the relapse rates were: isotretinoin group, 36 of 54 (67%); laser group, 12 of 16 (75%), and fractional RF microneedling group, 7 of 29 (24%).

Conclusions

In treating older acne scars, fractional RF microneedling technology has served as an effective tool to tighten skin and fill in atrophic scars when used in conjunction with other techniques. This technology is very effective and very safe for treating all skin types with acne and acne scars.
Explainable deep neural networks for predicting sample phenotypes from single-cell transcriptomics
Authors: Martorell-Marugán Jordi , López-Domínguez Raúl , Villatoro-García Juan Antonio , Toro-Domínguez Daniel , Chierici Marco , Jurman Giuseppe , Carmona-Sáez Pedro
Published: January 2025

Recent advances in single-cell RNA-Sequencing (scRNA-Seq) technologies have revolutionized our ability to gather molecular insights into different phenotypes at the level of individual cells. The analysis of the resulting data poses significant challenges, and proper statistical methods are required to analyze and extract information from scRNA-Seq datasets. Sample classification based on gene expression data has proven effective and valuable for precision medicine applications. However, standard classification schemas are often not suitable for scRNA-Seq due to their unique characteristics, and new algorithms are required to effectively analyze and classify samples at the single-cell level. Furthermore, existing methods for this purpose have limitations in their usability. Those reasons motivated us to develop singleDeep, an end-to-end pipeline that streamlines the analysis of scRNA-Seq data training deep neural networks, enabling robust prediction and characterization of sample phenotypes. We used singleDeep to make predictions on scRNA-Seq datasets from different conditions, including systemic lupus erythematosus, Alzheimer’s disease and coronavirus disease 2019. Our results demonstrate strong diagnostic performance, validated both internally and externally. Moreover, singleDeep outperformed traditional machine learning methods and alternative single-cell approaches. In addition to prediction accuracy, singleDeep provides valuable insights into cell types and gene importance estimation for phenotypic characterization. This functionality provided additional and valuable information in our use cases. For instance, we corroborated that some interferon signature genes are consistently relevant for autoimmunity across all immune cell types in lupus. On the other hand, we discovered that genes linked to dementia have relevant roles in specific brain cell populations, such as APOE in astrocytes.
A deep learning feature importance test framework for integrating informative high-dimensional biomarkers to improve disease outcome prediction
Authors: Zou Baiming , Xenakis James G , Xiao Meisheng , Ribeiro Apoena , Divaris Kimon , Wu Di , Zou Fei
Published: January 2025

Many human diseases result from a complex interplay of behavioral, clinical, and molecular factors. Integrating low-dimensional behavioral and clinical features with high-dimensional molecular profiles can significantly improve disease outcome prediction and diagnosis. However, while some biomarkers are crucial, many lack informative value. To enhance prediction accuracy and understand disease mechanisms, it is essential to integrate relevant features and identify key biomarkers, separating meaningful data from noise and modeling complex associations. To address these challenges, we introduce the High-dimensional Feature Importance Test (HdFIT) framework for machine learning models. HdFIT includes a feature screening step for dimension reduction and leverages machine learning to model complex associations between biomarkers and disease outcomes. It robustly evaluates each feature’s impact. Extensive Monte Carlo experiments and a real microbiome study demonstrate HdFIT’s efficacy, especially when integrated with advanced models like deep neural networks. Our framework shows significant improvements in identifying crucial features and enhancing prediction accuracy, even in high-dimensional settings.
Artificial intelligence in cryo-EM protein particle picking: recent advances and remaining challenges
Authors: Dhakal Ashwin , Gyawali Rajan , Wang Liguo , Cheng Jianlin
Published: January 2025

Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling the determination of high-resolution 3-Dimensional (3D) structures of large biological macromolecules. Protein particle picking, the process of identifying individual protein particles in cryo-EM micrographs for building protein structures, has progressed from manual and template-based methods to sophisticated artificial intelligence (AI)-driven approaches in recent years. This review critically examines the evolution and current state of cryo-EM particle picking methods, with an emphasis on the impact of AI. We conducted a comparative evaluation of popular AI-based particle picking methods, using both general machine learning metrics and specific cryo-EM structure determination metrics. This analysis involved constructing the 3D density map from the picked protein particles and assessing the obtained resolution and particle orientation diversity, underscoring the significant impact of AI on cryo-EM particle picking. Despite the advancements, we also identified key obstacles, such as handling complex micrographs with small proteins. The analysis provides insights into the future development of more sophisticated and fully automated AI methods in cryo-EM particle recognition.
N-methyl-d-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference
Authors: Weilnhammer Veith , Rothkirch Marcus , Yilmaz Deniz , Fritsch Merve , Ptasczynski Lena Esther , Reichenbach Katrin , Rödiger Lukas , Corlett Philip , Sterzer Philipp
Published: January 2025

Perception integrates external sensory signals with internal predictions that reflect prior knowledge about the world. Previous research suggests that this integration is governed by slow alternations between an external mode, driven by sensory signals, and an internal mode, shaped by prior knowledge. Using a double-blind, placebo-controlled, cross-over experiment in healthy human participants, we investigated the effects of the N-Methyl-D-aspartate receptor (NMDAR) antagonist S-ketamine on the balance between external and internal modes. We found that S-ketamine causes a shift of perception toward the external mode. A case-control study revealed that individuals with paranoid Scz, a disorder repeatedly associated with NMDAR hypofunction, spend more time in the external mode. This NMDAR-dependent increase in the external mode suggests that the symptoms of schizophrenia are caused by recurring dissociations of perception from prior knowledge about the world.
CYP24A1 is overexpressed in keloid keratinocytes and its inhibition alters profibrotic gene expression
Authors: Hahn Jennifer M , Combs Kelly A , Phillips Caitlin M , Warner Petra M , Qazi Uzair A , Powell Heather M , Supp Dorothy M
Published: January 2025

Background

Keloids are disfiguring, fibrotic scar-like lesions that are challenging to treat and commonly recur after therapy. A deeper understanding of the mechanisms driving keloid formation is necessary for the development of more effective therapies. Reduced vitamin D receptor (VDR) expression has been observed in keloids, implicating vitamin D signaling in keloid pathology. Vitamin D exhibits anti-proliferative and anti-inflammatory properties, suggesting it could have therapeutic utility in keloid disorder. The current study investigated vitamin D-regulated gene expression in keloid keratinocytes and the effects of inhibiting an enzyme involved in vitamin D metabolism on the phenotype of keloid-derived keratinocytes.

Methods

Normal and keloid-derived primary keratinocytes were isolated from normal skin and keloid lesions, respectively, and were cultured in the absence or presence of vitamin D. In some experiments, inhibitors of the vitamin D metabolizing enzyme CYP24A1, ketoconazole or VID400 were added in the absence or presence of vitamin D. Cellular proliferation, migration and gene expression were measured.

Results

We observed significant overexpression of CYP24A1 mRNA in keloid versus normal keratinocytes and increased CYP24A1 protein levels in keloids versus normal skin. CYP24A1 encodes 24 hydroxylase and is induced by vitamin D in a feedback loop that regulates vitamin D levels; thus, inhibition of CYP24A1 activity may locally increase active vitamin D levels. Ketoconazole, a non-specific cytochrome P-450 inhibitor, reduced proliferation of keloid and normal keratinocytes, but VID400, a specific CYP24A1 inhibitor, only significantly affected keloid keratinocyte proliferation. Neither inhibitor significantly reduced keratinocyte migration. The two inhibitors had different effects on vitamin D target gene expression in keratinocytes. Specifically, ketoconazole treatment reduced CYP24A1 expression in normal and keloid keratinocytes, whereas VID400 increased CYP24A1 expression. Both inhibitors decreased expression of profibrotic genes, including periostin and hyaluronan synthase 2, in keloid-derived cells. Combined treatment of keloid keratinocytes with vitamin D and ketoconazole or VID400 increased the effects of vitamin D treatment on target genes, although the effects were gene- and cell type-specific.

Conclusions

The data suggest that reduction of vitamin D inactivation with CYP24A1 inhibitors may reduce profibrotic gene expression in keloid-derived cells. Therefore, CYP24A1 inhibitors may serve as adjunctive therapies to suppress keloid-associated gene expression changes.
Colchicine as a treatment option for inherited epidermolysis bullosa
Authors: Sarsam Sera , Koszegi Ben J , Murrell Dedee F
Published: January 2025

Epidermolysis Bullosa (EB) is a rare inherited multisystem disorder. Colchicine is a medication classified as an anti-gout agent and anti-inflammatory drug. Currently, treatment options for EB are limited, with treatment focused on symptom management with no approved systemic treatments available. The article reports three cases of colchicine use in ameliorating EB wounds and systemic inflammation.
Teen Smoking and Chronic Skin Disease: An Ethical Crossroad in Hidradenitis Suppurativa Care
Authors: Sexton Fiona , Bowe Stephanie , Sheridan David , Murphy Michelle
Published: January 2025

Navigating an ethical dilemma in the adolescent dermatology clinic regarding a young teenager who is smoking in secret despite worsening hidradenitis suppurativa signs and symptoms.
Comment on ‘The risk of malignancy in patients with psoriasis treated with long-term tumor necrosis factor-α inhibitor: a systematic review and meta-analysis’ - Risk of Cancer Recurrence with Biologics in Psoriasis
Authors: Potluru Aparna , Nikookam Yasmin
Published: January 2025

This article reviews the findings of Wu et al. on the risk of malignancy in psoriasis patients treated with long-term TNF-α inhibitors (TNFi). While the study found no significant increase in the risk of most cancers, it highlighted a higher risk of non-melanoma skin cancers, particularly squamous cell carcinoma, in patients with psoriatic arthritis. The article discusses the clinical implications for psoriasis patients with a history of malignancy, advocating for a personalised treatment approach, vigilant monitoring, and the need for further research to better understand the relationship between biologic therapy and cancer recurrence.
Choroid plexus-targeted viral gene therapy for alpha-mannosidosis, a prototypical neurometabolic lysosomal storage disease
Authors: Choi Eun-Young , Wolfe John H , Kaler Stephen G
Published: January 2025

The choroid plexuses (CP) are highly vascularized structures that project into the ventricles of the vertebrate brain. The polarized epithelia of the CP produce cerebrospinal fluid by transporting water and ions into the ventricles from the blood and normally secrete a large number of proteins. We assessed the feasibility of selective CP transduction with recombinant adeno-associated virus (rAAV) gene therapy vectors for treatment of lysosomal storage disease (LSD), a broad category of neurometabolic illness associated with significant burdens to affected patients and their families. There are no ideal or complete therapeutic options currently available, especially for the central nervous system manifestations of LSDs. Alpha-mannosidosis (AMD) is an autosomal recessive prototypical LSD caused by deficiency of lysosomal alpha-mannosidase and characterized by cerebellar ataxia, neurocognitive disability, facial and skeletal abnormalities, hearing impairment, and mild immune deficiency. In a murine model of AMD, we compared the biochemical effects of CSF-directed rAAV serotypes 1, 4, 5, 6, and 9. Recombinant AAV1 and rAAV6, two closely related serotypes whose capsid sequences differ by only six amino acids, showed the most robust transduction of CP in mouse brain, consistent with their transduction of CPE in nonhuman primates and cats, as well as in other structures. We found restoration of LAMAN enzyme activity comparable to or higher than AMD heterozygote levels in the brain globally (olfactory bulb, cortex, cerebellum, brainstem). Further IND-generating preclinical experiments will advance rAAV6-LAMAN, which appears to be the most promising choroid plexus-targeting candidate serotype for future clinical translation to treat AMD.
Rare and common genetic variants underlying the risk of Hirschsprung’s disease
Authors: Xiao Jun , Feng Chenzhao , Zhu Tianqi , Zhang Xuan , Chen Xuyong , Li Zejian , You Jingyi , Wang Qiong , Zhuansun Didi , Meng Xinyao , Wang Jing , Xiang Lei , Yu Xiaosi , Zhou Bingyan , Tang Weibing , Tou Jinfa , Wang Yi , Yang Heying , Yu Lei , Liu Yuanmei , Jiang Xuewu , Ren Hongxia , Yu Mei , Chen Qi , Yin Qiang , Liu Xiang , Xu Zhilin , Wu Dianming , Yu Donghai , Wu Xiaojuan , Yang Jixin , Xiong Bo , Chen Feng , Hao Xingjie , Feng Jiexiong
Published: January 2025

Hirschsprung’s disease (HSCR) is a congenital enteric neuropathic disorder characterized by high heritability (>80%) and polygenic inheritance (>20 genes). The previous genome-wide association studies (GWAS) identified several common variants associated with HSCR and demonstrated increased predictive performance for HSCR risk in Europeans using a genetic risk score, there remains a notable gap in knowledge regarding Chinese populations. We conducted whole exome sequencing in a HSCR case cohort in Chinese. By using the common controls (505 controls from 1KG EAS and 10 588 controls from ChinaMAP), we conducted GWAS for the common variants in the exome and gene-based association for rare variants. We further validated the associated variants and genes in replicated samples and in vitro and vivo experiments. We identified one novel gene PLK5 by GWAS and suggested 45 novel putative genes based the gene-based test. By using genetic variant at RET and PLK5, we constructed a genetic risk score that could identify the individuals with very high genetic risk for HSCR. Compared with patients with zero or one risk allele from the three variants, the risk for HSCR was 36.61 times higher with six alleles. In addition, we delineated a HSCR risk gene landscape that encompasses 57 genes, which explains 88.5% and 54.5% of HSCR in Chinese and European, respectively. In summary, this study improved the understanding of genetic architecture of HSCR and provided a risk prediction approach for HSCR in the Chinese.
Adaptive kernel conditional density estimation
Authors: Zhao Wenjun , Tabak Esteban G
Published: January 2025

A methodology is proposed for the determination of factor-dependent bandwidths for the kernel-based estimation of the conditional density $\rho (x|z)$ underlying a set of observations. The adaptive determination of the bandwidths is based on a $z$-dependent effective number of samples and variance. The procedure extends to categorical factors, where a non-trivial ‘bandwidth’ can be designed that optimally uses across-class information while capturing class-specific traits. A hierarchy of algorithms is developed, and their effectiveness is demonstrated on synthetic and real-world data.
A World of Difference: Overcoming Normative Limits of the ECHR Framework through a Legally Binding Recognition of the Human Right to a Healthy Environment
Authors: Kobylarz Natalia
Published: January 2025

This article argues that while the Strasbourg human rights system provides a level of environmental protection through existing rights and their evolutive interpretation by the European Court of Human Rights, adopting an additional Protocol to the European Convention on Human Rights (‘ECHR’) on the right to a healthy environment (‘R2HE’) would strengthen safeguarding of environmental human rights. By comparing R2HE with the green human rights doctrine, I identify six normative limits within the current ECHR framework, which, as shown through an analysis of the historic and most recent case law, stem from the lack of legally binding recognition of an autonomous R2HE. In this vein, this study argues that the Protocol could enable forward-looking environmental adjudication and resolution of a wide range of situations affecting both the environment and human rights, foster a more consistent, predictable adjudication process, as well as support the Council of Europe’s goal of strengthening human rights protection in response to the triple planetary crisis.
Akoē Pisteōs (Gal. 3:2–5) and Martin Luther’s Place in Pauline Scholarship
Authors: Brewer Eric J
Published: January 2025

Few historical figures cast as long a shadow on Pauline scholarship as does Martin Luther. Pauline scholars espousing the ‘Old’ or ‘Lutheran’ Perspective will invoke his name in support of their interpretations while many from the ‘New’ Perspective will use him as a foil to distinguish their reading of Paul from traditional ones. At times, however, Luther himself does not relate to modern schools of Pauline scholarship in the ways many would expect. Luther’s interpretation of akoē pisteōs, a notoriously difficult phrase from Galatians 3:2–5, illustrates this particularly well. Far from agreeing with the Old/Lutheran Perspective in reading this phrase with an emphasis on subjective faith (e.g. ‘hearing with faith’), Luther’s reading of akoē pisteōs more closely resembles those of the modern Apocalyptic Perspective on Paul by emphasizing the power of the objective message (e.g. ‘proclamation of the gospel’). This finding supports the recent trend of recognizing more apocalyptic elements in Luther’s thought and challenges scholars of both Luther and Paul to reevaluate his place in the history of Pauline scholarship.
Synthetic [18F]FET-PET Generation and Hotspot Prediction Via Preoperative MRI Fusion of Glioma Lacking Radiographic High-Grade Characteristics
Authors: Suero Molina Eric , Tabassum Mehnaz , Azemi Ghasem , Özdemir Zeynep , Roll Wolfgang , Backhaus Philipp , Schindler Philipp , Chavarria Alex Valls , Russo Carlo , Liu Sidong , Stummer Walter , Di Ieva Antonio
Published: January 2025

Background

Limited amino acid availability for Positron Emission Tomography (PET) imaging hinders therapeutic decision-making for gliomas without typical high-grade imaging features. To address this gap, we evaluated a generative artificial intelligence (AI) approach for creating synthetic [18F]FET-PET and predicting high [18F]FET-uptake from magnetic resonance imaging (MRI).

Methods

We trained a deep learning (DL)-based model to segment tumors in MRI and extracted radiomic features using the pyradiomics package and classification with a Random Forest classifier. To generate [18F]FET-PET images, we employed a Generative Adversarial Network (GAN) framework and utilized a split-input fusion module for processing different MRI sequences through feature extraction, concatenation, and self-attention.

Results

We included MR and PET images from 215 studies for the hotspot classification and 211 studies for the synthetic PET generation task. The top-performing radiomic features achieved 80% accuracy for hotspot prediction. From the synthetic [18F]FET-PET, 85% were classified as clinically useful by senior physicians. Peak Signal-to-Noise Ratio analysis indicated high signal fidelity with a peak at 40 dB, while Structural Similarity Index values showed structural congruence. Root Mean Square Error analysis demonstrated lower values below 5.6. Most Visual Information Fidelity scores ranged between 0.6 and 0.7. This indicates that synthetic PET images retain the essential information required for clinical assessment and diagnosis.

Conclusion

For the first time, we demonstrate that predicting high [18F]FET-uptake and generating synthetic PET images from preoperative MRI in LGG and HGG is feasible. Advanced MRI modalities and other generative AI models will be used to improve the algorithm further in future studies.
Are Seed Oils the Culprit in Cardiometabolic and Chronic Diseases? A Narrative Review
Authors: Lee Kevin , Kurniawan Keszya
Published: January 2025

The demonization of seed oils “campaign” has become stronger over the decades. Despite the dietary guidelines provided by nutritional experts recommending the limiting of saturated fat intake and its replacement with unsaturated fat–rich food sources, some health experts ignore the dietary guidelines and the available human research evidence, suggesting the opposite. As contrarians, these individuals could easily shift public opinion so that dietary behavior moves away from intake of unsaturated fat-rich food sources (including seed oils) toward saturated fats, which is very concerning. Excess saturated fat intake has been known for its association with increased cholesterol serum levels in the bloodstream, which increase atherosclerotic cardiovascular disease risks. Furthermore, high saturated fat intake may potentially induce insulin resistance and non-alcoholic fatty liver disease, based on human isocaloric feeding studies. Hence, this current review aimed to assess and highlight the available human research evidence, and if appropriate, to counteract any misconceptions and misinformation about seed oils.
Correlation between cathepsins and the likelihood of renal cancer: a Mendelian randomization study
Authors: Peng Tuo , Li Tian , Zhang Caihua
Published: January 2025

Background

Previous studies have established a relationship between cathepsins and renal cancer. Nonetheless, the specific causal connection between the two factors continues to be ambiguous. The aim of this study is to evaluate the causal relationship between cathepsins and renal cancer via employing Mendelian randomization (MR).

Methods

The summary data of genome-wide association study were used for univariable MR (UVMR), reverse MR, and multivariable MR (MVMR) analyses. The primary MR method used in this study was Inverse variance weighting.

Results

UVMR analysis showed that cathepsin Z increased the overall risk of renal cancer and cathepsin F were observed increased the risk of clear cell renal cell carcinoma. Furthermore, the concentration of cathepsin S had a significant positive correlation with the risk of papillary renal cell carcinoma (pRCC), whereas that of cathepsin G was negatively correlated with the risk of pRCC. Reverse MR analysis showed that renal cancer reduced the concentration of cathepsin H. MVMR analysis showed that the concentration of cathepsin B had a significant positive correlation with overall risk of renal cancer and pRCC. In addition, a higher concentration of cathepsin S was significantly associated with an increased risk of pRCC.

Conclusion

This study confirmed a direct link between cathepsins and the risk of renal cancer. Specifically, cathepsin S has a significant positive correlation with the risk of pRCC. The findings of our research could provide significant contributions to both fundamental and clinical investigations pertaining to renal cancer.

Key message What is already known on this topic? – Previous studies have suggested the role of some cathepsins in renal cancer occurrence and progression. However, the causal link between different cathepsins and renal cancer is unknown. What this study adds? – Our Mendelian randomization (MR) study revealed that the effects of different cathepsins on the risk of renal cancer. Remarkably, both univariable MR and multivariable MR demonstrated that the levels of cathepsin S increases the risk of papillary renal cell carcinoma. How this study might affect research, practice or policy? – The findings offer novel insights into the relationship between cathepsins and renal cancer, which may have implications for the prevention and management of renal cancer.
Vascularized Iliac Crest Bone Graft for the Reconstruction of Anterior Vertebral Corpus Defects: A Literature Review and Cadaveric Feasibility Study
Authors: Jeger Jonathan L. , Martinez Casey J. , Shvedova Maria , Simoni Alec , Rebecca Alanna , Winocour Sebastian , Ropper Alexander E. , Bohl Michael , Casey William J. , Kalani Maziyar , Reece Edward M.
Published: January 2025

Background:

Vertebral body defects pose a significant challenge in spinal reconstructive surgery. Compression fractures of the vertebral corpus are typically treated with vertebral augmentation procedures. There are significant risks associated with the introduction of foreign material in the spine, including infection and pseudarthrosis. Vascularized bone grafts (VBGs) have become a popular alternative for spinal reconstruction in the last decade thanks to their robust blood supply and autologous nature. VBGs have been described predominantly for the reconstruction of posterior vertebral defects. The objective of this study is to describe a novel procedure for the reconstruction of vertebral corpus defects in the lumbar and distal thoracic spine.

Methods:

This is a cadaveric anatomy study. The authors performed the novel surgical technique on an anonymized cadaveric donor in the prone position and recorded the procedure through clinical photography. Consent for the procedure and photography was obtained from the Center for Procedural Innovation.

Results:

A 5-cm-long posterior iliac crest VBG (IC-VBG) was successfully harvested on a pedicle of the quadratus lumborum muscle. The VBG was rotated and mobilized anteromedially to the vertebral corpus. In this donor, the IC-VBG could be inset with minimal tension anywhere along the vertebral bodies of the spine from the L5 to the T9 level.

Conclusions:

A rotated, anteromedially mobilized IC-VBG represents a novel technique for reconstruction of the anterior vertebral corpus of the lumbar and distal thoracic spine with a lower risk of infection and pseudarthrosis than reconstruction with foreign materials.
Hydrogen peroxide damage to rat liver sinusoidal endothelial cells is prevented by n-acetyl-cysteine but not GSH
Authors: Kruse Larissa D. , Holte Christopher , Zapotoczny Bartlomiej , Struck Eike C. , Schürstedt Jasmin , Hübner Wolfgang , Huser Thomas , Szafranska Karolina
Published: January 2025

Background:

Reactive oxygen species (ROS) are prevalent in the liver during intoxication, infection, inflammation, and aging. Changes in liver sinusoidal endothelial cells (LSEC) are associated with various liver diseases.

Methods:

Isolated rat LSEC were studied under oxidative stress induced by H2O2 at different concentrations (0.5–1000 µM) and exposure times (10–120 min). LSEC functions were tested in a dose-dependent and time-dependent manner.

Results:

(1) Cell viability, reducing potential, and scavenging function decreased as H2O2 concentration and exposure time increased; (2) intracellular ROS levels rose with higher H2O2 concentrations; (3) fenestrations exhibited a dynamic response, initially closing but partially reopening at H2O2 concentrations above 100 µM after about 1 hour; (4) scavenging function was affected after just 10 minutes of exposure, with the impact being irreversible and primarily affecting degradation rather than receptor-mediated uptake; (5) the tubulin network was disrupted in high H2O2 concentration while the actin cytoskeleton appears to remain largely intact. Finally, we found that reducing agents and thiol donors such as n-acetyl cysteine and glutathione (GSH) could protect cells from ROS-induced damage but could not reverse existing damage as pretreatment with n-acetyl cysteine, but not GSH, reduced the negative effects of ROS exposure.

Conclusions:

The results suggest that LSEC does not store an excess amount of GSH but rather can readily produce it in the occurrence of oxidative stress conditions. Moreover, the observed thresholds in dose-dependent and time-dependent changes, as well as the treatments with n-acetyl cysteine/GSH, confirm the existence of a ROS-depleting system in LSEC.
Radon Re-entrainment Study—An Initial Investigation
Authors: Lewis Robert , Bleiler Denise , Coons Maria , Ruminski Jamie , Fox Ryan , Turk Bradley
Published: January 2025

Currently radon mitigation standards in United States residential homes and buildings require that the exhaust point for active fan-powered depressurization (ASD) systems exhaust be at or above the roofline of the building. There was very little evidence to support this requirement in the mid-1990s when the standards were published. This study was designed to examine the potential and safety of ground level exhaust. There are numerous advantages for ground level exhaust, such as aesthetics, safety, and reduced condensation, if properly placed along side of the building. A configurable exhaust point ASD design whereby we could change the exhaust from roofline to ground level was installed in 10 homes in the Harrisburg, PA, area. This design allowed us to change the configuration every 2 wk from roofline to ground level to baseline (off) conditions, with the house thereby acting as its own control, while extensively measuring the indoor and outdoor radon concentrations and other parameters over the course of 1 y. Over the year-long study, roofline and ground level exhaust configurations both showed very similar average indoor radon concentrations. Apart from the typical seasonal differences, there was little difference between average indoor radon levels for roof and ground level exhaust during each of the four seasons.
Diagnostic Role of Tissue Biopsy in Leukaemic or Lymphomatous Infiltrative Optic Neuropathy: A Case Report and Systematic Review of Literature
Authors: Younis Abdullah , Shiwani Haaris , Green Elspeth K. Y. , Foo Edward , Sharma Vinod , Dignan Fiona L. , Dharmasena Aruna
Published: January 2025

Purpose:

To explore the role of tissue biopsy in diagnosing leukemic or lymphomatous infiltrative optic neuropathy through a systematic literature review and presentation of a new case.

Methods:

A systematic literature review was conducted using PubMed, Scopus, and Google Scholar databases to identify cases of leukemic or lymphomatous optic neuropathy in which optic nerve or sheath biopsy was performed. A newly reported case was also included.

Results:

A total of 420 studies were identified, with 26 meeting inclusion criteria. In total 29 patients were included, with a mean age of 55.9 years. Of these, 48.3% had a known history of leukemia or lymphoma, and 50% were in remission at presentation. Imaging showed optic nerve enhancement and enlargement in most cases. Biopsies were performed on the optic nerve, sheath, chiasm, tract, or surrounding orbital tissue. Direct nervous tissue biopsies (optic nerve, chiasm, or tract) were diagnostic in 100% of cases, while only 18.2% of sheath biopsies were diagnostic. Visual outcomes were poor, with many presenting with no light perception. Postoperatively, vision remained stable in 40%, deteriorated in 20.7%, and improved in 17.2%.

Discussion:

Tissue biopsy remains a critical last-line investigation for diagnosing leukemic or lymphomatous optic neuropathy when noninvasive methods remain inconclusive. While highly diagnostic, optic nerve biopsy carries visual risk, especially for patients with residual vision. Direct nerve biopsy is recommended for severe vision loss, while a more cautious surgical approach, considering alternative diagnostic techniques, is advised for those with partially preserved vision. Optic nerve sheath biopsy, though theoretically safer, has a limited diagnostic yield.
Changes in Neutrophil-to-Lymphocyte Ratio During Venoarterial Extracorporeal Membrane Oxygenation
Authors: Nunez Jose I. , Uehara Mayuko , Patel Snehal R. , Forest Stephen J. , Rochlani Yogita , Madan Shivank , Sims Daniel B. , Mellas Nicholas , Ashley Justin E. , Rahmanian Marjan , Carlese Anthony , Goldstein Daniel J. , Jorde Ulrich P. , Saeed Omar
Published: January 2025

Mortality remains elevated during venoarterial extracorporeal membrane oxygenation support (VA-ECMO) for cardiogenic shock and the role of inflammation is uncertain. By using the neutrophil-to-lymphocyte ratio (NLR), we investigated inflammatory dynamics during VA-ECMO and their relation to clinical outcomes. A single-center, retrospective cohort study was conducted. Patients receiving steroids or on-device support for less than 48 hours were excluded. Patients were grouped as those who did and did not have a persistent rise in NLR during the 24–48 hour interval after VA-ECMO placement. Overall, 253 patients comprised the study cohort. In-hospital mortality was 56%. Neutrophil-to-lymphocyte ratio was higher at 24 hours after VA-ECMO placement compared to pre-ECMO (Δ4.36, interquartile range [IQR]: −0.23 to 8.61, p < 0.001). Persistent increase in NLR during the 24–48 hour interval after VA-ECMO placement was associated with higher in-hospital mortality (adjusted hazard ratio [aHR]: 1.51, 95% confidence interval [CI]: 1.02–2.25, p = 0.04). The magnitude of this rise in NLR was incrementally related to greater in-hospital mortality (Δ0–5: 72%, aHR: 1.61, 95% CI: 1.03–2.54, p = 0.039; Δ>5: 79%, aHR: 1.64, 95% CI: 1.03–2.63, p = 0.037) in comparison 52%, for those with a drop in NLR. Venoarterial extracorporeal membrane oxygenation exacerbates inflammation, as evident by a rise in NLR, which is progressively higher in nonsurvivors.
Evolution and spread of Xanthomonas citri subsp. citri in the São Paulo, Brazil, citrus belt inferred from 758 novel genomes
Authors: Zamunér Caio Felipe Cavicchia , Carhuaricra-Huaman Dennis , Ragupathy Roobinidevi , Redfern James , Rodriguez-Cueva Carmen L. , Behlau Franklin , Enright Mark C. , Ferreira Henrique , Setubal João C.
Published: January 2025

The São Paulo state citrus belt in Brazil is a major citrus production region. Since at least 1957, citrus plantations in this region have been affected by citrus canker, an economically damaging disease caused by Xanthomonas citri subsp. citri (Xcc). For about 50 years, until 2017, a citrus canker eradication programme was carried out in this region. In this work, our aim was to investigate the effects of the eradication programme on genetic variability and evolution of Xcc. To this end, we sequenced and analysed 758 Xcc genomes sampled in the São Paulo citrus belt, together with 730 publicly available Xcc genomes from around the world. Our phylogenomic analyses show that these genomes can be grouped into seven major lineages and that in São Paulo, lineage L7 is dominant. Our time estimate for its appearance closely matches the date when citrus production expanded. L7 can be subdivided into lineages L7.1 and L7.2. In our samples, L7.2, which we estimate to have emerged around 1964, is by far the most abundant, showing that the eradication programme had little impact on strain diversification. On the other hand, oscillations in the estimated effective population size of L7.2 strains over time closely match the shifts in the eradication programme. In sum, we present a detailed view of the genomic diversity of Xcc in the world and in São Paulo, the largest such effort in terms of a number of genomes for a crop pathogen undertaken so far. The methods employed here can form the basis for active genomic surveillance of Xcc in major citrus production areas.
Computational modeling of the temporal influences between cues, craving and use in addiction: A dynamical system analysis based on ecological momentary assessment
Authors: Gauld Christophe , Depannemaecker Damien , Serre Fuschia , Auriacombe Marc
Published: January 2025

Substance Use Disorders (SUD) can be conceptualized as a prospective link from cues to craving and use. To explore the nonlinear interplay between craving and cues, this study applied dynamical systems theory (DST) to ecological momentary assessment (EMA) data. Optimized linear Seasonal Auto-Regressive Integrated Moving Average with eXogenous variable (SARIMAX) models were used to phenotype patients with SUD (alcohol, tobacco, cannabis, opiates, and cocaine), considering the potential for complex interactions between cue exposure and craving intensity in daily life. These phenotypic profiles were replicated in computational DST models to analyze the nonlinear interactions between cues, craving, and use. The study involved 211 individuals and 8,260 observations, with 154 patients fitting the SARIMAX model for the influence of cues on craving, and 57 patients fitting the SARIMAX model for a possible influence of craving on cues. Two DST models were adjusted to replicate the complex temporal dynamics of SUD based on these two directions of influence. The first DST model (adjusted to the influence of cues on craving) showed that an increase in cues leads to a rise in craving, which then diminishes both cues and craving itself, with use patterns following craving’s trajectory. This patient profile is driven by a phenomenon of “maximum cue saturation”. The second DST model (adjusted to the influence of craving on cues) demonstrated that an increase in craving heightens cue perception, further increasing craving and leading to use, with use peaking and then reducing craving. This patient profile is characterized by a phenomenon of “maximum use saturation”. Both models underscore craving as an essential modulator between cues and use, opening new therapeutic avenues.