A Novel Approach to Extending Music Using Latent Diffusion

Using deep learning to synthetically generate music is a research domain that has gained more attention from the public in the past few years. A subproblem of music generation is music extension, or the task of taking existing music and extending it. This work proposes the Continuer Pipeline, a novel technique that uses deep learning to take music and extend it in 5 second increments. It does this by treating the musical generation process as an image generation problem; we utilize latent diffusion models (LDMs) to generate spectrograms, which are image representations of music. The Continuer Pipeline is able to receive a waveform as an input, and its output will be what the pipeline predicts the next five seconds might sound like. We trained the Continuer Pipeline using the expansive diffusion model functionality provided by the HuggingFace platform, and our dataset consisted of 256x256 spectrogram images representing 5-second snippets of various hip-hop songs from Spotify. The musical waveforms generated by the Continuer Pipeline are currently at a much lower quality compared to human-generated music, but we affirm that the Continuer Pipeline still has many uses in its current state, and we describe many avenues for future improvement to this technology

The E3 ubiquitin ligase TRIM25 regulates adipocyte differentiation via proteasomemediated degradation of PPAR gamma

Peroxisome proliferator-activated receptor gamma (PPAR??) is a ligand-dependent transcription factor that regulates adipocyte differentiation and glucose homeostasis. The transcriptional activity of PPAR?? is regulated not only by ligands but also by post-translational modifications (PTMs). In this study, we demonstrate that a novel E3 ligase of PPAR??, tripartite motif-containing 25 (TRIM25), directly induced the ubiquitination of PPAR??, leading to its proteasome-dependent degradation. During adipocyte differentiation, both TRIM25 mRNA and protein expression significantly decreased and negatively correlated with the expression of PPAR??. The stable expression of TRIM25 reduced PPAR?? protein levels and suppressed adipocyte differentiation in 3T3-L1 cells. In contrast, the specific knockdown of TRIM25 increased PPAR?? protein levels and stimulated adipocyte differentiation. Furthermore, TRIM25-knockout mouse embryonic fibroblasts (MEFs) exhibited an increased adipocyte differentiation capability compared with wild-type MEFs. Taken together, these data indicate that TRIM25 is a novel E3 ubiquitin ligase of PPAR?? and that TRIM25 is a novel target for PPAR??-associated metabolic diseases

Destination Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons both in the brain and spinal cord. The constantly evolving nature of ALS represents a fundamental dimension of individual differences that underlie this disorder, yet it involves multiple levels of functional entities that alternate in different directions and finally converge functionally to define ALS disease progression. ALS may start from a single entity and gradually becomes multifactorial. However, the functional convergence of these diverse entities in eventually defining ALS progression is poorly understood. Various hypotheses have been proposed without any consensus between the for-and-against schools of thought. The present review aims to capture explanatory hierarchy both in terms of hypotheses and mechanisms to provide better insights on how they functionally connect. We can then integrate them within a common functional frame of reference for a better understanding of ALS and defining future treatments and possible therapeutic strategies. Here, we provide a philosophical understanding of how early leads are crucial to understanding the endpoints in ALS, because invariably, all early symptomatic leads are underpinned by neurodegeneration at the cellular, molecular and genomic levels. Consolidation of these ideas could be applied to other neurodegenerative diseases (NDs) and guide further critical thinking to unveil their roadmap of destination ALS

Destination Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons both in the brain and spinal cord. The constantly evolving nature of ALS represents a fundamental dimension of individual differences that underlie this disorder, yet it involves multiple levels of functional entities that alternate in different directions and finally converge functionally to define ALS disease progression. ALS may start from a single entity and gradually becomes multifactorial. However, the functional convergence of these diverse entities in eventually defining ALS progression is poorly understood. Various hypotheses have been proposed without any consensus between the for-and-against schools of thought. The present review aims to capture explanatory hierarchy both in terms of hypotheses and mechanisms to provide better insights on how they functionally connect. We can then integrate them within a common functional frame of reference for a better understanding of ALS and defining future treatments and possible therapeutic strategies. Here, we provide a philosophical understanding of how early leads are crucial to understanding the endpoints in ALS, because invariably, all early symptomatic leads are underpinned by neurodegeneration at the cellular, molecular and genomic levels. Consolidation of these ideas could be applied to other neurodegenerative diseases (NDs) and guide further critical thinking to unveil their roadmap of destination ALS

Physician Role in Physical Activity for African-American Males Undergoing Radical Prostatectomy for Prostate Cancer

Purpose Physical activity is recognized as a complementary therapy to improve physical and physiological functions among prostate cancer survivors. Little is known about communication between health providers and African-American prostate cancer patients, a high risk population, regarding the health benefits of regular physical activity on their prognosis and recovery. This study explores African-American prostate cancer survivors’ experiences with physical activity prescription from their physicians. Methods Three focus group interviews were conducted with 12 African-American prostate cancer survivors in May 2014 in St. Louis, MO. Participants’ ages ranged from 49 to 79 years, had completed radical prostatectomy, and their time out of surgery varied from 7 to 31 months. Results Emerged themes included physician role on prescribing physical activity, patients’ perceived barriers to engaging in physical activity, perception of normalcy following surgery, and specific resources survivors’ sought during treatment. Of the 12 men who participated, 8 men (67%) expressed that their physicians did not recommend physical activity for them. Although some participants revealed they were aware of the importance of sustained physical activity on their prognosis and recovery, some expressed concerns that urinary dysfunction, incontinence, and family commitments prevented them from engaging in active lifestyles. Conclusions Transitioning from post radical prostatectomy treatment to normal life was an important concern to survivors. These findings highlight the importance of physical activity communication and prescription for prostate cancer patients

African American prostate cancer survivorship: Exploring the role of social support in quality of life after radical prostatectomy

PURPOSE: The aim of this study was to explore the African American prostate cancer survivorship experience following radical prostatectomy and factors contributing to quality of life during survival. DESIGN: African American men who were part of a larger prostate cancer cohort were invited to participate in a focus group. Eighteen open-ended questions were designed by the study team and an experienced moderator to elicit participants\u27 survivorship experiences. RESULTS: Twelve men consented to participate in the study. Emergent themes included views of prostate cancer in the African American community, perceptions of normalcy, emotional side effects following radical prostatectomy, and social support involvement and impact during recovery. CONCLUSIONS: Previous findings suggest that African American men may experience more distress than Caucasian men when facing typical prostate cancer side effects. Traditional masculine role norms and negative perceptions of disease disclosure in the African American community could be contributing to the distress reported by some in this study. Strengthening social support systems by promoting more prosocial coping and help-seeking behaviors early in the survivorship journey may help bypass the detrimental health effects associated with masculine role identification, resulting in improved quality of life throughout the lengthy survival period anticipated for these men

Unifying the Hepatopancreatobiliary Surgery Fellowship Curriculum via Delphi Consensus.

BackgroundHepatopancreatobiliary (HPB) Fellowship training in the Americas consists of 3 distinctive routes with variable curricula: Surgical Oncology Fellowship via the Society of Surgical Oncology (SSO), Abdominal Transplant Surgery Fellowship via the American Society of Transplant Surgeons (ASTS), and HPB Fellowship via the Americas Hepato-Pancreato-Biliary Association (AHPBA). Our objective was to establish a pan-American consensus among HPB surgeons, surgical oncologists, abdominal transplant surgeons, and general surgery residency program directors (GSPDs) on a core knowledge curriculum for HPB fellowship, and to identify topics appropriate for general surgery residency and subspecialty beyond HPB fellowship.Study designA 3-round modified Delphi process was used. Baseline statements were developed by the Education and Training Committee of the AHPBA, in collaboration with representatives of the SSO, ASTS, and GSPDs. The expert panel, consisting of members of the 3 societies together with GSPDs, rated the statements on a 5-point Likert scale and suggested editing or adding new statements. A statement was included in the final curriculum when Cronbach's alpha value was ≥ 0.8 and ≥ 80% of the panel agreed on inclusion.ResultsThe response rate was 100% for the first round, and 98% for the second and third rounds. Eighty-nine of 138 proposed statements were included in the final HPB fellowship curriculum. Curricula for general surgery residency and subspecialty beyond HPB fellowship included 50 and 29 statements, respectively.ConclusionsA multinational consensus on core knowledge for an HPB fellowship curriculum was achieved via the modified Delphi method. This core curriculum may be used to standardize HPB fellowship training across different pathways in the Americas

Allostatic load, educational attainment, and risk of cancer mortality among US men

IMPORTANCE: Health disparities among racial and ethnic minoritized populations, particularly for cancer mortality rates, remain a major public health concern. Men from underrepresented backgrounds (Black and Hispanic men, specifically) face the pervasive effects of discrimination in their daily lives, which also contribute to the complex associations among allostatic load (a marker of chronic stress), educational opportunities, and elevated risks of cancer mortality. OBJECTIVE: To elucidate the associations among educational attainment, allostatic load, and cancer mortality risk among men. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective cohort analysis of data from the National Health and Nutrition Examination Survey, a nationally representative sample of approximately 5000 people across the US, from 1988 to 2010 linked with data from the National Death Index, which served as follow-up data for the cohort and was available through December 31, 2019. Participants included men aged 18 years and older. Data were analyzed from June to October 2024. EXPOSURE: Allostatic load data were stratified by educational attainment levels, categorized as (1) less than high school education and (2) high school graduate and above. Allostatic load score was calculated as the sum of total abnormal biomarkers and health measures (9 total). Participants were considered to have high allostatic load if their score was 3 or more. MAIN OUTCOMES AND MEASURES: The primary outcome was cancer death. Weighted Cox proportional hazards models were fitted to estimate adjusted hazard ratios (HRs) of cancer death between educational attainment and allostatic load (adjusted for age, income, and smoking status). RESULTS: Among all 20 529 men (mean [SE] age, 41.00 [0.22] years), those with high AL and less than high school educational attainment had a greater than 4-fold increased risk of cancer mortality (unadjusted HR, 4.71; 95% CI, 3.36-6.60) compared with those with low allostatic load and a college degree or higher. Similarly, both Black men (HR, 4.19; 95% CI, 2.09-8.40) and White men (HR, 5.77; 95% CI, 4.06-8.20) with high allostatic load and less than high school educational attainment had higher risks for cancer death compared with race-specific counterparts with college education and low allostatic load. After adjustments for age, poverty-to-income ratio, smoking status, history of cancer, and ever congestive heart failure and heart attack, the associations were attenuated, but all men (HR, 1.69; 95% CI, 1.15-2.47) and White men (HR, 1.82; 95% CI, 1.16-2.85) still had greater than 50% increased risk of cancer death compared with men with college education and low allostatic load. CONCLUSIONS AND RELEVANCE: This study highlights the detrimental association of not attaining a high school degree, combined with high allostatic load as a marker of chronic stress, with cancer mortality. Efforts to promote educational attainment and address the underlying social determinants of health are imperative in reducing cancer disparities in this population