bluuebunny/crossref_metadata_2025_split huggingface dataset:
FM Synthesis
Authors: Edstrom Brent 
Published: October 2024

Abstract
This chapter examines the extent of FM synthesis and how it can be achieved with Teensy microcontrollers. It introduces Frequency Modulation (FM) as a category of synthesis popularized by Yamaha’s DX7 in the 1980s. The core concept of FM synthesis revolves around one periodic signal that is used to modulate another signal called the carrier wave or modulated signal. The chapter then details how to create sidebands at frequencies equal to the carrier frequency plus and minus integer multiples of the modulator frequency. It explains that hands-on experimentation will provide a good foundation for more advanced applications even though the FM synthesizer project is relatively simple.
Additive Synthesis
Authors: Edstrom Brent 
Published: October 2024

Abstract
This chapter looks into the process and components of additive synthesis. It explains that additive synthesis uses sine waves of differing frequencies and amplitudes to create a unique harmonic spectrum. The additive synthesizer project consists of four rotary encoders with integrated pushbuttons and an OLED display and is built around a Teensy 4 with an Audio Adapter Board. The chapter also explores the interplay between additive synthesis and the structures and elements of a user interface. It then provides an overview of how to marry components created in the Audio System Design Tool with code to create an interactive and expressive additive synthesizer.
Genetic Step Sequencer
Authors: Edstrom Brent 
Published: October 2024

Abstract
This chapter provides an overview on the genetic step sequencer. It explains how Evolutionary Algorithms provide a fascinating avenue of exploration for electronic musicians. Thus, genetic algorithms, a subclass of evolutionary algorithms, are modeled on natural systems and utilize stochastic search techniques. The chapter then elaborates on the use of genetic algorithms to drive a MIDI step sequencer with ever-changing genetic modifications, while also considering that microcontroller technology provides an opportunity for innumerable variations. It cites that the pseudo-Darwinian model forms the basis for the genetic step sequencer and will guide the creation of a virtual habitat for the algorithms to adapt and flourish.
Powering Eurorack Modules
Authors: Edstrom Brent 
Published: October 2024

Abstract
This chapter discusses how to power Eurorack modules. Some manufacturers offer Eurorack cases with built-in power supplies, but prices can be prohibitively expensive. The chapter then explains that Eurorack projects are built around a reliable power source, such as a voltage regulator to provide +5V and a shunt to provide a stable reference voltage. Another reliable power source includes using diodes to prevent damage from reverse polarity. The chapter offers the option of using a DC wall in conjunction with a switching regulator, while also warning about the real danger of electrocution whenever mains power is involved with DIY power supplies.
Voltage Control, Gates, and Triggers
Authors: Edstrom Brent 
Published: October 2024

Abstract
This chapter covers the significance of voltage control, gates, and triggers. While MIDI has many advantages over voltage control, including support for polyphonic performance, using voltage to control synthesizers can open to new expressive opportunities. Voltage is also used for triggers, gates, and clock pulses, but voltage control can provide unique opportunities for creative application including using a voltage source to modulate another voltage source. The chapter then looks into how MIDI to Control Voltage converters provide a useful addition to a Eurorack setup. It also mentions the possible enhancements like support for polyphonic output or USB MIDI input.
MIDI to Control-Voltage Converter
Authors: Edstrom Brent 
Published: October 2024

Abstract
This chapter tackles how the MIDI to Control-Voltage Converter project provides a useful addition to any Eurorack setup. It cites that the MIDI to control voltage conversion opens the door to using computers, MIDI keyboards, and other devices as sources of voltage control. Essentially, the converter is comprised of a modest collection of circuits and code and includes CV/octave and gate/trigger output, onboard 5-volt power supply, and MIDI input. Moreover, the modular approach to the MIDI to CV backpack enables its use in a variety of projects such as custom sequencers, arpeggiators, or real-time controllers. The chapter considers several enhancements and creative applications to the MIDI to Control-Voltage Converter.
Myeloid sarcomas with CBFA2T3
:
GLIS2 fusion: clinicopathologic characterization of 4 cases mimicking small round cell tumors
Authors: Malik Faizan , Eldomery Mohammad K , Wang Wei , Gheorghe Gabriela , Khanlari Mahsa 
Published: October 2024

Abstract

Objectives
Acute myeloid leukemia with CBFA2T3::GLIS2 fusion can initially present as extramedullary lesions (myeloid sarcoma), leading to a misdiagnosis of nonhematologic pediatric solid tumors.

Methods
We characterized the clinicopathologic features of 4 cases of CBFA2T3::GLIS2 fusion-positive myeloid sarcoma in pediatric patients where the sarcoma presented either without leukemic involvement (isolated myeloid sarcoma; 3/4 [75%]) or had concurrent leukemic disease (1/4 [25%]).

Results
All cases mimicked nonhematopoietic tumors at morphologic and immunophenotypic levels, so the initial evaluation did not raise suspicion for acute myeloid leukemia/myeloid sarcoma. After extensive workup, however, including molecular studies, the diagnosis of myeloid sarcoma with CBFA2T3::GLIS2 fusion was rendered.

Conclusions
This study highlights the need for a high suspicion index of GLIS2-rearranged myeloid sarcoma in the differential diagnosis of pediatric small round cell tumors in tissue biopsies and the application of adequate workup to avoid misdiagnosing this entity.
Characterizing metabolomic signatures related to coffee and tea consumption and their association with incidence and dynamic progression of type 2 diabetes: A multi-state analysis
Authors: Zheng Guzhengyue , Ran Shanshan , Zhang Jingyi , Qian Zhengmin (Min) , Tian Fei , Shi Hui , Elliott Michael , Tabet Maya , Yang Yin , Lin Hualiang 
Published: October 2024

Abstract
Our study aimed to investigate the impact of tea and coffee consumption and related metabolomic signatures on dynamic transitions from diabetes-free status to incident type 2 diabetes (T2D), and subsequently to T2D-related complications and death. We included 438,970 participants in the UK Biobank who were free of diabetes and diabetes complications at baseline. Of these, 212,146 individuals had information on all metabolic biomarkers. We identified tea- and coffee-related metabolomic signatures using elastic net regression models. We examined associations of tea and coffee intake and related metabolomic signatures with the onset and progression of T2D using multi-state regression models. We observed that tea and coffee consumption and related metabolomic signatures were inversely associated with the risk of five T2D transitions. For example, HRs (95% CIs) per SD increase of the tea-related metabolomic signature were 0.87 (0.85, 0.89), 0.97 (0.95, 0.99), 0.91 (0.90, 0.92), 0.92 (0.91, 0.94), and 0.91 (0.90, 0.92) for transitions from diabetes-free state to incident T2D, from diabetes-free state to total death, from incident T2D to T2D complications, from incident T2D to death, and from T2D complications to death. These findings highlight the benefit of tea and coffee intake in reducing the risk of occurrence and progression of T2D.
The metabolomic composition of the oviductal fluid is controlled by the periovulatory hormonal context in Bos indicus cows
Authors: Gonella-Diaza Angela , Sponchiado Mariana , Rodrigues França Moana , Liu Lihe , Pugliesi Guilherme , Guimarães Lo Turco Edson , Peñagaricano Francisco , Binelli Mario 
Published: October 2024

Abstract
In cattle, oviductal function is controlled by the ovarian sex-steroids estradiol and progesterone. Here, we tested the hypothesis that the exposure to contrasting sex-steroid milieus differentially impacts the oviductal fluid composition. Estrous cycles of non-lactating, multiparous Nelore cows were pre-synchronized and then synchronized with a protocol designed two induce ovulation of large or small follciles. Larger preovulatory follicle (day 0) and corpora lutea (day 4) and greater estradiol (day 0) and progesterone (day 4) concentrations were observed in the large follciles group. Four days after induced ovulation, oviductal fluid was collected post-mortem. Quantitative mass spectrometry was used to determine the concentration of amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, hexoses, prostaglandins, and related compounds. Multivariate analyses (orthogonal projections to latent structures discriminant analysis) were conducted to compare the metabolomic signatures of oviductal fluids. Correlation network analysis was conducted to measure the strength and hierarchy of associations among metabolites. Of the 205 metabolites quantified, 171 were detected in at least 50% of the samples and were included in further data analysis. After orthogonal projections to latent structures discriminant analysis analysis, samples of the large follciles and small follciles were divided clearly into two non-overlapping clusters. Twenty metabolites had different or tended to have different concentrations in the oviductal fluid when comparing groups. Seven of these 20 analytes had greater concentrations in large follciles cows. Moreover, total sum of biogenic amines, phosphatidylcholines, and prostaglandins were higher in the small follciles group. The correlation network showed that the large follciles group metabolites’ concentrations were highly intercorrelated, which was not observed in the small follciles group. We concluded that the periovulatory endocrine milieu regulates the composition of the oviductal fluid.
Functional principal component analysis with informative observation times
Authors: Sang Peijun , Kong Dehan , Yang Shu 
Published: October 2024

Summary
Functional principal component analysis has been shown to be invaluable for revealing variation modes of longitudinal outcomes, which serve as important building blocks for forecasting and model building. Decades of research have advanced methods for functional principal component analysis, often assuming independence between the observation times and longitudinal outcomes. Yet such assumptions are fragile in real-world settings where observation times may be driven by outcome-related processes. Rather than ignoring the informative observation time process, we explicitly model the observational times by a general counting process dependent on time-varying prognostic factors. Identification of the mean, covariance function and functional principal components ensues via inverse intensity weighting. We propose using weighted penalized splines for estimation and establish consistency and convergence rates for the weighted estimators. Simulation studies demonstrate that the proposed estimators are substantially more accurate than the existing ones in the presence of a correlation between the observation time process and the longitudinal outcome process. We further examine the finite-sample performance of the proposed method using the Acute Infection and Early Disease Research Program study.
Apelin levels in patients with polyuria-polydipsia syndrome upon copeptin stimulation tests
Authors: Bizzozero Chiara Angela , Monnerat Sophie , Chapman Fiona A , Dhaun Neeraj , Refardt Julie , Christ-Crain Mirjam 
Published: October 2024

Abstract

Objective
Differentiating between arginine vasopressin deficiency (AVP-D) and primary polydipsia (PP) requires a copeptin stimulation test. We aimed to characterize changes in apelin, an endogenous hormone antagonizing AVP, upon copeptin stimulation tests.

Design
Post hoc secondary analysis of a multi-centric cross-over diagnostic study (NCT03572166).

Setting
Outpatients included at the University Hospital Basel.

Participants
Patients with AVP-D and PP.

Interventions
Copeptin stimulation tests with hypertonic saline and arginine infusion.

Outcomes and Measures
The primary outcome was the absolute difference in apelin between baseline and peak of copeptin stimulation tests. Secondary objectives included the diagnostic ability of apelin.

Results
Thirty-eight patients were analysed, 23 (60%) had PP and 15 (40%) had AVP-D. No difference was seen between baseline median (IQR) apelin levels in PP and AVP-D (1079 [912, 1225] and 910 [756, 1039] pmol/L, respectively). Upon hypertonic saline, apelin decreased by −241 (−326, −124) pmol/L in PP and −47.2 (−198, 5.86) pmol/L in AVP-D (P = .022). The area under the curve (AUC) to differentiate PP from AVP-D was 97.1% (95% CI, 90.5-100) for copeptin and 49.3% (95% CI, 30.4-68.1) for apelin (P &lt; .001). Upon arginine, apelin decreased by −39.2 (−96.4, 39.8) pmol/L in PP and increased by 25.8 (2.8, 113.0) pmol/L in AVP-D (P = .1). The AUC was 97.1% (95% CI: 79.6-98.0) for copeptin and 60.5% (95% CI: 39.8-80.0) for apelin (P = .007).

Conclusions and Relevance
Our findings suggest that apelin decreases to a greater extent in PP compared with AVP-D upon copeptin stimulation tests. However, copeptin remains the best marker to differentiate AVP-D from PP.
Low Anti-Tumor Necrosis Factor Levels During Maintenance Phase Are Associated With Treatment Failure in Children With Crohn’s Disease
Authors: Moses Jonathan , Adler Jeremy , Saeed Shehzad A , Firestine Ann M , Galanko Joseph A , Ammoury Rana F , Bass Dorsey M , Bass Julie A , Bastidas Monique , Benkov Keith J , Bousvaros Athos , Cabrera José M , Chun Kelly Y , Dorsey Jill M , Ebach Dawn R , Gulati Ajay S , Herfarth Hans H , Ivanova Anastasia , Jester Traci W , Kaplan Jess L , Kusek Mark E , Leibowitz Ian H , Linville Tiffany M , Margolis Peter A , Minar Phillip , Molle-Rios Zarela , Niklinska-Schirtz Barbara Joanna , Olano Kelly K , Osaba Lourdes , Palomo Pablo J , Pashankar Dinesh S , Pitch Lisa , Samson Charles M , Sandberg Kelly C , Steiner Steven J , Strople Jennifer A , Sullivan Jillian S , Tung Jeanne , Wali Prateek , Wohl David A , Zikry Mike , Boyle Brendan M , Kappelman Michael D 
Published: October 2024

Abstract

Background
Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn’s disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (&gt;5 µg/mL for infliximab and &gt;7.5 µg/mL for adalimumab).

Methods
We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization.

Results
Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 μg/mL [P = .49]; adalimumab: 11.1 vs 10.5 μg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 μg/mL [P &lt; .01]; adalimumab: 9.1 vs 12.3 μg/mL [P &lt; .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14).

Conclusions
LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation.
MultiShape: a spectral element method, with applications to Dynamic Density Functional Theory and PDE-constrained optimization
Authors: Roden Jonna C , Mills-Williams Rory D , Pearson John W , Goddard Benjamin D 
Published: October 2024

Abstract
A new numerical framework is developed to solve general nonlinear and nonlocal PDEs on complicated two-dimensional domains. This enables the solution of a wide range of both steady and time-dependent problems on nonstandard geometries, as well as providing the ability to impose nonlinear and nonlocal boundary conditions (typical of those arising in the modelling of physical phenomena) in a flexible and automated way. This spectral element methodology, which we called MultiShape, is compatible with other state-of-the-art numerical methods, such as differential–algebraic equation solvers and optimization algorithms. MultiShape is an open-source Matlab library, in which the numerical implementation is designed to be user-friendly: the problem set-up and computations are done automatically through intuitive operator definitions and notation. Validation tests are presented, before we showcase the power and versatility of MultiShape with three motivating examples in Dynamic Density Functional Theory and PDE-constrained optimization.
Conceptual Decolonization, Conceptual Justice, and Religious Concepts
Authors: Burley Mikel 
Published: October 2024

Abstract
Calls for decolonization are on the rise in social and academic life, but ‘decolonization’ can mean various things. This article expounds and critically evaluates the programme of conceptual decolonization, chiefly as promulgated in relation to African philosophy by Kwasi Wiredu. The programme involves both resisting the unreflective acceptance of non-indigenous concepts and constructively utilizing indigenous conceptual resources to address philosophical questions. Examining recent objections from Olúfẹ́mi Táíwò and giving particular attention to Wiredu’s treatment of religious concepts, I concur with Wiredu that conceptual decolonization can encourage conceptual enlargement but argue that care is needed to avoid oversimplifying the non-indigenous concepts that are subjected to scrutiny.
PL02.2.A TRAMETINIB IN NEUROFIBROMATOSIS TYPE 1 RELATED SYMPTOMATIC PLEXIFORM NEUROFIBROMAS: ONE-YEAR FOLLOW-UP OF THE TRAIN STUDY
Authors: Noordhoek D C , van Dijk S A , French P J , Wiemer E A C , Hanff D F , Manintveld O C , Taal W 
Published: October 2024

Abstract

BACKGROUND
Plexiform neurofibromas (PN) are present in 50% of the patients with neurofibromatosis type 1 (NF1). They can cause pain, neurological deficit and cosmetic problems. Recent phase 2 clinical trials have shown promising results of treatment of inoperable PN with MEK inhibitors, especially in pediatric patients. Our aim was to evaluate the effect of the MEK inhibitor trametinib in adult NF1 patients.

MATERIAL AND METHODS
The TRAIN study is an open-label, single arm, phase 2 trial with trametinib 2 mg daily in 30 patients with NF1 and at least one symptomatic inoperable PN. The primary outcome measure is tumor volume decrease of the pre-defined target PN lesion(s) as measured by 3D volumetric analysis on 6-monthly MR imaging. A decrease of &gt;20% in total tumor volume is considered treatment response. Secondary outcome measures are pain, safety and tolerability.

RESULTS
Thirty patients have been enrolled since July 2020. The last patient completed one year follow-up end of May 2024. The current median follow-up is 29 months (range 12-46 months). Average age at study registration was 44 years (range 19-67 years). Eleven patients (37%) discontinued study treatment within the first year: 8 patients due to toxicity, 2 because of symptom progression and one patient because of a new contraindication for trametinib. Twenty-seven patients completed 12 months follow-up with MR imaging. The response rate was 48% within the first year of study treatment. Volume decrease ranged from: 21% to 57%. The remaining 52% of the patients had stable disease. The average Numeric Pain Rating Scale (NPRS) decreased from 5.2 at baseline to 3.5 at one year follow-up (p=0.027). The most common adverse events were acneiform rash, diarrhea, fatigue, asymptomatic anemia and hypoalbuminemia. Four severe adverse events (grade 3) occurred: pneumonitis (n=1), rhabdomyolysis (n=1) and erysipelas (n=2).

CONCLUSION
Approximately half of the adult NF1 patients with inoperable PNF showed a treatment response with trametinib within the first year. The average NPRS decreased significantly. However, adverse events are common and therefore more research is needed to select patients that will benefit the most from MEK inhibition.
KS01.5.A A BRAIN CANCER CELL ATLAS REVEALS SHARED ASTROCYTE-LIKE STEM CELL STATES DRIVE INTRATUMOURAL HETEROGENEITY AND SHAPE IMMUNE DYNAMICS IN ADULT-TYPE DIFFUSE GLIOMAS
Authors: Zaman A , Muskovic W , Holton E , Pandya M , Zakanovic R , Chin V , Lam E , Yeung J , Sughrue M , Teo C , Powell J 
Published: October 2024

Abstract

BACKGROUND
Adult-type diffuse gliomas pose significant clinical challenges due to their complex cellular makeup and evolving nature. Understanding this heterogeneity is crucial for developing effective targeted therapies.

MATERIALS AND METHODS
To understand glioma heterogeneity, we performed single-cell and single-nucleus RNA sequencing on 66 tumours (single surgery) and 54 paired (two surgeries) longitudinal samples. This dataset comprises approximately 900,000 cells, enabling us to investigate both the conserved cellular landscape and dynamic cellular evolution across different glioma subtypes.

RESULTS
Employing a novel phylogeny-based approach, we showed that the astrocyte-like glioma stem cell (GSC) is the origin of diverse glioma lineages. This finding represents a paradigm shift in our understanding of glioma development, highlighting the GSC as a potential therapeutic target. The GSC’s resemblance to healthy adult neural stem cells provides insight into the roots of glioma heterogeneity and suggests a shared origin for intratumoral diversity. Our analysis revealed a consistent cellular architecture spanning astrocytomas, oligodendrogliomas, and glioblastomas (GBMs). This architecture comprises seven recurring malignant cell states: neuro-, oligo-, neuro-oligo-lineage, cycling (G1/S, G2/M), hypoxia-associated, and a quiescent astrocyte-like GSC. Notably, the proportions of these cell states differ among glioma subtypes. We further show that GBMs exhibit significantly higher T-cell and myeloid cell infiltration than IDH-mutant gliomas. Paradoxically, this correlates with a worse prognosis, suggesting profound T-cell dysfunction and a complex interplay between myeloid cells and the tumour. Longitudinal analysis underscored the evolving nature of the glioma’s malignant cell populations and immune landscape. We identified subtype-specific T-cell and myeloid gene expression profiles, including targets like PARD6G (GBM) and CXCL13 (astrocytoma), which offer a foundation for developing targeted immunotherapies and prognostic biomarkers.

CONCLUSION
Our study provides a model of glioma heterogeneity and evolution. This model integrates a shared astrocyte-like GSC driving cellular diversity alongside distinct, dynamic immune landscapes across different glioma subtypes. These findings offer unprecedented potential for developing transformative treatment strategies. Future research functionally validating the GSC and its impact on tumour dynamics will be crucial for translating these insights into improved patient outcomes.