bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the van’t Hoff equation to phase equilibria
Authors: Carrero J. I.
Published: April 2024

van’t Hoff and Clausius–Clapeyron equations correspond to chemical and phase equilibria, respectively, but the Clausius–Clapeyron equation can be also a result of the application of van’t Hoff equation to the liquid–vapor or solid–vapor phase equilibrium of pure substances. Moreover, the application of van’t Hoff to gas–liquid and solid–liquid equilibrium data makes it possible to obtain enthalpies of dissolution. Examples based on published experimental data are included for all cases.
Knowing me, knowing you: an experiment on mutual payoff information in the stag hunt and Prisoner's Dilemma
Authors: Alshaikhmubarak Hazem , Hales David , Kogelnik Maria , Schwarz Molly , Strauss C. Kent
Published: April 2024

We experimentally study how mutual payoff information affects strategic play. Subjects play the Prisoner's Dilemma or Stag Hunt game against randomly re-matched opponents under two information treatments. In our partial-information treatment, subjects are shown only their own payoff structure, while in our full-information treatment they are shown both their own and their opponent's payoff structure. In both treatments, they receive feedback on their opponent's action after each round. We find that mutual payoff information initially facilitates reaching the socially optimal outcome in both games. Play in the Prisoner's Dilemma converges toward the unique Nash equilibrium of the game under both information treatments, while in the Stag Hunt mutual payoff information has a substantial impact on play and equilibrium selection in all rounds of the game. Belief-learning model estimations and simulations suggest these effects are driven by both initial play and the way subjects learn.
Effectiveness of Remote Implementation of the ACT Raising Safe Kids Program: A Pilot Study
Authors: Burkhart Kimberly , Rasiah Stephne S. , Knox Michele S. , Vatti Thanvi
Published: April 2024

The objective of the study was to evaluate the effectiveness of remote implementation of the ACT Raising Safe Kids (ACT-RSK) program. The ACT-RSK program is an evidence-based group parenting program designed to promote positive parenting. The COVID-19 pandemic precipitated the creation of a remote implementation guide to deliver the program via telehealth. A small (N = 21) sample of caregivers of children aged 1 to 10 living in the USA participated in the 9-week program and completed pre- and post-intervention questionnaires. ACT Facilitators provided feasibility and fidelity feedback through a focus group and questionnaires. There was a significant improvement in positive parenting skills and a decrease in verbal and physical punishment. There were no improvements in parental nurturing or limiting and monitoring children’s media use. Facilitators and participants found remote implementation to be feasible and acceptable. Facilitators were able to maintain high fidelity to the model. The remote implementation of the ACT-RSK program has benefits to positive parental behaviors and discipline, but possibly not limiting and monitoring of children’s media use and nurturing behavior. However, characteristics of families’ experiences during the COVID-19 pandemic may have influenced these results. Remote implementation of the ACT-RSK program can be useful for promoting positive parental behaviors and discipline.
Enhancing rock fragmentation assessment in mine blasting through machine learning algorithms: a practical approach
Authors: Gebretsadik Angesom , Kumar Rahul , Fissha Yewuhalashet , Kide Yemane , Okada Natsuo , Ikeda Hajime , Mishra Arvind Kumar , Armaghani Danial Jahed , Ohtomo Yoko , Kawamura Youhei
Published: April 2024

The optimization of blasting operations greatly benefits from the prediction of rock fragmentation. The main factors that affect fragmentation are rock mass characteristics, blast geometry, and explosive properties. This paper is a step towards the implementation of machine learning and deep learning algorithms for predicting the extent of fragmentation (in percentage) in open pit mining. While various parameters can affect rock fragmentation, this study considers ten among them (i.e., spacing, drill hole diameter, burden, average bench height, powder factor, number of holes, charge per delay, uniaxial compressive strength, specific drilling, and stemming) to train and test the models. However, due to a weak correlation with rock fragmentation, drill diameter, average bench height, compressive strength, stemming, and charge per delay are eliminated to reduce model complexity. A total of 219 data sets having five input features including the number of holes, spacing, burden, specific drilling, and powder factor are used to develop the models. Machine learning models (random forest regression, support vector regression, and XG boost), as well as a deep learning model (neural network regression), are applied to develop a practical way that can optimize the prediction of fragmentation. This study employs performance measures such as R-squared, RMSE, MSE, MAPE, and MAE. The optimization of the model revealed promising results, indicating that the architecture 5-64-32-16-1 exhibits strong performance. Specifically, the model achieved mean squared error (MSE) values of 41.32 and 28.59 on the training and test datasets, respectively. The R2 value for both training and test is 0.83. RFR is also performing well compared to SVR and XG boost with MSE values of 12.37 and 9.89 on training and testing data, respectively.in both sets, the R2 value is 94%. Based on permutation importance and shapely plot values, it is observed that the powder factor has the highest impact, while the burden has the lowest impact on fragmentation.
Determination of the Speed and Surface Temperature of Aircraft Using the Second Approximation of the System of Moment Equations
Authors: Sakabekov Auzhan , Auzhani Yerkanat , Yergazina Ryskul , Madaliyeva Saltanat
Published: April 2024

This study focuses on solving the initial-boundary value problem for a one-dimensional non-stationary nonlinear system of moment equations in the second approximation. We prove the existence of a unique local in-time solution of the problem under consideration in the space of functions that are continuous in time and square integrable over the spatial variable x. To solve the direct and inverse problems for this system, we develop an iterative numerical method and reduce the system of moment equations to canonical form. Furthermore, we present the software implementation of the algorithms and their application for solving inverse problems related to determining the speed and surface temperature of an aircraft, as well as atmospheric parameters. We provide the results of numerical experiments conducted to validate our approach.
Choral Tragedy
Authors: Calame Claude , Goldhill Simon
Published: April 2024

Ever since Aristotle opened the discussion on the role of the chorus in Greek tragedy, theories of the chorus have continued to proliferate and provoke debate to this day. The tragic chorus had its own story to tell; it was a collective identity, speaking within and to a collective citizen body, acting as an instrument through which stories of other times and places were dramatized into resonant heroic narratives for contemporary Athens. By including detailed case studies of three different tragedies (one each by Aeschylus, Euripides and Sophocles), Claude Calame's seminal study not only re-examines the role of the chorus in Greek tragedy, but pushes beyond this to argue for the 'polyphony' of choral performance. Here, he explores the fundamentally choral nature of the genre, and its deep connection to the cultic and ritual contexts in which tragedy was performed.
A Philosophy of Need
Authors: Brock Gillian
Published: April 2024

Appeals to need abound in everyday discussion. People make claims about their own needs all the time, and they do so in a way that suggests these should have a certain moral force. Needs also play an important role in contemporary popular discourse about social justice, climate change, obligations to future generations, dealing fairly with refugees, treating animals humanely, and critiques of consumerist lifestyles – to name just a few of the many examples. The idea of need is present in an increasing number of debates and domains. There is interest in need from several disciplines, not just philosophy, which also include psychology, economics, political science, social work and sociology. This volume, then, offers a fine introduction to an increasingly important concept in day-to-day life. In a new Foreword, Gillian Brock discusses the continuing significance of several innovative chapters in the book, indicating how they presaged new directions in philosophical conversation.
Quand Bourdieu découvrait Panofsky
Authors: Pasquali Paul
Published: April 2024

Fondé sur des archives inédites et la relecture de divers textes publiés, cet article retrace la fabrique éditoriale d’
Architecture gothique et pensée scolastique
, célèbre ouvrage d’Erwin Panofsky paru en français en 1967 aux éditions de Minuit, dans la collection de Pierre Bourdieu, qui l’a traduit, édité et postfacé. En examinant les conditions de possibilité de cette rencontre transatlantique et transdisciplinaire
a priori
improbable, survenue en 1966-1967, entre un jeune sociologue alors en début de carrière, établi à Paris, et un vieil historien mondialement connu résidant à Princeton, il vise à historiciser cette œuvre classique et à la relire de façon réflexive. Au carrefour de la sociologie historique des sciences sociales, de l’histoire de l’édition et de l’histoire des circulations intellectuelles transnationales, il invite plus largement à dénaturaliser nos pratiques de lecture en prenant pour objet nos héritages scientifiques. Pour ce faire, sont analysés successivement la formation du jeune Bourdieu et les premières réceptions de Panofsky en France dans les années 1950-1960, le contexte intellectuel et éditorial de cette importation dont les multiples enjeux sont explicités, les modalités concrètes de l’édition et de la traduction du livre, puis la genèse de la postface, où le concept bourdieusien d’habitus a été systématisé pour la première fois, au prix de malentendus que les archives permettent de documenter et de dissiper.
Enfermement et graffiti
Authors: Calafat Guillaume
Published: April 2024

Entrepris au début des années 2000, les travaux de restauration du bâtiment qui abritait les prisons de l’Inquisition de Palerme à l’époque moderne ont permis la redécouverte et l’étude historienne d’une impressionnante série de graffiti. Avec son livre,
Del Santo Uffizio in Sicilia e delle sue carceri
, Giovanna Fiume propose une riche synthèse de travaux individuels et collectifs qu’elle a consacrés à ces archives murales du tribunal palermitain. En faisant dialoguer l’histoire des procédures et l’histoire matérielle de la réclusion, elle parvient à identifier les auteurs possibles des inscriptions et des dessins exposés sur les parois des cellules. Elle met ainsi en lumière des trajectoires de prisonniers et des expériences de l’enfermement que les actes judiciaires taisent souvent. Ces graffiti offrent en effet une nouvelle strate documentaire pour mieux comprendre le système judiciaire, pénal et carcéral de l’Inquisition. Plus largement, cet ouvrage s’inscrit dans le sillage d’une efflorescence de recherches récentes, à la confluence des études littéraires, de l’anthropologie et de l’histoire de l’art, dédiées aux prisons et aux graffiti, qui s’intéressent tout à la fois à la dimension patrimoniale et scientifique, esthétique et ethnographique de ces empreintes graphiques. Cette note critique en propose une lecture et un état des lieux, comme autant de pistes méthodologiques et historiographiques pour documenter la vie sociale et intellectuelle à l’intérieur des prisons.
Monetizing Animal Welfare Impacts for Benefit–Cost Analysis
Authors: Budolfson Mark , Espinosa Romain , Fischer Bob , Treich Nicolas
Published: April 2024

Animal welfare is often ignored in decision-making, despite widespread agreement about its importance. This is partly because of a lack of quantitative methods to assess the impacts of policies on humans and nonhumans alike on a common scale. At the same time, recent work in economics, philosophy, and animal welfare science has made progress on the fundamental theoretical challenge of estimating the well-being potential of different species on a single scale. By combining these estimates of each species’ well-being potential with assessments of how various policies impact the quality of life for these species, along with the number of animals affected, we can arrive at a framework for estimating the impact of policies on animal health and well-being. This framework allows for a quantifiable comparison between policies affecting humans and animals. For instance, it enables us to compare human QALYs to animal QALYs tailored to specific species. Hence, the intrinsic value of animal welfare impacts of policies can be monetized on the same scale as market and non-market impact for humans, facilitating benefit–cost analysis. Many challenges remain though, including issues of population ethics, political feasibility, and new complexities in addressing equity and uncertainty.
A retrospective analysis of iv ketamine outcome on hospitalisations in an unselected psychiatric sample
Authors: Sandström Karl , Kampman Olli , Asellus Peter
Published: April 2024

Objective:

This study aims to explore the outcome with iv ketamine treatment in a real-world clinical setting, primarily measured as posttreatment days hospitalised.

Methods:

The psychiatric medical records of 46 patients having received iv ketamine on a psychiatric treatment indication between 2015 and 2018 were retrospectively examined. Analysis comparing the number and duration of hospital admissions before and after ketamine treatment as well as logistic regression analysis to investigate clinical predictors of effectiveness, were performed. To assess patients’ severity of depressed symptoms records were screened for MADRS-S scores.

Results:

No significant difference between pre- and posttreatment hospital days (p = 0.170), or number of hospitalisations (p = 0.740) were found. The response rate was 31% and remission rate 21%. None of the predictors showed statistical significance in the logistic model.

Conclusion:

Iv ketamine treatment showed effectiveness in reducing depressive symptoms even with complex patients in a real-world clinical setting. However, this did not translate to a reduction in hospitalisation. Highlighting the multifaceted challenges posed when implementing iv ketamine treatment in clinical practice.
Temporally resolved measurement of a force induced by a pulsed water-fuelled magnetron sputtering source
Authors: Shimizu Sota , Takahashi Kazunori
Published: April 2024

A high-speed solenoid-type pulsed valve is applied to a water-fuelled magnetron sputtering thruster, which can lead a compact and neutralizer-free electric propulsion device by generating a thrust due to the ejection of the sputtered target material, in order to minimize the size of the gas feeding system. The pulsed valve is opened for approximately 5 msec and the gaseous water is introduced into the source via a gas line connected to the source. A dc high voltage is firstly applied between the cathode and the anode; then the discharge is sustained for the period in which a gas pressure enough for the discharge is maintained and a change in the discharge mode is observed during the discharge pulse. To investigate the impact of the mode change on the thrust generation, a temporally resolved measurement of the force is equivalently performed by installing a pulsed voltage power supply and by changing the pulse width of the discharge voltage. The results show the temporal reduction of the thrust-to-power ratio during a pulsed discharge due to the nonlinear correlation between ion energy and sputtering yield. It is suggested that the use of a pulsed valve would be useful for downsizing of the electric propulsion system, while an optimization to properly control the gas flow rate is needed for further development.
Hindutva in the shadow of the Mahatma: M. S. Golwalkar, M. K. Gandhi, and the RSS in post-colonial India
Authors: Chaudhary Neha , Narayan Saarang
Published: April 2024

While many commentators have noted the Bharatiya Janata Party’s more recent attempts at appropriating Gandhian imagery and symbolism, few have diverted their attention towards earlier attempts by Hindu Nationalists to do so. M. S. Golwalkar is the most prominent example of Hindu Nationalists who attempted to incorporate Gandhi into the pantheon of Hindutva (Hindu-ness). This article argues that Golwalkar reproduced Gandhian ideas as part of Hindu Nationalist thought, alongside carefully and consciously portraying himself as an ascetic politician, much like Gandhi, in the post-colonial leg of his career. He crafted a mode of Hindutva politics whereby his image as an extraordinarily able-bodied yogi became an archetype that was touted as a model for every swayamsevak to follow. Furthermore, the ideological shifts that are visible in Golwalkar’s later publications created greater room in Hindutva thought to incorporate Gandhi’s ideas and legacy into the Rashtriya Swayamsevak Sangh’s (RSS) ideological fold. Doing so allowed Golwalkar to tackle the challenges the RSS faced after Gandhi’s assassination. This article locates Golwalkar and the RSS in the shadow of the Mahatma to not only broaden the understanding of Gandhi’s legacy in post-colonial India but also to prompt a reappraisal of the nature of Hindutva itself. By exploring the Sangh’s deep appropriation of Gandhi’s ideas and legacy, one can begin to understand the malleable and flexible nature of the otherwise narrow majoritarian Hindu Nationalist project.
Delegating legislative powers to the European Commission: the threat of non-compliance with tertiary legislation in the member states
Authors: Yordanova Nikoleta , Zhelyazkova Asya
Published: April 2024

When does the delegation of legislative powers to the executive endanger policy compliance? The European Union (EU) Lisbon Treaty introduced quasi-legislative tertiary legislation – delegated acts – which empowers the European Commission to amend secondary legislation. Formally, member states control delegated acts only ex post via a veto power in the Council, while they have both ex ante amendment powers and ex post veto over the alternative Commission legislation: implementing acts. However, as member states determine the choice of legislative instrument, we argue that they would consent to the Commission adopting delegated acts only on non-controversial issues. Such selection should result in their lower compliance with implementing than with delegated acts. Our analyses of member states’ transposition delays and infringement cases related to EU tertiary directives support this argument. The results suggest that the delegation of legislative powers to the executive does not increase non-compliance when the legislators have the means to moderate it ex ante.
A 6 year assessment of low sea-ice impacts on emperor penguins
Authors: Fretwell Peter T.
Published: April 2024

Sea ice, and particularly land-fast sea ice, is crucial for emperor penguins as a breeding and moulting platform and foraging habitat (Barbraud & Weimerskirch 2001). Emperor penguins use land-fast sea ice as a breeding platform to raise their chicks, from egg hatching in late July to mid-August until fledging, typically between mid-December and early January.
The Alagoas Antwren Myrmotherula snowi is in imminent danger of extinction
Authors: Vilela Hermínio A. L. S. , Andrade Arthur B. , Araujo Helder F. P. , Bichinski Tony A. , Cavalcante Bárbara , Develey Pedro F. , Reisfeld Alice , Phalan Benjamin T.
Published: April 2024

The “Critically Endangered” Alagoas Antwren Myrmotherula snowi is found only in the Atlantic Rainforest of north-east Brazil. We surveyed all sites where the species has been recorded, as well as 15 other potential sites. We summarise all observations of the species, focusing on the period from 2016 onwards, and including systematic censuses in three breeding seasons (October–March 2018/19, 2019/20, and 2020/21) at the type locality, Murici, where we also searched for nests of the species. We did not locate any individuals at sites other than Murici. The number of apparent individuals detected declined by 67% over seven years (a decline of 50% over the three years in which standardised systematic counts were made), and only six adults were observed in the most recent breeding season. The global population is now likely to be in single-digit figures. Of five nests found, four failed, through predation by snakes and opossums, and abandonment. We installed protective barriers to protect two of these nests from predators, which may have contributed to the single successful fledging. Such methods offer most hope for now of stalling the decline. Efforts to develop captive breeding methods with model species have been underway since 2019 but face many difficulties. Improving habitat protection and restoration is crucial but will only take effect in the long term.
Macro-financial imbalances and cyclical systemic risk dynamics: understanding the factors driving the financial cycle in the presence of non-linearities
Authors: O’Brien Martin , Velasco Sofia
Published: April 2024

This paper develops a multivariate filter based on an unobserved component model to estimate the financial cycle. Our model features: (1) a dynamic relationship between the financial cycle and key variables; (2) time-varying shock volatility for trend and cycle components. We demonstrate that our approach not only exhibits superior early warning properties for banking crises but also outperforms commonly used indicators in terms of data fit for decomposition exercises, as evidenced by the higher marginal likelihood. We document three important properties of the financial cycle. First, the sensitivity of the financial cycle to changes in real estate valuations increased during the post-90s period. Second, the sensitivity of the cycle to changes in financial conditions displays volatility and country specificities. Finally, our reduced form estimates suggest that the banking crisis of 1988 was preceded by positive contributions from the risk appetite shock, while the primary source of vulnerabilities emanated from the housing market in the run-up to the Global Financial Crisis.
Transience of (In)Formality: The Role of the Joint Initiatives in Reforming the WTO Negotiations
Authors: Peres Ana
Published: April 2024

This paper develops the concept of transience of (in)formality to refer to the intersection of formal and informal negotiating procedures in the WTO decision-making system. It argues that both formal and informal negotiating processes are essential for delivering negotiating outcomes in the WTO. Particularly, the article assesses how informal negotiating practices emerge within the WTO formal framework and align with it. The analysis highlights how negotiating practices (re)shape existing norms, both formal and informal, adapting the WTO to overcome challenges and meet current needs. It also disputes legal formalistic perspectives that permeate trade literature and offer limited accounts of Members' agency in the WTO. The paper uses the Joint Initiatives as a case study to illustrate the convergence between formality and informality and a possible way ahead for the WTO negotiations. By broadening the understanding of law-making, it contributes to the discussion on WTO reform. It provides alternatives that reflect the reality of WTO negotiations and underlines the institution's relevance.
Tracking the Nearfield Evolution of an Initially Shallow, Neutrally Buoyant Plane Jet Over a Sloping Bottom Boundary
Authors: Shi H. , Negretti M. E. , Chauchat J. , Blanckaert K. , Lemmin U. , Barry D. A.
Published: April 2024

Understanding coastal plane jets which occur when a body of water discharges into an ocean or a lake through a channel or outlet is important, since they play a significant role in sediment, nutrient, and pollutant exchange. This study investigates the nearfield of initially shallow, neutrally buoyant plane jets, bounded by a free surface and a sloping bottom (Sloping Bottom Jet; SBJ) that issue into a laterally unconfined quiescent ambient both experimentally and numerically, and compares them with a plane jet flowing over a horizontal bottom (Horizontal Bottom Jet; HBJ). Results revealed that, different from the HBJ, the width and centerline velocity of SBJ decrease near the mouth. The SBJ width gradually increases after that as the transverse longitudinal velocity profile progressively transforms from a “top‐hat” into a Gaussian distribution. Once the Gaussian distribution is established, both jets diverge and centerline velocity decreases. Shear layers are generated on the sides of both jets with Kelvin Helmholtz‐type Coherent Structures (KHCS) developing inside. KHCS produce periodic velocity fluctuations with a Strouhal number of ∼0.079 and contribute significantly to momentum exchange and turbulent kinetic energy production. Since the thickness of the SBJ increases longitudinally, the vertical extent of KHCS also increases. When the two shear layers meet and merge at the centerline, they cause a flapping motion of the jet. This location is closer to the jet mouth for SBJs than for the HBJ. These findings demonstrate that a sloping bottom modifies the flow field from quasi‐2D for the HBJ to strongly 3D for SBJs.
Advances in the multimodal analysis of the 3D chromatin structure and gene regulation
Authors: Han Man-Hyuk , Park Jihyun , Park Minhee
Published: April 2024

Recent studies have demonstrated that the three-dimensional conformation of the chromatin plays a crucial role in gene regulation, with aberrations potentially leading to various diseases. Advanced methodologies have revealed a link between the chromatin conformation and biological function. This review divides these methodologies into sequencing-based and imaging-based methodologies, tracing their development over time. We particularly highlight innovative techniques that facilitate the simultaneous mapping of RNAs, histone modifications, and proteins within the context of the 3D architecture of chromatin. This multimodal integration substantially improves our ability to establish a robust connection between the spatial arrangement of molecular components in the nucleus and their functional roles. Achieving a comprehensive understanding of gene regulation requires capturing diverse data modalities within individual cells, enabling the direct inference of functional relationships between these components. In this context, imaging-based technologies have emerged as an especially promising approach for gathering spatial information across multiple components in the same cell.
Gut microbiome predicts cognitive function and depressive symptoms in late life
Authors: Kolobaric A. , Andreescu C. , Jašarević E. , Hong C. H. , Roh H. W. , Cheong J. Y. , Kim Y. K. , Shin T. S. , Kang C. S. , Kwon C. O. , Yoon S. Y. , Hong S. W. , Aizenstein H. J. , Karim H. T. , Son S. J.
Published: April 2024

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.
Reduced intensity versus myeloablative conditioning for MDS: long-term results of an EBMT phase III study (RICMAC)
Authors: Niederwieser Christian , Iacobelli Simona , Franke Georg-Nikolaus , Koster Linda , van Os Marleen , Platzbecker Uwe , Hübel Kai , Scheid Christof , Müller Lutz Peter , Stelljes Matthias , Morozova Elena , Passweg Jakob , Onida Francesco , Dreger Peter , Saccardi Riccardo , Ladetto Marco , Salmenniemi Urpu , Bethge Wolfgang , Poiré Xavier , Kobbe Guido , McLornan Donal P. , Robin Marie , Kröger Nicolaus
Published: April 2024

Short-term outcome of myeloablative (MAC) and reduced intensity (RIC) conditioning in the prospective randomized international EBMT RICMAC study in patients with myelodyplastic syndrome (MDS) was comparable but longer follow up is lacking. Patients with MDS aged 18–65 years were randomized to receive MAC (N = 64) with busulfan/cyclophosphamide or RIC (n = 65) with busulfan/fludarabine followed by stem cell transplantation -(HCT) from HLA matched or mismatched donor. After a median follow-up of 6.2 (0.4–12.5) years, 10-year OS and RFS were 54.0% and 43.9% for RIC and 44.4% and 44.2% for MAC (p = 0.15 and p = 0.78), respectively. Since the first report, 6 patients died on NRM, 4 after RIC, and 2 after MAC. Similarly, 8 patients relapsed (4 in each arm), increasing the number of relapsed patients to 28. The second HCT was performed in 18 pts, 8 in the MAC, and 10 in the RIC arm. In a multivariate analysis, ECOG status and chemotherapy prior to HCT were independent risk factors for OS and RFS, ECOG and low cytogenetic risk for NRM and chemotherapy prior to HCT for RI. Patients with low cytogenetic risk had better OS [p = 0.002], RFS [p = 0.02], and NRM (p = 0.015) after RIC as compared to MAC.
The first genetically confirmed cohort of Facioscapulohumeral Muscular Dystrophy from Northern India
Authors: Vishnu Venugopalan Y. , Lemmers Richard J. L. F. , Reyaz Alisha , Mishra Rinkle , Ahmad Tanveer , van der Vliet Patrick J. , Kretkiewicz Marcelina M. , Macken William L. , Efthymiou Stephanie , Dominik Natalia , Morrow Jasper M. , Bhatia Rohit , Wilson Lindsay A. , Houlden Henry , Hanna Michael G. , Bugiardini Enrico , van der Maarel Silvère M. , Srivastava M. V. Padma
Published: April 2024

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of hereditary myopathy. Sixty per cent of the world’s population lives in Asia, so a significant percentage of the world’s FSHD participants is expected to live there. To date, most FSHD studies have involved individuals of European descent, yet small-scale studies of East-Asian populations suggest that the likelihood of developing FSHD may vary. Here, we present the first genetically confirmed FSHD cohort of Indian ancestry, which suggests a pathogenic FSHD1 allele size distribution intermediate between European and North-East Asian populations and more asymptomatic carriers of 4 unit and 5 unit FSHD1 alleles than observed in European populations. Our data provides important evidence of differences relevant to clinical diagnostics and underscores the need for global FSHD participation in research and trial-ready Indian FSHD cohorts.
Age related cerebrospinal fluid flow dynamics in the subarachnoid space of the optic nerve in patients with normal tension glaucoma, measured by diffusion weighted MRI
Authors: Berberat Jatta , Pircher Achmed , Remonda Luca , Killer Hanspeter E.
Published: April 2024

Background/objectives

We aimed to measure cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) by applying non-invasive diffusion-weighted MRI in patients with normal tension glaucoma (NTG) compared to age-matched controls.

Subjects/methods

In this prospective study, an analysis of diffusion-weighted images of 26 patients with NTG (49ONs) and age-matched volunteers (52ONs) was conducted. Subjects were classified into 4 groups: group I (50–59 y., n = 12 eyes), group II (60–69 y., n = 16 eyes), group III (70–79 y., n = 18 eyes) and group IV ( > 80 y., n = 6 eyes) for NTGs and healthy volunteers, respectively. The flow-range ratio (FRR) between the frontal lobe SAS and the SAS of the ON was calculated for each age category group and then compared between age-categories as well as between NTGs and controls.

Results

The mean FRR for age groups were (I) 0.54 ± 0.06 and 0.62 ± 0.03 (p < 0.05), (II) 0.56 ± 0.08 and 0.63 ± 0.03 (p < 0.05), (III) 0.54 ± 0.06 and 0.62 ± 0.02 (p < 0.001) as well as (IV) 0.61 ± 0.03 and 0.61 ± 0.04, for NTGs and controls, respectively. Using pooled data, the difference between the FRR in NTGs and controls was statistically significant (p < 0.0001). There were no statistically significant differences within the age categories of the control group. When comparing the FRR of NTGs by age categories, no statistically significant difference was found between the subgroups.

Conclusions

FRR was significantly reduced in NTGs compared to age-matched controls without any significant differences within the age groups themselves. Given the physiological importance of CSF for the integrity of neurons, axons and glial cells, reduced CSF flow dynamics might be part of the underlying neurodegenerative process of NTG.
Lysosomal genes contribute to Parkinson’s disease near agriculture with high intensity pesticide use
Authors: Ngo Kathie J. , Paul Kimberly C. , Wong Darice , Kusters Cynthia D. J. , Bronstein Jeff M. , Ritz Beate , Fogel Brent L.
Published: April 2024

Parkinson’s disease (PD), the second most common neurodegenerative disorder, develops sporadically, likely through a combination of polygenic and environmental factors. Previous studies associate pesticide exposure and genes involved in lysosomal function with PD risk. We evaluated the frequency of variants in lysosomal function genes among patients from the Parkinson’s, Environment, and Genes (PEG) study with ambient pesticide exposure from agricultural sources. 757 PD patients, primarily of White European/non-Hispanic ancestry (75%), were screened for variants in 85 genes using a custom amplicon panel. Variant enrichment was calculated against the Genome Aggregation Database (gnomAD). Enriched exonic variants were prioritized by exposure to a cluster of pesticides used on cotton and severity of disease progression in a subset of 386 patients subdivided by race/ethnicity. Gene enrichment analysis identified 36 variants in 26 genes in PEG PD patients. Twelve of the identified genes (12/26, 46%) had multiple enriched variants and/or a single enriched variant present in multiple individuals, representing 61% (22/36) of the observed variation in the cohort. The majority of enriched variants (26/36, 72%) were found in genes contributing to lysosomal function, particularly autophagy, and were bioinformatically deemed functionally deleterious (31/36, 86%). We conclude that, in this study, variants in genes associated with lysosomal function, notably autophagy, were enriched in PD patients exposed to agricultural pesticides suggesting that altered lysosomal function may generate an underlying susceptibility for developing PD with pesticide exposure. Further study of gene-environment interactions targeting lysosomal function may improve understanding of PD risk in individuals exposed to pesticides.
Large language models for preventing medication direction errors in online pharmacies
Authors: Pais Cristobal , Liu Jianfeng , Voigt Robert , Gupta Vin , Wade Elizabeth , Bayati Mohsen
Published: April 2024

Errors in pharmacy medication directions, such as incorrect instructions for dosage or frequency, can increase patient safety risk substantially by raising the chances of adverse drug events. This study explores how integrating domain knowledge with large language models (LLMs)—capable of sophisticated text interpretation and generation—can reduce these errors. We introduce MEDIC (medication direction copilot), a system that emulates the reasoning of pharmacists by prioritizing precise communication of core clinical components of a prescription, such as dosage and frequency. It fine-tunes a first-generation LLM using 1,000 expert-annotated and augmented directions from Amazon Pharmacy to extract the core components and assembles them into complete directions using pharmacy logic and safety guardrails. We compared MEDIC against two LLM-based benchmarks: one leveraging 1.5 million medication directions and the other using state-of-the-art LLMs. On 1,200 expert-reviewed prescriptions, the two benchmarks respectively recorded 1.51 (confidence interval (CI) 1.03, 2.31) and 4.38 (CI 3.13, 6.64) times more near-miss events—errors caught and corrected before reaching the patient—than MEDIC. Additionally, we tested MEDIC by deploying within the production system of an online pharmacy, and during this experimental period, it reduced near-miss events by 33% (CI 26%, 40%). This study shows that LLMs, with domain expertise and safeguards, improve the accuracy and efficiency of pharmacy operations.
Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review and meta-analysis
Authors: Pipek Leonardo Zumerkorn , Moraes Walter Augusto Fabio , Nobetani Rodrigo Massato , Cortez Vitor Santos , Condi Alberto Santos , Taba João Victor , Nascimento Rafaela Farias Vidigal , Suzuki Milena Oliveira , do Nascimento Fernanda Sayuri , de Mattos Vitoria Carneiro , Iuamoto Leandro Ryuchi , Hsing Wu Tu , Carneiro-D’Albuquerque Luiz Augusto , Meyer Alberto , Andraus Wellington
Published: April 2024

Obesity is a highly prevalent disease with numerous complications. Both intensive medical treatment with the use of pharmacological drugs and bariatric surgery are current options. The objective of this meta-analysis was to compare, in the long-term, intensive medical treatment and surgery based on twelve parameters related to weight loss, cardiovascular and endocrine changes. A review of the literature was conducted in accordance with the PRISMA guidelines (PROSPERO: CRD42021265637). The literature screening was done from inception to October 2023 through PubMed, EMBASE and Web of Science databases. We included randomized clinical trials that had separate groups for medical treatment and bariatric surgery as an intervention for obesity. The risk of bias was assessed through RoB2. A meta-analysis was performed with measures of heterogeneity and publication bias. Subgroup analysis for each surgery type was performed. Data is presented as forest-plots. Reviewers independently identified 6719 articles and 6 papers with a total 427 patients were included. All studies were randomized controlled trials, three had a follow up of 5 years and two had a follow up of 10 years. Both groups demonstrated statistical significance for most parameters studied. Surgery was superior for weight loss (− 22.05 kg [− 28.86; − 15.23), total cholesterol (− 0.88 [− 1.59; − 0.17]), triglycerides (− 0.70 [− 0.82; − 0.59]), HDL (0.12 [0.02; 0.23]), systolic pressure (− 4.49 [− 7.65; − 1.33]), diastolic pressure (− 2.28 [− 4.25; − 0.31]), Hb glycated (− 0.97 [− 1.31; − 0.62]), HOMA IR (− 2.94; [− 3.52; − 2.35]) and cardiovascular risk (− 0.08; [− 0.10; − 0.05]). Patient in the surgical treatment group had better long term outcomes when compared to the non-surgical group for most clinical parameters.
Comparative analysis of SEC61A1 mutant R236C in two patient-derived cellular platforms
Authors: Weiand Matthias , Sandfort Vanessa , Nadzemova Oksana , Schierwagen Robert , Trebicka Jonel , Schlevogt Bernhard , Kabar Iyad , Schmidt Hartmut , Zibert Andree
Published: April 2024

SEC61A1 encodes a central protein of the mammalian translocon and dysfunction results in severe disease. Recently, mutation R236C was identified in patients having autosomal dominant polycystic liver disease (ADPLD). The molecular phenotype of R236C was assessed in two cellular platforms. Cells were immortalized by retroviral transduction of an oncogene (UCi) or reprogrammed to induced pluripotent stem cells (iPSC) that were differentiated to cholangiocyte progenitor-like cells (CPLC). UCi and CPLC were subjected to analyses of molecular pathways that were associated with development of disease. UCi displayed markers of epithelial cells, while CPLCs expressed typical markers of both cholangiocytes and hepatocytes. Cells encoding R236C showed a stable, continuous proliferation in both platforms, however growth rates were reduced as compared to wildtype control. Autophagy, cAMP synthesis, and secretion of important marker proteins were reduced in R236C-expressing cells. In addition, R236C induced increased calcium leakiness from the ER to the cytoplasm. Upon oxidative stress, R236C led to a high induction of apoptosis and necrosis. Although the grade of aberrant cellular functions differed between the two platforms, the molecular phenotype of R236C was shared suggesting that the mutation, regardless of the cell type, has a dominant impact on disease-associated pathways.
Gingival proteomics reveals the role of TGF beta and YAP/TAZ signaling in Raine syndrome fibrosis
Authors: Costa Cláudio Rodrigues Rezende , Chalgoumi Rym , Baker Amina , Guillou Clément , Yamaguti Paulo Marcio , Simancas Escorcia Victor , Abbad Lilia , Amorin Bruna Rabelo , de Lima Caroline Lourenço , Cannaya Vidjea , Benassarou Mourad , Berdal Ariane , Chatziantoniou Christos , Cases Olivier , Cosette Pascal , Kozyraki Renata , Acevedo Ana Carolina
Published: April 2024

Raine syndrome (RNS) is a rare autosomal recessive osteosclerotic dysplasia. RNS is caused by loss-of-function disease-causative variants of the FAM20C gene that encodes a kinase that phosphorylates most of the secreted proteins found in the body fluids and extracellular matrix. The most common RNS clinical features are generalized osteosclerosis, facial dysmorphism, intracerebral calcifications and respiratory defects. In non-lethal RNS forms, oral traits include a well-studied hypoplastic amelogenesis imperfecta (AI) and a much less characterized gingival phenotype. We used immunomorphological, biochemical, and siRNA approaches to analyze gingival tissues and primary cultures of gingival fibroblasts of two unrelated, previously reported RNS patients. We showed that fibrosis, pathological gingival calcifications and increased expression of various profibrotic and pro-osteogenic proteins such as POSTN, SPARC and VIM were common findings. Proteomic analysis of differentially expressed proteins demonstrated that proteins involved in extracellular matrix (ECM) regulation and related to the TGFβ/SMAD signaling pathway were increased. Functional analyses confirmed the upregulation of TGFβ/SMAD signaling and subsequently uncovered the involvement of two closely related transcription cofactors important in fibrogenesis, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Knocking down of FAM20C confirmed the TGFβ-YAP/TAZ interplay indicating that a profibrotic loop enabled gingival fibrosis in RNS patients. In summary, our in vivo and in vitro data provide a detailed description of the RNS gingival phenotype. They show that gingival fibrosis and calcifications are associated with, and most likely caused by excessed ECM production and disorganization. They furthermore uncover the contribution of increased TGFβ–YAP/TAZ signaling in the pathogenesis of the gingival fibrosis.
The role of mood and arousal in the effect of background music on attentional state and performance during a sustained attention task
Authors: Kiss Luca , Linnell Karina J.
Published: April 2024

Across two online experiments, this study explored the effect of preferred background music on attentional state and performance, as well as on mood and arousal, during a vigilance task. It extended recent laboratory findings—showing an increase in task-focus and decrease in mind-wandering states with music—to environments with more distractions around participants. Participants—people who normally listen to background music during attention-demanding tasks—completed the vigilance task in their homes both with and without their chosen music and reported their attentional state, subjective arousal, and mood valence throughout the task. Experiment 1 compared music to relative silence and Experiment 2 compared music against the backdrop of continuous noise to continuous noise alone. In both experiments, music decreased mind-wandering and increased task-focus. Unlike in previous laboratory studies, in both experiments music also led to faster reaction times while increasing low-arousal external-distraction states. Importantly, mood and arousal increased with music and were shown to mediate its effects on reaction time and for the first time attentional state, both separately and together. Serial mediation effects were mostly confined to models where mood was entered first and arousal second and were consistent with the mood-arousal account of the impact of background music listening.
Development and validation of AI/ML derived splice-switching oligonucleotides
Authors: Fronk Alyssa D , Manzanares Miguel A , Zheng Paulina , Geier Adam , Anderson Kendall , Stanton Shaleigh , Zumrut Hasan , Gera Sakshi , Munch Robin , Frederick Vanessa , Dhingra Priyanka , Arun Gayatri , Akerman Martin
Published: April 2024

Splice-switching oligonucleotides (SSOs) are antisense compounds that act directly on pre-mRNA to modulate alternative splicing (AS). This study demonstrates the value that artificial intelligence/machine learning (AI/ML) provides for the identification of functional, verifiable, and therapeutic SSOs. We trained XGboost tree models using splicing factor (SF) pre-mRNA binding profiles and spliceosome assembly information to identify modulatory SSO binding sites on pre-mRNA. Using Shapley and out-of-bag analyses we also predicted the identity of specific SFs whose binding to pre-mRNA is blocked by SSOs. This step adds considerable transparency to AI/ML-driven drug discovery and informs biological insights useful in further validation steps. We applied this approach to previously established functional SSOs to retrospectively identify the SFs likely to regulate those events. We then took a prospective validation approach using a novel target in triple negative breast cancer (TNBC), NEDD4L exon 13 (NEDD4Le13). Targeting NEDD4Le13 with an AI/ML-designed SSO decreased the proliferative and migratory behavior of TNBC cells via downregulation of the TGFβ pathway. Overall, this study illustrates the ability of AI/ML to extract actionable insights from RNA-seq data.
Tetraphenylene-based semiconductive metal–organic framework crystals for direct X-ray detection and imaging
Authors: Luo Qi , Li Yuxia , Huang Xin , Zheng Yi , Gu Qi , Wang Shuaihua , Wu Shaofan
Published: April 2024

In this work, we prepared Pb-TCPE, a three-dimensional MOF that can be used for direct X-ray detection. The sensitivity of the single crystal reaches 4812.6 μC Gyair−1 cm−2 under a bias voltage of 50 V. And the detection limit is 93.3 nGyair s−1.
Percolation threshold in annealed ultrathin SiOx films by 2D Monte Carlo simulations
Authors: Sarikov Andrey , Semenenko Mykola , Shahan Serhii
Published: April 2024

The percolation threshold of a Si phase formed by phase separation of ultrathin SiOx films is determined by 2D Monte Carlo simulations.