bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical trials are becoming more complex: a machine learning analysis of data from over 16,000 trials
Authors: Markey Nigel , Howitt Ben , El-Mansouri Ilyass , Schwartzenberg Carel , Kotova Olga , Meier Christoph 
Published: February 2024

AbstractThe past decade has seen substantial innovation in clinical trials, including new trial formats, endpoints, and others. Also there have been regulatory changes, increasing competitive pressures and other external factors which impact clinical trials. In parallel, trial timelines have increased and success rates remain stubbornly low. This has led many observers to question whether clinical trials have become overly complex and if this complexity is always needed. Here we present a large-scale analysis of protocols and other data from over 16,000 trials. Using a machine learning algorithm, we automatically assessed key features of these trials, such as number of endpoints, number of inclusion–exclusion criteria and others. Using a regression analysis we combined these features into a new metric, the Trial Complexity Score, which correlates with overall clinical trial duration. Looking at this score across different clinical phases and therapeutic areas we see substantial increases over time, suggesting that clinical trials are indeed becoming more complex. We discuss drivers of increasing trial complexity, necessary or helpful (‘good’) complexity versus unnecessary (‘bad’) complexity, and we explore mechanisms of how sponsors of clinical trials can reduce trial complexity where appropriate.
A mathematically rigorous algorithm to define, compute and assess relevance of the probable dissociation constants in characterizing a biochemical network
Authors: Kundu Siddhartha 
Published: February 2024

AbstractMetabolism results from enzymatic- and non-enzymatic interactions of several molecules, is easily parameterized with the dissociation constant and occurs via biochemical networks. The dissociation constant is an empirically determined parameter and cannot be used directly to investigate in silico models of biochemical networks. Here, we develop and present an algorithm to define, compute and assess the relevance of the probable dissociation constant for every reaction of a biochemical network. The reactants and reactions of this network are modelled by a stoichiometry number matrix. The algorithm computes the null space and then serially generates subspaces by combinatorially summing the spanning vectors that are non-trivial and unique. This is done until the terms of each row either monotonically diverge or form an alternating sequence whose terms can be partitioned into subsets with almost the same number of oppositely signed terms. For a selected null space-generated subspace the algorithm utilizes several statistical and mathematical descriptors to select and bin terms from each row into distinct outcome-specific subsets. The terms of each subset are summed, mapped to the real-valued open interval $$\left(0,\infty \right)$$

0
,
∞

and used to populate a reaction-specific outcome vector. The p1-norm for this vector is then the probable dissociation constant for this reaction. These steps are continued until every reaction of a modelled network is unambiguously annotated. The assertions presented are complemented by computational studies of a biochemical network for aerobic glycolysis. The fundamental premise of this work is that every row of a null space-generated subspace is a valid reaction and can therefore, be modelled as a reaction-specific sequence vector with a dimension that corresponds to the cardinality of the subspace after excluding all trivial- and redundant-vectors. A major finding of this study is that the row-wise sum or the sum of the terms contained in each reaction-specific sequence vector is mapped unambiguously to a positive real number. This means that the probable dissociation constants, for all reactions, can be directly computed from the stoichiometry number matrix and are suitable indicators of outcome for every reaction of the modelled biochemical network. Additionally, we find that the unambiguous annotation for a biochemical network will require a minimum number of iterations and will determine computational complexity.
Social consequences of planned relocation in response to sea level rise: impacts on anxiety, well-being, and perceived safety
Authors: Abu Mumuni , Heath Stacey C , Adger W. Neil , Codjoe Samuel Nii Ardey , Butler Catherine , Quinn Tara 
Published: February 2024

AbstractGovernments globally are adapting to sea level rise through a range of interventions to improve everyday lives of communities at risk. One prominent response is planned relocation, where people and communities are enabled to move from localities exposed to coastal erosion and inundation as a result of sea level rise. Managed retreat has significant social consequences including under-reported impacts on health, well-being and social identity. Here we adopt well-established measures of well-being and document the outcomes of planned relocation on well-being in the Volta Delta region of Ghana. Data from a bespoke survey for individuals (n = 505) in relocated and non-relocated communities demonstrate that planned relocation negatively impacts well-being and anxiety of those relocated when compared to a community that is equally exposed but has not moved. Individuals in the relocated community reported significantly lower levels of overall wellbeing, significantly higher levels of anxiety, and lower perceptions of safety, compared to non-relocated community members. These outcomes are explained as being related to the disruption of community connection, identities, and feelings of efficacy. Relocated community members reported significantly lower levels of attachment to the local area and home, significantly lower levels of community-based self-efficacy, and significantly lower levels of overall community-based identity. The results demonstrate that planned relocation to address sea level rise has multiple social consequences with outcomes for well-being that are not straightforwardly related to risk reduction.
RETRACTED ARTICLE: Preliminary risk assessment of in-vessel leakage accident in ITER
Authors: Duan Qizhi , Fang Xingchen , Chen Shuai , Xie Hongyun , Wang Chunbing , Wang Dagui 
Published: February 2024

AbstractThe ITER project is one of the largest international cooperative scientific projects in the world, aiming to verify the feasibility of magnetic confinement controlled nuclear fusion technology and provide a technical basis for the subsequent construction of fusion energy power stations. The success or failure of ITER will greatly affect the commercialization process of fusion energy. The probabilistic safety assessment (PSA) was a powerful means to evaluate the risk and reliability of nuclear facility and achieved great success in safety assessment of fission power plants. Based on this, the PSA progress for ITER was proposed in this paper. And the in-vessel leakage accident was investigated to verify the effectiveness of proposed method. The result shows the maximum possible radiological consequences of ITER in-vessel leakage accident of ITER is 1.6E−3 mSv, and the frequencies of this consequence is 1.63E−8/year. The reason of this consequence was also discussed in this paper. Those result could provide some valuable reference for radiation risk assessment and safety supervision of fusion commercial reactor in the nuclear future.
Integrating aesthetics and efficiency: AI-driven diffusion models for visually pleasing interior design generation
Authors: Chen Junming , Shao Zichun , Zheng Xiaodong , Zhang Kai , Yin Jun 
Published: February 2024

AbstractThe interior design suffers from inefficiency and a lack of aesthetic appeal. With the development of artificial intelligence diffusion models, using text descriptions to generate aesthetically pleasing designs has emerged as a new approach to address these issues. In this study, we propose a novel method based on the aesthetic diffusion model, which can quickly generate visually appealing interior design based on input text descriptions while allowing for the specification of decorative styles and spatial functions. The method proposed in this study creates creative designs and drawings by computer instead of from designers, thus improving the design efficiency and aesthetic appeal. We demonstrate the potential of this approach in the field of interior design through our research. The results indicate that: (1) The method efficiently provides designers with aesthetically pleasing interior design solutions; (2) By modifying the text descriptions, the method allows for the rapid regeneration of design solutions; (3) Designers can apply this highly flexible method to other design fields through fine-tuning. (4) The method optimizes the workflow of interior design.
Distribution of infectious and parasitic agents among three sentinel bee species across European agricultural landscapes
Authors: Babin Aurélie , Schurr Frank , Delannoy Sabine , Fach Patrick , Huyen Ton Nu Nguyet Minh , Bougeard Stéphanie , de Miranda Joachim R. , Rundlöf Maj , Wintermantel Dimitry , Albrecht Matthias , Attridge Eleanor , Bottero Irene , Cini Elena , Costa Cecilia , De la Rúa Pilar , Di Prisco Gennaro , Dominik Christophe , Dzul Daniel , Hodge Simon , Klein Alexandra-Maria , Knapp Jessica , Knauer Anina C. , Mänd Marika , Martínez-López Vicente , Medrzycki Piotr , Pereira-Peixoto Maria Helena , Potts Simon G. , Raimets Risto , Schweiger Oliver , Senapathi Deepa , Serrano José , Stout Jane C. , Tamburini Giovanni , Brown Mark J. F. , Laurent Marion , Rivière Marie-Pierre , Chauzat Marie-Pierre , Dubois Eric 
Published: February 2024

AbstractInfectious and parasitic agents (IPAs) and their associated diseases are major environmental stressors that jeopardize bee health, both alone and in interaction with other stressors. Their impact on pollinator communities can be assessed by studying multiple sentinel bee species. Here, we analysed the field exposure of three sentinel managed bee species (Apis mellifera, Bombus terrestris and Osmia bicornis) to 11 IPAs (six RNA viruses, two bacteria, three microsporidia). The sentinel bees were deployed at 128 sites in eight European countries adjacent to either oilseed rape fields or apple orchards during crop bloom. Adult bees of each species were sampled before their placement and after crop bloom. The IPAs were detected and quantified using a harmonised, high-throughput and semi-automatized qPCR workflow. We describe differences among bee species in IPA profiles (richness, diversity, detection frequencies, loads and their change upon field exposure, and exposure risk), with no clear patterns related to the country or focal crop. Our results suggest that the most frequent IPAs in adult bees are more appropriate for assessing the bees’ IPA exposure risk. We also report positive correlations of IPA loads supporting the potential IPA transmission among sentinels, suggesting careful consideration should be taken when introducing managed pollinators in ecologically sensitive environments.
The value of computed tomography texture analysis in identifying chronic subdural hematoma patients with a good response to polytherapy
Authors: Sha Zhuang , Wu Di , Dong Shiying , Liu Tao , Wu Chenrui , Lv Chuanxiang , Liu Mingqi , Jiang Weiwei , Yuan Jiangyuan , Nie Meng , Gao Chuang , Liu Feng , Zhang Xinjie , Jiang Rongcai 
Published: February 2024

AbstractThis study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone.
Effect of vestibular loss on head-on-trunk stability in individuals with vestibular schwannoma
Authors: Aryan Raabeae , Zobeiri Omid A. , Millar Jennifer L. , Schubert Michael C. , Cullen Kathleen E. 
Published: February 2024

AbstractThe vestibulo-collic reflex generates neck motor commands to produce head-on-trunk movements that are essential for stabilizing the head relative to space. Here we examined the effects of vestibular loss on head-on-trunk kinematics during voluntary behavior. Head and trunk movements were measured in individuals with vestibular schwannoma before and then 6 weeks after unilateral vestibular deafferentation via surgical resection of the tumor. Movements were recorded in 6 dimensions (i.e., 3 axes of rotation and 3 axes of translation) using small light-weight inertial measurement units while participants performed balance and gait tasks. Kinematic measures differed between individuals with vestibular schwannoma (at both time points) and healthy controls for the more challenging exercises, namely those performed in tandem position or on an unstable surface without visual input. Quantitative assessment of the vestibulo-ocular reflex (VOR) revealed a reduction in VOR gain for individuals with vestibular schwannoma compared to control subjects, that was further reduced following surgery. These findings indicated that the impairment caused by either the tumor or subsequent surgical tumor resection altered head-on-trunk kinematics in a manner that is not normalized by central compensation. In contrast, we further found that head-on-trunk kinematics in individuals with vestibular schwannoma were actually comparable before and after surgery. Thus, taken together, our results indicate that vestibular loss impacts head-on-trunk kinematics during voluntary balance and gait behaviors, and suggest that the neural mechanisms mediating adaptation alter the motion strategies even before surgery in a manner that may be maladaptive for long-term compensation.
Synthesis and molecular docking simulations of novel azepines based on quinazolinone moiety as prospective antimicrobial and antitumor hedgehog signaling inhibitors
Authors: Noser Ahmed A. , El-Barbary A. A. , Salem Maha M. , El Salam Hayam A. Abd , shahien Mohamed 
Published: February 2024

AbstractA series of novel azepine derivatives based on quinazolinone moiety was synthesized through the reaction of quinazolinone chalcones (2a–d) either with 2-amino aniline in acidic medium to give diazepines (3a–d) or with 2-aminophenol to offer oxazepine (4a–d). The structure of the synthesized compounds was confirmed via melting points, elemental analyses, and different spectroscopic techniques. Moreover, these newly compounds mode of action was investigated in-silico using molecular docking against the outer membrane protein A (OMPA), exo-1,3-beta-glucanase for their antimicrobial activity, and against Smoothened (SMO), transcription factor glioma-associated homology (SUFU/GLI-1), the main proteins of Hedgehog signaling pathway to inspect their anticancer potential. Our results showed that, diazepine (3a) and oxazepine (4a) offered the highest binding energy against the target OMPA/ exo-1,3-beta-glucanase proteins and exhibited the potent antimicrobial activities against E. coli, P. aeruginosa, S. aureus, B. subtilis, C. Albicans and A. flavus. As well, diazepine (3a) and oxazepine (4a) achieved the best results among the other compounds, in their binding energy against the target SMO, SUFU/GLI-1 proteins. The in-vitro cytotoxic study was done for them on panel of cancer cell lines HCT-116, HepG2, and MCF-7 and normal cell line WI-38. Conclusively, it was revealed that molecular docking in-silico simulations and the in-vitro experiments were agreed. As a result, our findings elucidated that diazepine (3a) and oxazepine (4a), have the potential to be used as antimicrobial agents and as possible cancer treatment medications.
A novel CNN architecture for accurate early detection and classification of Alzheimer’s disease using MRI data
Authors: El-Assy A. M. , Amer Hanan M. , Ibrahim H. M. , Mohamed M. A. 
Published: February 2024

AbstractAlzheimer’s disease (AD) is a debilitating neurodegenerative disorder that requires accurate diagnosis for effective management and treatment. In this article, we propose an architecture for a convolutional neural network (CNN) that utilizes magnetic resonance imaging (MRI) data from the Alzheimer’s disease Neuroimaging Initiative (ADNI) dataset to categorize AD. The network employs two separate CNN models, each with distinct filter sizes and pooling layers, which are concatenated in a classification layer. The multi-class problem is addressed across three, four, and five categories. The proposed CNN architecture achieves exceptional accuracies of 99.43%, 99.57%, and 99.13%, respectively. These high accuracies demonstrate the efficacy of the network in capturing and discerning relevant features from MRI images, enabling precise classification of AD subtypes and stages. The network architecture leverages the hierarchical nature of convolutional layers, pooling layers, and fully connected layers to extract both local and global patterns from the data, facilitating accurate discrimination between different AD categories. Accurate classification of AD carries significant clinical implications, including early detection, personalized treatment planning, disease monitoring, and prognostic assessment. The reported accuracy underscores the potential of the proposed CNN architecture to assist medical professionals and researchers in making precise and informed judgments regarding AD patients.
Validation of sleep-staging accuracy for an in-home sleep electroencephalography device compared with simultaneous polysomnography in patients with obstructive sleep apnea
Authors: Seol Jaehoon , Chiba Shigeru , Kawana Fusae , Tsumoto Saki , Masaki Minori , Tominaga Morie , Amemiya Takashi , Tani Akihiro , Hiei Tetsuro , Yoshimine Hiroyuki , Kondo Hideaki , Yanagisawa Masashi 
Published: February 2024

AbstractEfforts to simplify standard polysomnography (PSG) in laboratories, especially for obstructive sleep apnea (OSA), and assess its agreement with portable electroencephalogram (EEG) devices are limited. We aimed to evaluate the agreement between a portable EEG device and type I PSG in patients with OSA and examine the EEG-based arousal index’s ability to estimate apnea severity. We enrolled 77 Japanese patients with OSA who underwent simultaneous type I PSG and portable EEG monitoring. Combining pulse rate, oxygen saturation (SpO2), and EEG improved sleep staging accuracy. Bland–Altman plots, paired t-tests, and receiver operating characteristics curves were used to assess agreement and screening accuracy. Significant small biases were observed for total sleep time, sleep latency, awakening after falling asleep, sleep efficiency, N1, N2, and N3 rates, arousal index, and apnea indexes. All variables showed > 95% agreement in the Bland–Altman analysis, with interclass correlation coefficients of 0.761–0.982, indicating high inter-instrument validity. The EEG-based arousal index demonstrated sufficient power for screening AHI ≥ 15 and ≥ 30 and yielded promising results in predicting apnea severity. Portable EEG device showed strong agreement with type I PSG in patients with OSA. These suggest that patients with OSA may assess their condition at home.
Efficacy and safety of rituximab in multiple sclerosis and neuromyelitis optica spectrum disorder
Authors: Ongphichetmetha Tatchaporn , Jitprapaikulsan Jiraporn , Siritho Sasitorn , Rattanathamsakul Natthapon , Detweeratham Thammachet , Prayoonwiwat Naraporn 
Published: February 2024

AbstractIn Thailand, resource limitations lead many multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients to use off-label immunosuppressants. This study assesses the efficacy and safety of rituximab (RTX) with a CD19-based reinfusion regimen among Thai MS and NMOSD patients. A retrospective review of patients at the Faculty of Medicine Siriraj Hospital from January 1994 to April 2023 was conducted. The primary outcome assessed was the change in annualized relapse rate (ARR) for patients using RTX for over a year. Secondary outcomes included changes in the Expanded Disability Status Scale (EDSS) scores, time to the first relapse after RTX initiation for patients using RTX for over a year, and an evaluation of the safety of RTX. The study encompassed 36 MS and 39 NMOSD patients. A majority of patients (91.7% of MS and 79.5% of NMOSD) experienced no relapses during a median follow-up of 30 months (Interquartile range [IQR] 20–46) and 31 months (IQR 23–41), respectively. The median ARR significantly decreased in both MS (from 0.77 [IQR 0.42–1.83] to 0 [IQR 0–0], p < 0.001) and NMOSD (from 0.92 [IQR 0.68–1.78] to 0 [IQR 0–0.17], p < 0.001) patients after switching to RTX, with no difference between those following a fixed 6-month time point regimen and a CD19-based reinfusion regimen. Median EDSS scores improved significantly at the last follow-up visit in both groups. The mean time to the first subsequent relapse was 8.3 ± 3.0 months in MS and 6.8 ± 1.7 months in NMOSD. Mild adverse drug reactions occurred in 44% of patients. RTX effectively prevents relapses in Thai MS and NMOSD patients, with no observed serious adverse drug reactions.
S-polarized light-sheets improve resolution and light-efficiency in oblique plane microscopy
Authors: Sommernes Jon-Richard , Millett-Sikking Alfred , Ströhl Florian 
Published: February 2024

AbstractOblique plane microscopy (OPM) offers 3D optically sectioned imaging with high spatial- and temporal-resolution while enabling conventional sample mounting. The technique uses a concatenation of three microscopes, two for remote focusing and a tilted tertiary microscope, often including an immersion objective, to image an oblique sample plane. This design induces Fresnel reflections and a reduced effective aperture, thus impacting the resolution and light efficiency of the system. Using vectorial diffraction simulations, the system performance was characterized based on illumination angle and polarization, signal to noise ratio, and refractive index of the tertiary objective immersion. We show that for samples with high fluorescent anisotropy, s-polarized light-sheets yield higher average resolution for all system configurations, as well as higher light-efficiency. We also provide a tool for performance characterization of arbitrary light-sheet imaging systems.