bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined RNA interference and gene replacement therapy targeting MFN2 as proof of principle for the treatment of Charcot–Marie–Tooth type 2A
Authors: Rizzo Federica , Bono Silvia , Ruepp Marc David , Salani Sabrina , Ottoboni Linda , Abati Elena , Melzi Valentina , Cordiglieri Chiara , Pagliarani Serena , De Gioia Roberta , Anastasia Alessia , Taiana Michela , Garbellini Manuela , Lodato Simona , Kunderfranco Paolo , Cazzato Daniele , Cartelli Daniele , Lonati Caterina , Bresolin Nereo , Comi Giacomo , Nizzardo Monica , Corti Stefania 
Published: November 2023

AbstractMitofusin-2 (MFN2) is an outer mitochondrial membrane protein essential for mitochondrial networking in most cells. Autosomal dominant mutations in the MFN2 gene cause Charcot–Marie–Tooth type 2A disease (CMT2A), a severe and disabling sensory-motor neuropathy that impacts the entire nervous system. Here, we propose a novel therapeutic strategy tailored to correcting the root genetic defect of CMT2A. Though mutant and wild-type MFN2 mRNA are inhibited by RNA interference (RNAi), the wild-type protein is restored by overexpressing cDNA encoding functional MFN2 modified to be resistant to RNAi. We tested this strategy in CMT2A patient-specific human induced pluripotent stem cell (iPSC)-differentiated motor neurons (MNs), demonstrating the correct silencing of endogenous MFN2 and replacement with an exogenous copy of the functional wild-type gene. This approach significantly rescues the CMT2A MN phenotype in vitro, stabilizing the altered axonal mitochondrial distribution and correcting abnormal mitophagic processes. The MFN2 molecular correction was also properly confirmed in vivo in the MitoCharc1 CMT2A transgenic mouse model after cerebrospinal fluid (CSF) delivery of the constructs into newborn mice using adeno-associated virus 9 (AAV9). Altogether, our data support the feasibility of a combined RNAi and gene therapy strategy for treating the broad spectrum of human diseases associated with MFN2 mutations.
At the intersection of humanity and technology: a technofeminist intersectional critical discourse analysis of gender and race biases in the natural language processing model GPT-3
Authors: Palacios Barea M. A. , Boeren D. , Ferreira Goncalves J. F. 
Published: November 2023

AbstractAlgorithmic biases, or algorithmic unfairness, have been a topic of public and scientific scrutiny for the past years, as increasing evidence suggests the pervasive assimilation of human cognitive biases and stereotypes in such systems. This research is specifically concerned with analyzing the presence of discursive biases in the text generated by GPT-3, an NLPM which has been praised in recent years for resembling human language so closely that it is becoming difficult to differentiate between the human and the algorithm. The pertinence of this research object is substantiated by the identification of race, gender and religious biases in the model’s completions in recent research, suggesting that the model is indeed heavily influenced by human cognitive biases. To this end, this research inquires: How does the Natural Language Processing Model GPT-3 replicate existing social biases?. This question is addressed through the scrutiny of GPT-3’s completions using Critical Discourse Analysis (CDA), a method which has been deemed as amply valuable for this research as it is aimed at uncovering power asymmetries in language. As such, the analysis is specifically centered around the analysis of gender and race biases in the model’s generated text. Research findings suggest that GPT-3’s language generation model significantly exacerbates existing social biases while replicating dangerous ideologies akin to white supremacy and hegemonic masculinity as factual knowledge.
Improved uniformity and anisotropy of through-mask electrochemical micromachining by localized etching and homogeneous flow
Authors: Jakob Leonie , Eckert Jonas , Podevijn Carl , Kluska Sven , Junginger Mathias , Ranzinger Christian , Bartsch Jonas 
Published: November 2023

AbstractThis contribution aims to point out the potential of through-mask electrochemical micromachining (TMEMM) as an environmentally friendly alternative for thin metal layer patterning for applications such as printed circuit boards (PCBs). Two process chamber concepts with shearing and impinging electrolyte flow, based on the concept of localized etching, are introduced. The etching results, obtained with simple mask designs, were investigated regarding homogeneity in etch depth and anisotropy. Compared to a simple setup with unspecific electrolyte flow and full area etching, a significant improvement in microscopic and macroscopic homogeneity (deviations reduced from >100 to <10%) and anisotropy (etch factors increased from ~4 to >7) could be shown. A comparison to an industrial chemical etching process using a simple mask design revealed equal macroscopic homogeneity and higher etch factors in TMEMM. Only the microscopic homogeneity leaves still room for improvement. It is presented for the first time that island formation can be prevented completely over a large area (5 × 20 mm2) with TMEMM. These results demonstrate the advantages and the potential that can be achieved with TMEMM by designing appropriate tools.
Functional limitations of people with rheumatoid arthritis or axial spondyloarthritis and severe functional disability: a cross-sectional descriptive study
Authors: Teuwen Max M. H. , van Weely Salima F. E. , Vliet Vlieland Thea P. M. , Douw Thom , van Schaardenburg Dirkjan , den Broeder Alfons A. , van Tubergen Astrid M. , van Wissen Maria A. T. , van den Ende Cornelia H. M. , Gademan Maaike G. J. 
Published: November 2023

AbstractThe objective of the study is to describe the nature of functional limitations in activities and participation in people with Rheumatoid Arthritis (RA) or axial SpondyloArthritis (axSpA) with severe functional disability. Baseline data from people with RA (n = 206) or axSpA (n = 155) and severe functional disability participating in an exercise trial were used. Their three most limited activities were derived from the Patient Specific Complaint (PSC) instrument and linked to the International Classification of Functioning and Health (ICF). The frequencies of ICF categories were calculated and compared with Activities and Participation items of the ICF Core Sets for RA (32 second-level categories) and Ankylosing Spondylitis (AS) (24 second-level categories). In total 618 and 465 PSC activities were linked to 909 (72 unique in total; 25 unique second-level) and 759 (57 unique in total; 23 unique second-level) ICF categories in RA and axSpA. Taking into account all three prioritized activities, the five most frequent limited activities concerned the ICF chapter “Mobility”, and included “Walking” (RA and axSpA 2 categories), “Changing basic body position” (RA and axSpA 1 category), “Stair climbing”(RA) and “Grasping” (RA),“Lifting” (axSpA) and “Maintaining a standing position” (axSpA). In RA, 21/32 (66%) and in axSpA 14/24 (58%) unique second-level categories identified in the prioritized activities are present in the Comprehensive Core Sets. Most limitations of people with RA or axSpA and severe functional disability were seen in the ICF chapter “Mobility”. Most of the identified ICF categories were covered by the corresponding items of the ICF RA and AS Core Sets.
Testing the accuracy of the DRNNAGE software for age estimation in a modern Greek sample
Authors: Rizos Leuteris , Garoufi Nefeli , Valakos Eustratios , Nikita Efthymia , Chovalopoulou Maria-Eleni 
Published: November 2023

AbstractEstimation of age-at-death from human skeletal remains is fundamental in forensic anthropology as part of the construction of the biological profile of the individual under study. At the same time, skeletal age-at-death estimation in adults is problematic due to the disparity between chronological and biological age, the important inter-individual variability at the rate of skeletal aging, and inherent biases in the available methodologies (e.g., age mimicry). A recent paper proposed a method for skeletal age-at-death estimation based on multiple anatomical traits and machine learning. A software was also created, DRNNAGE, for the easy implementation of this method. The authors of that study supported that their methods have very high repeatability and reproducibility, and the mean absolute error of the age estimation was ~6 years across the entire adult age span, which is particularly high and promising. This paper tests the proposed methodology on a modern documented Greek sample of 219 adult individuals from the Athens Collection, with age-at-death from 19 to 99 years old. The sample was split into males and females as well as into individuals under and over 50 years old. We also divided the sample in 10-year intervals. First, intra- and inter-observer error was estimated in order to assess repeatability and reproducibility of the variables employed for age-at-death estimation. Then, the validity (correct classification performance) of DRNNAGE for each anatomical region individually, as well as all combined, was evaluated on each demographic separately and on the pooled sample. According to the results, some of the variables showed very low repeatability and reproducibility, thus their use should be cautious. The DRNNAGE software showed overall highly accurate age-at-death estimates for individuals older than 50 years, but poor on younger adults, with only exception the cranial sutures, which performed surprisingly well for all age groups. Overall, these results support the importance of cross-validation and the use of population-specific methods in forensic anthropology.
Production of polyhydroxybutyrate by coupled saccharification–fermentation of inulin
Authors: Guzmán-Lagunes Fernando , Martínez-dlCruz Lorena , Wongsirichot Phavit , Winterburn James , Montiel Carmina 
Published: November 2023

AbstractInulin is a fructose-based polysaccharide that can be found in several plant species, from grass and onions to chicory roots; thus, it has the potential to be an excellent renewable source of fructose for several industrial applications. Among them, inulin hydrolysis can be coupled to a fermentation operation to produce polyhydroxybutyrate (PHB) using Cupriavidusnecator H16. This work reports the PHB production process involving chicory root inulin hydrolysis using inulinase Novozym 960 followed by a C.necator fermentation. It was found that the maximum saccharification (95% wt.) was reached at 269 U/ginulin after 90 min. The hydrolysates obtained were then inoculated with C.necator, leading to a biomass concentration of 4 g/L with 30% (w/w) polymer accumulation. Although PHB production was low, during the first hours, the cell growth and polymer accumulation detected did not coincide with a fructose concentration decrease, suggesting a simultaneous saccharification and fermentation process, potentially alleviating the product inhibition inherent to the inulinase–fructose system. The characterization of the obtained PHB showed a polymer with more homogeneous values of Mw, and better thermal stability than PHB produced using pure fructose as a fermentation substrate. The results obtained demonstrate a viable alternative carbon substrate for PHB production, opening the possibility for inulin-rich renewable feedstock valorization.
Association between continuous glucose monitoring-derived glycemic control indices and urinary biomarkers of diabetic kidney disease: Hyogo Diabetes Hypoglycemia Cognition Complications study
Authors: Takagi Ayako , Kusunoki Yoshiki , Ohigashi Mana , Osugi Keiko , Inoue Chikako , Inoue Maki , Tsunoda Taku , Kadoya Manabu , Konishi Kosuke , Katsuno Tomoyuki , Koyama Hidenori ,   Hyogo Diabetes Hypoglycemia Cognition Complications (HDHCC) study group
Published: November 2023

Abstract
Aims
Glomerular damage and proximal tubular damage play an important role in the pathogenesis of diabetic kidney disease. This study aimed to investigate the relationship between the urinary markers of proximal tubular injury, including urinary liver-type fatty acid-binding protein-to-creatinine ratio (uL-FABP/Cr) and urinary N-acetyl-β-d-glucosaminidase-to-creatinine ratio (uNAG/Cr), and glycemic control status.

Methods
This cross-sectional study included 245 and 39 patients with type 2 diabetes mellitus (T2DM) and non-T2DM (NDM), respectively. The participants of this study were fitted with retrospective CGM, and glycemic control indices, such as time in range (TIR) and glycemia risk index (GRI), were calculated.

Results
The results were presented as medians (interquartile ranges). The uL-FABP/Cr was significantly higher in the microalbuminuria than in the normo-albuminuria group [4.2 (2.7–7.1) and 2.2 (1.4–3.4) μg/gCr, respectively, P < 0.001], while the uNAG/Cr in the normo-albuminuria group [6.3 (4.5–10.1) U/gCr] was significantly higher than that in the NDM group [5.3 (3.8–6.3) U/gCr, P = 0.048] but significantly lower than that in the microalbuminuria group [9.2 (6.4–11.1) U/gCr, P = 0.004]. The multivariate logistic regression analysis indicated that CGM-derived TIR was significantly associated with the urinary albumin-to-creatinine ratio [uAlb/Cr, odds ratio (OR) 0.985, 95% confidence interval (CI) 0.971–0.998, P = 0.029] and uNAG/Cr (OR 0.973, 95% CI 0.957–0.989, P = 0.001) independent of renal function. GRI was similarly associated with uAlb/Cr and uNAG/Cr.

Conclusion
The findings of this study indicated that uNAG/Cr was elevated before albuminuria development and was associated with CGM-derived TIR and GRI.
Integrated statistical and graphical non-parametric trend analysis of annual and seasonal rainfall in the Shire River Basin, Malawi
Authors: Kavwenje Sheila , Zhao Lin , Chen Liang , Ngongondo Cosmo , Chaima Evance , Aborisade Moses Akintayo , Oba Belay Tafa , Kumambala Patsani 
Published: November 2023

AbstractThis study integrates purely statistical methods of Mann–Kendall (MK) and Spearman rho (SMR) with statistical-graphical methods of Onyutha trend (OT) test and innovative trend analysis (ITA) to examine annual and seasonal rainfall variations at 12 stations across the Shire River Basin (SRB) during 1976–2005. The results reveal a general decreasing trend for annual rainfall throughout the basin. At seasonal scale, the following trends were observed: an increase for the December-January–February (DJF) season, especially in the southern portion of the basin; a decrease for the March–April-May (MAM) and June-July–August (JJA) seasons; and inconclusive results for the September–October-November (SON) season. Despite nearly all time series indicating consistent trend direction as established by the four tests, the ITA identified the most significant rainfall patterns on both annual and seasonal basis. The performance abilities for the MK, SMR, and OT tests demonstrated the closest agreement at the verified significant level. In addition to the monotonic trend results obtained statistically, sub-trends are visually distinguished using the graphical features of the OT and ITA approaches. For the former, changes are seen as step jumps in the mean of the data, and for the latter, trends regarding high and low rainfall clusters are evaluated, hence offering more details regarding rainfall variability, such as the SRB’s sensitivity to both floods and droughts. Thus, the completely different aspects offered by the visually oriented methods complement the purely monotonic trend detection methods.
Challenging the universality of heatwave definitions: gridded temperature discrepancies across climate regions
Authors: Coughlan de Perez Erin , Arrighi Julie , Marunye Joalane 
Published: November 2023

AbstractAs global studies of climate change depict increasingly dire outcomes of extreme heat, there is an urgent need to understand the appropriateness of heatwave definitions and temperature datasets in different parts of the world. We carry out an intercomparison of the CHIRTS gridded station-satellite temperature dataset with three reanalysis products, ERA5, NCEP-DOE Reanalysis 2, and MERRA2, to assess biases in the absolute value of extreme heat events and the distribution of extreme events. We find close agreement between all four datasets in the magnitude and distribution of extreme temperatures, with a cold bias in the reanalyses over mountainous areas. However, there is little to no agreement between datasets on the timing of extreme heat events in the tropics, and the datasets do not even agree on which month is the hottest month climatologically in these regions. Second, we compare how the four datasets represent the frequency and timing of extreme heat events, using two different types of heatwave definitions: 5-day duration-based extremes and extreme temperature-humidity combinations (heat index). In the case of 5-day heatwaves, there are almost zero events recorded historically in tropical regions. In contrast, high absolute values of the heat index are most common in dry climates, likely due to the dominance of high temperature spikes in these regions, and high heat index events also occur in temperate and tropical regions. There is little agreement between datasets, however, on when these extreme heat index events have happened historically in the tropics. Given these results, we highlight the need for locally developed heatwave metrics for different parts of the world, and we urge against the use of a single heatwave definition in global studies. We also recommend that any studies assessing heat-health relationships in tropical regions beware of the lack of agreement between observational and reanalysis datasets and compare results from different gridded dataset products to estimate uncertainty in heat-health relationships.
Small cities: Regional motors or sponges? The case of Inland County, Norway
Authors: Hauge Atle , Calignano Giuseppe , Bern Aleksander , Lønningdal Karl Henrik 
Published: November 2023

AbstractIn the innovation and regional development literature, regional areas that lie between prosperous core regions and struggling peripheral areas have been largely neglected, both theoretically and empirically, in recent innovation and regional research. In this paper, we analyse the role that small cities play as agents in regional development in their hinterland. Are they catalysts for growth, or do they drain the surrounding cities and villages? One concept or analytical tool that deals with this issue more explicitly is ‘sponge cities’, which refers to small and medium-sized cities that appear to ‘soak up’ talent and resources from the surrounding hinterland. By adopting and expanding this largely unexplored concept, we analyse the role of regional cities in the Norwegian context. Building on the original concept, we believe that adding commuting to migration patterns provides a more nuanced and precise assessment of whether small cities and regional centres are a blessing or a curse for their hinterlands. Using regional data, we classify cities as ‘motors’ (those that positively affect the hinterland thanks to well-balanced commuting and migration patterns at various spatial scales) or ‘sponges’ (those that soak up people from surrounding areas through migration). Further expanding our analysis, we label a third group of municipalities as ‘local mobilizers’, as they seem to have the potential to influence positively the growth of adjacent areas, and a fourth group as ‘moderate attractors’, which show moderately positive external commuting and migration flows.
Cloud material handling systems: a cyber-physical system to enable dynamic resource allocation and digital interoperability
Authors: Aron Cosmin , Sgarbossa Fabio , Ballot Eric , Ivanov Dmitry 
Published: November 2023

AbstractThe existing logistics practices frequently lack the ability to effectively handle disruptions. Recent research called for dynamic, digital-driven approaches that can help prioritise allocation of logistics resources to design more adaptive and sustainable logistics networks. The purpose of this study is to explore inter-dependencies between physical and digital assets to examine how cyber-physical systems could enable interoperability in logistics networks. The paper provides an overview of the existing literature on cyber-physical applications in logistics and proposes a conceptual model of a Cloud Material Handling System. The model allows leveraging the use of digital technologies to capture and process real-time information about a logistics network with the aim to dynamically allocate material handling resources and promote asset and infrastructure sharing. The model describes how cloud computing, machine learning and real-time information can be utilised to dynamically allocate material handling resources to product flows. The adoption of the proposed model can increase efficiency, resilience and sustainability of logistics practices. Finally, the paper offers several promising research avenues for extending this work.
Spatial Interpolation Using Machine Learning: From Patterns and Regularities to Block Models
Authors: Nwaila Glen T. , Zhang Steven E. , Bourdeau Julie E. , Frimmel Hartwig E. , Ghorbani Yousef 
Published: November 2023

AbstractIn geospatial data interpolation, as in mapping, mineral resource estimation, modeling and numerical modeling in geosciences, kriging has been a central technique since the advent of geostatistics. Here, we introduce a new method for spatial interpolation in 2D and 3D using a block discretization technique (i.e., microblocking) using purely machine-learning algorithms and workflow design. This paper addresses the challenges of modeling spatial patterns and regularities in nature, and how different approaches have been used to cope with these challenges. We specifically explore the advantages and drawbacks of kriging while highlighting the long and complex sequence of procedures associated with block kriging. We argue that machine-learning techniques offer opportunities to simplify and streamline the process of mapping and mineral resource estimation, especially in cases of strong spatial relationships between sample location and resource concentration. To test the new method, synthetic 2D and 3D data were used for both 2D block modeling and geometallurgical modeling of a synthetic porphyry Cu deposit. The synthetic porphyry Cu data were very useful in validating the performance of the proposed microblocking technique as we were able to reproduce known values at unsampled locations. Our proposed method delivers the benefits of a machine learning-based block modeling approach, which includes its simplicity (a minimum of 2 hyperparameters), speed and familiarity to data scientists. This enables data scientists working on spatial data to employ workflows familiar to their training, to tackle problems that were previously solely in the domain of geoscience. In exchange, we expect that our method will be a gateway to attract more data scientist to become geodata scientists, benefitting the modern data-driven mineral value chain.
Three sources of social indeterminacy
Authors: Brännmark Johan 
Published: November 2023

AbstractSocial ontologists commonly think that our ideas about social entities, and about other people also inhabiting the social realm, play an important role in making those entities into what they are. At the same time, we know that our ideas are often indeterminate in character, which presumably would mean that this indeterminacy should carry over to the social realm. And yet social indeterminacy is a neglected topic in social ontology. It is argued that this neglect can be traced to how a particular approach that favors ahistorical reconstructions in making sense of social entities has come to dominate social ontology. If we think beyond the parameters set by this approach, however, we can see that recognizing indeterminacy as a pervasive phenomenon in the social realm might open up new interpretative possibilities in relation to different social categories. This argument is at least partly in line with recent calls for a move towards nonideal social ontology.