bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant huntingtin confers cell-autonomous phenotypes on Huntington’s disease iPSC-derived microglia
Authors: Stöberl Nina , Donaldson Jasmine , Binda Caroline S. , McAllister Branduff , Hall-Roberts Hazel , Jones Lesley , Massey Thomas H. , Allen Nicholas D. 
Published: November 2023

AbstractHuntington’s disease (HD) is a neurodegenerative disorder caused by a dominantly inherited CAG repeat expansion in the huntingtin gene (HTT). Neuroinflammation and microglia have been implicated in HD pathology, however it has been unclear if mutant HTT (mHTT) expression has an adverse cell-autonomous effect on microglial function, or if they are only activated in response to the neurodegenerative brain environment in HD. To establish a human cell model of HD microglia function, we generated isogenic controls for HD patient-derived induced pluripotent stem cells (iPSC) with 109 CAG repeats (Q109). Q109 and isogenic Q22 iPSC, as well as non-isogenic Q60 and Q33 iPSC lines, were differentiated to iPSC-microglia. Our study supports a model of basal microglia dysfunction in HD leading to elevated pro-inflammatory cytokine production together with impaired phagocytosis and endocytosis capacity, in the absence of immune stimulation. These findings are consistent with early microglia activation observed in pre-manifest patients and indicate that mHTT gene expression affects microglia function in a cell-autonomous way.
Safety and efficacy of remimazolam compared with midazolam during bronchoscopy: a single-center, randomized controlled study
Authors: Kim Sun-Hyung , Cho Jun Yeun , Kim Miyeon , Chung Ji Min , Yang Jiyoul , Seong Changhwan , Kim Eung-Gook , Seok Jeong Won , Shin Yoon Mi , Lee Ki Man , Choe Kang Hyeon , Han Joung-Ho , Yang Bumhee 
Published: November 2023

AbstractAlthough remimazolam is an ultra-short-acting benzodiazepine with a shorter elimination half-life and faster recovery time than midazolam, studies evaluating its safety and efficacy during bronchoscopy are limited. This study aimed to compare the safety and efficacy of remimazolam with those of midazolam for bronchoscopy. This prospective randomized parallel-group study was conducted at a single institution. The primary outcome was the time from the end of the procedure to full alertness. Other procedural time parameters, satisfaction profiles, and adverse effects were thoroughly evaluated. The time taken to reach peak sedation and the time from the end of the procedure to full alertness was significantly shorter in the remimazolam group than in the midazolam group (median [interquartile range], 2 min [1–4] vs. 3 min [2–5], P = 0.006; and median, 2 min [1–5] vs. 5 min [1–12], P = 0.035, respectively). In patients with non-biopsy procedures (n = 79), participant satisfaction was significantly higher in the remimazolam group than in the midazolam group (median rated scale, 10 vs. 7, P = 0.042). Physician satisfaction and willingness to repeat the procedure were similar between groups. Although the incidence of adverse effects was similar between the groups and there was no significant difference, the midazolam group had a higher antidote administration rate than the remimazolam group (15.7% vs. 4.1%, P = 0.092). Remimazolam is effective and safe for achieving adequate sedation, with a shorter onset time and faster neuropsychiatric recovery than midazolam. It may be a new option for sedation during bronchoscopy.Trial registration: The trial registration number is NCT05994547, and the date of first registration is 16/08/2023.
Platform for the interdisciplinary study of cardiovascular, metabolic and neurovascular diseases (PICMAN) protocol
Authors: Dalakoti Mayank , Leow Melvin Khee Shing , Khoo Chin Meng , Yang Hayang , Ling Lieng Hsi , Muthiah Mark , Tan Eunice , Lee Jonathan , Dan Yock Young , Chew Nicholas , Seow Wei Qiang , Soong Poh Loong , Gan Louis , Gurung Rijan , Ackers-Johnson Matthew , Hou Han Wei , Sachaphibulkij Karishma , MacAry Paul , Low Gwen , Ang Christy , Yeo Tee Joo , Djohan Andie Hartanto , Li Tony , Yeung Wesley , Soh Rodney , Sia Ching Hui , Panday Vinay , Loong Shaun S. E. , Tan Benjamin Y. Q. , Yeo Leonard L. L. , Teo Lynette , Chow Pierce , Foo Roger 
Published: November 2023

AbstractThrough extensive multisystem phenotyping, the central aim of Project PICMAN is to correlate metabolic flexibility to measures of cardiometabolic health, including myocardial diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease. This cohort will form the basis of larger interventional trials targeting metabolic inflexibility in the prevention of cardiovascular disease. Participants aged 21–72 years with no prior manifest atherosclerotic cardiovascular disease (ASCVD) are being recruited from a preventive cardiology clinic and an existing cohort of non-alcoholic fatty liver disease (NAFLD) in an academic medical centre. A total of 120 patients will be recruited in the pilot phase of this study and followed up for 5 years. Those with 10-year ASCVD risk ≥ 5% as per the QRISK3 calculator are eligible. Those with established diabetes mellitus are excluded. Participants recruited undergo a detailed assessment of health behaviours and physical measurements. Participants also undergo a series of multimodality clinical phenotyping comprising cardiac tests, vascular assessments, metabolic tests, liver and neurovascular testing. Blood samples are also being collected and banked for plasma biomarkers, ‘multi-omics analyses’ and for generation of induced pluripotent stem cells (iPSC). Extensive evidence points to metabolic dysregulation as an early precursor of cardiovascular disease, particularly in Asia. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) is a pilot, prospective, multi-ethnic cohort study.
Urbanization and a green corridor do not impact genetic divergence in common milkweed (Asclepias syriaca L.)
Authors: Breitbart Sophie T. , Agrawal Anurag A. , Wagner Helene H. , Johnson Marc T. J. 
Published: November 2023

AbstractUrbanization is altering landscapes globally at an unprecedented rate. While ecological differences between urban and rural environments often promote phenotypic divergence among populations, it is unclear to what degree these trait differences arise from genetic divergence as opposed to phenotypic plasticity. Furthermore, little is known about how specific landscape elements, such as green corridors, impact genetic divergence in urban environments. We tested the hypotheses that: (1) urbanization, and (2) proximity to an urban green corridor influence genetic divergence in common milkweed (Asclepias syriaca) populations for phenotypic traits. Using seeds from 52 populations along three urban-to-rural subtransects in the Greater Toronto Area, Canada, one of which followed a green corridor, we grew ~ 1000 plants in a common garden setup and measured > 20 ecologically-important traits associated with plant defense/damage, reproduction, and growth over four years. We found significant heritable variation for nine traits within common milkweed populations and weak phenotypic divergence among populations. However, neither urbanization nor an urban green corridor influenced genetic divergence in individual traits or multivariate phenotype. These findings contrast with the expanding literature demonstrating that urbanization promotes rapid evolutionary change and offer preliminary insights into the eco-evolutionary role of green corridors in urban environments.
Fast multiple-trait genome-wide association analysis for correlated longitudinal measurements
Authors: Abdel-Azim Gamal , Patel Parth , Li Shuwei , Guo Shicheng , Black Mary Helen 
Published: November 2023

AbstractLarge-scale longitudinal biobank data can be leveraged to identify genetic variation contributing to human diseases progression and traits trajectories. While methods for genome-wide association studies (GWAS) of multiple correlated traits have been proposed, an efficient multiple-trait approach to model longitudinal phenotypes is not currently available. We developed GAMUT, a genome-wide association approach for multiple longitudinal traits. GAMUT employs a mixed-effects model to fit longitudinal outcomes where a fast algorithm for inversion by recursive partitioning of the random effects submatrix is introduced. To evaluate performance of the algorithms introduced and assess their statistical power and type I error, stochastic simulation was conducted. Consistent with our expectation, power was greater for cross-sectional (CS) than longitudinal (LT) effects, particularly with a diminishing LT/CS ratio. With a minimum minor allele count of 3 within genotype by time categories, observed type I error was roughly equal to theoretical genome-wide significance. Additionally, 28 blood-based biomarkers measured at 2 time points on participants of the UK Biobank were used to compare GAMUT against single-trait standard and longitudinal GWAS (including rate of change). Across all biomarkers, we observed 539 (CS) and 248 (LT) significant independent variants for the GAMUT method, and 513 (CS) and 30 (LT) for single-trait longitudinal GWAS, respectively. Only 37 variants were identified by modeling rates of change using standard GWAS.
Forecasting the El Niño type well before the spring predictability barrier
Authors: Ludescher Josef , Bunde Armin , Schellnhuber Hans Joachim 
Published: November 2023

AbstractEl Niño events represent anomalous episodic warmings, which can peak in the equatorial Central Pacific (CP events) or Eastern Pacific (EP events). The type of an El Niño (CP or EP) has a major influence on its impact and can even lead to either dry or wet conditions in the same areas on the globe. Here we show that the difference of the sea surface temperature anomalies between the equatorial western and central Pacific in December enables an early forecast of the type of an upcoming El Niño (p-value < 10−3). Combined with a previously introduced climate network-based approach that allows to forecast the onset of an El Niño event, both the onset and type of an upcoming El Niño can be efficiently forecasted. The lead time is about 1 year and should allow early mitigation measures. In December 2022, the combined approach forecasted the onset of an EP event in 2023.
Phylogenetic comparative analysis of the cerebello-cerebral system in 34 species highlights primate-general expansion of cerebellar crura I-II
Authors: Magielse Neville , Toro Roberto , Steigauf Vanessa , Abbaspour Mahta , Eickhoff Simon B. , Heuer Katja , Valk Sofie L. 
Published: November 2023

AbstractThe reciprocal connections between the cerebellum and the cerebrum have been suggested to simultaneously play a role in brain size increase and to support a broad array of brain functions in primates. The cerebello-cerebral system has undergone marked functionally relevant reorganization. In particular, the lateral cerebellar lobules crura I-II (the ansiform) have been suggested to be expanded in hominoids. Here, we manually segmented 63 cerebella (34 primate species; 9 infraorders) and 30 ansiforms (13 species; 8 infraorders) to understand how their volumes have evolved over the primate lineage. Together, our analyses support proportional cerebellar-cerebral scaling, whereas ansiforms have expanded faster than the cerebellum and cerebrum. We did not find different scaling between strepsirrhines and haplorhines, nor between apes and non-apes. In sum, our study shows primate-general structural reorganization of the ansiform, relative to the cerebello-cerebral system, which is relevant for specialized brain functions in an evolutionary context.
Symmetrically dispersion-engineered microcombs
Authors: Li Jiaqi , Zhang Yanfeng , Xie Yaozu , Lin Shuqing , Zeng Shihao , Wu Zhaoyang , Yu Siyuan 
Published: November 2023

AbstractNormal-dispersion microcombs have gained significant attention for their features, including high conversion efficiency, deterministic generation, and thermal management-free operation. However, most of the demonstrated microcombs in the normal-dispersion regime heavily rely on asymmetric local dispersion anomalies, which introduce odd-order dispersion components and originate asymmetric spectral characteristics. In this study, we present a scheme that employs two symmetrically positioned local dispersion alterations on either side of the pump mode. This configuration enables direct mode-locked microcombs, referred to as ‘dark pulses’ or ‘platicons’, while preserving spectral symmetry. The platicon microcombs exhibit efficient conversion, spectral symmetry, and can be generated with high repeatability. Furthermore, we demonstrate the deterministic generation of perfect platicon crystals with highly symmetric spectra by precisely controlling the position of the two symmetric dispersion alterations relative to the pump mode. Our proposed method offers a reliable approach for achieving power-efficient microcombs with highly symmetric spectra, and can be transferred to other integrated nonlinear platforms.
An intermediate level of disturbance with customary agricultural practices increases species diversity in Maya community forests in Belize
Authors: Downey Sean S. , Walker Matthew , Moschler Jacob , Penados Filiberto , Peterman William , Pop Juan , Qin Rongjun , Scaggs Shane A. , Song Shuang 
Published: November 2023

AbstractAcross the planet, Indigenous societies control, use, and manage large tracts of tropical forest that are crucial for combating climate change. Here we investigate whether customary Indigenous agricultural practices can increase forest species diversity using swidden (aka, slash-and-burn) agriculture. We examine the community lands surrounding two Q’eqchi’ Maya villages in southern Belize using high-resolution multispectral imagery that we collected with drones, ground truth data related to land use and history, and a plant and tree biodiversity survey. We use computational methods including simulation and Bayesian modeling to analyze the relationship between spectral diversity, forest diversity, and landscape disturbance. Our key result, replicated in both villages, is that the highest level of spectral diversity (a proxy for forest diversity) is associated with an intermediate level of forest disturbance. In conclusion, we suggest that concepts from complex adaptive systems can provide an important conceptual framework for understanding how ecosystem enhancement can emerge from customary Indigenous land use practices.
Asynchronous SAR ADC with self‐timed track‐and‐hold
Authors: Bae Sunghyun , Lee Sewon , Seong Siheon , Woo Jiwon , Lee Minjae 
Published: November 2023

AbstractThis paper presents an asynchronous SAR ADC featuring a self‐timed track‐and‐hold (STH) architecture. The design aims to address the common timing issue of divider‐based clock generation, where the fixed‐time track‐and‐hold (FTH) period often results in incomplete conversions due to prolonged conversion times time due to comparator metastability. To alleviate the degradation of the ENOB induced by these delays, the proposed STH method is introduced so that more conversion period is secured without requiring a high‐speed input clock. Based on measurements, the proposed STH method achieves up to 0.7 bit improvement over the conventional FTH approach as conversion time increases.
Adaptive pseudo‐spectrum based track‐before‐detect for targets with uncertain existence
Authors: Li Peiyuan , Zhou Gongjian 
Published: November 2023

AbstractIn the existing velocity filtering based track‐before‐detect (VF‐TBD), target existence is generally assumed to be constant, and multiple successive frames in a sliding window are jointly processed. However, when the target existence changes abruptly in a processing batch, the incorporation of noise‐only frames may corrupt target energy integration. This results in degraded detection and estimation performances with serious decision delays. A pseudo‐spectrum based VF‐TBD is proposed to effectively detect and track targets with existence uncertainty. An adaptive integration strategy is developed to realise effective energy accumulation with only informative frames by matching target appearance and disappearance times in addition to the velocity. The change of target existence can be discovered in time, and the decision delay is reduced. An estimation strategy based on the maximum output SNR is presented to supply accurate estimations of not only target motion parameters (including the position and velocity) but also time parameters (including appearance and disappearance times). The target output envelope, SNR gain and receiver operating characteristic curve of targets with uncertain existence are analysed theoretically. Numerical simulations exhibit the validity of the proposed method.The cover image is based on the Original Article Adaptive pseudo‐spectrum based track‐before‐detect for targets with uncertain existence by Peiyuan Li et al., https://doi.org/10.1049/rsn2.12502.
Grain-size measurements in protoplanetary disks indicate fragile pebbles and low turbulence
Authors: Jiang Haochang , Macías Enrique , Guerra-Alvarado Osmar M. , Carrasco-González Carlos 
Published: November 2023

Context. Constraining the turbulence level and pebble size in protoplanetary disks is an essential initial step in understanding the aerodynamic properties of pebbles, which are crucial for planet formation. Recent laboratory experiments have revealed that destructive collisions of icy dust particles may occur at much lower velocities than previously believed. These low fragmentation velocities push down the maximum grain size in collisional growth models.
Aims. Motivated by the smooth radial distribution of pebble sizes inferred from ALMA/VLA multi-wavelength continuum analysis, we propose a concise model to explain this feature and aim to constrain the turbulence level at the midplane of protoplanetary disks.
Methods. Our approach is built on the assumption that the fragmentation threshold is the primary barrier limiting pebble growth within pressure maxima. Consequently, the grain size at the ring location can provide direct insights into the turbulent velocity governing pebble collisions and, by extension, the turbulence level at the disk midplane. We validate this method using the Dustpy code, which simulates dust transport and coagulation.
Results. We applied our method to seven disks, namely TW Hya, IM Lup, GM Aur, AS 209, HL Tau, HD 163296, and MWC 480, for which grain sizes have been measured from multi-wavelength continuum analysis. A common feature emerges from our analysis, with an overall low turbulence coefficient of α ~ 10−4 observed in five out of seven disks when assuming a fragmentation velocity υfrag = 1 m s−1. A higher fragmentation velocity would imply a significantly larger turbulence coefficient than that suggested by current observational constraints. IM Lup stands out, with a relatively high coefficient of 10−3. Notably, HL Tau exhibits an increasing trend in α with distance. This supports enhanced turbulence at its outer disk region, which is possibly associated with the infalling streamer onto this particular disk. Alternatively, if the turbulence were found to be low, this might indicate that grain sizes have not reached the growth barrier.
Conclusions. We conclude that the current (sub)mm pebble size constrained in disks implies low levels of turbulence; it also implies fragile pebbles, which is consistent with recent laboratory measurements.
Development of a prototype of monitor for alpha and beta radiation in water using new silicone-based contamination-safe detectors
Authors: Lunardon Marcello , Sartori Paolo , De Felice Pierino , Stevanato Luca 
Published: November 2023

We present here the main results of an experimental activity aimed at the realization of a prototype of monitor for alpha and beta radioactivity in water exploiting a novel type of contamination-safe scintillation detector developed by our research group.
Due to the short path-length of alpha and beta particles in water and the low detection limits needed to be compliant with the international legislations in matter of radiation safety for water, the detectors to be used for such a kind of instruments should have in general large area, very low intrinsic background and avoid any kind of window between the monitored water and the active volume of the detector. Even an extremely low contamination of the surface can therefore destroy the detector performance, while protecting the detector with a layer of passive material will reduce the detection efficiency, in particular for alpha particles, and the passive layer can get contaminated itself, making necessary its substitution and representing an important limitation to the realization of a radioactivity monitor that should work continuously for years.
The novel detectors are large-area silicone-based scintillators developed and produced in our laboratories. The technology we propose is a significant step forward in the direction of the realization of radioactivity monitors for water with high sensitivity and reasonable costs, to be used to improve security and quality of the water distributed to European and worldwide citizens.
The detection performance for alpha and beta particles was first tested in air with standard sources, showing results very close to similar detectors commercially available. Later a number of tests were carried out in the ENEA-INMRI laboratories with the aim to characterize the contamination and decontamination properties. Initial activity of each detector foil was checked by low background radioactivity measurements, then the detectors were immersed for fixed times and constant procedure in a variety of radioactive reference liquid solutions with different radionuclides in different chemical forms. After rinsing with distilled water the detector foils were again measured for residual radioactivity adsorbed on the foils surface.
After this preliminary campaign of contamination measurements carried out on small size samples, several large area detectors were realized and used to build a small demonstrator device for continuous monitoring of the radioactivity in water. The monitor was tested with distilled water (blank) and radioactive aqueous solutions, demonstrating the possibility to realize a new generation of radiation monitors for water with high sensitivity and with the possibility to easily manage the contamination issues.