bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranasal Fentanyl for On-the-Hill Analgesia by Ski Patrol
Authors: Lynch Tierra V. , Callas Peter W. , Peterson Timothy D. , Schlein Sarah M. 
Published: July 2022

Introduction Intranasal fentanyl offers a means for safe and effective pain management in austere environments. Prehospital analgesia traditionally involves intravenous or intramuscular medication. However, for wilderness rescuers, these methods are often impractical. Methods We conducted a retrospective review of health records to evaluate the safety and efficacy of intranasal fentanyl administered by EMT-Basic certified ski patrollers. Our primary aim was to measure the reduction in initial pain scores to subsequent measurements at 5, 10, and 15 min using the pain numeric rating scale (0–10). Clinically significant reduction in severe pain has been established as ≥1.8 points. We used paired t-tests and multilevel modeling to measure statistical significance and potential interactions and reviewed patient charts for adverse events, including respiratory depression or the use of naloxone. Results We compiled the results from the winter seasons for 2007 through 2012 and 2016 through 2020. A total of 247 patients were included. The initial pain score was 8.6±1.5 (mean±SD). The decrease in pain scores from 0 to 5, 10, and 15 min, respectively, was –1.8, –2.4, and –2.9 ( P<0.0001), which demonstrated a clinically and statistically significant decrease in pain scores. There were no adverse events. Conclusions Traditional standard of care analgesics are invasive, elongate scene times, and increase the risk of environmental exposure and provider needlestick. Intranasal fentanyl offers a safe, noninvasive, and rapid analgesia that is well-suited for austere winter environments, such as those encountered at ski resorts. This study demonstrates the safety and efficacy of the administration of intranasal fentanyl by EMT-Basic certified providers.
Simulated Lunar Surface Hydration Measurements Using Multispectral Lidar at 3 µm
Authors: Cremons D. R. , Honniball C. I. 
Published: July 2022

AbstractAccurately measuring the variability of spectroscopic signatures of hydration (H2O + OH) on the illuminated lunar surface at 3 μm as a function of latitude, lunar time of day, and composition is crucial to determining the generation and destruction mechanisms of OH species and understanding the global water cycle. A prime complication in analysis of the spectroscopic feature is the accurate removal of thermal emission, which can modify or even eliminate the hydration feature depending on the data processing methods used and assumptions made. An orbital multispectral lidar, with laser illumination at key diagnostic wavelengths, would provide uniform, zero‐phase geometry, complete latitude and time of day coverage from a circular polar orbit, and is agnostic to the thermal state of the surface. We have performed measurement simulations of a four‐wavelength multispectral lidar using spectral mixtures of hydrated mid‐ocean‐ridge basalt (MORB) glasses and lunar regolith endmembers to assess the lidar performance in measuring hydration signatures on the lunar surface. Our results show a feasible system with wavelengths at 1.5 μm, 2.65 μm, 2.8 μm, and 3.1 μm can measure lunar hydration with a precision of 52 ppm (1σ) or better. These results, combined with the uniform measurement capabilities of multispectral lidar make it a valuable spectroscopic technique for elucidating mechanisms of OH/H2O generation, migration, and destruction.
Comprehensive assessment of actionable genomic alterations in primary colorectal carcinoma using targeted next-generation sequencing
Authors: Jan Yi-Hua , Tan Kien Thiam , Chen Shu-Jen , Yip Timothy Tak Chun , Lu Cu tai , Lam Alfred King-yin 
Published: July 2022

Abstract
Background
The clinical utility of comprehensive genomic profiling (CGP) for guiding treatment has gradually become the standard-of-care procedure for colorectal carcinoma (CRC). Here, we comprehensively assess emerging targeted therapy biomarkers using CGP in primary CRC.

Methods
A total of 575 primary CRCs were sequenced by ACTOnco® assay for genomic alterations, tumour mutational burden (TMB), and microsatellite instability (MSI).

Results
Eighteen percent of patients were detected as MSI-High (MSI-H), and the remaining cases were classified as microsatellite stable (MSS). Driver mutation prevalence in MSS CRCs were APC (74%), TP53 (67%), KRAS (47%), PIK3CA (21%) and BRAF (13%). The median TMBs for MSI-H and MSS patients were 37.8 mutations per mega base (mut/Mb) and 3.9 mut/Mb, respectively. Forty-seven percent of MSI-H CRC harboured at least one loss-of-function mutations in genes that may hamper immune checkpoint blockade. Among MSS RAS/RAF wild-type CRCs, 59% had at least one actionable mutation that may compromise the efficacy of anti-EGFR therapy. For late-stage CRC, 51% of patients are eligible for standard care actionability and the remaining 49% could be enrolled in clinical trials with investigational drugs.

Conclusions
This study highlights the essential role of CGP for identifying rational targeted therapy options in CRC.
ATM rules neurodevelopment and glutamatergic transmission in the hippocampus but not in the cortex
Authors: Focchi Elisa , Cambria Clara , Pizzamiglio Lara , Murru Luca , Pelucchi Silvia , D’Andrea Laura , Piazza Silvano , Mattioni Lorenzo , Passafaro Maria , Marcello Elena , Provenzano Giovanni , Antonucci Flavia 
Published: July 2022

AbstractInterest in the function of ataxia-telangiectasia-mutated protein (ATM) is extensively growing as evidenced by preclinical studies that continuously link ATM with new intracellular pathways. Here, we exploited Atm+/− and Atm−/− mice and demonstrate that cognitive defects are rescued by the delivery of the antidepressant Fluoxetine (Fluox). Fluox increases levels of the chloride intruder NKCC1 exclusively at hippocampal level suggesting an ATM context-specificity. A deeper investigation of synaptic composition unveils increased Gluk-1 and Gluk-5 subunit-containing kainate receptors (KARs) levels in the hippocampus, but not in the cortex, of Atm+/− and Atm−/− mice. Analysis of postsynaptic fractions and confocal studies indicates that KARs are presynaptic while in vitro and ex vivo electrophysiology that are fully active. These changes are (i) linked to KCC2 activity, as the KCC2 blockade in Atm+/− developing neurons results in reduced KARs levels and (ii) developmental regulated. Indeed, the pharmacological inhibition of ATM kinase in adults produces different changes as identified by RNA-seq investigation. Our data display how ATM affects both inhibitory and excitatory neurotransmission, extending its role to a variety of neurological and psychiatric disorders.
KIT promotes tumor stroma formation and counteracts tumor-suppressive TGFβ signaling in colorectal cancer
Authors: Küçükköse Emre , Peters Niek A. , Ubink Inge , van Keulen Veere A. M. , Daghighian Roxanna , Verheem André , Laoukili Jamila , Kranenburg Onno 
Published: July 2022

AbstractExpression profiling has identified four consensus molecular subtypes (CMS1-4) in colorectal cancer (CRC). The receptor tyrosine kinase KIT has been associated with the most aggressive subtype, CMS4. However, it is unclear whether, and how, KIT contributes to the aggressive features of CMS4 CRC. Here, we employed genome-editing technologies in patient-derived organoids (PDOs) to study KIT function in CRC in vitro and in vivo. CRISPR-Cas9-mediated deletion of the KIT gene caused a partial mesenchymal-to-epithelial phenotype switch and a strong reduction of intra-tumor stromal content. Vice versa, overexpression of KIT caused a partial epithelial-to-mesenchymal phenotype switch, a strong increase of intra-tumor stromal content, and high expression of TGFβ1. Surprisingly, the levels of phosphorylated SMAD2 were significantly lower in KIT-expressing versus KIT-deficient tumor cells. In vitro analyses showed that TGFβ signaling in PDOs limits their regenerative capacity. Overexpression of KIT prevented tumor-suppressive TGFβ signaling, while KIT deletion sensitized PDOs to TGFβ-mediated growth inhibition. Mechanistically, we found that KIT expression caused a strong reduction in the expression of SMAD2, a central mediator of canonical TGFβ signaling. We propose that KIT induces a pro-fibrotic tumor microenvironment by stimulating TGFβ expression, and protects the tumor cells from tumor-suppressive TGFβ signaling by inhibiting SMAD2 expression.
The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis
Authors: De Marco Zompit Mara , Esteban Mònica Torres , Mooser Clémence , Adam Salomé , Rossi Silvia Emma , Jeanrenaud Alain , Leimbacher Pia-Amata , Fink Daniel , Shorrocks Ann-Marie K. , Blackford Andrew N. , Durocher Daniel , Stucki Manuel 
Published: July 2022

AbstractThe accurate repair of DNA double-strand breaks (DSBs), highly toxic DNA lesions, is crucial for genome integrity and is tightly regulated during the cell cycle. In mitosis, cells inactivate DSB repair in favor of a tethering mechanism that stabilizes broken chromosomes until they are repaired in the subsequent cell cycle phases. How this is achieved mechanistically is not yet understood, but the adaptor protein TOPBP1 is critically implicated in this process. Here, we identify CIP2A as a TOPBP1-interacting protein that regulates TOPBP1 localization specifically in mitosis. Cells lacking CIP2A display increased radio-sensitivity, micronuclei formation and chromosomal instability. CIP2A is actively exported from the cell nucleus in interphase but, upon nuclear envelope breakdown at the onset of mitosis, gains access to chromatin where it forms a complex with MDC1 and TOPBP1 to promote TOPBP1 recruitment to sites of mitotic DSBs. Collectively, our data uncover CIP2A-TOPBP1 as a mitosis-specific genome maintenance complex.
Nanoparticle elasticity affects systemic circulation lifetime by modulating adsorption of apolipoprotein A-I in corona formation
Authors: Li Mingyang , Jin Xinyang , Liu Tao , Fan Feng , Gao Feng , Chai Shuang , Yang Lihua 
Published: July 2022

AbstractNanoparticle elasticity is crucial in nanoparticles’ physiological fate, but how this occurs is largely unknown. Using core-shell nanoparticles with a same PEGylated lipid bilayer shell yet cores differing in elasticity (45 kPa – 760 MPa) as models, we isolate the effects of nanoparticle elasticity from those of other physiochemical parameters and, using mouse models, observe a non-monotonic relationship of systemic circulation lifetime versus nanoparticle elasticity. Incubating our nanoparticles in mouse plasma provides protein coronas varying non-monotonically in composition depending on nanoparticle elasticity. Particularly, apolipoprotein A-I (ApoA1) is the only protein whose relative abundance in corona strongly correlates with our nanoparticles’ blood clearance lifetime. Notably, similar results are observed when above nanoparticles’ PEGylated lipid bilayer shell is changed to be non-PEGylated. This work unveils the mechanisms by which nanoparticle elasticity affects nanoparticles’ physiological fate and suggests nanoparticle elasticity as a readily tunable parameter in future rational exploiting of protein corona.
Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance
Authors: Wrobel Lidia , Hill Sandra M. , Djajadikerta Alvin , Fernandez-Estevez Marian , Karabiyik Cansu , Ashkenazi Avraham , Barratt Victoria J. , Stamatakou Eleanna , Gunnarsson Anders , Rasmusson Timothy , Miele Eric W. , Beaton Nigel , Bruderer Roland , Feng Yuehan , Reiter Lukas , Castaldi M. Paola , Jarvis Rebecca , Tan Keith , Bürli Roland W. , Rubinsztein David C. 
Published: July 2022

AbstractEnhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for a number of neurodegenerative diseases, especially Huntington’s disease and various spinocerebellar ataxias. Ideally, such approaches should preferentially clear the mutant/misfolded species, while having minimal impact on the stability of wild-type/normally-folded proteins. Furthermore, activation of both ubiquitin-proteasome and autophagy-lysosome routes may be advantageous, as this would allow effective clearance of both monomeric and oligomeric species, the latter which are inaccessible to the proteasome. Here we find that compounds that activate the D1 ATPase activity of VCP/p97 fulfill these requirements. Such effects are seen with small molecule VCP activators like SMER28, which activate autophagosome biogenesis by enhancing interactions of PI3K complex components to increase PI(3)P production, and also accelerate VCP-dependent proteasomal clearance of such substrates. Thus, this mode of VCP activation may be a very attractive target for many neurodegenerative diseases.
A resource for assessing dynamic binary choices in the adult brain using EEG and mouse-tracking
Authors: Chen Kun , Wang Ruien , Huang Jiamin , Gao Fei , Yuan Zhen , Qi Yanyan , Wu Haiyan 
Published: July 2022

AbstractWe present a dataset combining high-density Electroencephalography (HD-EEG, 128-channels) and mouse-tracking intended as a resource for examining the dynamic decision process of semantics and preference choices in the human brain. The dataset includes resting-state and task-related (food preference choices and semantic judgments) EEG acquired from 31 individuals (ages: 18–33). Along with the dataset, we also provided the preliminary microstate analysis of resting-state EEG and the ERPs, topomap, and time-frequency maps of the task-related EEG. We believe that the simultaneous mouse-tracking and EEG recording would crack the core components of binary choices and further index the temporal dynamics of decision making and response hesitation. This publicly available dataset could support the development of neural signal processing methods in motor EEG, thus advancing research in both the decision neuroscience and brain-computer interface (BCI) applications.
Different colour predictions of facial preference by Caucasian and Chinese observers
Authors: Lu Yan , Xiao Kaida , Yang Jie , Pointer Michael , Li Changjun , Wuerger Sophie 
Published: July 2022

AbstractFacial colour characteristics convey vital personal information and influence social interactions and mate choices as contributing factors to perceived beauty, health, and age. How various colour characteristics affect facial preference and whether there are cultural differences are not fully understood. Here, we provide a useful and repeatable methodology for skin colour research based on a realistic skin model to investigate the effect of various facial colour characteristics on facial preference and compare the role of colour predictors in Caucasian (CA) and Chinese (CN) samples. Our results show that, although the average skin colour of facial areas plays a limited role, together with colour variation and contrast, there are stronger links between colour and facial preference than previously revealed. We also find large cultural differences in facial colour perceptions; Chinese observers tend to rely more heavily on colour and lightness cues to judge facial preference than Caucasian observers.
Analysis of three-dimensional chromatin packing domains by chromatin scanning transmission electron microscopy (ChromSTEM)
Authors: Li Yue , Agrawal Vasundhara , Virk Ranya K. A. , Roth Eric , Li Wing Shun , Eshein Adam , Frederick Jane , Huang Kai , Almassalha Luay , Bleher Reiner , Carignano Marcelo A. , Szleifer Igal , Dravid Vinayak P. , Backman Vadim 
Published: July 2022

AbstractChromatin organization over multiple length scales plays a critical role in the regulation of transcription. Deciphering the interplay of these processes requires high-resolution, three-dimensional, quantitative imaging of chromatin structure in vitro. Herein, we introduce ChromSTEM, a method that utilizes high-angle annular dark-field imaging and tomography in scanning transmission electron microscopy combined with DNA-specific staining for electron microscopy. We utilized ChromSTEM for an in-depth quantification of 3D chromatin conformation with high spatial resolution and contrast, allowing for characterization of higher-order chromatin structure almost down to the level of the DNA base pair. Employing mass scaling analysis on ChromSTEM mass density tomograms, we observed that chromatin forms spatially well-defined higher-order domains, around 80 nm in radius. Within domains, chromatin exhibits a polymeric fractal-like behavior and a radially decreasing mass-density from the center to the periphery. Unlike other nanoimaging and analysis techniques, we demonstrate that our unique combination of this high-resolution imaging technique with polymer physics-based analysis enables us to (i) investigate the chromatin conformation within packing domains and (ii) quantify statistical descriptors of chromatin structure that are relevant to transcription. We observe that packing domains have heterogeneous morphological properties even within the same cell line, underlying the potential role of statistical chromatin packing in regulating gene expression within eukaryotic nuclei.
Spatial heterogeneity of air pollution statistics in Europe
Authors: He Hankun , Schäfer Benjamin , Beck Christian 
Published: July 2022

AbstractAir pollution is one of the leading causes of death globally, and continues to have a detrimental effect on our health. In light of these impacts, an extensive range of statistical modelling approaches has been devised in order to better understand air pollution statistics. However, the time-varying statistics of different types of air pollutants are far from being fully understood. The observed probability density functions (PDFs) of concentrations depend very much on the spatial location and on the pollutant substance. In this paper, we analyse a large variety of data from 3544 different European monitoring sites and show that the PDFs of nitric oxide (NO), nitrogen dioxide ($$NO_2$$

N

O
2

) and particulate matter ($$PM_{10}$$

P

M
10

and $$PM_{2.5}$$

P

M

2.5

) concentrations generically exhibit heavy tails and are asymptotically well approximated by q-exponential distributions with a given width parameter $$\lambda$$
λ
. We observe that the power-law parameter q and the width parameter $$\lambda$$
λ
vary widely for the different spatial locations. For each substance, we find different patterns of parameter clouds in the $$(q, \lambda )$$

(
q
,
λ
)

plane. These depend on the type of pollutants and on the environmental characteristics (urban/suburban/rural/traffic/industrial/background). This means the effective statistical physics description of air pollution exhibits a strong degree of spatial heterogeneity.
Identification of heavy metal pollutants and their sources in farmland: an integrated approach of risk assessment and X-ray fluorescence spectrometry
Authors: Tian Xiaosong , Xie Qing , Fan Min , Chai Guanqun , Li Guanghui 
Published: July 2022

AbstractInvestigation and assessment of farmland pollution require an efficient method to identify heavy metal (HM) pollutants and their sources. In this study, heavy metals (HMs) in farmland were determined efficiently using high-precision X-ray fluorescence (HDXRF) spectrometer. The potential ecological risk and health risk of HMs in farmland near eight villages of Wushan County in China were quantified using an integrated method of concentration-oriented risk assessment (CORA) and source-oriented risk assessment (SORA). The CORA results showed that Cd in farmland near the villages of Liuping (LP) and Jianping (JP) posed a “very high” potential ecological risk, which is mainly ascribed to soil Cd (single potential ecological risk index ($${E}_{r}^{i}$$

E

r

i

) of Cd in villages LP and JP, $${E}_{r}^{i}$$

E

r

i

= 2307 and 568 > 320). A “moderate” potential ecological risk was present in other six villages. The overall non-carcinogenic risk (hazard index (HI) = 1.2 > 1) of HMs for children in village LP was unacceptable. The contributions of HMs decrease in the order of Cr > As > Cd > Pb > Ni > Cu > Zn. The total carcinogenic risk (TCR = 2.1 × 10–4 > 1.0 × 10–4) of HMs in village LP was unacceptable, with HMs contributions decreasing in the order of Cr > Ni > Cd > As > Pb. Furthermore, three source profiles were assigned by the positive matrix factorization: F1: agricultural activity; F2: geological anomaly originating from HMs-rich rocks; F3: the natural geological background. According to the results of SORA, F2 was the highest contributor to PER in village LP, up to 64.4%. Meanwhile, the contributions of three factors to HI in village LP were 19.0% (F1), 53.6% (F2), and 27.4% (F3), respectively. It is worth noting that TCR (1.2 × 10–4) from F2 surpassed the threshold of 1.0 × 10–4, with an unacceptable carcinogenic risk level. As mentioned above, the HM pollutants (i.e., Cd and Cr) and their main sources (i.e., F2) in this area should be considered. These results show that an integrated approach combining risk assessments with the determination of HM concentration and identification of HM source is effective in identifying HM pollutants and sources and provides a good methodological reference for effective prevention and control of HM pollution in farmland.
Time and phenotype-dependent transcriptome analysis in AAV-TGFβ1 and Bleomycin-induced lung fibrosis models
Authors: Strobel Benjamin , Klein Holger , Leparc Germán , Stierstorfer Birgit E. , Gantner Florian , Kreuz Sebastian 
Published: July 2022

AbstractWe have previously established a novel mouse model of lung fibrosis based on Adeno-associated virus (AAV)-mediated pulmonary overexpression of TGFβ1. Here, we provide an in-depth characterization of phenotypic and transcriptomic changes (mRNA and miRNA) in a head-to-head comparison with Bleomycin-induced lung injury over a 4-week disease course. The analyses delineate the temporal state of model-specific and commonly altered pathways, thereby providing detailed insights into the processes underlying disease development. They further guide appropriate model selection as well as interventional study design. Overall, Bleomycin-induced fibrosis resembles a biphasic process of acute inflammation and subsequent transition into fibrosis (with partial resolution), whereas the TGFβ1-driven model is characterized by pronounced and persistent fibrosis with concomitant inflammation and an equally complex disease phenotype as observed upon Bleomycin instillation. Finally, based on an integrative approach combining lung function data, mRNA/miRNA profiles, their correlation and miRNA target predictions, we identify putative drug targets and miRNAs to be explored as therapeutic candidates for fibrotic diseases. Taken together, we provide a comprehensive analysis and rich data resource based on RNA-sequencing, along with a strategy for transcriptome-phenotype coupling. The results will be of value for TGFβ research, drug discovery and biomarker identification in progressive fibrosing interstitial lung diseases.