bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRPF8 increases the aggressiveness of hepatocellular carcinoma by regulating FAK/AKT pathway via fibronectin 1 splicing
Authors: López-Cánovas Juan L. , Hermán-Sánchez Natalia , del Rio-Moreno Mercedes , Fuentes-Fayos Antonio C. , Lara-López Araceli , Sánchez-Frias Marina E. , Amado Víctor , Ciria Rubén , Briceño Javier , de la Mata Manuel , Castaño Justo P. , Rodriguez-Perálvarez Manuel , Luque Raúl M. , Gahete Manuel D. 
Published: January 2023

AbstractHepatocellular carcinoma (HCC) pathogenesis is associated with alterations in splicing machinery components (spliceosome and splicing factors) and aberrant expression of oncogenic splice variants. We aimed to analyze the expression and potential role of the spliceosome component PRPF8 (pre-mRNA processing factor 8) in HCC. PRPF8 expression (mRNA/protein) was analyzed in a retrospective cohort of HCC patients (n = 172 HCC and nontumor tissues) and validated in two in silico cohorts (TCGA and CPTAC). PRPF8 expression was silenced in liver cancer cell lines and in xenograft tumors to understand the functional and mechanistic consequences. In silico RNAseq and CLIPseq data were also analyzed. Our results indicate that PRPF8 is overexpressed in HCC and associated with increased tumor aggressiveness (patient survival, etc.), expression of HCC-related splice variants, and modulation of critical genes implicated in cancer-related pathways. PRPF8 silencing ameliorated aggressiveness in vitro and decreased tumor growth in vivo. Analysis of in silico CLIPseq data in HepG2 cells demonstrated that PRPF8 binds preferentially to exons of protein-coding genes, and RNAseq analysis showed that PRPF8 silencing alters splicing events in multiple genes. Integrated and in vitro analyses revealed that PRPF8 silencing modulates fibronectin (FN1) splicing, promoting the exclusion of exon 40.2, which is paramount for binding to integrins. Consistent with this finding, PRPF8 silencing reduced FAK/AKT phosphorylation and blunted stress fiber formation. Indeed, HepG2 and Hep3B cells exhibited a lower invasive capacity in membranes treated with conditioned medium from PRPF8-silenced cells compared to medium from scramble-treated cells. This study demonstrates that PRPF8 is overexpressed and associated with aggressiveness in HCC and plays important roles in hepatocarcinogenesis by altering FN1 splicing, FAK/AKT activation and stress fiber formation.
Tooth number abnormality: from bench to bedside
Authors: Zhang Han , Gong Xuyan , Xu Xiaoqiao , Wang Xiaogang , Sun Yao 
Published: January 2023

AbstractTooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.
Functional and molecular characterization of suicidality factors using phenotypic and genome-wide data
Authors: Quintero Reis Andrea , Newton Brendan A. , Kessler Ronald , Polimanti Renato , Wendt Frank R. 
Published: January 2023

AbstractGenome-wide association studies (GWAS) of suicidal thoughts and behaviors support the existence of genetic contributions. Continuous measures of psychiatric disorder symptom severity can sometimes model polygenic risk better than binarized definitions. We compared two severity measures of suicidal thoughts and behaviors at the molecular and functional levels using genome-wide data. We used summary association data from GWAS of four traits analyzed in 122,935 individuals of European ancestry: thought life was not worth living (TLNWL), thoughts of self-harm, actual self-harm, and attempted suicide. A new trait for suicidal thoughts and behaviors was constructed first, phenotypically, by aggregating the previous four traits (termed “suicidality”) and second, genetically, by using genomic structural equation modeling (gSEM; termed S-factor). Suicidality and S-factor were compared using SNP-heritability (h2) estimates, genetic correlation (rg), partitioned h2, effect size distribution, transcriptomic correlations (ρGE) in the brain, and cross-population polygenic scoring (PGS). The S-factor had good model fit (χ2 = 0.21, AIC = 16.21, CFI = 1.00, SRMR = 0.024). Suicidality (h2 = 7.6%) had higher h2 than the S-factor (h2 = 2.54, Pdiff = 4.78 × 10−13). Although the S-factor had a larger number of non-null susceptibility loci (πc = 0.010), these loci had small effect sizes compared to those influencing suicidality (πc = 0.005, Pdiff = 0.045). The h2 of both traits was enriched for conserved biological pathways. The rg and ρGE support highly overlapping genetic and transcriptomic features between suicidality and the S-factor. PGS using European-ancestry SNP effect sizes strongly associated with TLNWL in Admixed Americans: Nagelkerke’s R2 = 8.56%, P = 0.009 (PGSsuicidality) and Nagelkerke’s R2 = 7.48%, P = 0.045 (PGSS-factor). An aggregate suicidality phenotype was statistically more heritable than the S-factor across all analyses and may be more informative for future genetic study designs interested in common genetic factors among different suicide related phenotypes.
Multiscale molecular simulations for the solvation of lignin in ionic liquids
Authors: Mohan Mood , Simmons Blake A. , Sale Kenneth L. , Singh Seema 
Published: January 2023

AbstractLignin, the second most abundant biopolymer found in nature, has emerged as a potential source of sustainable fuels, chemicals, and materials. Finding suitable solvents, as well as technologies for efficient and affordable lignin dissolution and depolymerization, are major obstacles in the conversion of lignin to value-added products. Certain ionic liquids (ILs) are capable of dissolving and depolymerizing lignin but designing and developing an effective IL for lignin dissolution remains quite challenging. To address this issue, the COnductor-like Screening MOdel for Real Solvents (COSMO-RS) model was used to screen 5670 ILs by computing logarithmic activity coefficients (ln(γ)) and excess enthalpies (HE) of lignin, respectively. Based on the COSMO-RS computed thermodynamic properties (ln(γ) and HE) of lignin, anions such as acetate, methyl carbonate, octanoate, glycinate, alaninate, and lysinate in combination with cations like tetraalkylammonium, tetraalkylphosphonium, and pyridinium are predicted to be suitable solvents for lignin dissolution. The dissolution properties such as interaction energy between anion and cation, viscosity, Hansen solubility parameters, dissociation constants, and Kamlet–Taft parameters of selected ILs were evaluated to assess their propensity for lignin dissolution. Furthermore, molecular dynamics (MD) simulations were performed to understand the structural and dynamic properties of tetrabutylammonium [TBA]+-based ILs and lignin mixtures and to shed light on the mechanisms involved in lignin dissolution. MD simulation results suggested [TBA]+-based ILs have the potential to dissolve lignin because of their higher contact probability and interaction energies with lignin when compared to cholinium lysinate.
Urbanization and physical activity in the global Prospective Urban and Rural Epidemiology study
Authors: Boakye Kwadwo , Bovbjerg Marit , Schuna John , Branscum Adam , Varma Ravi Prasad , Ismail Rosnah , Barbarash Olga , Dominguez Juan , Altuntas Yuksel , Anjana Ranjit Mohan , Yusuf Rita , Kelishadi Roya , Lopez-Jaramillo Patricio , Iqbal Romaina , Serón Pamela , Rosengren Annika , Poirier Paul , Lakshmi P. V. M. , Khatib Rasha , Zatonska Katarzyna , Hu Bo , Yin Lu , Wang Chuangshi , Yeates Karen , Chifamba Jephat , Alhabib Khalid F , Avezum Álvaro , Dans Antonio , Lear Scott A , Yusuf Salim , Hystad Perry 
Published: January 2023

AbstractUrbanization may influence physical activity (PA) levels, although little evidence is available for low- and middle- income countries where urbanization is occurring fastest. We evaluated associations between urbanization and total PA, as well as work-, leisure-, home-, and transport-specific PA, for 138,206 adults living in 698 communities across 22 countries within the Prospective Urban and Rural Epidemiology (PURE) study. The 1-week long-form International PA Questionnaire was administered at baseline (2003–2015). We used satellite-derived population density and impervious surface area estimates to quantify baseline urbanization levels for study communities, as well as change measures for 5- and 10-years prior to PA surveys. We used generalized linear mixed effects models to examine associations between urbanization measures and PA levels, controlling for individual, household and community factors. Higher community baseline levels of population density (− 12.4% per IQR, 95% CI − 16.0, − 8.7) and impervious surface area (− 29.2% per IQR, 95% CI − 37.5, − 19.7), as well as the rate of change in 5-year population density (− 17.2% per IQR, 95% CI − 25.7, − 7.7), were associated with lower total PA levels. Important differences in the associations between urbanization and PA were observed between PA domains, country-income levels, urban/rural status, and sex. These findings provide new information on the complex associations between urbanization and PA.
Diffraction-limited hyperspectral mid-infrared single-pixel microscopy
Authors: Ebner Alexander , Gattinger Paul , Zorin Ivan , Krainer Lukas , Rankl Christian , Brandstetter Markus 
Published: January 2023

AbstractIn this contribution, we demonstrate a wide-field hyperspectral mid-infrared (MIR) microscope based on multidimensional single-pixel imaging (SPI). The microscope employs a high brightness MIR supercontinuum source for broadband (1.55 $$\upmu \hbox {m}$$

μ
m

–4.5 $$\upmu \hbox {m}$$

μ
m

) sample illumination. Hyperspectral imaging capability is achieved by a single micro-opto-electro-mechanical digital micromirror device (DMD), which provides both spatial and spectral differentiation. For that purpose the operational spectral bandwidth of the DMD was significantly extended into the MIR spectral region. In the presented design, the DMD fulfills two essential tasks. On the one hand, as standard for the SPI approach, the DMD sequentially masks captured scenes enabling diffraction-limited imaging in the tens of millisecond time-regime. On the other hand, the diffraction at the micromirrors leads to dispersion of the projected field and thus allows for wavelength selection without the application of additional dispersive optical elements, such as gratings or prisms. In the experimental part, first of all, the imaging and spectral capabilities of the hyperspectral microscope are characterized. The spatial and spectral resolution is assessed by means of test targets and linear variable filters, respectively. At a wavelength of 4.15 $$\upmu \hbox {m}$$

μ
m

a spatial resolution of 4.92 $$\upmu \hbox {m}$$

μ
m

is achieved with a native spectral resolution better than 118.1 nm. Further, a post-processing method for drastic enhancement of the spectral resolution is proposed and discussed. The performance of the MIR hyperspectral microsopce is demonstrated for label-free chemical imaging and examination of polymer compounds and red blood cells. The acquisition and reconstruction of Hadamard sampled 64 $$\times$$
×
64 images is achieved in 450 ms and 162 ms, respectively. Thus, combined with an unprecedented intrinsic flexibiliy gained by a tunable field of view and adjustable spatial resolution, the demonstrated design drastically improves the sample throughput in MIR chemical and biomedical imaging.
Ubiquilin-2 regulates pathological alpha-synuclein
Authors: Sandoval-Pistorius Stephanie S. , Gerson Julia E. , Liggans Nyjerus , Ryou Jaimie H. , Oak Kulin , Li Xingli , Negron-Rios Keyshla Y. , Fischer Svetlana , Barsh Henry , Crowley Emily V. , Skinner Mary E. , Sharkey Lisa M. , Barmada Sami J. , Paulson Henry L. 
Published: January 2023

AbstractThe key protein implicated in Parkinson’s disease and other synucleinopathies is α-synuclein, and a post-translationally modified form of the protein, phosphorylated at serine 129 (pS129), is a principal component in Lewy bodies, a pathological hallmark of PD. While altered proteostasis has been implicated in the etiology of Parkinson’s disease, we still have a limited understanding of how α-synuclein is regulated in the nervous system. The protein quality control protein Ubiquilin-2 (UBQLN2) is known to accumulate in synucleinopathies, but whether it directly regulates α-synuclein is unknown. Using cellular and mouse models, we find that UBQLN2 decreases levels of α-synuclein, including the pS129 phosphorylated isoform. Pharmacological inhibition of the proteasome revealed that, while α-synuclein may be cleared by parallel and redundant quality control pathways, UBQLN2 preferentially targets pS129 for proteasomal degradation. Moreover, in brain tissue from human PD and transgenic mice expressing pathogenic α-synuclein (A53T), native UBQLN2 becomes more insoluble. Collectively, our studies support a role for UBQLN2 in directly regulating pathological forms of α-synuclein and indicate that UBQLN2 dysregulation in disease may contribute to α-synuclein-mediated toxicity.
Efficacy and effectiveness of case isolation and quarantine during a growing phase of the COVID-19 epidemic in Finland
Authors: Auranen Kari , Shubin Mikhail , Erra Elina , Isosomppi Sanna , Kontto Jukka , Leino Tuija , Lukkarinen Timo 
Published: January 2023

AbstractBased on data collected as part of the contact tracing activity of the City of Helsinki Epidemiological Operations Unit, we evaluated the efficacy and effectiveness of isolating SARS-CoV-2 cases and quarantining their exposed contacts during a mildly growing phase of the COVID-19 epidemic in Finland in autumn 2020. Based on the observed symptom-to-symptom intervals in 1016 pairs of primary and secondary cases, we estimated that without case isolation or quarantine 40$$\%$$
%
(90$$\%$$
%
credible interval, CI 25–59) of transmission would have occurred on the day of or after symptom onset. One third of SARS-CoV-2 cases (N = 1521) had initially been quarantined, with a self-reported time until isolation (quarantine) of 0.8 days before symptom onset. This delay translates into an efficacy of 50$$\%$$
%
(90$$\%$$
%
CI 40–63) of averting secondary infections per quarantined case. Due to later isolation (mean 2.6 days after symptoms), the efficacy was smaller (24$$\%$$
%
; 90$$\%$$
%
CI 12–41) in those two third of the cases (N = 3101) whose isolation was prompted by their symptoms, i.e. without being previously quarantined. At the population level, we evaluated the effectiveness of case isolation and quarantine on the growth rate of the COVID-19 epidemic in the autumn of 2020. Under a wide range of underlying assumptions, the rate would have been at least 2 times higher without case isolation and quarantine. The numbers needed to isolate or quarantine to prevent one secondary case were 2 and 20, respectively.
Worldwide transmission and infection risk of mosquito vectors of West Nile, St. Louis encephalitis, Usutu and Japanese encephalitis viruses: a systematic review
Authors: Tolsá-García María José , Wehmeyer Magdalena Laura , Lühken Renke , Roiz David 
Published: January 2023

AbstractThe increasing trend of mosquito-borne pathogens demands more accurate global estimations of infection and transmission risks between mosquitoes. Here, we systematically review field and laboratory studies to assess the natural field infection and experimental laboratory transmission risk in Culex mosquitoes. We studied four worldwide flaviviruses: West Nile, Usutu, Japanese encephalitis, and St. Louis encephalitis, belonging to the Japanese encephalitis Serocomplex (JES). The PRISMA statement was carried out for both approaches. The Transmission-Infection Risk of the diverse mosquito species for the different viruses was estimated through seven variables. We considered 130 and 95 articles for field and experimental approach, respectively. We identified 30 species naturally infected, and 23 species capable to transmit some of the four flaviviruses. For the JES, the highest Transmission-Infection Risk estimate was recorded in Culex quinquefasciatus (North America). The maximum Infection-Transmission Risk values for West Nile was Culex restuans, for Usutu it was Culex pipiens (Europe), for St. Louis encephalitis Culex quinquefasciatus (North America), and for Japanese encephalitis Culex gelidus (Oceania). We conclude that on a worldwide scale, a combination of field and experimental data offers a better way of understanding natural infection and transmission risks between mosquito populations.
Meta-analysis of laparoscopic radical hysterectomy, excluding robotic assisted versus open radical hysterectomy for early stage cervical cancer
Authors: Marchand Greg , Masoud Ahmed Taher , Abdelsattar Ahmed , King Alexa , Ulibarri Hollie , Parise Julia , Arroyo Amanda , Coriell Catherine , Goetz Sydnee , Moir Carmen , Moberly Atley , Govindan Malini 
Published: January 2023

AbstractRecent evidence has shown an increase in recurrence and a decrease in overall survival in patients treated with laparoscopic radical hysterectomy (LRH) and robotic assisted radical hysterectomy (RRH) open techniques (ORH). In addition, several high quality trials were recently published regarding the laparoscopic treatment of early stage cervical cancer. We sought out to reassess the recurrence rates, overall survival, complications and outcomes associated with laparoscopic radical hysterectomy (LRH) techniques against open techniques (ORH) when robotic assisted techniques were excluded. We searched PubMed, Medline, Cochrane CENTRAL, SCOPUS, ClinicalTrials.Gov and Web of Science for relevant clinical trials and observational studies. We included all studies that compared with early stage cervical cancer receiving LRH compared with ORH. We included randomized clinical trials, prospective cohort, and retrospective cohort trials. We included studies that included LRH and RRH as long as data was available to separate the two arms. We excluded studies that combined LRH and RRH without supplying data to differentiate. Of 1244 total studies, we used a manual three step screening process. Sixty studies ultimately met our criteria. We performed this review in accordance with PRISMA guidelines. We analyzed continuous data using mean difference (MD) and a 95% confidence interval (CI), while dichotomous data were analyzed using odds ratio (OR) and a 95% CI. Review Manager and Endnote software were utilized in the synthesis. We found that when excluding RRH, the was no significant difference regarding 5-year overall Survival (OR = 1.24 [0.94, 1.64], (P = 0.12), disease free survival (OR = 1.00 [0.80, 1.26], (P = 0.98), recurrence (OR = 1.01 [0.81, 1.25], (P = 0.95), or intraoperative complications (OR = 1.38 [0.94, 2.04], (P = 0.10). LRH was statistically better than ORH in terms of estimated blood loss (MD = − 325.55 [− 386.16, − 264.94] (P < 0.001), blood transfusion rate (OR = 0.28 [0.14, 0.55], (P = 0.002), postoperative complication rate (OR = 0.70 [0.55, 0.90], (P = 0.005), and length of hospital stay (MD = − 3.64[− 4.27, − 3.01], (P < 0.001). ORH was superior in terms of operating time (MD = 20.48 [8.62, 32.35], (P = 0.007) and number of resected lymph nodes (MD = − 2.80 [− 4.35, − 1.24], (P = 0.004). The previously seen increase recurrence and decrease in survival is not seen in LRH when robotic assisted techniques are included and all new high quality is considered. LRH is also associated with a significantly shorter hospital stay, less blood loss and lower complication rate.Prospero Prospective Registration Number: CRD42022267138.
Functional analysis in a model sea anemone reveals phylogenetic complexity and a role in cnidocyte discharge of DEG/ENaC ion channels
Authors: Aguilar-Camacho Jose Maria , Foreman Katharina , Jaimes-Becerra Adrian , Aharoni Reuven , Gründer Stefan , Moran Yehu 
Published: January 2023

AbstractIon channels of the DEG/ENaC family share a similar structure but serve strikingly diverse biological functions, such as Na+ reabsorption, mechanosensing, proton-sensing, chemosensing and cell-cell communication via neuropeptides. This functional diversity raises the question of the ancient function of DEG/ENaCs. Using an extensive phylogenetic analysis across many different animal groups, we found a surprising diversity of DEG/ENaCs already in Cnidaria (corals, sea anemones, hydroids and jellyfish). Using a combination of gene expression analysis, electrophysiological and functional studies combined with pharmacological inhibition as well as genetic knockout in the model cnidarian Nematostella vectensis, we reveal an unanticipated role for a proton-sensitive DEG/ENaC in discharge of N. vectensis cnidocytes, the stinging cells typifying all cnidarians. Our study supports the view that DEG/ENaCs are versatile channels that have been co-opted for diverse functions since their early occurrence in animals and that respond to simple and ancient stimuli, such as omnipresent protons.
Singing and Speaking Ability in Parkinson's Disease and Spinocerebellar Ataxia
Authors: Kim Yoonji , Sidtis Diana , Sidtis John J. 
Published: January 2023

Purpose:
This study examined spontaneous, spoken-to-a-model, and two sung modes in speakers with Parkinson's disease (PD), speakers with cerebellar disease (CD), and healthy controls. Vocal performance was measured by intelligibility scores and listeners' perceptual ratings.

Method:
Participants included speakers with hypokinetic dysarthria secondary to PD, those with ataxic dysarthria secondary to CD, and healthy speakers. Participants produced utterances in four vocal modes: spontaneous speech, spoken-to-a-model, sung-to-a-model, and spontaneous singing. For spoken-to-a-model and sung-to-a-model modes, written material was provided the model. For spontaneous singing, participants sang songs that they endorsed as familiar. Dependent variables: In Experiment I, listeners orthographically transcribed the audio samples of the first three vocal modes. In Experiment IIa, raters evaluated the accuracy of the pitch and rhythm of the spontaneous singing of familiar songs. Finally, familiar songs and sung-to-a-model utterances were rated on a competency scale by a second group of raters (Experiment IIb).

Results:
Results showed increases in intelligibility during the spoken-to-a-model mode compared with the spontaneous mode in both PD and CD groups. Singing enhanced the vocal output of speakers with PD more than in speakers with CD, as measured by percent intelligibility. PD participants' pitch and rhythm accuracy and competency in singing familiar songs was rated more favorably than those produced by CD participants.

Conclusions:
The findings reveal a vocal task effect for spoken utterances in both groups. Sung exemplars, more impaired in CD, suggest a significant involvement of the cerebellum in singing.

Supplemental Material:

https://doi.org/10.23641/asha.21809544