bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithospheric double shear zone unveiled by microseismicity in a region of slow deformation
Authors: de Nardis Rita , Pandolfi Claudia , Cattaneo Marco , Monachesi Giancarlo , Cirillo Daniele , Ferrarini Federica , Bello Simone , Brozzetti Francesco , Lavecchia Giusy 
Published: December 2022

AbstractThe deformation style of the continental lithosphere is a relevant issue for geodynamics and seismic hazard perspectives. Here we show the first evidence of two well-distinct low-angle and SW-dipping individual reverse shear zones of the Italian Outer Thrust System in Central Italy. One corresponds to the down-dip prosecution of the Adriatic Basal Thrust with its major splay and the other to a hidden independent structure, illuminated at a depth between 25 and 60 km, for an along-strike extent of ~ 150 km. Combining geological information with high-quality seismological data, we unveil this novel configuration and reconstruct a detailed 3D geometric and kinematic fault model of the compressional system, active at upper crust to upper mantle depths. In addition, we report evidence of coexisting deformation volumes undergoing well-distinguished stress fields at different lithospheric depths. These results provide fundamental constraints for a forthcoming discussion on the Apennine fold-and-thrust system's geodynamic context as a shallow subduction zone or an intra-continental lithosphere shear zone.
Genome-resolved insight into the reservoir of antibiotic resistance genes in aquatic microbial community
Authors: Goodarzi Zahra , Asad Sedigheh , Mehrshad Maliheh 
Published: December 2022

AbstractAquatic microbial communities are an important reservoir of antibiotic resistance genes (ARGs). However, distribution and diversity of different ARG categories in environmental microbes with different ecological strategies is not yet well studied. Despite the potential exposure of the southern part of the Caspian Sea to the release of antibiotics, little is known about its natural resistome profile. We used a combination of Hidden Markov model (HMM), homology alignment and a deep learning approach for comprehensive screening of the diversity and distribution of ARGs in the Caspian Sea metagenomes at genome resolution. Detected ARGs were classified into five antibiotic resistance categories including prevention of access to target (44%), modification/protection of targets (30%), direct modification of antibiotics (22%), stress resistance (3%), and metal resistance (1%). The 102 detected ARG containing metagenome-assembled genomes of the Caspian Sea were dominated by representatives of Acidimicrobiia, Gammaproteobacteria, and Actinobacteria classes. Comparative analysis revealed that the highly abundant, oligotrophic, and genome streamlined representatives of taxa Acidimicrobiia and Actinobacteria modify the antibiotic target via mutation to develop antibiotic resistance rather than carrying extra resistance genes. Our results help with understanding how the encoded resistance categories of each genome are aligned with its ecological strategies.
Efficacy of a novel self-expandable metal stent with dumbbell-shaped flare ends for distal biliary obstruction due to unresectable pancreatic cancer
Authors: Miyazawa Masaki , Takatori Hajime , Okafuji Hirofumi , Hayashi Tomoyuki , Toyama Tadashi , Yamada Shinya , Kitamura Kazuya , Arai Kuniaki , Sakai Yoshio , Yamashita Taro , Yamashita Tatsuya , Mizukoshi Eishiro , Honda Masao , Kaneko Shuichi 
Published: December 2022

AbstractThis study aimed to evaluate the efficacy of a novel fully covered self-expandable metal stent (SEMS) with dumbbell-shaped flare ends for the palliation of distal biliary obstruction (DBO) due to unresectable pancreatic cancer (UPC). Patients with DBO due to UPC who received the novel HILZO fully covered stent (HFS), the WALLFLEX partially covered stent (WPS) or fully covered stent (WFS) were analyzed. The incidence of recurrent biliary obstruction (RBO), time to RBO (TRBO), and the incidence of complications were compared among the three SEMS groups. Eighty-four patients (HFS, n = 36; WPS, n = 20; WFS, n = 28) were included. The incidence of RBO was low in the HFS group (versus the WPS and WFS group, p = 0.033 and 0.023, respectively). TRBO in the HFS group was longer than that in the WFS group (p = 0.049). Placement of the HFS was an independent factor for long TRBO in multivariable analysis (p = 0.040). The incidence of pancreatitis and cholecystitis in the HFS group was low (one for each). It is recommended to use the HFS for the palliation of DBO due to UPC from the viewpoint of the low incidence of RBO and complications.
Novel expression cassettes for increasing apolipoprotein AI transgene expression in vascular endothelial cells
Authors: Sethuraman Meena , Dronadula Nagadhara , Bi Lianxiang , Wacker Bradley K. , Knight Ethan , De Bleser Pieter , Dichek David A. 
Published: December 2022

AbstractTransduction of endothelial cells (EC) with a vector that expresses apolipoprotein A-I (APOAI) reduces atherosclerosis in arteries of fat-fed rabbits. However, the effects on atherosclerosis are partial and might be enhanced if APOAI expression could be increased. With a goal of developing an expression cassette that generates higher levels of APOAI mRNA in EC, we tested 4 strategies, largely in vitro: addition of 2 types of enhancers, addition of computationally identified EC-specific cis-regulatory modules (CRM), and insertion of the rabbit APOAI gene at the transcription start site (TSS) of sequences cloned from genes that are highly expressed in cultured EC. Addition of a shear stress-responsive enhancer did not increase APOAI expression. Addition of 2 copies of a Mef2c enhancer increased APOAI expression from a moderately active promoter/enhancer but decreased APOAI expression from a highly active promoter/enhancer. Of the 11 CRMs, 3 increased APOAI expression from a moderately active promoter (2–7-fold; P < 0.05); none increased expression from a highly active promoter/enhancer. Insertion of the APOAI gene into the TSS of highly expressed EC genes did not increase expression above levels obtained with a moderately active promoter/enhancer. New strategies are needed to further increase APOAI transgene expression in EC.
Desloratadine, an FDA-approved cationic amphiphilic drug, inhibits SARS-CoV-2 infection in cell culture and primary human nasal epithelial cells by blocking viral entry
Authors: Morin-Dewaele Margot , Bartier Sophie , Berry François , Brillet Rozenn , López-Molina Dennis Salomón , Nguyễn Công Trung , Maille Pascale , Sereno Kevin , Nevers Quentin , Softic Laurent , Vaugeois Jean-Marie , Louis Bruno , Bequignon Emilie , Bruscella Patrice , Coste André , Pawlotsky Jean-Michel , Jamain Stéphane , Ahmed-Belkacem Abdelhakim 
Published: December 2022

AbstractThe 2019 global coronavirus (COVID-19) pandemic has brought the world to a grinding halt, highlighting the urgent need for therapeutic and preventive solutions to slow the spread of emerging viruses. The objective of this study was to assess the anti-SARS-CoV-2 effectiveness of 8 FDA-approved cationic amphiphilic drugs (CADs). SARS-CoV-2-infected Vero cells, Calu-3 cells and primary Human Nasal Epithelial Cells (HNEC) were used to investigate the effects of CADs and revealed their antiviral mode of action. Among the CADs tested, desloratadine, a commonly used antiallergic, well-tolerated with no major side effects, potently reduced the production of SARS-CoV-2 RNA in Vero-E6 cells. Interestingly, desloratadine was also effective against HCoV-229E and HCoV-OC43 showing that it possessed broad-spectrum anti-coronavirus activity. Investigation of its mode of action revealed that it targeted an early step of virus lifecycle and blocked SARS-CoV-2 entry through the endosomal pathway. Finally, the ex vivo kinetic of the antiviral effect of desloratadine was evaluated on primary Human Nasal Epithelial Cells (HNEC), showing a significant delay of viral RNA production with a maximal reduction reached after 72 h of treatment. Thus, this treatment could provide a substantial contribution to prophylaxis and systemic therapy of COVID-19 or other coronaviruses infections and requires further studies.
Atraumatic spinal needle indicates correct CSF opening pressure
Authors: Woo Marcel S. , Kessner Simon S. , Schlemm Eckhard , Gerloff Christian 
Published: December 2022

AbstractThe accurate assessment of cerebrospinal fluid opening pressure during spinal puncture provides important medical information in diagnosis, prognosis and therapy of several neurological conditions. However, purpose-specific spinal needle choice is debated. While atraumatic needles are associated with lower incidence of post-puncture headache and re-hospitalisation, some clinicians believe that they lack in accuracy of CSF opening pressure assessment. Our primary objective was to investigate different needle types on correctly assessing CSF opening pressure. We compared typical clinically utilised traumatic (0.9 mm outer diameter) and atraumatic (0.7 mm; 0.45 mm) spinal needles with regards to the assessment of the opening pressure in an experimental spinal puncture model testing experimental and cerebrospinal fluids in predefined pressures. Our goal was to measure the time until indicated pressure levels were correctly shown. Atraumatic needles of at least 0.7 mm diameter had a similar accuracy as traumatic needles without significant differences in time-to-equilibrium. These results were independent of protein and glucose concentration and the presence of haemoglobin. This study demonstrates that atraumatic needles can be used to accurately measure CSF opening pressure. This knowledge might guide clinicians in their choice of needle and help to reduce post-puncture headaches and re-hospitalisation.
Blood monocyte levels predict the risk of acute exacerbations of chronic obstructive pulmonary disease: a retrospective case–control study
Authors: Lin Ching-Hsiung , Li Yi-Rong , Lin Pei Ru , Wang Bing-Yen , Lin Sheng-Hao , Huang Kuo-Yang , Kor Chew-Teng 
Published: December 2022

AbstractMonocytes were critical cells in the innate immune system. Monocyte recruitment to the lungs is a crucial process of pathophysiology in chronic obstructive pulmonary disease (COPD). Current evidence on the association between the occurrence of acute exacerbations of COPD (AECOPD) and monocytes was unclear. This study aimed to examine whether blood monocytes are associated with the occurrence of AECOPD and to determine the specific blood monocyte level to predict AECOPD. A retrospective case–control study was conducted at Changhua Christian Hospital. A total of 444 eligible patients with COPD were included between January 2017 and December 2019. Restricted cubic splines were used to analyze the nonlinear relationships between continuous white blood cell values and the occurrence of AECOPD. The association between monocytes and the occurrence of AECOPD was assessed using the logistic, lasso, and ridge regression models. Restricted cubic splines revealed nonlinear associations among the monocyte level, the continuous value of the eosinophil-to-lymphocyte ratio, and the occurrence of AECOPD. The lowest risk of occurrence of AECOPD ranged from 7.4 to 10%; < 7.4% with an absolute count < 0.62 or > 10% indicated significant risk. No significant association was noted between the eosinophil-to-lymphocyte ratio categories in the tertiles (< 0.049, 0.049 to < 0.122, and ≥ 0.122) and the risk of AECOPD. A significantly higher risk was noted in the association of the occurrence of AECOPD with the CAT score; mMRC score; wheezing cough; preexisting chronic pulmonary disease; hypertension and malignancy; use of dual- and triple, and oral long-acting bronchodilators for COPD treatment; and WBC count. We reported a nonlinear relationship between monocytes and the occurrence of AECOPD. Patients with monocyte percentage of > 10% or < 7.4% with an absolute count < 0.62 had higher risk of occurrence of AECOPD. Overall, our study demonstrated the specific value of monocytes in identifying high risks of the occurrence of AECOPD; this value is an easy-to-obtain, inexpensive biomarker in patients with AECOPD and should be further investigated in future prospective clinical studies.
The evolutionary process of invasion in the fall armyworm (Spodoptera frugiperda)
Authors: Yainna Sudeeptha , Tay Wee Tek , Durand Karine , Fiteni Estelle , Hilliou Frédérique , Legeai Fabrice , Clamens Anne-Laure , Gimenez Sylvie , Asokan R. , Kalleshwaraswamy C. M. , Deshmukh Sharanabasappa S. , Meagher Robert L. , Blanco Carlos A. , Silvie Pierre , Brévault Thierry , Dassou Anicet , Kergoat Gael J. , Walsh Thomas , Gordon Karl , Nègre Nicolas , d’Alençon Emmanuelle , Nam Kiwoong 
Published: December 2022

AbstractThe fall armyworm (FAW; Spodoptera frugiperda) is one of the major agricultural pest insects. FAW is native to the Americas, and its invasion was first reported in West Africa in 2016. Then it quickly spread through Africa, Asia, and Oceania, becoming one of the main threats to corn production. We analyzed whole genome sequences of 177 FAW individuals from 12 locations on four continents to infer evolutionary processes of invasion. Principal component analysis from the TPI gene and whole genome sequences shows that invasive FAW populations originated from the corn strain. Ancestry coefficient and phylogenetic analyses from the nuclear genome indicate that invasive populations are derived from a single ancestry, distinct from native populations, while the mitochondrial phylogenetic tree supports the hypothesis of multiple introductions. Adaptive evolution specific to invasive populations was observed in detoxification, chemosensory, and digestion genes. We concluded that extant invasive FAW populations originated from the corn strain with potential contributions of adaptive evolution.
Exploring the response of a key Mediterranean gorgonian to heat stress across biological and spatial scales
Authors: Gómez-Gras D. , Bensoussan N. , Ledoux J. B. , López-Sendino P. , Cerrano C. , Ferretti E. , Kipson S. , Bakran-Petricioli T. , Serrao E. A. , Paulo D. , Coelho M. A. G. , Pearson G. A. , Boavida J. , Montero-Serra I. , Pagès-Escolà M. , Medrano A. , López-Sanz A. , Milanese M. , Linares C. , Garrabou J. 
Published: December 2022

AbstractUnderstanding the factors and processes that shape intra-specific sensitivity to heat stress is fundamental to better predicting the vulnerability of benthic species to climate change. Here, we investigate the response of a habitat-forming Mediterranean octocoral, the red gorgonianParamuricea clavata(Risso, 1826) to thermal stress at multiple biological and geographical scales. Samples from elevenP. clavatapopulations inhabiting four localities separated by hundreds to more than 1500 km of coast and with contrasting thermal histories were exposed to a critical temperature threshold (25 °C) in a common garden experiment in aquaria. Ten of the 11 populations lacked thermotolerance to the experimental conditions provided (25 days at 25 °C), with 100% or almost 100% colony mortality by the end of the experiment. Furthermore, we found no significant association between local average thermal regimes nor recent thermal history (i.e., local water temperatures in the 3 months prior to the experiment) and population thermotolerance. Overall, our results suggest that local adaptation and/or acclimation to warmer conditions have a limited role in the response ofP. clavatato thermal stress. The study also confirms the sensitivity of this species to warm temperatures across its distributional range and questions its adaptive capacity under ocean warming conditions. However, important inter-individual variation in thermotolerance was found within populations, particularly those exposed to the most severe prior marine heatwaves. These observations suggest thatP. clavatacould harbor adaptive potential to future warming acting on standing genetic variation (i.e., divergent selection) and/or environmentally-induced phenotypic variation (i.e., intra- and/or intergenerational plasticity).
A perceptual glitch in serial perception generates temporal distortions
Authors: Sierra Franklenin , Muralikrishnan R. , Poeppel David , Tavano Alessandro 
Published: December 2022

AbstractPrecisely estimating event timing is essential for survival, yet temporal distortions are ubiquitous in our daily sensory experience. Here, we tested whether the relative position, duration, and distance in time of two sequentially-organized events—standard S, with constant duration, and comparison C, with duration varying trial-by-trial—are causal factors in generating temporal distortions. We found that temporal distortions emerge when the first event is shorter than the second event. Importantly, a significant interaction suggests that a longer inter-stimulus interval (ISI) helps to counteract such serial distortion effect only when the constant S is in the first position, but not if the unpredictable C is in the first position. These results imply the existence of a perceptual bias in perceiving ordered event durations, mechanistically contributing to distortion in time perception. We simulated our behavioral results with a Bayesian model and replicated the finding that participants disproportionately expand first-position dynamic (unpredictable) short events. Our results clarify the mechanisms generating time distortions by identifying a hitherto unknown duration-dependent encoding inefficiency in human serial temporal perception, something akin to a strong prior that can be overridden for highly predictable sensory events but unfolds for unpredictable ones.
Impact of SNPs, off-targets, and passive permeability on efficacy of BCL6 degrading drugs assigned by virtual screening and 3D-QSAR approach
Authors: Karimi Solmaz , Shahabi Farzaneh , Mubarak Shaden M. H. , Arjmandi Hanie , Hashemi Zahra Sadat , Pourzardosht Navid , Zakeri Alireza , Mahboobi Mahdieh , Jahangiri Abolfazl , Rahbar Mohammad Reza , Khalili Saeed 
Published: December 2022

AbstractB-cell lymphoma 6 (BCL6) regulates various genes and is reported to be overexpressed in lymphomas and other malignancies. Thus, BCL6 inhibition or its tagging for degradation would be an amenable therapeutic approach. A library of 2500 approved drugs was employed to find BCL6 inhibitory molecules via virtual screening. Moreover, the 3D core structure of 170 BCL6 inhibitors was used to build a 3D QSAR model and predict the biological activity. The SNP database was analyzed to study the impact on the destabilization of BCL6/drug interactions. Structural similarity search and molecular docking analyses were used to assess the interaction between possible off-targets and BCL6 inhibitors. The tendency of drugs for passive membrane permeability was also analyzed. Lifitegrast (DB11611) had favorable binding properties and biological activity compared to the BI-3802. Missense SNPs were located at the essential interaction sites of the BCL6. Structural similarity search resulted in five BTB-domain containing off-target proteins. BI-3802 and Lifitegrast had similar chemical behavior and binding properties against off-target candidates. More interestingly, the binding affinity of BI-3802 (against off-targets) was higher than Lifitegrast. Energetically, Lifitegrast was less favorable for passive membrane permeability. The interaction between BCL6 and BI-3802 is more prone to SNP-derived variations. On the other hand, higher nonspecific binding of BI-3802 to off-target proteins could bring about higher undesirable properties. It should also be noted that energetically less desirable passive membrane translocation of Lifitegrast would demand drug delivery vehicles. However, further empirical evaluation of Lifitegrast would unveil its true potential.
N7-methylguanosine methylation-related regulator genes as biological markers in predicting prognosis for melanoma
Authors: Deng Jiehua , Lin Jiahua , Liu Chang , Li Jiasong , Cai Jun , Zhou Xiyu , Li Xiong 
Published: December 2022

AbstractThe aim of this study is to find those N7-methylguanosine (m7G) methylation-related regulator genes (m7GMRRGs) which were associated with melanoma prognosis and use them to develop a prognostic prediction model. Clinical information was retrieved online from The Cancer Gene Atlas (TCGA) and the Gene Expression Omnibus (GEO). R software was used to extract m7GMRRGs by differential expression analysis. To create a prognostic risk model, univariate and multivariate Cox regression analyses were employed for the evaluation of the prognostic significance of m7G methylation modifiers. Internal validation using cohort from TCGA (training set) and external validation using cohort from GEO (validation set) of the model were carried out. The model’s predictive performance was confirmed by using the Kaplan–Meier, univariate, and multivariate Cox regression, and receiver operating characteristic curve (ROC) by constructing column line plots incorporating clinical factor characteristics. Immune infiltration analyses were performed to assess the immune function of m7GMRRGs. Drug sensitivity analysis was conducted to study chemotherapeutic drug treatment cues. Prognostic models using four m7GMRRGs (EIF4E3, LARP1, NCBP3, and IFIT5) showed good prognostic power in training and validation sets. The area under the curve (AUC) at 1, 3, and 5 years for GEO-melanoma were 0.689, 0.704, and 0.726, respectively. The prediction model could distinctly classify patients with melanoma into different risk subgroups (P < 0.001 for TCGA-melanoma and P < 0.05 for GEO-melanoma). Clinical characteristics were taken into account in Cox regression and AUC analysis, which highlighted that the risk score served as an independent risk factor determining the prognosis of patients with melanoma. Immuno-infiltration analysis showed that m7GMRRGs could potentially regulate CD8+ T cells as well as regulatory T cells (Treg cells). Results of our study indicate a association between m7GMRRGs and melanoma prognosis, and the prognostic prediction model using m7GMRRGs may predict the prognosis of patients with melanoma well. Nevertheless, these results may provide a clue for potential better options of melanoma treatment but need further validation in futural studies.
Gamete dimorphism of the isogamous green alga (Chlamydomonas reinhardtii), is regulated by the mating type-determining gene, MID
Authors: Innami Ryoya , Miyamura Shinichi , Okoshi Masako , Nagumo Tamotsu , Ichihara Kensuke , Yamazaki Tomokazu , Kawano Shigeyuki 
Published: December 2022

AbstractThe gametes of chlorophytes differ morphologically even in isogamy and are divided into two types (α and β) based on the mating type- or sex-specific asymmetric positioning of the mating structure (cell fusion apparatus) with respect to the flagellar beat plane and eyespot, irrespective of the difference in gamete size. However, the relationship between this morphological trait and the mating type or sex determination system is unclear. Using mating type-reversed strains of the isogamous alga Chlamydomonas reinhardtii, produced by deletion or introduction of the mating type-determining gene MID, we revealed that the positioning of the mating structure is associated with conversion of mating types (mt– and mt+), implying that this trait is regulated by MID. Moreover, the dominant mating type is associated with the type β phenotype, as in the chlorophyte species Ulva prolifera. Our findings may provide a genetic basis for mating type- or sex-specific asymmetric positioning of the chlorophyte mating structure.