bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface Uplift and Topographic Rejuvenation of a Tectonically Inactive Range: Insights From the Anti‐Atlas and the Siroua Massif (Morocco)
Authors: Clementucci R. , Ballato P. , Siame L. , Fox M. , Lanari R. , Sembroni A. , Faccenna C. , Yaaqoub A. , Essaifi A. 
Published: February 2023

AbstractThe Atlas‐Meseta intracontinental orographic system of Morocco experienced recent, large‐scale surface uplift as documented by elevated late Miocene, shallow‐water marine deposits exposed in the Middle Atlas Mountains. The Anti‐Atlas Mountains do not present any stratigraphic records that document regional vertical movements, however, the presence of a high‐standing, erosional surface, and the transient state of the river network, provides insights into the uplift history of the belt and the mechanisms that drove it. Here, we combine geomorphic and stream profiles analyses, celerity of knickpoints and linear inverse landscape modeling with available geological evidence, to decipher the spatial and temporal variations of surface uplift in the Anti‐Atlas and the Siroua Massif. Our results highlight the presence of a transient landscape and document a long wave‐length topographic swell (∼100 × 600 km) with a maximum surface uplift of ∼1,500 m in the Siroua Massif and ∼1,100 m in the central Anti‐Atlas most likely starting from ∼14 to 10 Ma. Surface uplift occurred in association with the onset of late Miocene magmatism in the Siroua and Saghro Massif and contractional deformation in the High Atlas. Regional surface uplift was most likely due to deep‐seated mechanism, such as asthenospheric upwelling. Additional processes such as magma injection and faulting contributed to the surface uplift of the Siroua Massif. Overall, our approach allows to quantitatively constrain the transient state of the landscape and the contribution of regional surface uplift on mountain building processes.
BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression
Authors: Zeng Furong , Li Yayun , Meng Yu , Sun Huiyan , He Yi , Yin Mingzhu , Chen Xiang , Deng Guangtong 
Published: February 2023

AbstractTargeting bromodomain and extra-terminal domain (BET) proteins has shown a promising therapeutic effect on melanoma. The development of strategies to better kill melanoma cells with BET inhibitor treatment may provide new clinical applications. Here, we used a drug synergy screening approach to combine JQ1 with 240 antitumor drugs from the Food and Drug Administration (FDA)-approved drug library and found that sunitinib synergizes with BET inhibitors in melanoma cells. We further demonstrated that BET inhibitors synergize with sunitinib in melanoma by inducing apoptosis and cell cycle arrest. Mechanistically, BET inhibitors sensitize melanoma cells to sunitinib by inhibiting GDF15 expression. Strikingly, GDF15 is transcriptionally regulated directly by BRD4 or indirectly by the BRD4/IL6/STAT3 axis. Xenograft assays revealed that the combination of BET inhibitors with sunitinib causes melanoma suppression in vivo. Altogether, these findings suggest that BET inhibitor-mediated GDF15 inhibition plays a critical role in enhancing sunitinib sensitivity in melanoma, indicating that BET inhibitors synergize with sunitinib in melanoma.
Effects of bilateral sequential theta-burst stimulation on 5-HT1A receptors in the dorsolateral prefrontal cortex in treatment-resistant depression: a proof-of-concept trial
Authors: Murgaš Matej , Unterholzner Jakob , Stöhrmann Peter , Philippe Cécile , Godbersen Godber M. , Nics Lukas , Reed Murray B. , Vraka Chrysoula , Vanicek Thomas , Wadsak Wolfgang , Kranz Georg S. , Hahn Andreas , Mitterhauser Markus , Hacker Marcus , Kasper Siegfried , Lanzenberger Rupert , Baldinger-Melich Pia 
Published: February 2023

AbstractTheta-burst stimulation (TBS) represents a brain stimulation technique effective for treatment-resistant depression (TRD) as underlined by meta-analyses. While the methodology undergoes constant refinement, bilateral stimulation of the dorsolateral prefrontal cortex (DLPFC) appears promising to restore left DLPFC hypoactivity and right hyperactivity found in depression. The post-synaptic inhibitory serotonin-1A (5-HT1A) receptor, also occurring in the DLPFC, might be involved in this mechanism of action. To test this hypothesis, we performed PET-imaging using the tracer [carbonyl-11C]WAY-100635 including arterial blood sampling before and after a three-week treatment with TBS in 11 TRD patients compared to sham stimulation (n = 8 and n = 3, respectively). Treatment groups were randomly assigned, and TBS protocol consisted of excitatory intermittent TBS to the left and inhibitory continuous TBS to the right DLPFC. A linear mixed model including group, hemisphere, time, and Hamilton Rating Scale for Depression (HAMD) score revealed a 3-way interaction effect of group, time, and HAMD on specific distribution volume (VS) of 5-HT1A receptor. While post-hoc comparisons showed no significant changes of 5-HT1A receptor VS in either group, higher 5-HT1A receptor VS after treatment correlated with greater difference in HAMD (r = −0.62). The results of this proof-of-concept trial hint towards potential effects of TBS on the distribution of the 5-HT1A receptor. Due to the small sample size, all results must, however, be regarded with caution.
Low protein-induced intrauterine growth restriction as a risk factor for schizophrenia phenotype in a rat model: assessing the role of oxidative stress and neuroinflammation interaction
Authors: Allgäuer Larissa , Cabungcal Jan-Harry , Yzydorczyk Catherine , Do Kim Quang , Dwir Daniella 
Published: February 2023

AbstractA large body of evidence suggests that intrauterine growth restriction (IUGR) impedes normal neurodevelopment and predisposes the offspring to cognitive and behavioral deficits later in life. A significantly higher risk rate for schizophrenia (SZ) has been reported in individuals born after IUGR. Oxidative stress and neuroinflammation are both involved in the pathophysiology of SZ, particularly affecting the structural and functional integrity of parvalbumin interneurons (PVI) and their perineuronal nets (PNN). These anomalies have been tightly linked to impaired cognition, as observed in SZ. However, these pathways remain unexplored in models of IUGR. New research has proposed the activation of the MMP9-RAGE pathway to be a cause of persisting damage to PVIs. We hypothesize that IUGR, caused by a maternal protein deficiency during gestation, will induce oxidative stress and neuroinflammation. The activation of these pathways during neurodevelopment may affect the maturation of PVIs and PNNs, leading to long-term consequences in adolescent rats, in analogy to SZ patients. The level of oxidative stress and microglia activation were significantly increased in adolescent IUGR rats at postnatal day (P)35 as compared to control rats. PVI and PNN were decreased in P35 IUGR rats when compared to the control rats. MMP9 protein level and RAGE shedding were also increased, suggesting the involvement of this mechanism in the interaction between oxidative stress and neuroinflammation. We propose that maternal diet is an important factor for proper neurodevelopment of the inhibitory circuitry, and is likely to play a crucial role in determining normal cognition later in life, thus making it a pertinent model for SZ.
LncRNA TINCR impairs the efficacy of immunotherapy against breast cancer by recruiting DNMT1 and downregulating MiR-199a-5p via the STAT1–TINCR-USP20-PD-L1 axis
Authors: Wang Qin , Li Guozheng , Ma Xin , Liu Lei , Liu Jiena , Yin Yanling , Li Hui , Chen Yihai , Zhang Xin , Zhang Lei , Sun Liyang , Ai Jing , Xu Shouping 
Published: February 2023

AbstractAlthough programmed death-ligand 1 (PD-L1) inhibitors have achieved some therapeutic success in breast cancer, their efficacy is limited by low therapeutic response rates, which is closely related to the immune escape of breast cancer cells. Tissue differentiation inducing non-protein coding RNA (TINCR), a long non-coding RNA, as an oncogenic gene associated with the progression of various malignant tumors, including breast cancer; however, the role of TINCR in tumor immunity, especially in breast cancer, remains unclear. We confirmed that TINCR upregulated PD-L1 expression in vivo and in vitro, and promoted the progression of breast cancer. Next, we revealed that TINCR knockdown can significantly improve the therapeutic effect of PD-L1 inhibitors in breast cancer in vivo. Mechanistically, TINCR recruits DNMT1 to promote the methylation of miR-199a-5p loci and inhibit its transcription. Furthermore, in the cytoplasm, TINCR potentially acts as a molecular sponge of miR-199a-5p and upregulates the stability of USP20 mRNA through a competing endogenous RNA (ceRNA) regulatory mechanism, thus promoting PD-L1 expression by decreasing its ubiquitination level. IFN-γ stimulation activates STAT1 by phosphorylation, which migrates into the nucleus to promote TINCR transcription. This is the first study to describe the regulatory role of TINCR in breast cancer tumor immunity, broadening the current paradigm of the functional diversity of TINCR in tumor biology. In addition, our study provides new research directions and potential therapeutic targets for PD-L1 inhibitors in breast cancer.
Reaction profiles for quantum chemistry-computed [3 + 2] cycloaddition reactions
Authors: Stuyver Thijs , Jorner Kjell , Coley Connor W. 
Published: February 2023

AbstractBio-orthogonal click chemistry based on [3 + 2] dipolar cycloadditions has had a profound impact on the field of biochemistry and significant effort has been devoted to identify promising new candidate reactions for this purpose. To gauge whether a prospective reaction could be a suitable bio-orthogonal click reaction, information about both on- and off-target activation and reaction energies is highly valuable. Here, we use an automated workflow, based on the autodE program, to compute over 5000 reaction profiles for [3 + 2] cycloadditions involving both synthetic dipolarophiles and a set of biologically-inspired structural motifs. Based on a succinct benchmarking study, the B3LYP-D3(BJ)/def2-TZVP//B3LYP-D3(BJ)/def2-SVP level of theory was selected for the DFT calculations, and standard conditions and an (aqueous) SMD model were imposed to mimic physiological conditions. We believe that this data, as well as the presented workflow for high-throughput reaction profile computation, will be useful to screen for new bio-orthogonal reactions, as well as for the development of novel machine learning models for the prediction of chemical reactivity more broadly.
Effects of medwakh smoking on salivary metabolomics and its association with altered oral redox homeostasis among youth
Authors: Aghila Rani K. G. , Soares Nelson C. , Rahman Betul , Al-Hroub Hamza M. , Semreen Mohammad H. , Al Kawas Sausan 
Published: February 2023

AbstractThe use of alternative tobacco products, particularly medwakh, has expanded among youth in the Middle East and around the world. The present study is conducted to investigate the biochemical and pathophysiological changes caused by medwakh smoking, and to examine the salivary metabolomics profile of medwakh smokers. Saliva samples were collected from 30 non-smokers and 30 medwakh smokers and subjected to metabolomic analysis by UHPLC-ESI-QTOF-MS. The CRP and Glutathione Peroxidase 1 activity levels in the study samples were quantified by ELISA and the total antioxidant capacity (TAC) by TAC assay kits. Statistical measurements and thorough validation of data obtained from untargeted metabolomics identified 37 uniquely and differentially abundant metabolites in saliva of medwakh smokers. The levels of phthalate, L-sorbose, cytosine, uridine, alpha-hydroxy hippurate, and L-nicotine were noticeably high in medwakh smokers. Likewise, 20 metabolic pathways were differentially altered in medwakh smokers. This study identified a distinctive saliva metabolomics profile in medwakh smokers associated with altered redox homeostasis, metabolic pathways, antioxidant system, and CRP levels. The impact of the altered metabolites in medwakh smokers and their diagnostic utility require further research in large cohorts.
In silico protein engineering shows that novel mutations affecting NAD+ binding sites may improve phosphite dehydrogenase stability and activity
Authors: Baammi Soukayna , Daoud Rachid , El Allali Achraf 
Published: February 2023

AbstractPseudomonas stutzeri phosphite dehydrogenase (PTDH) catalyzes the oxidation of phosphite to phosphate in the presence of NAD, resulting in the formation of NADH. The regeneration of NADH by PTDH is greater than any other enzyme due to the substantial change in the free energy of reaction (G°′ = − 63.3 kJ/mol). Presently, improving the stability of PTDH is for a great importance to ensure an economically viable reaction process to produce phosphite as a byproduct for agronomic applications. The binding site of NAD+ with PTDH includes thirty-four residues; eight of which have been previously mutated and characterized for their roles in catalysis. In the present study, the unexplored twenty-six key residues involved in the binding of NAD+ were subjected to in silico mutagenesis based on the physicochemical properties of the amino acids. The effects of these mutations on the structure, stability, activity, and interaction of PTDH with NAD+ were investigated using molecular docking, molecular dynamics simulations, free energy calculations, and secondary structure analysis. We identified seven novel mutations, A155I, G157I, L217I, P235A, V262I, I293A, and I293L, that reduce the compactness of the protein while improving PTDH stability and binding to NAD+.
Method for 3D atomic structure determination of multi-element nanoparticles with graphene liquid-cell TEM
Authors: Heo Junyoung , Kim Dongjun , Choi Hyesung , Kim Sungin , Chun Hoje , Reboul Cyril F. , Van Cong T. S. , Elmlund Dominika , Choi Soonmi , Kim Kihyun , Park Younggil , Elmlund Hans , Han Byungchan , Park Jungwon 
Published: February 2023

AbstractDetermining the 3D atomic structures of multi-element nanoparticles in their native liquid environment is crucial to understanding their physicochemical properties. Graphene liquid cell (GLC) TEM offers a platform to directly investigate nanoparticles in their solution phase. Moreover, exploiting high-resolution TEM images of single rotating nanoparticles in GLCs, 3D atomic structures of nanoparticles are reconstructed by a method called “Brownian one-particle reconstruction”. We here introduce a 3D atomic structure determination method for multi-element nanoparticle systems. The method, which is based on low-pass filtration and initial 3D model generation customized for different types of multi-element systems, enables reconstruction of high-resolution 3D Coulomb density maps for ordered and disordered multi-element systems and classification of the heteroatom type. Using high-resolution image datasets obtained from TEM simulations of PbSe, CdSe, and FePt nanoparticles that are structurally relaxed with first-principles calculations in the graphene liquid cell, we show that the types and positions of the constituent atoms are precisely determined with root mean square displacement values less than 24 pm. Our study suggests that it is possible to investigate the 3D atomic structures of synthesized multi-element nanoparticles in liquid phase.
Modeling the impact of national and regional lockdowns on the 2020 spring wave of COVID-19 in France
Authors: Roux Jonathan , Massonnaud Clément R. , Colizza Vittoria , Cauchemez Simon , Crépey Pascal 
Published: February 2023

AbstractSeveral countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like “where” and “when” still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increase. However, the public health costs associated with these delays tend to grow with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality, and stress on the healthcare system.
Association between low handgrip strength and obesity with mortality in peritoneal dialysis patients
Authors: Do Jun Young , Kang Seok Hui 
Published: February 2023

AbstractThe association between sarcopenia and obesity in peritoneal dialysis (PD) patients is more complex than that of the general population. The aim of this study was, therefore, to evaluate the association of patient survival with sarcopenia or sarcopenic components and obesity in groups of patients with PD. We retrospectively analyzed a dataset from 199 prevalent PD patients. Measurements including handgrip strength (HGS), appendicular lean mass index, and baseline characteristics, were obtained during the period of study. Patients were divided into four groups according to their HGS and obesity: NH-NO (normal HGS and non-obesity, n = 60), NH-O (normal HGS and obesity, n = 31), LH-NO (low HGS and non-obesity, n = 71), and LH-O (low HGS and obesity, n = 37). The median follow-up interval was 17 months. The Kaplan–Meier curve analysis showed that the LH-O group had the poorest patient survival outcome among the four groups (P < 0.001). The NH-NO group had a better patient survival outcome compared with the LH-NO group. Univariate and multivariate Cox regression analyses showed that the LH-O group had the highest mortality rate compared with the other groups. The NH-NO group had lower mortality compared with the LH-NO group. The present study demonstrated that obesity with low HGS was associated with the greatest mortality rate in groups defined by HGS and obesity.
Prediction model for the compressive strength of green concrete using cement kiln dust and fly ash
Authors: Bakhoum Emad S. , Amir Arsani , Osama Fady , Adel Mohamed 
Published: February 2023

AbstractIntegrating artificial intelligence and green concrete in the construction industry is a challenge that can help to move towards sustainable construction. Therefore, this research aims to predict the compressive strength of green concrete that includes a ratio of cement kiln dust (CKD) and fly ash (FA), then recommend the optimum sustainable mixture design. The artificial neural network (ANN) and multiple linear regression techniques are used to build prediction models and statistics using MATLAB and IBM SPSS software. The input parameters are based on 156 data points of concrete components and compressive strengths that are collected from the literature. The developed models have been trained, validated, and tested for each technique. TOPSIS method is used to assign the optimum mixture design according to three sustainable criteria: compressive strength, carbon dioxide (CO2) emission, and cost. The results of ANN models showed a better prediction of the compressive strength with regression (R) equal to 0.928 and 0.986. The optimum mixture includes CKD 10–20% and FA 0–30%. Predicting the compressive strength of green concrete is a non-destructive approach that has sustainable returns including preservation of natural resources, reduction of greenhouse gas emissions, cost, time, and waste to landfill as well as saving energy.
Vedolizumab is superior to infliximab in biologic naïve patients with ulcerative colitis
Authors: Sablich Renato , Urbano Maria Teresa , Scarpa Marco , Scognamiglio Federico , Paviotti Alberto , Savarino Edoardo 
Published: February 2023

AbstractThere are no prospective, head-to-head, controlled trials comparing the efficacy and safety of Infliximab (IFX) and Vedolizumab (VDZ) for the treatment of moderate-to-severe ulcerative colitis (UC), while only a few real-life retrospective studies have been published so far. We assessed the efficacy of IFX vs. VDZ in two cohorts of biologic-naïve outpatients with moderate-to-severe UC or mild, but refractory, disease. Data were extracted from patients’ files and reviewed. The duration of follow-up (FU) was 52 weeks. The primary endpoint was the clinical remission (CR) at the end of FU. Secondary endpoints were: drug persistency, time to obtain CR, clinical response at the end of the induction phase (IP), steroid-free CR (compared to patients who used steroids at baseline) at the end of FU, need for drug optimization, adverse events (AEs), and normalization of C-reactive protein (CRP). We also analyzed the causes of dropping out (primary non-response), or secondary loss of response (immunogenic or not), for each group. We enrolled 82 patients (50 IFX and 32 VDZ) who met the inclusion criteria. At the end of FU, CR was obtained in 32% of the patients on IFX and 75% on VDZ (p = 0.0003). Drug persistency was superior for VDZ compared to IFX (78% vs. 52%, p = 0.033). Clinical response at the end of induction was reached in 54% and in 81% in the IFX and VDZ group, respectively (p = 0.014). Steroid-free clinical remission at the end of FU was 62% and 94% in the IFX vs. VDZ group, respectively (p = 0.036). The need for drug optimization was higher for VDZ than for IFX (28% vs. 57%, p = 0.009), while the time to obtain CR, the incidence of AEs, mean duration of FU, and rate of CRP normalization at the end of IP were comparable between the two groups. There was a prevalence of patients dropping out because of primary non-response in IFX group (p = 0.027), while the incidence of secondary loss of response was similar in the two groups. At the multivariate analysis, CRP and Partial Mayo Score (PMS) at T0 did not correlate with CR at the end of FU in both groups. In this retrospective, real world data study in biologic-naïve patients, VDZ was superior to IFX in CR, clinical response rate at the end of IP, drug persistency, steroid-free remission, and need for optimization at the end of FU.
The effect of obesity on chronic diseases in USA: a flexible copula approach
Authors: Dettoni Robinson , Bahamondes Cliff , Yevenes Carlos , Cespedes Cristian , Espinosa Javier 
Published: February 2023

AbstractWe analyze the effect of obesity on the incidence of hypertension, hyperlipidemia and diabetes in USA using a health production theoretical framework along with a bivariate flexible semi-parametric recursive copula model that account for endogeneity. In this approach, the effects of control variables are flexibly determined using additive predictors that allow for a variety of effects. Our findings suggest that there exist a positive and significant effect of obesity on the prevalence of all chronic diseases examined. In particular, after endogeneity is accounted for, the probability of having hypertension, hyperlipidemia and diabetes for obese individuals are, respectively, 35%, 28% and 11% higher than those under the obesity threshold. These findings suggest that lowering obesity rates could lead to significant reductions in the morbidity and mortality associated with these diseases.