bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary analysis of actinins(ACTN) gene family for positive selective sites by finding the dn/ds (ω) value
Authors: Din Ihsan Ud , Sun Li , Hu Lina 
Published: August 2023

Identifying positively selected amino acid sites is an important approach for making a conclusion about the function of proteins; an amino acid site that is undergoing positive selection is likely to play a key role in the function of the protein. Here, we used codon-based substitution models and maximum-likelihood (ML) methods to identify positively selected sites that are likely to influence the cohesiveness and mechanics of the cytoskeleton by cross-linking actinins filaments and other cytoskeleton components to create a scaffold that imparts stability and forms a bridge between the cytoskeleton and signaling pathways. We use MEGA 7 and PAML for polygenetic Analysis and positive selective Sites. Alpha-actinins from skeletal muscle as a protein factor promoting the super precipitation of actomyosin and inducing the gelation of F-actin solutions. The protein is located in Z-bands of sarcomeres in skeletal and cardiac muscles as well as near the fascia adherents of intercalated discs in cardiac muscle. In smooth muscle, it exists in cytoplasmic dense bodies and membrane-associated dense plaques. We used PAMLX to find out specific sites in these DNA sequences. These results show the location and identification of positively selected sites in the ACTININS gene family. ACTN1, ACTN2, ACTN3 and ACTN4 had (248G,250L), (234I,236N ,238P, 239K, 252F, 260E, 261Q, 314Q, 590N, 607L, 869S), (NO) and (248G, 250L) positive selective sites respectively. The aims of our work are the prediction of these sites to find the specific location of these sites in 3D structure and to replace it with suitable amino acids for the cure of obesity, muscles, cancer, and other chronic diseases
Gpr18 agonist dampens inflammation, enhances myogenesis, and restores muscle function in models of Duchenne muscular dystrophy
Authors: Dort Junio , Orfi Zakaria , Fiscaletti Melissa , Campeau Philippe M. , Dumont Nicolas A. 
Published: August 2023

Introduction: Muscle wasting in Duchenne Muscular Dystrophy is caused by myofiber fragility and poor regeneration that lead to chronic inflammation and muscle replacement by fibrofatty tissue. Our recent findings demonstrated that Resolvin-D2, a bioactive lipid derived from omega-3 fatty acids, has the capacity to dampen inflammation and stimulate muscle regeneration to alleviate disease progression. This therapeutic avenue has many advantages compared to glucocorticoids, the current gold-standard treatment for Duchenne Muscular Dystrophy. However, the use of bioactive lipids as therapeutic drugs also faces many technical challenges such as their instability and poor oral bioavailability.Methods: Here, we explored the potential of PSB-KD107, a synthetic agonist of the resolvin-D2 receptor Gpr18, as a therapeutic alternative for Duchenne Muscular Dystrophy.Results and discussion: We showed that PSB-KD107 can stimulate the myogenic capacity of patient iPSC-derived myoblasts in vitro. RNAseq analysis revealed an enrichment in biological processes related to fatty acid metabolism, lipid biosynthesis, small molecule biosynthesis, and steroid-related processes in PSB-KD107-treated mdx myoblasts, as well as signaling pathways such as Peroxisome proliferator-activated receptors, AMP-activated protein kinase, mammalian target of rapamycin, and sphingolipid signaling pathways. In vivo, the treatment of dystrophic mdx mice with PSB-KD107 resulted in reduced inflammation, enhanced myogenesis, and improved muscle function. The positive impact of PSB-KD107 on muscle function is similar to the one of Resolvin-D2. Overall, our findings provide a proof-of concept that synthetic analogs of bioactive lipid receptors hold therapeutic potential for the treatment of Duchenne Muscular Dystrophy.
Multicomponent synthesis and photophysical study of novel α,β-unsaturated carbonyl depsipeptides and peptoids
Authors: González Ricelia , Murillo-López Juliana , Rabanal-León Walter , Prent-Peñaloza Luis , Concepción Odette , Olivares Pedro , Duarte Yorley , de la Torre Alexander F. , Gutiérrez Margarita , Caballero Julio 
Published: August 2023

Multicomponent reactions were performed to develop novel α,β-unsaturated carbonyl depsipeptides and peptoids incorporating various chromophores such as cinnamic, coumarin, and quinolines. Thus, through the Passerini and Ugi multicomponent reactions (P-3CR and U-4CR), we obtained thirteen depsipeptides and peptoids in moderate to high yield following the established protocol and fundamentally varying the electron-rich carboxylic acid as reactants. UV/Vis spectroscopy was utilized to study the photophysical properties of the newly synthesized compounds. Differences between the carbonyl-substituted chromophores cause differences in electron delocalization that can be captured in the spectra. The near UV regions of all the compounds exhibited strong absorption bands. Compounds P2, P5, U2, U5, and U7 displayed absorption bands in the range of 250–350 nm, absorbing radiation in this broad region of the electromagnetic spectrum. A photostability study for U5 showed that its molecular structure does not change after exposure to UV radiation. Fluorescence analysis showed an incipient emission of U5, while U6 showed blue fluorescence under UV radiation. The photophysical properties and electronic structure were also determined by TD-DFT theoretical study.
Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features
Authors: Liu Xing-Li , Wang Guan-Zhong , Rui Mao-Ping , Fan Dong , Zhang Jie , Zhu Zheng-Hua , Perez Rosario , Wang Tony , Yang Li-Chuan , Lyu Liang , Zheng Jie , Wang Gang 
Published: August 2023

IntroductionThe availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.MethodsThe NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF &lt; 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained.ResultsNo LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p &lt; 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p &lt; 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p &lt; 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups.ConclusionOur preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.
High-resolution record of temporal change in organic matter burial over the past ∼8,600 years on the northwestern continental slope of the South China Sea
Authors: Tong Gang , Chen Lilei , Zhang Guangxu , Liu Jian , Chen Bin , Xu Gang , Liu Ming , An Yuhui , Chen Duanxin 
Published: August 2023

Sedimentary organic matter (SOM) on continental slopes in marine regions can sensitively record climatic and environmental changes. In this study, total organic carbon content (TOC), total nitrogen content (TN), and their stable isotope compositions (δ13C and δ15N) for sediments of core G02 were investigated (at ∼24.2-year resolution) to reveal the temporal variations in organic matter sources and the main controls on the sources and distribution of buried organic matter on the northwestern continental slope of the South China Sea over the last ∼8600 years. Results of a δ13C binary mixing model reveal that ∼82.3 ± 3% of SOM is derived from marine autochthonous sources. We suggest that the carbon and nitrogen contents and compositions of SOM are governed by distinct factors. The more positive δ15N values before the Pulleniatina Minimum Event occurrence are ascribed to stronger subsurface water intrusion by the Kuroshio Current, which led to enhanced subsurface denitrification and in turn counteracted the effect of mixing with surface water caused by the East Asian winter monsoon. Sedimentary δ13C values show a fluctuant decrease during ca. 8.6–3.0 cal kyr BP and a conspicuous increase during ca. 3.0–1.4 cal kyr BP. These changes are attributed to the decrease of marine productivity induced by the continuous weakening East Asian monsoon effect and the decrease of terrigenous organic carbon input induced by the weakened Indian summer monsoon precipitation, respectively. Since ca. 1.4 cal kyr BP, human activities have become the dominant factor in controlling the production and distribution of organic carbon. The results provide an important basis for understanding of source-sink processes of organic matter and the factors influencing these processes on continental slopes in low-latitude marginal seas.
Effects of ovarian stimulation protocols on outcomes of assisted reproductive technology in adenomyosis women: a retrospective cohort study
Authors: Ge Li , Li Yexing , Guan Shengnan , Cui Linlin , Chen Zi-Jiang 
Published: August 2023

ObjectiveTo evaluate the effects of different ovarian stimulation protocols on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in infertile women with adenomyosis.MethodsWe carried out a retrospective cohort study among infertile women with adenomyosis receiving IVF/ICSI treatment, including 257 fresh embryo transfer (ET) cycles and 305 frozen embryo transfer (FET) cycles. In fresh ET cycles, ultra-long, long, short, and antagonist protocols were adopted. In FET cycles, patients received long-acting GnRH agonist (GnRHa) pretreatment or not. The primary outcome was clinical pregnancy rate (CPR), and the secondary outcomes included implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR).ResultsIn fresh ET cycles, compared with ultra-long and long protocols, IR (49.7%, 52.1% versus 28.2%, P=0.001) and CPR (64.3%, 57.4% versus 35.6%, P=0.004) significantly decreased in the short protocol. Similarly, compared with ultra-long and long protocols, a decreased inclination of IR (49.7%, 52.1% versus 33.3%) and CPR (57.4%, 64.3% versus 38.2%) existed in the antagonist protocol, although no statistical significance was detected because of strict P adjustment of Bonferroni method (Padj=0.008). Compared with long protocol, LBR in short protocol decreased obviously (48.2% versus 20.3%, P&lt;0.001). In FET cycles, no matter which origin of embryos, there were no statistical differences in IR, CPR, and LBR. For women ≥35 years receiving fresh ET, CPR was higher in ultra-long and long protocols (52.1%, 50.0% versus 20.0%, 27.5%, P=0.031) compared to antagonist and short protocols. For women ≥35 years receiving FET, compared with ultra-long and antagonist protocols, cycles with embryos originating from long and short protocols had higher proportions of long-acting GnRHa pretreatment (30.4%,30.00 versus 63.9%, 51.4%, P=0.009). IR (61.1%, 48.6% versus 32.6%, 25.0%, P=0.020) and CPR (58.3%, 48.6% versus 30.4%, 25.0%, P=0.024) in long and short protocols were higher than rates of ultra-long and antagonist protocols, but no statistical differences were supported because of strict Bonferroni method (Padj=0.008).ConclusionIn infertile women with adenomyosis, if a fresh embryo was planned for transfer, an ultra-long or long protocol might be beneficial. If antagonist and short protocols were used, whole embryos frozen followed by FET was recommended. In FET cycles, embryos derived from different protocols had no impact on pregnancy outcomes.
Metabolic signature and proteasome activity controls synovial migration of CDC42hiCD14+ cells in rheumatoid arthritis
Authors: Malmhäll-Bah Eric , Andersson Karin M.E. , Erlandsson Malin C. , Silfverswärd Sofia T. , Pullerits Rille , Bokarewa Maria I. 
Published: August 2023

ObjectiveActivation of Rho-GTPases in macrophages causes inflammation and severe arthritis in mice. In this study, we explore if Rho-GTPases define the joint destination of pathogenic leukocytes, the mechanism by which they perpetuate rheumatoid arthritis (RA), and how JAK inhibition mitigates these effects.MethodsCD14+ cells of 136 RA patients were characterized by RNA sequencing and cytokine measurement to identify biological processes and transcriptional regulators specific for CDC42hiCD14+ cells, which were summarized in a metabolic signature (MetSig). The effect of hypoxia and IFN-γ signaling on the metabolic signature of CD14+ cells was assessed experimentally. To investigate its connection with joint inflammation, the signature was translated into the single-cell characteristics of CDC42hi synovial tissue macrophages. The sensitivity of MetSig to the RA disease activity and the treatment effect were assessed experimentally and clinically.ResultsCDC42hiCD14+ cells carried MetSig of genes functional in the oxidative phosphorylation and proteasome-dependent cell remodeling, which correlated with the cytokine-rich migratory phenotype and antigen-presenting capacity of these cells. Integration of CDC42hiCD14+ and synovial macrophages marked with MetSig revealed the important role of the interferon-rich environment and immunoproteasome expression in the homeostasis of these pathogenic macrophages. The CDC42hiCD14+ cells were targeted by JAK inhibitors and responded with the downregulation of immunoproteasome and MHC-II molecules, which disintegrated the immunological synapse, reduced cytokine production, and alleviated arthritis.ConclusionThis study shows that the CDC42-related MetSig identifies the antigen-presenting CD14+ cells that migrate to joints to coordinate autoimmunity. The accumulation of CDC42hiCD14+ cells discloses patients perceptive to the JAKi treatment.
Association between gestational levels of toxic metals and essential elements and cerebral palsy in children
Authors: Weyde Kjell Vegard F. , Winterton Adriano , Surén Pål , Andersen Guro L. , Vik Torstein , Biele Guido , Knutsen Helle K. , Thomsen Cathrine , Meltzer Helle M. , Skogheim Thea S. , Engel Stephanie M. , Aase Heidi , Villanger Gro D. 
Published: August 2023

IntroductionCerebral palsy (CP) is the most common motor disability in childhood, but its causes are only partly known. Early-life exposure to toxic metals and inadequate or excess amounts of essential elements can adversely affect brain and nervous system development. However, little is still known about these as perinatal risk factors for CP. This study aims to investigate the associations between second trimester maternal blood levels of toxic metals, essential elements, and mixtures thereof, with CP diagnoses in children.MethodsIn a large, population-based prospective birth cohort (The Norwegian Mother, Father, and Child Cohort Study), children with CP diagnoses were identified through The Norwegian Patient Registry and Cerebral Palsy Registry of Norway. One hundred forty-four children with CP and 1,082 controls were included. The relationship between maternal blood concentrations of five toxic metals and six essential elements and CP diagnoses were investigated using mixture approaches: elastic net with stability selection to identify important metals/elements in the mixture in relation to CP; then logistic regressions of the selected metals/elements to estimate odds ratio (OR) of CP and two-way interactions among metals/elements and with child sex and maternal education. Finally, the joint effects of the mixtures on CP diagnoses were estimated using quantile-based g-computation analyses.ResultsThe essential elements manganese and copper, as well as the toxic metal Hg, were the most important in relation to CP. Elevated maternal levels of copper (OR = 1.40) and manganese (OR = 1.20) were associated with increased risk of CP, while Hg levels were, counterintuitively, inversely related to CP. Metal/element interactions that were associated with CP were observed, and that sex and maternal education influenced the relationships between metals/elements and CP. In the joint mixture approach no significant association between the mixture of metals/elements and CP (OR = 1.00, 95% CI = [0.67, 1.50]) was identified.ConclusionUsing mixture approaches, elevated levels of copper and manganese measured in maternal blood during the second trimester could be related to increased risk of CP in children. The inverse associations between maternal Hg and CP could reflect Hg as a marker of maternal fish intake and thus nutrients beneficial for foetal brain development.
The Toronto Concussion Study: a prospective investigation of characteristics in a cohort of adults from the general population seeking care following acute concussion, 2016–2020
Authors: Comper Paul , Foster Evan , Chandra Tharshini , Langer Laura , Wiseman-Hakes Catherine , Mochizuki George , Ruttan Lesley , Lawrence David W. , Inness Elizabeth L. , Gladstone Jonathan , Saverino Cristina , Tam Alan , Kam Alice , Al-Rawi Firas , Bayley Mark Theodore 
Published: August 2023

PurposeThere is limited research regarding the characteristics of those from the general population who seek care following acute concussion.MethodsTo address this gap, a large cohort of 473 adults diagnosed with an acute concussion (female participants = 287; male participants = 186) was followed using objective measures prospectively over 16 weeks beginning at a mean of 5.1 days post-injury.ResultsFalls were the most common mechanism of injury (MOI) (n = 137, 29.0%), followed by sports-related recreation (n = 119, 25.2%). Male participants were more likely to be injured playing recreational sports or in a violence-related incident; female participants were more likely to be injured by falling. Post-traumatic amnesia (PTA) was reported by 80 participants (16.9 %), and loss of consciousness (LOC) was reported by 110 (23.3%). In total, 54 participants (11.4%) reported both PTA and LOC. Male participants had significantly higher rates of PTA and LOC after their injury compared to their female counterparts. Higher initial symptom burden was associated with a longer duration of recovery for both male and female participants. Female participants had more symptoms and higher severity of symptoms at presentation compared to male participants. Female participants were identified to have a longer recovery duration, with a mean survival time of 6.50 weeks compared to 5.45 weeks in male participants (p &lt; 0.0001). A relatively high proportion of female and male participants in this study reported premorbid diagnoses of depression and anxiety compared to general population characteristics.ConclusionAlthough premorbid diagnoses of depression and/or anxiety were associated with higher symptom burden at the initial visit, the duration of symptoms was not directly associated with a pre-injury history of psychological/psychiatric disturbance. This cohort of adults, from the general population, seeking care for their acute concussion attained clinical and functional recovery over a period of 4–12 weeks.
Functional electrical stimulation therapy controlled by a P300-based brain–computer interface, as a therapeutic alternative for upper limb motor function recovery in chronic post-stroke patients. A non-randomized pilot study
Authors: Ramirez-Nava Ana G. , Mercado-Gutierrez Jorge A. , Quinzaños-Fresnedo Jimena , Toledo-Peral Cinthya , Vega-Martinez Gabriel , Gutierrez Mario Ibrahin , Pacheco-Gallegos María del Refugio , Hernández-Arenas Claudia , Gutiérrez-Martínez Josefina 
Published: August 2023

IntroductionUp to 80% of post-stroke patients present upper-limb motor impairment (ULMI), causing functional limitations in daily activities and loss of independence. UMLI is seldom fully recovered after stroke when using conventional therapeutic approaches. Functional Electrical Stimulation Therapy (FEST) controlled by Brain–Computer Interface (BCI) is an alternative that may induce neuroplastic changes, even in chronic post-stroke patients. The purpose of this work was to evaluate the effects of a P300-based BCI-controlled FEST intervention, for ULMI recovery of chronic post-stroke patients.MethodsA non-randomized pilot study was conducted, including 14 patients divided into 2 groups: BCI-FEST, and Conventional Therapy. Assessments of Upper limb functionality with Action Research Arm Test (ARAT), performance impairment with Fugl–Meyer assessment (FMA), Functional Independence Measure (FIM) and spasticity through Modified Ashworth Scale (MAS) were performed at baseline and after carrying out 20 therapy sessions, and the obtained scores compared using Chi square and Mann–Whitney U statistical tests (𝛼 = 0.05).ResultsAfter training, we found statistically significant differences between groups for FMA (p = 0.012), ARAT (p &lt; 0.001), and FIM (p = 0.025) scales.DiscussionIt has been shown that FEST controlled by a P300-based BCI, may be more effective than conventional therapy to improve ULMI after stroke, regardless of chronicity.ConclusionThe results of the proposed BCI-FEST intervention are promising, even for the most chronic post-stroke patients often relegated from novel interventions, whose expected recovery with conventional therapy is very low. It is necessary to carry out a randomized controlled trial in the future with a larger sample of patients.