bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretreatment of human retinal pigment epithelial cells with sterculic acid forestalls fenretinide-induced apoptosis
Authors: William Samuel , Duncan Todd , Redmond T. Michael 
Published: December 2022

AbstractThe ratio of saturated to monounsaturated fatty acids, thought to play a critical role in many cellular functions, is regulated by stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids. Previously, we observed a decrease in both SCD protein and enzymatic activity in apoptosis induced by fenretinide, a synthetic analog of retinoic acid, in the human retinal pigment epithelial (RPE) cell line ARPE-19. Here, we investigated the effect of pretreating ARPE-19 with sterculic acid, a cyclopropenoic fatty acid inhibitor of SCD, on preventing fenretinide-induced apoptosis, given the role of SCD in cell proliferation and apoptosis. We show that sterculic acid pretreatment prevents the effects of fenretinide-induced apoptosis shown by changes in cell morphology, viability, and caspase-3 activation. Analysis of endoplasmic reticulum (ER)-associated proteins shows that sterculic acid pretreatment reduced the fenretinide-induced upregulation of heme oxygenase-1, ATF3 and GADD153 expression that are in response to reactive oxygen species (ROS) generation. Sterculic acid is as effective as allopurinol in inhibition of xanthine oxidase (XDH), and this may play a role in reducing the potential role of XDH in fenretinide-induced ROS generation. Sterculic acid pretreatment also results in a reduction in SOD2 mRNA expression. Dihydroceramide accumulation, compared to ceramide, and ROS generation indicate that a ceramide-independent pathway mediates fenretinide-induced apoptosis, and ROS mediation is borne out by activation of the NF-κBp50 and NF-κBp65 downstream signaling cascade. Its prevention by sterculic acid pretreatment further indicates the latter’s antioxidant/anti-inflammatory effect. Taken together, our results suggest that sterculic acid pretreatment can mitigate ROS-mediated fenretinide-induced apoptosis. Thus, sterculic acid may serve as a potential antioxidant and therapeutic agent. These effects may be independent of its effects on SCD activity.
Effects of age and sex on vasomotor activity and baroreflex sensitivity during the sleep–wake cycle
Authors: Yeh Chia-Hsin , Kuo Terry B. J. , Li Jia-Yi , Kuo Kuan-Liang , Chern Chang-Ming , Yang Cheryl C. H. , Huang Hsin-Yi 
Published: December 2022

AbstractCardiovascular function is related to age, sex, and state of consciousness. We hypothesized that cardiovagal baroreflex sensitivity (BRS) demonstrates different patterns in both sexes before and after 50 years of age and that these patterns are associated with patterned changes during the sleep–wake cycle. We recruited 67 healthy participants (aged 20–79 years; 41 women) and divided them into four age groups: 20–29, 30–49, 50–69, and 70–79 years. All the participants underwent polysomnography and blood pressure measurements. For each participant, we used the average of the arterial pressure variability, heart rate variability (HRV), and BRS parameters during the sleep–wake stages. BRS and HRV parameters were significantly negatively correlated with age. The BRS indexes were significantly lower in the participants aged ≥ 50 years than in those aged < 50 years, and these age-related declines were more apparent during non-rapid eye movement sleep than during wakefulness. Only BRS demonstrated a significantly negative correlation with age in participants ≥ 50 years old. Women exhibited a stronger association than men between BRS and age and an earlier decline in BRS. Changes in BRS varied with age, sex, and consciousness state, each demonstrating a specific pattern. The age of 50 years appeared to be a crucial turning point for sexual dimorphism in BRS. Baroreflex modulation of the cardiovascular system during sleep sensitively delineated the age- and sex-dependent BRS patterns, highlighting the clinical importance of our results. Our findings may aid in screening for neurocardiac abnormalities in apparently healthy individuals.
Modified moving average methodology applied to the treadmill stress testing analysis of microvolt T-wave alternans
Authors: Pereira Filho Horacio Gomes , Samesima Nelson , Madaloso Bruna Affonso , de Oliveira Tobias Nancy Maria Martins , Facin Mirella , Pastore Carlos Alberto 
Published: December 2022

AbstractSudden cardiac death is impactful. There has been an increase in the search for tools capable of identifying individuals who are most susceptible, such as the microvolt T-wave alternans. This study aims to analyze the applicability of the modified moving average methodology to obtain the microvolt T-wave alternans using treadmill specific protocols. Medical records of patients during the period August 2006–December 2014 were retrospectively analyzed. Five hundred and thirty nine exams were then included, divided into groups according to the protocol and updating factor used: Ellestad factor 8 or 32, Naughton factor 8 or 32. The topics for analysis were the alternans behavior, noise and confirmation according to the groups of leads analyzed (frontal, transversal and orthogonal planes). The greater microvolt T-wave alternans was found during the stress phase in most of the tests. Group Naughton 8 presented lower noise in this phase for the transverse and orthogonal planes (p = 0.0082 and p < 0.0001), with greater confirmation of frontal and orthogonal planes in comparison with group Ellestad 8 (p = 0.0002 and 0.0008). The results indicate the viability of simultaneous performance of the stress test and measurement of the T wave alternans with Naughton protocol with 1/8 updating factor.
Rapid yield optimization of miniaturized microwave passives by response features and variable-fidelity EM simulations
Authors: Pietrenko-Dabrowska Anna , Koziel Slawomir 
Published: December 2022

AbstractThe operation of high-frequency devices, including microwave passive components, can be impaired by fabrication tolerances but also incomplete knowledge concerning operating conditions (temperature, input power levels) and material parameters (e.g., substrate permittivity). Although the accuracy of manufacturing processes is always limited, the effects of parameter deviations can be accounted for in advance at the design phase through optimization of suitably selected statistical performance figures. Perhaps the most popular one is the yield, which provides a straightforward assessment of the likelihood of fulfilling performance conditions imposed upon the system given the assumed deviations of designable parameters. The latter are typically quantified by means of probability distributions pertinent to the fabrication process. The fundamental obstacle of the yield-driven design is its high computational cost. The primary mitigation approach nowadays is the employment of surrogate modeling methods. Yet, a construction of reliable metamodels becomes problematic for systems featuring a large number of degrees of freedom. Our work proposes a technique for fast yield optimization of microwave passives, which relies on response feature technology as well as variable-fidelity simulation models. Utilization of response features enables efficient handling of issues related to the system response nonlinearities. Meanwhile, the incorporation of variable-resolution simulations allows for accelerating the yield estimation process, which translates into remarkably low overall cost of the optimizing the yield. Our approach is verified with the use of three microstrip couplers. Comprehensive benchmarking demonstrates its superiority in terms of computational efficiency over the state-of-the-art algorithms, whereas reliability is corroborated by electromagnetic-driven Monte Carlo simulations.
Reaction of the carbonate Sibillini Mountains Basal aquifer (Central Italy) to the extensional 2016–2017 seismic sequence
Authors: Cambi Costanza , Mirabella Francesco , Petitta Marco , Banzato Francesca , Beddini Giulio , Cardellini Carlo , Fronzi Davide , Mastrorillo Lucia , Tazioli Alberto , Valigi Daniela 
Published: December 2022

AbstractHydrogeological perturbations in response to earthquakes are widely described worldwide. In carbonate aquifers, a post-seismic discharge increase is often attributed to an increase of bulk permeability due to co-seismic fracturing and the attention on the role of faults to explain the diversion of groundwater is increasing. We focus on the reaction of carbonate hydrogeological basins to extensional seismicity, taking as an example the effects of the Central Italy 2016–2017 seismic sequence, on the Basal aquifer of the Sibillini Mountains area. Geo-structural, seismological and ground deformation data were collected and merged with artificial tracer tests results and with a 4-years discharge and geochemical monitoring campaign. The main NNW-directed groundwater flow was diverted to the west and a discharge deficit was observed at the foot-wall of the activated fault system with a relevant discharge increase, accompanied by geochemical variations, at the fault system hanging-wall. The observed variations are consistent with the combined action of a permeability increase along the activated fault systems, which modified the predominant pre-seismic along-strike regional flow, and with hydraulic conductivity increase due to fracturing, determining a fast aquifers emptying. We show that the prevailing mechanism depends on the aquifer systems position with respect to the activated faults.
Electrostatic regulation of the cis- and trans-membrane interactions of synaptotagmin-1
Authors: Ali Moussa Houda Yasmine , Park Yongsoo 
Published: December 2022

AbstractSynaptotagmin-1 is a vesicular protein and Ca2+ sensor for Ca2+-dependent exocytosis. Ca2+ induces synaptotagmin-1 binding to its own vesicle membrane, called the cis-interaction, thus preventing the trans-interaction of synaptotagmin-1 to the plasma membrane. However, the electrostatic regulation of the cis- and trans-membrane interaction of synaptotagmin-1 was poorly understood in different Ca2+-buffering conditions. Here we provide an assay to monitor the cis- and trans-membrane interactions of synaptotagmin-1 by using native purified vesicles and the plasma membrane-mimicking liposomes (PM-liposomes). Both ATP and EGTA similarly reverse the cis-membrane interaction of synaptotagmin-1 in free [Ca2+] of 10–100 μM. High PIP2 concentrations in the PM-liposomes reduce the Hill coefficient of vesicle fusion and synaptotagmin-1 membrane binding; this observation suggests that local PIP2 concentrations control the Ca2+-cooperativity of synaptotagmin-1. Our data provide evidence that Ca2+ chelators, including EGTA and polyphosphate anions such as ATP, ADP, and AMP, electrostatically reverse the cis-interaction of synaptotagmin-1.
Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma
Authors: Rattanasinchai Chotirat , Navasumrit Panida , Ruchirawat Mathuros 
Published: December 2022

AbstractIntrahepatic cholangiocarcinoma (iCCA) arises along the peripheral bile ducts and is often accompanied by a tumor microenvironment (TME) high in extracellular matrices (ECMs). In this study, we aimed to evaluate whether an ECM-rich TME favors iCCA progression. We identified ITGA2, which encodes collagen-binding integrin α2, to be differentially-expressed in iCCA tumors compared with adjacent normal tissues. Elevated ITGA2 is also positively-correlated with its ligand, collagen type I. Increased ITGA2 expression and its role in collagen type I binding was validated in vitro using four iCCA cell lines, compared with a non-cancerous, cholangiocyte cell line. Robust interaction of iCCA cells with collagen type I was abolished by either ITGA2 depletion or integrin α2β1-selective inhibitor treatment. In a phenotypic study, collagen type I significantly enhances clonogenic growth of HuCCA-1 and HuCCT-1 cells by three and sixfold, respectively. Inhibition of integrin α2 expression or its activity significantly blocks collagen type I-induced colony growth in both cell lines. Taken together, our data provide mechanistic evidence that collagen type I promotes growth of iCCA colonies through integrin α2 suggesting that the collagen type I—integrin α2 axis could be a promising target for cancer prevention and a therapeutic opportunity for this cancer.
Executive function during exercise is diminished by prolonged cognitive effort in men
Authors: Tsukamoto Hayato , Dora Kento , Stacey Benjamin S. , Tsumura Hibiki , Murakami Yoshino , Marley Christopher J. , Bailey Damian M. , Hashimoto Takeshi 
Published: December 2022

AbstractThe speed and accuracy of decision-making (i.e., executive function (EF) domains) is an integral factor in many sports. At rest, prolonged cognitive load (pCL) impairs reaction time (RT). In contrast, exercise improves RT and EF. We hypothesized that RT and EF during exercise would be diminished by prolonged ‘dual tasking’ as a consequence of pCL. To test the hypothesis, twenty healthy male participants performed four conditions [resting control (Rest), pCL only (pCLRest), exercise only (EX), and pCL + exercise (pCLEX)] in a randomized-crossover design. Both exercise conditions utilized a 50-min cycling exercise protocol (60% VO2 peak) and the pCL was achieved via a 50-min colour-word Stroop task (CWST). Compared with Rest, pCLRest caused a slowed CWST RT (P < 0.05) and a large SD (i.e., intraindividual variability) of CWST RT (P < 0.01). Similarly, compared with EX, the slowed CWST RT (P < 0.05) and large SD of CWST RT (P < 0.01) were also observed in pCLEX. Whereas the reverse-Stroop interference was not affected in pCLRest (P = 0.46), it was larger (i.e., declined EF) in pCLEX than EX condition (P < 0.05). These observations provide evidence that the effort of pCL impairs RT and EF even during exercise.
Microbial rewilding in the gut microbiomes of captive ring-tailed lemurs (Lemur catta) in Madagascar
Authors: Bornbusch Sally L. , Clarke Tara A. , Hobilalaina Sylvia , Reseva Honore Soatata , LaFleur Marni , Drea Christine M. 
Published: December 2022

AbstractMicrobial rewilding, whereby exposure to naturalistic environments can modulate or augment gut microbiomes and improve host-microbe symbiosis, is being harnessed as an innovative approach to human health, one that may also have significant value to animal care and conservation. To test for microbial rewilding in animal microbiomes, we used a unique population of wild-born ring-tailed lemurs (Lemur catta) that were initially held as illegal pets in unnatural settings and, subsequently, relocated to a rescue center in Madagascar where they live in naturalistic environments. Using amplicon and shotgun metagenomic sequencing of lemur and environmental microbiomes, we found multiple lines of evidence for microbial rewilding in lemurs that were transitioned from unnatural to naturalistic environments: A lemur’s duration of exposure to naturalistic settings significantly correlated with (a) increased compositional similarly to the gut communities of wild lemurs, (b) decreased proportions of antibiotic resistance genes that were likely acquired via human contact during pethood, and (c) greater covariation with soil microbiomes from natural habitats. Beyond the inherent psychosocial value of naturalistic environments, we find that actions, such as providing appropriate diets, minimizing contact with humans, and increasing exposure to natural environmental consortia, may assist in maximizing host-microbe symbiosis in animals under human care.
Climate influences the genetic structure and niche differentiation among populations of the olive field mouse Abrothrix olivacea (Cricetidae: Abrotrichini)
Authors: Quiroga-Carmona Marcial , D’Elía Guillermo 
Published: December 2022

AbstractEven when environmental variation over time and space is commonly considered as an important driver of population divergence, few evaluations of intraspecific genetic variation explicitly assess whether observed structure has been caused by or is correlated with landscape heterogeneity. Several phylogeographic studies have characterized the mitochondrial diversity ofAbrothrix olivacea, but none has incorporated landscape genetics analyses and ecological niche modeling, leaving a gap in the understanding of the species evolutionary history. Here, these aspects were addressed based on 186 single nucleotide polymorphisms, extracted from sequences of 801 bp of Cytb gene, gathered from 416 individuals collected at 103 localities in Argentina and Chile. Employing multivariate statistical analyses (gPCA, Mantel and Partial Mantel Tests, Procrustes Analysis, and RDA), associations between genetic differences and geographic and climatic distances were evaluated. Presence data was employed to estimate the potential geographic distribution of this species during historical and contemporary climatic scenarios, and to address differences among the climatic niches of their main mitochondrial lineages. The significant influence of landscape features in structuring mitochondrial variability was evidenced at different spatial scales, as well as the role of past climatic dynamics in driving geographic range shifts, mostly associated to Quaternary glaciations. Overall, these results suggest that throughout geographic range gene flow is unevenly influenced by climatic dissimilarity and the geographic distancing, and that studied lineages do not exhibit distributional signals of climatic niche conservatism. Additionally, genetic differentiation occurred by more complex evolutionary processes than mere disruption of gene flow or drift.
Develop an efficient and specific AAV-based labeling system for Muller glia in mice
Authors: Gao Yanxia , Fang Kailun , Yan Zixiang , Zhang Haiwei , Geng Guannan , Wu Weiwei , Xu Ding , Zhang Heng , Zhong Na , Wang Qifang , Cai Minqing , Zuo Erwei , Yang Hui 
Published: December 2022

AbstractReprogramming Müller glia (MG) into functional cells is considered a promising therapeutic strategy to treat ocular diseases and vision loss. However, current AAV-based system for MG-tracing was reported to have high leakage in recent studies. Here, we focused on reducing the leakage of AAV-based labeling systems and found that different AAV serotypes showed a range of efficiency and specificity in labeling MG, leading us to optimize a human GFAP-Cre reporter system packaged in the AAV9 serotype with the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) removed. The leakage ratio of the AAV9-hGFAP-Cre-ΔWPRE decreased by an approximate 40-fold compared with the AAV9-hGFAP-Cre-WPRE labeling system. In addition, we validated the specificity of the AAV-ΔWPRE system for tracing MG reprogramming under Ptbp1-suppression and observed strict non-MG-conversion, similar to previous studies using genetic lineage tracking mouse models. Thus, the AAV9-hGFAP-Cre-ΔWPRE system showed high efficiency and specificity for MG labeling, providing a promising tool for tracing cell fate in vivo.
Phase Ib/II study of nivolumab combined with palliative radiation therapy for bone metastasis in patients with HER2-negative metastatic breast cancer
Authors: Takada Masahiro , Yoshimura Michio , Kotake Takeshi , Kawaguchi Kosuke , Uozumi Ryuji , Kataoka Masako , Kato Hironori , Yoshibayashi Hiroshi , Suwa Hirofumi , Tsuji Wakako , Yamashiro Hiroyasu , Suzuki Eiji , Torii Masae , Yamada Yosuke , Kataoka Tatsuki , Ishiguro Hiroshi , Morita Satoshi , Toi Masakazu 
Published: December 2022

AbstractRadiation therapy (RT) can enhance the abscopal effect of immune checkpoint blockade. This phase I/II study investigated the efficacy and safety of nivolumab plus RT in HER2-negative metastatic breast cancer requiring palliative RT for bone metastases. Cohort A included luminal-like disease, and cohort B included both luminal-like and triple-negative disease refractory to standard systemic therapy. Patients received 8 Gy single fraction RT for bone metastasis on day 0. Nivolumab was administered on day 1 for each 14-day cycle. In cohort A, endocrine therapy was administered. The primary endpoint was the objective response rate (ORR) of the unirradiated lesions. Cohorts A and B consisted of 18 and 10 patients, respectively. The ORR was 11% (90% CI 4–29%) in cohort A and 0% in cohort B. Disease control rates were 39% (90% CI 23–58%) and 0%. Median progression-free survival was 4.1 months (95% CI 2.1–6.1 months) and 2.0 months (95% CI 1.2–3.7 months). One patient in cohort B experienced a grade 3 adverse event. Palliative RT combined with nivolumab was safe and showed modest anti-tumor activity in cohort A. Further investigations to enhance the anti-tumor effect of endocrine therapy combined with RT plus immune checkpoint blockade are warranted.Trial registration number and date of registration UMIN: UMIN000026046, February 8, 2017; ClinicalTrials.gov: NCT03430479, February 13, 2018; Date of the first registration: June 22, 2017.
Pregnancy outcomes after living kidney donation from a nationwide population-based cohort study from Korea
Authors: Lee Juhan , Huh Kyu Ha , Yoon So Ra , Lee Soo Yeun , Lee Hyung Soon 
Published: December 2022

AbstractWhile most living kidney donors experience good outcomes and high rates of satisfaction, kidney donation can increase the risk of gestational hypertension or preeclampsia. However, pregnancy outcomes in non-white donors are limited. We conducted a nationwide cohort study of 112 living kidney donors and 672 matched healthy non-donors using the Korean National Health Insurance Claims Database. Donors and healthy non-donors were matched according to age, year of cohort entry, residency, income, number of pregnancies, and the time to the first pregnancy after cohort entry. We assessed pregnancy outcomes of live kidney donors compared with matched healthy non-donors using the nationwide database. Gestational hypertension or preeclampsia was more common in kidney donors than in non-donors (8.9% vs. 1.8%; adjusted odds ratio, 2.68; 95% confidence interval, 1.11–6.50). However, the incidence of severe gestational hypertension or preeclampsia that required antihypertensive medication was comparable (2.7% vs. 0.9%; P = 0.121). The time from donation to delivery within 5 years and primiparity were risk factors for preeclampsia in donors. Low birth weight, stillbirth, and ectopic pregnancy were not significantly different between the two groups. Maternal death occurred in two non-donor cases, but none occurred in donors compared to non-donors. Our findings indicate that kidney donors are associated with an increased risk of gestational hypertension or preeclampsia than matched healthy non-donors. However, the probabilities of serious maternal and fetal outcomes remained low and are not increased significantly after kidney donation.