bluuebunny/crossref_metadata_2025_split huggingface dataset:
IP3R2 null mice display a normal acquisition of somatic and neurological development milestones
Authors: Guerra‐Gomes Sónia , Cunha‐Garcia Daniela , Marques Nascimento Diana Sofia , Duarte‐Silva Sara , Loureiro‐Campos Eduardo , Morais Sardinha Vanessa , Viana João Filipe , Sousa Nuno , Maciel Patrícia , Pinto Luísa , Oliveira João Filipe 
Published: March 2020

AbstractAstrocytes are key players in the regulation of brain development and function. They sense and respond to the surrounding activity by elevating their intracellular calcium (Ca2+) levels. These astrocytic Ca2+ elevations emerge from different sources and display complex spatio‐temporal properties. Ca2+ elevations are spatially distributed in global (soma and main processes) and/or focal regions (microdomains). The inositol 1,4,5‐trisphosphate receptor type 2 knockout (IP3R2 KO) mouse model lacks global Ca2+ elevations in astrocytes, and it has been used by different laboratories. However, the constitutive deletion of IP3R2 during development may trigger compensating phenotypes, which could bias the results of experiments using developing or adult mice. To address this issue, we performed a detailed neurodevelopmental evaluation of male and female IP3R2 KO mice, during the first 21 days of life, as well as an evaluation of motor function, strength and neurological reflexes in adult mice. Our results show that male and female IP3R2 KO mice display a normal acquisition of developmental milestones, as compared with wild‐type (WT) mice. We also show that IP3R2 KO mice display normal motor coordination, strength and neurological reflexes in adulthood. To exclude a potential compensatory overexpression of other IP3Rs, we quantified the relative mRNA levels of all 3 subtypes, in brain tissue. We found that, along with the complete deletion of Itpr2, there is no compensatory expression of Itpr1 or Itrp3. Overall, our results show that the IP3R2 KO mouse is a reliable model to study the functional impact of global IP3R2‐dependent astrocytic Ca2+ elevations.
KCNT1‐related epilepsy: An international multicenter cohort of 27 pediatric cases
Authors: Borlot Felippe , Abushama Ahmed , Morrison‐Levy Nadine , Jain Puneet , Puthenveettil Vinayan Kollencheri , Abukhalid Musaad , Aldhalaan Hesham M. , Almuzaini Hanin S. , Gulati Sheffali , Hershkovitz Tova , Konanki Ramesh , Lingappa Lokesh , Luat Aimee F. , Shafi Shatha , Tabarki Brahim , Thomas Maya , Yoganathan Sangeetha , Alfadhel Majid , Arya Ravindra , Donner Elizabeth J. , Ehaideb Salleh N. , Gowda Vykuntaraju K. , Jain Vivek , Madaan Priyanka , Myers Kenneth A. , Otsubo Hiroshi , Panda Prateek , Sahu Jitendra K. , Sampaio Letícia P. B. , Sharma Suvasini , Simard‐Tremblay Elisabeth , Zak Maria , Whitney Robyn 
Published: March 2020

AbstractObjectiveThrough international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1‐related epilepsy and explored genotype‐phenotype correlations associated with frequently encountered variants.MethodsA cross‐sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.ResultsTwenty‐seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two‐thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray‐white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%‐50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.SignificanceOur cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence‐based practice is still unavailable.
Rate of dyslipidemia higher among women living with HIV: A comparison of metabolic and cardiovascular health in a cohort to study aging in HIV
Authors: Russell EAB , Albert AYK , Côté HCF , Hsieh AYY , Nesbitt A , Campbell AR , Maan EJ , Brophy J , Pick N , Murray MCM 
Published: March 2020

ObjectivesCombination antiretroviral therapy has largely restored the lifespan of persons living with HIV. Data suggest early comorbidities of aging in this population. Past studies focused on men; limited data exist regarding the prevalence of dyslipidaemia in women living with HIV (WLWH). We investigated the prevalence of cardiometabolic abnormalities among WLWH and HIV‐negative women in the Children and Women: Antiretrovirals and Markers of Aging (CARMA) cohort, and their relationships to cellular aging markers.MethodsWe conducted a cross‐sectional analysis of nonpregnant female patients (156 WLWH and 133 HIV‐negative controls, aged 12–69 years) enrolled in CARMA between 2013 and 2017. The Framingham risk score (FRS) and the prevalences of hypertension, diabetes, metabolic syndrome and dyslipideamia were determined using self‐report, anthropometrics, chart review and laboratory data. Cellular aging was determined by assessing leukocyte telomere length and blood mitochondrial DNA content. Diagnoses were based on current Canadian guidelines and definitions.ResultsHIV‐infected status was associated with dyslipidaemia [odds ratio (OR) 2.89; 95% confidence interval (CI) 1.69–5.01], but not diabetes, higher FRS, hypertension or metabolic syndrome. The median age was 43.5 [interquartile range (IQR) 36.8–50.9] years in WLWH and 46.2 (IQR 30.3–54.9) years in HIV‐negative controls. WLWH were less likely to be menopausal or use alcohol, and more often had hepatitis C virus infection or a current or past smoking history. Lower mitochondrial DNA content was associated with metabolic syndrome; no other associations were noted between cardiometabolic abnormalities and markers of cellular aging.ConclusionsDespite their relatively young age, almost two‐thirds of WLWH had dyslipidaemia, a significantly greater proportion than in controls. Strategies to address dyslipidaemia and decrease smoking rates may improve long‐term outcomes among WLWH.
Density dependence in Golden Eagle Aquila chrysaetos fecundity better explained by individual adjustment than territory heterogeneity
Authors: Chambert Thierry , Imberdis Ludovic , Couloumy Christian , Bonet Richard , Besnard Aurélien 
Published: March 2020

Density‐dependence effects acting on fecundity can be explained by two competing hypotheses. The individual adjustment hypothesis (IAH) states that, as population density increases, interference among individuals negatively affects their breeding performance. The second hypothesis, the habitat heterogeneity hypothesis (HHH), proposes that, as more individuals occupy the space available, lower quality habitats are increasingly used, causing average population fecundity to decline. In territorial species, it is often predicted that interference mechanisms (IAH) should be of less importance than spatial heterogeneity (HHH). Here, we test this prediction in Golden Eagles, using 35 years of reproduction monitoring data from a population that has been recolonizing the grounds of a French National Park (Ecrins) in the Alps. During the study period, the Eagle population increased from c. 11 to 41 territorial pairs, providing a good opportunity to explicitly assess fecundity across a gradient of densities. Under the IAH, we expect the fecundity of all territories to diminish as density rises. Under strict HHH, older territories should maintain higher fecundity across time, and a positive relationship between fecundity and the seniority of a territory should be observed. A density‐dependent pattern was clearly detected at the population level. At the territory level, the decrease of fecundity was strongly related to population size but not to territory seniority. Fecundity decreased similarly in all territories, suggesting that the IAH better explains the observed pattern. Two alternative mechanisms, related to the IAH, could be at play in this population: (1) negative interference by neighbours and non‐territorial Eagles and (2) the contraction of individual territories over time. Our results provide new insights into density dependence in territorial raptors, suggesting that, in addition to habitat heterogeneity, interference mechanisms might actually also play an important role.
Bacterial cellulose–assisted synthesis of glass‐ceramic scaffolds with TiO2 crystalline domains
Authors: Jinga Sorin‐Ion , Draghici Alina‐Denisa , Mocanu Alexandra , Nicoara Adrian‐Ionut , Iordache Florin , Busuioc Cristina 
Published: March 2020

AbstractGlass‐ceramic 3D porous structures were obtained by from a polymeric template, which was successively loaded with calcium phosphates, by chemical reaction and a dried gel based on barium and titanium by physical attachment. The resulting composite was subjected to a freeze‐drying procedure in order to maintain the spongy morphology. Under the effect of the subsequent thermal treatment at temperatures above 1000°C, the biocellulose membrane was completely removed, the mineral phases combined with each other through intense diffusion processes, and the mineral scaffolds acquired enough mechanical strength to become self‐sustained. The as‐prepared and thermally treated samples were characterized from physicochemical and biological point of view. The only crystalline phase emerged in the final masses was TiO2, while the microstructure was individualized as peculiar 3D architectures with porous and branched appearance. All prepared materials were proven to be biocompatible with the mesenchymal stem cells, showing no cytotoxic effect and suitability for the field of tissue engineering.
Current approach to diagnosis and management of retroperitoneal fibrosis
Authors: Tanaka Toshiaki , Masumori Naoya 
Published: March 2020

AbstractRetroperitoneal fibrosis is characterized by fibrotic lesions around the abdominal aorta and common ileac artery causing ureteral obstruction. Secondary retroperitoneal fibrosis is associated with malignant disease, drugs, exposure to radiation and surgery. In contrast, the majority of retroperitoneal fibrosis is classified into idiopathic retroperitoneal fibrosis, for which immunological etiology has been suggested. Recently, idiopathic retroperitoneal fibrosis has been considered to be a spectrum of immunoglobulin G4‐related disease, a systemic inflammatory disease, the concept of which has been developed during the past decade. In the management of retroperitoneal fibrosis, assessment of systemic lesions associated with immunoglobulin G4‐related disease and the exclusion of secondary retroperitoneal fibrosis is mandatory. Histological examination of retroperitoneal lesions is desired for accurate diagnosis and management. Laparoscopic or open biopsy is often beneficial, although it is more invasive than needle biopsy. Treatment for idiopathic retroperitoneal fibrosis consists of meticulous glucocorticoid therapy based on that for immunoglobulin G4‐related disease, which is expected to be highly effective. Ureteral obstruction is usually managed with conservative procedures, such as ureteral stenting or percutaneous nephrostomy. The goal of treatment for retroperitoneal fibrosis should be freedom from the stent/nephrostomy with withdrawal of the glucocorticoid in addition to salvage of renal function; however, conservative management does not always provide favorable outcomes. In contrast, aggressive surgical treatment, such as ureterolysis, can achieve the goal; however, the procedure is associated with high morbidity. Establishment of a consensus about treatment for idiopathic retroperitoneal fibrosis, including the optimal indications for the invasive surgical procedure and conservative management, is desired.
The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo
Authors: He Rui , Li Qin , Shen Wenqi , Wang Tao , Lu Huijuan , Lu Junxi , Lu Fendi , Luo Ming , Zhang Jiankang , Gao Haiwei , Wang Dong , Xing Wanli , Jia Weiping , Liu Fang 
Published: March 2020

AbstractCold atmospheric plasma (CAP) is a group of various chemical active species, such as ozone and nitric oxide, generated by working gas. CAP was demonstrated to have an effect on tissue regeneration and wound healing. We conducted this study to evaluate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and in vivo. The plasma consists of ionised helium gas that is produced by a high‐voltage and high‐frequency power supply. Eight‐week‐old male db/db mice and C57BL mice were treated with helium gas (control group), 90s' CAP (low‐dose group), and 180s' CAP (high‐dose group). Mice were treated and observed for 2 weeks. Skin samples from around the wound and blood samples were collected. Our in vitro analysis included scratch wound‐healing assays by using human HaCaT immortalised human epidermal cells. After 14 days of treatment, CAP could obviously promote diabetic wound healing. Wound closure rates were significantly higher in the low‐dose group and high‐dose groups compared with the control group. Meanwhile, compared with the control group, the protein expression of IL‐6, tumour necrosis factor‐α, inducible nitric oxide synthase, and superoxide dismutase in two CAP groups significantly decreased, while the protein expression of vascular endothelial growth factor and transforming growth factor‐β in two CAP groups significantly increased (all P < .05); these data show good agreement with the change in mRNA level (all P < .05). In vitro, scratch wound‐healing assays showed that plasma treatment could effectively ensure healing within 3 minutes of exposure (all P < .05). In addition, no difference was found in histological observations of normal skin and the level of serum alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, and white blood cells among the CAP groups and control group. CAP treatment for 3 minutes every day improves wound healing in diabetic mice by suppressing inflammation, reducing oxidative stress, and enhancing angiogenesis, involving several proteins signalling, and it is safe for the liver and kidney.
Oridonin inhibits the migration and epithelial‐to‐mesenchymal transition of small cell lung cancer cells by suppressing FAK‐ERK1/2 signalling pathway
Authors: Xu Linhao , Bi Yanli , Xu Yizhou , Zhang Zhuocheng , Xu Wenjie , Zhang Sisi , Chen Jian 
Published: March 2020

AbstractSmall cell lung cancer (SCLC) is a severe malignant with high morbidity; however, few effective and secure therapeutic strategy is used in current clinical practice. Oridonin is a small molecule from the traditional Chinese herb Rabdosia rubescens. This study mainly aimed to investigate the role of oridonin on inhibiting the process of H1688, a kind of small cell lung cancer cells from human. Oridonin could suppress H1688 cell proliferation and induce their apoptosis in a high dosage treatment (20 μmol/L). Meanwhile, cell migration was suppressed by oridonin (5 and 10 μmol/L) that did not affect cell proliferation and apoptosis. The expression level of E‐cadherin was significantly increased, and the expression of vimentin, snail and slug was reduced after administration of oridonin. These expression changes were associated with the suppressed integrin β1, phosphorylation of focal adhesion kinase (FAK) and ERK1/2. In addition, oridonin (5 and 10 mg/kg) inhibited tumour growth in a nude mouse model; however, HE staining revealed a certain degree of cytotoxicity in hepatic tissue after treatment oridonin (10 mg/kg). Furthermore, the concentration of alanine aminotransferase (ALP) was significantly increased and lactate dehydrogenase (LDH) was reduced after oridonin treatment (10 mg/kg). Immunohistochemical analysis further revealed that oridonin increased E‐cadherin expression and reduced vimentin and phospho‐FAK levels in vivo. These findings indicated that oridonin can inhibit the migration and epithelial‐to‐mesenchymal transition (EMT) of SCLC cells by suppressing the FAK‐ERK1/2 signalling pathway. Thus, oridonin may be a new drug candidate to offer an effect of anti‐SCLC with relative safety.
Extracellular vesicle‐mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling
Authors: Lerner Natalie , Schreiber‐Avissar Sofia , Beit‐Yannai Elie 
Published: March 2020

AbstractPrimary open‐angle glaucoma is a leading cause of irreversible blindness, often associated with increased intraocular pressure. Extracellular vesicles (EVs) carry a specific composition of proteins, lipids and nucleotides have been considered as essential mediators of cell‐cell communication. Their potential impact for crosstalk between tissues responsible for aqueous humour production and out‐flow is largely unknown. The study objective was to investigate the effects of EVs derived from non‐pigmented ciliary epithelium (NPCE) primary cells on the expression of Wnt proteins in a human primary trabecular meshwork (TM) cells and define the mechanism underlying exosome‐mediated regulation that signalling pathway. Consistent with the results in TM cell line, EVs released by both primary NPCE cells and NPCE cell line showed diminished pGSK3β phosphorylation and decreased cytosolic levels of β‐catenin in primary TM cells. At the molecular level, we showed that NPCE exosome treatment downregulated the expression of positive GSKβ regulator‐AKT protein but increased the levels of GSKβ negative regulator‐PP2A protein in TM cells. NPCE exosome protein analysis revealed 584 miRNAs and 182 proteins involved in the regulation of TM cellular processes, including WNT/β‐catenin signalling pathway, cell adhesion and extracellular matrix deposition. We found that negative modulator of Wnt signalling miR‐29b was abundant in NPCE exosomal samples and treatment of TM cells with NPCE EVs significantly decreased COL3A1 expression. Suggesting that miR‐29b can be responsible for decreased levels of WNT/β‐catenin pathway. Overall, this study highlights a potential role of EVs derived from NPCE cells in modulating ECM proteins and TM canonical Wnt signalling.
A time‐to‐event analysis on air pollutants with the risk of cardiovascular disease and mortality: A systematic review and meta‐analysis of 84 cohort studies
Authors: Pranata Raymond , Vania Rachel , Tondas Alexander Edo , Setianto Budhi , Santoso Anwar 
Published: March 2020

AbstractObjectiveAir pollution is one of the most substantial problems globally. Aerodynamic toxic of particulate matter with <10 mm in diameter (PM10), or <2.5 mm (PM2.5), as well as nitric dioxide (NO2), have been linked with health issues. We aimed to perform a comprehensive analysis of the time‐to‐event for different types of air pollutants on cardiovascular disease (CVD) events based on cohort studies.MethodsA comprehensive search on topics that assesses air pollution and cardiovascular disease with keywords up until July 2019 was performed.ResultsThere were a total of 28 215 394 subjects from 84 cohorts. Increased PM2.5 was associated with composite CVD [HR 1.10 (1.02, 1.19)], acute coronary events [HR 1.15 (1.12, 1.17)], stroke [HR 1.13 (1.06, 1.19)], and hypertension [HR 1.07 (1.01, 1.14)], all‐cause mortality [HR 1.07 (1.04, 1.09)], CVD mortality [HR 1.10 (1.07, 1.12)], and ischemic heart disease (IHD) mortality [HR 1.11 (1.07, 1.16)]. Association with AF became significant after removal of a study. Increased PM10 was associated with heart failure [HR 1.25 (1.04, 1.50)], all‐cause mortality [HR 1.16 (1.06, 1.27)], CVD mortality [HR 1.17 (1.04, 1.30)], and IHD mortality [HR 1.03 (1.01, 1.05)]. Increased of NO2 was associated with increased composite CVD [HR 1.15 (1.02, 1.29)], atrial fibrillation [HR 1.01 (1.01, 1.02)], acute coronary events [HR 1.08 (1.02, 1.13)], all‐cause mortality [HR 1.23 (1.14, 1.32)], CVD mortality [HR 1.17 (1.10, 1.25)], and IHD mortality [HR 1.05 (1.03, 1.08)].ConclusionAir pollutants are associated with an increased incidence of cardiovascular diseases, all‐cause mortality, and CVD mortality.
Trehalose‐6‐phosphate phosphatase E modulates ABA‐controlled root growth and stomatal movement in Arabidopsis
Authors: Wang Wenjing , Chen Qingbin , Xu Shouming , Liu Wen‐Cheng , Zhu Xiaohong , Song Chun‐Peng 
Published: March 2020

AbstractTrehalose plays important roles in plant growth and stress responses and is synthesized from trehalose‐6‐phosphate by trehalose‐6‐phosphate phosphatase (TPP). Here, we show that trehalose and abscisic acid (ABA) have synergistic effects on root growth and stomatal closure. The Arabidopsis thaliana genome contains ten genes encoding TPPs and the expression level of one, TPPE, and trehalose contents increased in response to ABA. In the presence of ABA, the ABA‐responsive transcription factor ABA RESPONSE ELEMENT BINDING FACTOR2 (ABF2) directly binds to the TPPE promoter to activate its expression. Genetic analysis revealed that TPPE acts downstream of ABF2, which is supported by the findings that TPPE expression and trehalose content are reduced in the abf2 mutant and that a mutation in TPPE abolished the ABA‐sensitive root elongation phenotype of 35S:ABF2 plants. Reactive oxygen species (ROS) accumulation in response to ABA failed to occur in tppe mutant plants, suggesting that TPPE is involved in ABA‐controlled root elongation and stomatal movement by inducing ROS accumulation. This study uncovers a new branch of the ABA signaling pathway and provides a molecular basis for the role of trehalose in plant responses to abiotic stress.