Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Anoctamin‐1 Limits Pulmonary Endothelial Cell Proliferation via p38‐Mitogen‐activated Protein Kinase‐Dependent Apoptosis

&NA; Hyperproliferative endothelial cells (ECs) play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). Anoctamin (Ano)‐1, a calcium‐activated chloride channel, can regulate cell proliferation and cell cycle in multiple cell types. However, the expression and function of Ano1 in the pulmonary endothelium is unknown. We examined whether Ano1 was expressed in pulmonary ECs and if altering Ano1 activity would affect EC survival. Expression and localization of Ano1 in rat lung microvascular ECs (RLMVECs) was assessed using immunoblot, immunofluorescence, and subcellular fractionation. Cell counts, flow cytometry, and caspase‐3 activity were used to assess changes in cell number and apoptosis in response to the small molecule Ano1 activator, Eact. Changes in mitochondrial membrane potential and mitochondrial reactive oxygen species (mtROS) were assessed using 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethylbenzimidazolylcarbocyanine, iodide (mitochondrial membrane potential dye) and mitochondrial ROS dye, respectively. Ano1 is expressed in RLMVECs and is enriched in the mitochondria. Activation of Ano1 with Eact reduced RLMVEC counts through increased apoptosis. Ano1 knockdown blocked the effects of Eact. Ano1 activation increased mtROS, reduced mitochondrial membrane potential, increased p38 phosphorylation, and induced release of apoptosis‐inducing factor. mtROS inhibition attenuated Eact‐mediated p38 phosphorylation. Pulmonary artery ECs isolated from patients with idiopathic PAH (IPAH) had higher expression of Ano1 and increased cell counts compared with control subjects. Eact treatment reduced cell counts in IPAH cells, which was associated with increased apoptosis. In summary, Ano1 is expressed in lung EC mitochondria. Activation of Ano1 promotes apoptosis of pulmonary ECs and human IPAH‐pulmonary artery ECs, likely via increased mtROS and p38 phosphorylation, leading to apoptosis.
Solving finite-domain linear constraints in presence of the alldifferent

In this paper, we investigate the possibility of improvement of the widely-used filtering algorithm for the linear constraints in constraint satisfaction problems in the presence of the alldifferent constraints. In many cases, the fact that the variables in a linear constraint are also constrained by some alldifferent constraints may help us to calculate stronger bounds of the variables, leading to a stronger constraint propagation. We propose an improved filtering algorithm that targets such cases. We provide a detailed description of the proposed algorithm and prove its correctness. We evaluate the approach on five different problems that involve combinations of the linear and the alldifferent constraints. We also compare our algorithm to other relevant approaches. The experimental results show a great potential of the proposed improvement.
Randomized trial of the short-term effects of dieting compared with dieting plus aerobic exercise on lactation performance.

BACKGROUND Limiting postpartum weight retention is important for preventing adult obesity, but the effect of weight loss on lactation has not been studied adequately. OBJECTIVE We evaluated whether weight loss by dieting, with or without aerobic exercise, adversely affects lactation performance. DESIGN At 12+/-4 wk postpartum, exclusively breast-feeding women were randomly assigned for 11 d to a diet group (35% energy deficit; n = 22), a diet plus exercise group (35% net energy deficit; n = 22), or a control group (n = 23). Milk volume, composition, and energy output; maternal weight, body composition, and plasma prolactin concentration; and infant weight were measured before and after the intervention. RESULTS Weight loss averaged 1.9, 1.6, and 0.2 kg in the diet, diet + exercise, and control groups, respectively (P < 0.0001) and was composed of 67% fat in the diet group and nearly 100% fat in the diet + exercise group. Change in milk volume, composition, and energy output and infant weight did not differ significantly among groups. However, there was a significant interaction between group and baseline percentage body fat: in the diet group only, milk energy output increased in fatter women and decreased in leaner women. The plasma prolactin concentration was higher in the diet and diet + exercise groups than in the control group. CONCLUSIONS Short-term weight loss (approximately 1 kg/wk) through a combination of dieting and aerobic exercise appears safe for breast-feeding mothers and is preferable to weight loss achieved primarily by dieting because the latter reduces maternal lean body mass. Longer-term studies are needed to confirm these findings.
Review: Chikungunya Arthritis: Implications of Acute and Chronic Inflammation Mechanisms on Disease Management

In the past decade, arboviruses—arthropod‐borne viruses—have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus, an arbovirus that belongs to the alphavirus genus, is a reemerging arthritogenic virus that has caused explosive outbreaks since 2006, notably on Réunion Island, and more recently in the Caribbean, South America, India, and Southeast Asia. The severity of arthritic disease caused by chikungunya virus has prompted public health authorities in affected countries to develop specific guidelines to tackle this pathogen. Chikungunya virus disease manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, during which patients may experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of chikungunya virus pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of chikungunya virus to date. In addition, the review explores the practical aspects of treatment and management of both acute and chronic chikungunya virus based on clinical experience during chikungunya virus outbreaks. Finally, recent findings on potential therapeutic solutions—from antiviral agents to immunomodulators—are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a reemerging arboviral disease of significant public health concern, and insight into future therapeutic approaches to better address the treatment and management of chikungunya virus.
An inactivating mutation in the histone deacetylase SIRT6 causes human perinatal lethality

Ferrer et al. demonstrate that a homozygous inactivating mutation in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses. Human induced pluripotent stem cells derived from D63H homozygous fetuses fail to differentiate into embryoid bodies, functional cardiomyocytes, and neural progenitor cells due to a failure to repress pluripotent genes.
Improvement of Antioxidant Defences and Mood Status by Oral GABA Tea Administration in a Mouse Model of Post-Stroke Depression

Green GABA (GGABA) and Oolong GABA (OGABA) teas are relatively new varieties of tea, whose chemical composition and functional properties are largely under-studied, despite their promising health capacities. Post stroke depression (PSD) is a complication of stroke with high clinical relevance, yielding increasing mortality and morbidity rates, and a lower response to common therapies and rehabilitation. Methods: Two chemically characterized commercial samples of GGABA and OGABA were investigated for effects on mood following oral administration using a mouse model of PSD, through common validated tests including the Despair Swimming Test and Tail Suspension Test. Moreover, the antioxidant activity of GGABA and OGABA was evaluated by determining the levels of lipid peroxidation products and the activity of antioxidant enzymes in the mouse brain in vivo. Results: GGABA and OGABA attenuated depressed mood by influencing behavioral parameters linked to depression. GGABA was more active than OGABA in this study, and this effect may be likely due to a higher content of polyphenolic substances and amino acids in GGABA compared to OGABA. GGABA also exerted a greater antioxidant activity. Conclusions: Our data suggests that GABA tea is a promising candidate that can be used as an adjuvant in the management of PSD.
Dietary potential renal acid load and renal net acid excretion in healthy, free-living children and adolescents.

BACKGROUND There is increasing evidence that acid-base status has a significant effect on high-intensity physical performance, urolithiasis, and calcium metabolism. Experimental studies in adults showed that renal net acid excretion (NAE) can be reliably estimated from the composition of diets. OBJECTIVE We investigated whether a reasonable estimation of NAE is also possible from the dietary records of free-living children and adolescents. DESIGN Healthy children (aged 8 y; n = 165) and adolescents (aged 16-18 y; n = 73) each collected a 24-h urine sample and completed a weighed diet record on the same day. Urinary NAE was analyzed (NAE(an)) and estimated (NAE(es)). Potential renal acid load (PRAL), the diet-based component of NAE(es), corrects for intestinal absorption of ingested minerals and sulfur-containing protein. A urinary excretion rate of organic acids (OAs) proportional to body surface area was assumed for the complete estimate (NAE(es) = PRAL + OA(es)). RESULTS Significant (P < 0.001) correlations between NAE(es) and NAE(an) were seen in the children (r = 0.43) and the adolescents (r = 0.51). A simplified estimate based on only 4 components of dietary PRAL (protein, phosphorus, potassium, and magnesium) yielded almost identical associations. Mean simplified NAE(es) (32.6 +/- 13.9 and 58.4 +/- 22.0 mEq/d in the children and the adolescents, respectively) agreed reasonably with NAE(an) (32.4 +/- 15.5 and 52.8 +/- 24.3 mEq/d, respectively). CONCLUSIONS Predicting NAE from dietary intakes, food tables, and anthropometric data is also applicable during growth and yields appropriate estimates even when self-selected diets are consumed. The PRAL estimate based on only 4 nutrients may allow relatively simple assessment of the acidity of foods and diets.
Comparing the Nutritional Impact of Dietary Strategies to Reduce Discretionary Choice Intake in the Australian Adult Population: A Simulation Modelling Study

Dietary strategies to reduce discretionary choice intake are commonly utilized in practice, but evidence on their relative efficacy is lacking. The aim was to compare the potential impact on nutritional intake of three strategies to reducing discretionary choices intake in the Australian adult (19–90 years) population. Dietary simulation modelling using data from the National Nutrition and Physical Activity Survey 2011–2012 was conducted (n = 9341; one 24 h dietary recall). Strategies modelled were: moderation (reduce discretionary choices by 50%, with 0%, 25% or 75% energy compensation); substitution (replace 50% of discretionary choices with core choices); reformulation (replace 50% SFA with unsaturated fats, reduce added sugars by 25%, and reduce sodium by 20%). Compared to the base case (observed) intake, modelled intakes in the moderation scenario showed: −17.3% lower energy (sensitivity analyses, 25% energy compensation −14.2%; 75% energy compensation −8.0%), −20.9% lower SFA (−17.4%; −10.5%), −43.3% lower added sugars (−41.1%; −36.7%) and 17.7% lower sodium (−14.3%; −7.5%). Substitution with a range of core items, or with fruits, vegetables and core beverages only, resulted in similar changes in energy intake (−13.5% and −15.4%), SFA (−17.7% and −20.1%), added sugars (−42.6% and −43%) and sodium (−13.7% and −16.5%), respectively. Reformulating discretionary choices had minimal impact on reducing energy intake but reduced SFA (−10.3% to −30.9%), added sugars (−9.3% to −52.9%), and alcohol (−25.0% to −49.9%) and sodium (−3.3% to −13.2%). The substitution and reformulation scenarios minimized negative changes in fiber, protein and micronutrient intakes. While each strategy has strengths and limitations, substitution of discretionary choices with core foods and beverages may optimize the nutritional impact.
Pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein in men and women after consumption of a soy beverage.

BACKGROUND The soy isoflavones genistein and daidzein are found in blood and tissues as aglycones, glucuronides, and sulfates. Isoflavone conjugates may serve as sources of aglycones at specific target tissues and may have bioactivity. Yet, very little is known about the plasma pharmacokinetics of isoflavone conjugates after soy ingestion. OBJECTIVE The objective of this study was to determine the plasma pharmacokinetics of glucuronide and sulfate conjugates of genistein and daidzein in humans after the consumption of a drink made with soy-protein isolate. DESIGN Six men and 6 women ( +/- SD age: 40.8 +/- 3 y) consumed a soy-protein-isolate drink. The pharmacokinetics of isoflavone glucuronide and sulfate conjugates were studied with the use of beta-glucuronidase (EC 3.2.1.31) and sulfatase (EC 3.1.6.1) digestion and liquid chromatography-mass spectrometry. RESULTS Glucuronides of genistein and daidzein made up a significantly lower percentage (P < 0.05) of the total isoflavone concentration in plasma (48% and 33%, respectively) than in urine. The percentages of sulfates of genistein and daidzein in plasma (8% and 26%, respectively) were 2- to 6-fold those in urine (P < 0.05). Approximately 30% of the total genistein or daidzein was comprised of mixed conjugates (one glucuronide and one sulfate). For daidzein sulfate, genistein sulfate, daidzein glucuronide, and genistein glucuronide, the time to peak (t(max)) was 4.5, 4.5, 4.5, and 6.0 h, respectively, and the apparent half-life (t(1/2 lambdaz)) was 3.1, 5.7, 3.2, and 8.4 h, respectively. CONCLUSIONS These data suggest that there are significant differences in the pharmacokinetics of sulfate and glucuronide conjugates of isoflavones. This may have important implications for the meal frequency and maintenance of target tissue bioactivity required to elicit potential health benefits.
Molecular determinants of permeation in a fluoride-specific ion channel

Fluoride ion channels of the Fluc family combat toxicity arising from accumulation of environmental F-. Although crystal structures are known, the densely packed pore region has precluded delineation of the ion pathway. Here we chart out the Fluc pore and characterize its chemical requirements for transport. A ladder of H-bond donating residues creates a ‘polar track’ demarking the ion-conduction pathway. Surprisingly, while track polarity is well conserved, polarity is nonetheless functionally dispensable at several positions. A threonine at one end of the pore engages in vital interactions through its β-branched methyl group. Two critical central phenylalanines that directly coordinate F- through a quadrupolar-ion interaction cannot be functionally substituted by aromatic, non-polar, or polar sidechains. The only functional replacement is methionine, which coordinates F- through its partially positive γ-methylene in mimicry of phenylalanine’s quadrupolar interaction. These results demonstrate the unusual chemical requirements for selectively transporting the strongly H-bonding F- anion.
Safety and efficacy of parenteral iron in children with inflammatory bowel disease

AIMS Iron deficiency anaemia frequently complicates inflammatory bowel disease (IBD) in children and adults. Oral iron may exacerbate gastrointestinal symptoms and absorption may be insufficient in intestinal inflammation. Even where oral iron is successful, repletion of iron stores can be unacceptably slow. Intravenous iron compounds were in the past associated with serious adverse reactions and historically were considered a last resort in children. New generation preparations have a safer profile in adults, although reluctance to use them in children may persist, where safety data are lacking. We investigate the safety and efficacy of ferric carboxymaltose and iron sucrose in children. METHODS We retrospectively identified all children with IBD who received parenteral iron over a 38-month period in a single regional referral centre. Safety, tolerability and adverse events were established by case note review. Efficacy was assessed by change in haematinic indices pre- and post-treatment. RESULTS Forty-one children (18 male; median age 14 years, range 3-17) received a total of 104 iron infusions. Of these, 44% (18) had Crohn's disease; 56% (23) ulcerative colitis. Thirty-five received ferric carboxymaltose, seven iron sucrose and one both. Three children developed mild rash post infusion which resolved quickly with chlorphenamine. Mean increase in haemoglobin was 2.5 g dl-1 (0.3-5.8). Iron levels increased by a mean of 8.4 g dl-1 (1-25), transferrin saturation by 16.2% (2-47). Transferrin decreased by 0.84 g dl-1 (0.3-3.4). CONCLUSIONS New generation parenteral iron preparations are safe, well tolerated and efficacious in children with iron deficiency anaemia and IBD.
Construction, expression, and characterization of a single‐chain variable fragment (ScFv) antibody targeting to the encephalomyocarditis virus

Encephalomyocarditis virus (EMCV) is as a potential zoonotic agent with a wide host range. Here, applying gene splicing by overlap extension PCR (SOE‐PCR), we describe a simple method for producing single‐chain variable fragment (scFv) antibody against EMCV that configurates in the orientation of VH‐(GGGGS)4‐VL. DNA template was resverse transcribed by total RNA that derived from hyperimmunized antibody positive mice spleen after inoculation inactivated EMCV‐PV21 as antigen. Using the degenerate primers designed for the variable regions of IgG of murine antibody, the 417 bp of gene encoding VH‐linker (VHL) and 360 bp of gene encoding linker‐VL (LVL) of the anti‐EMCV was individually amplified from DNA template by PCR, repectively. The 762 bp gene encoding anti‐EMCV scFv was constructed by SOE‐PCR when the mixed VHL and LVL genes were used as the template. The amplified gene subcloned into pGEX‐6P1 to yield pGEX‐6P1/EMCV‐scFv. Recombinant vector transformed into the Escherichia coli BL21 (DE3) and a 53 KDa GST‐scFv fusion protein was obtained by SDS‐PAGE electrophoresis. Animal experiment results showed that the pretective rate of mice in group A which challenged 500 μL 104 TCID50 EMCV per mouse for 7 d post‐inoculation scFv 3 d (0.5 mg purified recombinant scFv per mouse) was 91.67% (11/12). The serum anti‐EMCV antibody titer in group A mice was most significantly higher than that in positive control mouse (P < 0.01), coversely the serum relative mRNA copies were significantly lower than that in positive control mouse (P < 0.05). These findings indicated that recombinant anti‐EMCV scFv has remarkable anti‐EMCV effect in mice.
Embedded Distributed Optical Fiber Sensors in Reinforced Concrete Structures—A Case Study

When using distributed optical fiber sensors (DOFS) on reinforced concrete structures, a compromise must be achieved between the protection requirements and robustness of the sensor deployment and the accuracy of the measurements both in the uncracked and cracked stages and under loading, unloading and reloading processes. With this in mind the authors have carried out an experiment where polyimide-coated DOFS were installed on two concrete beams, both embedded in the rebar elements and also bonded to the concrete surface. The specimens were subjected to a three-point load test where after cracking, they are unloaded and reloaded again to assess the capability of the sensor when applied to a real loading scenarios in concrete structures. Rayleigh Optical Frequency Domain Reflectometry (OFDR) was used as the most suitable technique for crack detection in reinforced concrete elements. To verify the reliability and accuracy of the DOFS measurements, additional strain gauges were also installed at three locations along the rebar. The results show the feasibility of using a thin coated polyimide DOFS directly bonded on the reinforcing bar without the need of indention or mechanization. A proposal for a Spectral Shift Quality (SSQ) threshold is also obtained and proposed for future works when using polyimide-coated DOFS bonded to rebars with cyanoacrylate adhesive.
Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment

Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer’s disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe 18F-florbetapir (AV-45). 18F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia.