Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Chronic Low Dose Aspirin on Platelet and Vascular Eicosanoid Metabolism in Nonhuman Primates (Macaca fascicularis)

It has been suggested that inhibition of platelet cyclooxygenase by chronic low dose aspirin may spare vascular prostacyclin production. Conventional doses of aspirin (>5 mglkg) have been shown to inhibit the generation of both thromboxane A2 and prostacyclin. Low dose aspirin inhibits prostacyclin production by excised human venous tissue, thus questioning the selectivity of such regimens. However, many clinical and surgical conditions requiring platelet inhibition involve the arterial system. We have studied the effects of various aspirin regimens on platelet, venous, and arterial cyclooxygenase activity in a nonhuman primate (Macaca fascicularis). We determined the lowest chronic dose of oral aspirin required to effectively inhibit platelet cyclooxygenase and aggregation to be 1 mglkg. After 14 days of 0, 1, or 2 mglkg aspirin, intact veins and arteries were surgically removed and perfused, and luminal prostacyclin (6-keto-PGF1α,) generation was assessed. Levels of 6-keto-PGF1α in venous perfusates were reduced by 89% and 86% (p>0.05) after 1 and 2 mglkg, respectively. Arterial 6-keto-PGF1α levels were unchanged by 1 mg/kg aspirin, but after 2 mglkg were reduced by 66% (p>0.05). Preferential inhibition of platelet over arterial cyclooxygenase is thus achievable, but only over a narrow dose range.
GEOGRAPHIC DISTRIBUTION OF MOLECULAR VARIANCE WITHIN THE BLUE MARLIN (MAKAIRA NIGRICANS): A HIERARCHICAL ANALYSIS OF ALLOZYME, SINGLE‐COPY NUCLEAR DNA, AND MITOCHONDRIAL DNA MARKERS

This study presents a comparative hierarchical analysis of variance applied to three classes of molecular markers within the blue marlin (Makaira nigricans). Results are reported from analyses of four polymorphic allozyme loci, four polymorphic anonymously chosen single‐copy nuclear DNA (scnDNA) loci, and previously reported restriction fragment length polymorphisms (RFLPs) of mitochondrial DNA (mtDNA). Samples were collected within and among the Atlantic and Pacific Oceans over a period of several years. Although moderate levels of genetic variation were detected at both polymorphic allozyme (H = 0.30) and scnDNA loci (H = 0.37), mtDNA markers were much more diverse (h = 0.85). Allele frequencies were significantly different between Atlantic and Pacific Ocean samples at three of four allozyme loci and three of four scnDNA loci. Estimates of allozyme genetic differentiation (θO) ranged from 0.00 to 0.15, with a mean of 0.08. The θO values for scnDNA loci were similar to those of allozymes, ranging from 0.00 to 0.12 with a mean of 0.09. MtDNA RFLP divergence between oceans (θO = 0.39) was significantly greater than divergence detected at nuclear loci (95% nuclear confidence interval = 0.04–0.11). The fourfold smaller effective population size of mtDNA and male‐mediated gene flow may account for the difference observed between nuclear and mitochondrial divergence estimates.
How Predictive are Cost Forecasts for Broadband Stimulus? Evidence from the Recovery Act

I examine cost forecasts for 49 fiber-optic and wireless networks funded by the Recovery Act. I find that grantees did not systematically underbid for projects. They did, however, underestimate and overestimate costs with nearly equal frequency, and escalate costs on average by 202 percent in cost per institution and 37 percent in cost per fiber mile. For four outputs, I ask whether cost forecasts predicted actual construction. I find that grantees overestimated fiber miles and indirectly connected institutions, while meeting targets for directly connected institutions and points of interconnection. I do not find budget, technology, or institution effects to explain the quality of cost forecasts in these outputs. My findings suggest that low-price bids can be cost-effective across project types. With data from the applicant pool, I compare offers from 116 projects with 657 rejected proposals.
New options for outpatient chemotherapy--the role of oral fluoropyrimidines.

For several decades fluoropyrimidines, especially 5-fluorouracil (5-FU), have played a role in standard chemotherapy regimens for a range of solid tumours, including breast and colorectal cancers. In recent years, schedule modification and biomodulation have achieved improved efficacy and tolerability. However, the complications arising from infused intravenous administration are well-recognized and there is an unmet medical need for oral agents with improved efficacy and tolerability, offering more convenient outpatient therapy. Several oral fluoropyrimidines are in development, including capecitabine, UFT (uracil plus tegafur), S-1 and eniluracil. As yet, only UFT/leucovorin and capecitabine have been evaluated in randomized phase III clinical trials in metastatic colorectal cancer. Both have demonstrated safety benefits and equivalent survival compared with the Mayo Clinic regimen, and capecitabine has demonstrated a significantly superior response rate. Time to disease progression was equivalent to the Mayo Clinic regimen with capecitabine, but inferior with UFT/leucovorin. Capecitabine is also effective in patients with taxoid-pretreated metastatic breast cancer, a population which previously had no established treatment options. Both capecitabine and UFT/leucovorin are being evaluated in combination with irinotecan and oxaliplatin in colorectal cancer, and vinorelbine and docetaxel/paclitaxel in breast cancer. In the future, these more convenient, oral fluoropyrimidines may replace intravenous 5-FU in the treatment of breast and colorectal cancer.
Role of NF-κβ and oxidative pathways in atherosclerosis: cross-talk between dyslipidemia and candesartan.

PURPOSE The objective of this study is to assess the effect of the candesartan on the progression of atherosclerosis through the downregulation of NF-κβ and interference with oxidative pathway. METHODS Twenty-four rabbits were assigned to three groups: control group fed normal diet; induced untreated group fed 1% cholesterol diet; and treated candesartan group also fed 1% cholesterol diet. Plasma lipid profiles were measured, and ELISA for plasma cytokines and chemokine was performed. Analyses of NF-κβ and VCAM-1 were performed using Western blotting with RT-PCR for NF-κB activity at mRNA. Doppler ultrasound was used to evaluate aortic intima-media thickness, and atheroma was detected by H&E staining. Immunofluorescent staining was performed to confirm accumulation of monocytes and PMNs. RESULTS Candesartan markedly reduced the levels of the plasma lipid profile including total cholesterol [TC], triglycerides [TG], and LDL-C, while significantly elevating levels in the plasma HDL-C, in addition to reducing cytokine (TNF-α, IL-6, IL-1β) and chemokine levels (MCP-1). Also, it decreased the aortic malondialdehyde (MDA) concentration and elevated the aortic glutathione (GSH) level compared with untreated animals (P < 0.05). The triplex Doppler ultrasound study confirmed that the candesartan attenuated intima-media thickness at 6 months of study. All candesartan-treated rabbits showed significantly attenuated atherosclerosis lesions with reduced accumulation of monocytes and had significantly reduced VCAM-1 expression and NF-κβ activity. CONCLUSION Candesartan retards the progression of atherosclerosis via interference with NF-κβ and oxidative pathways.
Selective Estrogen Receptor Modulators: An Update on Recent Clinical Findings

Recent clinical data on selective estrogen receptor modulators (SERMs) have provided the basis for reassessment of the SERM concept. The molecular basis of SERM activity involves binding of the ligand SERM to the estrogen receptor (ER), causing conformational changes which facilitate interactions with coactivator or corepressor proteins, and subsequently initiate or suppress transcription of target genes. SERM activity is intrinsic to each ER ligand, which accomplishes its unique profile by specific interactions in the target cell, leading to tissue selective actions. We discuss the estrogenic and anti-estrogenic effects of early SERMs, such as clomiphene citrate, used for treatment of ovulation induction, and the triphenylethylene, tamoxifen, which has ER antagonist activity in the breast, and is used for prevention and treatment of ER-positive breast cancer. Since the development of tamoxifen, other triphenylethylene SERMs have been studied for breast cancer prevention, including droloxifene, idoxifene, toremifene, and ospemifene. Other SERMs have entered clinical development more recently, including benzothiophenes (raloxifene and arzoxifene), benzopyrans (ormeloxifene, levormeloxifene, and EM-800), lasofoxifene, pipendoxifene, bazedoxifene, HMR-3339, and fulvestrant, an anti-estrogen which is approved for breast cancer treatment. SERMs have effects on tissues containing ER, such as the breast, bone, uterine and genitourinary tissues, and brain, and on markers of cardiovascular risk. Current evidence indicates that each SERM has a unique array of clinical activities. Differences in the patterns of action of SERMs suggest that each clinical end point must be evaluated individually, and conclusions about any particular SERM can only be established through appropriate clinical trials. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to summarize the complex function and interactions of selective estrogen receptor modulators (SERMs); recall their suppression or initiation of target genes leading them to their actions; and explain their important roles in breast cancer treatment and possible side effects on bone, the genitourinary system, and on markers of cardiovascular risk.
Effects of nitrous oxide on baroreflex gain and heart rate variability

Background: Spontaneous baroreflex method allows continuous assessment of cardiovagal reflex function within resting blood pressure, but effects of nitrous oxide, per se, on the spontaneous baroreflex response remain unknown. This study was designed to determine the effects of nitrous oxide on spontaneous baroreflex gain and heart rate variability assessed by power spectral analysis in humans.
Aerodynamic and acoustic effects of abrupt frequency changes in excised larynges.

PURPOSE To determine the aerodynamic and acoustic effects due to a sudden change from chest to falsetto register or vice versa. It was hypothesized that the continuous change in subglottal pressure and flow rate alone (pressure-flow sweep [PFS]) can trigger a mode change in the canine larynx. METHOD Ten canine larynges were each mounted over a tapered tube that supplied pressurized, heated, and humidified air. Glottographic signals were recorded during each PFS experiment, during which airflow was increased in a gradual manner for a period of 20-30 s. RESULTS Abrupt changes in fundamental frequency (F(0)) and mode of vibration occurred during the PFS in the passive larynx without any change in adduction or elongation. The lower frequency mode of oscillation of the vocal folds, perceptually identified as the chest register, had relatively large amplitude oscillation, significant vocal fold contact, a rich spectral content, and a relatively loud audio signal. The higher frequency mode of oscillation, perceptually identified as falsetto, had little or no vocal fold contact and a dominant first partial. Relatively abrupt F(0) changes also occurred for gradual adduction changes, with the chest register corresponding to greater adduction, falsetto to less adduction.
Immunosenescence and Autoimmunity: Exploiting the T-Cell Receptor Repertoire to Investigate the Impact of Aging on Multiple Sclerosis

T-cell receptor (TCR) repertoire diversity is a determining factor for the immune system capability in fighting infections and preventing autoimmunity. During life, the TCR repertoire diversity progressively declines as a physiological aging progress. The investigation of TCR repertoire dynamics over life represents a powerful tool unraveling the impact of immunosenescence in health and disease. Multiple Sclerosis (MS) is a demyelinating, inflammatory, T-cell mediated autoimmune disease of the Central Nervous System in which age is crucial: it is the most widespread neurological disease among young adults and, furthermore, patients age may impact on MS progression and treatments outcome. Crossing knowledge on the TCR repertoire dynamics over MS patients’ life is fundamental to investigate disease mechanisms, and the advent of high- throughput sequencing (HTS) has significantly increased our knowledge on the topic. Here we report an overview of current literature about the impact of immunosenescence and age-related TCR dynamics variation in autoimmunity, including MS.
Association of leptin and leptin receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population

To explore the association of LEP and leptin receptor (LEPR) gene single‐nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.
Divergent Roles of SPINK1 and PRSS2 Variants in Tropical Calcific Pancreatitis

Background/Aims: Tropical calcific pancreatitis (TCP) refers to a type of idiopathic pancreatitis prevalent in Asia. The trypsin inhibitor (SPINK1) N34S variant partially explains the genetic susceptibility to TCP. As anionic trypsinogen (PRSS2) G191R protects against chronic pancreatitis in Europeans, we investigated whether this variant protects from TCP in Indians. Methods: We enrolled 174 patients and 794 controls from two Indian tertiary care referral hospitals. We analyzed PRSS2 and SPINK1 variants by melting curve analysis, allele-specific discrimination assay, and sequencing. Results: G191R was detected in 1 TCP patient (0.6%) compared to 13 controls (1.6%; OR 0.27, 95% CI 0.03–2.1; p = 0.33). SPINK1 N34S was enriched in the TCP population 67/174 (38.5%) compared to controls 10/234 (4.3%; OR 14, 95% CI 6.9–28.3; p < 0.001). Conclusion: G191R PRSS2 is a rare allele in the Indian population and the data suggest a nonsignificant trend towards a protective effect. N34S SPINK1 represents the major genetic risk factor in TCP.
Education Poverty in Pakistan: A Spatial Analysis at District Level

This study aims, first to construct an education poverty index (EPI) for Pakistan using household data; second, to investigate the spatial differences of education poverty (EP) at district level; and third to find the socio-economic determinants of EP. Four different dimensions are used to construct EPI using the Alkire Foster (AF) method. The results show that 26 per cent households are below the poverty cut-off in Pakistan. The ratio is high in rural area of Pakistan (33 per cent) as compared to urban areas of Pakistan (12 per cent). Similar trend has been observed across all provinces. The majority of the households are deprived in terms of cost of education. Empirical analysis shows that various socio-economic variables such as income, regional variation and awareness play very important role in explaining EP. To eradicate education deprivation, area- and dimension-specific policies are required to make efficient use of scarce resources.
A honey bee Dscam family member, AbsCAM, is a brain‐specific cell adhesion molecule with the neurite outgrowth activity which influences neuronal wiring during development

The immunoglobulin superfamily (IgSF) has been indicated as functioning in the development and maintenance of nervous systems through cell–cell recognition and communication in several model invertebrates, Drosophila melanogaster and Caenorhabditis elegans. To further explore the functions of the IgSF in the brain of an invertebrate with more complex behavior, we identified and characterized a novel brain‐specific Dscam family member, AbsCAM, from honey bee (Apis mellifera). The level of the AbsCAM protein was high in newly hatched bees and was dramatically reduced with age. The AbsCAM protein level was constant among worker bees of the same age performing different tasks, suggesting that it was primarily determined by age and not task in adult brains. Two different AbsCAM transcripts (AbsCAM‐Ig7A and B) were generated by the alternative splicing of exon 11 encoding immunoglobulin domain 7 in an age‐dependent manner. AbsCAM was expressed in the major brain neuropils where the synaptic density was high. AbsCAM can mediate the isoform‐specific homophilic cell adhesion in vitro, and affected the axonal projections in Drosophila embryonic central nervous system and adult mushroom body by ectopic expression. Furthermore, AbsCAM promoted the neurite outgrowth of cultured neurons isolated from honey bee pupal brains. These results thus suggest that AbsCAM is the first honey bee IgSF implicated as functioning in neuronal wiring during honey bee brain development.
Norcantharidin induce apoptosis in human nasopharyngeal carcinoma through caspase and mitochondrial pathway

While Nasopharyngeal carcinoma (NPC) is uncommon in western countries, it is endemic in Southeast Asia and Southern China. Previous study of norcantharidin (NCTD), isolated from blister beetles, has proved its anticancer effect on various tumors. However, the effect of NCTD in NPC has never been studied. The purpose of this study is to inspect the suppression activity of NCTD on NPC, along with the underlying mechanism. NPC cell line NPC‐BM was treated with NCTD. NCTD remarkably inhibited proliferation and induce apoptosis in NPC‐BM cell. Activation of caspase‐3, −8, −9 was observed through western blotting. The expression of antiapoptotic protein Bcl‐XL was significantly reduced, but expression of proapoptotic protein Bak was increased after treatment of NCTD. The cytotoxic effect of NCTD on NPC‐BM cell is mainly due to apoptosis, mediated by caspase and mitochondrial pathway. These results suggested that NCTD could be a potential anticancer agent for NPC.
Handgrip strength as a simple indicator of possible malnutrition and inflammation in men and women on maintenance hemodialysis.

OBJECTIVE To assess the validity of handgrip strength (HGS) as a simple screening instrument for malnutrition and inflammation in patients on maintenance hemodialysis (MHD) by correlating it with malnutrition-inflammation score (MIS). DESIGN Cross-sectional analysis of the Prospective Study of the Prognosis in Chronic Hemodialysis Patients (PROHEMO). SETTING Satellite dialysis units in the city of Salvador, Brazil. PATIENTS The sample included 274 men and 162 women on MHD. MAIN PREDICTOR VARIABLE: HGS was chosen as the main predictor variable in this study. MAIN OUTCOME MEASURE An MIS ≥6. RESULTS As compared with men, women were found to have lower HGS values (19.38 ± 6.48 kg vs. 29.07 ± 8.67 kg; P < .001) and higher MIS (6.38 ± 3.84 vs. 5.57 ± 3.39; P = .032). HGS was found to be inversely correlated with MIS among women (Spearman's ρ = -.360; P < .001) as well as men (Spearman's ρ = -0.384; P < .001); this inverse correlation was observed in patients with and without diabetes, different racial groups, younger and older subjects, incident (<3 months) and prevalent patients, in the case of both genders. Among both men and women, every one standard deviation lower of HGS was associated with more than two-fold higher odds for MIS ≥6, after adjusting for age, race, duration of dialysis, and Kt/V. These associations remained statistically significant after more extensive adjustments. The optimized cutoff point of HGS for MIS ≥6 was 28.3 kg for men (sensitivity = 70.0%; specificity = 66.0%) and 23.4 kg for women (sensitivity = 87.0%; specificity = 43.0%). CONCLUSIONS Lower HGS values were independently associated with higher MIS among patients on MHD across several subgroups. These results suggest that HGS is a valid screening instrument for malnutrition and inflammation in patients on MHD.
Lower Back Pain as an Occupational Hazard Among Ugandan Health Workers

Background: Lower back pain is a public health concern affecting 70–85% of the world's population. There is paucity of published data on the prevalence, disability and risk factors for lower back pain among health workers in Uganda. Objective: To determine the frequency rate (note that is it implicit that frequency is a rate like incidence so including rate seems redundant here. This is bounded by zero and infinity. In contrast, prevalence is bounded by 0 and 1 and is thus a proportion not a rate) of lower back pain and its associated risks amongst health professionals in the Arua District of Uganda. Methods: Cross-sectional descriptive study of 245 consecutive participants conducted during February-April 2020. We stratified risks as individual or work related and analyzed the data using IBM SPSS version 25. Chi-square was used to measure the significance of association between categorical variables at 95% confidence interval, regarding a p ≤ 0.05 as significant. Results: The mean age of participants was 40.87 years ± 8.74 (SD), with female predominance (69.8%). Majority were either general nurses or midwives (64.9%) and more than half had practiced for over 6–10 years. The frequency rate of lower back pain was 39.6% (n = 97). Individual factors associated with LBP were; cigarette smoking (X2 = 33.040; P ≤ 0.001), alcohol consumption (X2 = 13.581; P ≤ 0.001), age (X2 = 14.717; P = 0.002), and female gender (X2 = 4.802; P = 0.028). The work related factors significantly associated with lower back pain were: being a nurse/midwife (X2 = 9.829; P = 0.007), working in the outpatient department (X2 = 49.752; P ≤ 0.001), bending (X2 = 43.912; P ≤ 0.001), lifting (X2 = 33.279; P < 0.001), over standing (X2 = 40.096; P ≤ 0.001), being in awkward positions (X2 = 15.607; P= < 0.001), and pushing patients (X2 = 21.999; P ≤ 0.001). Conclusion: The frequency rate of low back pain was high amongst health workers and its main associated individual and work related factors could have been prevented. Health workers should strike a balance between caring for their personal back-health and meeting clients' needs while manually handling patients. Ergonomic structuring, job organization, back health care courses and use of assistive equipment could reduce such occupational hazards in our low resourced settings.