Miracle-dz/UniFAR-FTUs huggingface dataset:
Nutrition and physical activity recommendations from the United States and European cardiovascular guidelines: a comparative review.

PURPOSE OF REVIEW A healthy lifestyle throughout one's lifespan is the core foundation for both primary and secondary prevention of cardiovascular disease (CVD). Risk-based decisions for pharmacological therapy is added on-top of lifestyle management. Thus, understanding lifestyle-based recommendations is central to CVD prevention. RECENT FINDINGS In 2018 and 2019, the American Heart Association (AHA) and American College of Cardiology (ACC) published new guidelines for lipid management and primary prevention of cardiovascular disease (CVD), respectively. The European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) published new guidelines on lipids and diabetes management in 2019. These guidelines provide recommendations on diet and lifestyle for reducing cardiovascular risk. Both encourage heart-healthy diets consistent with Mediterranean, DASH, or healthy vegetarian patterns. Both provide guidance for recommended physical activity levels but acknowledge any physical activity, even less than recommended, is better than inactivity. Although both ACC/AHA and ESC/EAS guidelines have similar approaches to achieve the same goal of CVD prevention, there were some differences between them. SUMMARY In this review, we discussed similarities and differences between the American and European guidelines to familiarize clinicians with both sets of lifestyle recommendations in an effort to provide best practices in individualized patient-care for CVD prevention.
Discrimination of regular and irregular rhythms by accumulation of time differences

Perceiving the temporal regularity in a sequence of repetitive sensory events facilitates the preparation and execution of relevant behaviors with tight temporal constraints. How we estimate temporal regularity from repeating patterns of sensory stimuli is not completely understood. We developed a decision-making task in which participants had to decide whether a train of visual, auditory, or tactile pulses, had a regular or an irregular temporal pattern. We tested the hypothesis that subjects categorize stimuli as irregular by accumulating the time differences between the predicted and observed times of sensory pulses defining a temporal rhythm. Results show that instead of waiting for a single large temporal deviation, participants accumulate timing-error signals and judge a pattern as irregular when the amount of evidence reaches a decision threshold. Model fits of bounded integration showed that this accumulation occurs with negligible leak of evidence. Consistent with previous findings, we show that participants perform better when evaluating the regularity of auditory pulses, as compared with visual or tactile stimuli. Our results suggest that temporal regularity is estimated by comparing expected and measured pulse onset times, and that each prediction error is accumulated towards a threshold to generate a behavioral choice.
Drug Resistance in Multiple Myeloma: How to Cross the

Multiple myeloma is a hematological malignancy of plasma cells, characterized by a high level of genetic instability, with various gene mutations and chromosomal translocations. Despite the introduction of effective novel agents in the treatment of myeloma, i.e., proteasome inhibitors and Immunomodulatory Drugs (IMiDs), disease relapse and progression occur almost universally, due to innate and acquired drug resistance. We here describe molecular mechanisms and pathways of resistance so far elucidated. Due to the genetic complexity of myeloma, characterized by intra-clonal heterogeneity and progressing with branching evolutionary patterns, we believe that a single general strategy to overcome drug resistance in all patients cannot be developed. However, it is possible that in the future drug resistance will be prevented or treated with the individualized application of genomic and proteomic analyses, targeting the vulnerable pathways of a specific patient in a specific phase of the disease.
GABAB Receptor-Mediated PI3K/Akt Signaling Pathway Alleviates Oxidative Stress and Neuronal Cell Injury in a Rat Model of Alzheimer's Disease.

BACKGROUND Oxidative stress has been implicated in Alzheimer's disease (AD) as a common pathway underlying neuronal damage causing huge impacts on cognitive functions in the AD process. OBJECTIVE Reduction and remodeling of γ-aminobutyric acid (GABA) signaling in AD may promote neuronal survival by regulating PI3K/Akt axis. Moreover, its activation exerts beneficial effects on AD by alleviating the neuronal oxidative stress injury. Considering these facts, we hypothesized the GABAB receptor as a novel therapeutic target for AD. METHODS To evaluate this hypothesis, a rat AD model was established by intraperitoneal injection of the GABAB receptor agonist (baclofen), PI3K/Akt signaling pathway agonist (740 Y-P), and antagonist (LY294002), respectively. The effects of GABAB activation on spatial memory and learning ability in the AD rats were measured by Morris water maze. Whereas the effects of GABAB and PI3K/Akt signaling pathway on apoptosis and oxidative stress injury were determined in vivo and in vitro using primary neuronal cultures. RESULTS We found that GABAB receptor activation restored spatial memory and learning ability of AD rats and suppressed the neuronal apoptosis and hippocampal atrophy by activating the PI3K/Akt signaling pathway. Additionally, GABAB receptor activation reduced the oxidative stress injury by lowering the MDA levels and increased the SOD, GSH-Px, and CAT levels via activation of the PI3K/Akt signaling pathway. CONCLUSION Taken together, our results suggest that GABAB receptor activation repressed the oxidative stress injury implicated in neurons in AD rats via PI3K/Akt signaling pathway activation which may suggest a potential new therapeutic target for AD.
Digestion of Phosphorus and Other Nutrients: the Role of Phytases and Factors Influencing Their Activity

Phytase may well be the miracle enzyme of the 1990s, as soybeans were described as the miracle crop for producing high quality plant protein in the 1940s. Dietary addition of microbial phytase or the inclusion of high phytase ingredients in pig, poultry and fish diets is now well documented to release a large portion of the naturally occurring phytate P, and thus greatly reduce the amount of inorganic P that must be added to meet the animal’s P requirement. The net result is a reduction in P excretion that can range from 20 to 50%. Microbial phytase was initially used as a tool to reduce P excretion because modern commercial production of pigs and poultry had led to large amounts of manure which, when applied to the land in excess, resulted in a build-up of nutrients in and on the soil. This had a potential for environmental pollution that continues to lead to legislation in many countries that require nutrient management plans for manure from these farms. It is becoming increasingly clear that the use of adequate amounts of phytase in most pig and poultry diets results in improved availability of Ca, Zn, protein/amino acids (AA) and energy. This is because seeds or products from seeds, which are the major ingredients in pig and poultry diets, contain 60–80% of the P in the form of phytic acid or phytate. Phytate is known to complex with other nutrients. Thus, the unavailable phytate P and nutrients complexed with it cannot be utilized and are excreted. This chapter will provide a brief review of phytate, phytase, and the effectiveness of microbial phytase in pig, poultry and fish diets for enhancing the utilization of P,
Role of Helicobacters in Neuropsychiatric Disease: A Systematic Review in Idiopathic Parkinsonism

Interest in an aetiopathogenic role for Helicobacter in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively. This systematic review, using an EMBASE database search, addresses Oxford Centre for Evidence-Based Medicine based questions on the inter-relationship of Helicobacter and IP, the benefits of eradicating Helicobacter in IP and the outcome of not treating. The search strategy was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines: 21 of 204 articles met the inclusion criteria. The results show that the assumption that any benefit of Helicobacter eradication results from improved levodopa bioavailability is unjustified. The inter-relationship between Helicobacter and IP is well-established. H. pylori virulence markers (associated with autoimmunity and immune tolerance) influence the risk, severity and progression of IP. The birth cohort effect for virulence marker antibodies, seen in controls, is obliterated in IP, suggesting causality. Successful H. pylori eradication in IP is disease-modifying (even in anti-parkinsonian treatment-naïve patients) but not preventive. Hypokinesia regresses with eradication and overall motor severity lessens. Eradication may influence gastrointestinal microbiota adversely, unlocking the next stage in the natural history, the development of rigidity. Failed eradication worsens hypokinesia, as does the presence/persistence of H. pylori at molecular level only. Adequate prognostic assessment of the consequences of not treating Helicobacter, for IP, is prevented by a short follow-up. We conclude that Helicobacter is a pathophysiological driver of IP.
When Tissue Is Not the Issue: A Case of Antisynthetase Syndrome Complicated by Disseminated Mycobacterium avium Complex.

A ntisynthetase syndrome is a rare autoimmune disease characterized by variable expression of fever, myositis, interstitial lung disease, arthritis, Raynaud phenomenon, and distinctive dermatologic features. Opportunistic infections are commonwith this condition and can present with nonspecific symptoms, which are difficult to differentiate from the underlying rheumatic disease. We present a patient with antisynthetase syndromewho developed constitutional symptoms, eyelid nodules with heliotrope rash, and tender soft tissue masses of the extremities. Initial biopsy of these masses was favored to be panniculitis secondary to dermatomyositis (DM), which will generally present in a lobular pattern with a lymphocytic predominant inflammatory infiltrate and mucin deposition in the deep dermis. The histology of these soft tissue lesions, coupled with persistently negative cultures, created considerable diagnostic uncertainty in a patient ultimately found to have a disseminatedMycobacterium avium complex (MAC) infection. A high level of clinical suspicion is required in cases such as this to avoid inappropriate escalation of immunosuppression. A 33-year-old woman with a 6-year history of anti-PL12– positive antisynthetase syndrome presented with tender palpable masses of her right posterior and lateral thigh. Her autoimmune disease, which had initially manifested as myositis, arthritis, fever, interstitial lung disease, Raynaud phenomenon, heliotrope rash, and Gottron's papules, had recently been well controlled on lowdose azathioprine and prednisone. She endorsed 2 months of subjective fevers, chills, night sweats, and a 20-pound weight loss. Physical examination was notable for 2 new erythematous eyelid nodules overlying her chronic heliotrope rash (Figs. 1A–D). A punch biopsy of the right posterior thigh revealed a lobular panniculitis with mixed inflammatory infiltrate and increased mucin in the deep dermis, favoring panniculitis related to DM (Fig. 2). Despite these histologic findings, a high level of concern for infection remained and further evaluation was pursued. Magnetic resonance imaging (MRI) and computed tomography
EZH2 in Myeloid Malignancies

Our understanding of the significance of epigenetic dysregulation in the pathogenesis of myeloid malignancies has greatly advanced in the past decade. Enhancer of Zeste Homolog 2 (EZH2) is the catalytic core component of the Polycomb Repressive Complex 2 (PRC2), which is responsible for gene silencing through trimethylation of H3K27. EZH2 dysregulation is highly tumorigenic and has been observed in various cancers, with EZH2 acting as an oncogene or a tumor-suppressor depending on cellular context. While loss-of-function mutations of EZH2 frequently affect patients with myelodysplastic/myeloproliferative neoplasms, myelodysplastic syndrome and myelofibrosis, cases of chronic myeloid leukemia (CML) seem to be largely characterized by EZH2 overexpression. A variety of other factors frequently aberrant in myeloid leukemia can affect PRC2 function and disease pathogenesis, including Additional Sex Combs Like 1 (ASXL1) and splicing gene mutations. As the genetic background of myeloid malignancies is largely heterogeneous, it is not surprising that EZH2 mutations act in conjunction with other aberrations. Since EZH2 mutations are considered to be early events in disease pathogenesis, they are of therapeutic interest to researchers, though targeting of EZH2 loss-of-function does present unique challenges. Preliminary research indicates that combined tyrosine kinase inhibitor (TKI) and EZH2 inhibitor therapy may provide a strategy to eliminate the residual disease burden in CML to allow patients to remain in treatment-free remission.
5.2.9 Marteiliasis and Marteilioidiasis of Shellfish

The disease in shellfish known as Marteiliasis may result from infection of the upper digestive tract (rarely gills) by protozoan parasites in the phylum Paramyxea, class Marteiliidae of the genus Marteilia. Related parasites of the same class in the genus Marteilioides infect gills and oocytes. The type species is Marteilia refringens causing Abers Disease and “maladie de la glande digestive” in the European flat oyster Ostrea edulis. Marteilia maurini (Comps et al. 1982) was suggested to be a junior synonym of M. refringens based on the lack of significantly different ultrastructural morphologies (Longshaw, et al. 2001). Although this continues to make differentiation difficult, maurini has been validated by sequencing of the rRNA gene cluster (Berthe et al. 2000, Le Roux et al. 2001, Zrncic et al. 2001). Marteilia sydneyi is responsible for QX Disease in Australian Sydney rock oysters Saccostrea commercialis (glomerata).
Cardiac Involvement in Dystrophin-Deficient Females: Current Understanding and Implications for the Treatment of Dystrophinopathies

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive condition caused primarily by out-of-frame mutations in the dystrophin gene. In males, DMD presents with progressive body-wide muscle deterioration, culminating in death as a result of cardiac or respiratory failure. A milder form of DMD exists, called Becker muscular dystrophy (BMD), which is typically caused by in-frame dystrophin gene mutations. It should be emphasized that DMD and BMD are not exclusive to males, as some female dystrophin mutation carriers do present with similar symptoms, generally at reduced levels of severity. Cardiac involvement in particular is a pressing concern among manifesting females, as it may develop into serious heart failure or could predispose them to certain risks during pregnancy or daily life activities. It is known that about 8% of carriers present with dilated cardiomyopathy, though it may vary from 0% to 16.7%, depending on if the carrier is classified as having DMD or BMD. Understanding the genetic and molecular mechanisms underlying cardiac manifestations in dystrophin-deficient females is therefore of critical importance. In this article, we review available information from the literature on this subject, as well as discuss the implications of female carrier studies on the development of therapies aiming to increase dystrophin levels in the heart.
Phytoplankton sinking rates in the Rhine region of freshwater influence

According to Stokes' law, colony formation in phytoplankton would lead to enhanced sinking rates and higher sedimentation losses if colonies had the same densities as the phytoplankton cells they contain. In the Dutch coastal zone of the North Sea, algae settling out of the water column are subject to zoobenthos grazing or to physical mixing into the sediment and, therefore, the formation of colonies by common diatom species and the prymnesiophyte Phaeocystis globosa seems paradoxical: it would increase the probability that sedimentation becomes a significant loss factor. However, sinking rate measurements in the Rhine region of freshwater influence (ROFI) using SetCol settling columns did not reveal a straightforward relationship between phytoplankton sizes (1000 mum) and sinking rates (-0.4 to >2.2 m day(-1)) of 24 autotrophic phytoplankton species and groups. In fact, under nutrient-replete conditions, the sinking rates of the diatoms Chaetoceros radicans, Rhizosolenia shrubsolei and Rhizosolenia stolterfothii decreased with size. The sinking rates of large colonies of the prymnesiophyte P. globosa were also negatively correlated with their size and positive buoyancy was observed. Chlorophyll a sinking rates exceeded 1 m day(-1) periodically, which is sufficient to cause significant surface layer loss rates over 0.2 day(-1). Under stratified conditions, both chlorophyll a concentrations and sinking rates in the bottom layer were significantly higher (+49% and +16%, respectively) than in the surface layer. These observations are discussed in relation to Stokes' law, together with a critical analysis of the SetCol technique. It is concluded that: (i) SetCol gives adequate results when incubations are performed at or near in situ irradiance and temperature; (ii) sinking rates are predominantly determined by cell or colony density rather than their size; (iii) periodic sedimentation is an important species-specific loss process for phytoplankton in the Dutch coastal zone. It is speculated that for diatoms with low sinking rates, autolysis is an important loss factor.
Evaluating interventions to delay the progression of prediabetes to type-2 diabetes mellitus in an uninsured Hispanic population

ABSTRACT Background: Diabetes is a chronic progressive disease affecting 34 million Americans. The Centers for Disease Control and Prevention estimates that 12.5% of people aged 20 years or older diagnosed with diabetes are Hispanic. The American Diabetes Association further estimates that 84.1 million Americans aged 20 years and older have prediabetes based on fasting blood sugar and hemoglobin A1c (HbA1c) levels alone. Local problem: In Georgia, the overall rate of diagnosed diabetes is 9.7%, undiagnosed is 6.5%, and prediabetes is 1.1%. The prevalence of diabetes for the Hispanic population in Georgia is 9% and is 10% among Clayton County residents. The purpose of this quality improvement project (QIP) was to evaluate interventions implemented to delay the progressions of prediabetes to type-2 diabetes in an uninsured Hispanic population. Methods: Retrospective chart review was conducted comparing pre- and postmeasurements for HbA1c and body mass index (BMI) in Hispanic patients identified as having prediabetes. Interventions: Patients with HbA1c of 5.7–6.1% were provided with a diabetes tool kit, whereas patients with an HbA1c of 6.2–6.4% were given the diabetes tool kit plus metformin. Results: A decrease in mean HbA1c was noted in both groups of patients. However, a paired sample t-test indicated nonsignificant decrease in HbA1c for the diabetes tool kit group (p = .51) but significant decrease for the diabetes tool group kit plus metformin group (p < .01). Conclusions: Although this QIP did not reveal statistically significant changes in HbA1c and BMI for both groups, the results were clinically significant among this Hispanic population.
Hepatitis C virus genotype/subtype distribution and evolution among Chinese blood donors: Revealing recent viral expansion

Hepatitis C virus (HCV) genotype (GT) distribution in China shows significant geographical and demographic difference. As a routinely tested virus in Chinese blood bank systems, rare molecular epidemiology research in blood donors is reported. Our purpose is to investigate the HCV GT/subtypes distribution, phylogenetic analysis and population genetics in Chinese blood donors. Anti-HCV screen positive samples and donor demographics were collected. HCV Core and E1 gene fragments were amplified by RT-PCR, followed by sequencing and phylogenetic analysis to determine HCV GTs/subtypes using MEGA 7.0. The population genetics were performed using Arlequin v3.0 and Beast v1.10. 4. SPSS Statistics 17.0 software was used to analyze the correlation between HCV GTs/subtypes distribution and demographic characteristics. 419 and 293 samples based on Core and E1 gene respectively were successfully amplified. HCV la, lb, 2a, 3a, 3b, 6a, 6e and 6n were found, and the corresponding proportions were 0.66% (3/455), 58.68% (267/455), 17.80% (81/455) and 5.05% (23/455), 3.52% (16/455), 12.31% (56/455), 0.88% (4/455) and 0.66% (3/455). Samples from Guangxi showed the most abundant genetic diversity with 8 subtypes were found. The number of haplotypes in HCV-1b is higher than 2a and 6a. The negative Tajima's D and Fu's Fs values of HCV-1b, 2a and 6a suggested the population expansion of those HCV subtypes. The distribution of HCV GT showed significant statistical difference by age and ethnicity. Conclusion: An abundance of HCV genetic diversity was found in Chinese blood donors with mainly 1b and then 2a subtype. There were significant geographical and demographic differences in HCV GTs/subtypes among Chinese blood donors. HCV subtype 1b has stronger viability and HCV subtype 6a has experienced significant expansion.
Impacts of wind disturbance on fragmented tropical forests: A review and synthesis

Wind disturbance is an important ecological force in the tropics, especially in the cyclonic and hurricane zones from about 7-20 degrees latitude. Damage from intense winds may be especially severe in fragmented forests because of their abrupt artificial margins and denuded surrounding landscapes. We review available information on the effects of windstorms on fragmented forests, synthesizing studies from Australasia, Amazonia and elsewhere in the tropics. Wind damage in fragmented landscapes can be influenced by a range of factors, such as forest-edge orientation, edge structure, the size of nearby clearings and local topography. We argue that wind disturbances are likely to interact with, and exacerbate, a range of deleterious environmental changes in fragmented forests. Among the most important of these are altered forest structure, shifts in plant species composition, exotic-plant invasions, reduced carbon storage and elevated vulnerability to fire. The damaging impacts of winds on fragmented forests could potentially increase in the future, particularly if global warming leads to increasingly severe or frequent windstorms.
Safety and Antiviral Activity of MK-5172, a Novel HCV NS3/4a Protease Inhibitor with Potent Activity Against Known Resistance Mutants, in Genotype 1 and 3 HCV-Infected Patients

• MK-5172 is a novel, competitive inhibitor of the HCV NS3/4a protease with selective, potent in vitro activity against a broad range of HCV genotypes (GTs) and known viral variants that are resistant to other protease inhibitors in development. • MK-5172 exhibits excellent selectivity over other serine proteases such as elastase and trypsin (no measurable inhibition), and shows only modest inhibitory potency with chymotrypsin (IC 50 = 1.5 μM; 75,000-fold selective). • In the genotype 1b replicon assay, MK-5172 potently inhibits viral replication (IC 50 = 2 nM) and demonstrates a modest shift in the presence of 50% NHS (EC 50 = 9.5 nM). In vitro, MK-5172 inhibits the NS3/4A enzyme from genotypes 1b, 2a, 2b, and 3a with K i values of <0.02, 0.15, 0.02, and 0.7 nM, respectively. The genotype 2a replicon is also potently inhibited by MK-5172 (EC 50 = 5 nM).