Miracle-dz/UniFAR-FTUs huggingface dataset:
Intramuscular vaccination of mice with the human herpes simplex virus type-1(HSV-1) VC2 vaccine, but not its parental strain HSV-1(F) confers full protection against lethal ocular HSV-1 (McKrae) pathogenesis

Herpes simplex virus type-1 (HSV-1) can cause severe ocular infection and blindness. We have previously shown that the HSV-1 VC2 vaccine strain is protective in mice and guinea pigs against genital herpes infection following vaginal challenge with HSV-1 or HSV-2. In this study, we evaluated the efficacy of VC2 intramuscular vaccination in mice against herpetic keratitis following ocular challenge with lethal human clinical strain HSV-1(McKrae). VC2 vaccination in mice produced superior protection and morbidity control in comparison to its parental strain HSV-1(F). Specifically, after HSV-1(McKrae) ocular challenge, all VC2 vaccinated- mice survived, while 30% of the HSV-1(F)- vaccinated and 100% of the mock-vaccinated mice died post challenge. VC2-vaccinated mice did not exhibit any symptoms of ocular infection and completely recovered from initial conjunctivitis. In contrast, HSV-1(F)-vaccinated mice developed time-dependent progressive keratitis characterized by corneal opacification, while mock-vaccinated animals exhibited more severe stromal keratitis characterized by immune cell infiltration and neovascularization in corneal stroma with corneal opacification. Cornea in VC2-immunized mice exhibited significantly increased infiltration of CD3+ T lymphocytes and decreased infiltration of Iba1+ macrophages in comparison to mock- or HSV-1(F)-vaccinated groups. VC2 immunization produced higher virus neutralization titers than HSV-1(F) post challenge. Furthermore, VC-vaccination significantly increased the CD4 T central memory (TCM) subsets and CD8 T effector memory (TEM) subsets in the draining lymph nodes following ocular HSV-1 (McKrae) challenge, then mock- or HSV-1(F)-vaccination. These results indicate that VC2 vaccination produces a protective immune response at the site of challenge to protect against HSV-1-induced ocular pathogenesis.
Phenolic Fractions from Dandelion Leaves and Petals as Modulators of the Antioxidant Status and Lipid Profile in an In Vivo Study

Alcoholic leaf and petal fractions of Taraxacum officinale (dandelion) were previously demonstrated to exert in vitro antioxidant and antithrombotic activities in blood plasma and platelets. Eight-week-old male Wistar rats (n = 6) were supplemented for four weeks with dandelion fractions (694 mg/kg of diet = 11.9 ± 0.6 mg daily). Dandelion leaf and petal fractions, which delivered daily 4.10 ± 0.05 and 1.41 ± 0.07 mg l-chicoric acid, respectively, were shown to exert antioxidative actions, measured as decreased levels of thiobarbituric acid-reactive substances (TBARS) in the spleen (≈0.8-fold, leaves and petals), brain (0.53-fold, leaves) and thoracic arteries (0.59-fold, petals). Moreover, petal fraction increased thiols in the blood plasma (1.58-fold), while leaf fraction decreased protein carbonylation levels (0.59-fold). Additionally, dandelion leaf fractions modified the lipid profile: decreased triglyceride (0.44-fold), total cholesterol (0.73-fold), lipoprotein combine index (0.32-fold) and the atherogenic index of plasma (0.62-fold). Dandelion fractions showed a beneficial decrease effect in the participation of cyclooxygenase products in the noradrenaline-induced vascular contractions of thoracic arteries. Meanwhile, only the dandelion leaf fraction augmented acetylcholine-induced vasodilation and upregulated KATP channels. The heart rate and blood pressure were not modified. Dandelion leaf and petal phenolic fractions, enriched with l-chicoric acid, are promising plant materials that may exert in vivo beneficial antioxidant effects.
New Insight into Plant Signaling: Extracellular ATP and Uncommon Nucleotides

New players in plant signaling are described in detail in this review: extracellular ATP (eATP) and uncommon nucleotides such as dinucleoside polyphosphates (NpnN’s), adenosine 5′-phosphoramidate (NH2-pA), and extracellular NAD+ and NADP+ (eNAD(P)+). Recent molecular, physiological, and biochemical evidence implicating concurrently the signaling role of eATP, NpnN’s, and NH2-pA in plant biology and the mechanistic events in which they are involved are discussed. Numerous studies have shown that they are often universal signaling messengers, which trigger a signaling cascade in similar reactions and processes among different kingdoms. We also present here, not described elsewhere, a working model of the NpnN’ and NH2-pA signaling network in a plant cell where these nucleotides trigger induction of the phenylpropanoid and the isochorismic acid pathways yielding metabolites protecting the plant against various types of stresses. Through these signals, the plant responds to environmental stimuli by intensifying the production of various compounds, such as anthocyanins, lignin, stilbenes, and salicylic acid. Still, more research needs to be performed to identify signaling networks that involve uncommon nucleotides, followed by omic experiments to define network elements and processes that are controlled by these signals.
Genomics of Detoxification: How Genomics can be Used for Targeting Potential Intervention and Prevention Strategies Including Nutrition for Environmentally Acquired Illness

Abstract Due to their genomic variants, some individuals are more highly affected by toxicants than others. Toxicant metabolizing and activating variants have been linked with a wide variety of health issues including an increased risk of miscarriages, birth defects, Alzheimer’s, benzene toxicity, mercury toxicity and cancer. The study of genomics allows a clinician to identify pathways that are less effective and then gives the clinician the opportunity to counsel their patients about diet, supplements and lifestyle modifications that can improve the function of these pathways or compensate to some extent for their deficits. This article will review a few of these critical pathways relating to phase I and phase 2 detox such as GSTP1, GPX1, GSTT1 deletions, PON1 and some of the CYP 450 system as examples of how an individual's genomic vulnerabilities to toxicants can be addressed by upregulating or downregulating specific pathways via genomically targeted use of foods, supplements and lifestyle changes.
Inter- and intraindividual variability in daily resting heart rate and its associations with age, sex, sleep, BMI, and time of year: Retrospective, longitudinal cohort study of 92,457 adults

Background Heart rate is routinely measured as part of the clinical examination but is rarely acted upon unless it is well outside a population-based normal range. With wearable sensor technologies, heart rate can now be continuously measured, making it possible to accurately identify an individual’s “normal” heart rate and potentially important variations in it over time. Our objective is to describe inter- and intra-individual variability in resting heart rate (RHR) collected over the course of two years using a wearable device, studying the variations of resting heart rate as a function of time of year, as well as individuals characteristics like age, sex, average sleep duration, and body mass index (BMI). Methods and findings Our retrospective, longitudinal cohort study includes 92,457 de-identified individuals from the United States (all 50 states), who consistently—over at least 35 weeks in the period from March 2016 to February 2018, for at least 2 days per week, and at least 20 hours per day—wore a heart rate wrist-worn tracker. In this study, we report daily RHR and its association with age, BMI, sex, and sleep duration, and its variation over time. Individual daily RHR was available for a median of 320 days, providing nearly 33 million daily RHR values. We also explored the range in daily RHR variability between individuals, and the long- and short-term changes in the trajectory of an individual’s daily RHR. Mean daily RHR was 65 beats per minute (bpm), with a range of 40 to 109 bpm among all individuals. The mean RHR differed significantly by age, sex, BMI, and average sleep duration. Time of year variations were also noted, with a minimum in July and maximum in January. For most subjects, RHR remained relatively stable over the short term, but 20% experienced at least 1 week in which their RHR fluctuated by 10 bpm or more. Conclusions Individuals have a daily RHR that is normal for them but can differ from another individual’s normal by as much as 70 bpm. Within individuals, RHR was much more consistent over time, with a small but significant seasonal trend, and detectable discrete and infrequent episodes outside their norms.
Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer’s Disease

Worldwide, Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease and is characterized by unique pathological hallmarks in the brain, including plaques composed of amyloid β-protein (Aβ) and neurofibrillary tangles of tau protein. Genetic studies, biochemical data, and animal models have suggested that Aβ is responsible for the pathogenesis of AD (i.e., the amyloid hypothesis). Indeed, Aβ molecules tend to aggregate, forming oligomers, protofibrils, and mature fibrils. However, while these Aβ species form amyloid plaques of the type implicated in AD neurodegeneration, recent clinical trials designed to reduce the production of Aβ and/or the plaque burden have not demonstrated clinical efficacy. In addition, recent studies using synthetic Aβ peptides, cell culture models, Arctic transgenic mice, and human samples of AD brain tissues have suggested that the pre-fibrillar forms of Aβ, particularly Aβ protofibrils, may be the most critical species, compared with extracellular fibrillar forms. We recently reported that protofibrils of Aβ1-42 disturbed membrane integrity by inducing reactive oxygen species generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and synaptic toxicity. Therefore, the therapeutic reduction of protofibrils may prevent the progression of AD by ameliorating neuronal damage and cognitive dysfunction through multiple mechanisms.
Endovascular Thrombectomy of Calcified Emboli in Acute Ischemic Stroke: A Multicenter Study

BACKGROUND AND PURPOSE: Large intracranial vessel occlusion due to calcified emboli is a rare cause of major stroke. We assessed the prevalence, imaging appearance, the effectiveness of mechanical thrombectomy, and clinical outcome of patients with large-vessel occlusion due to calcified emboli. MATERIALS AND METHODS: We performed a retrospective analysis of clinical and procedural data of consecutive patients who underwent mechanical thrombectomy due to calcified emboli in 7 European stroke centers. RESULTS: We screened 2969 patients, and 40 patients matched the inclusion criteria, accounting for a prevalence of 1.3%. The mean maximal density of the thrombus was 327 HU (range, 150–1200 HU), and the mean thrombus length was 9.2 mm (range, 4–20 mm). Four patients had multiple calcified emboli, and 2 patients had an embolic event during an endovascular intervention. A modified TICI score of ≥2b was achieved in 57.5% (23/40), with minimal-to-no reperfusion (modified TICI 0–1) in 32.5% (13/40) and incomplete reperfusion (modified TICI 2a) in 10% (4/40). Excellent outcome (mRS 0–1) was achieved in only 20.6%, functional independence (mRS 0–2) in 26.5% and 90-day mortality was 55.9%. CONCLUSIONS: Acute ischemic stroke with large-vessel occlusion due to calcified emboli is a rare entity in patients undergoing thrombectomy, with considerably worse angiographic outcome and a higher mortality compared with patients with noncalcified thrombi. Good functional recovery at 3 months can still be achieved in about a quarter of patients.
My body is not working right: a cognitive behavioral model of body image and chronic pain.

Chronic pain profoundly affects several areas of a person’s life. One facet which has received relatively little attention is the relationship between a person’s perception of their body—ie, their body image (BI)—and their pain experience. Within the pain literature, BI is mostly understood from a sensorimotor perspective where BI refers to implicit cortical maps that encodemovement and position of the body. Lotze and Moseley defined BI as the conscious experience of how one’s body feels to its owner and proposed that BI is a dynamic construct maintained by ongoing tactile, proprioceptive, and visual input, which can be modulated by memory, belief, and psychosocial factors. An important assumption is that pain influences how patients perceive their body (through sensorimotor neurological processes), but the reverse is not highlighted, ie, how one’s BI may influence one’s experience of pain. The psychological literature defines BI similarly but emphasizes the multifaceted experience that entails imagery, appraisals, feelings, and behaviors related to one’s body, with a particular focus on appearance. The same processes are involved in pain, with the addition of functional limitations, which in turn may influence BI.We argue for broadening the conceptualization of BI in chronic pain, with a stronger focus on the bidirectional link between BI and pain. Although BI distortions are well known in clinical psychology, less is known about whether BI distortions play a role in the experience of chronic pain. There is cause, however, to believe this because how we view our body and our pain is influenced by several internal and external factors including psychological processes involved in both chronic pain and BI disorders. Because BI disturbances (eg, eating disorders and body dysmorphic disorder) revolve around perceptual exaggerations of particular aspects and areas of the body, people with such problems might experience pain differently, eg, more intensely. Furthermore, since pain is known to alter thought patterns and cognitions, this might also contribute to changes in BI. For example, hypervigilant scanning of the pain area may lead to perceptual distortions of that body area and preoccupation with it. Similarly, because both pain and BI distortions can trigger intense negative emotions (such as anger, fear, and shame), these may contribute to mutual maintenance of these problems. Finally, recent theoretical advances in the pain literature on mind–body interactions also propose that the experience of pain can alter nonpain perceptions, including distorted body perceptions. This article reviews the literature on the relationship between BI and pain, and incorporating ideas from psychopathology, we propose a cognitive behavioral model emphasizing the bidirectional links between distorted BI and chronic pain.
Positioning ustekinumab in moderate-to-severe ulcerative colitis: new kid on the block

ABSTRACT Introduction: Ulcerative colitis (UC) is a chronic relapsing disorder of the colonic tract. Dysregulated innate and adaptive immune pathways contribute to intestinal inflammation in IBD, and cytokines, including IL-12 and IL-23, play a key role. The blockade of both IL-12 and IL-23 may have an impact on different pathways of inflammation and could be effective for the treatment of inflammatory bowel diseases. Ustekinumab is a fully human IgG1κ monoclonal antibody which binds to the shared p40 protein subunit of IL-12 and −23. It is currently approved for several immune-mediated diseases such as moderate to severe plaque psoriasis, psoriatic arthritis, and Crohn’s disease, and has shown promising results in UC. Areas covered: A review of the literature was performed to understand several aspects including the role of IL-12 and −23 in UC, the potential therapeutic role of ustekinumab in inflammatory bowel disease, and the positioning of ustekinumab in the therapeutic algorithm of UC, based on extrapolated data from available randomized clinical trials. Expert opinion: Ustekinumab is effective and safe in UC, and shows potential advantages compared to other drugs in moderate-to-severe UC.
Hospital-based surveillance of influenza A(H1N1)pdm09 virus in Saudi Arabia, 2010-2016

ABSTRACT BACKGROUND: Influenza is a highly contagious acute viral respiratory tract infection. The emergence of influenza A(H1N1)pdm09 in 2009 caused a pandemic. Since then it has become a seasonal influenza virus. It causes symptoms ranging from mild to severe illness, which might be fatal, particularly in people with underlying chronic medical conditions, immunocompromised people, the elderly, and pregnant women. OBJECTIVE: Describe the data generated by the influenza A(H1N1) pdm09 surveillance in Saudi Arabia from 2010 to 2016. DESIGN: Retrospective, descriptive. SETTING: Hospitals reporting to the Ministry of Health. MATERIALS AND METHODS: We studied aggregate data on hospitalized cases of influenza A(H1N1)pdm09 in Saudi Arabia between 2010 and 2016. The surveillance system used the case definition proposed by the WHO. The cases were confirmed by performing the real-time PCR (polymerase chain reaction) on upper respiratory samples. MAIN OUTCOME MEASURES: Suspected and confirmed influenza A(H1N1)pdm09 cases. SAMPLE SIZE: 113 502 suspected H1N1 cases and 17 094 (15.1%) confirmed cases. RESULTS: Most of the reported cases were registered in the Riyadh region. During the period of the study, the highest number of confirmed cases, 9262 (54.2 %), was in 2015. The case fatality rate for confirmed cases was 3.6%. CONCLUSION: Influenza A(H1N1)pdm09 showed seasonal trends. The number of suspected influenza cases each year was proportionate to the number of confirmed cases for that year. Riyadh, Jeddah and the Eastern areas (regions with the highest population) reported most of the cases. LIMITATION: Only one strain of H1N1 was tested. CONFLICT OF INTEREST: None.
Microalbuminuria in arterial hypertension

Microalbuminuria is a considerable good indicator of atherogenic disease and cardiovascular risk. In the arterial hypertension, the main centre organ is the kidney. Structural and functional changes that happen in the hypertensive nephropathy are going to cause alterations m the albumin urinary excretion. The authors have done a revision of the main factors which can origin the existence of microalbuminuria in patients with arterial hypertension, and they conclude that this is an useful biochemist indicator in order to evaluate the degree of renal disease in these patients.
Testosterone and Adult Neurogenesis

It is now well established that neurogenesis occurs throughout adulthood in select brain regions, but the functional significance of adult neurogenesis remains unclear. There is considerable evidence that steroid hormones modulate various stages of adult neurogenesis, and this review provides a focused summary of the effects of testosterone on adult neurogenesis. Initial evidence came from field studies with birds and wild rodent populations. Subsequent experiments with laboratory rodents have tested the effects of testosterone and its steroid metabolites upon adult neurogenesis, as well as the functional consequences of induced changes in neurogenesis. These experiments have provided clear evidence that testosterone increases adult neurogenesis within the dentate gyrus region of the hippocampus through an androgen-dependent pathway. Most evidence indicates that androgens selectively enhance the survival of newly generated neurons, while having little effect on cell proliferation. Whether this is a result of androgens acting directly on receptors of new neurons remains unclear, and indirect routes involving brain-derived neurotrophic factor (BDNF) and glucocorticoids may be involved. In vitro experiments suggest that testosterone has broad-ranging neuroprotective effects, which will be briefly reviewed. A better understanding of the effects of testosterone upon adult neurogenesis could shed light on neurological diseases that show sex differences.
Early neuromuscular blockade in acute respiratory distress syndrome: to personalize or paralyze?

Acute respiratory distress syndrome (ARDS) is an inflammatory condition of the lungs characterized by acute hypoxemic respiratory failure and non-cardiogenic pulmonary edema (1). This is typically caused by direct lung injury (e.g., pneumonia); however, it can also be the result of indirect injury as well (e.g., non-pulmonary sepsis). ARDS is associated with significant mortality (1-3). Severity is graded using the arterial to inspired oxygen ratio (PF ratio) and can prognosticate survival and ventilator-free days (1-3). Those that survive are often left with significant reductions in functional capacity (4).
Trajectories of change in well-being during cognitive behavioral therapies for anxiety disorders: Quantifying the impact and covariation with improvements in anxiety.

Cognitive behavioral therapy (CBT) has been found to be very effective in reducing many forms of mental illness, but much less is known about whether CBT also promotes mental health or well-being. The goals of the present study were to (a) quantify the magnitude and timing of changes in overall well-being and specific facets of well-being during different CBTs for anxiety disorders, (b) determine whether these effects vary across transdiagnostic and disorder-specific CBT, and (c) examine how changes in well-being during treatment relate to changes in anxiety. A total of 223 adults (55.6% female, Mage = 31.1 years) were randomized to 1 of 5 CBT protocols for anxiety disorders at an outpatient clinic. Analyses included standardized mean gain effect sizes (ESsg) and latent growth curve modeling. Moderate-to-large increases in overall well-being and the 3 components of subjective, psychological, and social well-being were observed, mainly during the second half of CBT, and these increases were maintained at a 6-month follow-up. The magnitude of effects was comparable for transdiagnostic and disorder-specific CBT protocols and greater than in the waitlist condition. Parallel process latent growth curve models indicated that trajectories of change in well-being across treatment were strongly correlated with trajectories of change in clinician-rated and self-reported anxiety. Together, these findings suggest that different CBT protocols for anxiety consistently produce robust and lasting changes in well-being, and these changes are strongly linked to changes in anxiety during treatment. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Comparable Postprandial Amino Acid and Gastrointestinal Hormone Responses to Beef Steak Cooked Using Different Methods: A Randomised Crossover Trial

Cooking changes the texture and tenderness of red meat, which may influence its digestibility, circulatory amino acids (AA) and gastrointestinal (GI) hormonal responses in consumers. In a randomised crossover intervention, healthy males (n = 12) consumed a beef steak sandwich, in which the beef was cooked by either a pan-fried (PF) or sous-vide (SV) method. Plasma AA were measured by ultrahigh performance liquid chromatography (UPLC), while plasma GI hormones were measured using a flow cytometric multiplex array. Following meat ingestion, the circulatory concentrations of some of the essential AA (all the branched-chain AA: leucine, isoleucine and valine; and threonine), some of the nonessential AA (glycine, alanine, tyrosine and proline) and some of the nonproteogenic AA (taurine, citrulline and ornithine) were increased from fasting levels by 120 or 180 min (p < 0.05). There were no differences in circulating AA concentrations between cooking methods. Likewise, of the measured GI hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) concentrations increased from fasting levels after consumption of the steak sandwich (p < 0.05), with no differences between the cooking methods. In the healthy male adults, protein digestion and circulating GI hormone responses to a beef-steak breakfast were unaltered by the different cooking methods.