Miracle-dz/UniFAR-FTUs huggingface dataset:
Theoretical Analysis and Computational Predictions of Protein Thermostability

The interest in finding the keys to the thermal stabilization of proteins has remained constant and unquestionable throughout the last twenty years. This article reviews the most recent theoretical and computer advances related to the problem of thermally stabilizing proteins. Although comparison between mesophilic and thermophilic sequences has suggested some thermostabilization mechanisms, it has not been able 'per se' to provide unambiguous thermostabilization rules applicable for every case. Two of the mechanisms used by nature are seen as the major factors governing thermostability: the electrostatic forces of charged amino acids within a protein and the packing of its hydrophobic core on the other. Other mechanisms that have also been implicated (i.e. hydrogen bonding, �� helix stabilization, backbone rigidifying, etc), may play a refining role, based on the principle that nature has punctually and opportunistically thermostabilized proteins in each particular case, thereby solving each specific problem. How electrostatic and hydrophobic forces affect each other is still remains a largely open question and some recently developed criteria based on these two effects have been analyzed in the review.
The Remarkable Effectiveness of Time-Dependent Damping Terms for Second Order Evolution Equations

We consider a second order linear evolution equation with a dissipative term multiplied by a time-dependent coefficient. Our aim is to design the coefficient in such a way that all solutions decay in time as fast as possible. We discover that constant coefficients do not achieve the goal and neither do time-dependent coefficients, if they are uniformly too big. On the contrary, pulsating coefficients which alternate big and small values in a suitable way prove to be more effective. Our theory applies to ordinary differential equations, systems of ordinary differential equations, and partial differential equations of hyperbolic type.
Phosphodiesterase 4B Mediates Extracellular Signal-regulated Kinase-dependent Up-regulation of Mucin MUC5AC Protein by Streptococcus pneumoniae by Inhibiting cAMP-protein Kinase A-dependent MKP-1 Phosphatase Pathway*

Background: Mucus overproduction is a hallmark of otitis media (OM) induced by Streptococcus pneumoniae. Results: PDE4B mediates S. pneumoniae-induced MUC5AC up-regulation by inhibiting the expression of a negative regulator MKP-1. Conclusion: PDE4-specific inhibitor rolipram inhibits S. pneumoniae-induced MUC5AC up-regulation. Significance: Identifying PDE4B as a molecular target for inhibiting MUC5AC by up-regulating MKP-1 may have significant therapeutic potential for treating OM. Otitis media (OM) is the most common childhood bacterial infection and the major cause of conductive hearing loss in children. Mucus overproduction is a hallmark of OM. Streptococcus pneumoniae is the most common Gram-positive bacterial pathogen causing OM. Among many mucin genes, MUC5AC has been found to be greatly up-regulated in the middle ear mucosa of human patients with OM. We previously reported that S. pneumoniae up-regulates MUC5AC expression in a MAPK ERK-dependent manner. We also found that MAPK phosphatase-1 (MKP-1) negatively regulates S. pneumoniae-induced ERK-dependent MUC5AC up-regulation. Therapeutic strategies for up-regulating the expression of negative regulators such as MKP-1 may have significant therapeutic potential for treating mucus overproduction in OM. However, the underlying molecular mechanism by which MKP-1 expression is negatively regulated during S. pneumoniae infection is unknown. In this study we show that phosphodiesterase 4B (PDE4B) mediates S. pneumoniae-induced MUC5AC up-regulation by inhibiting the expression of a negative regulator MKP-1, which in turn leads to enhanced MAPK ERK activation and subsequent up-regulation of MUC5AC. PDE4B inhibits MKP-1 expression in a cAMP-PKA-dependent manner. PDE4-specific inhibitor rolipram inhibits S. pneumoniae-induced MUC5AC up-regulation both in vitro and in vivo. Moreover, we show that PDE4B plays a critical role in MUC5AC induction. Finally, topical and post-infection administration of rolipram into the middle ear potently inhibited S. pneumoniae-induced MUC5AC up-regulation. Collectively, these data demonstrate that PDE4B mediates ERK-dependent up-regulation of mucin MUC5AC by S. pneumoniae by inhibiting cAMP-PKA-dependent MKP-1 pathway. This study may lead to novel therapeutic strategy for inhibiting mucus overproduction.
Spread of Oropouche Virus into the Central Nervous System in Mouse

Oropouche virus (OROV) is an important cause of arboviral illness in Brazil and other Latin American countries, with most cases clinically manifested as acute febrile illness referred to as Oropouche fever, including myalgia, headache, arthralgia and malaise. However, OROV can also affect the central nervous system (CNS) with clinical neurological implications. Little is known regarding OROV pathogenesis, especially how OROV gains access to the CNS. In the present study, neonatal BALB/c mice were inoculated with OROV by the subcutaneous route and the progression of OROV spread into the CNS was evaluated. Immunohistochemistry revealed that OROV infection advances from posterior parts of the brain, including the periaqueductal gray, toward the forebrain. In the early phases of the infection OROV gains access to neural routes, reaching the spinal cord and ascending to the brain through brainstem regions, with little inflammation. Later, as infection progresses, OROV crosses the blood-brain barrier, resulting in more intense spread into the brain parenchyma, with more severe manifestations of encephalitis.
Evidence‐based Epileptology, Randomized Controlled Trials, and SANAD: A Critical Clinical View

This commentary, by a clinical epileptologist, contributes to a debate about evidence-based medicine (EBM) and randomized controlled trials (RCTs) in epilepsy, and about the newly published RCT which compares standard with new antiepileptic drugs (SANAD). Some of my comments may be critical but are not unique from a clinician’s point of view (Caplan, 2001). Finding solutions first requires the identification of the problem, and diagnostic precision is at the nub. I acknowledge the magnitude of dilemmas facing methodological experts in conducting RCTs. However, diagnostic precision, high-quality methodology, and accurate interpretation are of paramount importance. I should first clarify that like most clinical epileptologists I employ the same rules and procedures as applied in any other discipline of clinical medicine, emphasizing diagnostic precision through a process of thorough differentiation as the basis for any management decision (Panayiotopoulos, 2007). It is through this approach that key advances in epileptology have been made, including the differentiation of focal from generalized onset epilepsies, and the recognition of common epileptic syndromes. Other clinicians approach epilepsy as a unitary diagnosis or as a simple dichotomy between focal and generalized epilepsies. Such an approach may have pragmatic advantages when trying to undertake large-scale populationbased epidemiological or RCTs. However, as in other areas of medicine, diagnostic precision in the epilepsies has become more refined over time and treatment has become more disease-specific.
Semantic Annotation for Places in LBSN through Graph Embedding

With the prevalence of location-based social networks (LBSNs), automated semantic annotation for places plays a critical role in many LBSN-related applications. Although a line of research continues to enhance labeling accuracy, there is still a lot of room for improvement. The crucial problem is to find a high-quality representation for each place. In previous works, the representation is usually derived directly from observed patterns of places or indirectly from calculated proximity amongst places or their combination. In this paper, we also exploit the combination to represent places but present a novel semi-supervised learning framework based on graph embedding, called Predictive Place Embedding (PPE). For place proximity, PPE first learns user embeddings from a user-tag bipartite graph by minimizing supervised loss in order to preserve the similarity of users visiting analogous places. User similarity is then transformed into place proximity by optimizing each place embedding as the centroid of the vectors of its check-in users. Our underlying idea is that a place can be considered as a representative of all its visitors. For observed patterns, a place-temporal bipartite graph is used to further adjust place embeddings by reducing unsupervised loss. Extensive experiments on real large LBSNs show that PPE outperforms state-of-the-art methods significantly.
Predictors of distress associated with psychotic-like anomalous experiences in clinical and non-clinical populations.

OBJECTIVES Psychotic-like anomalous experiences are not inherently distressing, nor do they inevitably lead to clinical conditions. However, distress is an important predictor of onset and relapse in psychosis, and a primary indicator of problematic mental health. This study aimed to identify factors that predict distress across three groups with anomalous experiences. DESIGN AND METHODS This study used a cross-sectional design. Participants in 'Diagnosed' (n = 35), 'At Risk' (n = 20), and 'Undiagnosed' (n = 36) groups completed the Appraisals of Anomalous Experiences Interview (AANEX; Brett et al., 2007, Br. J. Psychiatry, 191, s23), which taps anomalies experienced, appraisals, and other psychological and contextual variables. A series of ordinal logistic regression analyses was conducted to investigate which variables predicted anomaly-related distress. RESULTS Predictors of higher distress were anomalous states characterized by changes in awareness and cognitive functioning (rather than more typical positive symptoms), appraisals of experiences as caused by 'other people', and greater attempted control over experiences. Predictors of lower distress were 'spiritual' appraisals, greater perceived social support/understanding, greater perceived controllability, and reacting with a 'neutral response'. CONCLUSIONS While psychotic-like experiences themselves are not necessarily distressing, appraisals and responses to anomalies do predict distress, as do factors relating to the social context. This adds support to the cognitive-behavioural models, and continuum models, of positive psychotic symptoms.
Macrophage responses to implants: prospects for personalized medicine

Implants, transplants, and implantable biomedical devices are mainstream solutions for a wide variety of human pathologies. One of the persistent problems around nondegradable metallic and polymeric implants is failure of macrophages to resolve the inflammation and their tendency to stay in a state, named “frustrated phagocytosis. ” During the initial phase, proinflammatory macrophages induce acute reactions to trauma and foreign materials, whereas tolerogenic anti‐inflammatory macrophages control resolution of inflammation and induce the subsequent healing stage. However, implanted materials can induce a mixed pro/anti‐inflammatory phenotype, supporting chronic inflammatory reactions accompanied by microbial contamination and resulting in implant failure. Several materials based on natural polymers for improved interaction with host tissue or surfaces that release anti‐inflammatory drugs/bioactive agents have been developed for implant coating to reduce implant rejection. However, no definitive, long‐term solution to avoid adverse immune responses to the implanted materials is available to date. The prevention of implant‐associated infections or chronic inflammation by manipulating the macrophage phenotype is a promising strategy to improve implant acceptance. The immunomodulatory properties of currently available implant coatings need to be improved to develop personalized therapeutic solutions. Human primary macrophages exposed to the implantable materials ex vivo can be used to predict the individual's reactions and allow selection of an optimal coating composition. Our review describes current understanding of the mechanisms of macrophage interactions with implantable materials and outlines the prospects for use of human primary macrophages for diagnostic and therapeutic approaches to personalized implant therapy.
Effectiveness of a mind-body skills training program for healthcare professionals.

CONTEXT Because of the increased use and benefits of mind-body therapies, it is important that healthcare professionals receive training in these modalities. OBJECTIVE To determine whether healthcare professionals who attended the Center for Mind-Body Medicine's training program were incorporating mind-body skills into their professional or personal practices and whether they had a greater sense of life satisfaction. DESIGN Repeated measures analysis. SETTING Annual training programs were held in hotels and conference centers in the US. PARTICIPANTS Four hundred fifty-one healthcare professionals attended the programs from 1998 to 2001. Two hundred fifty-nine completed the one-year follow-up survey, and 307 completed the well-being survey. INTERVENTION The week-long program included didactic and experiential training in biofeedback, meditation, autogenics, imagery, and movement/exercise, as well as self-expression in small groups through drawings, written exercises, and genograms. MAIN OUTCOME MEASURES Questionnaires on previous training and personal and professional use of mind-body approaches were administered before and one year after the program. The Existential Well-Being (EWB) scale also was administered before and immediately after the training. RESULTS There was a significant increase in the personal use of mind-body skills and the number of participants who were teaching their clients to use all modalities and a significant decrease in the number of participants who were referring clients to others for training. Participants also had significantly higher life satisfaction scores after the program. CONCLUSION This professional training program was effective in promoting the personal and professional use of mind-body skills and in enhancing the personal fulfillment of trainees.
Predicting response to anti‐TNF‐alpha treatment in Hidradenitis suppurativa

Hidradenitis suppurativa (HS) is comparatively common, frequently causes impairment and almost always presents a therapeutic challenge. In spite of this, it remains an understudied disease, and studies linking existing knowledge and experience are therefore particularly valuable as they provide insight and perspective. Using flow cytometry, in 2007, Giamarellos-Bourboulis et al. described an altered immune response in patients with HS, suggesting a role for tumour necrosis factor (TNF)-a and the innate immune system in the pathogenesis of the disease. Later, increased amounts of circulating, as well as lesional, TNF-a were found, supporting the previous observations. In parallel, the use of TNF-a blockers for the treatment of HS was being studied in case series. In consequence of these observational studies, small investigator-initiated randomized controlled trials were published indicating a positive treatment effect of TNF-a blockers on HS. Not all patients however respond, and other immune mechanisms such as an excessive T helper 17 response, a lack of interleukin-22 and abnormalities of the innate immune system have been studied. For the innate immune system both low and high expression of various markers have been described, making the interpretation of the findings more complex. In spite of the increased interest in HS, the underlying reasons for these immunological abnormalities remain obscure, but leave the reader with the impression that early suggestions of immune dysregulation are gradually gaining support. In their article in this issue of BJD, Giamarellos-Bourboulis’ group links genetic polymorphisms in the promoter region of the TNF gene to both disease severity and response to antiTNF-a treatment, suggesting a genetic background for the inflammatory consequences of the immunological abnormalities of HS as well as response to therapy. Many questions remain to be answered, but this paper begins to link some of the known islands in the sea of unknown.
PLATELETS AND THROMBOPOIESIS Platelets lacking PIP5KI g have normal integrin activation but impaired cytoskeletal-membrane integrity and adhesion

anchoring of their integrins to the underlying cytoskeleton. Platelets lacking both the p90 and p87 PIP5KI g isoforms had normal integrin activation and actin dynamics, but impaired anchoring of their integrins to the cytoskeleton. Most importantly, they formed weak shear-resistant adhesions ex vivo and unstable vascular occlusions in vivo. Together, our studies demonstrate that, although PIP5KI g is essential for normal platelet function, individual isoforms of PIP5KI g fulfill unique roles for the integrin-dependent integrity of the membrane cytoskeleton and for the stabilization of platelet adhesion. ( Blood . 2013;121(14):2743-2752) found that mice lacking the p90 splice variant of PIP5KI g develop normally as well. Together, these data suggest that p87 PIP5KI g is essential for the development of the cardiovascular system.
Increased tissue factor pathway inhibitor in patients with acute myocardial infarction

We examined hemostatic abnormalities in 23 patients with acute myocardial infarction (AMI), 10 with pulmonary embolism (PE), and 10 with deep vein thrombosis (DVT). At the onset of AMI, plasma levels of tissue‐type plasminogen activator (t‐PA), PA inhibitor‐I (PAI‐I), fibrin‐D‐dimer, thrombin‐antithrombin complex (TAT), and plasmin‐plasmin inhibitor complex (PPIC) were significantly increased. Both the plasma total TFPI and free‐TFPI levels in the AMI patients were significantly higher than those in the healthy volunteers, PE patients, and DVT patients. There was no significant difference in total TFPI or free‐TFPI among patients with PE, those with DVT, and healthy volunteers. One hour after percutaneous transluminal coronary angioplasty (PTCA) in the AMI group, the total TFPI level was further increased, and it was significantly reduced 24 hr after PTCA, to a level similar to that in healthy volunteers. Free‐TFPI showed a pattern similar to that of total TFPI. The ratio of free‐TFPI/total TFPI was highest 1 hr after PTCA. Increased TFPI in AMI patients might be released from ischemic tissues. Am. J. Hematol. 55:183–187, 1997. © 1997 Wiley‐Liss, Inc.
Coconut oil and palm oil's role in nutrition, health and national development: A review.

Coconut and palm oils which were the major sources of dietary fats for centuries in most of West Africa have been branded as unhealthy highly saturated fats. Their consumption has been peddled to supposedly raise the level of blood cholesterol, thereby increasing the risk of coronary heart disease. This adverse view has led to a reduction in their consumption in West Africa and they have been substituted for imported vegetable oils. Recent information however, indicates some beneficial effects of these oils particularly their roles in nutrition, health and national development. There is the need for a better understanding of their effects on health, nutritional status and national development. This paper therefore attempts to review the roles which coconut and palm oils play in these respects in developing countries, as a means of advocating for a return to their use in local diets. FUNDING None declared.
Propentofylline and Other Adenosine Transport Inhibitors Increase the Efflux of Adenosine Following Electrical or Metabolic Stimulation of Rat Hippocampal Slices

Abstract: Propentofylline is a novel neuroprotective agent that has been shown to act as an adenosine transport inhibitor as well as an adenosine receptor antagonist. In the present series of experiments we have compared the effects of propentofylline with those of known adenosine transport inhibitors and receptor antagonists on the formation of adenosine in rat hippocampal slices. The ATP stores were labeled by incubating the slices with [3H]‐adenine. The total 3H overflow and the overflow of endogenous and 3H‐labeled adenosine, inosine, and hypoxanthine were measured. Adenosine release, secondary to ATP breakdown, was induced both by hypoxia/hypoglycemia and by electrical field stimulation. Propentofylline (20–500 µM) increased the release of endogenous and radiolabeled adenosine, without increasing the total release of purines. Thus, the drug altered the pattern of released purines, i.e., increasing adenosine and decreasing inosine and hypoxanthine. This pattern, which was observed when purine release was induced both by electrical field stimulation and by hypoxia/hypoglycemia, was shared by the nucleoside transport inhibitor dipyridamole (1 µM) and by mioflazine (1 µM) and nitrobenzylthioinosine (1 µM). By contrast, other xanthines, including theophylline (100 µM) and 8‐cyclopentyltheophylline (10 µM), enprofylline (100 µM), or torbafylline (300 µM), if anything, increased the total release of purines without alterations of the pattern of release. These results indicate that nucleoside transport inhibitors can decrease the release of purines from cells and at the same time increase the concentration of extracellular adenosine, possibly by preventing its uptake and subsequent metabolism. This change in purine metabolism may be beneficial with regard to cell damage after ischemia. The results also indicate that propentofylline behaves in such a potentially beneficial manner.
Weissellicin 110, a Newly Discovered Bacteriocin from Weissella cibaria 110, Isolated from Plaa-Som, a Fermented Fish Product from Thailand

ABSTRACT Weissella cibaria 110, isolated from the Thai fermented fish product plaa-som, was found to produce a bacteriocin active against some gram-positive bacteria. Bacteriocin activity was not eliminated by exposure to high temperatures or catalase but was destroyed by exposure to the proteolytic enzymes proteinase K and trypsin. The bacteriocin from W. cibaria 110 was purified, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the purified bacteriocin contained one protein band that was approximately 2.5 kDa in size. Mass spectrometry analysis showed the mass of the peptide to be approximately 3,487.8 Da. N-terminal amino acid sequence analysis was performed, and 27 amino acids were identified. Because it has no similarity to other known bacteriocins, this bacteriocin was defined as a new bacteriocin and termed weissellicin 110.
Association Among SNAP-25 Gene DdeI and MnlI Polymorphisms and Hemodynamic Changes During Methylphenidate Use

Objective: To investigate the interaction of treatment-related hemodynamic changes with genotype status for Synaptosomal associated protein 25 (SNAP-25) gene in participants with attention deficit hyperactivity disorder (ADHD) on and off single dose short-acting methylphenidate treatment with functional near-infrared spectroscopy (fNIRS). Method: A total of 15 right-handed adults and 16 right-handed children with DSM-IV diagnosis of ADHD were evaluated. Ten milligrams of short-acting methylphenidate was administered in a crossover design. Results: Participants with SNAP-25 DdeI T/T genotype had decreased right deoxyhemoglobin ([HHb]) with treatment. SNAP-25 MnlI genotype was also associated with right deoxyhemoglobin ([HbO2]) and [HHb] changes as well as left [HHb] change. When the combinations of these genotypes were taken into account, the participants with [DdeI C/C or T/C and MnlI G/G or T/G] genotype had increased right [HHb] with MPH use whereas the participants with [DdeI T/T and MnlI T/T] or [DdeI T/T and MnlI G/G or T/G] genotypes had decreased right prefrontal [HHb]. Conclusions: These results suggested that SNAP-25 polymorphism might be associated with methylphenidate induced brain hemodynamic changes in ADHD participants.