Miracle-dz/UniFAR-FTUs huggingface dataset:
Some factors influencing adoption of sheltered dogs

Abstract In Italy the law forbids euthanizing shelter dogs unless they are severely ill or dangerous. This has created a problem: many dogs are housed for long periods of time in shelters. It is important to the welfare of these dogs for us to find methods to increase successful adoption rates. The aim of this study was to evaluate the effect of different management factors such as the number of dogs in a pen, Temporary Adoption Programs (TAPs), and animal-owner-related characteristics on successful adoptions of kenneled dogs. The study included 763 dogs, 92 of whom were dogs showing behavioral problems. The age of the dogs upon arrival at the shelter was the most important determinant for length of stay, with younger dogs being adopted faster (Kruskal-Wallis, H = 150.27; df = 3; n = 733; p < 0.001). Dogs up to six months of age (n = 73) were adopted more quickly than older dogs (average length of stay: 1.4 vs. 6.4 months). The year of admittance was also significant since dogs who were admitted in a year in which more dogs were brought to the shelter spent more time in the shelter before being re-homed (Kruskal-Wallis, H = 96.18; df = 2; n = 733; p < 0.001). Dogs' gender had no effect on length of stay (Mann-Whitney, U = 64563; Z = 0.81; p = ns; n1 = 389; n2 = 344). Temporary Adoption Programs had a significant positive effect in reducing the return rate when the final adopter was the same person who had “temporarily” adopted the dog (Fisher exact test, p = 0.0063). Return rate was also associated with behavioral problems. Fearful dogs were returned more often than dogs with other problems (Fisher exact test, p = 0.029). It is concluded that, although young age is the most important factor leading to quick adoption, programs which include increased human interaction, and special training for dogs with behavioral problems, could aid in the successful re-homing of shelter dogs.
Predictors of response to serotonin reuptake inhibitors in obsessive-compulsive disorder

ABSTRACT Introduction: 40–60% of patients with obsessive compulsive disorder (OCD) do not respond adequately to serotonin reuptake inhibitors (SRIs). It is important to identify predictors of response to help individualize treatment and identify refractory patients early in the course of treatment. Areas covered: We review the current literature on predictors of response to SRIs in adult patients with OCD including clinical features, neuropsychological profile, neuroimaging, genetics and other biological factors. We conducted a literature search in PUBMED database using the MeSH terms ‘Obsessive-Compulsive Disorder’, ‘drug therapy’, ‘treatment outcome’, ‘neuroimaging’, ‘genetics’ ‘cytokines’ and obtained 60 articles. Expert commentary: Poor-insight into obsessions, symmetry/hoarding and contamination/washing dimension and the presence of certain personality disorders are associated with poor response to SRIs. Orbitofrontal cortex, anterior cingulate cortex, caudate, putamen and thalamus volume changes in structural imaging studies and altered activity in the same regions in functional imaging studies were found predictive of poor response. However, there is inconsistency with regards to direction of change. Genes involving serotonergic and glutamatergic signalling pathways have emerged as predictors in recent studies. Studies with large sample size, standardised methodology and rigorous statistical analyses are required before predictors can be utilised in routine clinical practice.
Omega-3 fatty acids (ῳ-3 fatty acids) in epilepsy: animal models and human clinical trials

ABSTRACT Introduction: There is growing interest in alternative and nutritional therapies for drug resistant epilepsy. ῳ-3 fatty acids such as fish or krill oil are widely available supplements used to lower triglycerides and enhance cardiovascular health. ῳ-3 fatty acids have been studied extensively in animal models of epilepsy. Yet, evidence from randomized controlled clinical trials in epilepsy is at an early stage. Areas covered: This report focuses on the key ῳ-3 fatty acids DHA and EPA, their incorporation into the lipid bilayer, modulation of ion channels, and mechanisms of action in reducing excitability within the central nervous system. This paper presents pre-clinical evidence from mouse, rat, and canine models, and reports the efficacy of n-3 fatty acids in randomized controlled clinical trials. An English language search of PubMed and Google scholar for the years 1981–2016 was performed for animal studies and human randomized controlled clinical trials. Expert commentary: Basic science and animal models provide a cogent rationale and substantial evidence for a role of ῳ-3 fatty acids in reducing seizures. Results in humans are limited. Recent Phase II RCT evidence suggests that low to moderate dose of ῳ-3 fatty acids reduce seizures; however, larger multicenter randomized trials are needed to confirm or refute the evidence. The safety, health effects, low cost and ease of use make ῳ-3 fatty acids an intriguing alternative therapy for drug resistant epilepsy. Though safety of profile is excellent, the human data is not yet sufficient to support efficacy in drug resistant epilepsy at this time.
Myasthenia gravis: recent advances in immunopathology and therapy

ABSTRACT Introduction: Myasthenia gravis is the most frequent acquired disorder of neuromuscular transmission. In the majority of cases, pathogenic antibodies against components of the postsynaptic muscle endplate membrane can be detected. In recent years there have been significant advances in the pathophysiological understanding and therapy of the disease. Areas covered: PubMed searches were conducted for the term ‘myasthenia gravis’ cross-referenced with the terms ‘immunology’, ‘subgroups’, ‘antibody’, ‘ocular’, ‘thymoma’, ‘treatment’ and ‘thymectomy’. Additionally, we summarized the current state of immunopathology and therapy. Expert commentary: Immunological research defined new target antigens at the postsynaptic neuromuscular junction which along with clinical features allow a refined definition of disease subgroups. Overall the prognosis of myasthenia gravis with best possible symptomatic, immunosuppressive and supportive treatment is good but new immunomodulatory treatment options are developed for patients who do not respond well to the first line therapy. For most patients individually adapted long-term drug therapy is needed.
Beyond serotonin: newer antidepressants in the future

ABSTRACT Introduction: There are numerous antidepressants for the treatment of major depressive disorder (MDD) on the market. However, inadequate treatment response, therapeutic lag between drug administration and the onset of clinical improvement, and safety/tolerability issues with the use of contemporary antidepressants have accelerated the search for newer antidepressants with novel mechanisms of action. Areas covered: The authors review novel antidepressants with rapid efficacy for diverse MDD symptoms and have fewer adverse effects (AEs). Mechanisms of action for novel therapeutic molecules are through glutamatergic, opiate, cholinergic receptors and neuroplasticity. We enumerate results from human trials with novel agents in all phases, highlighting proximity to approval and therapeutic potential based on quality of evidence. Expert commentary: There is a huge unmet need to diversify conventional antidepressant targets. Glutamatergic and opiate agents may be most promising among newer therapeutic agents. It is also important to develop advanced but flexible synergistic treatment strategies with newer therapeutic agents that are usable in routine clinical practice. This would include combining newer molecules with existing antidepressants and using molecules that target specific symptom dimensions of MDD. These strategies would lead to a systematic approach to tackle treatment resistant depression (TRD) and treatment of residual symptoms in partially remitted MDD.
Pharmacological treatment of tardive dyskinesia: recent developments

ABSTRACT Introduction: Tardive dyskinesia (TD) occurs in patients receiving antipsychotic treatment with dopamine receptor antagonists. Despite the prevalence of TD and its negative impact on patients’ lives, there has been a lack of approved treatments and limited evidence from controlled trials of pharmacological treatment. Areas covered: PubMed was searched for English-language papers published during 2007–2016 using terms ‘tardive dyskinesia’ or ‘drug-induced movement disorder’, and ‘treatment’. Studies evaluating pharmacological agents for the treatment of TD were selected. A total of 26 studies (five meta-analyses, twelve randomized controlled trials, and nine open-label observational studies) are reviewed. Expert commentary: Treatment of TD necessitates a stepwise approach. Optimization of antipsychotic therapy should be considered before initiation of antidyskinetic therapies. Data from some recent studies indicate possible improvements in TD after switching antipsychotics or with the use of amantadine, levetiracetam, piracetam, zonisamide, propranolol, vitamin B6, or certain unregulated herbal medicines; although significance of these improvements is unclear and require further investigation in randomized controlled trials. By contrast, recent evidence from Phase III trials of novel vesicular monoamine transporter-2 inhibitors demonstrates they could have a significant effect on TD symptom severity and suggests these agents may have the potential to transform treatment of TD in coming years.
Renal Medullary Infusion of Indomethacin and Adenosine

Perfusion of the renal medulla and osmotic hypertonicity of its interstitium are the two important features of this zone which can influence body fluid homeostasis, especially arterial blood pressure. Separate manipulation of the two variables is best obtained with the intramedullary infusion of active agents. In this study, a set-up combining the possibility of infusion into the medulla with measurement of local blood flow (MBF, laser-Doppler flux) and extracellular ion concentration (tissue electrical admittance, Y) was used to determine effects of intramedullary indomethacin (Indo) and adenosine (Ado) in anaesthetized rats. Intramedullary Indo, 1 mg kg–1 h–1, significantly increased tissue Y, by 12 ± 3%, and significantly decreased MBF by 20 ± 3%. There was also an unexplained increase of sodium excretion (UNaV) by 169 ± 24% and of urine flow (V) by 62 ± 6% (n = 10, both p < 0.03). Intramedullary Ado, 5 µg kg–1 h–1, did not alter Y, MBF or UNaV, whereas V increased 45 ± 6% and urine osmolality decreased 25 ± 4% (both changes significant). Elevation of medullary interstitial Ado to a level that did not alter MBF or UNaV induced a moderate defect of urine concentration that was not due to a decrease in ionic medullary hypertonicity.
Motivation to Quit Smoking and to Refrain From Drinking in a Sample of Alcohol-dependent Inpatients: Importance of Abstinence, Self-efficacy, and Treatment Outcome

ObjectivesHeavy smoking is likely to increase the risk of relapse after treatment for alcohol dependence. Research on smoking cessation motivation in alcohol-dependent individuals may facilitate the development of individually tailored interventions aimed at abstinence from tobacco. MethodsTwo hundred and eighty-seven alcohol-dependent smokers being treated for alcohol dependence were asked to complete measures of importance of abstinence from alcohol, alcohol abstinence self-efficacy, importance of abstinence from tobacco, and tobacco abstinence self-efficacy. Treatment outcome was evaluated 12 weeks after discharge from the hospital in a subsample of 110 individuals. ResultsBoth importance of abstinence and abstinence self-efficacy differed across types of drug. Likewise, the strength of the correlation between importance and self-efficacy differed across types of drug. Neither importance nor self-efficacy predicted the risk of relapse. Most interestingly, however, tobacco abstinence self-efficacy was positively related to the duration of the first drinking episode after discharge from the hospital. ConclusionsTobacco abstinence self-efficacy might more accurately predict an individual's future success to cope with the urge to drink than alcohol abstinence self-efficacy.
The Core Diseasome.

Large amounts of protein-protein interaction (PPI) data are available. The human PPI network currently contains over 56 000 interactions between 11 100 proteins. It has been demonstrated that the structure of this network is not random and that the same wiring patterns in it underlie the same biological processes and diseases. In this paper, we ask if there exists a subnetwork of the human PPI network such that its topology is the key to disease formation and hence should be the primary object of therapeutic intervention. We demonstrate that such a subnetwork exists and can be obtained purely computationally. In particular, by successively pruning the entire human PPI network, we are left with a "core" subnetwork that is not only topologically and functionally homogeneous, but is also enriched in disease genes, drug targets, and it contains genes that are known to drive disease formation. We call this subnetwork the Core Diseasome. Furthermore, we show that the topology of the Core Diseasome is unique in the human PPI network suggesting that it may be the wiring of this network that governs the mutagenesis that leads to disease. Explaining the mechanisms behind this phenomenon and exploiting them remains a challenge.
Utility function design for strategic radio resource management games: An overview, taxonomy, and research challenges

Radio resource management is important for wireless communication networks. Game theory has been extensively used to model, analyze, and design interactive behaviors and the strategic decision‐making for radio resource management. It is known that utility function is one of the critical elements in a game, which characterizes the preferred relationship of the rational players and is a function of the action of players and their opponents. We first overview the basics of game theory and utility functions. We then present a taxonomy of utility functions with respect to different types of players, the nature of actions, and preferences in terms of the fairness, quality of service, and quality of experience. We provide some insights based on the taxonomy of utility functions, which provides the readers with a comprehensive view. Following that, we also discuss other types of traffic‐aware utility functions with different fairness and the potential and super modular game‐theoretic utility functions. In addition, we summarize the desired properties and observations for the design of suitable utility functions. Finally, we investigate impacts of the pricing in utility functions. This article ends with the conclusions and a promising view on open problems and challenges with possible future research directions.
CNS immune privilege: hiding in plain sight

Summary: Central nervous system (CNS) immune privilege is an experimentally defined phenomenon. Tissues that are rapidly rejected by the immune system when grafted in sites, such as the skin, show prolonged survival when grafted into the CNS. Initially, CNS immune privilege was construed as CNS isolation from the immune system by the blood–brain barrier (BBB), the lack of draining lymphatics, and the apparent immunoincompetence of microglia, the resident CNS macrophage. CNS autoimmunity and neurodegeneration were presumed automatic consequences of immune cell encounter with CNS antigens. Recent data have dramatically altered this viewpoint by revealing that the CNS is neither isolated nor passive in its interactions with the immune system. Peripheral immune cells can cross the intact BBB, CNS neurons and glia actively regulate macrophage and lymphocyte responses, and microglia are immunocompetent but differ from other macrophage/dendritic cells in their ability to direct neuroprotective lymphocyte responses. This newer view of CNS immune privilege is opening the door for therapies designed to harness autoreactive lymphocyte responses and also implies (i) that CNS autoimmune diseases (i.e. multiple sclerosis) may result as much from neuronal and/or glial dysfunction as from immune system dysfunctions and (ii) that the severe neuronal and glial dysfunction associated with neurodegenerative disorders (i.e. Alzheimer’s disease) likely alters CNS‐specific regulation of lymphocyte responses affecting the utility of immune‐based therapies (i.e. vaccines).
A paradigm shift in therapeutic vaccination of cancer patients: the need to apply therapeutic vaccination strategies in the preventive setting

Summary: An extraordinary variety of potential therapeutic vaccine strategies directed against a wide variety of tumor antigens has been explored in clinical trials. To date, none of these cancer immunotherapies have been approved by the Food and Drug Administration for use in humans. A significant problem is that the vast majority of such clinical trials are carried out in patients with advanced or metastatic cancer. The immune systems of these patients are considerably compromised as a result of tumor‐ and treatment‐mediated immunosuppression. Even in cases where patients are immunized in the adjuvant setting, where there is minimal residual disease, vaccines directed against tumor‐associated antigens have failed to mediate eradication of tumors in the overwhelming majority of cases. Recently, we and others have experimented with administering therapeutic cancer vaccines in the preventive setting. This is achieved by vaccinating at the earliest possible stage of carcinogenesis. These studies have demonstrated that early vaccination is extremely effective in eliciting an anti‐tumor immune response that leads to unprecedented improvements in the survival of mice that spontaneously develop cancer. Certain human cancers, notably prostate adenocarcinoma and cervical cancer, can currently be detected at very early stages of carcinogenesis. Therapeutic vaccines are available for these diseases, opening up the possibility of administering vaccinations early to patients diagnosed with pre‐malignant lesions to halt disease progression. In addition, new technologies have become available in the past decade that will soon yield very sensitive and specific diagnostic tests for a plethora of other cancers. Earlier detection of these cancers, combined with existing vaccines directed against them, will soon make them targets for therapeutic vaccination in the preventive setting. The ability to immunize patients at the very earliest stages of carcinogenesis, when they have fully competent immune systems, has the potential to cause a paradigm shift in how therapeutic cancer vaccines are tested and used clinically.
Formulary Drug Reviews - Tocilizumab

Each month, subscribers to The Formulary Monograph Service receive five to six well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I. X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I. X. , call The Formulary at 800-322-4349. The June 2010 monograph topics are on rifaximin in hepatic encephalopathy, ticagrelor, fingolimod, doxepin hydrochloride tablets, and carglumic acid tablets. The DUE/MUE is on rifaximin.
Molecular and cellular regulation of pancreatic duct cell function

Purpose of review The pancreatic duct epithelium is remarkable for its capacity to secrete HCO3− ions at concentrations as high as 140 mmol/l. The properties of the key transporters involved in this process and the central role played by cystic fibrosis transmembrane conductance regulator (CFTR) are the main focus of this review. Recent findings The Cl−/HCO3− exchanger at the apical membrane of pancreatic duct cells is now known to be SLC26A6. The 1: 2 stoichiometry and electrogenicity of this exchanger enable it to contribute to the secretion of HCO3− at high concentrations. The apical CFTR channels also appear to have sufficient HCO3− permeability to contribute directly to HCO3− secretion. There is a strong possibility that the Ca2+-activated Cl− channels at the apical membrane are members of the bestrophin family which, like CFTR, are also permeable to HCO3−. More has been learned about the complex interactions between CFTR and other transporters within macromolecular complexes coordinated at the apical membrane by scaffolding proteins. Further details are also emerging of the protective paracrine roles of nucleotides, nucleosides, bile acids and trypsin in the regulation of ductal secretion. Summary Most of the key transporters involved in Cl− and HCO3− secretion have now been identified and characterized. Current research focuses on the molecular interactions between these transporters and the ways in which they are regulated by extracellular signals.
An update on cholangiocarcinoma associated with primary sclerosing cholangitis

Purpose of review Primary sclerosing cholangitis (PSC) is being diagnosed with increasing frequency. The most feared complication is the presence or development of cholangiocarcinoma (CCA). The present review summarizes recent data with regards to diagnosis, pathobiology and treatment. Recent findings Several investigations have focused on aspects of the molecular biology of CCA in general; such data should be explored now in the context of PSC-related CCA to yield new diagnostic markers and approaches for therapy. Summary CCA has to be suspected in any new PSC patient presenting with jaundice. Exploration should include carbohydrate antigen19-9 and two imaging techniques. Endoscopic cholangioscopy might become very rewarding. Important progress has been achieved in liver transplantation by the use of preoperative radio-chemotherapy. Molecular biology points to inflammation-induced cytokines with mutagenic action and to the relevance of extracellular matrix proteins for invasion but also for proliferation. Micro-RNAs prove to be very important in the control of cell proliferation, differentiation and apoptosis. Mutated p53, cyclins, wnt/β-catenin signaling, proliferation indices, mucins, carbohydrate antigen19-9, CRP and aneuploidy appear to hold significant potential as predictors of outcome in CCA. It is expected that the further unraveling of these molecular processes will ultimately lead to development of tests allowing early diagnosis and to development of medical approaches to retard tumor formation or recurrence following surgical interventions.