Miracle-dz/UniFAR-FTUs huggingface dataset:
Bridging the gap between research into biological and psychosocial models of psychosis

Summary Paul Bebbington’s recent Special Article provides an excellent synthesis of recent advances in psychosocial research on psychosis. However, we doubt that a model based solely on social epidemiology and cognitive theory can totally describe psychosis, and to be fair, Bebbington does not suggest that it does. A complete model must also incorporate what we have learned from non-social epidemiology, neuroscience, and genetics. Evidence indicates that both the social risk factors that interest Bebbington and biological risk factors, such as abuse of stimulants and cannabis, can provoke psychotic symptoms by dysregulating striatal dopamine. The role of neurodevelopmental deviance also needs to be considered in the etiology of schizophrenia-like psychosis. Moreover, the striking advances in our understanding of the genetic architecture of psychosis open an exciting door into studies examining gene-environment correlation and gene-environment interaction. In short, Bebbington demonstrates the value of cognitive and social researchers talking to each other, but the occasional chat with the more biologically inclined could produce a more comprehensive model.
Potential role of poly(adenosine 5′-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock

Objective:Sepsis is associated with increased production of superoxide and nitric oxide, with consequent peroxynitrite generation. Cardiodepression is induced in the heart during oxidative stress associated with septic shock. Oxidative and nitrosative stress can lead to activation of the nuclear enzyme poly(adenosine 5′-diphosphate [ADP]-ribose) polymerase (PARP), with subsequent loss of myocardial contractile function. The aim of the study was to investigate whether cardiodepression found in septic patients is associated with plasma markers of myocardial necrosis and with myocardial PARP activation. Design:Prospective and observational study. Setting:University hospital intensive care unit for clinical and surgical patients. Patients:Twenty-five patients older than 18 yrs presenting with severe sepsis or septic shock. Patients with history of chronic heart failure, cancer, coronary artery disease, diabetes, or acquired immune deficiency syndrome were excluded. Interventions:Patients were followed for 28 days, and biochemical and hemodynamic data were collected on days 1, 3, and 6 of sepsis. The groups were survivors and nonsurvivors, defined only after the end of clinical patient evolution. Heart sections from patients who died were analyzed with hematoxylin-eosin and Picro Sirius-Red immunostaining and with electron microscopy. Measurements and Main Results:The study population included 25 individuals, of whom 12 (48%) died during the 6 days of follow-up. The initial data of the inflammation marker C-reactive protein and Acute Physiologic and Chronic Health. Evaluation severity were similar in both groups (nonsurvivors, 26 ± 2; survivors, 24 ± 5; NS). Overall, an increase in plasma troponin level was related to increased mortality risk. In patients who died, significant myocardial damage was detected, and histologic analysis of heart sections showed inflammatory infiltration, increased collagen deposition, and derangement of mitochondrial cristae. Immunohistochemical staining for poly(ADP-ribose) (PAR), the product of activated PARP, was demonstrated in septic hearts. There was a positive correlation between PAR staining densitometry and troponin I (r2 = 0.73; p < .05), and the correlation of PAR staining densitometry and left ventricular systolic stroke work index was r2 = 0.33 (p = .0509). Conclusion:There is significant PARP activation in the hearts of septic patients with impaired cardiac function. We hypothesize that PARP activation may be partly responsible for the cardiac depression seen in humans with severe sepsis.
Honey and Health: A Review of Recent Clinical Research

Honey is one of the most appreciated and valued natural products introduced to humankind since ancient times. Honey is used not only as a nutritional product but also in health described in traditional medicine and as an alternative treatment for clinical conditions ranging from wound healing to cancer treatment. The aim of this review is to emphasize the ability of honey and its multitude in medicinal aspects. Traditionally, honey is used in the treatment of eye diseases, bronchial asthma, throat infections, tuberculosis, thirst, hiccups, fatigue, dizziness, hepatitis, constipation, worm infestation, piles, eczema, healing of ulcers, and wounds and used as a nutritious supplement. The ingredients of honey have been reported to exert antioxidant, antimicrobial, anti-inflammatory, antiproliferative, anticancer, and antimetastatic effects. Many evidences suggest the use of honey in the control and treatment of wounds, diabetes mellitus, cancer, asthma, and also cardiovascular, neurological, and gastrointestinal diseases. Honey has a potential therapeutic role in the treatment of disease by phytochemical, anti-inflammatory, antimicrobial, and antioxidant properties. Flavonoids and polyphenols, which act as antioxidants, are two main bioactive molecules present in honey. According to modern scientific literature, honey may be useful and has protective effects for the treatment of various disease conditions such as diabetes mellitus, respiratory, gastrointestinal, cardiovascular, and nervous systems, even it is useful in cancer treatment because many types of antioxidant are present in honey. In conclusion, honey could be considered as a natural therapeutic agent for various medicinal purposes. Sufficient evidence exists recommending the use of honey in the management of disease conditions. Based on these facts, the use of honey in clinical wards is highly recommended.
Improve Performance Management in Flexible Business Processes

The performance of business processes is evaluated and monitored with the aim of identifying whether strategic and operational goals are being achieved. Most approaches about performance measurement have been defined over traditional highly repetitive and well-structured processes. However, current organizational and business needs have encouraged the appearance of customizable processes to manage collections of process variants derived from a process, and loosely specified processes to manage non-repeatable and unpredictable processes. However, current techniques of performance measurement have not evolved to the same pace that business processes, thus generating a gap between processes and the measurement of their performance. The thesis introduced in this paper, is focused on enhancing the performance measurement of business processes by means of the improvement of existing techniques for the definition of process performance indicators and their applicability to different types of processes. With this purpose a set of artifacts, including a metamodel, notations, tools and methodologies will be developed. They will be validated by means of case studies based on real scenarios.
Detection of pulmonary hypertension with multidetector CT and echocardiography alone and in combination.

PURPOSE To test the reliability of potentially new computed tomographic (CT) indicators of pulmonary hypertension (PH) and to establish whether a combination of CT and echocardiographic measurements was more predictive of PH than either test alone. MATERIALS AND METHODS The institutional review board approved this retrospective study; patient consent was not required. Seventy-seven patients undergoing right-sided heart catheterization were examined. CT diameters of the main pulmonary artery, ascending aorta, and thoracic vertebra and cross-sectional area of the main pulmonary artery were measured. Segmental and subsegmental arterial diameters were recorded, and segmental artery size was compared with adjacent bronchus size by using a semiquantitative scoring system. The relationship between CT measurements and mean pulmonary arterial pressure (mPAP) was tested with linear regression. Multivariate regression was used to establish a composite index of mPAP by using CT markers of PH with echocardiography-derived right ventricular systolic pressure (RVSP). Post hoc logistic regression and receiver operating characteristic curve analysis were performed to test the diagnostic ability of the CT-echocardiography composite. RESULTS The ratios of the diameter of the main pulmonary artery to the diameter of the ascending aorta (R(2) = 0.45; P < . 001) and of the cross-sectional area of the pulmonary artery to the diameter of the ascending aorta (R(2) = 0.45; P < . 001) correlated equally with mPAP. The ratio of the diameter of the main pulmonary artery to the diameter of the thoracic vertebra, the segmental arterial diameter, and the segmental artery-to-bronchus ratio were related to mPAP but did not strengthen correlations compared with the ratio of the diameter of the main pulmonary artery to the diameter of the ascending aorta alone. A composite index of the ratio of the diameter of the main pulmonary artery to the diameter of the ascending aorta and echocardiography-derived RVSP was more strongly related (R(2) = 0.55) to mPAP and was more significantly predictive of PH than either measure alone. CONCLUSION A combination of CT and echocardiographic markers of PH is more closely related to mPAP than either test in isolation.
Risk to the treating ophthalmologist when using the laser.

To the Editor. —Laser energy may be reflected back into the eyes of the treating ophthalmologist secondary to the filters falling off the shutter mechanism. During the last 2 years at our institution, two incidents have occurred in which the protective filters mounted onto the shutter of our argon/krypton laser fell off the shutter during treatment (Figure). A laser (Model 41AK) was purchased by our institution in June 1982 and was involved in both instances. On our laser, the filter for each eye is individually glued onto the shutter. Apparently, the glue did not maintain its bond over time, and one of the filters fell off the shutter. If the filters are mounted onto the shutter with glue only and not reinforced by some other mechanical means, the risk of the filters dislodging appears to be increased. An incident somewhat similar to ours has been reported with a Coherent Radiation
Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus

Staphylococcus aureus secretes the SSL7 protein as part of its immune evasion strategy. The protein binds both complement C5 and IgA, yet it is unclear whether SSL7 cross-links these two proteins and, if so, what purpose this serves the pathogen. We have isolated a stable IgA-SSL7-C5 complex, and our crystal structure of the C5-SSL7 complex confirms that binding to C5 occurs exclusively through the C-terminal β-grasp domain of SSL7 leaving the OB domain free to interact with IgA. SSL7 interacts with C5 >70 Å from the C5a cleavage site without inducing significant conformational changes in C5, and efficient inhibition of convertase cleavage of C5 is shown to be IgA dependent. Inhibition of C5a production and bacteriolysis are all shown to require C5 and IgA binding while inhibition of hemolysis is achieved by the C5 binding SSL7 β-grasp domain alone. These results provide a conceptual and structural basis for the development of a highly specific complement inhibitor preventing only the formation of the lytic membrane attack complex without affecting the important signaling functions of C5a.
From Active Ingredients to the Discovery of the Targets: The Cannabinoid Receptors

The story of the identification of cannabinoid receptors represents a fascinating interplay between chemistry, behavior, pharmacology, and molecular biology. In several ways, it parallels the discovery of the receptors for other neuromodulators; however, the complex nature of cannabis, the unique chemistry of the cannabinoids, and the social use of cannabis have all provided an extra 2zing4 to the story. In this paper
Synthesis, crystal structure, and anti-breast cancer activity of a novel metal-porphyrinic complex [YK(TCPP)(OH)2·(solvents)x]

A novel heterometallic metal-porphyrinic framework (MPFs) built from Y and K ions as nods and meso-tetra(4-carboxyphenyl)porphyrin as linkers has been successfully synthesized and characterized. The single crystal X-ray diffraction indicated that this complex 1 exhibited a bilayered architecture of the porphyrins, which is seldom seen in MPFs. In addition, in vitro anticancer activity of complex 1 on three human breast cancer cells (BT474, SKBr-3 and ZR-75-30) was further determined.
A highly efficient AgarTrap method for genetic transformation of mature thalli of the liverwort Marchantia polymorpha L.

Marchantia polymorpha L. has been established as a model liverwort species for understanding plant evolution, and several genetic transformation technologies have been developed. Recently, we described a simplified Agrobacteriummediated genetic transformation method termed AgarTrap (Agar-utilized Transformation with Pouring Solutions) that uses sporelings (S-AgarTrap) or gemmae/gemmalings (G-AgarTrap), both of which easily produce a sufficient number of independent transformants. In this study, we report the development of a novel AgarTrap protocol using mature pieces of liverwort thalli (T-AgarTrap). Optimal transformation efficiency was approximately 70%, and 100% transformation was achieved in a few experimental cases. The efficiency of T-AgarTrap was much greater than those of Sand G-AgarTrap methods. This highly efficient T-AgarTrap protocol seems to promote molecular research with M. polymorpha.
Her odours make him deaf: crossmodal modulation of olfaction and hearing in a male moth

SUMMARY All animals have to cope with sensory conflicts arising from simultaneous input of incongruent data to different sensory modalities. Nocturnal activity in moths includes mate-finding behaviour by odour detection and bat predator avoidance by acoustic detection. We studied male moths that were simultaneously exposed to female sex pheromones indicating the presence of a potential mate, and artificial bat cries simulating a predation risk. We show that stimulation of one sensory modality can modulate the response to information from another, suggesting that behavioural thresholds are dynamic and depend on the behavioural context. The tendency to respond to bat sounds decreased as the quality and/or the amount of sex pheromone increased. The behavioural threshold for artificial bat cries increased by up to 40 dB when male moths where simultaneously exposed to female sex pheromones. As a consequence, a male moth that has detected the pheromone plume from a female will not try to evade an approaching bat until the bat gets close, hence incurring increased predation risk. Our results suggest that male moths' reaction to sensory conflicts is a trade-off depending on the relative intensity of the input to CNS from the two sensory modalities.
Cation fluxes and volume regulation by human lymphocytes

The ionic basis of volume regulation by human peripheral blood lymphocytes in hypotonic Tyrode's medium has been studied. The intracellular water space of lymphocytes increased to a maximum after 1 min in 0.68 × isotonic Tyrode's but returned to the isotonic value by 20 min at 37°C. During this phase of volume regulation (1–20 min) both 42K+ efflux and 42K+ influx were stimulated severalfold, but the increase in 42K+ efflux exceeded the influx, resulting in a net loss of 20% of the lymphocyte K+. The increase in 42K+ efflux during the phase of cell shrinkage was unaffected by ouabain or by quinidine. Hypotonicity increased both the ouabain‐sensitive (active) and ouabain‐insensitive components of 42K+ influx by 76% and 123% respectively. Hypotonic shock stimulated 22Na+ influx by only 25%, but cell Na+ content was unchanged at 1 min and even decreased after 20 min. Thus active K+ influx and Na+ extrusion is increased by hypotonicity, but greater pumping cannot explain the net decrease in cell cations that leads to volume regulation. The 45Ca2+ uptake was not significantly changed by hypotonicity. Although volume regulation was abolished in a hypotonic high K medium, 42K+ efflux was still stimulated 2‐fold by the reduction in tonicity. These findings support the hypothesis that volume regulation in hypotonic media occurs largely by a passive loss of cell K+, which results from a selective increase in membrane permeability to this ion. The increase in K+ permeability in hypotonic media is observed even in the absence of volume regulation by the cell.
Lyn‐coupled LacCer‐enriched lipid rafts are required for CD11b/CD18‐mediated neutrophil phagocytosis of nonopsonized microorganisms

The integrin CD11b/CD18 plays a central role in neutrophil phagocytosis. Although CD11b/CD18 binds a wide range of ligands, including C3bi and β‐glucan, and transmits outside‐in signaling, the mechanism of this signaling responsible for phagocytosis remains obscure. Here, we report that lactosylceramide (LacCer)‐enriched lipid rafts are required for CD11b/CD18‐mediated phagocytosis of nonopsonized zymosans (NOZs) by human neutrophils. Anti‐CD11b and anti‐LacCer antibodies inhibited the binding of NOZs to neutrophils and the phagocytosis of NOZs. During phagocytosis of NOZ, CD11b and LacCer were accumulated and colocalized in the actin‐enriched phagocytic cup regions. Immunoprecipitation experiments suggested that CD11b/CD18 was mobilized into the LacCer‐enriched lipid rafts during phagocytosis of NOZs. DMSO‐treated, neutrophil‐like HL‐60 cells (D‐HL‐60 cells) lacking Lyn‐coupled, LacCer‐mediated signaling showed little phagocytosis of NOZs. However, loading of D‐HL‐60 cells with C24 fatty acid chain‐containing LacCer (C24‐LacCer) reconstructed functional Lyn‐associated, LacCer‐enriched lipid rafts, and restored D‐HL‐60 cell NOZ phagocytic activity, which was inhibited by anti‐LacCer and anti‐CD11b antibodies. Lyn knockdown by small interfering RNA blocked the effect of C24:1‐LacCer loading on D‐HL‐60 cell phagocytosis of NOZs. CD11b/CD18 activation experiments indicated phosphorylation of LacCer‐associated Lyn by activation of CD11b. Taken together, these observations suggest that CD11b activation causes translocation of CD11b/CD18 into Lyn‐coupled, LacCer‐enriched lipid rafts, allowing neutrophils to phagocytose NOZs via CD11b/CD18.
The clinical features and treatment outcome of chronic hepatitis C with pegylated interferon and ribavirin in routine care.

AIM To describe the clinical characteristic of hepatitis C (HCV) patients and the results of pegylated interferon and ribavirin (PegIFN/RBV) therapy in a routine clinical practice. METHODS A retrospective review of consecutive HCV patients treated with PegIFN/RBV in 2004 to 2012. RESULTS A total of 273 patients received treatment. The mean age was 44.16 ± 10.5 years and 76% were male. The top 2 self-reported risks were blood or blood product transfusion before 1994 and injection drug use, found in 57.1% of patients. The predominant HCV genotype (GT) was 3 at 60.6%, second was GT1 at 36.1% and other GTs were uncommon at about 1% or less. About half of our patients have high baseline viral load (>800,000 iu/ml), 18.3% had liver cirrhosis and 22.3% had HIV co-infection. Co-morbid illness was found in 42.9%, hypertension and type 2 diabetes were the two most common. The overall sustained virological response (SVR) by intention-to-treat analysis were 54.9% (n=150/273), 41.2% (40/97) for GT1, 100% (5/5) for GT2 and 62% (101/163) for GT3. Subgroup analysis for HCV monoinfected, treatment naïve showed SVR of 49.2% (31/63) for GT1, 100% (5/5) for GT2 and 67% (69/103) for GT3. In HCV mono-infected and treatment experienced (n=29), the SVR was 28.6% (4/14) for GT1, 21.4% (69/103) for GT3. In the HIV/HCV co-infected, treatment naïve (n=56), the SVR was 28.6% (4/14) for GT1 and 64.3% (27/42) for GT3. Treatment naïve GT3 mono-infected patients had a statistically significant higher SVR compared to treatment experienced patients (P=0.001). In GT3 patients who achieved rapid virological response, the SVR was significantly higher at 85.2% (P< 0.001). The SVR for cirrhotics were low especially for GT1 at 21% (4/19) and 31% (4/13) based on all patients and treatment naïve HCV monoinfected respectively. In GT3 cirrhotics the corresponding SVR were 57.1% (16/28) and 60.9% (14/23). Premature discontinuation rate was 21.2% with the majority due to intolerable adverse events at 12.1%. CONCLUSIONS In our routine clinical practice, the HCV patients we treated were young, predominantly of GT3 and many had difficult-to-treat clinical characteristics. The SVR of our patients were below those reported in Asian clinical trials but in keeping with some "real world" data.
Oxalate, Germins, and Higher‐Plant Pathogens

Earlier surveys ( 1, B. G. Lane. [1991] FASEB J. 5, 2983‐2901; 2, B. G. Lane. [1994] FASEB J. 8, 294‐301) helped to uproot entrenched views of plant oxalate as a static substance. It is now recognized that oxalate oxidases (OXOs) found in the “true cereals” (barley, maize, oat, rice, rye, wheat), the so‐called germin OXOs (G‐OXOs), or simply germins, are involved in cereal defence responses to invasion by fungal pathogens and that they show promise of being valuable agents of plant defence in dicotyledons, where they are not found naturally. G‐OXOs have very peculiar properties: (a) their water‐soluble oligomeric structures and enzymic activity are stable during SDS‐PAGE and nitrocellulose blotting, (b) their undenatured water‐soluble forms are refractory to the action of broad‐specificity proteases, (c) their water‐insoluble forms occur abundantly (∼50%) in the extracellular matrix (cell walls) of wheat, and probably in varying amounts in the cell walls of other true cereals. Transfer of the wheat G‐OXO coding element to dicotyledons has been found, in all cases so far examined, to result in improved resistance to fungal pathogens. The possible nature of the improved resistance is discussed in relation to (a) generation of microcidal concentrations of hydrogen peroxide when the G‐OXOs act on oxalate, (b) elicitation of hypersensitive cell death at lower concentrations of hydrogen peroxide, (c) formation of effective barriers against predator penetration by the hydrogen‐peroxide‐mediated lignification of cell walls, and (d) destruction of oxalate, which is an inhibitor of the hypersensitive response, a strategy of particular importance in the case of ubiquitous predator organisms such as Sclerotinia sclerotiorum, which secrete high concentrations of oxalate as a toxin.