Miracle-dz/UniFAR-FTUs huggingface dataset:
Age‐related macular degeneration: using morphological predictors to modify current treatment protocols

To assess predictors of treatment response in neovascular age‐related macular degeneration (AMD) in an attempt to develop a patient‐centric treatment algorithm. We conducted a systematic search using PubMed, EMBASE and Web of Science for prognostic indicators/predictive factors with the key words: ‘age related macular degeneration’, ‘neovascular AMD’, ‘choroidal neovascular membrane (CNV)’, ‘anti‐vascular endothelial growth factor (anti‐VEGF)’, ‘aflibercept’, ‘ranibizumab’, ‘bevacizumab’, ‘randomized clinical trials’, ‘post‐hoc’, ‘prognostic’, ‘predictive’, ‘response’ ‘injection frequency, ‘treat and extend (TAE), ‘pro re nata (PRN)’, ‘bi‐monthly’ and ‘quarterly’. We only included studies that had an adequate period of follow‐up (>1 year), a single predefined treatment regimen with a predetermined re‐injection criteria, an adequate number of patients, specific morphological [optical coherence tomography (OCT)] criteria that predicted final visual outcomes and injection frequency and did not include switching from one drug to the other. We were able to identify seven prospective studies and 16 retrospective studies meeting our inclusion criteria. There are several morphological and demographic prognostic indicators that can predict response to therapy in wet AMD. Smaller CNV size, subretinal fluid (SRF), retinal angiomatous proliferation (RAP) and response to therapy at 12 weeks (visual, angiographic or OCT) can all predict good visual outcomes in patients receiving anti‐VEGF therapy. Patients with larger CNV, older age, pigment epithelial detachment (PED), intraretinal cysts (IRC) and vitreomacular adhesion (VMA) achieved less visual gains. Patients having VMA/VMT required more intensive treatment with increased treatment frequency. Patients with both posterior vitreous detachment (PVD) and SRF require infrequent injections. Patients with PED are prone to recurrences of fluid activity with a reduction in visual acuity (VA). A regimen that involves less intensive therapy and extended follow‐up intervals (4 weekly) can be suggested for patients who show adequate visual response and have both SRF and PVD at baseline. In addition, patients with poor prognostic indicators such as IRC, VMA, large CNV size, older age and poor response at 12 weeks should be extended very cautiously with the possibility of fixed monthly/bimonthly (every 2 months) treatments if they fail to achieve dryness. Patients with PED at baseline should receive monthly/bimonthly injections of anti‐VEGF therapy or can be extended very cautiously (two weekly intervals) using a TAE protocol.
Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies

Cyclosporine and tacrolimus reduce allograft rejection, improve allograft half-life and patient survival. Ironically, the nephrotoxicity of these agents may adversely affect allograft survival in renal transplant recipients or cause end-stage renal diseases in other solid organ and bone marrow transplant recipients. Acute dose-dependent and chronic non-dose-dependent nephrotoxicity has been reported in both transplant recipients and patients with autoimmune disorders. Preliminary evidence suggests that drug therapeutic monitoring has little value in the diagnosis or management of nephrotoxicity associated with calcineurin inhibitors. Although the exact mechanism of nephrotoxicity is not fully understood, several factors have been implicated in the pathogenesis of immunosuppressive-induced nephrotoxicity. Renal and systemic vasoconstriction, increased release of endothelin-1, decreased production of nitric acid and increased expression of TGF-beta are the major adverse pathophysiologic abnormalities of these agents. Reducing the dose of a calcineurin inhibitor, or using protocols without calcineurin inhibition may ultimately minimize the risk of drug toxicity and improve allograft and patient survival. New experiences with non-nephrotoxic agents and protocols including mycophenolate and sirolimus allow for early calcineurin inhibitor reduction or elimination without increasing the risk of allograft rejection.
Numerical investigation of microfluidic flow under AC applied electric field: Enhanced of binding reaction for a biosensor

Binding reaction is a natural characteristic that is applied to design biosensors. In this study we simulate the binding reaction kinetics between the immobilized antibody and the targeted antigen in a reaction chamber (microchannel) of a biosensor under AC applied electric field. The diffusion boundary layer on the sensitive area of the biosensor would hinder the binding reaction from association and dissociation. We studied the influence of the shape and position of reaction surface under AC applied voltage on the binding reaction. The electrothermal force, produced by the AC electric field can induce a pair of vortices to stir the flow field over the reacting surface allowing accelerate the binding reaction. Our approach may contribute to efficient development and optimization of a biosensor for medical applications.
Ion channels in cultured microglia

Inward and, depending on activation state, outward potassium currents are the dominant ion channels in microglial cells in culture. During transition between resting and activated phases, there is also an upregulated expression of stretch/swelling‐activated chloride currents. Pharmacological blockade of the specific potassium channels does not prevent the transition, whereas blockade of chloride channels does, suggesting that this current may be involved in phase changes. Interestingly, this chloride current is far less studied than the potassium currents with regard to the different microglial phases. One puzzling finding when studying microglial state is that despite changes in current densities and membrane oscillations during transition, there is no evidence of an accompanying change in membrane potential. In other cells of the immune system, membrane oscillations and alterations in membrane potential are correlated with transitions in cellular phases. This discrepancy in microglia may be a result of the fact that almost all ion channel and membrane potential studies in culture are undertaken with concomitant dialysis of cytoplasm with pipette solution. Further complicating matters is that the few studies that use microglia in situ, find fundamental differences in ion channel current patterns of “resting” microglia as well as different temporal changes to pathological events or stimuli. Microsc. Res. Tech. 54:26–33, 2001. © 2001 Wiley‐Liss, Inc.
Human leptospirosis in eastern Croatia, 1969–2003: Epidemiological, clinical, and serological features

This survey presents epidemiological, serological and clinical features of 270 patients (85% males, 18% children) treated for leptospirosis from 1969 to 2003 at the Clinic for Infective Diseases, University Hospital Osijek, Osijek, eastern Croatia. 75% of the admissions were between July and October. The route of transmission was mostly by indirect contact with domestic animals, less frequently by direct contact with urine or tissue of infected animals. Clinical presentation included signs and symptoms with expected and common frequency, with the exception of jaundice (62%) and aseptic meningitis (60%), which occurred with higher incidence than previously reported. Acute renal failure ensued in 53% of patients, 7% of whom required haemodialysis. No deaths were observed. Therapy consisted of antimicrobials (penicillin and doxycycline) and symptomatic measures. Diagnosis was confirmed by microscopic agglutination test (MAT). There were in total 18 serological types of Leptospira detected, and types L. sejroe, L.pomona, L. australis and L. icterohaemorrhagiae prevailed. During the last 10 y some new types were observed. Leptospirosis was not rare in the region of eastern Croatia, and its course could be life-threatening if not recognized and adequately treated.
Functionalised AFM Probes for the Investigation of Integrin Distribution on the Surface of Osteosarcoma-Derived Osteoblasts

Integrens are transmembrane glycoproteins made of non-covalently bonded alpha and beta chains involved in fundamental biological processes such as cell growth, tissue development and wound repair. The expression of proper cell surface receptors plays a pivotal role to promote such phenomena. To this regard the possibility to investigate cell membrane at the single molecule level is of high potential in the field of cell biology and tissue engineering to gain insights into molecular mechanisms governing cell functions and tissue regeneration. In this work functionalized Atomic Force Microscopy (AFM) probes have been successfully developed and tested for the detection of integrins expressed on the surface of a line of osteosarcoma-derived osteoblasts named MG-63. The obtained results demonstrate the high potential of the AFM technique for the investigation of cell surface functional molecules at the nanoscale.
Fluoxetine augmentation of clozapine treatment in patients with schizophrenia.

OBJECTIVE The authors examined the efficacy of fluoxetine augmentation of clozapine treatment response in schizophrenic outpatients who, despite adequate treatment with clozapine, continued to exhibit persistent positive or negative symptoms. METHOD Thirty-three patients completed on 8-week, double-blind, parallel-groups comparison of adjunctive fluoxetine and placebo. RESULTS There were no significant differences in positive, negative, depressive, or obsessive-compulsive symptoms between patients given adjunctive fluoxetine or placebo. CONCLUSIONS These results suggest that fluoxetine is not effective in augmenting clozapine treatment response.
Prioritizing regions of candidate genes for efficient mutation screening

The availability of the complete sequence of the human genome has dramatically facilitated the search for disease‐causing sequence variations. In fact, the rate‐limiting step has shifted from the discovery and characterization of candidate genes to the actual screening of human populations and the subsequent interpretation of observed variations. In this study we tested the hypothesis that some segments of candidate genes are more likely than others to contain disease‐causing variations and that these segments can be predicted bioinformatically. A bioinformatic technique, prioritization of annotated regions (PAR), was developed to predict the likelihood that a specific coding region of a gene will harbor a disease‐causing mutation based on conserved protein functional domains and protein secondary structures. This method was evaluated by using it to analyze 710 genes that collectively harbor 4,498 previously identified mutations. Nearly 50% of the genes were recognized as disease‐associated after screening only 9% of the complete coding sequence. The PAR technique identified 90% of the genes as containing at least one mutation, with less than 40% of the screening resources that traditional approaches would require. These results suggest that prioritization strategies such as PAR can accelerate disease‐gene identification through more efficient use of screening resources. Hum Mutat 27(2), 195–200, 2006. © 2006 Wiley‐Liss, Inc.
Fibrin D‐dimer: A marker of psychosocial distress and its implications for research in stress‐related coronary artery disease

Psychosocial factors might mediate their adverse impact on coronary arteries by eliciting a hypercoagulable state via changes in sympathetic nervous system activity. A recent meta‐analysis of prospective studies reported an association of the hypercoagulability marker D‐dimer with an increased risk for coronary events. This review provides evidence that an elevated plasma D‐dimer level is a suitable marker for acute and chronic psychosocial distress. Prospective studies need to show whether stress‐related changes in D‐dimer may help explain the increased coronary risk with psychosocial distress.
Bifurcation theory of a square lattice economy: Racetrack economy analogy in an economic geography model

Bifurcation theory for an economic agglomeration in a square lattice economy is presented in comparison with that in a racetrack economy. The existence of a series of equilibria with characteristic agglomeration patterns is elucidated. A spatial period doubling bifurcation cascade between these equilibria is advanced as a common mechanism to engender fewer and larger agglomerations in both economies. Analytical formulas for a break point, at which the uniformity is broken under reduced transport costs, are proposed for an economic geography model by synthetically encompassing both economies.
Adaptive subcarrier and bit allocation for multiuser OFDM system based on genetic algorithm

An adaptive subcarrier and bit allocation method based on genetic algorithm for multiuser OFDM system is proposed. With the goal of minimize the overall transmit power while ensuring the fulfillment of each user's rate and bit error rate (BER) requirement, our algorithm acquires the needed allocation through genetic search. We also improve the convergence of the genetic algorithm through the method of adding some individuals with 'good' genes to the initial population. Simulation results show that the proposed algorithm outperforms static subcarrier allocation schemes TDMA and FDMA considerably in multiuser OFDM system and is better than the algorithm in Zhang (2004).
Increase in outpatient knee arthroscopy in the United States: a comparison of National Surveys of Ambulatory Surgery, 1996 and 2006.

BACKGROUND This study was proposed to investigate the changes in the utilization of knee arthroscopy in an ambulatory setting over the past decade in the United States as well as its implications. METHODS The National Survey of Ambulatory Surgery, last carried out in 1996, was conducted again in 2006 by the Centers for Disease Control and Prevention. We analyzed the cases with procedure coding indicative of knee arthroscopy or anterior cruciate ligament reconstruction. To produce estimates for all arthroscopic procedures on the knee in an ambulatory setting in the United States for each year, we performed a design-based statistical analysis. RESULTS The number of arthroscopic procedures on the knee increased 49% between 1996 and 2006. While the number of arthroscopic procedures for knee injury had dramatically increased, arthroscopic procedures for knee osteoarthritis had decreased. In 1996, knee arthroscopies performed in freestanding ambulatory surgery centers comprised only 15% of all orthopaedic procedures, but the proportion increased to 51% in 2006. There was a large increase in knee arthroscopy among middle-aged patients regardless of sex. In 2006, >99% of arthroscopic procedures on the knee were in an outpatient setting. Approximately 984,607 arthroscopic procedures on the knee (95% confidence interval, 895,999 to 1,073,215) were performed in an outpatient setting in 2006. Among those, 127,446 procedures (95% confidence interval, 95,124 to 159,768) were for anterior cruciate ligament reconstruction. Nearly 500,000 arthroscopic procedures were performed for medial or lateral meniscal tears. CONCLUSIONS This study revealed that the knee arthroscopy rate in the United States was more than twofold higher than in England or Ontario, Canada, in 2006. Our study found that nearly half of the knee arthroscopic procedures were performed for meniscal tears. Meniscal damage, detected by magnetic resonance imaging, is commonly assumed to be the source of pain and symptoms. Further study is imperative to better define the symptoms, physical findings, and radiographic findings that are predictive of successful arthroscopic treatment.
Resistance of Glycine Species and Various Cultivated Legumes to the Soybean Aphid (Homoptera: Aphididae)

Abstract The soybean aphid, Aphis glycines Matsumura, is a new pest of soybean, Glycine max (L.) Merr. , in North America. It has become widespread on soybean in North America since it was first identified in the Midwest in 2000. Species of Rhamnus L. (buckthorn) are the primary hosts of A. glycines, and soybean is known as a secondary host. There is limited information about the secondary host range of A. glycines. Aphid colonization on various legume hosts was compared in choice experiments. Aphid colonization occurred on species in the genus Glycine Wild. No colonization occurred on Lablab purpureus (L.) Sweet, Lens culinaris Medik, Phaseolus vulgaris L. , Pisum sativum L. , or species of Vicia L. and Vigna Savi. Colonization was limited or aphids were transient on species of Medicago L. , Phaseolus L. , and Trifolium L. There were significant differences in aphid colonization among Medicago truncatula accessions with numbers ranging from 7 to 97 aphids per plant. Six Glycine soja Sieb. & Zucc. accessions were as resistant as G. max accessions to A. glycines; these may represent novel sources of A. glycines resistance not found in G. max. Antibiosis was found to play a large role in the expression of resistance in three of the G. soja accessions. Results of this study indicated that G. max and G. soja were the best secondary hosts of A. glycines; however, its secondary host range may include other leguminous species. Therefore, A. glycines did not seem to have a highly restricted monophagous secondary host range.
Proteolysis of α-amylase from Saccharomycopsis fibuligera: characterization of digestion products

Abstractα-Amylase from Saccharomycopsis fibuligera R-64 was successfully purified by butyl Toyopearl hydrophobic interaction chromatography, followed by Sephadex G-25 size exclusion and DEAE Toyopearl anion exchange chromatography. The enzyme has a molecular mass of 54 kDa, as judged by SDS PAGE analysis. Upon tryptic digestion, two major fragments with relative molecular masses of 39 kDa and 10 kDa, which resemble the A/B and C-terminal domains in the homologous Taka-amylase, were obtained and were successfully separated with the Sephadex G-50 size exclusion column. The 39-kDa fragment demonstrated a similar amylolytic activity to that of the undigested enzyme. However, it was found that the Km value of the 39-kDa fragment was about two-times higher than that of the undigested enzyme. Moreover, thermostability studies showed a lower half-life time for the 39-kDa fragment. These findings suggest that the 39-kDa fragment is the catalytic domain, while the 10-kDa fragment is the C-terminal one, which plays a role in thermostability and starch binding. Although the undigested enzyme is able to act on raw starches at room temperature, with maize starches as the best substrate, neither the undigested enzyme nor the fragments adsorb the tested raw starches. These results propose Saccharomycopsis fibuligera α-amylase as a raw starch-digesting but not adsorbing amylase, with a similar domain organization to that of Taka-amylase A.
An area-overhead-oriented monitoring-path selection algorithm for suspicious timing error prediction

As process technologies advance, the importance of timing error correction techniques is increasing as well. In this paper, We propose an area-overhead-oriented monitoring-path selection algorithm for suspicious timing error prediction circuits (STEPCs). STEPC predicts timing errors by monitoring the middle points of several speed-paths in a circuit. However, we need many STEPCs with a high area overhead to predict timing errors in an overall circuit. Our proposed method moves the STEPC insertion positions to minimize the number of inserted STEPCs. We apply a max-flow and min-cut approach to determine the optimal positions of inserted STEPCs. Our proposed algorithm reduces the required number of STEPCs to 1/19 and their area to 1/5 compared with a naive algorithm. Furthermore, our algorithm realizes 2.25X overclocking compared with just inserting STEPCs into several speed-paths.
Death‐signalling cascade in mouse cerebellar granule neurons

Molecular mechanisms of neuronal cell death are still largely unknown. In the present study, the signal transduction pathway of cell death in cerebellar granule neurons was examined by employing various death‐preventative agents. When death was induced by the depletion of serum and a depolarizing level of potassium, transient increase in active c‐Jun, mitochondrial membrane potential (Δψ) loss, activation of caspase‐3 (‐like) proteases, and nuclear condensation and fragmentation were observed. The protein synthesis inhibitor cycloheximide blocked all these phenomena, whereas RNA synthesis inhibitor actinomycin‐D, survival factor such as insulin‐like growth factor‐1, brain‐derived neurotrophic factor, high K+ (25 mm) and overproduced antiapoptotic protein Bcl‐2, prevented Δψ loss, caspase activation, and nuclear change, but not an increase in active c‐Jun. The caspase inhibitor z‐Asp‐CH2‐DCB (carbobenzoxy‐l‐aspartyl‐α‐[(2,6‐dichlorobenzoyl) oxy]methane) only inhibited activation of caspases and nuclear change. These results suggest that the death signal in cerebellar granule neurons is sequentially transduced in the order of c‐Jun activation, de novo RNA synthesis, mitochondrial Δψ loss, activation of caspase‐3 (‐like) proteases and nuclear change.
Asian travel from EU countries in the emerging global economy.

The globalisation trend of the past five decades has resulted in the freer movement of goods capital and people across borders. Most people who cross borders are considered international visitors which the World Tourism Organisation (WTO) defines as ‘any person who travels to a country other than that in which s/he has his/her usual residence but outside his/her usual environment for a period not exceeding 12 months and whose main purpose of visiting is other than the exercise of any activity remunerated from within the country visited. ’ The roots of tourism as a leisure product were established in 19th and 20th century Western culture. In both Europe and North America tourism is promoted as being vital to life and health and serves as a symbol of socioeconomic status. Belief in these ideas has led to increasing demand for resorts and exotic cross-cultural tourist packages. The demand was also fueled by the emphasis in the mid-1960s of paid holidays as a central part of many compensation packages offered by employers and governments more so in Europe than in the US. The combination of increased real income paid holidays changing attitudes towards tourism and substantial growth in commercial aviation supported the development of international tourism in the latter part of the 20th century. (excerpt)
Birth Weight Predicts Scores on the ADHD Self-Report Scale and Attitudes towards Casual Sex in College Men: A Short-Term Life History Strategy?

Early development can have long-term effects on physiology and behavior. While severe disturbances predictably lead to dysfunction, recent work in humans and animals has led to a growing appreciation for the more subtle ways in which early conditions can modulate behavioral tendencies later in life. Life history theory predicts that early cues signaling a stressful or suboptimal environment might lead an organism to adopt a strategy favoring short-term gains and early reproduction. Fifty college men reported their birth weight, completed the Attention-Deficit/Hyperactivity Disorder (ADHD) Self-Report Scale, and answered a series of questions about their sexual history and attitudes towards short-term sexual encounters. Lower birth weights were associated with higher scores on the ADHD scale (r = −.352; p ≤ .05) and more favorable attitudes towards casual sex (r = −.456; p ≤ 0.001). There was a significant interaction between birth weight and casual sex favorability in predicting number of sexual partners (F1,46 = 4.994; p ≤ .05). This suggests that, although men who are smaller at birth may otherwise be at a disadvantage in reproductive terms, they may offset their reduced fitness by being more willing to engage in casual sex.