Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated Neutrophil to Lymphocyte Ratio Predicts Poor Prognosis in Advanced Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy

Background: The aim of this study was to assess whether the neutrophil to lymphocyte ratio (NLR) and other laboratory markers may predict the prognosis of advanced colorectal cancer (CRC) patients receiving palliative chemotherapy. Methods: The study population included 50 patients with far advanced or recurrent unresectable CRC who received oxaliplatin-based combination chemotherapy as first-line treatment in our hospital between June 2005 and November 2010. Seven clinical variables and 7 laboratory indices before chemotherapy were evaluated retrospectively as the possible prognostic factors of overall and progression-free survival. Results: During the study period, 27 patients (54%) died of CRC. Elevated NLR (≥4.0) was observed in 15 patients (30%). By univariate analysis, elevated NLR, performance status and hypoalbuminemia were significantly associated with both poor overall and progression-free survivals. Multivariate analysis showed that elevated NLR (hazard ratio 4.39, 95% confidence interval 1.82–10.7; p = 0.0013) and thrombocytosis (hazard ratio 5.02, 95% confidence interval 1.69–13.4; p = 0.0066) were independently associated with overall survival. Conclusion: Elevated NLR is a powerful predictor of poor response to oxaliplatin-based chemotherapy in patients with unresectable CRC. The ratio is a simply accessible and inexpensive but useful biomarker in CRC patients receiving chemotherapy.
Analyses of Socioeconomic Factors influencing on-farm Conservation of Remnant Forest Tree Species: Evidence from Ghana

The contribution of remnant trees in traditional agro forestry systems in recent times has attracted significant attention from policy makers, stakeholders, and academicians due to their important role in conserving biodiversity within agricultural systems, reserves of genetic resources and provision of other important environmental services. The study seeks to determine socioeconomic factors influencing farmers’ decision to maintain remnant trees in agricultural landscape. Data was solicited from 220 households in three rural communities through structured interviews and on farm visitations. We employed Poison and Negative Binomial Regressions to determine factors influencing rural farm households’ decision to retain remnants forest tree species in agro ecosystem. The regression results indicated that the key factors strongly affecting farmers’ on-farm conservation decision to retain remnant forest trees in agricultural landscape were age, gender, years of schooling, religion, land tenure, farmers’ perceptions to current environmental problems, distance to farm land, erosion and the size of the landholdings. The study recommends that forest governance with focus on collaborative forest resource management and equitable distribution of benefits generated from extraction of forest resources should be given high impetus in policy formulation. The needs and concerns of forest fringe communities should feature paramount in this regard.
Ascorbate Peroxidase 1 Plays a Key Role in the Response of Arabidopsis thaliana to Stress Combination*

Within their natural habitat plants are subjected to a combination of different abiotic stresses, each with the potential to exacerbate the damage caused by the others. One of the most devastating stress combinations for crop productivity, which frequently occurs in the field, is drought and heat stress. In this study we conducted proteomic and metabolic analysis of Arabidopsis thaliana plants subjected to a combination of drought and heat stress. We identified 45 different proteins that specifically accumulated in Arabidopsis in response to the stress combination. These included enzymes involved in reactive oxygen detoxification, malate metabolism, and the Calvin cycle. The accumulation of malic enzyme during the combined stress corresponded with enhanced malic enzyme activity, a decrease in malic acid, and lower amounts of oxaloacetate, suggesting that malate metabolism plays an important role in the response of Arabidopsis to the stress combination. Cytosolic ascorbate peroxidase 1 (APX1) protein and mRNA accumulated during the stress combination. When exposed to heat stress combined with drought, an APX1-deficient mutant (apx1) accumulated more hydrogen peroxide and was significantly more sensitive to the stress combination than wild type. In contrast, mutants deficient in thylakoid or stromal/mitochondrial APXs were not more sensitive to the stress combination than apx1 or wild type. Our findings suggest that cytosolic APX1 plays a key role in the acclimation of plants to a combination of drought and heat stress.
Oral immunization with attenuated Salmonella vaccine expressing Escherichia coli O157:H7 intimin gamma triggers both systemic and mucosal humoral immunity in mice

Human infections with EHEC such as O157:H7 have been a great concern for worldwide food‐industry surveillance. This pathogen is commonly associated with bloody diarrhea that can evolve to the life‐threatening hemolytic uremic syndrome. Animals are the natural reservoir where this pathogen remains asymptomatically, in steps of ingestion and colonization of the bowel. The bacterium is shed in the feces, contaminating the surroundings, including water and food that are directed for human consumption. A major player in this colonization process is intimin, an outer membrane adhesion molecule encoded by the E. coli attachment and effacement (eae) gene that has been shown to be essential for intimate bacterial attachment to eukaryotic host cells. In an attempt to reduce the colonization of animal reservoirs with EHEC O157:H7, we designed a vaccine model to induce an immune response against intimin gamma. The model is based on its recombinant expression in attenuated Salmonella, used as a suitable vaccine vector because of its recognized ability to deliver recombinant antigens and to elicit all forms of immunity: mucosal, systemic, and humoral responses. To test this model, mice were orally immunized with a S. enterica serovar Typhimurium strain carrying the pYA3137eaeA vector, and challenged with E. coli O157:H7. Here we show that immunization induced the production of high levels of specific IgG and IgA antibodies and promoted reduction in the fecal shedding of EHEC after challenge. The live recombinant vaccine reported herein may contribute to the efforts of reducing animal intestinal mucosa colonization.
Exchange Rate Flexibility and the Effect of Remittances on Economic Growth

This paper studies the question of whether exchange rate policy affects the impact of remittances on economic growth in recipient countries. The paper utilizes a comprehensive data set that comprises annual observations for 135 developing and transition countries, spanning 1970-2007. The data for exchange rate regimes is based on the Reinhart and Rogoff exchange rate regime classification, whereas the data for remittances and all other variables are from the World Bank's World Development Indicators database. The findings indicate that more flexible exchange rate regimes are associated with a greater increase in economic growth following an increase in remittances, but also that the impact of remittances on growth is positive under a fixed exchange rate regime. The estimates suggest that a 1 percent increase in remittances increases per capita growth by about 0.79 percent under a fixed exchange rate regime, and that this effect increases by about 0.13 percent for a 1 point increase in the exchange rate flexibility index. The results further suggest that the effect of remittances under a fixed exchange rate regime is positive in less financially developed countries as well, but do not provide conclusive evidence that this effect varies inversely with exchange rate flexibility in such economies as theorized.
When Entomological Evidence Crawls Away: Phormia regina en masse Larval Dispersal

ABSTRACT In criminal and civil legal investigations the forensic entomologist usually assists in providing an estimate of the postmortem interval, which closely couples with the time or period of insect activity. A minimum period of insect activity is often interpreted and estimated by dipteran larval developmental age of the oldest specimens collected at a crime scene and /or autopsy. In entomological evidence protocols investigators are recommended to search a 2–10 m perimeter area for the oldest larvae that may have begun to disperse away from the body for burial and pupation. In this study, we described a case of a large aggregate (>90% larvae) en masse postfeeding dispersal of blow fly larvae away from replicate swine carcasses serving as models of human decomposition. Larval dispersal was evaluated for a spring and a summer trial, with en masse characteristics only occurring during the latter. This en masse dispersal occurred in five out of six replicate carcasses and masses moved from 2 to 26 m away. These data and observations suggest the importance of performing searches >10 m from human remains for entomological evidence at crime scenes. Ry missing the oldest larvae at a crime scene, interpretation of entomological evidence can be compromised and erroneous. Based on these data and observations we recommend the crime scene investigators and researchers consider increasing the search radius around crime scene remains to increase the likelihood that the oldest larvae have been collected for analysis.
Social Anxiety and Fear of Causing Discomfort to Others: Diagnostic Specificity, Symptom Correlates and CBT Treatment Outcome

Background: Patients with social anxiety disorder (SAD) report fear content relating to the perceived aversive consequences of their anxiety for others in their social environment. However, no studies to date have examined the diagnostic specificity of these fears to SAD as well as predictors to treatment response of these fears. Aims: To examine relative specificity of fears related to causing discomfort to others, as measured by Social Anxiety–Fear of Causing Discomfort to Others (SA-DOS), among patients with anxiety disorders, obsessive compulsive disorder (OCD) and major depressive disorder (MDD), in addition to relation between dysfunctional attitudes and treatment response among patients with SAD. Method: In study 1, a large (n=745) sample of DSM diagnosed OCD, MDD and anxiety disorder participants completed the SA-DOS. In study 2, patient participants with SAD (n=186) participated in cognitive behavioural group therapy (CBGT) and completed measures of social anxiety symptoms and dysfunctional attitudes. Results: In study 1, the SAD group demonstrated significantly elevated SA-DOS scores compared with participants with generalized anxiety disorder (GAD), OCD and panic disorder with or without agoraphobia (PD/A), but not the MDD group. In study 2, CBGT treatment was found to lead to significant reductions in SA-DOS scores. Need for approval (NFA) but not perfectionism, predicted treatment response to fears related to causing discomfort to others, with greater change in NFA relating to greater change in SA-DOS scores. Conclusions: These findings extend previous research linking allocentric fears to the phenomenology and treatment of SAD.
U1-Small Nuclear Ribonucleoprotein Activates the NLRP3 Inflammasome in Human Monocytes

The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is a caspase-1–containing cytosolic protein complex that is essential for processing and secretion of IL-1β. The U1-small nuclear ribonucleoprotein (U1-snRNP) that includes U1-small nuclear RNA is a highly conserved intranuclear molecular complex involved in splicing pre-mRNA. Abs against this self nuclear molecule are characteristically found in autoimmune diseases like systemic lupus erythematosus, suggesting a potential role of U1-snRNP in autoimmunity. Although endogenous DNA and microbial nucleic acids are known to activate the inflammasomes, it is unknown whether endogenous RNA-containing U1-snRNP could activate this molecular complex. In this study, we show that U1-snRNP activates the NLRP3 inflammasome in CD14+ human monocytes dependently of anti–U1-snRNP Abs, leading to IL-1β production. Reactive oxygen species and K+ efflux were responsible for this activation. Knocking down the NLRP3 or inhibiting caspase-1 or TLR7/8 pathway decreased IL-1β production from monocytes treated with U1-snRNP in the presence of anti–U1-snRNP Abs. Our findings indicate that endogenous RNA-containing U1-snRNP could be a signal that activates the NLRP3 inflammasome in autoimmune diseases like systemic lupus erythematosus where anti–U1-snRNP Abs are present.
Pattern of Childhood Onset Vitiligo at a Tertiary Care Centre in South- West Rajasthan

Context: Onset of vitiligo during childhood is not uncommon but the data is limited on this subject. Aims: This study was planned to assess the magnitude of childhood onset vitiligo (COV) and adulthood onset vitiligo (AOV), and compare their clinical pattern. Settings and Design: A cross sectional hospital based clinical study. Materials and Methods: Consecutive patients with vitiligo attending the Dermatology OPD of RNT Medical College and MB Government Hospital, Udaipur, from April 2012 to September 2012 were the subjects of this study. A detailed history taking followed by general, systemic and cutaneous examination, and relevant investigations were carried out. The findings were recorded in a proforma for analysis and interpretation of data. Statistical analysis used: Statistical analysis of data was done using chi- square and Z test. Results: Of the 295 patients seen during the study period, 109 (36.95%) were patients with COV while 186 (63.05%) had AOV; the COV: AOV ratio being 1: 1.71. Amongst COV patients, females (65/109; 59.63%) outnumbered males (44/109; 40.37%). Maximum (51; 46.79%) patients of COV had onset of their disease on head and neck, out of which eyelid was the initial site of lesion in 29 (26.61%) patients. None of COV patients had universal and isolated mucosal vitiligo. Conclusions: Female predominance, affection of eyelids as initial site, and less frequent mucosal involvement in COV were the clinical features different from AOV.
Understanding Homeopathic Decision-Making: A Qualitative Study

Background: Understanding how homeopaths make clinical decisions is important in terms of optimising patient care, yet currently little is understood about this process. Most current literature investigating decision-making has focussed on conventional medicine; to date only two studies, both quantitative, have explored this area, with both studies investigating this in homeopathy. The aim of this qualitative study was to explore how homeopaths make prescribing decisions primarily during their first consultation with a patient. Method: In-depth, semistructured, face to face interviews were carried out with 14 private homeopaths working in private practice. Interpretative phenomenological analysis (IPA) was carried out on the data by 3 researchers. Findings: Cognitive processes that homeopaths used in decision-making emerged from the analysis included the use of pattern recognition (P), hypothetico-deductive reasoning (H) and intuition (I), which led to a precise remedy match (R-M). Four themes emerged from the data: three related to the process of making a decision; one theme to those factors that influence this process. These themes fitted into a decision-making model, which we describe: the P.H. I.RM decision-making model. Two further themes emerged, which contributed to the model: the practitioners’ awareness of avoiding major bias and the role of the patient practitioner relationship in influencing decision-making. Conclusion: The P.H. I.R-M decision-making model describes how homeopathic practitioners’ used an evidence-based process to make decisions. This study also contributes more weight to the accumulating evidence that intuition is a valuable component of decisionmaking for homeopathic practitioners.
Project I See in NC: Initial results of a program to increase access to retinal examinations among diabetic individuals in North Carolina.

BACKGROUND Diabetic retinopathy is the leading cause of preventable blindness in adults. Project I See in NC was begun to determine whether access to eye screening for Medicaid recipients and uninsured patients with diabetes in North Carolina could be improved. METHODS We targeted Medicaid recipients and uninsured adults with diabetes for screening in 2 Community Care of North Carolina Networks. Screenings were performed in primary care settings throughout 6 counties in the Northwest Community Care Network and 6 counties in Access III of Community Care of the Lower Cape Fear. Patients were screened using a high-resolution digital retinal camera with images read at a centralized reading center at Wake Forest School of Medicine. RESULTS A total of 1,688 patients were screened from October 2005 through September 2007. Nearly 15% (282) were found to have mild, nonproliferative-to-proliferative retinopathy, while the majority of patients had no evidence of diabetic retinopathy. Nearly 12% (196) required referral to an ophthalmologist, with 5% (86) requiring urgent referral for potentially sight-threatening retinopathy. LIMITATIONS We were not able to confirm which patients kept their ophthalmologic appointments; however, we are currently analyzing data from the Medicaid patients in our study who required ophthalmologic referral. CONCLUSIONS Remote digital retinal screening for diabetic retinopathy is feasible in primary care settings in both urban and rural areas of North Carolina, and it may prove to be an effective means of reaching more patients who require annual screening examinations.
A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits

Background—Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis. Aims—To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis. Methods—Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis. Results—Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor α (TNF-α) from three to six hours after induction of acute pancreatitis (p=0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-α, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose. Conclusion—WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-α, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.
Bacteriophage and bacteriocin typing scheme for Clostridium difficile

The study of the epidemiology of infection with Clostridium difficile would be aided by a way to type individual bacterial isolates. We therefore sought bacteriophages for use in typing. With mitomycin C exposure (3 micrograms/ml), filtrates from 10 strains of C. difficile had plaque-forming lytic activity on other C. difficile strains. Individual phage were passaged and made into high-titer stock preparations for typing. Electron microscopy revealed tailed phage particles from one such preparation. In addition to phage, inhibitory activity without distinct plaque formation consistent with bacteriocins was observed for 20 strains. C. difficile isolates from 16 patients taken 1 to 14 days apart were similar in their phage sensitivity pattern, whereas isolates from separate geographic locations showed a great variety of patterns. We conclude that bacteriophage should be useful for typing strains of C. difficile.
HIV and Noncommunicable Cardiovascular and Pulmonary Diseases in Low- and Middle-Income Countries in the ART Era: What We Know and Best Directions for Future Research

Abstract:With the advent of effective antiretroviral therapy (ART), HIV is becoming a chronic disease. HIV-seropositive (+) patients on ART can expect to live longer and, as a result, they are at risk of developing chronic noncommunicable diseases related to factors, such as aging, lifestyle, long-term HIV infection, and the potential adverse effects of ART. Although data are incomplete, evidence suggests that even in low- and middle-income countries (LMICs), chronic cardiovascular and pulmonary diseases are increasing in HIV-positive patients. This review summarizes evidence-linking HIV infection to the most commonly cited chronic cardiovascular and pulmonary conditions in LMICs: heart failure, hypertension, coronary artery disease/myocardial infarction, stroke, obstructive lung diseases, and pulmonary arterial hypertension. We describe the observed epidemiology of these conditions, factors affecting expression in LMICs, and key populations that may be at higher risk (ie, illicit drug users and children), and finally, we suggest that strategic areas of research and training intended to counter these conditions effectively. As access to ART in LMICs increases, long-term outcomes among HIV-positive persons will increasingly be determined by a range of associated chronic cardiovascular and pulmonary complications. Actions taken now to identify those conditions that contribute to long-term morbidity and mortality optimize early recognition and diagnosis and implement effective prevention strategies and/or disease interventions are likely to have the greatest impact on limiting cardiovascular and pulmonary disease comorbidity and improving population health among HIV-positive patients in LMICs.
Regulation of Cardiac L-Type Calcium Channels by Protein Kinase A and Protein Kinase C

Abstract— Voltage-dependent L-type Ca2+ channels are multisubunit transmembrane proteins, which allow the influx of Ca2+ (ICa) essential for normal excitability and excitation-contraction coupling in cardiac myocytes. A variety of different receptors and signaling pathways provide dynamic regulation of ICa in the intact heart. The present review focuses on recent evidence describing the molecular details of regulation of L-type Ca2+ channels by protein kinase A (PKA) and protein kinase C (PKC) pathways. Multiple G protein–coupled receptors act through cAMP/PKA pathways to regulate L-type channels. &bgr;-Adrenergic receptor stimulation results in a marked increase in ICa, which is mediated by a cAMP/PKA pathway. Growing evidence points to an important role of localized signaling complexes involved in the PKA-mediated regulation of ICa, including A-kinase anchor proteins and binding of phosphatase PP2a to the carboxyl terminus of the &agr;1C (Cav1.2) subunit. Both &agr;1C and &bgr;2a subunits of the channel are substrates for PKA in vivo. The regulation of L-type Ca2+ channels by Gq-linked receptors and associated PKC activation is complex, with both stimulation and inhibition of ICa being observed. The amino terminus of the &agr;1C subunit is critically involved in PKC regulation. Crosstalk between PKA and PKC pathways occurs in the modulation of ICa. Ultimately, precise regulation of ICa is needed for normal cardiac function, and alterations in these regulatory pathways may prove important in heart disease.