Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive value of “Marsh 1” type histology in subjects with suspected cealic disease

Abstract Introduction. The diagnosis of celiac disease (CD) is based on histology in combination with anti-tissue transglutaminase (a-tTG) and anti-endomysial antibodies (EMAs). The increase of intraepithelial lymphocytes defines the Marsh 1 histology that appears not to be specific for CD. Aim: To explore the positive predictive value (PPV) and clinical relevance of Marsh 1 histology in suspected CD. Methods. We carried out an observational prospective study including all consecutive subjects with a Marsh 1 histology. All patients were tested for a-tTG and EMAs. Diagnosis of potential CD was defined in the presence of Marsh 1 with positive a-tTG and EMAs. Patients were investigated for symptoms, CD familial aggregation, other diseases, and current medication. Results. Sixty-three patients with Marsh 1 were included. Diagnosis of potential CD was made in 23 subjects (36%), so that Marsh 1 histology showed a PPV of 36%. With regard to familial aggregation, patients with potential CD showed a higher frequency of familiarity for CD (60.8% vs. 15.0%; p < 0.01). No significant difference was detected between CD and non-CD in terms of intestinal and extra-intestinal symptoms. We also documented the presence of conditions other than CD in the remaining population: 7 patients (17.5%) with immuno-mediated diseases while 5 patients (12.5%) showed Helicobacter pylori (HP) infection. About medication, 3 patients (7.5%) were on non-steroidal anti-inflammatory drugs, while another 4 (10%) patients were being treated with other drugs. Conclusion. The Marsh 1 type histology is not specific for CD and it can also be associated with immuno-mediated disorders, HP infection, and drugs.
Prevalence of impaired glucose tolerance and the components of metabolic syndrome in Canadian Tsimshian Nation youth.

INTRODUCTION Canadian Aboriginal people have been disproportionately affected by obesity and type 2 diabetes (T2D). Our objective was to determine the prevalence of obesity, glucose intolerance and the components of metabolic syndrome (MetS) in Tsimshian Nation youth living in 3 remote coastal communities. METHODS A medical history, anthropometric measurements and an oral glucose tolerance test were performed in youth aged 6-18 years. We defined "overweight" by a body mass index (BMI) at the 85th percentile or higher and "obese" by a BMI at the 95th percentile or higher, by age and sex. We used the International Diabetes Federation criteria for MetS. RESULTS Of the 224 eligible youth, 192 (85%) participated in the study. Nineteen percent were overweight, 26% were obese and 36% had central obesity (waist circumference > or = 90th percentile for age and sex). No new cases of T2D were identified. The prevalence of impaired fasting glucose (IFG 5.6-6.9 mmol/L) and impaired glucose tolerance (IGT 2-hr glucose 7.8-11.0 mmol/L) were 19.3% and 5.2%, respectively. Five of the 10 youth with IGT had a fasting glucose less than 5.6 mmol/L. The prevalence of MetS was 4.7% and increased to 8.3% when pediatric hypertension norms were applied. CONCLUSION Tsimshian Nation youth have a high prevalence of central obesity, impaired glucose homeostasis and other components of MetS. The oral glucose tolerance test may be a more appropriate screening test to identify IGT in Aboriginal youth.
MHC-Antigens: Constituents of the Envelopes of Human and Simian Immunodeficiency

Immunoelectron microscopy was applied to study the antigenic make-up of human and simian immunodeficiency viruses (HIV, SIV) grown in cells expressing either MHC class I (Molt-3) or MHC class I and II (H9) antigens. A variety of antibodies directed against the surface glycopro tein gpl20 of HIV and against MHC class I and II antigens were employed. Consistent with earlier observations on the loss of HIV envelope components, gp120 was only weakly demonstra ble on the mature virion. MHC class I determinants were present regularly in small amounts on HIV and SIV. Class II antigens, e.g. HLA-DR were found in high density on HIV and SIV grown in H9 cells, but were absent, as expected, on virus grown in Molt-3 cells. These cellular surface antigens are con stituents of the virion. The presence of MHC class II antigens in virus preparations used for diagnostic purposes might explain some of the false positive results in HIV serology. Possible biological implications of these virus associated cellular antigens for the pathogenicity of HIV are discussed.
Neutrophil/granulocyte transfusions collected from G-CSF + dexamethasone-stimulated donors

Purpose of reviewThe purpose of this review is to report a recently completed multicenter randomized controlled trial of neutrophil/granulocyte transfusions collected from G-CSF + dexamethasone donors to treat neutropenic infections in oncology and transplant patients, within the context of other historic and current clinical trials.The multicenter trial (RING Study) was funded by the NHLBI transfusion medicine/hemostasis clinical trials network. Recent findingsThere was no significant benefit of therapeutic neutrophil/granulocyte transfusions versus antibiotics per intention to treat analysis, but 32% of patients received substandard neutrophil doses. Separate analysis suggested patients given a higher neutrophil doses had better outcomes. SummaryEfficacy of ‘high-dose’ therapeutic neutrophil/granulocyte transfusions remains unproven, but promising.
At-risk individuals in Feline Immunodeficiency Virus epidemiology: evidence from a multivariate approach in a natural population of domestic cats (Felis catus)

Prevalence of Feline Immunodeficiency Virus (FIV) infection was measured during 6 consecutive years in a natural rural population of domestic cats. Sex, age, weight, origin, group size and presence of antibodies to FIV were recorded for each sampled cat. Logistic regressions were used to estimate the influence of the recorded parameters on infection. FIV prevalence rates are as high as 19·6% in the total population, and do not statistically change between years, after controlling for changes in samples' age structure. FIV infection is characterized by risk factors linked to aggressive behaviour: old mature male adults having dispersed are more likely to be infected. A study of the cats group size and of the spatial distribution of infected individuals indicates the absence of infection clusters in males, and suggests the importance of roaming in the spreading of FIV. In conclusion, FIV infection spreads, with low contagiousness, mainly between particularly aggressive individuals, and the virus is endemic in this population.
Surgical Treatment for Scoliosis in Patients WithShprintzen-Goldberg Syndrome

Background Shprintzen-Goldberg syndrome (SGS) is characterized by craniosynostosis and marfanoid habitus. The clinical findings of SGS include neurological, cardiovascular, connective tissue, and skeletal abnormalities. Among these skeletal findings, developmental scoliosis is recognized in half of all patients with SGS. However, no earlier reports have described the surgical treatment of scoliosis associated with SGS. Methods Four patients (2 boys and 2 girls; mean age at the time of surgery, 7.3±4.4 y) with SGS who underwent surgical treatment for progressive scoliosis were reviewed. The radiologic findings, operative findings, and perioperative complications were evaluated. Results The mean preoperative Cobb angle was 102.8±16.9 degrees. The curve patterns were a double curve in 2 cases and a triple curve in 2 cases. Local kyphosis at the thoracolumbar area was recognized in all the cases with a mean kyphosis angle of 49±16 degrees. Growing rod procedures were performed in 2 patients, and posterior correction and fusion were performed in 2 patients. The mean correction rate was 45% in the patients who underwent the growing rod procedures at the time of growing rod placement and 51% in the patients who underwent posterior correction and fusion. Dislodgement of the proximal anchors occurred in 3 of the 4 patients. One patient developed pseudoarthrosis. Two patients developed deep wound infections, and implant removal was necessary in 1 patient. Conclusions Surgical treatment for scoliosis in patients with SGS was associated with a high incidence of perioperative and postoperative complications including implant dislodgements and deep wound infections attributable to poor bone quality and a thin body habitus, which are characteristic clinical features of this syndrome. Careful preoperative surgical planning and postoperative care are critical for the surgical treatment of scoliosis associated with SGS, especially in infants requiring multiple surgeries. Level of Evidence Level IV.
Novel protease and polymerase inhibitors for the treatment of hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection remains a global health concern with nearly 200 million carriers worldwide. Present treatment consists of the use of pegylated interferon plus the purine analogue ribavirin. Serious side effects and the fact that an overall 40 – 50% of patients do not accomplish sustained virological response with the present treatment warrant the need for novel anti-HCV therapies. The HCV serine protease and the RNA-dependent RNA polymerase have shown to be excellent targets for selective antiviral therapy. Early clinical studies have resulted in encouraging results. However, and not unexpectedly, preclinical evidence suggests that the virus may become rapidly resistant to such inhibitors. Therefore, combination therapy of drugs with different mode of action and resistance profiles may be required. This review focuses on the present status of these two families of HCV inhibitors that are in development.
Vaccines prepared from chimeras of foot-and-mouth disease virus (FMDV) induce neutralizing antibodies and protective immunity to multiple serotypes of FMDV

The G-H loop of VP1 (residues 132 to 159) of foot-and-mouth disease virus (FMDV) is a prominent feature on the virion surface and has an important role in vaccine efficacy, generation of antigenic variants, and cell binding. Using an infectious cDNA of FMDV, we have constructed serotype A viruses in which the G-H loop has been substituted with the homologous sequences from serotype O or C. These chimeric viruses replicated to high titer and displayed plaque morphologies similar to those of wild-type viruses, demonstrating that the functions provided by the loop can be readily exchanged between serotypes. Monoclonal antibody analyses showed that epitopes contained within the loop were transferred to the chimeras and that epitopes encoded by the type A backbone were maintained. Chemically inactivated vaccines prepared from chimeric viruses induced antibodies in guinea pigs that neutralized both type A and either type O or type C viruses. Swine inoculated with the A/C chimera vaccine also produced cross-reactive antibodies, were protected from challenge with the type A virus, and partially protected against challenge with type C. These studies emphasize the importance of epitopes outside of the G-H loop in protective immunity in swine, which is a natural host of FMDV.
Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer simulation.

PURPOSE A 3-dimensional computer simulation was developed in order to estimate the impact of tumor shrinkage on reoxygenation of chronic hypoxic tumor cells during a full course of fractionated irradiation. MATERIAL AND METHODS The growth of a small tumor situated in a vascularized stroma with 350 capillary cross-sections/mm3 which were displaced by the growing tumor was simulated. Tumors contained 10(4) cells when irradiation started, intrinsic radiosensitivity was set to either low (alpha = 0.3 Gy-1, beta = 0.03 Gy-2) or high (alpha = 0.4 Gy-1, beta = 0.04 Gy-2) values. Oxygen enhancement ratio was 3.0, potential tumor doubling time Tpot = 1.2 or 5 days. A simulated fractionated radiotherapy was carried out with daily fractions of 2.0 Gy, total dose 50 to 70 Gy. The presence or absence of factors preventing tumor cord shrinkage was also included. RESULTS During the growth phase, all tumors developed a necrotic core with a hypoxic cell fraction of 25% under these conditions. During irradiation, the slower growing tumors (Tpot = 2 to 5 days) showed complete reoxygenation of the hypoxic cells after 30 to 40 Gy independent from radiosensitivity, undisturbed tumor shrinkage provided. If shrinkage was prevented, the hypoxic fraction rose to 100% after 30 to 50 Gy. Local tumor control, defined as the destruction of all clonogenic and hypoxic tumor cells increased by 20 to 100% due to reoxygenation and 50 Gy were enough in order to sterilize the tumors in these cases. In the fast growing tumors (Tpot = 1 day), reoxygenation was only observed in the case of high radiosensitivity and undisturbed tumor shrinkage. In these tumors reoxygenation increased the control rates by up to 60%. CONCLUSION The simulation results suggests that shrinking of a homogeneous tumor during irradiation with restoration of the normal vascular architecture can contribute significantly to reoxygenation, which in turn has a major effect on tumor control.
Debt-Ridden Borrowers and Economic Slowdown

Economic growth slows for an extended period after a financial crisis. We construct a model in which the one-time buildup of debt can depress the economy persistently even when there is no shock on financial technology. We consider the debt dynamics of a firm under an endogenous borrowing constraint. When the initial debt is large, the borrowing constraint binds tight and production is inefficient for an extended period. A firm is called debt-ridden when it owes the maximum sustainable amount of debt. A debt-ridden firm pays all income every period as the interest payment on the debt. A noticeable result in the deterministic case is that a debt-ridden firm continues inefficient production permanently. Further, if the initial debt exceeds a certain threshold, the firm chooses to increase borrowing and become debt-ridden intentionally. The emergence of a substantial number of debt-ridden firms lowers economic growth persistently by reducing the growth rate of aggregate productivity. As lenders have no incentive to reduce debt, a policy intervention that provides debtridden borrowers with relief from excessive debt may thus be necessary to restore economic growth.
Intraoperative Methadone Improves Postoperative Pain Control in Patients Undergoing Complex Spine Surgery

BACKGROUND:Patients undergoing complex spine surgery frequently experience severe pain in the postoperative period. The combined opiate receptor agonist/N-methyl-D-aspartate receptor antagonist methadone may be an optimal drug for these patients given the probable involvement of N-methyl-D-aspartate systems in the mechanism of opioid tolerance and hyperalgesia. METHODS:Twenty-nine patients undergoing multilevel thoracolumbar spine surgery with instrumentation and fusion were enrolled in this prospective study and randomized to receive either methadone (0.2 mg/kg) before surgical incision or a continuous sufentanil infusion of 0.25 &mgr;g/kg/h after a load of 0.75 &mgr;g/kg. Postoperative analgesia was provided using IV opioids by patient-controlled analgesia. Patients were assessed with respect to pain scores (visual analog scale from 0 to 10), cumulative opioid requirement, and side effects at 24, 48, and 72 hours after surgery. RESULTS:Demographic data, duration, and type of surgery were comparable between the groups. Methadone reduced postoperative opioid requirement by approximately 50% at 48 hours (sufentanil versus methadone group, median [25%/75% interquartile range]: 63 mg [27.3/86.1] vs 25 mg [16.5/31.5] morphine equivalents, P = 0.023; and 72 hours: 34 mg [19.9/91.5] vs 15 mg [8.8/27.8] morphine equivalents, P = 0.024) after surgery. In addition, pain scores were lower by approximately 50% in the methadone group at 48 hours after surgery (sufentanil versus methadone group [mean ± SD] 4.8 ± 2.4 vs 2.8 ± 2.0, P = 0.026). The incidence of side effects was comparable in both groups. CONCLUSION:Perioperative treatment with a single bolus of methadone improves postoperative pain control for patients undergoing complex spine surgery.
On facts and conceptual systems: young children's integration of their understandings of germs and contagion.

Five studies argue against claims that preschoolers understand a biological germ theory of illness. In Studies 1-3, participants were read stories in which characters develop symptoms (e.g., a bellyache) caused by germs, poisons, or events (e.g., eating too much candy) and were asked whether another character could catch the symptoms from the first. Few children made judgments in terms of germs as part of an underlying causal process linking the origin of a symptom to its subsequent transmission. Some children may have reasoned simply that certain kinds of symptoms are likely to be contagious. Studies 4 and 5 undermined the claim that preschoolers understand germs to be uniquely biological causal agents. Young children did not attribute properties to germs as they did for animate beings or for plants. It is suggested that children undergo conceptual reorganization in constructing a Western adult understanding of germs.
Corruption: What Everyone Needs to Know®

Corruption regularly makes front page headlines: public officials embezzling government monies, selling public offices, and trading bribes for favors to private companies generate public indignation and calls for reform. In Corruption: What Everyone Needs to KnowRG, renowned scholars Ray Fisman and Miriam A. Golden provide a deeper understanding of why corruption is so damaging politically, socially, and economically. Among the key questions examined are: is corruption the result of perverse economic incentives? Does it stem from differences in culture and tolerance for illicit acts of government officials? Why don't voters throw corrupt politicians out of office? Vivid examples from a wide range of countries and situations shed light on the causes of corruption, and how it can be combated.
The Monoamine-Mediated Antiallodynic Effects of Intrathecally Administered Milnacipran, a Serotonin Noradrenaline Reuptake Inhibitor, in a Rat Model of Neuropathic Pain

Antidepressants are often used to treat neuropathic pain. In the present study, we determined the antiallodynic effects of selective monoamine reuptake inhibitors in the spinal cord in a rat model of neuropathic pain. Mechanical allodynia was produced by tight ligation of the left L5 and L6 spinal nerves and determined by applying von Frey filaments to the left hindpaw. A serotonin noradrenaline reuptake inhibitor, milnacipran, a selective serotonin reuptake inhibitor, paroxetine, or a selective noradrenaline reuptake inhibitor, maprotiline, was administered intrathecally via a chronically implanted catheter. Milnacipran produced dose-dependent antiallodynic effects at doses between 3 &mgr;g and 100 &mgr;g. The effect lasted for 7 h after injection of 100 &mgr;g (P < 0.05). The antiallodynic effect of 30 &mgr;g of milnacipran was attenuated by intrathecal coadministration of 30 &mgr;g of yohimbine, an α2-adrenoceptor antagonist, 30 &mgr;g of methysergide, a serotonin receptor antagonist, or 30 &mgr;g of atropine, a muscarinic receptor antagonist (P < 0.01, respectively). Intraperitoneal administration of milnacipran had no antiallodynic effects at doses of 3 to 30 mg/kg. Antiallodynic effects were not produced by intrathecal administration of paroxetine (10 to 100 &mgr;g) or maprotiline (10 to 100 &mgr;g). These findings suggest that simultaneous inhibition of serotonin and noradrenaline reuptake in the spinal cord is essential to mediate antiallodynic effects. Milnacipran might be effective for suppression of neuropathic pain.
Bacterial synergy of Treponema denticola and Porphyromonas gingivalis in a multinational population.

Treponema denticola and Porphyromonas gingivalis have been associated with human adult severe periodontitis. In this study, we quantified these putative pathogens in subgingival plaque samples collected from 74 Fijians, 74 Colombians and 73 U.S. Americans stationed at the Multinational Force and Observers encampment in the Sinai Desert, Egypt. A contingency table of T. denticola and P. gingivalis frequency revealed a highly significant synergistic relationship. We discovered that the occurrence of T. denticola apparently requires the presence of P. gingivalis. This represents the first observation of a synergistic relationship between these putative oral pathogens associated with adult severe periodontal disease.
The Aftermarket Performance of Initial Public Offerings in Pakistan

This paper estimates the aftermarket performance of initial public offerings (IPOs) listed on the Karachi Stock Exchange. The evidence confirms that IPOs generate statistically significant abnormal returns in the short run, which indicates that underwriters initially underprice IPOs when analyzed using a short time horizon. However, when using longer time horizons to estimate abnormal performance, the results indicate that IPOs underperform in the long-run. There is an apparent dislocation between the initial valuation set by underwriters and the premium paid by the market for these new issues. The market sentiment that causes this temporary disequilibrium eventually fades and the market reprices the newly issued shares. We conduct an extreme bounds analysis to test the sensitivity and robustness of 16 explanatory variables in determining the long-term performance of unseasoned newly issued shares. The results indicate that the long-term investment ratio, industry affiliation, market-adjusted abnormal returns, financial leverage, return on assets, IPO activity period, the aftermarket risk level of unseasoned issues, and the post-issue promoter’s holdings variables significantly affect IPOs’ aftermarket performance. Theoretically, the overreaction hypothesis, ex-ante uncertainty hypothesis and window-of-opportunity hypothesis best explain IPOs’ aftermarket performance in this study.
Task‐Specific Human Capital and Organizational Inertia

Employees' incentive to invest in their task proficiency depends on the likelihood that they will execute the same tasks in the future. Changes in tasks can be warranted as a result of technological progress and changes in firm strategy as well as from fine-tuning job design and from monitoring individuals' performance. However, the possibility of a change in tasks reduces employees' incentive to invest in task-specific skills. We develop a simple two-period principal-agent model showing that some degree of inertia benefits the principal. We then analyze how organizations can optimally combine several policies to approach the optimal degree of inertia. In particular, we consider the optimal mixture of (abstaining from) exploration, managerial vision, organizational task-specific investments, and incentive pay. Our analysis yields testable predictions concerning the relations between these organizational policies.
Association of Lyn tyrosine kinase to the GM‐CSF and IL‐3 receptor common βc subunit and role of Src tyrosine kinases in DNA synthesis and anti‐apoptosis

After GM‐CSF or IL‐3 stimulation, the activation of JAK2 tyrosine kinase and members of the Src family of tyrosine kinases takes place, followed by phosphorylation of βc tyrosine residues and the recruitment of SH2 containing molecules to the receptor complex. The exact role of Src kinases such as Lyn in this and other downstream signal transduction events remains unclear.