Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and validation of two models for early prediction of response to therapy in genotype 1 chronic hepatitis C

Early prediction of response to therapy in genotype 1 chronic hepatitis C is difficult. Two predictive models, a pretreatment scoring model (PreT‐SM) and a fourth week of therapy scoring model (4w‐SM) were constructed in a cohort of 104 patients from a single center (estimation cohort) and validated in a cohort of 141 patients from four independent centers (validation cohort). Individual scores were calculated using variables independently associated with sustained virological response (SVR). Baseline viral load, aspartate aminotransferase/alanine aminotransferase ratio, serum cholesterol, and a numerical score for noninvasive estimation of liver fibrosis were included in the PreT‐SM; HCV RNA clearance and PreT‐SM scores were included in the 4w‐SM. Receiver operating characteristic analysis revealed the area under the curve in the estimation cohort and in the validation cohort to be, respectively, 0.856 and 0.847 for the PreT‐SM and 0.908 and 0.907 for the 4w‐SM. Low scores were associated with SVR, high scores with non‐SVR. The best cutoff scores from the PreT‐SM (7 and 9.70) identified, respectively, 36% of patients with SVR and 41% of those with non‐SVR from the validation cohort, with high accuracy (≥90% positive predictive value [PPV] and specificity). Similarly, cutoff scores of 3.20 and 5.60 from the 4w‐SM identified, respectively, 71% of patients with SVR and 53% of those with non‐SVR from the same cohort with high accuracy (PPV and specificity >92%). In conclusion, these models predicted response to therapy before or after 4 weeks of treatment in approximately 60% of genotype 1 patients and may be valuable for the management of this condition. (HEPATOLOGY 2006;43:72–80.)
Variation among twin beef cattle in maintenance energy requirements.

The genetic variation in energy expenditures of cattle at fasting (FHP) and maintenance (MEm) was determined by using 12 pairs of monozygous twins at 20 mo of age. The pairs were of two breed types, eight Angus x Hereford (three steers, five heifers) and four Barzona x Hereford (three steers, one heifer). The heifers were 132 +/- 13 d pregnant at the time of measurement. The pairs were fed at 1.15 x maintenance energy requirements for a minimum of 30 d prior to heat production (HP) measurements in dual indirect respiration calorimetry chambers. The diet fed was cracked corn:alfalfa hay (45:55) with a determined ME of 2.47 +/- . 02 Mcal/kg DM. This diet was fed individually for 7 d prior to and during two consecutive 22-h HP measurements. The animals then were fasted for 2 d and fasting heat production measurements (FHP) were made on d 3 and 4 of the fast. Metabolizable energy required for MEm was calculated iteratively by assuming a semi-log relationship between HP and metabolizable energy intake. There were no differences (P greater than .10) in measured energy expenditures due to different breed type. The FHP and efficiency of ME use for MEm (Km) were similar between sexes, although heifers had lower (P less than .025) MEm than steers. Twin pair effects were detected for FHP (P less than .005) and MEm (P less than .05) but not for Km. Broad sense heritability estimates were calculated as the intraclass correlation between members of monozygous twin pairs. Heritability estimates for MEm, FHP, and Km were . 52 +/- . 22, . 75 +/- . 13, and . 34 +/- . 27, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
AQP8 transports NOX2‐generated H2O2 across the plasma membrane to promote signaling in B cells

H2O2 acts as a second messenger in key signaling circuits, transiently modulating tyrosine phosphatases and kinases. We investigated its origin, membrane transport, and functional role during B cell activation and differentiation. Our data identified NADPH‐oxidase 2 as the main source of H2O2 and aquaporin 8 as a transport facilitator across the plasma membrane. On aquaporin 8 silencing, inducible B lymphoma cells responded poorly to TLR and BCR stimulation. Their differentiation was severely impaired, as demonstrated by retarded onset of IgM polymerization, low amounts of IgM secretion, and prolonged BCR expression on the cell surface. A silencing‐resistant aquaporin 8 rescued responsiveness, confirming that the import of H2O2 across the membrane is essential for B cell activation. The addition of exogenous catalase to primary B splenocytes severely impaired the tyrosine phosphorylation induced by BCR cross‐linking, as did the absence of NOX2 in a murine model of chronic granulomatous disease. Importantly, re‐expression of gp91phox through gene therapy restored the specific B cell signaling deficiency in NOX2−/− cells. Thus, efficient induction of B cell activation and differentiation requires intact H2O2 fluxes across the plasma membrane for signal amplification.
Distribution of blood pressure, body mass index and smoking habits in the urban population of Dar es Salaam, Tanzania, and associations with socioeconomic status.

OBJECTIVE To estimate the distribution of blood pressure (BP), body mass index (BMI), smoking habits and their associations with socioeconomic status (SES) in an urban population in early epidemiological transition. METHODS Cross-sectional survey of the entire population aged 25-64 years in five branches of Dar es Salaam (Tanzania) through visits to all homes in the study area. Blood pressure was based on the mean of the second and third readings with an automated device. Socioeconomic status was estimated with indicators of education, occupation and wealth. RESULTS In all 9254 people were examined. Age-adjusted prevalence (%) among men/ women aged 35-64 years was 27.1/30.2 for BP > or = 140/90 mmHg or antihypertensive medication, 13.1/17.7 for BP > or = 160/95 mmHg or antihypertensive medication, 28.0/27.4 for BMI of 25.0-29.9 kg/m(2), 6.9/17.4 for BMI > or = 30 kg/m(2), and 22.0/2.6 for smoking (> or = 1 cigarette per day). Prevalence of categories of drinking frequency and history of diabetes are also reported. After adjustment for covariates, SES was associated inversely with BP and smoking and directly with BMI. Body mass index was associated positively with BP (1.01 and 0.91 mmHg systolic BP per 1 kg/m(2) BMI in men and women, respectively) and inversely with smoking (-1.14 kg/m(2) in male smokers versus non-smokers). Hypertension treatment rates were low, particularly in people of low SES. CONCLUSIONS High prevalence of several cardiovascular risk factors in the urban population of a low-income country stresses the need for early public health interventions and adaptation of the health care infrastructure to meet the emerging challenge of cardiovascular disease. The direct SES-BMI association may drive increasing BMI and BP while the population becomes more affluent.
A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer

To decrease the toxicity of hepatic arterial fluorodeoxyuridine (FUDR) administered through an Infusaid pump (Shiley Infusaid, Inc., Norwood, MA), 50 patients with liver metastases from colorectal cancer were selected randomly to receive FUDR, 0.3 mg/kg/d, for 14 of 28 days, with or without a total dose of 20 mg of hepatic arterial dexamethasone for 14 of 28 days. Patients were stratified according to the percentage of liver involvement by tumor and the perfusion pattern on macroaggrated albumin perfusion scan (MAA) scan. There was a trend toward decreased frequency of bilirubin levels in the group receiving dexamethasone plus FUDR versus the group receiving FUDR alone (9% and 30%, respectively, had a 200% or greater increase from baseline; P = 0.07). Patients in the group treated with dexamethasone and FUDR received higher doses of FUDR in the second, third, fifth, and sixth months than those receiving FUDR alone; however, this was statistically significant only in the fifth month (percentages of planned dose received: 42% and 19%, respectively; P = 0.05), and there was no overall difference for the total 6‐month period. The complete and partial response rates were increased in patients receiving dexamethasone and FUDR versus FUDR alone (8% and 63% versus 4% and 36%, respectively; P = 0.03), and there was a trend toward increased survival with the addition of dexamethasone (median, 23 months and 15 months, respectively; P = 0.06). In conclusion, the use of hepatic arterial dexamethasone is associated with an increased response rate and a trend toward increased survival and decreased bilirubin levels. Therefore, the authors recommend additional investigation of the use of dexamethasone with chemotherapy to treat hepatic metastases.
Advanced Endoscopic Imaging for Surveillance for Dysplasia and Colorectal Cancer in inflammatory Bowel Disease: Could the Pathologist be Further Helped?

Patients with inflammatory bowel disease (IBD) have an increased risk of developing intestinal cancer. The magnitude of that increased risk as well as how best to mitigate it remain a topic of ongoing investigation in the field. It is important to quantify the risk of colorectal cancer in association with IBD. The reported risk varies widely between studies. This is partly due to the different methodologies used in the studies. Because of the limitations of surveillance strategies based on the detection of dysplasia, advanced endoscopic imaging and techniques involving the detection of alterations in mucosal antigens and genetic abnormalities are being investigated. Development of new biomarkers, predicting future occurrence of colonic neoplasia may lead to more biomarker-based surveillance. There are promising results that may lead to more efficient surveillance in IBD patients and more general acceptance of its use. A multidisciplinary approach, involving in particular endoscopists and pathologists, together with a centralized patient management, could help to optimize treatments and follow-up measures, both of which could help to reduce the IBD-associated cancer risk.
Clinical features and therapeutic interventions in 17 cases of Bacillus bacteremia in an immunosuppressed patient population

We retrospectively examined episodes of Bacillus bacteremia at a hospital with a large proportion of immunosuppressed patients. Seventeen episodes in 9.5 years met our case definition: two of two bottles of one blood culture or one of two bottles of two or more separately obtained blood cultures drawn on the same date. During the same period, there were 59 additional episodes in which a single blood culture had only one of two bottles positive for Bacillus species. Only 2 of 59 such episodes resulted in recurrent bacteremia (3%), as compared with 5 of 17 episodes meeting our case definition (29%) (P = 0.004). In four of five episodes complicated by recurrent bacteremia and in which appropriate antibiotics were used, a Hickman-Broviac catheter was in place and was not removed. We suggest that our case definition permits the differentiation of infection from contamination based on outcome and that patients with Bacillus bacteremia have chronic venous catheters removed as well as receive antibiotic treatment.
Comparison of Higher-Order Aberration and Contrast Sensitivity in Monofocal and Multifocal Intraocular Lenses

Purpose The visual performance of pseudophakic eyes depends on the type of intraocular lenses (IOLs) that are implanted. Aspherical and multifocal IOLs have recently been developed to improve visual quality after cataract surgery, but multifocal IOLs can be associated with decreased contrast sensitivity (CS), halos, and glare. This study compares the visual performance of monofocal and multifocal IOLs by measurement of higher-order aberrations (HOAs) and CS values. Materials and Methods HOAs and CS values of 42 eyes with implanted monofocal IOLs and 40 eyes with implanted multifocal IOLs were measured preoperatively and more than 6 months after surgery. In the multifocal IOL group, HOAs and CS values were also measured with addition of a trial lens of -0.5 diopter (D) to evaluate the compensatory effect on spherical aberration. Results CS values of the multifocal IOL group were significantly lower than those of the monofocal IOL group for all spatial frequencies tested (p < 0.01), and the spherical aberration was significantly higher in the multifocal IOL group than in the monofocal IOL group (p < 0.001). Addition of a -0.5 D lens to the multifocal IOL group decreased the difference in CS between the two groups (p = 0.003). Conclusion Increased spherical aberration may contribute to lower CS in the multifocal IOL group. In such cases, CS can be improved by addition of a -0.5 D lens to compensate for the spherical aberration.
The value of fixed rasburicase dosing versus weight-based dosing in the treatment and prevention of tumor lysis syndrome

Background Rasburicase is a recombinant urate oxidase enzyme used for the treatment and prevention of tumor lysis syndrome. Our objective was to assess the efficacy of indication-based, low-dose rasburicase administration compared to the Food and Drug Administration-approved weight-based dosing. Methods This was a retrospective cohort study utilizing data from a tertiary medical center including patients admitted from 2012 to 2016, who received at least one dose of rasburicase. The primary outcome was achieving a uric acid level less than 7.5 mg/dl after a single dose of rasburicase in the preprotocol (Food and Drug Administration-approved weight-based dosing) and postprotocol (indication-based, low-dose) groups. Secondary outcomes included the change in uric acid levels between the pre- and postprotocol groups, adherence to the new institutional protocol, need for repeat rasburicase doses, and a cost analysis. Results Sixty-four patients received at least one dose of rasburicase between 1 January 2012 and 1 December 2016. Twenty-seven (79.4%) doses in the preprotocol group and 28 (82.4%) doses in the postprotocol group successfully achieved a uric acid level less than 7.5 mg/dl after a single dose of rasburicase (p=1.000). The average total monthly cost of rasburicase was reduced by 59.9% after adoption of the new protocol. Conclusions Indication-based, low-dose rasburicase displayed significantly more value when compared to weight-based dosing as shown by achieving cost savings without compromising clinical efficacy.
The epidemiology of HIV infection among young people aged 15–24 years in southern Africa

Objectives:To investigate epidemiological patterns and trends of HIV infection and sexual behaviour among young people aged 15–24 years in the nine countries in southern Africa most affected by the HIV epidemic. Methods:Data on HIV prevalence among young people in the general population were obtained from national population-based surveys conducted between 2000 and 2007, whereas data on sexual behaviour were obtained from repeat surveys between 1994 and 2007. Linear or exponential regression was used to analyse HIV prevalence trends among young women attending antenatal clinics in recent years. Results:Patterns of HIV infection among young people are similar across the countries included in this analysis. The prevalence of HIV increases after the age of 15 years, more rapidly among women than among men, reaching a peak among women in their twenties and men in their thirties. Between 2000 and 2007 the prevalence of HIV among antenatal clinic attendees was constant in Mozambique and South Africa and declining in Lesotho, Namibia, Swaziland, Zambia, Botswana, Malawi and Zimbabwe, but only reached statistical significance (P < 0.05) in the last three. Changes towards safer sexual behaviour were observed over time among young men and women in the general population in this region. Conclusion:Sexual behaviour changes among young people are encouraging and are associated with declines in HIV prevalence among young antenatal clinic attendees over time. More research is needed to understand the recent changes and the very high prevalence among young women in this region. Interventions aimed at reducing risky behaviour need to be supported and expanded while incorporating new approaches to prevention.
Bedaquiline Inhibits the ATP Synthase in Mycobacterium abscessus and Is Effective in Infected Zebrafish

ABSTRACT Pulmonary infections caused by Mycobacterium abscessus are emerging as a global threat, especially in cystic fibrosis patients. Further intensifying the concern of M. abscessus infection is the recent evidence of human-to-human transmission of the infection. M. abscessus is a naturally multidrug-resistant fast-growing pathogen for which pharmacological options are limited. Repurposing antitubercular drugs represents an attractive option for the development of chemotherapeutic alternatives against M. abscessus infections. Bedaquiline (BDQ), an ATP synthase inhibitor, has recently been approved for the treatment of multidrug-resistant tuberculosis. Herein, we show that BDQ has a very low MIC against a vast panel of clinical isolates. Despite being bacteriostatic in vitro, BDQ was highly efficacious in a zebrafish model of M. abscessus infection. Remarkably, a very short period of treatment was sufficient to protect the infected larvae from M. abscessus-induced killing. This was corroborated with reduced numbers of abscesses and cords, considered to be major pathophysiological signs in infected zebrafish. Mode-of-action studies revealed that BDQ triggered a rapid depletion of ATP in M. abscessusin vitro, consistent with the drug targeting the FoF1 ATP synthase. Importantly, despite a failure to select in vitro for spontaneous mutants that are highly resistant to BDQ, the transfer of single nucleotide polymorphisms leading to D29V or A64P substitutions in atpE conferred high resistance, thus resolving the target of BDQ in M. abscessus. Overall, this study indicates that BDQ is active against M. abscessusin vitro and in vivo and should be considered for clinical use against the difficult-to-manage M. abscessus pulmonary infections.
Chicken lateral septal organ and other circumventricular organs form in a striatal subdomain abutting the molecular striatopallidal border

The avian lateral septal organ (LSO) is a telencephalic circumventricular specialization with liquor‐contacting neurons (Kuenzel and van Tienhoven [1982] J. Comp. Neurol. 206:293–313). We studied the topological position of the chicken LSO relative to molecular borders defined previously within the telencephalic subpallium (Puelles et al. [2000] J. Comp. Neurol. 424:409–438). Differential expression of Dlx5 and Nkx2.1 homeobox genes, or the Shh gene encoding a secreted morphogen, allows distinction of striatal, pallidal, and preoptic subpallial sectors. The chicken LSO complex was characterized chemoarchitectonically from embryonic to posthatching stages, by using immunohistochemistry for calbindin, tyrosine hydroxylase, NKX2.1, and BEN proteins and in situ hybridization for Nkx2.1, Nkx2.2, Nkx6.1, Shh, and Dlx5 mRNA. Medial and lateral parts of LSO appear, respectively, at the striatal part of the septum and adjacent bottom of the lateral ventricle (accumbens), in lateral continuity with another circumventricular organ that forms along a thin subregion of the entire striatum, abutting the molecular striatopallidal boundary; we called this the “striatopallidal organ” (SPO). The SPO displays associated distal periventricular cells, which are lacking in the LSO. Moreover, the SPO is continuous caudomedially with a thin, linear ependymal specialization found around the extended amygdala and preoptic areas. This differs from SPO and LSO in some molecular aspects. We tentatively identified this structure as being composed of an “extended amygdala organ” (EAO) and a “preoptohypothalamic organ” (PHO). The position of LSO, SPO, EAO, and PHO within a linear Dlx5‐expressing ventricular domain that surrounds the Nkx2.1‐expressing pallidopreoptic domain provides an unexpected insight into possible common and differential causal mechanisms underlying their formation. J. Comp. Neurol. 499:745–767, 2006. © 2006 Wiley‐Liss, Inc.
Is the short insulin tolerance test safe and reproducible?

The short insulin tolerance test (SITT) is described as a simple method to measure insulin sensitivity. To investigate the safety and reproducibility of the SITT, 16 healthy volunteers underwent two SITTs within 1 week. Intravenous insulin (0.05 U kg−1 body weight) was injected into an antecubital vein. Blood samples were collected from the contralateral antecubital vein. The insulin‐induced glucose disposal rate (Kitt) was calculated from the slope of the regression line of the logarithm of blood glucose against time during the first 3–15 min. Plasma glucose concentrations fell below 2.8 mmol l−1 in 4 of the 32 tests and below 2.2 mmol l−1 in 1 of these 4. Five subjects had mild hypoglycaemic symptoms, three of whom had plasma glucose concentrations below 2.8 mmol l−1 in at least one SITT. The mean Kitt was 4.2 % min−1 (range 0.8–8.4) for the first test and 3.4 % min−1 (range 0.1–6.8) for the second test. The mean within‐subject coefficient of variation was 30.7 %. We conclude that SITT should be applied with caution especially on insulin sensitive subjects and has poor reproducibility using 0.05 U kg−1 body weight of insulin injection, venous sampling, uncontrolled physical activity and uncontrolled dietary composition. Whether 0.1 U kg−1 body weight of insulin injection and arterialized venous blood sampling as in the original description of this test can improve the reproducibility of the SITT needs further investigation. © 1998 John Wiley & Sons, Ltd.
Ischemia-Induced Degeneration of CA1 Pyramidal Cells Decreases Seizure Severity in a Subgroup of Epileptic Gerbils and Affects Parvalbumin Immunoreactivity of CA1 Interneurons

Mongolian gerbils are epilepsy-prone animals. In adult gerbils two major groups can be differentiated according to their seizure behavior: Highly seizure-sensitive gerbils exhibit facial and forelimb clonus or generalized tonic-clonic seizures from the first test on, while kindled-like gerbils are seizure free for the first three to six consecutive tests, later develop forelimb myoclonus, and eventually progress to generalized tonic-clonic seizures. In the hippocampus, seizure history of the individual animal is mirrored in the intensity in which GABAergic neurons are immunostained for the calcium-binding protein parvalbumin: they lose parvalbumin with increasing seizure incidence. In a first step to clarify the influence of hippocampal projection neurons on spontaneous seizure behavior and related parvalbumin expression, we induced degeneration of the CA1 pyramidal cells by transient forebrain ischemia. This results in a decreased seizure sensitivity in highly seizure-sensitive gerbils. The kindling-like process, however, is not permanently blocked by the ischemic nerve cell loss, suggesting that an intact CA1 field is not a prerequisite for the development of seizure behavior. The seizure-induced loss of parvalbumin from the ischemia-resistant interneurons recovers after ischemia. Thus, changes in parvalbumin content brought about by repeated seizures are not permanent but can rather be modulated by novel stimuli.