Miracle-dz/UniFAR-FTUs huggingface dataset:
Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus

Some individuals who are chronically infected with hepatitis B virus (HBV) eventually lose hepatitis B surface antigen (HBsAg). Hepatocellular carcinoma (HCC) has been demonstrated to occur in a few patients after loss of HBsAg. Neither factors associated with loss of HBsAg nor the incidence of HCC thereafter have been clearly elucidated. We performed a prospective population‐based cohort study in 1,271 Alaska Native persons with chronic HBV infection followed for an average of 19.6 years to determine factors associated with loss of HBsAg and risk of developing HCC thereafter. HBsAg loss occurred in 158 persons for a rate of HBsAg clearance of 0.7%/year. Older age, but not sex, was associated with clearance of HBsAg, and loss of HBsAg was not associated with any particular HBV genotypes (A, B, C, D, and F) found in this population. Participants were followed for an average of 108.9 months after HBsAg loss. Six patients, two with cirrhosis and four without, developed HCC a mean of 7.3 years after HBsAg clearance (range, 2.0–15.5 years). The incidence of HCC after clearance of HBsAg was 36.8 per 100,000 per year (95% CI 13.5–80.0) which was significantly lower than the rate in those who remained HBsAg‐positive (195.7 cases per 100,000 person‐years of follow‐up [95% CI 141.1–264.5; P < 0.001]). After loss of HBsAg, HBV DNA was detected in the sera of 28 (18%) of those who cleared a median of 3.6 years after clearance. Conclusion: HCC can occur in persons with chronic hepatitis B who have lost HBsAg, even in the absence of cirrhosis. These persons should still be followed with periodic liver ultrasound to detect HCC early. (HEPATOLOGY 2010.)
Optimization of the Expression of Reteplase in Escherichia coli TOP10 Using Arabinose Promoter

Background: Reteplase is a mutant version of t-PA (tissue plasminogen activator) with prolonged half-life. In the present study, E. coli Top 10 bacteria were utilized in the production of reteplase, which is the nonglycosylated active domain of t-PA. Reteplase gene was ligated into pBAD/gIII plasmid which, allows secretion of this protein in periplasmic space. It would allow the correct formation of disulfide bonds in protein structure. Objectives: This study aimed at expression of reteplase in optimum condition. In this study, the reteplase gene was cloned and expressed in Escherichia coli top 10 as a suitable host cell and its expression was optimized. Materials and Methods: The recombinant plasmid, pET15b/reteplase was digested by NcoI and BamHI restriction enzymes; while pBAD/gIIIA vector was digested by NcoI and BglII. Then the insert and vector were ligated and used for transformation of E. coli Top10 cells by heat shock method. Overnight culture of transformed bacteria was induced by L-arabinose in various concentrations (0.2, 0.02, 0.002, and 0.0002%) and at various temperatures. Results: The obtained recombinant plasmid was sequenced to confirm the presence and correct framing of reteplase gene regarding the expression of reteplase. Maximum production of this enzyme was obtained under the following condition: 0.0002% L-arabinose at 37°C for 2 hours incubation. The purified protein was detected on SDS-PAGE (sodium dodecyl sulfate Polyacrylamide gel electrophoresis) as a 66 kDa band. The concentration of t-PA standard was 1 unit which is equal to 12 µg/mL. The enzymatic activity of samples was measured as 0.8 units compared to the standards. Conclusions: Reteplase was expressed in E. coli Top 10 after activation of pBAD/gIIIA promoter region by arabinose and optimized.
Bright-Dark Pulse Pair in a Passively Mode-Locked Fiber Laser Based on Thulium-Doped Fiber

A dual-wavelength bright-dark pulse pair has been experimentally demonstrated in a mode-locked fiber laser based on thulium-doped fiber (TDF). By appropriately adjusting the polarization state, the dual-wavelength bright-dark pulse pairs with fundamental frequency of 20.56 MHz can be successfully obtained under the pump power ranging from 150 to 500 mW. The largest pulse energy is 2.84 nJ, and the conversion efficiency exceeds 10%. The generation mechanism of the bright-dark pulse pair in the cavity is primarily attributed to the cross-phase modulation (XPM) induced by the interaction of the bright soliton and dark soliton locating at different wavebands. Additionally, the dynamics of the bright-dark pulse pair is influenced by the polarization effect. To the best of our knowledge, this is the first demonstration of a bright-dark pulse pair laser employing TDF as the saturable absorber (SA). Its superiority for mode-locking has been fully proved, making it enormous potential in the fields of ultrafast lasers and nonlinear optics. Furthermore, this pulsed laser may offer a novel path for the development of high-power fiber lasers.
A synthetic peptide derived from the parasite Toxoplasma gondii triggers human dendritic cellsˈ migration

The migration of DCs is a critical function, enabling information to be carried to where the immunological response occurs. Parasites are known to weaken host immunity by interfering with the functions of DCs and thus, may be a source of molecules with immunomodulatory properties. Here, we demonstrate that the soluble protein, GRA5, specific to Toxoplasma gondii, is able to increase the migration of human CD34‐DCs toward CCL19. A synthetic Pep29 derived from the GRA5 hydrophilic NT region (Pep29) was found to be internalized by macropinocytosis and to trigger in vitro migration of CD34‐DCs via CCR7 expression without activating DCs. Pep29 also induced a decrease in the number of LCs from human skin epidermis. As local depletion of DCs and migration of immature DCs lead to a disruption of the specific innate response, our results highlight the potential of using pathogen‐derived synthetic peptides as novel cell modulators with a therapeutic potential to reduce symptoms in inflammatory disorders.
Intraepidermal proliferation of Merkel cells within a seborrheic keratosis: Merkel cell carcinoma in situ or Merkel cell hyperplasia?

Intradepidermal proliferation of Merkel cells without any dermal component has been interpreted as either a hyperplastic process secondary to chronic ultraviolet radiation or a neoplastic process, namely Merkel cell carcinoma (MCC) in situ. The recent criteria that have been proffered to diagnose MCC in situ, unfortunately, are identical to those that have been applied to Merkel cell hyperplasia in the past, posing a diagnostic quandary when faced with an intraepidermal proliferation of Merkel cells. Most previously reported cases of MCC in situ have occurred within associated epithelial lesion that includes solar (actinic) keratosis and squamous‐cell carcinoma in situ. Similarly, Merkel cell hyperplasia has been reported to occur in association with a variety of epithelial lesions as well as on chronically sun‐damaged skin. Herein, a case of an intraepidermal proliferation of Merkel cells within a seborrheic keratosis is presented accompanied by a discussion on whether the proliferation represents another case of Merkel cell carcinoma in situ or an incidental hyperplastic process on chronically sun‐damaged skin.
Metabolism of a fl atoxin B 1 in Turkey liver microsomes : The relative roles of cytochromes P 450 1 A 5 and 3 A 37

Abbreviations: AFB1, aflatoxin B1; AFM1, aflatoxin AFB1-8,9-epoxide; AFBO-GSH, AFB1-8,9-epoxide glutath aflatoxin B1-8,9-epoxide; endo-AFBO, endo-aflatoxin B G1; BHA, Butylated hydroxyanisole; BHT, butylated hyd S-transferase; P450, cytochrome P450; TLM, turkey live ⁎ Corresponding author at: Graduate Toxicology Pr 4620 Old Main Hill, Logan, UT 84322. Fax: +1 435 797 E-mail address: roger@usu.edu (R.A. Coulombe).
Which arterial and cardiac parameters best predict left ventricular mass?

BACKGROUND Many cardiovascular and noncardiovascular parameters are thought to be determinants of left ventricular mass (LVM). Complicated interactions necessitate the simultaneous measurement and consideration of each to determine their individual and collective impact on LVM. We undertook such a comprehensive study. METHODS AND RESULTS The influence of anthropometry, cardiac size and contractility, arterial structure and function, as well as indices of lifestyle, physical activity, and dietary salt intake on LVM (by two-dimensionally guided M-mode echocardiography) was analyzed in 1315 Chinese subjects who were either normotensive or had untreated hypertension. Effects of many cardiac and arterial factors were assessed. In univariate analysis, almost all measured noncardiovascular, cardiac, and arterial variables were significantly correlated with LVM. In multivariate linear regression analyses, when age, sex, body habitus, fasting serum C-peptide level, dietary salt, physical activity, and lifestyle were accounted for, the optimum multivariate linear regression main effects model had an adjusted model r2 of 0.740, with 98% of the model variance accounted for by the 5 independent determinants of LVM: stroke volume (49.6%), systolic blood pressure (30.7%), contractility (14.7%), body mass index (1.8%), and aortic root diameter (1.6%). Other proposed arterial indices were significant independent determinants of LVM only when blood pressure was removed from the model and, even then, these indices not only resulted in less powerful prediction but also accounted for only a very small percentage of the total variance of LVM. CONCLUSIONS In a large population, we (1) confirmed that age, body habitus, and some indexes of arterial structure and function are independent determinants of LVM; (2) found aortic diameter to be an independent structural determinant of LVM; (3) demonstrated that the effects of the derived measures of arterial function were small and provided no better predictive power than blood pressure alone; and (4) showed that when the best measures of cardiac and vascular load were included, the single most potent predictor was an index of left ventricular size.
Differential Anti-APOBEC3G Activity of HIV-1 Vif Proteins Derived from Different Subtypes*

Antiretroviral cytidine deaminase APOBEC3G, which is abundantly expressed in peripheral blood lymphocytes and macrophages, strongly protects these cells against HIV-1 infection. The HIV-1 Vif protein overcomes this antiviral effect by enhancing proteasome-mediated APOBEC3G degradation and is key for maintaining viral infectivity. The 579-bp-long vif gene displays high genetic diversity among HIV-1 subtypes. Therefore, it is intriguing to address whether Vif proteins derived from different subtypes differ in their viral defense activity against APOBEC3G. Expression plasmids encoding Vif proteins derived from subtypes A, B, C, CRF01_AE, and CRF02_AG isolates were created, and their anti-APOBEC3G activities were compared. Viruses produced from cells expressing APOBEC3G and Vif proteins from different subtypes showed relatively different viral infectivities. Notably, subtype C-derived Vif proteins tested had the highest activity against APOBEC3G that was ascribed to its increased binding activity, for which the N-terminal domain of the Vif protein sequences was responsible. These results suggest that the biological differences of Vif proteins belonging to different subtypes might affect viral fitness and quasispecies in vivo.
Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome

Objective Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, may play a critical role in many chronic pain conditions. The possible involvement of BDNF in the altered gut sensation in patients with irritable bowel syndrome (IBS) was investigated in the present study. Methods Rectosigmoid biopsies were collected from 40 patients with IBS fulfilling the Rome II criteria and 21 healthy controls. Abdominal pain was quantified by a validated questionnaire. The presence of BDNF and nerve fibres in the mucosa was assessed by immunohistochemistry. The structure of mucosal nerve fibres was assessed by transmission electron microscopy. Mucosal BDNF release was measured by ELISA and correlated with abdominal pain scores. Animal studies using BDNF+/− mice were carried out to evaluate visceral sensitivity, mucosal nerve fibre density and ultrastructural changes. Alterations of visceral sensitivity and TrkB expression in dorsal root ganglia were examined in BDNF+/+ mice following different doses of BDNF administration. Results Biopsies from patients with IBS revealed a significant upregulation of BDNF (p=0.003), as compared with controls. Total nerve fibres were also substantially increased in patients with IBS. Electron microscopy showed ultrastructural damage on the mucosal nerve fibres (eg, swollen mitochondria and nerve axons). Elevated BDNF release was significantly correlated with the abdominal pain scores. Meanwhile, abdominal withdrawal reflex scores to colorectal distension and mucosal protein gene product 9.5 immunoreactivity were significantly lowered in BDNF+/− than in BDNF+/+ mice. Electron microscopy showed degenerative changes on the mucosal nerve fibres in BDNF+/− mice. Exogenous BDNF induced an obvious dose-dependent increase in TrkB expression in dorsal root ganglia and dose-dependent decrease in threshold pressure in BDNF+/+ mice. Conclusions The increased expression of BDNF in colonic mucosa, together with the structural alterations of mucosal innervation, may contribute to the visceral hyperalgesia in IBS.
Experimental infection of pregnant rabbits with hepatitis E virus demonstrating high mortality and vertical transmission

A high mortality rate of approximately 20% in pregnant women with hepatitis E has been reported in previous studies. However, other studies showed no difference between pregnant and nonpregnant women in the severity of hepatitis E. To determine the effects of HEV infection on pregnancy, we successfully established HEV infection in six pregnant rabbits (PR) and six nonpregnant rabbits (NPR) with a rabbit HEV isolate, taking three PR and one NPR without HEV infection as controls. Tests for HEV RNA by RT‐PCR, anti‐HEV antibodies by ELISA and HEV antigen via immunohistochemistry and histopathology were carried out. Two of six infected PR miscarried and three of the remaining four PR died which may be attributed to severe liver necrosis caused by HEV infection. Moreover, vertical transmission was found to be associated with the replication of HEV in placenta, indicated by the presence of HEV RNA and antigen in placenta from the infected PR. Our findings strongly suggest that HEV infection could lead to adverse outcomes in pregnancy and vertical transmission, suggesting the necessity for pregnant women at risk of HEV infection to be vaccinated.
Surveying Farmers: A Case Study

A large percentage of farmers do not respond to mail surveys. To gain insight into why farmers do not respond and how to improve response rates, a three-step research design was developed. First, an initial survey, based on in-person interviews with 15 farmers, was sent to 100 farmers. Second, farmers who did not respond to this mail survey were contacted by phone to investigate the reasons for not responding. Third, based on the information from these nonrespondents, the survey instrument was revised and sent to 3,990 U.S. farmers. Our studies show that the period in which the survey is sent is a crucial factor in the willingness to participate, along with the form and amount of compensation, the sender of the questionnaire, and the perceived length of the questionnaire.
Comparative phosphoproteomic analysis of mammalian glomeruli reveals conserved podocin C‐terminal phosphorylation as a determinant of slit diaphragm complex architecture

Glomerular biology is dependent on tightly controlled signal transduction networks that control phosphorylation of signaling proteins such as cytoskeletal regulators or slit diaphragm proteins of kidney podocytes. Cross‐species comparison of phosphorylation events is a powerful mean to functionally prioritize and identify physiologically meaningful phosphorylation sites. Here, we present the result of phosphoproteomic analyses of cow and rat glomeruli to allow cross‐species comparisons. We discovered several phosphorylation sites with potentially high biological relevance, e.g. tyrosine phosphorylation of the cytoskeletal regulator synaptopodin and the slit diaphragm protein neph‐1 (Kirrel). Moreover, cross‐species comparisons revealed conserved phosphorylation of the slit diaphragm protein nephrin on an acidic cluster at the intracellular terminus and conserved podocin phosphorylation on the very carboxyl terminus of the protein. We studied a highly conserved podocin phosphorylation site in greater detail and show that phosphorylation regulates affinity of the interaction with nephrin and CD2AP. Taken together, these results suggest that species comparisons of phosphoproteomic data may reveal regulatory principles in glomerular biology. All MS data have been deposited in the ProteomeXchange with identifier PXD001005 (http://proteomecentral.proteomexchange.org/dataset/PXD001005).
Salt-Induced Nephropathy in Obese Spontaneously Hypertensive Rats Via Paradoxical Activation of the Mineralocorticoid Receptor: Role of Oxidative Stress

Aldosterone is implicated in the pathogenesis of proteinuria and chronic kidney disease. We previously demonstrated the contribution of elevated serum aldosterone in the early nephropathy of SHR/NDmcr-cp (SHR/cp), a rat model of metabolic syndrome. In the present study, we investigated the effect of salt loading on renal damage in SHR/cps and explored the underlying mechanisms. SHR/cps fed a high-sodium diet for 4 weeks developed severe hypertension, massive proteinuria, and advanced renal lesions. High salt also worsened glomerular podocyte impairment. Surprisingly, selective mineralocorticoid receptor (MR) antagonist eplerenone dramatically ameliorated the salt-induced proteinuria and renal injury in SHR/cps. Although salt loading reduced circulating aldosterone, it increased nuclear MR and expression of aldosterone effector kinase Sgk1 in the kidney. Gene expressions of transforming growth factor-&bgr;1 and plasminogen activator inhibitor-1 were also enhanced in the kidneys of salt-loaded SHR/cps, and eplerenone completely inhibited these injury markers. To clarify the discrepancy between decreased aldosterone and enhanced MR signaling by salt, we further investigated the role of oxidative stress, a putative key factor mediating salt-induced tissue damage. Interestingly, antioxidant Tempol attenuated the salt-evoked MR upregulation and Sgk1 induction and alleviated proteinuria and renal histological abnormalities, suggesting the involvement of oxidative stress in salt-induced MR activation. MR activation by salt was not attributed to increased serum corticosterone or reduced 11&bgr;-hydroxysteroid dehydrogenase type 2 activity. In conclusion, sodium loading exacerbated proteinuria and renal injury in metabolic syndrome rats. Salt reduced circulating aldosterone but caused renal MR activation at least partially via induction of oxidative stress, and eplerenone effectively improved the nephropathy.
Extra‐uterine myoid tumours in patients with acquired immunodeficiency syndrome: a clinicopathological reappraisal

Ramdial P K, Sing Y, Deonarain J, Vaubell J I, Naicker S, Sydney C, Hadley L G P, Singh B, Kiratu E, Gundry B & Sewram V (2011) Histopathology 59, 1122–1134 Extra‐uterine myoid tumours in patients with acquired immunodeficiency syndrome: a clinicopathological reappraisal
Hemodynamic alterations in cirrhosis and portal hypertension

Portal hypertension (PHT) is associated with hemodynamic changes in intrahepatic, systemic, and portosystemic collateral circulation. Increased intrahepatic resistance and hyperdynamic circulatory alterations with expansion of collateral circulation play a central role in the pathogenesis of PHT. PHT is also characterized by changes in vascular structure, termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. Angiogenesis, the formation of new blood vessels, also occurs with PHT related in particular to the expansion of portosystemic collateral circulation. The complementary processes of vasoreactivity, vascular remodeling, and angiogenesis represent important targets for the treatment of portal hypertension. Systemic and splanchnic vasodilatation can induce hyperdynamic circulation which is related with multi-organ failure such as hepatorenal syndrome and cirrhotic cadiomyopathy.
Closing in on a Short-Hard Burst Progenitor: Constraints from Early-Time Optical Imaging and Spectroscopy of a Possible Host Galaxy of GRB 050509b

The localization of the short-duration, hard-spectrum gamma-ray burst GRB 050509b by the Swift satellite was a watershed event. We report the discovery of the probable host galaxy, a bright elliptical galaxy at z = 0.2248. This is the first known redshift and host of a short-hard GRB and shows that at least some short-hard GRBs are cosmological in origin. We began imaging the GRB field 8 minutes after the burst and continued for 8 days. We present a reanalysis of the XRT afterglow and report the absolute position of the GRB. Based on positional coincidences, the GRB and the elliptical are likely to be physically related, unlike any known connection between a long-duration GRB and an early-type galaxy. Similarly unique, GRB 050509b likely also originated from within a rich cluster of galaxies with detectable diffuse X-ray emission. We demonstrate that while the burst was underluminous, the ratio of the blast wave energy to the γ-ray energy is consistent with that of long-duration GRBs. Based on this analysis, on the location of the GRB (40 ± 13 kpc from the putative host), on the galaxy type (elliptical), and the lack of a coincident supernova, we suggest that there is now observational support for the hypothesis that short-hard bursts arise during the merger of a compact binary. We limit the properties of any Li-Paczyński "minisupernova" that is predicted to arise on ~1 day timescales. Other progenitor models are still viable, and new Swift bursts will undoubtedly help to further clarify the progenitor picture.
Schistosomiasis: A Rare Cause of Acute Appendicitis -

Schistosomiasis is a water-borne trematode infestation and is one of the most widespread parasitic diseases in the world. Schistosomiasis can affect any organ, but is rare in the appendix. In this paper, the authors report a new case of appendicular schistosomiasis that was incidentally discovered in a 27-year-old male patient from Mali who underwent appendectomy for acute appendicitis. Appendectomy specimens removed from patients with appendicular schistosomiasis often appear macroscopically normal, but histopathological analysis of these cases confirms the diagnosis by revealing schistosomal eggs. The authors strongly recommend that all appendectomy specimens be examined histopathologically regardless of whether the specimens are macroscopically normal.