Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial‐like cells derived directly from human tumor xenografts

Tumor‐associated endothelial cells (TAECs) harboring various genomic abnormalities have been described in human cancers although their origins remain obscure. We generated 4 human cancer cell lines tagged with multiple markers, grew them as xenografts, and characterized their TAECs. Depending on their tumor of origin, 5–40% of TAECs reproducibly expressed all tags. Tagged TAECs (tTAECS) were morphologically, immunologically and functionally similar, although not identical, to normal endothelial cells (ECs) and contained only human chromosomes. tTAECs underwent a senescent‐like proliferative arrest after several in vitro passages, but could be immortalized by telomerase, thus allowing us to show that the retention of the EC phenotype was of long‐term duration. In contrast, nonimmortalized tTAECs could be propagated in vivo where they incorporated into the tumor neo‐vasculature. Although consistent with previous reports that some tumor cells may undergo “vasculogenic mimicry” (VM), the tumor‐derived endothelial‐like cells described here appear distinctly different. Moreover, their properties and behaviors are more durable than expected for cells undergoing VM, are not the result of fusions between ECs and tumor cells, and are cell autonomous. These findings could have significant implications for therapies that target tumor angiogenesis.
Effects of free and liposomized praziquantel on worm burden and antibody response in mice infected with Mesocestoides corti tetrathyridia

Abstract The parasite burden in the liver and peritoneal cavity and antibody levels directed to whole worm extract, have been monitored in serum from ICR-strain mice, infected orally with 55 tetrathyridia of Mesocestoides corti (Cestoda, Cyclophyllidea). The subcurative doses (3x or 6x) of praziquantel (PZQ) (10 mg.kg−1 body weight) were administered to mice from day 14 post infection (p.i.) in two drug formulations: as PZQ suspended in Dorfman vehicle, or as PZQ incorporated in liposomes (lip.PZQ). The appearance of antibodies was time-dependent and correlated with the rate of reduction in numbers of tetrathyridia. PZQ in three and six doses caused the highest fall of parasite numbers in the liver on day 1 post therapy (p.t.). In the peritoneal cavity, a similar reduction in worm burden occurred but only after six doses of the drug. The worm count in the peritoneal cavity from groups of mice injected with lip.PZQ decreased most markedly on day 7 p.t. , in the group treated with six doses of the drug. In the liver, the highest larvicidal effect, compared with the controls, was observed 6 days later (i.e. day 13 p.t.), following three doses of lip.PZQ. In all treated groups, two peak values of antitetrathyridial antibody levels were detected between days 1 and 13 p.t. (i.e. days 17 to 29 p.i.), after which there was a gradual but continuous increase in antibody titre. After treatment with six doses of both drug formulations (PZQ and lip.PZQ), the occurrence of the first maximum and minimum of antibody serum levels was delayed 6 days, compared to those groups treated with three doses of the drugs. Empty liposomes had some immunomodulatory effect on the antibody response, with significant decrease in antibody titres after three doses over the experimental period, but not after six doses.
Spontaneous Findings in the Heart of Mauritian-Origin Cynomolgus Macaques (Macaca fascicularis)

The cynomolgus macaque is the most commonly used nonhuman primate in nonclinical toxicity testing, but the impact of the geographic source of cynomolgus macaque on differences in spontaneous pathology and response to xenobiotics has only recently been explored. Previous work from the authors' facility has described spontaneous cardiac findings in predominantly Indonesian-source animals; however, the authors have recently observed a novel spectrum of cardiac findings in Mauritian-source animals. This review evaluated the spontaneous macroscopic and microscopic cardiac findings in vehicle control Mauritian-source macaques used for routine toxicity testing. When compared to the prior review in predominantly Indonesian macaques, a higher incidence of myocardial degeneration was observed with additional novel findings including macroscopic and microscopic subendocardial hemorrhage with hemosiderin, myocardial fibrosis, and arterial medial degeneration/hemorrhage. Other findings including inflammatory cell infiltrates, anisokaryosis, and squamous plaques were observed with a comparable incidence as previously reported in Indonesian macaques. Myocardial degeneration, subendocardial hemorrhage, and myocardial fibrosis can mimic test-article-related cardiac toxicity, and a thorough understanding of the incidence and severity of these spontaneous findings is necessary to prevent misidentifying test-article-related cardiac findings in this genetic source of cynomolgus macaque in nonclinical safety testing.
Highly Birefringent Two-Mode Photonic Crystal Fibers With Near-Zero Flattened Dispersion

Through introducing three sizes of holes in cladding, highly birefringent two-mode photonic crystal fibers (PCFs) are proposed. The full-vector finite-element method (FEM) is applied in the calculation of the transverse electric field vector distributions of the two modes, their effective indices, modal birefringence, chromatic dispersion, and confinement losses. The defect holes near the core region are deliberately designed to obtain high birefringence. Furthermore, the structural parameters are carefully selected to flatten chromatic dispersion curve and reduce confinement losses.
Fatty Acids and Immune Function: Relevance to Inflammatory Bowel Diseases

Fatty acids may influence immune function through a variety of mechanisms; many of these are associated with changes in fatty acid composition of immune cell membranes. Eicosanoids produced from arachidonic acid have roles in inflammation and immunity. Increased membrane content of n-3 fatty acids results in a changed pattern of production of eicosanoids, resolvins, and cytokines. Changing the fatty acid composition of immune cells also affects T cell reactivity and antigen presentation. Little attention has been paid to the influence of fatty acids on the gut-associated lymphoid tissue. However, there has been considerable interest in fatty acids and gut inflammation.
Immediate recurrence of atrial fibrillation after internal cardioversion: importance of right atrial conduction variations.

This study investigates the importance of right atrial conduction features in predicting of immediate recurrence of atrial fibrillation (AF) after internal cardioversion (IC). Patients with chronic AF who were resistant to external cardioversion were studied. Twenty-four patients (16 female, 8 male mean age 58 +/- 7 years) who were successfully converted to sinus rhythm (SR) by IC, and experienced recurrence of AF within 1 minute of restoration of SR were enrolled in group A. Thirty-four patients, who were converted to SR by IC and in whom SR was maintained at least 1 minute after IC, were enrolled in group B (24 female, 10 male mean age 56 +/- 6 years) as control. There was no difference in age, left atrial diameter, use of antiarrhythmic drug, etiology and duration of AF between the groups. After successful IC, His bundle electrocardiograms via placed electrode catheters, and surface electrocardiograms were recorded for 1 minute. P-A interval duration, as a marker of right atrial conduction, was measured from the onset of the earliest registered surface P wave to the onset of the atrial deflection on His-bundle catheter recording. The difference between the recorded maximum P-A duration and minimum P-A duration obtained in 1 minute after IC was described as P-A interval absolute difference. There were no differences in the maximum P-A duration and minimum P-A duration between two groups. But, the P-A absolute difference was more pronounced in group A compared to group B (16.9 +/- 7.7 ms versus 10.3 +/- 6.4 ms, P < .001) and was significantly correlated with P wave dispersion derived from the surface electrocardiogram (r = .72, P < .001) In conclusion, variations in right atrial conduction might play an important role in predicting immediate recurrence of AF in patients converted to SR by IC.
The NPC1L1 Polymorphism 1679C>G Is Associated with Gallstone Disease in Chinese Patients

Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone-free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk.
Utility of serum procalcitonin for screening and risk stratification of medullary thyroid cancer.

CONTEXT The clinical utility of procalcitonin has not been demonstrated across the whole spectrum of medullary thyroid cancer (MTC). OBJECTIVE This serum biomarker validation study aimed at defining the diagnostic accuracy of procalcitonin for screening and risk stratification of MTC and delineating biochemical thresholds predictive of lymph node involvement in the neck and mediastinum. DESIGN AND SETTING This was a retrospective analysis at a tertiary referral center. PATIENTS Included in this study were 457 consecutive patients with previously untreated MTC, 112 of whom had procalcitonin and calcitonin serum levels determined before the initial operation. INTERVENTION The intervention was compartment-oriented surgery. MAIN OUTCOME MEASURES Main outcome measures included primary tumor diameter, extrathyroidal extension, lymph node metastases, distant metastases, and biochemical cure. RESULTS Receiver operating characteristics analyses revealed similar diagnostic accuracy for procalcitonin vs the current calcitonin standard, yielding comparable areas under the curve for primary tumors at thresholds of 10 (0.94 vs 0.93) and 40 (0.92 vs 0.84) mm; extrathyroidal extension (0.84 vs 0.83), lymph node metastasis (0.88 vs 0.86), and distant metastasis (0.93 vs 0.91). Lymph node metastases were present in the ipsilateral lateral neck with procalcitonin levels ≤1.0 ng/mL and the ipsilateral central neck with procalcitonin levels ≤0.25 ng/mL. Above a threshold of 1.0 ng/mL, lymph node metastases emerged in the contralateral central and lateral neck and above 5.0 ng/mL also in the upper mediastinum. When procalcitonin levels exceeded 1, 5, 10, and 50 ng/mL, biochemical cure rates declined to no more than 71%, 36%, 23%, and 10%, respectively. CONCLUSION Serum procalcitonin, having comparable diagnostic accuracy, has great potential to replace serum calcitonin as a new standard of care in the management of MTC because it does not need to be kept cool on ice or frozen and is easier to manage at the community level.
Platelet-Rich Plasma in Grafted Maxillae: Growth Factor Quantification and Dynamic Histomorphometric Evaluation

Purpose:Validation of platelet-rich plasma (PRP) system and assessing its enhancing effect on the healing of iliac crest grafts before implant placement. Materials and Methods:Patients randomly allocated to test (n = 13) and control (n = 9) groups. Iliac crest grafts were mixed with PRP in the test group. Tetracycline labeling preceded implant placement. Bone samples were harvested for histomorphometrical analysis. Platelet and growth factor quantifications were performed. Analysis:Data were analyzed using SPSS software package. Independent t test was used and statistical significance was set at 5%. Results:The PRP group showed significantly higher platelet counts, PDGF-BB, and TGF-&bgr;1 concentrations. Tendency to higher volume of woven bone was observed in the PRP group (13 ± 11 vs 4 ± 6, P = 0.1). Histomorphometry showed increased seam separation in the PRP group (8.8 ± 9 &mgr;m vs 1.5 ± 3 &mgr;m, P = 0.039). Remodeling activity was higher in PRP-woven bone sections and comparable in trabecular sections. Conclusion:PRP significantly increased platelet and growth factor concentrations and was of possible enhancing effect on the rate of bone formation at 3 to 4 months of grafting. The clinical significance of this enhancement is yet to be established.
Conditional knockout of CTGF affects corneal wound healing.

PURPOSE This study aimed to elucidate the role of connective tissue growth factor (CTGF) in healthy eyes and wounded corneas of mice and rabbits. Conditional knockout mice were used to determine the role of CTGF in corneal healing. METHODS CTGF expression was determined using transgenic mice carrying CTGF promoter driven-eGFP, quantitative RT-PCR, and immunofluorescent staining. Mice that carried two floxed CTGF alleles and a Cre/ERT2 transgene under the control of human ubiquitin C (ubc) promoter were used to conditionally delete CTGF gene in a tamoxifen-inducible manner. Phototherapeutic keratectomy (PTK) was used to generate an acute corneal wound and corneal re-epithelialization was assessed by fluorescein staining. RESULTS Connective tissue growth factor expression was found in multiple ocular tissues with relatively high levels in the corneal endothelium, lens subcapsular epithelium, and in the vasculature of the iris and retina. Wounded corneas responded with an immediate upregulation of CTGF in the epithelium at the wound margin and a sustained CTGF induction during re-epithelialization. At the onset of haze formation, CTGF protein becomes more focused in the basal epithelium. Deletion of the CTGF gene caused a 40% reduction (P < 0.01) in the cornea re-epithelialization rate in knockout mice compared with wild-type mice. CONCLUSIONS Connective tissue growth factor is expressed in the naïve cornea, lens, iris, and retina, and is expressed immediately after epithelial injury. Loss of CTGF impairs efficient re-epithelialization of corneal wounds.
Adipose Overexpression of Desnutrin Promotes Fatty Acid Utilization and Attenuates Diet-induced Obesity

Objective: To investigate the role of desnutrin in adipose tissue triacylglycerol (TAG) and fatty acid metabolism. Design: We generated transgenic mice overexpressing desnutrin in adipocytes (aP2-desnutrin) and also performed adenoviral-mediated overexpression of desnutrin in 3T3-L1 adipocytes. Results: aP2-desnutrin mice were leaner with decreased adipose tissue TAG content and smaller adipocyte size. Overexpression of desnutrin increased lipolysis but did not result in increased serum fatty acid levels or ectopic TAG storage. We found increased cycling between diacylglycerol and TAG, increased fatty acid oxidation in adipocytes from these mice, as well as improved insulin sensitivity. Conclusions: In conclusion, we show that by increasing lipolysis, desnutrin overexpression causes reduced adipocyte TAG content and attenuation of diet-induced obesity. Furthermore, desnutrin-mediated lipolysis promotes fatty acid oxidation and reesterification within adipocytes.
Human immunodeficiency virus-type 1 (HIV-1) and the brain.

Infection with human immunodeficiency virus Type-1 (HIV-1), the causative agent of AIDS, can be associated with central nervous system as well as immune system disease. Advanced AIDS can be complicated by a dementia. Short of frank dementia, many AIDS patients manifest neuropsychological (NP) impairment including disturbance in speeded information processing, abstraction, learning, and recall. Data conflict on whether medically asymptomatic HIV-1 carriers have subtle NP deficits. Variations in tests chosen, criterion specification, and sample selection may all be contributing to disparate results. Longitudinal research is needed, and this should examine representative samples of HIV-1 seropositive individuals for whom approximate date of seroconversion is known and in whom sources of comorbidity (e.g., drug abuse, concurrent infections, CNS injuries) can be specified.
Predicting intention to adopt B2B electronic commerce in Jordan: The moderating role of trust and dependency

Business to Business Electronic Commerce (B2B EC) has great potentials to extend firms’ competency and efficiency. As such, Jordan has an objective to increase the diffusion of this technology. Despite extensive government efforts, the adoption of B2B EC is still limited. Consequently, there have been extensive efforts to better understand the phenomena. Yet, documented findings regarding the determinants of the adoption are not altogether consistent. To provide more insight, this study developed a research model utilizing the Technological, Organizational, and Environmental (TOE) framework to identify the determinants of the firms’ propensity to adopt B2B EC. Since B2B EC is an inter-organizational phenomenon supporting transactions of partnerships, this study emphasizes the context of partnership characteristics. Grounded on inter-organizational theories, this study hypothesized that partnership characteristics, namely trust and dependency, moderate the role of TOE motivating factors. Moreover, given that B2B EC is used on both sides of the buyer/seller relationship, this study examined the differences and similarities in the perception of the marketing and purchasing departments regarding the determinants of the B2B EC adoption. A total of 798 questionnaires were self administrated to marketing and purchasing managers in 462 firms that have large registered capital in Jordan. In total, 114 marketing and 125 purchasing managers participated in this study. Marketing and purchasing responses were analyzed separately using the Partial Least Squares approach. The result revealed that the marketing and purchasing departments do have different views regarding the determinants of the adoption, specifically in terms of the role of Relative Advantage and Competition Pressure. Moreover, the results showed that the moderating role of trust was less pronounced. Meanwhile, the moderating role of dependency was partially supported particularly in the purchasing perspective. These findings have demonstrated how dependence asymmetries between trading partners may change the adoption motivations. They further explain the importance of considering the views of the business partner for the adoption to be done successfully.
Quantification of Human Cytomegalovirus DNA in Bone Marrow Transplant Recipients by Real-Time PCR

ABSTRACT A real-time PCR assay was developed to quantify human cytomegalovirus (CMV) DNA in peripheral blood leukocytes (PBLs) of bone marrow transplantation patients. Unlike other teams, we quantified CMV and the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene using a plasmid containing both sequences as an external standard. Tenfold serial dilutions of this plasmid yielded overlapping standard curves that allowed the quantification of CMV and GAPDH gene copies in an efficient and accurate manner. Sequential blood samples (164 specimens) were collected from 16 patients. PBLs were tested by the pp65 antigenemia assay and quantitative CMV and GAPDH gene PCRs. CMV DNA was detected by PCR in 13 patients a mean of 15 days prior to the appearance of antigenemia. The administration of anti-CMV drugs led to a rapid decrease in the numbers of viral copies and positive nuclei. Real-time PCR assay results correlated with those of the CMV pp65 antigenemia assay (P < 0.00001). The TaqMan assay may be a useful tool for rapid quantification of CMV infection and for monitoring of CMV reactivation in bone marrow transplantation recipients.
Demographic and clinical variation of adult intensive care unit utilization from a geographically defined population

Objective:To determine population-based rates of adult intensive care unit (ICU) use and evaluate the effects that demographic variables and chronic illness have on ICU utilization. Design:Retrospective, population-based cohort study. Setting:Olmsted County, Minnesota. Participants:Adult residents admitted to an ICU in 1998. Interventions:None. Measurements and Main Results:Measurements included demographics, Acute Physiology and Chronic Health Evaluation III score, ICU admission diagnosis, ICU interventions, Charlson comorbidity index and conditions, ICU length of stay (LOS), and ICU, hospital, 1-month, and 1-yr mortalities. Risk of ICU admission and rates of ICU utilization increased substantially with increasing age, peaking in the very elderly. The rates of ICU admission and utilization in those ≥85 yrs old were 58.2 admissions/1,000 residents and 195.8 days/1,000 residents compared with 3.8 admissions/1,000 residents and 11.5 days/1,000 residents in those 18 to 44 yrs old. Residents ≥85 yrs old were 3.75 times as likely (p < .001) to be admitted to the ICU compared with those 18–44 yrs old after controlling for the presence of comorbid illness. ICU admission rates increased with an increasing number of comorbid illnesses. Residents with cardiovascular conditions and renal disease had high rates of ICU admission. Repeat users of the ICU were more likely to have a chronic condition and higher degree of comorbid illness compared with nonrepeat users. ICU mortality was similar across all age groups, except in those ≥85 yrs old, for whom mortality was greater. One-year mortality after ICU admission increased with increasing age. Conclusions:Population-based rates of ICU admission and utilization in Olmsted County, Minnesota, increased with age and are highest in the very elderly. The presence of chronic illness, particularly cardiovascular conditions, significantly increases ICU utilization and risk of ICU admission.
Auditor Litigation: Deterrence Implications for Non-sued Auditors

Litigation poses a significant business risk for auditors. We argue that auditors learn from other auditors’ litigation events and examine the consequences of such events for future accounting misstatements. Using a hand-collected sample of auditor litigation events, we find a significant subsequent decrease in misstatement frequency in within-industry audits conducted by auditors who did not face litigation. This industry-based across-auditor learning effect is (a) intensified when the litigation signal is stronger; (b) is associated with an audit-fee increase; and (c) is robust to a battery of controls including the use of a difference-in-difference approach. No evidence is found for region-based across-auditor learning. Since non-sued auditors conduct a larger share of audits than the sued auditor, a deterrence effect of litigation for the non-sued auditor significantly enhances the impact of litigation beyond the sued auditor.