Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression.

OBJECTIVES Nuclear factor-kB (NF-kB) is a transcription factor that participates in the induction of several genes for cytokines and enzymes that play important functional roles in various cell types. The aim of this study was to determine NF-kB activation status in human colorectal carcinoma and its correlation to the clinicopathological characteristics of patients. MATERIALS AND METHODS We examined the activation status of NF-kB in 28 resected colorectal carcinomas and in colonic mucosa from uninvolved portions of these specimens by electrophoretic mobility shift assay (EMSA) and immunohistochemical staining for the p65 subunit of NF-kB. RESULTS EMSA showed much greater activation in the tumors than in normal mucosa, as did epithelial p65 immunostaining. NF-kB activation significantly increased in the more progressed cases (T3 + T4 cases or Stage II< cases). In vitro studies using lipopolysaccharide (LPS)-responsive colon carcinoma cells suggested a correlation between NF-kB activation and cell proliferation. CONCLUSION Our findings indicated that NF-kB is constitutively activated in human colorectal carcinoma tissue and correlates with tumor progression. The regulation of this transcription factor might be therapeutically useful against these tumors.
Florid Vulval Paget Disease Exhibiting p16 Immunoreactivity and Mimicking Classic VIN

The diagnosis of vulval Paget disease is generally relatively straightforward but may be difficult, especially when the Paget cells are few in number. We report 2 cases of the opposite scenario where the Paget cells were present in such large numbers and formed confluent sheets such that they effaced the residual keratinocytes. There were associated epidermal hyperplastic changes in the form of acanthosis, papillomatosis, and hyperkeratosis, and the overall morphology resulted in close mimicry of classic (undifferentiated/human papillomavirus-related) vulval intraepithelial neoplasia. There was focal intraepidermal clefting in both cases, resulting in an acantholytic appearance. In both cases, the Paget cells were strongly positive with p16 that further heightened the mimicry of vulval intraepithelial neoplasia. The Paget cells were diffusely positive with cytokeratin 7, CAM5.2, carcinoembryonic antigen, and epithelial membrane antigen and with mucin stains, and molecular tests for human papillomavirus were negative. The p16 immunoreactivity, which has not previously been reported in vulval Paget disease, prompted us to stain a small number of additional cases of more typical vulval Paget disease with this marker. Four of 5 additional cases were positive with varying degrees and patterns of immunoreactivity. Florid vulval Paget disease may morphologically mimic vulval intraepithelial neoplasia, and this mimicry may be exacerbated by p16 immunoreactivity.
Retromer and the dynamin Vps1 cooperate in the retrieval of transmembrane proteins from vacuoles

ABSTRACT Endosomes are dynamic organelles that need to combine the ability to successfully deliver proteins and lipids to the lysosome-like vacuole, and recycle others to the Golgi or the plasma membrane. We now show that retromer, which is implicated in retrieval of proteins from endosomes to the Golgi or to the plasma membrane, can act on vacuoles. We explore its function using an assay that allows us to dissect the required cofactors during recycling. We demonstrate that recycling of the transmembrane receptor Vps10 from vacuoles requires the retromer, the dynamin-like Vps1, and the Rab7 GTPase Ypt7. Retromer and Vps1 leave the vacuole together with the cargo, whereas Ypt7 stays behind, in agreement with its regulatory function. Recycled cargo then accumulates at endosomes and later at the Golgi, implying consecutive sorting steps to the final destination. Our data further suggest that retromer and Vps1 are essential to maintain vacuole membrane organization. Taken together, our data demonstrate that retromer can cooperate with Vps1 and the Rab Ypt7 to clear the vacuole of selected membrane proteins.
Proteomics, genomics and transcriptomics: their emerging roles in the discovery and validation of colorectal cancer biomarkers

Colorectal cancer (CRC) is the second most common cancer in females and the third in males. Since CRC is often diagnosed at an advanced stage when prognosis is poor, identification of biomarkers for early diagnosis is urgently required. Recent advances in proteomics, genomics and transcriptomics have facilitated high-throughput profiling of data generated from CRC-related genes and proteins, providing a window of information for biomarker discovery and validation. However, transfer of candidate biomarkers from bench to bedside remains a dilemma. In this review, we will discuss emerging proteomic technologies and highlight various sample types utilized for proteomics-based identification of CRC biomarkers. Moreover, recent breakthroughs in genomics and transcriptomics for the identification of CRC biomarkers, with particular emphasis on the merits of emerging methylomic and miRNAomic strategies, will be discussed. Integration of proteomics, genomics and transcriptomics will facilitate the discovery and validation of CRC biomarkers leading to the emergence of personalized medicine.
Energy Expenditure Associated With Softening and Stiffening of Echinoderm Connective Tissue

Catch connective tissue of echinoderms at rest (in the standard state) either stiffens or softens in response to different kinds of stimulation. The energy consumption associated with the changes was estimated by measurement of the oxygen consumption rate (VO2) in three types of connective tissues—echinoid catch apparatus (CA), holothuroid body-wall dermis (HD), and asteroid body-wall dermis (AD). Mechanical stimulation by repetitive compression (10%–15% strain), which increased viscosity measured by creep tests, was employed for inducing the stiff state. Noradrenaline (10–3 mol l–1), which decreased viscosity of CA, and static 80% compressive strain, which decreased viscosity of HD, were used to induce the soft state in the respective tissues. The VO2 (in μl/g/h) values of the standard state were 2.91 (CA), 1.41 (HD), and 0.56 (AD), which were less than 1/4 of the VO2 of the resting body-wall muscle of the starfish. The VO2 of the stiff state was about 1.5 times greater than that of the standard state in all types of connective tissues. The VO2 of the soft state was 3.4 (CA)–9.1 (HD) times greater than that of the standard state. The economical nature of catch connective tissue in posture maintenance is discussed.
Grief Reactions to Perinatal Death — a Follow-Up Study *

Thirty mothers who experienced a perinatal death were offered crisis intervention aimed at facilitating their grief process at a few days, 3 weeks and 3 months after the loss. Evaluaticn of maternal grief reactions and their general psychological adjustment took place at these 3 early contacts and 1 to 2 years later. This last assessment included a semi-structured clinical interview and a number of self-rating scales (Life Events Schedule, Beck Depression Inventory (BDI) and a Mourning Scale). Six of the 30 mothers showed inappropriate grief reactions at the 3 week and 3 month assessment. By the long term follow up only 1 of these 6 displayed depression or other psychiatric disorder. Three other women not identified as high risk candidates by the 3 month evaluation developed high BDI scores and clinical depressions at the 1 to 2 year assessment. Variables associated with abnormal grief and depression such as social support systems, communication between the parents, maternal dreams, and hospital practices were examined and discussed indicating possibilities for future research.
Rivaroxaban in treatment refractory heparin-induced thrombocytopenia

Following orthopaedic surgery, a 56-year-old woman developed heparin-induced thrombocytopenia (HIT), complicated by extensive proximal deep vein thrombosis. The patient did not respond to multiple conventional therapies; however, a prompt treatment response occurred after starting rivaroxaban at standard dosing. This case represents the first documentation of efficacy for rivaroxaban in the setting of treatment refractory HIT and strengthens the limited existing evidence for this agent in HIT.
Heterogeneity of insulin-like growth factor binding proteins between structure and affinity. 2. Forms released by human and rat liver in culture.

Since the liver is considered to be the major source both of circulating insulin-like growth factors (IGFs) and of their specific binding proteins (BPs), human and rat liver explants were cultured in serum-free medium with a view to characterizing the binding proteins released into the medium and to comparing them with serum binding proteins. In the culture media, as in the serum, IGFs are associated with their binding proteins in the form of complexes. In gel filtration experiments the liver IGF-BP complexes eluted as a single, homogeneous peak with a relative molecular mass of about 40,000, which is similar to that of the 'small' complex of serum. Their sedimentation coefficient, estimated from sucrose gradient centrifugation, was 2.9 S. Polyacrylamide gel electrophoresis (SDS-PAGE) of human liver culture media, in which the binding proteins were cross-linked to 125I-labelled IGF I revealed molecular heterogeneity. Three specific bands corresponding to Mr 46,000, 40,000 and 37,000 were observed, which resemble those of the serum small complex, but none of the higher-Mr bands seen in serum. SDS-PAGE followed by transfer onto nitrocellulose and incubation with 125I-labelled IGF I (western blot) led to the identification in human liver culture media of five molecular forms of binding protein with Mr of 41,500, 38,500, 34,000, 30,000 and 24,000, identical to those seen in serum. The relative concentrations of the 41,500 and 38,500-Mr forms varied from one medium to another, but the 34,000 and 30,000-Mr forms were regularly more abundant in the liver culture media than in normal serum. The binding proteins produced by the liver therefore represent the native forms in the circulation (although this does not exclude other sources). The absence of high-Mr IGF-BP complexes in the liver culture media, and yet the presence of the 41,500 and 38,500-Mr forms, which are the only binding units of the serum 'large' complex (150,000 Mr), indicates that these two binding proteins are capable of binding IGFs to form 'monomeric' IGF-BP complexes. Western-blot analysis of rat binding proteins revealed a certain analogy with the human proteins, three forms having their Mr between 43,000 and 39,000 and three between 32,000 and 24,000. Liver binding proteins in human adults and foetuses were found to be identical, whereas in the case of serum the 41,500 and 38,500-Mr forms were more abundant in the adult and the 34,000 and 30,000-Mr forms more abundant in the foetus. (ABSTRACT TRUNCATED AT 400 WORDS)
Characterization of Vestibulopathy in Individuals with Type 2 Diabetes Mellitus

Objective Previous observational studies suggest higher rates of vestibular dysfunction among patients with type 2 diabetes mellitus (DM) compared with those without diabetes. This study aims to functionally localize vestibular dysfunction in adults with type 2 DM. Study Design Prospective cohort study. Setting Tertiary academic medical center. Subjects and Methods Adults 50 years of age and older with ≥10-year history of type 2 DM were recruited (December 2011–February 2013, n = 25). Vestibular function was assessed by cervical and ocular vestibular-evoked myogenic potentials (VEMPs), testing the saccule and utricle, respectively. Head thrust dynamic visual acuity testing assessed semicircular canal (SCC) function in all canal planes. Results were compared with nondiabetic age-matched controls (n = 25). Results Subjects were 64.7 ± 7.6 years old, were 40% female, and had a mean hemoglobin A1c of 8.3% ± 1.7%. SCC dysfunction was more common than otoconial organ dysfunction, with 70% of subjects with DM demonstrating impaired performance of at least 1 SCC (ΔlogMAR ≥0.18) and 50% demonstrating otoconial organ impairment (absent ocular VEMP and/or cervical VEMP). Adults with type 2 DM had poorer lateral and superior SCC performance (P < .05) but similar posterior SCC performance compared with controls (P = .16). Both cervical VEMP peak-to-peak amplitude and ocular VEMP n1 amplitude were also decreased with diabetes (P < .01). Conclusion Adults with type 2 DM have poorer performance on tests of vestibular function related to both SCC and otoconial organ function compared with nondiabetic age-matched adults. Future studies are needed to better understand the relationship between vestibular function and functional disability in persons with diabetes.
Vascular angiotensin converting enzyme activity in spontaneously hypertensive rats and its inhibition with cilazapril.

Angiotensin converting enzyme (ACE) activity was examined in large arteries and veins of rats and found to be present in most of the arteries and to a lesser extent in the veins, except for the femoral vessels which showed higher ACE activity in the vein than in the artery. For the aorta and all its branches, ACE activity was higher in the aorta and its branches in spontaneously hypertensive rats (SHR) than in age-matched normotensive Wistar-Kyoto rats (WKY), with the exception of the hepatic, pulmonary and basilar arteries where the levels were similar for SHR and WKY. For the vena cava and brachial vein, ACE activity was also higher in SHR than WKY but for most other veins the activity was the same with the exception of the pulmonary vein where ACE activity was higher in WKY. The acute treatment of SHR with cilazapril, an ACE inhibitor (0.3 and 3 mg/kg orally, for 4h) decreased aortic blood pressure and ACE activity in arterial and venous mesenteric and renal vessels in a dose-dependent fashion. Cilazapril, at the threshold hypotensive dose, markedly decreased ACE activity in each pair of aortic segments, carotid, pulmonary, subclavian, brachial and femoral vessels to a degree which was equivalent to that caused by the high dose. The effect outlasted a fall in blood pressure 24 h later. This was associated with a marked decrease in plasma angiotensin II and III and accumulation of angiotensin 1 at 4 h. No increase in plasma bradykinin or kallidin levels was detected. (ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of bioactivities, binding properties and intrafollicular levels of bovine follistatins.

Five isoforms of follistatin (FST) (Mr 31, 33, 35, 37, and 41 kDa) were purified from bovine follicular fluid (bFF). Comparison of their activin and heparan sulphate proteoglycan (HSP) binding properties and biopotencies in the neutralisation of activin A action in vitro revealed that all five isoforms bound activin A, but they did so with different affinities. Only the 31 kDa isoform (FST-288) bound to HSP. FST-288 also showed the greatest biopotency, and the 35 and 41 kDa isoforms were the least potent. To determine whether bovine follicle development is associated with changing intrafollicular FST and activin profiles, we analysed bFF from dominant follicles (DFs) and subordinate follicles (SF) collected at strategic times during a synchronised oestrous cycle. Total FST, activin A and activin AB were measured by immunoassay, whereas individual FST isoforms were quantified by immunoblotting. Follicle diameter was positively correlated with oestrogen:progesterone ratio (r=0.56) in bFF but negatively correlated with activin A (r=-0.34), activin AB (r=-0.80) and 'total' FST (r=-0.70) levels. Follicle diameter was positively correlated with the abundance of the 41 kDa isoform (r=0.59) but negatively correlated with the abundance of the 33 and 31 kDa isoforms (r=-0.56 and r=-0.41 respectively). Both follicle statuses (DF and SF) and cycle stage affected total FST, activin A and activin B levels, whereas follicle status, but not cycle stage, affected the abundance of the 41, 37, 33 and 31 kDa FST isoforms. Collectively, these findings indicate that intrafollicular FST isoforms, which differ in their ability to bind and neutralise activins and to associate with cell-surface proteoglycans, show divergent changes during follicle development. Enhanced FST production may play an important negative role, either directly or via the inhibition of the positive effects of activins, on follicle growth and function during follicular waves.
Cost-effectiveness of adalimumab for the maintenance of remission in patients with Crohn's disease

Objective Adalimumab is a fully human, monoclonal antibody clinically effective for the treatment of active Crohn's disease. The cost-effectiveness of adalimumab versus conventional, nonbiologic pharmacotherapies is unknown. This study evaluated the cost-effectiveness of adalimumab versus conventional, nonbiologic pharmacotherapies in the maintenance of Crohn's disease. Methods Trial data from two randomized controlled studies [Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM) and CLinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn's Disease (CLASSIC I)] were analyzed within a cost-utility framework using a 1-year horizon from the perspective of the National Health Service (UK). The treatment efficacy and use for the adalimumab arm were based on observations from CHARM. A regression model used data from CLASSIC I to predict efficacy in patients who received nonbiologic pharmacotherapy. Unit costs of drugs, hospitalization, and other medical resources were derived from the literature. Primary standard gamble-calculated data were used to derive health-utility estimates. Results Compared with conventional, nonbiologic pharmacotherapy, adalimumab seemed to be cost-effective for the treatment of patients with severe disease and moderate-to-severe disease. The 56-week incremental cost-effectiveness ratio was £16 064/quality-adjusted life-year and £33 731/quality-adjusted life-year for severe and moderate-to-severe groups, respectively. Sensitivity analyses showed that the findings were robust. In the treatment of patients over their lifetimes, the incremental cost-effectiveness ratio was £6550/quality-adjusted life-year and £17 873/quality-adjusted life-year for patients with severe Crohn's disease and those with moderate-to-severe Crohn's disease, respectively. Conclusion Adalimumab maintenance therapy seems to be cost-effective versus conventional, nonbiologic therapies for the maintenance of remission in patients with active Crohn's disease.
Jaw Clenching Results in Concurrent Activation Potentiation During the Countermovement Jump

Ebben, WP, Flanagan, EP, and Jensen, RL. Jaw clenching results in concurrent activation potentiation during the countermovement jump. J Strength Cond Res 22(6): 1850-1854, 2008-The study assessed the effect of current activation potentiation by evaluating jaw clenching and its effect on the rate of force development (RFD), time to peak force (TTPF), and peak force (PF) during the countermovement jump. Fourteen subjects performed the countermovement jump on a force platform while maximally clenching their jaw on a dental vinyl mouthguard (JAW) as well as without clenching their jaw by jumping with an open mouth (NON-JAW). Results reveal that the RFD was 19.5% greater in the JAW compared with the NON-JAW condition (p < 0.05). The TTPF was 20.15% less in the JAW compared with the NON-JAW condition (p < 0.05). There were no significant differences (p = 0.60) in PF between the JAW and NON-JAW conditions. These findings indicate that concurrent activation potentiation is manifested through jaw clenching during the countermovement jump. As a result, athletes may employ this strategy of maximally clenching their jaws to gain an ergogenic advantage during the countermovement jump.
Location of Prostate Cancers Determined by Multiparametric and MRI-Guided Biopsy in Patients With Elevated Prostate-Specific Antigen Level and at Least One Negative Transrectal Ultrasound-Guided Biopsy.

OBJECTIVE The purpose of this article is to identify histopathologically proven prostate cancer locations using MRI followed by MRI-guided biopsy in patients with elevated prostate-specific antigen (PSA) levels and at least one negative transrectal ultrasound (TRUS)-guided biopsy session. Our hypothesis is that in this patient group most cancers are located in the anterior portion of the prostate. This may have implications for the biopsy strategy regarding the location of sampling. MATERIALS AND METHODS This retrospective study consisted of 872 consecutive men who had undergone MRI-guided prostate biopsy. Inclusion criteria were PSA level greater than or equal to 4 ng/mL, one or more negative TRUS-guided biopsy session, the presence of suspicious lesions on previous multiparametric MRI, and prostate cancer histopathologically proven by MRI-guided biopsy. Thereafter, the location of intermediate- or high-risk cancers and cancers with a maximum cancer core length of 6 mm or longer were determined. The proportion of cancer locations was compared using a chi-square test. One-way ANOVA analyses were performed to compare patient characteristics. RESULTS Results were presented on both a patient and lesion basis because a single patient can have multiple lesions. In total, 176 of 872 patients met the inclusion criteria. Prostate cancer was detected in 202 of 277 (73%) suspicious lesions. In total, 76% of patients had cancer of the transition zone and anterior fibromuscular stroma. Peripheral zone cancers were found in 30% of the patients, and 6% had cancers in both zones. In 70% of cases (141/202; 95%, CI, 63-76%), lesions were located anteriorly; this included 75% (132/176; 95%, CI, 69-81%) of patients. Intermediate- or high-risk prostate cancer was found in 93% (128/138; 95%, CI, 88-96%) of patients. Of these patients, 73% (94/128; 95%, CI, 66-81%) had anterior involvement. Cancers with a maximum cancer core length of 6 mm or more were more likely to be located in the anterior part of the prostate than were cancers with a core length of less than 6 mm (66% vs 6%). Most cancers 58% (102/176; 95% CI, 51-65%) were found in the mid prostate. Anterior involvement of prostate cancer detected by MRI-guided biopsy was statistically significantly (p = 0.04) higher in patients with two or more negative TRUS-guided biopsy sessions (79%) than in those with one negative TRUS-guided biopsy session (55%). CONCLUSION Anterior involvement was high (76%) in patients with an elevated PSA level and one or more negative TRUS-guided biopsy session, and the majority of these cancers (93%) were intermediate or high risk.