Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated FOSB‐expression; a potential marker of valproate sensitivity in AML

Histone deacetylase inhibitors (HDIs) are emerging as valuable new agents in the treatment of acute myeloid leukaemia (AML). However, since response rates to these agents alone are low, we sought to identify markers associated with responsiveness. In a trial of 20 patients treated with the HDI sodium valproate (VPA) in combination with all trans retinoic acid and theophylline, three patients responded clinically with one complete remission (CR) and two partial remissions. The in vivo response of the CR patient was mirrored by high in vitro sensitivity of their blasts to VPA, indicating that similar factors determine both in vivo and in vitro sensitivity. Microarray analysis of the primary AMLs and a panel of haemato‐lymphoid cell lines, with a similar range of VPA sensitivities as the primary leukaemic blasts, identified elevated FOSB‐expression as a potential marker of VPA sensitivity. Quantitative polymerase chain reaction confirmed overexpression of FOSB in the CR patient blasts compared to patients failing to achieve CR, and in a subset of a larger panel of AML samples. Overexpression of FOSB in K562 myeloid cells significantly increased in vitro sensitivity to VPA. Thus, we propose that FOSB is a novel, potential marker of VPA sensitivity in AML.
Expression and characterization of tissue inhibitor of metalloproteinase 4 from complex canine mammary carcinomas

ABSTRACT All four members of the tissue inhibitors of metalloproteinase (TIMP) family have been reported to be over-expressed in breast cancer cells in vitro. Dysregulation of TIMP-4 expression predicts poor prognosis in cancers. The present study evaluated the association of the expression levels of TIMP-4 with mammary tumor development in dogs, measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mammary tissue samples were collected from healthy canine mammary gland and from tumor subjects. TIMP-4 expression was found to be upregulated (5.856 times) in complex canine mammary carcinomas. Also, TIMP-4 mature peptide was expressed heterologously in E. coli. The recombinant protein was purified by Ni- NTA affinity chromatography and further confirmed by western blotting. The rTIMP-4 was found to be functionally active and could inhibit matrix metalloproteinase 11(MMP-11) activity. Immunization of mice with rTIMP-4 resulted in increased antigen specific serum antibody titer, and this serum could be suitably used to detect and quantify the protein in sera of dogs with mammary tumors. TIMP-4 could act as a marker of canine mammary tumors. To the best of our knowledge, this is the first report of heterologous expression of TIMP-4 from complex canine mammary carcinomas.
Is consent for hip fracture surgery for older people adequate? The case for pre-printed consent forms

Ojectives Low energy hip fractures are one of the greatest causes of morbidity and mortality in orthopaedics. This study aims to evaluate written consent forms with respect to basic standards as set out in the Good Practice in Consent Initiative. In particular the stated risks and benefits of each procedure were assessed. Methods 100 consecutive consent forms were reviewed prospectively. The stated procedure, side and complications were recorded. Appropriate signature and legibility was assessed. 13 consultant orthopaedic surgeons were surveyed to identify what risks and benefits they thought should be stated. Results Of 100 consent forms, 31 were for patients who are unable to consent. All 100 consent forms were correctly filled in with patient details and signed. 98% were legible. All stated the side of the operation. The number of complications listed per form ranged from 4 to 11. Infection, bleeding and thromboembolic complications were stated in the majority of consent forms. In total, 30 different complications were recorded; some were only stated once. Discussion and Conclusions This work suggests consent forms are completed well with respect to patient identifiers, legibility and procedure. The variability of complications stated is vast. We suggest standard pre-printed consent forms containing risks and benefits should be used as this may improve standards of informed consent. This has also been recently supported by the British Orthopaedic Association.
Early detection of high-grade squamous intraepithelial lesions in the cervix with quantitative spectroscopic imaging

Abstract. Quantitative spectroscopy has recently been extended from a contact-probe to wide-area spectroscopic imaging to enable mapping of optical properties across a wide area of tissue. We train quantitative spectroscopic imaging (QSI) to identify cervical high-grade squamous intraepithelial lesions (HSILs) in 34 subjects undergoing the loop electrosurgical excision procedure (LEEP subjects). QSI’s performance is then prospectively evaluated on the clinically suspicious biopsy sites from 47 subjects undergoing colposcopic-directed biopsy. The results show the per-subject normalized reduced scattering coefficient at 700 nm (An) and the total hemoglobin concentration are significantly different (p<0.05) between HSIL and non-HSIL sites in LEEP subjects. An alone retrospectively distinguishes HSIL from non-HSIL with 89% sensitivity and 83% specificity. It alone applied prospectively on the biopsy sites distinguishes HSIL from non-HSIL with 81% sensitivity and 78% specificity. The findings of this study agree with those of an earlier contact-probe study, validating the robustness of QSI, and specifically An, for identifying HSIL. The performance of An suggests an easy to use and an inexpensive to manufacture monochromatic instrument is capable of early cervical cancer detection, which could be used as a screening and diagnostic tool for detecting cervical cancer in low resource countries.
Fractured families: Parental perspectives of the effects of adolescent drug abuse on family life

Abstract Drug use in young people has serious ramifications for health and well-being of young people and their families and continues to be an area of major concern for health workers. Though the task of dealing with drug-related problems falls on families, particularly parents, very little literature has explored parental experiences of managing drug use within the context of family life. Eighteen parents of drug-abusing young people were recruited into this qualitative study that aimed to develop understandings into the effects of adolescent drug use on family life. Findings revealed that the experience of having a drug-abusing adolescent family member had a profound effect on other members of the immediate family. Family relationships were fractured and split as a result of the on-going destructive and damaging behaviour of the drug-abusing young person. Five themes were identified that captured the concept of fractured families. These are: •Betrayal and loss of trust: ‘You had to have the doors locked’; •Abuse, threats and violence: ‘There were holes in the wall’; •Sibling anger and resentment: ‘Better off now with him gone’; •Isolated, disgraced and humiliated: ‘You are on your own with it’; and •Feeling blamed: ‘You are not a good parent. ’ Implications for practice and further research are drawn from the findings of this paper.
Expression of GCDFP‐15 and AR decreases in larger or node‐positive apocrine carcinomas of the breast

Aims : Apocrine carcinoma of the breast is typically, though not always, positive for gross cystic disease fluid protein‐15 (GCDFP‐15). In order to clarify the clinical significance of GCDFP‐15 in apocrine carcinomas, GCDFP‐15 expression was examined in apocrine carcinomas of different stages and compared with clinicopathological factors. Apocrine lesions reportedly exhibit an unusual immunohistochemical status, expressing androgen receptors (AR) instead of oestrogen receptors (ER), progesterone receptors (PR), or bcl‐2. Their expression was also examined.
Modification of a phospholipid stabilized emulsion interface by bile salt: effect on pancreatic lipase activity.

Lipase is activated by binding to an insoluble emulsified or aggregated substrate. The extent of binding is related to the physicochemical as well as the compositional structure of the interface, the quality of the interface. 'Quality' is as yet undefined but thought to contain contributions from electrostatic interactions, orientation of substrate, and hydration forces. To investigate the electrostatic and compositional factors we have used olive oil-in-water emulsions prepared with phosphatidylcholine and four bile salts of varying hydrophobicities. By measurement of the droplet zeta potential we have monitored semi-quantitatively the incorporation of bile salts within the interface. No correlation was found between droplet surface charge as monitored by the zeta potential and lag phase. The duration of the observed lag phase was found to be inversely related to the degree of incorporation of the bile salts. Simultaneously there was evidence of lipase binding to monomeric bile salts, reducing its availability for adsorption. Calcium ions reduced the surface charge but there was no correlation with lag phase duration. The evidence presented here agrees with a more specific role for calcium ions, i.e., the formation of a new catalytically active enzyme complex, (enzyme)-(mixed micelle)-(calcium ion).
Tpl2 and ERK transduce antiproliferative T cell receptor signals and inhibit transformation of chronically stimulated T cells

The protein kinase encoded by the Tpl2 protooncogene plays an obligatory role in the transduction of Toll-like receptor and death receptor signals in macrophages, B cells, mouse embryo fibroblasts, and epithelial cells in culture and promotes inflammatory responses in animals. To address its role in T cell activation, we crossed the T cell receptor (TCR) transgene 2C, which recognizes class I MHC presented peptides, into the Tpl2−/− genetic background. Surprisingly, the TCR2Ctg/tg/Tpl2−/− mice developed T cell lymphomas with a latency of 4–6 months. The tumor cells were consistently TCR2C+CD8+CD4−, suggesting that they were derived either from chronically stimulated mature T cells or from immature single positive (ISP) cells. Further studies showed that the population of CD8+ ISP cells was not expanded in the thymus of TCR2Ctg/tg/Tpl2−/− mice, making the latter hypothesis unlikely. Mature peripheral T cells of Tpl2−/− mice were defective in ERK activation and exhibited enhanced proliferation after TCR stimulation. The same cells were defective in the induction of CTLA4, a negative regulator of the T cell response, which is induced by TCR signals via ERK. These findings suggest that Tpl2 functions normally in a feedback loop that switches off the T cell response to TCR stimulation. As a result, Tpl2, a potent oncogene, functions as a tumor suppressor gene in chronically stimulated T cells.
On the basal ganglia of amphibians: dopaminergic mesostriatal projections.

Recent studies have revealed a rather dense dopaminergic innervation of basal forebrain areas in anurans and urodeles. The aim of the present study is not only to extend these observations to the third order of amphibians, i.e. the Gymnophiona, but also to determine the cells of origin of the dopaminergic projection to the basal forebrain by means of combined tract-tracing/transmitter-immunohistochemical techniques. Immunohistochemistry with antibodies against tyrosine hydroxylase (TH) and dopamine (DA) demonstrated some remarkable differences in the distribution of DA fibers within the basal forebrain. Whereas in anurans the nucleus accumbens receives a major DA input, in urodeles the DA input to the striatum prevails. In gymnophionans, both basal forebrain structures receive an equally dense DA innervation. The double-labeling studies revealed also differences in the distribution of the cells of origin of the DA striatal input. Although in anurans and urodeles DA cells in both the posterior tubercle and the midbrain tegmentum contribute to this projection, the mesostriatal projection of urodeles is more elaborated than that of anurans.
Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER)

Because of the very short half-life of factor VII, prophylaxis in factor VII deficiency is considered a difficult endeavor. The clinical efficacy and safety of prophylactic regimens, and indications for their use, were evaluated in factor VII-deficient patients in the Seven Treatment Evaluation Registry. Prophylaxis data (38 courses) were analyzed from 34 patients with severe factor VII deficiency (<1-45 years of age, 21 female). Severest phenotypes (central nervous system, gastrointestinal, joint bleeding episodes) were highly prevalent. Twenty-one patients received recombinant activated factor VII (24 courses), four received plasma-derived factor VII, and ten received freshfrozen plasma. Prophylactic schedules clustered into “frequent” courses (three times weekly, n=23) and “infrequent” courses (≤2 times weekly, n=15). Excluding courses for menorrhagia, “frequent” and “infrequent” courses produced 18/23 (78%) and 5/12 (41%) “excellent” outcomes, respectively; relative risk, 1.88; 95% confidence interval, 0.93-3.79; P=0.079. Long term prophylaxis lasted from 1 to >10 years. No thrombosis or new inhibitors occurred. In conclusion, a subset of patients with factor VII deficiency needed prophylaxis because of severe bleeding. Recombinant activated factor VII schedules based on “frequent” administrations (three times weekly) and a 90 μg/kg total weekly dose were effective. These data provide a rationale for long-term, safe prophylaxis in factor VII deficiency (clinicaltrials.gov: NCT01269138).
Wireless capsule endoscopy versus ileocolonoscopy for the diagnosis of postoperative recurrence of Crohn’s disease: a prospective study

Background and aims: Following ileocolonic resection for Crohn’s disease (CD), early endoscopic recurrence predicts recurrence of symptoms. The aim of the study was to compare ileocolonoscopy and wireless capsule endoscopy (WCE) for the detection of postoperative recurrence in CD. Methods: WCE and ileocolonoscopy were performed within six months following surgery in 32 prospectively enrolled patients. Two independent observers interpreted the results of WCE. Recurrence in the neoterminal ileum was defined by a Rutgeerts score ⩾1. When observers at WCE did not concur, WCE results were considered as either true negative or true positive and sensitivity and specificity were calculated according to both assumptions. Results: Recurrence occurred in 21 patients (68%) and was detected by ileocolonoscopy in 19 patients. Sensitivity was 90% and specificity 100%. Sensitivity of WCE was 62% and 76% and specificity was 100% and 90%, respectively, depending on assumptions. There was a correlation between the severity of the lesions measured by both methods (p<0.05). Lesions located outside the scope of conventional endoscopy were detected by WCE in two thirds of patients with excellent interobserver agreement (kappa >0.9) for all lesions with the exception of ulceration (kappa = 0.7). Conclusions: The sensitivity of WCE in detecting recurrence in the neoterminal ileum was inferior to that of ileocolonoscopy. In contrast, WCE detected lesions outside the scope of ileocolonoscopy in more than two thirds of patients. Additional follow up studies are needed to assess the clinical relevance of such lesions. At the present time, it seems that WCE cannot systematically replace ileocolonoscopy in the regular management of patients after surgery.
Gamow-Teller strengths and electron-capture rates for pf-shell nuclei of relevance for late stellar evolution

Background: Electron-capture reaction rates on medium-heavy nuclei are an important ingredient for modeling the late evolution of stars that become core-collapse or thermonuclear supernovae. The estimation of these rates requires the knowledge of Gamow-Teller strength distributions in the β + direction. Astrophysical models rely on electron-capture rate tables largely based on theoretical models, which must be validated and tested against experimental results. Purpose: This paper presents a systematic evaluation of the ability of theoretical models to reproduce experimental Gamow-Teller transition strength distributions measured via (n,p)-type charge-exchange reactions at intermediate beam energies. The focus is on transitions from stable nuclei in the pf shell (45 A 64). In addition, the impact of deviations between experimental and theoretical Gamow-Teller strength distributions on derived stellar electron-capture rates is investigated. Method: Data on Gamow-Teller transitions from 13 nuclei in the pf shell measured via charge-exchange reactions and supplemented with results from β-decay experiments where available, were compiled and compared with strength distributions calculated in shell models (using the GXPF1a and KB3G effective interactions) and quasiparticle random-phase approximation (QRPA) using ground-state deformation parameters and masses from the finite-range droplet model. Electron-capture rates at relevant stellar temperatures and densities were derived for all distributions and compared. Results: With few exceptions, shell-model calculations in the pf model space with the KB3G and GXPF1a interactions qualitatively reproduce experimental Gamow-Teller strength distributions of 13 stable isotopes with 45 A 64. Results from QRPA calculations exhibit much larger deviations from the data and overestimate the total experimental Gamow-Teller strengths. For stellar densities in excess of 10 7 g/cm 3 , ground-state electroncapture rates derived from the shell-model calculations using the KB3G (GXPF1a) interaction deviate on average less than 47% (31%) from those derived from experimental data for which the location of daughter states at low excitation energies are well established. For electron-capture rates derived from Gamow-Teller strengths calculated in QRPA, the deviations are much larger, especially at low stellar densities. Conclusions: Based on the limited set of test cases available for nuclei in the pf shell, shell-models using the GXPF1a and KB3G interactions can be used to estimate electron-capture rates for astrophysical purposes with relatively good accuracy. Measures of the uncertainties in these rates can serve as input for sensitivity studies in stellar evolution models. Ground-state electron-capture rates based on the QRPA formalism discussed in the paper exhibit much larger deviations than those based on the shell-model calculations and should be used with caution, especially at low stellar densities.
A Study on Caregiver Burden

Purpose: The purpose of this qualitative study was to explore factors impacting caregiver burden and to explore possible solutions for family caregivers of terminally ill patients. Results: The majority of caregivers reported experiencing role conflict and inadequate stress management. Caregivers who worked outside the home, those who cared for two parents concurrently, those with the least amount of outside assistance, and caregivers who spent a longer period of time caregiving reported the highest levels of health problems and overall burden. Caregivers stated a need for more support from Hospice agencies, more education on caregiver training, and more public education about Hospice services. Faith played a positive role in alleviating caregiver burden. Conclusion: Early identification, intervention, education and coordination of services may help to alleviate caregiver burden, which will improve quality of life for both patient and caregiver.
Informal Mental Health Support in the Asian American Community and Culturally Appropriate Strategies for Community-Based Mental Health Organizations

ABSTRACT Much of the literature on culturally appropriate services is focused on barriers to service provision; less is known about how organizations can reduce these barriers. Through qualitative interviews, this study examined how informal helpers within the Asian American community are helping individuals with unmet mental health needs and how mainstream mental health organizations might learn from their experiences. Themes identified include (a) informal assistance, (b) working with the community, (c) gaining trust, and (d) cultural and language appropriateness. By implementing some of the strategies suggested in this paper, mainstream organizations can better serve the mental health needs of Asian Americans.
New histochemical and ultrastructural observations on normal bovine tonsils

Samples of normal bovine palatine tonsils were examined by light and electron microscopy. Like human tonsils, they were composed of crypts, subepithelial areas, follicles, and T-dependent zones, but their welldeveloped capsule subdivided the lymphoid tissue by connective septa. B cells formed the major lymphoid component. The follicles and T-dependent zones had morphological and histochemical features typical of peripheral lymph organs. Follicular dendritic cells were isolated and shown to be similar to human follicular dendritic cells.