Miracle-dz/UniFAR-FTUs huggingface dataset:
Incidence of breast cancer and estimates of overdiagnosis after the initiation of a population-based mammography screening program

Background: There has been growing interest in the overdiagnosis of breast cancer as a result of mammography screening. We report incidence rates in British Columbia before and after the initiation of population screening and provide estimates of overdiagnosis. Methods: We obtained the numbers of breast cancer diagnoses from the BC Cancer Registry and screening histories from the Screening Mammography Program of BC for women aged 30–89 years between 1970 and 2009. We calculated age-specific rates of invasive breast cancer and ductal carcinoma in situ. We compared these rates by age, calendar period and screening participation. We obtained 2 estimates of overdiagnosis from cumulative cancer rates among women between the ages of 40 and 89 years: the first estimate compared participants with nonparticipants; the second estimate compared observed and predicted population rates. Results: We calculated participation-based estimates of overdiagnosis to be 5.4% for invasive disease alone and 17.3% when ductal carcinoma in situ was included. The corresponding population-based estimates were −0.7% and 6.7%. Participants had higher rates of invasive cancer and ductal carcinoma in situ than nonparticipants but lower rates after screening stopped. Population incidence rates for invasive cancer increased after 1980; by 2009, they had returned to levels similar to those of the 1970s among women under 60 years of age but remained elevated among women 60–79 years old. Rates of ductal carcinoma in situ increased in all age groups. Interpretation: The extent of overdiagnosis of invasive cancer in our study population was modest and primarily occurred among women over the age of 60 years. However, overdiagnosis of ductal carcinoma in situ was elevated for all age groups. The estimation of overdiagnosis from observational data is complex and subject to many influences. The use of mammography screening in older women has an increased risk of overdiagnosis, which should be considered in screening decisions.
Load and lock: the molecular mechanisms of B‐lymphocyte commitment

Summary: The maturation of B‐lymphoid cells from hematopoietic stem cells in the bone marrow is a complex process under control of interplay between extrinsic and intrinsic factors. In addition to serving as a model for normal cell differentiation, disturbances in this process results in immunodeficiencies and malignancies, such as leukemia and lymphoma, making the subject of high relevance for modern medicine. Although the process of B lymphopoiesis has been under intense investigation, recent methodological developments within the area of cell sorting, genome‐wide expression, and DNA‐binding analysis has allowed for a rapid development of the understanding of B‐lymphocyte differentiation. This has suggested that the path to B‐lymphoid cell fate may be initiated by lineage priming reflected in the expression of lymphoid associated genes already in multipotent hematopoietic progenitors. Upon differentiation, the gene expression profile is changed to involve an increasing number of B‐lineage‐restricted genes linked to loss of alternative developmental potentials and B‐lineage commitment. This review focuses on the molecular regulation of early B‐lymphoid development and aims to provide an up to date summary of the current status of the research area.
Is Customer Satisfaction an Indicator of Customer Loyalty

Customer satisfaction and loyalty is a well known and established concept in several areas like marketing, consumer research, economic psychology, welfare-economics, and economics. And has long been a topic of high interest in both academia and practice. The aim of the study was to investigate whether customer satisfaction is an indicator of customer loyalty. The findings of the study supported the contention that strong relationship exist between customer satisfaction and loyalty. However, customer satisfaction alone cannot achieve the objective of creating a loyal customer base. Some researchers also argued, that customer satisfaction and loyalty are not directly correlated, particularly in competitive business environments because there is a big difference between satisfaction, which is a passive customer condition, and loyalty, which is an active or proactive relationship with the organization.
Uterine artery embolization along with the administration of methotrexate for cervical ectopic pregnancy: technical and clinical outcomes.

OBJECTIVE The objective of our study was to evaluate the technical and clinical outcomes of uterine artery embolization (UAE) along with the administration of methotrexate (MTX) for cervical ectopic pregnancy with vaginal bleeding as an alternative nonsurgical treatment to control bleeding and preserve fertility. MATERIALS AND METHODS Eight patients (age range, 24-37 years; mean age, 30.1 years) with cervical ectopic pregnancy were treated with UAE using gelatin sponge particles to control vaginal bleeding. In seven patients, the administration of MTX was performed before, after, or before and after UAE. The follow-up periods after UAE ranged from 4 to 46 months (median, 8 months). We evaluated the UAE technique, clinical outcomes, complications, and fertility. RESULTS In all patients, UAE could control active vaginal bleeding on gynecologic examination. In six patients, the cervical ectopic pregnancy was dramatically resolved. In the other two patients presenting with both fetal heartbeat before UAE and persistent high HCG levels, active vaginal rebleeding was observed. The rebleeding was successfully controlled by a second UAE procedure. No major complication related to UAE was detected. The uterus could be preserved in all patients. In seven patients, normal menses resumed within 2 months after UAE. In only one patient, amenorrhea continued 8 months after UAE. In all three patients who could be followed for 2 years or more, three had subsequent successful natural pregnancies, and two patients had live births. CONCLUSION UAE along with the administration of MTX is effective in treating cervical ectopic pregnancy with vaginal bleeding while allowing the preservation of fertility.
The Lantibiotic NAI-107 Binds to Bactoprenol-bound Cell Wall Precursors and Impairs Membrane Functions*

Background: NAI-107 is a potent lantibiotic with an unknown mode of action. Results: NAI-107 targets bactoprenol-bound cell envelope precursors, e.g. lipid II, and in addition affects the bacterial membrane. Conclusion: Cell wall biosynthesis is blocked by sequestration of lipid II and functional disorganization of the cell wall machinery. Significance: The dual mechanism of action may explain the potency of NAI-107 and related lantibiotics. The lantibiotic NAI-107 is active against Gram-positive bacteria including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. To identify the molecular basis of its potency, we studied the mode of action in a series of whole cell and in vitro assays and analyzed structural features by nuclear magnetic resonance (NMR). The lantibiotic efficiently interfered with late stages of cell wall biosynthesis and induced accumulation of the soluble peptidoglycan precursor UDP-N-acetylmuramic acid-pentapeptide (UDP-MurNAc-pentapeptide) in the cytoplasm. Using membrane preparations and a complete cascade of purified, recombinant late stage peptidoglycan biosynthetic enzymes (MraY, MurG, FemX, PBP2) and their respective purified substrates, we showed that NAI-107 forms complexes with bactoprenol-pyrophosphate-coupled precursors of the bacterial cell wall. Titration experiments indicate that first a 1:1 stoichiometric complex occurs, which then transforms into a 2:1 (peptide: lipid II) complex, when excess peptide is added. Furthermore, lipid II and related molecules obviously could not serve as anchor molecules for the formation of defined and stable nisin-like pores, however, slow membrane depolarization was observed after NAI-107 treatment, which could contribute to killing of the bacterial cell.
A strategy for developing new treatment paradigms for neuropsychiatric and neurocognitive symptoms in Alzheimer’s disease

Successful disease modifying drug development for Alzheimer’s disease (AD) has hit a roadblock with the recent failures of amyloid-based therapies, highlighting the translational disconnect between preclinical animal models and clinical outcome. Although disease modifying therapies are the Holy Grail to pursue, symptomatic therapies addressing cognitive and neuropsychiatric aspects of the disease are also extremely important for the quality of life of patients and caregivers. Despite the fact that neuropsychiatric problems in Alzheimer patients are the major driver for costs associated with institutionalization, no good preclinical animal models with predictive validity have been documented. We propose a combination of quantitative systems pharmacology (QSP), phenotypic screening and preclinical animal models as a novel strategy for addressing the bottleneck in both cognitive and neuropsychiatric drug discovery and development for AD. Preclinical animal models such as transgene rats documenting changes in neurotransmitters with tau and amyloid pathology will provide key information that together with human imaging, pathology and clinical data will inform the virtual patient model. In this way QSP modeling can partially overcome the translational disconnect and reduce the attrition of drug programs in the clinical setting. This approach is different from target driven drug discovery as it aims to restore emergent properties of the networks and therefore likely will identify multitarget drugs. We review examples on how this hybrid humanized QSP approach has been helpful in predicting clinical outcomes in schizophrenia treatment and cognitive impairment in AD and expand on how this strategy could be applied to neuropsychiatric symptoms in dementia. We believe such an innovative approach when used carefully could change the Research and Development paradigm for symptomatic treatment in AD.
Alcoholic hepatitis: from pathogenesis to treatment

ABSTRACT Alcoholic hepatitis is a serious complication of alcohol abuse due to its high mortality rates particularly at short term. It may complicate pre-existing alcoholic fatty liver or cirrhosis and is mainly diagnosed on clinical and laboratory grounds although liver biopsy is occasionally needed to exclude other pathology and confirm the diagnosis. Accumulating evidence suggests that cytokines and immunity are actively involved in its pathogenesis. Management includes abstinence and supportive care. Treatment with corticosteroids has been studied in several clinical trials with conflicting results. However, recent evidence supporting the beneficial effect of TNF‐α inhibition provides an encouraging alternative. Here we summarise the current state in diagnosis and management of alcoholic hepatitis and briefly review the latest advances in pathophysiology that may lead to new therapeutic strategies for this difficult clinical condition. Data sources: Medline 1966–2005, EMBASE/Excerpta Medica 1980–2005, The Cochrane Library (2005 Issue 2) and contact with authors of published reports.
The RAGE receptor and its ligands are highly expressed in astrocytes in a grade‐dependant manner in the striatum and subependymal layer in Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of the CAG repeat in the huntingtin gene. One of the brain changes that occurs in HD is the expression of the receptor for advanced glycation end products (RAGE), a receptor protein capable of activating multiple signalling pathways by interacting with a range of ligands leading to either beneficial or harmful effects to the cell. Here, we demonstrate in human HD brains a high degree of co‐localization of RAGE with its putative ligands S100B and N‐carboxymethyllysine (CML) in the caudate nucleus (CN) and the subependymal layer (SEL). The level of co‐staining for both RAGE‐S100B and RAGE‐CML was the highest in the astrocytes but was low in neurons and microglia. The immunostaining for RAGE, S100B and CML extended in a medio‐lateral (SEL‐CN) direction with increasing grade, such that any change in the expression and co‐localization pattern between grades was less prominent in the lateral CN. Additionally, signalling molecules that are downstream of RAGE activation showed changes in their activation status in HD brains. A larger number of RAGE‐positive astrocytic cells had NF‐kB translocated to the nucleus and the level of phospho‐ERK1/2 was also increased in HD brains. Interestingly, the level of mDia‐1, that interacts directly with the cytoplasmic domain of RAGE, decreased in HD. Overall, the results suggest a correlation between the functions of RAGE and the HD pathology, but the influence of RAGE on astrocytes and the impact of this on HD progression requires further study.
Improving pseudo-relevance feedback in web information retrieval using web page segmentation

In contrast to traditional document retrieval, a web page as a whole is not a good information unit to search because it often contains multiple topics and a lot of irrelevant information from navigation, decoration, and interaction part of the page. In this paper, we propose a VIsion-based Page Segmentation (VIPS) algorithm to detect the semantic content structure in a web page. Compared with simple DOM based segmentation method, our page segmentation scheme utilizes useful visual cues to obtain a better partition of a page at the semantic level. By using our VIPS algorithm to assist the selection of query expansion terms in pseudo-relevance feedback in web information retrieval, we achieve 27% performance improvement on Web Track dataset.
The Essential Impact of Context on Organizational Behavior

I argue that the impact of context on organizational behavior is not sufficiently recognized or appreciated by researchers. I define context as situational opportunities and constraints that affect the occurrence and meaning of organizational behavior as well as functional relationships between variables, and I propose two levels of analysis for thinking about context–one grounded in journalistic practice and the other in classic social psychology. Several means of contextualizing research are considered.
Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies

Objectives: Ki-67 is expressed in the nuclei of dividing cells and can be used to assess proliferation of synovial inflammatory and stromal cells. We evaluated subintimal Ki-67+ cell density as a tissue biomarker for inflammatory arthropathies and compared it to subintimal CD68, a synovial biomarker of RA. Methods: Subintimal Ki-67+ and CD68+ cell densities were measured immunohistochemically in synovial specimens obtained from patients with rheumatoid arthritis (RA; n = 19), osteoarthritis (OA; n = 18), “non-inflammatory” orthopaedic arthropathies (avascular necrosis, meniscus injury, femur fracture; n = 16), chronic septic arthritis (n = 9), and histologically normal synovium (n = 10). Results were correlated with a histological synovitis score. Utilising the areas under receiver operating characteristic curves (AUCs), we compared the abilities of Ki-67 and CD68 to differentiate among these arthropathies. Results: Ki-67 was expressed widely in the subintima of inflamed specimens and in RA pannus invading hard tissues. Compared to normal controls, it was highly overexpressed in RA (26.6-fold) and chronic septic arthritis (55-fold), and mildly elevated in OA (3.9-fold) and orthopaedic arthropathies (2.1-fold). Ki-67 and CD68 differentiated similarly well between RA and OA (AUC: Ki-67 = 0.91, CD68 = 0.94), Ki-67 better between chronic septic arthritis and RA, and CD68 better between OA and normal controls. Ki-67 (r = 0.80) and CD68 (r = 0.79) correlated positively with the synovitis score. Conclusions: Subintimal Ki-67 was overexpressed in inflammatory arthropathies, distinguished among differentially inflamed arthropathies, and correlated positively with the histological severity of synovitis. It may prove useful in synovial tissue classification and as a synovial marker of disease activity in clinical trials when biopsies are available.
Exploring the Effectiveness of Mandatory Premarital Screening and Genetic Counselling Programmes for β-Thalassaemia in the Middle East: A Scoping Review

Background: β-Thalassaemia is a common genetic blood disorder in the Middle Eastern region. Mandatory premarital screening and genetic counselling (PMSGC) programmes are implemented in 8 Middle East countries to reduce at-risk marriages and thus disease prevalence. A scoping review was conducted to explore the effectiveness of these programmes. Methods: The 6-stage scoping framework of Arksey and O'Malley [Int J Soc Res Methodol 2005;8:19-32] was used. Reported outcomes were analysed per country, with success defined as achieving a 65% reduction in at-risk marriages and/or thalassaemia-affected births. Emergent enablers and barriers were analysed thematically. Results: Twenty-one sources were included from the 1,348 identified, discussing 7 country programmes, with 95% (20/21) published during 2003-2013. Five publications each were included for Iran and Saudi Arabia, 3 for Turkey, 2 each for Bahrain and Iraq (Kurdistan), and 1 for the United Arab Emirates, plus 2 multi-country evaluations. No programme achieved a 65% at-risk marriage cancellation rate. Though data on thalassaemia-affected birth reductions were minimal, programmes in Iran, Turkey and Iraq reported at least 65% reductions. A thematic analysis found that screening timing, access to prenatal detection and abortion, socio-religious issues, awareness and counselling affected decisions. Conclusion: This review found that PMSGC programmes were unsuccessful in discouraging at-risk marriages but successful in reducing the prevalence of affected births in countries providing prenatal detection and therapeutic abortion. A life cycle approach to prevention, incorporation of school screening, awareness campaigns, reconsideration of therapeutic abortion, and screening and counselling of couples married prior to programme inception are likely to improve the effectiveness of such programmes in the Middle Eastern region.
Distinct local circuit properties of the superficial and intermediate layers of the rodent superior colliculus

The superior colliculus (SC) is critical in localizing salient visual stimuli and making decisions on the location of the next saccade. Lateral interactions across the spatial map of the SC are hypothesized to help mediate these processes. Here, we investigate lateral interactions within the SC by applying whole‐cell recordings in horizontal slices of mouse SC, which maintained the local structure of the superficial (SCs) visual layer, which is hypothesized to participate in localizing salient stimuli, and the intermediate (SCi) layer, which is supposed to participate in saccade decision‐making. When effects of either electrical or chemical (uncaging of free glutamate) stimuli were applied to multiple sites with various distances from the recorded cell, a pattern of center excitation‐surround inhibition was found to be prominent in SCs. When the interactions of synaptic effects induced by simultaneous stimulation of two sites were tested, non‐linear facilitatory or inhibitory interactions were observed. In contrast, in the SCi, stimulation induced mainly excitation, which masked underlying inhibition. The excitatory synaptic effects of stimulation applied at remote sites were summed in a near linear manner. The result suggested that SCs lateral interactions appear suitable for localizing salient stimuli, while the lateral interactions within SCi are more suitable for faithfully accumulating subthreshold signals for saccadic decision‐making. Implementation of this laminar‐specific organization makes the SC a unique structure for serially processing signals for saliency localization and saccadic decision‐making.
The Role of Physical Attractiveness in the Observation of Adult-Child Interactions: Eye of the Beholder or Behavioral Reality?.

The susceptibility of observations of adult-child interactions to bias due to the physical attractiveness of target persons was examined. Facial features of target persons were occluded in one version of a videotape and unoccluded in another, otherwise identical version. Using a global rating system and a molecular coding strategy, 38 trained observers coded occluded and unoccluded versions of four videotapes, two of which were of attractive targets and two of unattractive targets. Findings indicated that the observers were significantly and favorably biased toward attractive women, when making global judgments about behavioral interactions. No bias was obtained, however, when observers used a molecular coding strategy. The results demonstrate the need to be cautious about employing and interpreting global ratings and suggest that molecular coding techniques may insulate observers from bias due to the attractiveness of the observed person. (Author/RH) *********************************************************************** * Reproductions supplied by EDRS are the best that can be made * * from the original document. * ***********************************************************************
Metformin versus lifestyle changes in treating women with polycystic ovary syndrome

Objective: To compare the efficacy of metformin with that of lifestyle changes in patients with polycystic ovary syndrome (PCOS). Design: Prospective, randomized clinical trial of 40 women with PCOS to analyze the effects of metformin and lifestyle intervention treatments on menstrual pattern and hormone and metabolic profile. The duration of treatment was 6 months. Statistical analysis was done using Student’s t-test.Results: Fifteen women in the metformin group and 12 in the lifestyle changes group completed the study. The menstrual pattern improved by ~67% in both groups. There was a significant decrease in waist circumference in the lifestyle changes group (101.8 ± 3.9 and 95.1 ± 3.6, at baseline and at 6 months of treatment, respectively; p < 0.001) and in body mass index (BMI) in both groups. The predictor of menstrual pattern improvement was BMI.Conclusions: Both metformin and lifestyle changes may increase the number of menstrual cycles in PCOS. This effect was related to a decrease in BMI.
Biopolitics, Biopower, and the Return of Sovereignty

In this paper we want to open up for discussion what counts as ‘biopolitics’—a term frequently used by critics and devotees alike to describe the organization of political power and authority in a world after Bretton Woods, the Cold War, and 9/11. We do so on two fronts. On the one hand, we contrast Foucault on war and the normalizing society, Agamben on thanatopolitics, and Hardt and Negri on biopotenza. Our goal here is to draw attention to multiple competing definitions of biopolitics, and in so doing problematize the term as a catchall category to describe either the ‘nonsovereign’ or the ‘postsovereign’ operation of power. On the other hand, while refusing some baseline definition of what counts as biopolitics, we develop our own specifically geographical criticisms of Agamben and Hardt and Negri on the topic of biopolitics. Following Sparke's recent interrogation of postfoundational thought on account of its oftentimes buried metaphysics of geopresence, we submit that Agamben as well as Hardt and Negri deploy biopolitics in both metaphysical and metageographical ways. We contrast this with Foucault's inductive, genealogical, and time-specific and place-specific use of the concept.