Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequent Loss of BRCA1 Nuclear Expression in Young Women With Breast Cancer: An Immunohistochemical Study From an Area of Low Incidence but Early Onset

Young women with breast cancer have a more unfavorable outcome and advanced disease than older women. This study was initiated to determine the difference in tumor biology between younger and older groups. One hundred fifty-five patients with invasive ductal carcinoma, not otherwise specified, comprised the study group, including 50 women aged less than 35 years, 50 aged 36 to 50 years, and 55 aged more than 50 years. Histopathologic parameters, including tumor size, combined histologic grade, and axillary lymph node status, were studied. Biomarkers, including estrogen receptor status, tumor proliferation rate as determined by Ki-67, and gene expressions of c-erb B-2, p53, bcl-2, and BRCA1, were determined by immunohistochemistry. Comparisons of the distribution of these parameters in three age groups were performed. Breast cancer occurring in women aged less than 35 years had a significantly higher incidence of large tumor, high proliferation rate, and loss of nuclear BRCA1 expression (44.0% versus 22.0% or 23.6%) than in the two older age groups. Breast cancer in women aged less than 35 years also had higher histologic grade and higher frequency of bcl-2–negative tumor than that found in the 36- to 50-year age group. No difference was found in lymph node status and c-erb B-2 and p53 gene expressions between the age groups. Loss of BRCA1 nuclear expression significantly correlated with higher histologic grade and high Ki-67 index (P < 0.05) in group A. These findings suggested that women aged less than 35 years have frequent loss of nuclear BRCA1 expression, which may be responsible for the specific tumor biology different from older women. However, c-erb B-2 and p53 gene expressions seem to have no important role in the adverse tumor behavior of breast cancer in young women.
The linear-quadratic formula and progress in fractionated radiotherapy.

Clinical gains have been reported from the use of nonstandard fractionation schedules planned with a radiobiological basis. Hyperfractionation provides the leading example, as described below, with accelerated fractionation being developed more recently. Although examples of almost every kind of fractionated schedule can be found in the literature over the past 90 years, it is only within the last decade that the biological factors concerning overall time and delayed proliferation after irradiation, and the effect of dose per fraction, have been understood. Both these factors operate differently on late- and early-reacting tissues, because cell proliferation in late-reacting tissues is slow or absent, but early reacting tissues and tumours depend upon cells that proliferate rapidly. This basic knowledge is still diffusing through the radiotherapy community and I hope this review will help the diffusion process. The biological factors concerning fractionation seem to apply to the majority of tissues and tu.
Zipf's Law in Aphasia Across Languages: A Comparison of English, Hungarian and Greek

Abstract We investigated Zipf’s law in fluent and non-fluent aphasics’ spontaneous speech in English, Hungarian, and Greek. A previous study showed that the word frequency distribution in Dutch non-fluent aphasic speech conforms to Zipf’s law, although with a different slope. In this project we investigated to what extent these results can be generalized to other languages and to fluent aphasic speech. The results suggest that both the fluent and the non-fluent aphasic speech of English, Hungarian and Greek conform to Zipf’s law, and that differences in slope can be related to a language’s morphological properties and a group’s particular language impairments.
Cytoplasmic tail motifs mediate endoplasmic reticulum localization and export of transmembrane reporters in the protozoan parasite Toxoplasma gondii

In mammalian cells and yeasts, amino acid motifs in the cytoplasmic tails of transmembrane proteins play a prominent role in protein targeting in the early secretory pathway by mediating localization to or rapid export from the endoplasmic reticulum (ER). However, early sorting events are poorly characterized in protozoan parasites. Here, we show that a C‐terminal QKTT sequence mediates the ER localization of chimeric reporter constructs consisting of bacterial alkaline phosphatase (BAP) fused to the transmembrane domain (TMD) and truncated cytoplasmic tail of the human low‐density lipoprotein receptor (LDL) receptor or of murine lysosome‐associated membrane protein (lamp‐1) in Toxoplasma gondii. The cytoplasmic tail of human TGN46 also determines ER localization of BAP chimeras in the parasite, but this can be overcome by the addition at the C‐terminus of the tail of an acidic patch, which functions as an ER export signal in conjunction with an upstream tyrosine motif. These results suggest that COPI‐dependent ER retrieval and COPII‐dependent export mechanisms mediated by KKXX and DXE motifs of mammalian cells are generally conserved in T. gondii. In contrast, the failure of the QKTT motif and TGN46 cytoplasmic tail to induce steady‐state ER localization of vesicular stomatitis virus glycoprotein (VSVG) chimeras in HeLa and NRK cells indicates that significant differences in early secretory trafficking also exist.
Vascular Endothelial Growth Factor Expression and Cyclosporine Toxicity in Renal Allograft Rejection

The aim of this study was to evaluate the influence of vascular endothelial growth factor (VEGF) on renal function and on development of interstitial fibrosis (IF) in renal allografts. Tubular and interstitial expressions of VEGF and TNF‐α, and density of macrophages in the interstitium were examined in 92 patients with nonrejected kidneys, acute rejection (AR), chronic allograft nephropathy (CAN), borderline changes (BC) and acute cyclosporin A (CsA) toxicity. Follow‐up biopsy specimens from patients with AR and BC were evaluated for development of IF. A significant difference in tubular and interstitial VEGF expressions was found between patients with AR, BC, CAN and CsA toxicity (p < 0.001). Macrophage infiltration was positively correlated with VEGF and TNF‐α expressions (p < 0.001). VEGF expression increased with increasing expression of TNF‐α (p < 0.001). Renal function in first 6 months after initial biopsy was better in patients with marked tubular VEGF expression (p < 0.01); however, in follow‐up, development of IF and graft loss was found earlier in these patients (p < 0.01 and p < 0.05, respectively). Increased renal VEGF expression has protective properties immediately following renal allograft but allows for increased risk of early IF, and therefore poor graft outcome in the long term.
Response: "A Propensity Score-matched Analysis of Open Versus Minimally Invasive Transthoracic Esophagectomy in the Netherlands".

anastomotic leakage was around 15.2% in highly dedicated centers, with a 30-day mortality rate of 2.1%. It is probably the case that this quick implementation of the Ivor Lewis MIE has been accompanied with a high rate of anastomotic leakages and reinterventions with no increase of the postoperative mortality. Moreover, Ivor Lewis MIE has evolved, in the Dutch centers, so that since 2015, the intrathoracic anastomosis has been standardized in many centers, whereby the percentage of leakages and reintervention seems to have been importantly reduced. It is important to regard this propensity study of the Dutch Register between 2011 and 2015 as an analysis of surgical practices during period of time in which important changes in esophageal surgery in the Netherlands has come about. Questions arise as what to do with the outcome here published, particularly regarding the 3 possible measures: to stop the MIE program; to adopt some hybrid procedure as suggested in the discussion; or to adopt corrective measures and perfect the procedures to get the best and optimal outcome for the patients. Up to now, the last option has been chosen in the Netherlands. In conclusion, the paper by Dr Seesing and co-authors addresses a very relevant subject. This serves as an important step in establishing what the future of the MIE can be and how important it is to register and analyze the data produced by every surgical community. Accordingly, we would have liked to receive more information and feedback concerning the addressed remarks.
Nuclear Localization of Flavonoid Enzymes in Arabidopsis*

Flavonoids represent one of the oldest, largest, and most diverse families of plant secondary metabolites. These compounds serve a wide range of functions in plants, from pigmentation and UV protection to the regulation of hormone transport. Flavonoids also have interesting pharmacological activities in animals that are increasingly being characterized in terms of effects on specific proteins or other macromolecules. Although flavonoids are found in many different locations both inside and outside the cell, biosynthesis has long been believed to take place exclusively in the cytoplasm. Recent reports from a number of different plant species have documented the presence of flavonoids in nuclei, raising the possibility of novel mechanisms of action for these compounds. Here we present evidence that not only flavonoids, but also at least two of the biosynthetic enzymes, are located in the nucleus in several cell types in Arabidopsis. This is the first indication that differential targeting of the biosynthetic machinery may be used to regulate the deposition of plant secondary products at diverse sites of action within the cell.
Endogenous gamma interferon mediates resistance to Brucella abortus infection

Depletion of endogenous gamma interferon (IFN-gamma) with anti-IFN-gamma monoclonal antibody resulted in increased numbers of Brucella abortus in the spleen and liver of infected CBA mice. This increase was accompanied by a decrease in splenomegaly and a lower proportion of macrophages in the spleen. Furthermore, treatment of recipient mice with anti-IFN-gamma antibody blocked the adoptive transfer of resistance with immune T cells. Together, the results indicated that endogenous IFN-gamma plays an important role in mediating resistance to primary and secondary Brucella infection.
Patient-Reported Dental Safety Events: A South African Perspective

Supplemental digital content is available in the text. Objectives In recent years, there has been an increase in research studies highlighting patients’ experiences of adverse events (AEs) as well as the role of patients in promoting safety. The primary goal of the study was to assess the prevalence of dental AEs (DAEs) among dental patients in South Africa and its associated factors. The integration of the patient perspective into dental patient safety research will enhance our collective understanding of DAEs. Methods We conducted a cross-sectional study of adult patients at a large dental academic institution in South Africa from May to June 2015, evaluating their previous experiences of DAEs at any dental clinic in South Africa. Descriptive statistics and bivariate and multivariate analyses were performed to identify the factors associated with an increased likelihood of experiencing a DAE. Results A total of 440 questionnaires were returned during the 6-week study period (response rate = 97.8%). Overall, 45.5% of participants reported experiencing one or more DAEs. Two hundred participants reported a total of 717 DAEs giving us a lifetime prevalence of 1.6 DAEs per respondent. Our results suggest that respondents who were younger (18–24 y), from high-income families (>R150,000 or US $9200), dissatisfied with their last dental visit and oral health had an increased likelihood of reporting a previous experience of a DAE. Conclusions This study provides an insight into the nature of information that can be gleaned from dental patients regarding safety and helps lay the foundation for patient involvement in patient safety reporting.
Supporting whistleblowers in academic medicine: training and respecting the courage of professional conscience

Conflicts between the ethical values of an organisation and the ethical values of the employees of that organisation can often lead to conflict. When the ethical values of the employee are considerably higher than those of the organisation the potential for catastrophic results is enormous. In recent years several high profile cases have exposed organisations with ethical weaknesses. Academic medical institutions have exhibited such weaknesses and when exposed their employees have almost invariably been vindicated by objective inquiry. The mechanisms that work to produce such low ethical standards in what should be exemplary organisations are well documented and have been highlighted recently. The contribution of elements of medical training in eroding ethical standards of medical students have also been emphasised recently and strategies proposed to reduce or reverse this process. The ability to rapidly change the ethical and professional culture of graduate medical trainees may help to deal with some of the perceived problems of declining ethical standards in academic medicine.
Identifying the features of an easy-to-use and intuitive dry powder inhaler for asthma and chronic obstructive pulmonary disease therapy: results from a 28-day device handling study, and an airflow resistance study

Background: Many patients with asthma and chronic obstructive pulmonary disease (COPD) symptoms remain insufficiently controlled despite inhalation treatment, with poor inhaler technique recognized as a significant contributor. Dry powder inhalers (DPIs) need less coordination of actuation and inspiration than pressured metered dose inhalers. Objectives: To assess whether consideration of ‘ideal inhaler’ features during design and development of a new DPI device (Forspiro® Sandoz AG, Switzerland) led to an easy-to-use and reliable inhaler. Methods: Two studies are reported here: i) 24 adult Accuhaler® users received either limited written instructions (n = 12) or fully illustrated instructions (n = 12) for the Forspiro device; and ii) peak inspiratory flow rates through the Forspiro device were assessed in 30 adult and 10 pediatric patients with asthma and 10 adult patients with COPD. Results: All subjects understood the correct sequence of actions for the Forspiro device and rated all aspects of handling the device as ‘very easy’ or ‘fairly easy’ (except one uninstructed subject who rated ‘ease of determining number of doses left’ as ‘fairly difficult’). All patients achieved ≥ 35 l/min, thus demonstrating that the Forspiro device provides low-medium airflow resistance. Conclusions: Inhaler design providing good drug delivery with maximum ease of use may lead to more reliable therapy and improved control of airway diseases.
Organic matter breakdown and ecosystem metabolism: functional indicators for assessing river ecosystem health

Abstract River health monitoring traditionally has made use of structural measurements (water quality or taxonomic composition of aquatic organisms). We argue that a more complete assessment of river health should include functional metrics, such as rates of organic matter decomposition and ecosystem metabolism. Leaf breakdown links the characteristics of riparian vegetation with the activity of both aquatic invertebrates and microbial organisms and is affected by natural and human-induced variation in a wide range of environmental factors. Measurement of leaf breakdown is relatively simple and has modest equipment requirements. River metabolism (gross primary productivity and ecosystem respiration) measures the rates of production and use of organic C in river ecosystems as a whole, providing a direct estimate of the food base that determines life-supporting capacity. Metabolism measurements require more sophisticated equipment than do measurements of leaf breakdown, but improvements in technology have made metabolism measurements relatively easy. We review the factors that influence leaf breakdown and river metabolism and pay particular attention to the effects of human-induced environmental stressors. We also describe how measurements can be standardized and suggest criteria for interpreting functional measures in terms of river ecosystem health. Last, we consider the strengths and weaknesses of both methods as functional measures and provide recommendations for their use as biomonitoring tools.
Extraction of Blood Vessels in Retinal Images Using Resampling High-Order Background Estimation

In retinal blood vessel extraction through background removal, the vessels in a fundus image which appear in a higher illumination variance area are often missing after the background is removed. This is because the intensity values of the vessel and the background are nearly the same. Thus, the estimated background should be robust to changes of the illumination intensity. This paper proposes retinal blood vessel extraction using background estimation. The estimated background is calculated by using a weight surface fitting method with a high degree polynomial. Bright pixels are defined as unwanted data and are set as zero in a weight matrix. To fit a retinal surface with a higher degree polynomial, fundus images are reduced in size by different scaling parameters in order to reduce the processing time and complexity in calculation. The estimated background is then removed from the original image. The candidate vessel pixels are extracted from the image by using the local threshold values. To identify the true vessel region, the candidate vessel pixels are dilated from the candidate. After that, the active contour without edge method is applied. The experimental results show that the efficiency of the proposed method is higher than the conventional low-pass filter and the conventional surface fitting method. Moreover, rescaling an image down using the scaling parameter at 0.25 before background estimation provides as good a result as a non-rescaled image does. The correlation value between the non-rescaled image and the rescaled image is 0.99. The results of the proposed method in the sensitivity, the specificity, the accuracy, the area under the receiver operating characteristic (ROC) curve (AUC) and the processing time per image are 0.7994, 0.9717, 0.9543, 0.9676 and 1.8320 seconds for the DRIVE database respectively. key words: retinal blood vessel extraction, retinal background estimation, rescaling image, high order degree polynomial
Initial Results of Radio Occultation Observations of Earth's Atmosphere Using the Global Positioning System

Recent radio occultation measurements using Global Positioning System satellite transmitters and an orbiting receiver have provided a globally distributed set of high-resolution atmospheric profiles, suggesting that the technique may make a significant contribution to global change and weather prediction programs. Biases in occultation temperatures relative to radiosonde and model data are about 1 kelvin or less in the tropics and are generally less than 0.5 kelvin at higher latitudes. Data quality is sufficient to quantify significant model errors in remote regions. Temperature profiles also reveal either an equatorial Rossby-gravity or an inertio-gravity wave. Such waves provide a fundamental source of momentum for the stratospheric circulation.
Anterograde balloon valvuloplasty for the treatment of neonatal critical valvar aortic stenosis

We report our experience with anterograde balloon valvuloplasty in 17 neonates treated between November 1996 and June 2001 for critical aortic stenosis. Patients with hypoplastic left heart syndrome were excluded. Anterograde balloon valvoplasty of the aortic valve was possible in all 17 patients. The mean peak systolic gradient prior to cardiac catheterization was 73 mm Hg (range, 30–117 mm Hg) and decreased to 37 mm Hg (range, 21–60 mm Hg) after the dilation. Aortic regurgitation after balloon valvoplasty was absent or mild in 14/17 patients, moderate in 2 patients, and severe in 1 patient. There was no mortality or echocardiographic evidence for aortic cusp perforation or mitral regurgitation associated with the procedure. Redilation was necessary in 3/17 patients. Two patients are awaiting elective Ross operation. One patient with endocardial fibroelastosis died at 11 months of age. Anterograde balloon valvoplasty can be safely and effectively performed to palliate neonates with critical aortic valve stenosis. Cathet Cardiovasc Intervent 2002;56:516–520. © 2002 Wiley‐Liss, Inc.
Participação orçamentária e assimetria informacional: um estudo em uma empresa multinacional

RESUMO As empresas incentivam a participacao orcamentaria como forma de obter maior controle e reduzir a diferenca de informacao entre superior e subordinado. Assim, a pesquisa objetiva verificar a influencia da participacao orcamentaria na reducao da assimetria informacional no processo orcamentario em uma empresa multinacional, tendo-se por pressuposto que o orcamento participativo minimiza a assimetria de informacao. Para tanto, realizou-se uma pesquisa descritiva, na forma de estudo de caso e do tipo qualitativa, por meio de entrevista adaptada de Milani (1975) e Dunk (1993), bem como de observacao direta. O estudo foi aplicado em uma unidade de negocio de uma empresa multinacional que possui a pratica orcamentaria consolidada. Os resultados da pesquisa apontaram que a empresa possui um orcamento participativo, pois todos os setores e gestores estao envolvidos diretamente na sua elaboracao, alem disso, sao realizadas varias reunioes para a discussao e definicao das metas orcamentarias. No entanto, tal condicao neste estudo nao minimizou a assimetria informacional, pois a maioria das respostas se concentrou em um unico item evidenciando que o gestor/subordinado (agente) possui mais informacoes do que seu gerente/superior (principal), corroborando com estudos anteriores.
Tryptophan availability selectively limits NO‐synthase induction in macrophages

We studied the effects of tryptophan (TRP) availability on the synthesis and release of nitric oxide (NO) and tumor necrosis factor α (TNF‐α) in interferon‐γ (IFN‐γ)‐activated murine macrophages of the BAC1.2F5 cell line. IFN‐γ (100 U/ml) not only increased the synthesis and release of NO and TNF‐α from these cells but also induced indoleamine‐2,3‐dioxygenase, the rate‐limiting enzyme of TRP catabolism. This led to an increased metabolic flow through the kynurenine pathway and significantly decreased TRP levels in macrophage incubation media. Low TRP concentrations in the media, however, modified IFN‐γ effects. In TRP‐“starved” cultures, in fact, the IFN‐γ‐mediated NO synthase induction was significantly reduced, and the increased TNF‐α synthesis and release were not affected. Our results suggest hat a reduced local TRP availability may modify macrophage function and possibly the outcome of immune responses.