Miracle-dz/UniFAR-FTUs huggingface dataset:
Declining incidence of breast cancer after decreased use of hormone-replacement therapy: magnitude and time lags in different countries

Throughout the latter half of the 20th century, hormone-replacement therapy (HRT) use steadily increased in the Western world. In 2002, the early termination of the Women's Health Initiative trial due to an excess of adverse events attributable to HRT, led to a precipitous decline in its use. Breast cancer incidence began to decline soon thereafter in the USA and several other countries. However, the magnitude of the decline in breast cancer incidence, and its timing with respect to HRT cessation, shows considerable variability between nations. The impact of HRT cessation appears most significant and immediate in countries with the largest absolute decline in HRT use. In countries in which peak prevalence of HRT use was high, several studies have convincingly excluded decreasing rates of mammographic screening as an explanation for the decline in breast cancer incidence. Conversely, in some countries, no decline in breast cancer incidence is apparent that can be readily attributed to declining trends in HRT use. In such cases, declines in breast cancer incidence may be related instead to saturation or decreased utilisation of mammographic screening programmes. In other cases, it is difficult to disentangle the respective influence of trends in HRT use, and the influence of changes relating to mammographic screening. However, irrespective of time lags and varying magnitudes of effect, the data convincingly support a direct association between decreasing HRT use and declining breast cancer incidence.
Increased levels of fucosyltransferase IX and carbohydrate Lewisx adhesion determinant in human NT2N neurons

The expression of the fucosylated carbohydrate Lewisx (Lex) determinant (Gal(β1–4)[Fuc(α1–3)]GlcNAc‐R) has been found in glycoproteins, proteoglycans, and glycolipids from the nervous system. Evidence suggests its association with cell–cell recognition, neurite outgrowth, and neuronal migration during central nervous system development. In the present work, we detected increased levels of Lex in differentiated human NT2N neurons cultured in vitro. To identify which fucosyltransferase (FUT) synthesized the Lex in NT2N neurons, RT‐PCR, FUT substrate specificity and Western blot analysis were carried out. Strong activity toward acceptors Galβ4GlcNAc‐O‐R and Fucα2Galβ4GlcNAc‐O‐R [R = ‐(CH2)3NHCO(CH2)5NH‐biotin], together with strong FUT9 detection by Western blot and presence of transcripts showed that FUT9 was the enzyme associated with Lex biosynthesis in NT2N neurons. Lex was detected at the plasma membrane of NT2N neurons, in lysosomes marked with lysosomal‐associated membrane protein 1 (LAMP‐1), and it was found for the first time to colocalize with the tetanus neurotoxin‐insensitive vesicle‐associated membrane protein (TI‐VAMP) that defines the TI‐VAMP exocytic compartment that is involved in neurite outgrowth. Furthermore, incubation with anti‐Lex monoclonal antibody L5 led to impaired adhesion of NT2N neurons to the surface matrix and inhibited neurite initiation. In conclusion, FUT9 and its product Lex are detected specifically in human NT2N neurons and our results indicate that they underlie cell differentiation, cell adhesion, and initiation of neurite outgrowth in those neurons. © 2007 Wiley‐Liss, Inc.
A Collaborative Analysis of Stereotactic Lung Radiotherapy Outcomes for Early-Stage Non–Small-Cell Lung Cancer Using Daily Online Cone-Beam Computed Tomography Image-Guided Radiotherapy

Introduction: We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography. Methods: Five hundred and five stage I–IIB (T1-3N0M0) non–small-cell lung cancer (NSCLC) cases underwent SBRT using cone-beam computed tomography image guidance at five international institutions from 1998 to 2010. Median age was 74 years (range, 42–92) whereas median forced expiratory volume in 1 second/diffusing lung capacity for carbon monoxide were 1.4 liter (65%) and 10.8 ml/min/mmHg (53%). Of the 505 cases, 64% were biopsy proven and 87% medically inoperable. Staging was: IA 63%, IB 33%, IIA 2%, and recurrent 1%. Median max tumor dimension was 2.6 cm (range, 0.9–8.5). Median heterogeneously calculated volumetric prescription dose (PD) was 54 Gy (range, 20–64 Gy) in three fractions (range, 1–15) over 8 days (range, 1–27). Median biologically equivalent PD biological equivalent doses (BED10) was 132 Gy (range, 60–180). Results: With a median follow-up of 1.6 years (range, 0.1–7.3), the 2-year Kaplan–Meier local control (LC), regional control, and distant metastasis (DM) rates were 94%, 89%, and 20%, respectively, whereas cause-specific and overall survival were 87% and 60% (78% operable, 58% inoperable, p = 0.01), respectively. Stage, gross-tumor volume size (≥ 2.7 cm) and PD(BED10) predicted local relapse (LR) and DM. LR was 15% for BED10 less than 105 Gy versus 4% for BED10 of 105 Gy or more (p < 0.001); DM was 31% versus 18% for BED10 less than 105 versus 105 Gy or more (p = 0.01). On multivariate analysis, PD(BED10) and elapsed days during radiotherapy predicted LR; gross-tumor volume size predicted DM. Grade 2 or higher pneumonitis, rib fracture, myositis, and dermatitis were 7%, 3%, 1%, and 2%, respectively. Conclusions: In the largest early-stage NSCLC SBRT data set to date, a high rate of local control was achieved, which was correlated with a PD(BED10) of 105 Gy or more. Failures were primarily distant, severe toxicities were rare, and overall survival was encouraging in operable patients.
Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease

Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease‐modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention.
Indigenization of Depression: Understanding its Impression, Expression and Experiences among selected Indigenous Peoples (IPs) of Luzon, Philippines

Depression is an alarming psychological condition among indigenous peoples throughout the world. Ethnic minorities are identified as a population that is vulnerable to mental health problems. Depressive disorders have significant cultural variation in clinical presentation. Using Interpretative Phenomenological Analysis (IPA), this study aims to understand the indigenous peoples’ experiences and the manifestation of their depressive symptoms which are based on the context of their cultural knowledge. The central question that this phenomenological study purported to answer was: How do indigenous peoples collectively characterize their cultural understanding on the impression, expression and experiences of depression? Indigenous peoples attributed depression to pain (sakit) , suffering (hirap) and to endure (tiis). For the Dumagats, the indigenous concept of depression is related to “kakawitang palakol”/ “mamatay na mulat” ( lack of resources and loss of options ), while for the Aetas, they experience “dungos” or “pasma sa tiyan dahil sa gutom” ( stomach ache, dizziness and loss of appetite ), This study found that there are different depressive symptoms profiles among the three tribes: the Dumagats were more likely to emphasize affective and cognitive symptoms (e.g., mahirap kalooban at mahina ang katawan ( weak-spirited and the body is weak) , nag-alala saan kukuha ng makakain sa araw na iyon dahil wala ng mukuha sa kalikasan (worried where to get food for that day because nature has nothing left), the Aeta experienced somatic and affective complaints (e.g., sakit sa tiyan/napasma ( stomach ache and pains ),di makatulog (could not sleep) , sakit ulo sanhi ng gutom ( headache due to hunger ), and the Igorots reported more affected and cognitive complaints (e.g., walang gana magtrabaho ( lack of motivation to work ), nag-mumukmok o di nakiki-halubilo sa mga pag-titipon ( does not participate in gatherings ). This study recommends an audible call for a culturally sensitive guided intervention for this special population that requires a holistic approach. (a) How (b) What are the indigenous ways of understanding depression? (c) How is depression expressed and experienced from ethnic perspective? (d) How do their cultural beliefs and practices affect their impression, expression and understanding of depression?
Secondary school students' technology practices in their everyday lives and at school

Schools have a role to play in preparing students for their digital futures, but need to do more to cater for all students. Despite significant government investment and increased prominence in educational curriculums worldwide, there is a lack of conclusive evidence to demonstrate that technology has had a significant impact on student learning. Despite its use in schools, research suggests that disparities in the technology practices, skills and knowledge of school students still exists. In fact, there is much that is not fully understood about students’ experiences with technologies, specifically how and why they use technologies in particular contexts. In order to effectively integrate technologies in secondary schools to benefit all students’ learning and future opportunities, there is a pressing need for evidence-based practice. This study extends educational technology research into secondary school students’ technology practices by investigating how and why students use technology at school and in their everyday lives. Guided by the sociological framework of Bourdieu’s theory of practice, the study design considers not only technology use but also context to provide an understanding of the interrelations between technology practices, the students and their surroundings. The multiple embedded case study reported in this thesis comprised four class cases and 12 student cases from two Australian public secondary schools. Student questionnaires and teacher interviews were conducted with 64 Year 9 and Year 10 students and four teachers from the class cases. From these class cases, 12 student cases provided in-depth accounts of students’ technology practices through interviews and diary records. In reviewing the study findings and literature, this thesis presents a theoretical framework that conceptualises student technology practices. Data analysis was guided, first, by the emergent themes and patterns from the data and, second, by the theoretical framework. The study found that students tended to use technologies in similar ways each day and often used only basic functions of the technologies both in their everyday lives and at school. Still, their technology practices were personalised, thus displaying varied technological dispositions, skills and knowledge. Students’ varied experiences and dispositions towards technology practices were shaped by a multitude of factors,
Correlation of different NADPH oxidase homologues with late endothelial progenitor cell senescence induced by angiotensin II: effect of telmisartan.

OBJECTIVE Involvement of different NADPH oxidase (NOX) homologues in late endothelial progenitor cell (EPC) senescence induced by angiotensin II (Ang II) remains rarely studied systemically. The goal of our study was to determine NOX homologues which are correlated with late EPCs senescence induced by Ang II. The inhibitory effect of telmisartan was also studied. METHODS AND MATERIALS Late EPCs were obtained from mononuclear cells isolated from peripheral venous blood. Stimulated by Ang II with telmisartan (Tel) or VAS2870 pretreatment or siRNA prior silencing, NOX was detected by RT-PCR and Western blot. Cell senescence was measured by the acidic β-galactosidase activity assay and cell cycle analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometer based on DCFH-DA. RESULTS A bi-phasic change existed in NOX level after Ang II stimulation. Translocated NOX5 was correlated with early and rapid ROS production, but it contributed little to EPCs senescence. NOX2 and NOX4 were correlated with the late and slow phase and contributed greatly to EPCs senescence. There were no significant changes in NOX1 or NOX3. Telmisartan effectively depressed NOX change and delayed late EPCs senescence. CONCLUSION Ang II accelerates late EPCs senescence mainly via increased ROS originating from NOX2 and NOX4 up-regulation or translocated NOX5. Telmisartan effectively inhibited that cascade reaction and delayed EPCs senescence.
The Relationship between HLA-G Gene Polymorphisms and Repeated Implantation Failure in Infertile Couples Undergoing Assisted Reproductive Technique.

HLA-G is a tolerogenic molecule that expresses in cytotrophoblast cells and plays an important role in immune response suppression in maternal decidua. Interactions between the extracellular domains of the HLA-G protein with cell receptors of the immune system are well-known.This study investigated the association between HLA-G gene polymorphism with repeated implantation failure (RIF). We used PCR followed by the sequencing technique for exons 2, 3, and 4, as well as intron 2 of the HLA-G gene in 100 couples with histories of two or more failed assisted reproductive technique (ART) attempts. The data were compared with the results of our previous study.The results indicated that some alleles of the HLA-G gene such as: 0106, 010106, 01010106 and 0105N (null) alleles were significantly higher in the patient group compared to the control group (p<0.05). There were higher SNPs at the +482 T/C and +506 -/C positions in failed ART couples compared to controls (p=0.03; p=0.01, respectively). HLA-G gene polymorphisms do not clearly affect the risk for implantation failure in most couples who undergo ART. However allelic variations, particularly in exons 3 and 4, and intron 2 of the HLA-G gene can lead to ART failure in human embryos.
Short-Run Effects of Lower Productivity Growth. A Twist on the Secular Stagnation Hypothesis

Since 2010, U.S. GDP growth has been anemic, averaging 2.1% a year, and this despite interest rates very close to zero. Historically, one would have expected such low sustained rates to lead to much stronger demand. They have not. For a while, one could point to plausible culprits, from a weak financial system to fiscal consolidation. But, as time passed, the financial system strengthened, fiscal consolidation came to an end, and still growth did not pick up. We argue that this is due, in large part, not to legacies of the past but to lower optimism about the future, more specifically to downward revisions in forecast potential growth. Put simply, the anticipation of a less bright future is leading to temporarily weaker demand. If our explanation is correct, it has important implications for policy and for forecasts. It may weaken the case for secular stagnation, as it suggests that the need for very low interest rates may be partly temporary.
A closed-loop optimal control of the plasma glycemia

The paper investigates the problem of the optimal tracking of a desired plasma glucose evolution by means of a continuous intravenous infusion. The model for the glucose-insulin system here adopted, and recently published, belongs to the class of nonlinear single-distributed delay models. The closed-loop control law is performed according to the feedback linearization theory: a state-feedback is designed in order to exactly linearize the model with respect to a suitably defined change of coordinates. Then, the optimal tracking is achieved by minimizing a performance index. The methodology here proposed allows both to decrease and increase the glycemia. Simulations support theoretical results and show the physical reliability of the approach proposed
Central regulation of motor cortex neuronal responses to forelimb nerve inputs during precision walking in the cat

1 The responses of neurones in forelimb motor cortex to impulse volleys evoked by single pulse electrical stimulation (at 1.5 or 2 times the threshold for most excitable nerve fibres) of the superficial radial (SR) and ulnar (UL) nerves of the contralateral forelimb were studied in awake cats both resting quietly and walking on a horizontal ladder. Nerve volley amplitude was monitored by recording the compound action potential elicited by the stimulus. 2 In the resting animal 34/82 (41 %) cells yielded statistically significant responses to SR stimulation, and 20/72 (28 %) responded to UL stimulation. Some responses were confined to or began with an increase in firing probability (‘excitatory’ responses) and others with a decrease in firing (‘inhibitory’ responses), typically including a brief interruption of the spike train (zero rate). Cells responding to both nerves usually yielded responses similar in type. Most (78 %) response onset latencies were less than 30 ms. Responses involved the addition or subtraction of from 3.4 to 0.1 impulses stimulus−1 (most < 1 impulse stimulus−1). The distribution of response sizes was continuous down to the smallest values, i.e. there was no ‘gap’ which would represent a clear separation into ‘responsive’ and ‘unresponsive’ categories. Responses were commonest in the lateral part of the pericruciate cortex, and commoner among pyramidal tract neurones (PTNs) than non‐PTNs. 3 During ladder walking most cells generated a rhythmic step‐related discharge; in assessing the size of responses to nerve stimulation (20 studied, from 13 cells) this activity was first subtracted. Response onset latencies (90 % < 30 ms) and durations showed little or no change. Although most cells were overall more active than during rest both ‘excitatory’ and ‘inhibitory’ responses in both PTNs and non‐PTNs were often markedly reduced in large parts of the step cycle; over some (usually brief) parts responses approached or exceeded their size during rest, i.e. response size was step phase dependent. Such variations occurred without parallel change in the nerve compound action potential, nor were they correlated with the level of background firing at the time that the response was evoked. When responses to both nerves were studied in the same neurone they differed in their patterns of phase dependence. 4 The findings are interpreted as evidence for central mechanisms that, during ‘skilled’, cortically controlled walking, powerfully regulate the excitability of the somatic afferent paths from forelimb mechanoreceptors (including low threshold cutaneous receptors) to motor cortex. Retention (or enhancement) of responsiveness often occurred (especially for ulnar nerve) around footfall, perhaps reflecting a behavioural requirement for sensory input signalling the quality of the contact established with the restricted surface available for support.
Effects of NMD A‐ and AMPA‐Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V‐methyl‐D‐aspartate (NMDA)‐ and non‐NMDA‐receptor antagonists. As NMDA‐receptor antagonist we used dextrorphan, ket‐amine, and 2‐aminophosphonovalerate (2APV); as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid (AMPA)‐receptor antagonist we employed the quinoxaline derivative glutamate 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA‐receptor antagonists. However, when dextrorphan was employed to suppress seizure‐like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μMm. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.
Fetal plasma MMP-9 concentrations are elevated in preterm premature rupture of the membranes.

OBJECTIVE The objective of this study was to determine whether the concentrations of matrix metalloproteinase-9 (MMP-9) in the fetal (fetal plasma and amniotic fluid) and maternal compartments (plasma) are different in patients presenting with preterm premature rupture of membranes (PROM) than in those with preterm labor and intact membranes. STUDY DESIGN Fetal plasma MMP-9, interleukin-1beta (IL-1beta), IL-6, soluble tumor necrosis factor receptors 1 (sTNF-R1) and 2 (sTNF-R2) were measured in fetuses with preterm labor and intact membranes (n = 96) and preterm PROM (n = 43). The concentrations of analytes were determined with sensitive and specific immunoassays. A P value <. 05 was considered significant. RESULTS (1) The median fetal plasma MMP-9 concentration was significantly higher in fetuses with preterm PROM than in those with preterm labor (P =.035). (2) In contrast, fetal plasma IL-1beta, sTNF-R1, and sTNF-R2 were significantly higher in patients with preterm labor than in those with preterm PROM (IL-1beta, P =.01; sTNF-R1, P =.003; and sTNF-R2, P =.02). (3) The median amniotic fluid concentration of MMP-9 was higher in patients with preterm PROM than in those with preterm labor (P <.001). CONCLUSION Fetuses with preterm PROM have increased concentrations of an enzyme (MMP-9) implicated in the mechanism of membrane rupture but lower concentrations of IL-1beta, sTNF-R1, and sTNF-R2 than fetuses with preterm labor and intact membranes. A role for the fetus in the genesis of preterm PROM deserves consideration.
Falling between two stools; how a weak co-operation between the social security and the unemployment agencies obstructs rehabilitation of unemployed sick-listed persons

Purpose. To explore significant factors behind the weak co-operation between local social insurance and unemployment agencies impairing the rehabilitation of unemployed sick-listed persons. Method. Individual, semi-structured face-to-face interviews with main actors directly involved in the sick-listing and rehabilitation process were conducted in the year 2000. In all 39 persons were interviewed: 25 professionals (physicians, public employment and social insurance officers) and 14 clients. Data were analysed according to Grounded theory method. Results. The majority of unemployed sick-listed persons were declared too sick to work and were erased from the unemployment registers. This measure weakened the incentives for co-operation between the two main rehabilitation actors. The implication was that the unemployed sick-listed persons lost the opportunity of the co-ordinated rehabilitation they were entitled to. Three significant factors behind this process were identified by the main actors: indistinct regulation of co-operation, shifting political goals over time and conflicting goals between agencies; the last factor mainly a consequence of the other two. Conclusions. The findings suggest that labour market changes and manifest political goals influence the rehabilitation efforts giving low priority to difficult-to-place individuals such as unemployed sick-listed persons. In fact, a labour market problem turns into a medical problem. The hypothesis needs further testing in quantitative studies.