The Wnt Co-Receptor Lrp6 Is Required for Normal Mouse Mammary Gland Development

Canonical Wnt signals are transduced through a Frizzled receptor and either the LRP5 or LRP6 co-receptor; such signals play central roles during development and in disease. We have previously shown that Lrp5 is required for ductal stem cell activity and that loss of Lrp5 delays normal mammary development and Wnt1-induced tumorigenesis. Here we show that canonical Wnt signals through the Lrp6 co-receptor are also required for normal mouse mammary gland development. Loss of Lrp6 compromises Wnt/β-catenin signaling and interferes with mammary placode, fat pad, and branching development during embryogenesis. Heterozygosity for an inactivating mutation in Lrp6 is associated with a reduced number of terminal end buds and branches during postnatal development. While Lrp6 is expressed in both the basal and luminal mammary epithelium during embryogenesis, Lrp6 expression later becomes restricted to cells residing in the basal epithelial layer. Interestingly, these cells also express mammary stem cell markers. In humans, increased Lrp6 expression is associated with basal-like breast cancer. Taken together, our results suggest both overlapping and specific functions for Lrp5 and Lrp6 in the mammary gland

Clinical XLNet: Modeling Sequential Clinical Notes and Predicting Prolonged Mechanical Ventilation

Clinical notes contain rich data, which is unexploited in predictive modeling compared to structured data. In this work, we developed a new text representation Clinical XLNet for clinical notes which also leverages the temporal information of the sequence of the notes. We evaluated our models on prolonged mechanical ventilation prediction problem and our experiments demonstrated that Clinical XLNet outperforms the best baselines consistently

Adherence and Concordance between Serious Illness Care Planning Conversations and Oncology Clinician Documentation among Patients with Advanced Cancer

Background:Serious illness conversations are part of advance care planning (ACP) and focus on prognosis, values, and goals in patients who are seriously ill. To be maximally effective, such conversations must be documented accurately and be easily accessible. Objectives:The two coprimary objectives of the study were to assess concordance between written documentation and recorded audiotaped conversations, and to evaluate adherence to the Serious Illness Conversation Guide questions. Methods:Data were obtained as part of a trial in patients with advanced cancer. Clinicians were trained to use a guide to conduct and document serious illness conversations. Conversations were audiotaped. Two researchers independently compared audiorecordings with the corresponding documentation in an electronic health record (EHR) template and free-text progress notes, and rated the degree of concordance and adherence. Results:We reviewed a total of 25 audiorecordings. Clinicians addressed 87% of the conversation guide elements. Prognosis was discussed least frequently, only in 55% of the patients who wanted that information. Documentation was fully concordant with the conversation 43% of the time. Concordance was best when documenting family matters and goals, and least frequently concordant when documenting prognostic communication. Most conversations (64%) were documented in the template, a minority (28%) only in progress notes and two conversations (8%) were not documented. Concordance was better when the template was used (62% vs. 28%). Conclusion:Clinicians adhered well to the conversation guide. However, key information elicited was documented and fully concordant less than half the time. Greater concordance was observed when clinicians used a prespecified template. The combined use of a guide and EHR template holds promise for ACP conversations

The Wnt Receptor, Lrp5, Is Expressed by Mouse Mammary Stem Cells and Is Required to Maintain the Basal Lineage

Background: Ectopic Wnt signaling induces increased stem/progenitor cell activity in the mouse mammary gland, followed by tumor development. The Wnt signaling receptors, Lrp5/6, are uniquely required for canonical Wnt activity. Previous data has shown that the absence of Lrp5 confers resistance to Wnt1-induced tumor development. Methodology/Principal Findings: Here, we show that all basal mammary cells express Lrp5, and co-express Lrp6 in a similar fashion. Though Wnt dependent transcription of key target genes is relatively unchanged in mammary epithelial cell cultures, the absence of Lrp5 specifically depletes adult regenerative stem cell activity (to less than 1%). Stem cell activity can be enriched by.200 fold (over 80 % of activity), based on high Lrp5 expression alone. Though Lrp5 null glands have apparent normal function, the basal lineage is relatively reduced (from 42 % basal/total epithelial cells to 22%) and Lrp52/2 mammary epithelial cells show enhanced expression of senescence-associated markers in vitro, as measured by expression of p16 Ink4a and TA-p63. Conclusions/Significance: This is the first single biomarker that has been demonstrated to be functionally involved in stem cell maintenance. Together, these results demonstrate that Wnt signaling through Lrp5 is an important component o

Dammet, vår minsta gemensamma nämnare : En känsla av tillhörighet

Dust, our smallest common denominator                                                                                                                                                                  Charlotta Lindvall   ABSTRACT   I find it fascinating to know that we are all made of the same material as the stars and that everything is connected to each other and in a constant movement and transformation, a recycle of material. We are all made of stardust. In fact all life is sprung out of dust. In my essay I investigate the dust and ask the question if there are any traces in the dust. I look at the history of the dust and how it has affected us and our world through the decades. What does this small and airy but oh so unappreciated dust tell us? Why do we want to get rid of it? Is it possible to find a sense of belonging in the big context by investigating the dust and its origin and could I transform such a low material as dust into something magic that makes people reflect on our origin and belonging and how everything is connected? In my work I use dust as a material and in the essay I compare my work with other artists who have worked with dust as a material. Dust is everywhere because its source is from everything. I as a crafter also contribute to the dust making when I mechanically process material. We all share the atmosphere and breathe the same air and by that means we all share the dust particles. With every breath we take we inhale 1000 of dust particles and without knowing it the wind could have brought invisible camelhair from the Sahara desert that you just know have inhaled into your system. The most fascinating is that under your bed you can find traces of particles that have come all the way from outer space. In fact, each year it rains down 100 tons of cosmic dust from outer space down to our planet, particles that come from asteroids or comets and could contain hundred thousand of smaller particles of diamonds and sapphires that might come from a time when our planet was formed. I found that through the dust you can read the whole history of the universe. It holds the information of what has happened, what happened right now and what will happen. The dust reveals all our secrets; it holds the past and present at the same time. The dust is on its way to become and at the same time on its way from being.  In the dust you can find traces of me, you and the universe. By investigating the dust I have found a new view of the world. I have found a sense of belonging in the big context, where everything is connected and part of the same origin. Even in the darkest corner you can find magic. We are all diamonds fallen from the sky.The full thesis contains copyrighted material which has been removed in the published version.</p

The importance of stimulation in school for the well-being of gifted students

Students who learn quickly and who have a complex way of thinking and analyzing do not always receive the support they need at school in Sweden (Skolinspektionen, 2022). At the same time, international research shows that prolonged lack of stimulation can lead to challenges such as those with neuropsychiatric disorders (Amend &amp; Beljan, 2009) and can lead to school difficulties, such as problematic school absence (Gross, 2009). The purpose of this ongoing research is to find out whether wellbeing differs between the students identified by the school as gifted and the rest of the student population. There are such indications internationally (Casino-García et al., 2021), but no research has yet been done in Sweden to be able to establish that this is indeed the case. The study is part of a larger research project and based on a social constructivist theory with a salutogenic perspective. It has a quantitative approach, and the data collection includes Swedish municipalities that have initiatives aimed at potentially gifted students in grades 4–8. In Sweden, there is no general aptitude testing of students, so to be able to identify the right target group, an estimation tool developed, not a guarantee of giftedness but to give an indication, will be used (Nissen, 2019). Through surveys based on previously published survey tools the results will illustrate whether there is any difference between the well-being of gifted students compared to the wider population. This provides an empirical basis to subsequently explore the effects of school- based interventions, such as acceleration, enrichment, and mentoring, and in turn see whether mental health improves if students are offered such support. References Amend, E. R., &amp; Beljan, P. (2009). The antecedents of misdiagnosis: When normal behaviors of gifted children are misinterpreted as pathological. Gifted Education International, 25(2), 131–143. https://doi.org/10.1177/026142940902500204 Casino-García AM, Llopis-Bueno MJ, Gómez-Vivo MG, JuanGrau A, Shuali-Trachtenberg T and Llinares-Insa LI (2021) “Developing Capabilities”. Inclusive Extracurricular Enrichment Programs to Improve the Well-Being of Gifted Adolescents. Front. Psychol. 12:731591. doi: 10.3389/fpsyg.2021.731591 Gross, M. U. M. (2009). Highly gifted children and adolescents. In J. A. Plucker &amp; C. M. Callahan (Eds.), Critical issues and practices in gifted education: What the research says (pp. 241– 251). Prufrock Press Inc. Nissen, P. (2019). Detecting talent from the perspectives of students, parents, and teachers. US-China Education Review B, 9(4), 119-127. https://doi.org/10.17265/2161- 6248/2019.04.001 Skolinspektionen (2022). Stimulerande undervisning för elever som ligger långt fram i sin kunskapsutveckling. https://www.skolinspektionen.se/beslut-rapporterstatistik/publikationer/kvalitetsgranskning/2022/stimulerandeundervisnin

Molecular studies of acute myeloid leukemia and the telomerase reverse transcriptase gene

Multiple chromosome rearrangements (MCRs) are detected in approximately 10% of patients with acute myeloid leukemia (AML), and are associated with an adverse prognosis. Comprehensive analysis of the chromosome rearrangements in these complex karyotypes has previously been hampered by the limitations of conventional cytogenetic techniques such as G-banding. As a consequence, our knowledge concerning the genetic alterations in these malignancies is limited. We applied spectral karyotyping (SKY), comparative genomic hybridization (CGH) and cDNA microarrays to bone marrow cells from AML patients with MCRs in order to characterize these rearrangements on the genomic and transcriptional level. Using SKY and CGH we resolved 12 complex AML karyotypes, and also detected novel chromosome rearrangements. We showed that many of the deletions scored by G-banding harboured cryptic chromosome rearrangements. Ile majority were unbalanced translocations and most frequently resulted in chromosome loss of 5q, 7q and 17p, and chromosome gain of 11q. In addition, the SKY analysis revealed a number of balanced translocations that had not been described before. Some seem recurrent and may reflect novel fusion genes directly involved in leukemogenesis. (Paper I) The chimeric transcripts of one reciprocal translocation detected by SKY, a t(8;16)(p11;p13);(MOZCBP), was analyzed at the sequence level using RT-PCR. The resulting RT-PCR method could be diagnostically useful, since the detection of t(8;16) in AML has clinical ramifications and may be difficult to identify by chromosome banding alone. (Paper II) In order to investigate the transcriptional profiles of leukemic cells with MCRs we also developed and applied a high-density cDNA microarray assay. We showed that most of the chromosome rearrangements were manifested in aberrant gene expression profiles in a gene-dosage dependent manner. (Paper III) We also investigated the role of hTERT/telomerase in turnorigenesis and disease. Telomeres, which constitute the ends of chromosomes and are essential for genomic stability and integrity, are synthesized by a ribonucleoprotein reverse transcriptase called telomerase. Telomerase consists of an RNA template, a reverse transcriptase (hTERT) and telomerase associated proteins. Because hTERT/telomerase activation is critical for cellular immortalization and tumorigenesis we investigated the copy numbers of hTERT in human tumors and found that hTERT is a frequent target for DNA amplification. (Paper IV) Chri-du-Chat syndrome (CdCs) is one of the most common human deletion syndromes and results from a deletion of the distal part of chromosome arm 5p, where the hTERT gene is located. We showed that a heterozygous loss of hTERT is present in CdCs and that hTERT is limiting for telomere maintenance in humans. Therefore, CdCs might be used as a model to study hTERT regulation and telomerase biology in humans. (Paper V) Certain somatic cells can acquire an immortal phenotype by forced expression of hTERT/telomerase. Treatment with exogenous hTERT has been proposed as a cell-based therapy to allow indefinite expansion of normal human cells without damaging their genomes. However, using cDNA microarrays we showed that the gene expression profile of hTERT-immortalized fibroblasts (hTERT-BJ cells) is significantly different from that of normal mortal fibroblasts. One of the highly expressed genes in the hTERT-BJ cells encodes epiregulin and we found its expression was required to maintain the immortal phenotype. Given the significant difference in gene expression profiles between the normal and hTERTimmortalized fibroblasts and the dose relationship between epiregulin and turnorigenesis, we concluded that the use of hTERT for expansion of normal human cells for therapeutic purposes must be approached with great caution. (Paper VI

I Mend It With Sugar

I mend it with sugar         Abstract   "Gluttony" and "sloth" is the sugar addictions best friend, or could it be that the addiction comes out of a disturbed hormone production caused by the environment that surrounds us? Trying to understand my own sugar addiction I weave in my personal story into my artistic research around this subject. The sugar might be the cause of the pandemic obesity and that's why it has to bee brought up into the light from its darkness down the basement of the food giants that roles over the world economy.   There might be no answer yet to the questions I ask myself but it is time that we all do what it takes to get closer to the answers, by questioning the nature of the food that we stuff our self full of, we all have a part of it, or do we? Have our brain already been kidnapped by the white gold that we're no longer capable to think clear?   This is a subject that suits very well to be highlighted through body related art, such as jewellery and corpus. We use our body when we eat, our feelings is coming from the inside of our body, by looking at our body and how it acts we can easily see the signs of how we really feel it's just that we forgot to look, we forgot to listen to our body, maybe it's the sugar that has numb our bodies…  

School development with a cognitive focus : successes and challenges in meeting students' differences and similarities

The purpose of the study is to acquire knowledge and understanding of successful school development, with a focus on students' cognitive abilities. The survey focuses on the implementation of development work and its effects on the organization and students' development. The theoretical framework is based on special educational perspectives, salutogenic perspective and organizational theory. Two contiguous preschool class‑third grade schools are included in the study and primary data consists of interview responses from school staff. The study also includes questionnaire responses from guardians of children in third grade. However, the response rate from the guardians is insufficient for conclusions. The results show that school development changed the view of students' differences and needs. Furthermore, the schools have shifted their focus to group and organizational level, as well as to more promotional and preventive work. Fewer students are included in the student health team and the number of action plans has decreased. The development of the schools is characterized by a shift towards a more critical perspective and has been conducted through strengthened meaningfulness in the form of defined values, consensus in purpose and vision and collegial cooperation. The conditions that enable successful school development are characterized by a strong sense of coherence, in both leadership and conditions. Increased focus on the environment, as well as enhancement of comprehensibility, manageability and meaningfulness, are also factors that have benefited students' development. Factors that hinder school development can be traced to a compensatory and dilemma perspective, as well as to a lack of sense of coherence. Above all concerning attitudes among school staff and external demands placed on the school activities. Our conclusion is that both school development and students' cognitive abilities can be promoted through the application of a salutogenic perspective