bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia
Authors: Sonnet Miriam , Claus Rainer , Becker Natalia , Zucknick Manuela , Petersen Jana , Lipka Daniel B , Oakes Christopher C , Andrulis Mindaugas , Lier Amelie , Milsom Michael D , Witte Tania , Gu Lei , Kim-Wanner Soo-Zin , Schirmacher Peter , Wulfert Michael , Gattermann Norbert , Lübbert Michael , Rosenbauer Frank , Rehli Michael , Bullinger Lars , Weichenhan Dieter , Plass Christoph 
Published: April 2014

Abstract
Background
Aberrant DNA methylation is frequently found in human malignancies including acute myeloid leukemia (AML). While most studies focus on later disease stages, the onset of aberrant DNA methylation events and their dynamics during leukemic progression are largely unknown.

Methods
We screened genome-wide for aberrant CpG island methylation in three disease stages of a murine AML model that is driven by hypomorphic expression of the hematopoietic transcription factor PU.1. DNA methylation levels of selected genes were correlated with methylation levels of CD34+ cells and lineage negative, CD127-, c-Kit+, Sca-1+ cells; common myeloid progenitors; granulocyte-macrophage progenitors; and megakaryocyte-erythroid progenitors.

Results
We identified 1,184 hypermethylated array probes covering 762 associated genes in the preleukemic stage. During disease progression, the number of hypermethylated genes increased to 5,465 in the late leukemic disease stage. Using publicly available data, we found a significant enrichment of PU.1 binding sites in the preleukemic hypermethylated genes, suggesting that shortage of PU.1 makes PU.1 binding sites in the DNA accessible for aberrant methylation. Many known AML associated genes such as RUNX1 and HIC1 were found among the preleukemic hypermethylated genes. Nine novel hypermethylated genes, FZD5, FZD8, PRDM16, ROBO3, CXCL14, BCOR, ITPKA, HES6 and TAL1, the latter four being potential PU.1 targets, were confirmed to be hypermethylated in human normal karyotype AML patients, underscoring the relevance of the mouse model for human AML.

Conclusions
Our study identified early aberrantly methylated genes as potential contributors to onset and progression of AML.
SMCHD1 accumulates at DNA damage sites and facilitates the repair of DNA double-strand breaks
Authors: Coker Heather , Brockdorff Neil 
Published: April 2014

ABSTRACT
SMCHD1 is a structural maintenance of chromosomes (SMC) family protein involved in epigenetic gene silencing and chromosome organisation on the female inactive X chromosome and at a limited number of autosomal loci. Here, we demonstrate that SMCHD1 also has a role in DNA repair of double-strand breaks; SMCHD1 is recruited to sites of laser micro-irradiated damage along with other DNA repair factors, including Ku80 (also known as XRCC5 in mammals) and RAD51. Cells deficient in SMCHD1 show evidence of decreased efficiency of repair and cell viability after DNA damage. We suggest that SMCHD1 responds to DNA double-strand breaks in a manner that is likely to involve its ability to alter chromatin states to facilitate DNA repair.
Distinct c-Met activation mechanisms induce cell rounding or invasion through pathways involving integrins, RhoA and HIP1
Authors: Mai Anja , Muharram Ghaffar , Barrow-McGee Rachel , Baghirov Habib , Rantala Juha , Kermorgant Stéphanie , Ivaska Johanna 
Published: April 2014

ABSTRACT
Many carcinomas have acquired oncogenic mechanisms for activating c-Met, including c-Met overexpression and excessive autocrine or paracrine stimulation with hepatocyte growth factor (HGF). However, the biological outcome of c-Met activation through these distinct modes remains ambiguous. Here, we report that HGF-mediated c-Met stimulation triggers a mesenchymal-type collective cell invasion. By contrast, the overexpression of c-Met promotes cell rounding. Moreover, in a high-throughput siRNA screen that was performed using a library of siRNAs against putative regulators of integrin activity, we identified RhoA and the clathrin-adapter protein HIP1 as crucial c-Met effectors in these morphological changes. Transient RhoA activation was necessary for the HGF-induced invasion, whereas sustained RhoA activity regulated c-Met-induced cell rounding. In addition, c-Met-induced cell rounding correlated with the phosphorylation of filamin A and the downregulation of active cell-surface integrins. By contrast, a HIP1-mediated increase in β1-integrin turnover was required for the invasion triggered by HGF. Taken together, our results indicate that c-Met induces distinct cell morphology alterations depending on the stimulus that activates c-Met.
Teaching practices and text comprehension in students during the transition from the first to second stage of school
Authors: Uibu Krista , Männamaa Mairi 
Published: April 2014

Tekstimõistmine on seotud verbaalse võimekusega, info kodeerimise ja integreerimisega ning sõnatähenduse tundmisega. Õpetajad kasutavad erinevaid õpetamistegevusi, et toetada õpilaste keelelist, sh tekstimõistmise arengut. Uurimuse eesmärk oli välja selgitada õpetajate õpetamistegevuste (mehaanilise õpetamise, arusaamise arendamise, teadmiste rakendamise) mõju õpilaste tekstimõistmisele üleminekul esimesest kooliastmest teise astmesse. Töös hinnati klassiõpetajate (N = 48) õpetamistegevusi ja nende muutust 3. ja 4. klassis ning õpetamistegevuste seoseid õpilaste (N = 609) tekstimõistmise ja verbaalse võimekuse muutusega 4. ja 5. klassis. Analüüsimisel kasutati nii rühma- kui ka indiviidikeskseid meetodeid. Õpetamistegevuste eelistuste alusel eristusid õpetajate profiilirühmad ning tekstimõistmise komponentide ja verbaalse võimekuse alusel õpilaste rühmad. Selgus, et tekstimõistmise testi tulemused olid stabiilselt halvemad õpilastel, kes olid verbaalselt vähem võimekad ja kelle õpetajad eelistasid kõiki õpetamistegevusi vähe. Samas esines sarnaseid õpetamistegevuste kombinatsioone erinevates õpilaste profiilirühmades. Arendamaks õpilaste tekstimõistmisoskust, on oluline, et õpetajad arvestaksid õpilaste verbaalse võimekusega ja kasutaksid õpetamistegevusi kooskõlas laste keelelise arenguga.
Summary
Pupil well-being and the development of word meaning structure: Differences in school satisfaction resilience in the context of class teacher parenting style and school-related adverse experiences
Authors: Ots Aivar 
Published: April 2014

Artiklis käsitletakse seoseid õpilaste kognitiivse arengu ja koolis kogetava heaolu vahel, tuginedes kolmanda kuni viienda klassi õpilastega (N = 495) tehtud pikiuuringule, millega selgitati koolilaste psühholoogilise resilientsuse seoseid mõistestruktuuri arenguga. Resilientsus tähendab psüühilist toimetulekut stressi ja üleelatud õnnetustega viisil, millega säilitatakse või taastatakse enda heaolu ja tegevusvõime (vt Rutter, 2006; Shiner & Masten, 2012). Resilientsuse avaldumisena käsitleti uurimuses kooliga rahulolu säilitamist kõrge ebameeldivate tundeelamuste taseme korral. Selliste tundeelamuste taseme määramisel lähtuti asjaomaste kogemuste subjektiivsetest kirjeldustest. Lisaks selgitati õpilaste heaolu ja resilientsuse seoseid klassiõpetaja kasvatusstiiliga. Oletati, et arenguliselt hilisema mõistestruktuuri kasutamine (Toomela, 2003a; Võgotski, 1934/1999) võiks soodustada õpilasel suurema resilientsuse esinemist. Tulemused on oletusega kooskõlas, näidates, et kolme aasta vältel arenguliselt hilisemat mõistestruktuuri kasutanud õpilased säilitasid kõrgema negatiivsete elamuste taseme puhul sagedamini kooliga rahulolu. Samuti leiti, et klassiõpetaja hoolivust väljendavad ja toetavad tegevused soodustavad õpilaste sagedasemat rahulolu kooliga ning psühholoogilist ja käitumuslikku kontrolli taotlevad tegevused sagedasemat rahulolematust. Statistilise andmetöötluse jaoks kasutati konfiguratsioonilisi sagedusanalüüse (von Eye, 1990).
Summary
No deed goes unnoticed? Associations between teachers’ noticing academic procrastination and individual differences in students
Authors: Aus Kati , Arro Grete , Jõgi Anna-Liisa , Malleus Elina 
Published: April 2014

Algkoolist põhikooli liikudes muutub õpitav keerulisemaks ja abstraktsemaks. Õpilaste eneseregulatsioonioskus ja selle arengu toetamine on seetõttu vaieldamatult olulised. Üks teadaolev eneseregulatsiooniprobleem on õpikohustuste täitmise edasilükkamine ehk akadeemiline prokrastineerimine. Prokrastineerimiskäitumine võib välja kujuneda juba põhikoolis, kuid jääda õpetajatele seejuures märkamata. Siinses uurimuses võrdlesime 8. klasside õpilaste (N = 551) hinnanguid oma prokrastineerimiskäitumisele kolme aineõpetaja (N = 118) hinnangutega. Leidsime, et õpilaste ja õpetajate hinnangud ei lange alati kokku ning õpetajad näevad prokrastineerijatena pigem vähem võimekaid õpilasi, olenemata sellest, kas õpilane ise peab end prokrastineerijaks või mitte. Samuti tõid õpetajad prokrastineerijatena esile pigem keskmisest ekstravertsemaid lapsi. Et uurida, kas õpetaja vaatevälja jäämiseks on olulisemad pigem õpilaste isiksuseomadused või vaimne võimekus, pöörasime eraldi tähelepanu neile õpilastele, kes on endi sõnul sagedased prokrastineerijad. Leidsime, et mida võimekam on õpilane olnud juba algklassides ning mida introvertsem 7. klassis, seda väiksem on tõenäosus, et õpetajad tema prokrastineerimiskalduvust 8. klassis märkavad. Tulemused lubavad järeldada, et õpetajatel on raske tuvastada võimekamate ja introvertsemate õpilaste eneseregulatsiooniprobleeme. Õpetajad peaksid peale ainealaste õpitulemuste hindamise pöörama kindlasti tähelepanu ka õpilaste õpioskuste süstemaatilisele hindamisele.
Summary
Acetabular changes associated with avascular necrosis of the femoral head in a piglet model
Authors: Shapiro F. , Connolly S. , Zurakowski D. , Flynn E. , Jaramillo D. 
Published: April 2014

Objectives An experimental piglet model induces avascular necrosis (AVN) and deformation of the femoral head but its secondary effects on the developing acetabulum have not been studied. The aim of this study was to assess the development of secondary acetabular deformation following femoral head ischemia. Methods Intracapsular circumferential ligation at the base of the femoral neck and sectioning of the ligamentum teres were performed in three week old piglets. MRI was then used for qualitative and quantitative studies of the acetabula in operated and non-operated hips in eight piglets from 48 hours to eight weeks post-surgery. Specimen photographs and histological sections of the acetabula were done at the end of the study. Results The operated-side acetabula were wider, shallower and misshapen, with flattened labral edges. At eight weeks, increased acetabular cartilage thickness characterised the operated sides compared with non-operated sides (p < 0.001, ANOVA). The mean acetabular width on the operated side was increased (p = 0.015) while acetabular depth was decreased anteriorly (p = 0.007) and posteriorly (p = 0.44). The cartilage was thicker, with delayed acetabular bone formation, and showed increased vascularisation with fibrosis laterally and focal degenerative changes involving chondrocyte hypocellularity, chondrocyte cloning, peripheral pannus formation and surface fibrillation. Conclusions We demonstrate that femoral head AVN in the young growing piglet also induced, and was coupled with, secondary malformation in acetabular shape affecting both articular and adjacent pelvic cartilage structure, and acetabular bone. The femoral head model inducing AVN can also be applied to studies of acetabular maldevelopment, which is less well understood in terms of developing hip malformation. Cite this article: Bone Joint Res 2014;3:130–8.
Histopathological Pattern of Salivary Gland Tumors
Authors: Shrestha S , Pandey GK , Pun CB , Bhatta R , Shahi R 
Published: April 2014

Background: The tumors of the salivary glands are uncommon head and neck neoplasms. The aim of this study was to evaluate the relative frequencies, types, site distribution and the histopathological features of salivary gland tumors. Materials and Methods: This was a retrospective study of 176 cases of salivary gland tumors collected from medical record section and department of pathology at B.P.Koirala Memorial Cancer Hospital from Jan. 2005 to Dec. 2010. Tumors were analyzed based on demographics, anatomic location and histopathological type. Results: Out of 176 cases, 66 (37.5 %) were benign and 110 (62.5 %) were malignant with M:F ratio of 1.7:1. The mean age observed was 44.76 years with age range of 12 to 75 years. Pleomorphic adenoma was found to be the commonest benign tumor (72.7 %), followed by Warthin tumor (15.1%), monomorphic adenoma (3.0 %) and basal cell adenoma (3.0 %). The mucoepidermoid carcinoma was the most common malignant tumor (38.1 %), followed by adenoid cystic carcinoma (25.4%), acinic cell carcinoma (10.9%), adenocarcinoma NOS (6.3%), carcinoma ex pleomorphic adenoma (5.4%) and unclassified malignant tumor (4.5 %). Parotid was the most common site for the location of tumors (70.4%) followed by submandibular (19.3%) and minor salivary glands (10.2 %). Conclusion: Pleomorphic adenoma was the commonest salivary gland tumor observed in both sexes. Mucoepidermoid carcinoma was the most common malignant salivary gland tumor. The parotid gland was the most common site of origin in both benign and malignant tumors. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10291 Journal of Pathology of Nepal (2014) Vol. 4, 520-524
Influence of donor demographics on the platelet yield during plateletpheresis - experience of 1100 procedures at a tertiary-care hospital
Authors: Mangwana S 
Published: April 2014

Background: Transfusion of plateletpheresis is effective for treating patients with platelet relatedinsufficiencies while limiting recipient’sexposure to platelets from multiple donors. A larger yield isobtained when donor has a greater number of initial platelets and separation done in a shorter time. Theaim of the study was to analyze the effect of various donors and procedure related parameters on the yieldof single donor platelet so that blood donors can be screened effectively in less time.Materials and Methods: One thousand and one hundred plateletpheresis procedures were performed ina tertiary-care super-specialty hospital onFenwal AMICUS machine using closed system kits. Statisticalanalysis was done to establish cause and effect relationship and to find the extent of relationship betweendifferent variables.Results: Height, weight,BMI, platelet count and total leucocyte count had significant correlation withplatelet yield, processing time and blood volume processed while haemoglobin especially in femalescorrelated significantlywith processing time(p<0.0001)and blood volume processed. Rh “negative”donors had shorter processing time than Rh “positive” donors while ABO group did not show anycorrelation with machine variables.Conclusion: Platelet yield correlated positively with pre-donation count, height, weight and BMI.Haemoglobin correlated with processing time and blood volume processed. Optimization of platelet yieldis an emerging issue to identify factors which may help in selecting donors to obtain higher platelet yieldsin shorter time and consequently better clinical outcome.DOI: http://dx.doi.org/10.3126/jpn.v4i7.10292 Journal of Pathology of Nepal (2014) Vol. 4, 525-529
Clinicopathological features of pilomatricoma cases: Analysis of 21 cases
Authors: Ghartimagar D , Ghosh A , Gautam K , Thapa S , Shrestha SR , Narasimhan R 
Published: April 2014

Background: Pilomatricoma is a slow-growing, asymptomatic tumour originating from outer sheath cells of hair follicle. In this study, we describe the clinical presentation and histopathological features of pilomatricoma. Materials and Methods: This was a hospital based retrospective study carried out in all patients who were diagnosed as pilomatricoma over a period of January 2001 to December 2013. The study was done in department of pathology, Manipal Teaching Hospital, Nepal. Results: A total of 21 cases of pilomatricoma were reported with age range of 9-53 years (mean age 23.7) and male female ratio of 1:1.1. The most common site of occurrence was neck and preauricular region. The size of the tumour ranged from 0.3 to 4.7cm with a mean of 1.2cm. Multiple occurrences were seen in 3 patients and ossifying pilomarticoma was seen in 4 cases. Conclusion: Pilomatricoma is a benign skin neoplasm of hair follicle matrix cells. Calcification is a common finding while dystrophic ossification also can occur in the tumour. Histopathology gives the definite diagnosis as fine needle aspiration cytology and clinical impression may be misleading. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10293 Journal of Pathology of Nepal (2014) Vol. 4, 530-533
Spectrum of ovarian tumors in a referral hospital in Nepal
Authors: Vaidya S , Sharma P , KC S , Vaidya SA 
Published: April 2014

Background: Ovarian tumors are common forms of neoplasia in women. Among cancers of the female genital tract, it ranks only below carcinoma of the cervix and the endometrium, but is responsible for approximately 50% of the deaths. They arise from different cell lineages and hence constitute a wide variety of neoplastic entities with diverse morphological and clinical manifestations. Materials and Methods: A descriptive study of 363 cases of ovarian tumors was carried out during a three year period from January 2011 to December 2013. Results: Of the 363 ovarian tumors, 293 (80.72%) cases were benign, 57 (15.70%) were malignant and 13 (3.58%) were borderline. Germ cell tumour was the most common class of tumour and seen in 187 (51.52%) cases, followed by surface epithelial in 158 (43.53%) cases. The age distribution of the patients ranged from 10-82 years with a median age of 33 years. Benign tumors were more common than malignant ones in all age groups. Conclusion: Most of the ovarian tumors in this study were of germ cell origin. The incidence of malignant germ cell tumors was also significantly higher than in other studies. Mature cystic teratoma was the most common benign tumour while serous carcinoma was the most common malignancy. The incidence of malignant germ cell tumors was higher compared to other studies. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10295 Journal of Pathology of Nepal (2014) Vol. 4, 539-543
Automated urinalysis: First experiences and comparison of automated urinalysis system and manual microscopy
Authors: Gautam K , Pyakurel D 
Published: April 2014

Background: Urinary tract infection is a common condition which needs laboratory evaluation of urine to substantiate the clinical diagnosis and initiate treatment. The conventional urinalysis consists of using a test strip for chemical examination to identify the various urine sediments after which visual microscopy is done. We evaluate the analytical performance of automated microscopic technique (UF 500i) and compare results with those from manual microscopy. Materials and Methods: A total of 382 urine specimens were collected during a period of one month out of which 128 samples which had abnormal cell counts were analyzed for cells and particles by manual and automated microscopy by UF-500i flow cytometer. Results: The concordance of UF 500i and the manual microscopy which is considered to be the gold standard for urine microscopic examination was 90.6% for white blood cells, red blood cell, epithelial cells, cast and bacterial count. Conclusion: Automated urine sediment analyzer, UF 500i was considered reliable in the measurement of white blood cells, red blood cells, epithelial cells, cast and bacteria. Automation will surely reduce the work load, increase accuracy and reliability, and increase the throughput and turn-around time of the laboratory DOI: http://dx.doi.org/10.3126/jpn.v4i7.10316 Journal of Pathology of Nepal (2014) Vol. 4, 576-579
The molecular pathology of thyroid neoplasms
Authors: Thapa JB 
Published: April 2014

The Bethesda system of reporting thyroid cytology is being currently adopted worldwide. Rapid advances have been made in the understanding of the genetics of thyroid cancers. Common genetic mutations include RAS, BRAF, p53, B Catenin, and PAX8/PPARγ, genes. BRAF mutations tumours are often aggressive. BRAF mutations commonly affect papillary carcinomas in the BRAF MEK ERF intracellular pathway, whereas RAS mutations commonly affect follicular carcinoma in the PL3 kinase pathway. TK inhibitors, RAS, RET, non RET, PL3, HDAC, DNMT etc. inhibitors are also being considered for therapy against these tumours. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10317 Journal of Pathology of Nepal (2014) Vol. 4, 580-583
Invasive lobular carcinoma co-existing with benign phylloides tumor
Authors: Shrestha S , Sigdel B , Pande K , Gurung B 
Published: April 2014

Phylloides tumor constitutes less than 1% of all breast tumors and 2 - 3% of fibroepithelial breast tumors. Several histological parameters should be evaluated, including stromal cellularity, atypia, mitoses, stromal overgrowth, infiltrative borders, and presence or absence of necrosis. Here we report a case of a 60 years- old female who presented with left breast lump. Fine needle aspiration cytology was done which suggested epithelial hyperplasia with fibrocystic changes. Biopsy was performed which showed predominance of stromal hypercellularity with proliferation of spindle cells (no atypia, mitosis and stromal overgrowth were noticed). However, a focus showed proliferation of discohesive tumor cells arranged singly and in single file. A diagnosis of benign phylloides tumor with foci of invasive lobular carcinoma was made. The diagnosis was confirmed with IHC which showed intense 80%positivity for estrogen and progesterone receptor and spindle cells showing positivity for bcl-2. In situ lobular carcinoma component was not observed. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10321 Journal of Pathology of Nepal (2014) Vol. 4, 597-599
Primary pure squamous cell carcinoma of breast in a young female - a rare occurrence
Authors: Raje P , Bhandari S , Gujrati R 
Published: April 2014

Primary squamous cell carcinoma of breast is a rare disease. Incidence for primary SCC breast is 0.04-0.1 % of all malignancies of breast. A pure form of primary SCC breast is also described and its incidence is still less. Biologically it behaves differently and usually doesn’t metastasize to lymph nodes, though distant metastasis is more common. They occur usually in elderly women. Mean age of presentation is 54 years. We report the youngest patient so far - a 27 years old woman diagnosed initially as having fibrocystic disease and later as primary pure SCC breast. She did not have any other focus of malignancy in the body and is doing well 3-1/2 years post surgery and radiotherapy. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10322 Journal of Pathology of Nepal (2014) Vol. 4, 600-602