Miracle-dz/UniFAR-FTUs huggingface dataset:
La pharmacogénétique : application aux anticoagulants oraux

Au cours des traitements anticoagulants oraux par les antivitamines K (AVK), de grandes variations dans la reponse sont observees. Il s‘agit soit de reactions exagerees avec un risque hemorragique majeur (les accidents hemorragiques lies au AVK constituent la premiere cause d‘hospitalisations liees a des accidents iatrogenes), soit de resistances necessitant des posologies elevees. Des facteurs genetiques lies au metabolisme expliquent en partie ces differences interindividuelles dans la reponse. Le metabolisme des AVK est principalement hepatique et le cytochrome P450 2C9 (CYP2C9) est l‘enzyme majoritairement responsable de leur elimination, en particulier pour les derives coumariniques (warfarine ou Coumadine ®, acenocoumarol ou Sintrom ®). L‘activite du CYP2C9 peut varier sous l‘influence de facteurs environnementaux (alimentation, medicaments), physiopathologiques ou genetiques (polymorphismes genetiques). Dans les populations caucasiennes, il existe deux principaux alleles variants (CYP2C9*2 et CYP2C9*3) qui sont a l‘origine d‘une baisse de l‘activite enzymatique. De nombreuses etudes cliniques ont maintenant etabli que les sujets porteurs de ces alleles variants necessitaient des doses moyennes plus faibles de warfarine ou d‘acenocoumarol, plus particulierement chez les porteurs de l‘allele CYP2C9*3. De plus, la presence de l‘allele CYP2C9*3 a ete associee a une augmentation du risque hemorragique. Les bases moleculaires de la resistance aux AVK restent a etablir, mais une augmentation du metabolisme liee a une activite elevee du CYP2C9 ou des variations de la cible pharmacologique des AVK sont possibles. Le genotypage des sujets pour le CYP2C9 avant l‘initiation d‘un traitement par AVK devrait permettre une amelioration de la prise en charge therapeutique et une meilleure prediction du risque hemorragique.
Macroscopic Single‐Walled‐Carbon‐Nanotube Fiber Self‐Assembled by Dip‐Coating Method

Pure macroscopic single-walled-carbon-nanotube (SWNT) fibers are fabricated by using a dip-coating method without any additive or additional electrical equipment or complex apparatus. The present method only utilizes microfluidics, which includes capillary condensation, capillary flow, and surface tension, and results in the self-assembly and self-alignment of SWNT colloids.
Integration of Problem Based Learning with Conventional Teaching for Understanding Anatomy among First Year Medical Students.

ABSTRACT The objective of learning anatomy is its application in patient care and it may be prudent to consider that problem based learning early in medical curriculum. Time tested learning anatomy by dissecting cadaver and small group discussions apart from regular class room lectures cannot be disgraced. This study was done to evaluate the effectiveness of integrated the problem based learning approach with conventional teaching for first year medical students. This study also emphasises the objective evaluation method of assessing the learning process in small groups. Twelve problem based learning sessions were conducted along with conventional learning process involving class room lectures, small group discussions and cadaver dissection in groups of twenty five students. Groups were rotated after each test so that each group gets differential training process for three times. Learning process was assessed objectively through multiple choice and assertion – reasoning type questions. Results showed that students’ performance after learning process involving integrated problem based learning with conventional learning methods was superior to other methods.
Identification of candidate cooperative genes of the Apc mutation in transformation of the colon epithelial cell by retroviral insertional mutagenesis

The mutation of Apc is an important early genetic event in colon carcinogenesis. However, it remains to be clarified what kinds of cooperative genes are required for complete carcinogenesis. To identify cooperative genes for the ApcMin mutation the authors carried out retroviral insertional mutagenesis (RIM) using Min mouse‐derived IMCE colon epithelial cells. Anchorage‐independent transformed colonies were induced by retroviral infection only in IMCE cells, while no transformation was found in young adult mouse colon (YAMC) cells that are normal for Apc. One hundred and fifty‐seven retroviral integration sites (RIS) were identified in 101 independent transformants, and four common integration sites (CIS), Dnah3, Ahnak, Stk17b and Rbm9, were observed. Upregulation of Dnah3 and Ahnak, and truncation of Dnah3 due to the viral integration, was revealed. In addition, Dnah3‐overexpressing IMCE cells showed impairment of microtubule function. These data suggest the importance of cytoskeletal function in Apc‐related tumor development and the usefulness of RIM in non‐hematopoietic tissues, providing new insight into the early stage of colon carcinogenesis. (Cancer Sci 2008; 99: 979–985)
A combinatorial approach to the repertoire of RNA kissing motifs; towards multiplex detection by switching hairpin aptamers

Loop–loop (also known as kissing) interactions between RNA hairpins are involved in several mechanisms in both prokaryotes and eukaryotes such as the regulation of the plasmid copy number or the dimerization of retroviral genomes. The stability of kissing complexes relies on loop parameters (base composition, sequence and size) and base combination at the loop–loop helix - stem junctions. In order to identify kissing partners that could be used as regulatory elements or building blocks of RNA scaffolds, we analysed a pool of 5.2 × 106 RNA hairpins with randomized loops. We identified more than 50 pairs of kissing RNA hairpins. Two kissing motifs, 5′CCNY and 5′RYRY, generate highly stable complexes with KDs in the low nanomolar range. Such motifs were introduced in the apical loop of hairpin aptamers that switch between unfolded and folded state upon binding to their cognate target molecule, hence their name aptaswitch. The aptaswitch–ligand complex is specifically recognized by a second RNA hairpin named aptakiss through loop–loop interaction. Taking advantage of our kissing motif repertoire we engineered aptaswitch–aptakiss modules for purine derivatives, namely adenosine, GTP and theophylline and demonstrated that these molecules can be specifically and simultaneously detected by surface plasmon resonance or by fluorescence anisotropy.
Molecules on Si: Electronics with Chemistry

Basic scientific interest in using a semiconducting electrode in molecule‐based electronics arises from the rich electrostatic landscape presented by semiconductor interfaces. Technological interest rests on the promise that combining existing semiconductor (primarily Si) electronics with (mostly organic) molecules will result in a whole that is larger than the sum of its parts. Such a hybrid approach appears presently particularly relevant for sensors and photovoltaics. Semiconductors, especially Si, present an important experimental test‐bed for assessing electronic transport behavior of molecules, because they allow varying the critical interface energetics without, to a first approximation, altering the interfacial chemistry. To investigate semiconductor‐molecule electronics we need reproducible, high‐yield preparations of samples that allow reliable and reproducible data collection. Only in that way can we explore how the molecule/electrode interfaces affect or even dictate charge transport, which may then provide a basis for models with predictive power.
The DBHS proteins SFPQ, NONO and PSPC1: a multipurpose molecular scaffold

Nuclear proteins are often given a concise title that captures their function, such as ‘transcription factor,’ ‘polymerase’ or ‘nuclear-receptor. ’ However, for members of the Drosophila behavior/human splicing (DBHS) protein family, no such clean-cut title exists. DBHS proteins are frequently identified engaging in almost every step of gene regulation, including but not limited to, transcriptional regulation, RNA processing and transport, and DNA repair. Herein, we present a coherent picture of DBHS proteins, integrating recent structural insights on dimerization, nucleic acid binding modalities and oligomerization propensity with biological function. The emerging paradigm describes a family of dynamic proteins mediating a wide range of protein–protein and protein–nucleic acid interactions, on the whole acting as a multipurpose molecular scaffold. Overall, significant steps toward appreciating the role of DBHS proteins have been made, but we are only beginning to understand the complexity and broader importance of this family in cellular biology.
Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms

Abstract Acetylcholinesterase (AChE), encoded by the ACHE gene, hydrolyzes the neurotransmitter acetylcholine to terminate synaptic transmission. Alternative splicing close to the 3΄ end generates three distinct isoforms of AChET, AChEH and AChER. We found that hnRNP H binds to two specific G-runs in exon 5a of human ACHE and activates the distal alternative 3΄ splice site (ss) between exons 5a and 5b to generate AChET. Specific effect of hnRNP H was corroborated by siRNA-mediated knockdown and artificial tethering of hnRNP H. Furthermore, hnRNP H competes for binding of CstF64 to the overlapping binding sites in exon 5a, and suppresses the selection of a cryptic polyadenylation site (PAS), which additionally ensures transcription of the distal 3΄ ss required for the generation of AChET. Expression levels of hnRNP H were positively correlated with the proportions of the AChET isoform in three different cell lines. HnRNP H thus critically generates AChET by enhancing the distal 3΄ ss and by suppressing the cryptic PAS. Global analysis of CLIP-seq and RNA-seq also revealed that hnRNP H competitively regulates alternative 3΄ ss and alternative PAS in other genes. We propose that hnRNP H is an essential factor that competitively regulates alternative splicing and alternative polyadenylation.
EPIDEMIOLOGY OF PREMENSTRUAL SYNDROME (PMS) IN STUDENTS OF MASHHAD UNIVERSITY OF MEDICAL SCIENCES

Introduction:Since premenstrual syndrome (PMS) is a frequent disorder of women that interferes in their functions and different frequencies of PMS have been reported in literature and higher rates of it in college students, we decided to study its epidemiology in students of Mashhad University of Medical Sciences (MUMS). Methods and Material: In this descriptive study, 210 female students of MUMS filled the demographic (including age, marriage status and level and field of study) and PMS questionnaire . The results were analyzed by chi square and independent T test. Result: One hundred and one students fulfilled the criteria of PMS (48.1). Mean age of participants was 22.45 years. PMS were seen in 47.9 of singles and 48.8 of married students. The highest and lowest rates of PMS were seen in associate and bachelor students, respectively (66.7 and 41.4). Also PMS was seen in laboratory sciences students most frequently. (66.9) and 54.9 of medical students fulfilled the PMS criteria. The most frequent reported symptoms of PMS were “significant anxiety and tension” (45.7). Sex, marital status and level of study were not correlated to symptoms of PMS significantly (P>0.05) but there were statistically significant differences of rates of PMS in different fields of study (P=0.006). Conclusion: PMS is prevalent among MUMS students. Lack of a national questionnaire seems to cause reports of different prevalence’s of PMS in Iran.
Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

In the present paper, recent advances in the molecular pathology of soft tissue sarcomas (STS) and the implications for their prognostic value are reviewed, and the potential targets of molecular therapy are discussed. According to the molecular genetic aspect, STS are divided into two groups: chromosome translocation‐associated sarcomas and sarcomas without specific translocation. In the former group, specific fusion transcripts, such as SS18–SSX, EWS–FLI1, and PAX3–FKHR, could be detected in synovial sarcoma, Ewing's sarcoma and primitive neuroectodermal tumor, and alveolar rhabdomyosarcoma, respectively. The direct or indirect interactions between these fusion transcripts and cell cycle regulators have been elucidated by several investigators. Therefore, these fusion transcripts are promising candidates as molecular targets. As evaluated in carcinomas, alterations of several tumor‐suppressor genes and adhesion molecules and overexpression of growth factors and their receptors have been extensively assessed in STS. In mixed‐type STS, epidermal growth factor receptor overexpression was associated with decreased overall survival, suggesting the beneficial role of epidermal growth factor receptor inhibitors in STS. In malignant rhabdoid tumor and epithelioid sarcoma, frequent alteration of the SMARCB1/INI1tumor‐suppressor gene and the loss of its protein have been demonstrated, indicating that this molecule could be an effective target of these sarcomas. In sarcomas with epithelioid differentiation, such as synovial sarcoma and epithelioid sarcoma, overexpression of dysadherin, which downregulates E‐cadherin expression, was a poor prognostic factor. In conclusion, further studies are necessary to search for effective and specific molecules for the inhibition of tumor growth in each type of STS, especially in sarcomas without specific translocation. (Cancer Sci 2009; 100: 200–208)
Clinicopathological relevance of UbcH10 in breast cancer

Abrogated mitotic progression is a common hallmark of cancer. UbcH10, one of the components of the ubiquitin/proteasome pathway, plays a pivotal role in the regulation of mitotic progression. Abnormal UbcH10 activity is reported in certain types of human cancers; its overexpression is occasionally encountered in cancerous tissue compared with adjacent normal tissue. Current studies have suggested the critical role of UbcH10 in the spindle assembly checkpoint and the subsequent accurate separation of sister chromatids, which is orchestrated by a series of molecular interactions governed by the complex and diverse cell cycle machinery. To validate the potential role of UbcH10 in cell proliferation in cancer, we have analyzed the clinicopathological relevance of UbcH10 in progression of breast cancer using a combinatorial approach of human tumor arrays and biochemical analyses. Our results show that the percentage of tested samples which stained positive for UbcH10 in breast cancer tissues is significantly higher compared to the adjacent nonmalignant tissue. Furthermore, results from the clinicopathological analysis have revealed that elevated expression of UbcH10 is associated with higher histological grade tumors. In addition, depletion of UbcH10 by RNA interference in breast cancer cells resulted in decreased cellular proliferation, while overexpression of UbcH10 significantly enhanced cellular growth in breast cancer. Our results suggest a pathological correlation between UbcH10 and cell proliferation in breast cancer. Thus, aberrant UbcH10 activity may induce the dysfunction of proper cell cycle progression and result in the aggressive behavior of tumor cells in patients with breast cancer. (Cancer Sci 2009; 100: 238–248)
Neurocognition and brain structure in pediatric patients with type 1 diabetes

Abstract Recent findings suggest that in addition to severe hypoglycemia, chronic hyperglycemia may also hamper the cognitive development of patients with type 1 diabetes. Executive and memory dysfunctions mediated by frontoparietal and temporal brain structures are frequently reported to be associated with type 1 diabetes. However, most studies investigating pediatric patients with diabetes focus on either brain function or brain structure. The current study combines neuropsychological and structural brain imaging methods (i.e., voxel-based-morphometry) to study the neurofunctional integrity of frontoparietal brain areas. We investigated 30 children with type 1 diabetes and 19 healthy controls. Children with diabetes were divided into two groups representing better (HbA1c ≤ 7.9%) and worse (HbA1c ≥ 8.0%) glycemic control. Our findings were threefold: First, results revealed significant group differences with respect to neuropsychological performance (i.e. response accuracies on a marker task tapping frontoparietal brain functions). Second, structural imaging disclosed significant group differences between patients and controls regarding gray matter volume in frontal (anterior cingulate) and occipital (cuneus, bordering precuneus) brain regions and regarding white matter in middle temporal and occipital gyri as well as in the ventromedial temporal lobe (uncus). Third, disease duration, age at diagnosis and white matter volume in a hippocampal region-of-interest (but not HbA1c levels, intelligence, total gray/white matter or other white/gray matter regions-of-interest) explained 56% of neuropsychological performance variance. Taken together, our findings are among the first to provide evidence of a direct link between brain function and brain structure in pediatric patients with type 1 diabetes.
Magnetic Liquid Marbles: Manipulation of Liquid Droplets Using Highly Hydrophobic Fe3O4 Nanoparticles

Magnetic liquid marbles exhibit a remarkable ability to be opened and closed reversibly under the action of a magnetic field. Liquid can be either extracted from or added to the opened liquid marble simply with a capillary needle. Two opened liquid marbles can also be coalesced into a larger one. The magnetic liquid marbles can be maneuvered two- and three-dimensionally.
Women’s Knowledge of Coronary Heart Disease Risk Factors and Prevention at Primary Care Level, Eastern Saudi Arabia. -

Background: Worldwide, coronary heart disease (CHD) has an increasing role as a major cause of morbidity and mortality. Women's knowledge about CHD risk factors is inadequate. Objectives: The aim of this study was to determine knowledge about coronary heart disease risk factors and preventive measures among women attending primary health care centers in Alkhobar city, Eastern Saudi Arabia. Methods: A cross-sectional study was conducted among a random sample of 700 Saudi females ages 18 years and above, selected from five primary health care centers in Alkhobar city. Knowledge about coronary heart disease risk factors and preventive measures was evaluated by an interviewer-administered questionnaire. Results: Regarding coronary heart disease risk factors, high consumption of fatty food was mentioned by 254 (36.3%) of the women, followed by smoking (249; 35.6%). Hypertension, diabetes mellitus and lack of physical exercise were mentioned by less than 30.0% of the women [202 (28.9%), 152 (21.7%) and 96 (13.7%) respectively]. Similarly the main preventive measures mentioned by women were low fat diet and smoking cessation [404 (57.7%) and 343 (49.1%) respectively]. Education, income, occupation, self-reported history of coronary heart disease and obesity were strong predictors of women’s knowledge of coronary heart disease risk factors and preventive measures (p
Efficient Organic Solar Cells Using a High‐Quality Crystalline Thin Film as a Donor Layer

An efficient organic solar cell is fabricated by the weak-epitaxy-growth method and the achieved power conversion efficiency is over 3% (see figure). A Single-crystal-like thin film improves the carrier mobility and reduces the electron hole recombination. Deposition of a zinc phthalocyanine (ZnPc):C60 mixed layer at 100 degrees C results in a better interpenetrating interface and the device performance is improved.
Chromosome segregation machinery and cancer

Loss or gain of chromosomes is associated with many cancer cells. This property, called chromosome instability, might arise from a lesion in the chromosome segregation machinery. Essential for chromosome segregation are the proper connection of microtubules to kinetochores, and the synchronous segregation of sister chromatids in anaphase. Accuracy of these processes is ensured by two sophisticated machineries called the correction mechanism and the spindle assembly checkpoint. Here we outline the current understanding of the underlying mechanisms, and highlight recent challenging experiments to address how chromosome segregation failure might relate to tumorigenesis. Understanding these mechanisms may lead to the discovery of new and improved anticancer therapies. (Cancer Sci 2009; 100: 1158–1165)
Combination of peritumoral mast cells and T‐regulatory cells predicts prognosis of hepatocellular carcinoma

The peritumoral inflammatory environment is critical for the progression of intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resections. Here, we investigated the relevance of peritumoral mast cells (MCs) to HCC outcomes. Peritumoral tryptase+ MCs in addition to Foxp3+ T‐regulatory cells (Tregs) were evaluated using immunohistochemistry enumeration in tissue microarrays containing 207 randomly selected HCC patients. Clinicopathological factors and postoperative outcomes were compared between high and low subgroups of MCs or Tregs. Compared to low denstiy, higher peritumoral MCs were associated with poorer clinical outcomes, and independently related to elevated 5‐year recurrence incidence (54.1%vs 39.2%, P = 0.026). High‐dense MCs were especially related to increased probability of early recurrence (within 2 years) (P = 0.004). We also found that peritumoral Tregs were positively correlated with MCs in density (r = 0.353, P < 0.001) and reversely related to HCC outcomes. Notably, MCs in combination with Tregs displayed better prognostic performances than MCs alone (area under curve [AUC]survival = 0.629 vs 0.589, AUCrecurrence = 0.632 vs 0.591). Moreover, MCs were positively correlated to alanine aminotransferase, a serum inflammatory marker (P = 0.014). Therefore, peritumoral MCs are promising prognostic parameters for HCC mainly through inflammation response–related mechanisms, and we propose that MCs and Tregs may cooperate with each other and result in poorer prognosis. (Cancer Sci 2009; 100: 1267–1274)
Rapid disease progression is an important cause of death in IPF

▴ Martinez FJ, Safrin S, Weycker D, et al for the IPF Study Group. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med2005;142:963–8 The authors examined data generated from the placebo arm of a large multicentre double blind trial of interferon-γ1b in patients with mild to moderate idiopathic pulmonary fibrosis (IPF), collected over a median period of 76 weeks at 12 weekly intervals. IPF was diagnosed according to the ATS criteria, by surgical lung biopsy or established HRCT criteria in 168 patients …