Miracle-dz/UniFAR-FTUs huggingface dataset:
STIL is required for centriole duplication in human cells

Centrioles are key structural elements of centrosomes and primary cilia. In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication. STIL (SCL/TAL1 interrupting locus, also known as SIL) is a centrosomal protein that is essential for mouse and zebrafish embryonic development and mutated in primary microcephaly. Here, we show that STIL localizes to the pericentriolar material surrounding parental centrioles. Its overexpression results in excess centriole formation. siRNA-mediated depletion of STIL leads to loss of centrioles and abrogates PLK4-induced centriole overduplication. Additionally, we show that STIL is necessary for SAS6 recruitment to centrioles, suggesting that it is essential for daughter centriole formation, interacts with the centromere protein CPAP and rapidly shuttles between the cytoplasm and centrioles. Consistent with the requirement of centrioles for cilia formation, Stil–/– mouse embryonic fibroblasts lack primary cilia – a phenotype that can be reverted by restoration of STIL expression. These findings demonstrate that STIL is an essential component of the centriole replication machinery in mammalian cells.
Pharmacokinetic Modeling and Development of Bayesian Estimators in Kidney Transplant Patients Receiving the Tacrolimus Once-Daily Formulation

Background: The once-daily formulation of tacrolimus has been reported to exhibit the same efficacy and safety profile as compared with the immediate-release form administered twice daily. However, as a result of differences in their pharmacokinetic (PK) profile, the PK models or Bayesian estimators (MAP-BE) previously developed for the immediate-release formulation cannot be used for the new once-daily formulation. Using the PK information obtained from a Phase II trial, the aim of this study was to explore the feasibility of developing a PK model and a MAP-BE able to estimate, on the basis of a routinely applicable limited sampling strategy, tacrolimus individual PK parameters and AUC0-24h in de novo renal transplant patients given the once-daily formulation. Methods: Twelve de novo kidney transplant recipients receiving once-daily tacrolimus as part of their immunosuppressive regimen provided full PK profiles (17 concentration time points over 24 hours) on Days 14 and 42 posttransplantation. On the basis of a one-compartment open model with absorption described as following a double gamma distribution, a classic iterative two-stage method was applied to develop MAP-BEs. All the limited sampling strategies with a maximum of three sampling times within 4 hours postdose were tested for Bayesian forecasting with the aim of accurately estimating the AUC0-24h. Results: Once-daily tacrolimus exhibited a high interpatient PK variability with coefficients of variation of 34.3% and 36.2% for AUC0-24h/dose (mg/kg) on Days 14 and 42, respectively. Regression analysis between C0 and AUC0-24h yielded r2 = 0.68 and 0.76 at these two periods, respectively. The iterative two-stage approach led to the development of a different MAP-BE for each posttransplantation period, which allowed estimation of once-daily tacrolimus pharmacokinetics and AUC0-24h on the basis of a C0-C1h-C3h sampling schedule. The mean bias of the Bayesian versus reference (trapezoidal) AUCs was 4.2% ± 6.1% (range, -11.8% to +11.2%; root mean square error = 7.1%) on Day 14 and 0.2% ± 7.9% (range, −12.9% to +14.1%; root mean square error = 7.8%) on Day 42. Conclusion: A PK model and Bayesian estimators allowing estimation of tacrolimus AUC0-24h based on a routinely applicable limited sampling strategy were developed for once-daily tacrolimus in renal transplantation. Further validation in independent groups of patients is required to confirm their applicability for optimizing the monitoring of once-daily tacrolimus in routine clinical practice or to conduct observational or comparative therapeutic drug monitoring clinical trials.
Mecp2 Organizes Juvenile Social Behavior in a Sex-Specific Manner

Methyl-CpG-binding protein 2 (MeCP2) binds methylated DNA and recruits corepressor proteins to modify chromatin and alter gene transcription. Mutations of the MECP2 gene can cause Rett syndrome, whereas subtle reductions of MeCP2 expression may be associated with male-dominated social and neurodevelopmental disorders. We report that transiently decreased amygdala Mecp2 expression during a sensitive period of brain sexual differentiation disrupts the organization of sex differences in juvenile social play behavior. Interestingly, neonatal treatment with Mecp2 small interfering RNA within the developing amygdala reduced juvenile social play behavior in males but not females. Reduced Mecp2 expression did not change juvenile sociability or anxiety-like behavior, suggesting that this disruption is associated with subtle behavioral modification. This suggests that Mecp2 may have an overlooked role in the organization of sexually dimorphic behaviors and that male juvenile behavior is particularly sensitive to Mecp2 disruption during this period of development.
Investigation of the relationship between arterial stiffness and sleep architecture in patients with essential hypertension

Abstract A change in sleep architecture might increase the risk of hypertension and worsen target organs. This study thus aimed to study the features of sleep architecture and examine its relationship with pulse wave velocity (PWV), a measure of arterial stiffness, in patients with essential hypertension and healthy people aged 45–65 years (n = 106). We collected data on demographics, the serum index, overnight polysomnography, vascular testing and ambulatory blood pressure in addition to measuring arterial stiffness and monitoring sleep respiration. We found that patients with hypertension had longer sleep latency and shorter duration. Their sleep efficiency and the ratio of N3 in non-rapid eye movement (NREM) and rapid eye movement were lower, while the micro-arousal index (MI), N1 and N2 in NREM, and the apnea-hypopnea index were higher than normal people in controls. PWV raised with a decrease in N3 and an increase in the MI. In summary, there were notable changes in sleep architecture and with a decrease in N3 and increase in MI can accelerate arterial stiffness and then worsen target organ damage in patients with hypertension.
Radiological Findings, Pulmonary Function and Dyspnea in Underground Coal Miners

Background: Respiratory disability induced by dust exposure in coal workers is assessed by pulmonary function tests and radiological evidence of pneumoconiosis. High-resolution computed tomography (HR-CT) improves the visibility of tissue changes, but the value of the findings for the clinical evaluation is controversial. Objectives: It was the aim of this study to evaluate the correlation between the International Labour Office (ILO) classification and the degree of emphysema in HR-CT with self-reported dyspnea and pulmonary function tests including diffusion capacity for CO (DL,CO). Methods: We investigated 87 coal miners (aged 67 ± 6 years), having worked underground for 26 ± 9 years, with pulmonary function tests and HR-CT. Univariate associations were tested with correlation coefficients, and multivariable analyses used a stepwise forward regression model. Results: No aspect of the ILO classification showed a univariate correlation with dyspnea or forced expiratory flow in 1 s (FEV1). Emphysema CT score was strongly associated with DL,CO (rs = –0.40; p < 0.001) and FEV1/maximal vital capacity (r = –0.38; p < 0.001) in univariate analysis, but not with the clinical grade of dyspnea (r = –0.14; p = 0.256). CT emphysema score but not ILO classification was associated with FEV1 in multivariable analyses (rs = –0.37; p < 0.001). Dyspnea was best approximated by DL,CO (r = –0.312; p = 0.008). Conclusion: The clinical grade of breathlessness was best approximated by DL,CO. HR-CT showed a good association with expiratory flow limitation. ILO classification of the chest radiograph may be a marker of exposure but conveys little information about the degree of respiratory impairment.
Epithelioid Sarcoma of the Parotid Gland of a Child

Epithelioid sarcoma is a rare soft-tissue tumor that usually occurs in young adults, with a median age of 26 years. This malignancy has been divided into distal and proximal types. The latter is found in proximal body sites including the head and neck region. We present a rare case of parotid proximal-type epithelioid sarcoma in a 1-year-old male child; this is the 4th reported case in the literature and the youngest in a pediatric patient to date. The tumor showed prominent rhabdoid features by light microscopy. Immunohistochemical studies revealed positive staining to cytokeratin (AE1/AE3), epithelial membrane antigen, vimentin, and BAF47. Thus, while the tumor resembled a malignant rhabdoid tumor, the positive staining for BAF47 supported instead a diagnosis of epithelioid sarcoma, according to our current understanding of these 2 tumor types. Also, the clinical course was not the typical aggressive behavior of a rhabdoid tumor. The patient underwent radical parotidectomy without adjuvant therapy and remained disease-free at follow-up, 14 months after surgery.
Estimation of Productivity and Efficiency of Cotton Farmers: A Case Study of District Dera Ghazi Khan

This study estimates total technical (TEcrs), pure technical (TEvrs), allocative (AE), and economic (EE) efficiencies of cotton growers in the district Dera Gazi Khan using data envelopment analysis (DEA) technique. The study finds 0.67, 0.94, 0.57, 0.54 and 0.71 average values of the total technical, pure technical, allocative, economic, and scale efficiencies, respectively. The study also tries to investigate the determinants of technical inefficiency of cotton growers and the slacks of inputs. The results indicate that human capital, research and development, and easy access to markets are major determinants of technical efficiency. The output orientation analysis shows that production of cotton can be increased by 6 maunds (240kgs) per acre under present availability of resources. The slack estimates show that 43 percent cost of inputs is used extra and on average Rs.11, 833 per acre can be saved in this account without loss of output. This study suggests that government should make a strategy to improve irrigation system and provide trainings for optimal utilization of inputs, and ban agro-shops that do not have licenses
A methodology of contextualized educational robotics

Just as in educational robotics the students solve problems in order to build their own knowledge, so too in contextualized learning the students learn by solving problems. The difference is that the former works with interdisciplinary problems that are solved by the construction and use of a robotic model, and the later approaches cultural or socioeconomic problems related to the students reality. Therefore both approaches are based in constructivism and problem based learning, but each one has specific characteristics and benefits. Thus, a teaching and learning approach that combines the two could have different or perhaps more promising results than with just one of the individual methodologies. In this work we propose a teaching and learning methodology that combines educational robotics and contextualized learning. This methodology is described in order to be replicated by other teachers or research groups. After that, we present as an example a course planned and executed with such methodology for a school located in a small town in the semiarid area of Brazil. Finally, we discuss the methodology and some of the outcomes from the course at short and long terms. Although new experiments are necessary to achieve conclusive results, the partial results are promising.
Pediatric pharmacoepidemiology - safety and effectiveness of medicines for ADHD

ABSTRACT Introduction: Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder in children and adolescents that comprises core symptoms of developmentally inappropriate levels of inattention and/or hyperactivity and impulsivity. Stimulant (methylphenidate, amphetamines) and non stimulant (atomoxetine, clonidine and guanfacine) are the treatment usually prescribed for ADHD. Area covered: This review covers the safety of ADHD medications in children and adolescents. MEDLINE, EMBASE and PsycINFO databases were searched with the aim to retrieve prospective studies that monitored the incidence of adverse events (AEs) in children receiving drug therapy for ADHD. Many of the studies investigated the risk of specific AEs. In particular, the cardiovascular safety, the impact on growth and on sleep pattern, the risk of substance use disorders and of suicidal ideation are among the topics more studied. Expert opinion: Effective drugs for ADHD appears to be safe and well tolerated. Most of the adverse events reported in the randomised controlled trials are mild and transient. Decreased appetite, growth decrease and the impact on sleep (insomnia for stimulants and somnolence for alpha2-agonists) are among the most common events. Concerns exist about cardiovascular and psychiatric AEs, even if the available evidence does not support an association with medications.
Professional Communication in a Global Business Context: The Notion of Global Communicative Competence

On the basis of an extensive survey study conducted among business professionals engaging in global communication, this paper discusses communicative competence. Rapid changes in work environments, particularly advancing globalization and new technology, have highlighted the need for expanding our knowledge of the elements that constitute communicative competence in global encounters. Competence has been investigated by several researchers; however, the language perspective, particularly the language used for international communication, that is, English as a Lingua Franca (ELF), has largely been ignored. Our findings indicate that global communicative competence (GCC) consists of three layers: multicultural competence, competence in English as a Business Lingua Franca (BELF) and the communicator's business know-how. Based on our findings, we present a model for GCC, which includes language as a key component. Implications for theory, practice, and education include the need for a multidisciplinary approach and the acknowledgement of ELF/BELF as the language of global interaction. ELF IBELF assumes a shared "core" of the English language, but focuses on interactional skills, rapport building, and the ability to ask for and provide clarifications.
Normative data of optic nerve head in Thai population by laser scanning tomography: Siriraj study.

OBJECTIVE To study the normative values of topographic optic disc parameters in a Thai population. MATERIAL AND METHOD Two hundred and six eyes of 103 normal subjects aging from 30-80 years were studied Thirteen topographic disc parameters were analyzed by confocal scanning laser ophthalmoscope using Heidelburg retina tomography (HRT II). The average value of two eyes in the same subject was used as the unit of statistical analysis, and then the normal values and means were statistically calculated at 95% reference interval (95% RI). Ethnic differences of the calculated optic nerve topography were compared with previous studies. The relationship of age, intraocular pressure (IOP), central corneal thickness (CCT), and optic disc parameters were assessed by Pearson correlation. RESULTS Mean values with 95% RI of all 13 parameters were analyzed Whole parameters except cup volume demonstrated normal distribution. Mean value (95% RI) of disc area in normal Thai people was 2.67 mm2 (1.96, 3.71) which was larger than Caucasian people. Ethnic differences in topographic optic disc parameters were found among Thai and other races including Asians, Caucasians, African-Americans, and Hispanics. The results also revealed that age, IOP, and CCT had no significant relation to all optic disc parameters. CONCLUSION Thai people had a larger optic disc area than Caucasians. There are marked differences of topographic optic nerve parameters among different ethnic groups. These differences need to be taken into account when evaluating glaucomatous optic neuropathy and when comparing results of studies completed among population of different ethnic and racial origins.
Elderly patients with head and neck cancer: physical, social and psychological aspects after 1 year

Objective Elderly patients with head and neck cancer often receive non-standard treatment for reasons other than comorbidity. In this prospective study we investigated how elderly patients fare 1 year after treatment in comparison with their younger counterparts. Material and Methods Seventy patients aged 45–60 years and 51 patients aged ≥70 years with cancer of the oral cavity, pharynx (stage II–IV) or larynx (stage III–IV) participated in the study before treatment and 1 year later. Each patient was interviewed and given a questionnaire concerning physical functioning, social contacts, depressive symptoms, satisfaction with treatment and future expectations. Results At 12 months, patients in both age groups reported significantly more depressive symptoms and less social support than before treatment, and their Karnofsky Performance Score was lower. However, there were no differences between elderly and younger patients. Approximately 90% of those in both age groups said that they would choose the same treatment again, and there was no age difference regarding the impact of treatment or expectations for the future. Conclusion This study shows that the impact of treatment on quality of life did not differ between elderly and younger patients with head and neck cancer. Therefore, standard treatment should be considered in elderly patients if no severe contraindications exist.
Fabrication of BioInspired Inorganic Nanocilia Sensors

In nature, microscale hair-like projections called cilia are used ubiquitously for both sensing and motility. In this paper, biomimetic nanoscale cilia arrays have been fabricated through templated growth of Co in anodized aluminum oxide. The motion of arrays of Co cilia was then detected using magnetic sensors. These signals were used to prove the feasibility of two types of sensors: flow sensors and vibration sensors. The flow sensors were tested in a microfluidic channel. They showed the ability to detect flows from 0.5 ml/min to 6 ml/min with a signal to noise (SNR) of 44 using only 140 μW of power and no amplification. The vibration sensors were tested using a shake table in the low earthquake-like frequency range of 1-5 Hz. The vibration response was a mW signal at twice the frequency of the shake table.
Nucleotide Variation at Msn and Alas2, Two Genes Flanking the Centromere of the X Chromosome in Humans

The centromeric region of the X chromosome in humans experiences low rates of recombination over a considerable physical distance. In such a region, the effects of selection may extend to linked sites that are far away. To investigate the effects of this recombinational environment on patterns of nucleotide variability, we sequenced 4581 bp at Msn and 4697 bp at Alas2, two genes situated on either side of the X chromosome centromere, in a worldwide sample of 41 men, as well as in one common chimpanzee and one orangutan. To investigate patterns of linkage disequilibrium (LD) across the centromere, we also genotyped several informative sites from each gene in 120 men from sub-Saharan Africa. By studying X-linked loci in males, we were able to recover haplotypes and study long-range patterns of LD directly. Overall patterns of variability were remarkably similar at these two loci. Both loci exhibited (i) very low levels of nucleotide diversity (among the lowest seen in the human genome); (ii) a strong skew in the distribution of allele frequencies, with an excess of both very-low and very-high-frequency derived alleles in non-African populations; (iii) much less variation in the non-African than in the African samples; (iv) very high levels of population differentiation; and (v) complete LD among all sites within loci. We also observed significant LD between Msn and Alas2 in Africa, despite the fact that they are separated by ∼10 Mb. These observations are difficult to reconcile with a simple demographic model but may be consistent with positive and/or purifying selection acting on loci within this large region of low recombination.
An Analytical Model for Elucidating Tendon Tissue Structure and Biomechanical Function from in vivo Cellular Confocal Microscopy Images

Fibered confocal laser scanning microscopes have given us the ability to image fluorescently labeled biological structures in vivo and at exceptionally high spatial resolutions. By coupling this powerful imaging modality with classic optical elastography methods, we have developed novel techniques that allow us to assess functional mechanical integrity of soft biological tissues by measuring the movements of cells in response to externally applied mechanical loads. Using these methods we can identify minute structural defects, monitor the progression of certain skeletal tissue disease states, and track subsequent healing following therapeutic intervention in the living animal. Development of these methods using a murine Achilles tendon model has revealed that the hierarchical and composite anatomical structure of the tendon presents various technical challenges that can confound a mechanical analysis of local material properties. Specifically, interfascicle gliding can yield complex cellular motions that must be interpreted within the context of an appropriate anatomical model. In this study, we explore the various classes of cellular images that may result from fibered confocal microscopy of the murine Achilles tendon, and introduce a simple two-fascicle model to interpret the images in terms of mechanical strains within the fascicles, as well as the relative gliding between fascicles.
Signal-to-noise performance of the optical receiver using a distributed amplifier and p-i-n photodiode combination

The signal to noise performance of grounded source amplifier and distributed amplifier optical receiver configurations has been theoretically investigated. This predicts that an improvement of signal to noise ratio up to 12.7 dB is achievable for the distributed amplifier configuration compared with the grounded source in a bandwidth of 40 GHz. Our preliminary experimental results support the theoretical analysis. An optical receiver with 3 dB bandwidth of 20 GHz was fabricated by embedding the p-i-n photodiode into a T-network at the gate line in the distributed amplifier and an average equivalent input noise of 20 pA/Hz/sup 1/2/ was achieved over a bandwidth of 2-18 GHz. >
Web-Based Intervention to Improve Implantable Cardioverter Defibrillator Patients’ Shock-Related Anxiety and Quality of Life: A Randomized Controlled Trial

In spite of its effectiveness, implantable cardioverter defibrillator (ICD) patients face psychological problems such as shock-related anxiety due to device shocks. The aim of this study was to evaluate whether a web-based intervention program for ICD patients would reduce shock-related anxiety and improve quality of life compared with usual care. This was a randomized controlled trial study including a total of 76 patients. Data were collected using Turkish versions of the Florida Shock Anxiety Scale and Short Form Health Survey (SF-36) at 0 (baseline), 3, and 6 months. Following intervention, there was a significant decrease in shock anxiety levels of patients and a statistically significant increase in social functioning, role-physical, mental health, vitality, and bodily pain subdimensions of SF-36. While no statistically significant difference was found between groups in terms of summary scores of SF-36, our results suggest that web-based interventions can be useful for ICD patients.