Miracle-dz/UniFAR-FTUs huggingface dataset:
Association Between Prevalence of Peripheral Artery Disease and Radiation Exposure in the Atomic Bomb Survivors

Background Past reports suggested that total‐body irradiation at 0.5 to 1.0 Gy could be responsible for atherosclerosis. Peripheral artery disease (PAD) is a manifestation of systematic atherosclerosis. Whether the consequences of a low‐to‐moderate dose of radiation include increased risk of PAD remains to be determined. The purpose of this study was to examine the association between radiation exposure and prevalence of PAD among Japanese atomic bomb survivors. Methods and Results Radiation exposure from the atomic bombing was assessed in 3476 participants (41.1% men, mean age 74.8 years with SD 6.4 years) with a cross‐sectional survey in 2010 to 2014. Left‐ and right‐side ankle‐brachial indexes and upstroke time (UT) were obtained using oscillometric VP‐2000. PAD was defined as an ankle‐brachial index of 1.0 or less or a prior history related to revascularization. UT was considered a sensitive marker of early‐stage PAD. Association between radiation exposure and PAD or UT was assessed using multivariable regression analyses with adjustment for potential confounding factors. Of 3476 participants, 79 (2.3%) were identified as having prevalent PAD. Multivariate logistic regression analysis indicated that radiation dose was unrelated to PAD prevalence (odds ratio, 0.83; 95% confidence interval [0.57‐1.21]). UT appeared to increase with radiation dose, but the increase was not statistically significant (1.09 ms/Gy; 95% confidence interval [−0.17 to 2.36]). Conclusions We found no clear association of radiation dose with PAD, but it remains to be determined whether UT is associated with radiation dose.
CD56 and CD11b Positivity with Low Smac/DIABLO Expression as Predictors of Chemoresistance in Acute Myeloid Leukaemia: Flow Cytometric Analysis

Background: Resistance to chemotherapy is a major obstacle to curing acute myeloid leukaemia (AML), and several antigens are claimed to play primary roles in this resistance. Purpose: The aim of this study was to evaluate the roles of CD56, CD11b and Smac/DIABLO gene expression levels as prognostic markers of the clinical outcome, response to chemotherapy and survival of AML patients. Materials and Methods: A cross-sectional observational study was conducted on 60 naïve-AML patients who received induction therapy with mitoxantrone and cytarabine combined with a high dose of cytarabine. The CD56,CD11b and Smac/DIABLO expression levels were assessed using flow cytometry at diagnosis and were analysed for correlation with the possible associated risk factors, response to chemotherapy, and median duration of disease-free survival (DFS) and overall survival (OS). Results: The overall results revealed that AML patients who exhibited positive expression for CD56 and CD11b had short median durations of DFS and OS. (P = 0.019, 0.006, 0.029 and 0.024, respectively). Additionally, low Smac/DIABLO expression had a negative impact on treatment outcome in terms of CR rate (p=0.012) and reduced DFS (p=0.000) and OS(p=0.000) values. Conclusions: CD56 and CD11b positivity and low Smac/DIABLO expression are important predictive factors for the occurrence of chemoresistance, in addition to other risk factors, among AML patients.
A Synthetic Close-Loop Controller Circuit for the Regulation of an Extracellular Molecule by Engineered Bacteria

Feedback control is ubiquitous in biological systems. It can also play a crucial role in the design of synthetic circuits implementing novel functions in living systems, to achieve self-regulation of gene expression, noise reduction, rise time decrease, or adaptive pathway control. Despite in vitro, in vivo, and ex vivo implementations have been successfully reported, the design of biological close-loop systems with quantitatively predictable behavior is still a major challenge. In this work, we tested a model-based bottom-up design of a synthetic close-loop controller in engineered Escherichia coli, aimed to automatically regulate the concentration of an extracellular molecule, N-(3-oxohexanoyl)-L-homoserine lactone (HSL), by rewiring the elements of heterologous quorum sensing/quenching networks. The synthetic controller was successfully constructed and experimentally validated. Relying on mathematical model and experimental characterization of individual regulatory parts and enzymes, we evaluated the predictability of the interconnected system behavior in vivo. The culture was able to reach an HSL steady-state level of 72 nM, accurately predicted by the model, and showed superior capabilities in terms of robustness against cell density variation and disturbance rejection, compared with a corresponding open-loop circuit. This engineering-inspired design approach may be adopted for the implementation of other close-loop circuits for different applications and contribute to decreasing trial-and-error steps.
Two functionally redundant sources of retinoic acid secure spermatogonia differentiation in the seminiferous epithelium

ABSTRACT In mammals, all-trans retinoic acid (ATRA) is instrumental to spermatogenesis. It is synthesized by two retinaldehyde dehydrogenases (RALDH) present in both Sertoli cells (SCs) and germ cells (GCs). In order to determine the relative contributions of each source of ATRA, we have generated mice lacking all RALDH activities in the seminiferous epithelium (SE). We show that both the SC- and GC-derived sources of ATRA cooperate to initiate and propagate spermatogenetic waves at puberty. In adults, they exert redundant functions and, against all expectations, the GC-derived source does not perform any specific roles despite contributing to two-thirds of the total amount of ATRA present in the testis. The production from SCs is sufficient to maintain the periodic expression of genes in SCs, as well and the cycle and wave of the SE, which account for the steady production of spermatozoa. The production from SCs is also specifically required for spermiation. Importantly, our study shows that spermatogonia differentiation depends upon the ATRA synthesized by RALDH inside the SE, whereas initiation of meiosis and expression of STRA8 by spermatocytes can occur without ATRA. Summary: All-trans retinoic acid made by Sertoli cells is instrumental to spermatogenesis and is specifically required for spermatid release.
Maternal separation induces long-term changes in mineralocorticoid receptor in rats subjected to chronic stress and treated with tianeptine

Abstract Purpose: The aim of this study was to analyze whether early maternal separation would result in long-term, persistent alterations in stress response in adulthood, altering mineralocorticoid receptor immunoreactivity (MR-ir) in the dorsal hippocampal areas [CA1, CA2, CA3 and dentate gyrus (DG)], paraventricular nucleus of the hypothalamus and medial and central nucleus of the amygdala, key structures involved in stress response regulation. We also analyzed whether chronic treatment with the antidepressant tianeptine reverses these possible changes. Material and methods: Male Wistar rats were subjected to daily maternal separation for 4.5 h during 3 weeks or left undisturbed. As adults, they were exposed to chronic stress during 24 days or left undisturbed, and they were also daily treated with tianeptine (10 mg/kg i.p.) or isotonic solution. Results: In the CA2 and DG areas of the dorsal hippocampus, there was an increase in MR-ir in non-maternally separated and chronic stressed groups. Tianeptine raised MR-ir in the CA3. In the DG, control and maternally separated + chronic stress groups treated with tianeptine showed more MR-ir than their respective vehicle groups. In the paraventricular nucleus, tianeptine decreased MR-ir in non-separated groups, but not in maternally separated rats. Conclusions: Our results support findings that early-life events induce long-term changes in stress response regulation, persistent into adulthood, which are manifested during challenges in later life, and that treatment with tianeptine, which tends to attenuate the hypothalamus-pituitary-adrenal axis dysregulation, depends on the individual experience of each rat.
The Effect of Publication Bias on the Q Test and Assessment of Heterogeneity

Abstract One of the main goals of meta-analysis is to test for and estimate the heterogeneity of effect sizes. We examined the effect of publication bias on the Q test and assessments of heterogeneity as a function of true heterogeneity, publication bias, true effect size, number of studies, and variation of sample sizes. The present study has two main contributions and is relevant to all researchers conducting meta-analysis. First, we show when and how publication bias affects the assessment of heterogeneity. The expected values of heterogeneity measures H2 and I2 were analytically derived, and the power and Type I error rate of the Q test were examined in a Monte Carlo simulation study. Our results show that the effect of publication bias on the Q test and assessment of heterogeneity is large, complex, and nonlinear. Publication bias can both dramatically decrease and increase heterogeneity in true effect size, particularly if the number of studies is large and population effect size is small. We therefore conclude that the Q test of homogeneity and heterogeneity measures H2 and I2 are generally not valid when publication bias is present. Our second contribution is that we introduce a web application, Q-sense, which can be used to determine the impact of publication bias on the assessment of heterogeneity within a certain meta-analysis and to assess the robustness of the meta-analytic estimate to publication bias. Furthermore, we apply Q-sense to 2 published meta-analyses, showing how publication bias can result in invalid estimates of effect size and heterogeneity.
The Dangers of Assuming Before Analysis: Three Case Studies of Argumentation and Cognition

: In this article, we argue that researchers in the hypothetico-deductive tradition expose themselves to dangers when they first make assumptions about theoretical constructs and second, when they gather data specifically in order to test the predictions arising from hypotheses about these constructs. We review our own research in computer supported collaborative learning and in computer supported collaborative work on argumentation and cognition to show ways to partially surmount these dangers while raising new methodological concerns. We conclude by underlining the importance of the role of theory and the importance of reflecting on these issues, especially in a multidisciplinary community such as the learning sciences.
Genomics: New Light on Alzheimer’s Disease Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that represents a major cause of death in many countries. AD is characterized by profound memory loss, disruptions in thinking and reasoning, and changes in personality and behavior followed by malfunctions in various bodily systems. Although AD was first identified over 100 years ago, and tremendous efforts have been made to cure the disease, the precise mechanisms underlying the onset of AD remain unclear. The recent development of next-generation sequencing tools and bioinformatics has enabled us to investigate the role of genetics in the pathogenesis of AD. In this review, we discuss novel discoveries in this area, including the results of genome-wide association studies (GWAS) that have implicated a number of novel genes as risk factors, as well as the identification of epigenetic regulators strongly associated with the onset and progression of AD. We also review how genetic risk factors may interact with age-associated, progressive decreases in cognitive function in patients with AD.
Characterization of a Carbonyl Reductase from Rhodococcus erythropolis WZ010 and Its Variant Y54F for Asymmetric Synthesis of (S)-N-Boc-3-Hydroxypiperidine

The recombinant carbonyl reductase from Rhodococcus erythropolis WZ010 (ReCR) demonstrated strict (S)-stereoselectivity and catalyzed the irreversible reduction of N-Boc-3-piperidone (NBPO) to (S)-N-Boc-3-hydroxypiperidine [(S)-NBHP], a key chiral intermediate in the synthesis of ibrutinib. The NAD(H)-specific enzyme was active within broad ranges of pH and temperature and had remarkable activity in the presence of higher concentration of organic solvents. The amino acid residue at position 54 was critical for the activity and the substitution of Tyr54 to Phe significantly enhanced the catalytic efficiency of ReCR. The kcat/Km values of ReCR Y54F for NBPO, (R/S)-2-octanol, and 2-propanol were 49.17 s−1 mM−1, 56.56 s−1 mM−1, and 20.69 s−1 mM−1, respectively. In addition, the (S)-NBHP yield was as high as 95.92% when whole cells of E. coli overexpressing ReCR variant Y54F catalyzed the asymmetric reduction of 1.5 M NBPO for 12 h in the aqueous/(R/S)-2-octanol biphasic system, demonstrating the great potential of ReCR variant Y54F for practical applications.
Analisis Perencanaan Obat di Dinas Kesehatan Kabupaten Minahasa

Abstrak Pengelolaan obat kabupaten/kota merupakan tanggung jawab penuh dari pemerintah kabupaten/kota. Mulai dari aspek perencanaan kebutuhan obat untuk pelayanan kesehatan dasar berdasarkan sistem “ bottom up ”, perhitungan rencana kebutuhan obat, serta mengkoordinasikan perencanaan kebutuhan obat dari beberapa sumber dana. Kepala Dinas Kesehatan Kabupaten/Kota mengajukan Rencana Kebutuhan Obat (RKO) dan melaporkan penggunaan obat kepada Pemerintah Kabupaten/Kota, Provinsi dan Pusat. Setiap kabupaten/kota mempunyai struktur dan kebijakan sendiri dalam pengelolaan obat, selanjutnya Pengelola Obat Kabupaten/Kota disebut dengan Unit Pengelola Obat Publik dan Perbekalan Kesehatan (UPOPPK) Kabupaten/Kota. Penelitian ini menggunakan metode kualitatif yang bertujuan untuk mendapatkan informasi yang lebih mendalam tentang proses perencanaan obat di Dinas Kesehatan Kabupaten Minahasa Tenggara. Penelitian ini akan dilaksanakan di Dinas Kesehatan Kabupaten Minahasa Tenggara pada bulan Januari – Maret 2015. Data diperoleh dengan cara wawancara mendalam terhadap informan penelitian. Data diolah dengan menggunakan content analysis. Hasil penelitian menunjukkan bahwa Proses perencanaan kebutuhan obat di Dinas Kesehatan Kabupaten Minahsa Tenggara belum sesuai dengan Pedoman Teknis Pengelolaan dan Pengadaan Obat Publik dan Perbekalan Kesehatan yang ditetapkan oleh Menteri Kesehatan Republik Indonesia. Kata kunci : Obat, Perencanaan, Content Analysis . Abstract Medication management districts / cities are the sole responsibility of the district / city. Starting from the planning aspect of medicine needs for a basic health care system is based on "bottom up", the calculation of the plan needs the drug, and the drug needs to coordinate planning of several sources of funds. Chief Medical Officer / City filed a Drug Needs Plan (RKO) and report the use of drugs to the District / City, State and Central. Each district / city has its own structures and policies in the management of drugs, Drug next business district / city called Public Drug Unit business and Medical Supplies (UPOPPK) Regency / City. This study used a qualitative method that aims to gain a more in-depth information about the planning process drugs in Southeast Minahasa District Health Office. This study will be conducted in Southeast Minahasa District Health Office in January to March 2015. The data were obtained by means of in-depth interviews to research informants. Data were processed using content analysis. The results showed that the planning process needs medicine in Southeast Minahsa District Health Office is not in accordance with the Guidelines for Technical Management and Public Procurement of Drugs and Medical Supplies specified by the Minister of Health of the Republic of Indonesia. Keyword : Drugs , Planning, Content Analysis.
Automated techniques for formal verification of SoCs

System-on-a-chip (SoC) designs have gained immense popularity as they provide designers with the ability of integrating all components (called IPs) of an application-specific computer system onto a single chip. However, one of the main bottlenecks of the SoC design cycle is the validation of complex designs. As system size grows, validation time increases beyond manageable limits. It is desirable that design inconsistences are found and fixed early in the design process, as validation overheads are significantly higher after IPs are integrated. This thesis presents a range of techniques for the automatic verification and design of SoCs that aim to reduce post-integration validation costs. Firstly, local module checking algorithm, a practical implementation of module checking, is presented. This technique allows for the comprehensive verification of IPs such that they guarantee the satisfaction of critical specifications regardless of the SoC they are used in. Local module checking is shown to be able to validate IPs in much lesser time on average than global module checking, and can help in handling many important validation tasks much before the integration stage. Next, a number of protocol conversion techniques that assist in the composition of IPs with incompatible protocols is presented. The inconsistencies between IP protocols, called mismatches, are bridged by the automatic generation of some extra glue-logic, called a converter. Converters generated by the proposed techniques can handle control, datawidth and clock mismatches between multiple IPs in a unified manner. These approaches ensure that the integration of IPs is correct-by-construction, such that the final system is guaranteed to satisfy key specifications without the need for further validation. Finally, a technique for automatic IP reuse using forced simulation is presented, which involves automatically generating an adaptor that guides an IP such that it satisfies desired specifications. The proposed technique can generate adaptors in many cases where existing IP techniques fail. As it is guaranteed that reused IPs satisfy desired specifications, post-integration validation costs are significantly reduced. For each proposed technique, a comprehensive set of results is presented that highlights the significance of the solution. It is noted that the proposed approaches can help automate SoC design and achieve significant savings in post-integration validation costs.
RESULTS OF TRANSARTERIAL CHEMOEMBOLIZATION (TACE) IN A GROUP OF IRANIAN PATIENTS WITH HEPATOCELLULAR CARCINOMA

Background: Hepatocellular carcinoma (HCC) is a primary liver cancer that frequently causes mortalities. Transarterial chemoembolization (TACE) is a new palliative treatment for advanced stages of HCC. In this study, we have assessed the results of TACE on a group of Iranian patients with advanced HCC treated at Imam Khomeini General Hospital. Materials and Methods: This was a case series, cohort study conducted on 36 patients with HCC who met the study criteria. Patients underwent two sessions of TACE at a 4-6 week interval. All patients underwent triphasic computerized scans (CT scan) before treatment and at six weeks after the second session. Results: After at least a one year follow up period, 20 (55.6%) patients died and 16 (41.7%) survived. Survival at 6 months was 58% and at 12 months, it was 33.3%. Post-TACE tumor necrosis (>50%) was significantly associated with 6 ( p = 0.029) and 12 ( p = 0.00) month survival. There was a significant association between 6 and 12 month survival and Okuda stage ( p -V= 0.001 and 0.003), ascites ( p -V = 0.058 and 0.012) and branch portalÂ vein thrombosis ( p -V= 0. 036 and 0.024). There was no association of WHO criteria to 6 ( p -V = 0.139) and 12 ( p -V =0.139) month survival. Conclusion: Tumor necrosis less than 50%, presence of ascites and thrombosis of the portal branches are associated with lower survival. Suitable selection and taking into consideration post-TACE tumor necrosis is suggested to enhance survival.
"With great power comes great responsibility": Understanding the behavioural determinants of residential energy efficiency in Wellington

Recognition of the need for a transformation in our global energy systems to combat climate change has brought about an increased drive to curb energy consumption and increase energy efficiency. The residential sector is a prominent energy user and a key focus for this transition to a low carbon future. Psychology has played an increasingly important role in energy policy with an understanding that individuals act on motivators beyond economic explanations. This study provides a psychological evaluation of a residential energy efficiency intervention based in Wellington, New Zealand in order to develop a deeper understanding of how energy interventions engage participants in change and how they can be made more effective. The Wellington intervention uses a tailored information approach through a home energy audit to promote both efficiency and curtailment behaviours in local homes. By measuring before and after energy consumption changes in combination with salient psychological determinants, this quantitative study examines energy changes following the audit programme and the motivations involved in making these changes. The psychological determinants explored are the fundamental values held by programme participants as well as their level of concern for the environment. Analysis showed energy consumption changes following the audit to be variable and inconclusive as to the effectiveness of the overall programme. Values contributed a significant influence with self-transcendent values being a positive predictor of the number of efficiency behaviours implemented after the programme. This suggests that appealing to the altruistic concerns and collective interests salient within the self-transcendence value dimension when designing and implementing an intervention could aid uptake of energy conservation behaviour in future interventions.