Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Dissection of Marfan Syndrome and Related Connective Tissue Disorders: An Update 2012

Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue characterized by early development of thoracic aortic aneurysms/dissections together with symptoms of the ocular and skeletal systems. While most patients/families with a classic phenotypic expression of MFS harbour mutations in the gene encoding fibrillin-1 (FBN1), genetic studies of the recent years revealed that the clinical features, as well as the mutated genes, show a high degree of overlap between MFS and other connective tissue diseases (e.g. Loeys-Dietz syndrome, Ehlers-Danlos syndrome, familial thoracic aneurysms and dissections and others). We summarize herein the current knowledge about the wide spectrum of differential diagnoses and their genetic background as well as novel therapeutic approaches in order to provide appropriate counselling and clinical follow-up for the patients.
Treating the chronic-phase chronic myeloid leukemia patient: which TKI, when to switch and when to stop?

ABSTRACT Introduction: With the discovery of imatinib mesylate nearly 20 years ago, tyrosine kinase inhibitors (TKIs) were found to be effective in chronic myeloid leukemia (CML). TKI therapy has since revolutionized the treatment of CML and has served as a paradigm of success for targeted drug therapy in cancer. Several new TKIs for CML have been approved over the last two decades that exhibit improved potency over imatinib and have different off-target profiles, providing options for individualized therapy selection. Areas covered: Current management of chronic phase CML, including guidance on the sequential use of imatinib and newer-generation TKIs and evolving treatment strategies such as TKI discontinuation. Relevant literature was identified by searching biomedical databases (i.e. PubMed) for primary research material. Expert commentary: Although survival outcomes have drastically improved for CML patients, treatment for CML has grown more complex with the introduction of next-generation TKIs and the advent of treatment-free remissions (TFR). Goals of therapy have shifted accordingly, with increased focus on improving quality of life, managing patient expectations and optimizing patient adherence.
Incipient speciation within a subgenus of rock W sh ( Sebastosomus ) provides evidence of recent radiations within an ancient species

The high frequency of speciation events associated with species Xocks (i.e., radiations of closely related species) provides invaluable insight into the speciation process. Investigations of the speciation process in the marine environment are rare, and therefore, the genetic analysis of the rockWsh genus Sebastes, considered an ancient marine species Xock, provides an opportunity to investigate this process in the sea. Using both mitochondrial and nuclear markers, we analyzed Wve closely related species within the rockWsh subgenus Sebastosomus. Our goal was to understand the evolutionary history and genetic relationships among species within this group and to provide evidence of recent speciation events within the subgenus. In the genetic analysis of the subgenus, we found diVerent stages of the speciation process, with greater genetic divergences among three of the Wve species, evidence of recent divergence between two of the Wve species, Sebastes entomelas and S. mystinus, and signiWcant genetic divergence between two lineages within S. mystinus revealing a signature of incipient speciation. We also found frequency diVerences of the two S. mystinus lineages among sample locations and found no evidence of introgression between the lineages at the location where both coexist. Although Sebastes is an example of an ancient species Xock, this study provides evidence of ongoing speciation within the genus and reveals stages of this process from incipient to distinct species.
Analyse und Modellierung der Prozess-Strukturwechselwirkungen beim Werkzeugschleifen

As final machine processing mostly grinding is used so failur e of this production step leads to high economic losses. To avoid instable process condition, o adapt the grinding wheel path, and to simulate grinding setups in advance, efficient and phy sically based models are need. In this work especially the tool grinding process is analyse d and characteristically effects are investigated to build up an overall grinding model. The main effects are thereby the time variant dynamical properties of the workpiece due to strong geometr y changes during the flute grinding process and the excitation due to the rotation and topograph y of t e grinding wheel. Additionally analysis of the contact conditions and grinding forces in dependency of the predefined process parameters are carried out. Based on the results of th ese investigation efficient models are build up to represent the behaviour mostly by physical la ws. With the coupled model, grinding processes of one-sided cla mped and long cantilevering workpieces can be simulated high dynamically over several minut es. I is possible to predict grinding forces and geometry errors of the ground flute due to deformat ion of the workpiece. Additionally the temperature of the workpiece can be estimated. Furt hermore the grinding wheel path can be adapted and tested to reduce geometrical errors and to i crease the efficiency of the manufacturing process. With these physically based models systematically investigations of the grinding process and the interaction are possible. With thi s simulation the understanding of grinding can be enhanced which is important to adapt the manu facturing process.
American Journal of Epidemiology Original Contribution Night Work and Breast Cancer Risk among Norwegian Nurses: Assessment by Different Exposure Metrics

Associations between night work and breast cancer risk were investigated in a nested case-control study within a cohort of 49,402 Norwegian nurses. A total of 699 (74%) of the live cases diagnosed in 1990–2007 and 895 (65%) controls, cancer free at the time of sampling, were interviewed about work history and potential risk factors. The odds ratios for risk of breast cancer in relation to different exposure metrics were estimated by multivariate unconditional logistic regression models. No increase of risk was found after long duration of work by nurses working 3 night shifts per month. Small, nonsignificantly increased risks were observed for exposure to 30 years in hospitals or other institutions (odds ratio (OR) ¼ 1.1), 12 years in schedules including night work (OR ¼ 1.3), 1,007 night shifts during the lifetime (OR ¼ 1.2), and lifetime average number of 4 night shifts per month (OR ¼ 1.2). Nonsignificantly increased risks of breast cancer were observed in nurses who worked 5 years with 4 (OR ¼ 1.4) and 5 (OR ¼ 1.6) consecutive night shifts. Significantly increased risks were seen in nurses who worked 5 years with 6 consecutive night shifts (OR ¼ 1.8, 95% confidence interval: 1.1, 2.8). The results suggest that risk may be related to number of consecutive night shifts. Breast cancer is the most common cancer in women in Western societies. Shift work, implying exposure to light at night and the subsequent reduction in the synthesis of the hormone melatonin, has been suggested as a contributing cause of this cancer (1). In 2007, the International Agency for Research on Cancer classified shift work that involves disruption of circadian rhythms as a probable human carcinogen , 2A (2), on the basis of limited evidence from epidemiologic studies and sufficient evidence from animal models. The inconsistent results from the epidemiologic studies might partly be due to different designs and to shortcomings, such as crude assessment of shift and night work characteristics and incomplete adjustment for confounding factors. Previous studies have characterized night work mainly by duration of work in jobs including night shifts. Studies considering additional factors characterizing shift systems, such as length of shift cycle, direction of shift cycle, start time of the work shifts, and number of nights worked in succession, have been requested (3). The aspects of night work that might be associated with breast cancer risk have not been sufficiently understood. It has been …
biDCG: A New Method for Discovering Global Features of DNA Microarray Data via an Iterative Re-Clustering Procedure

Biclustering techniques have become very popular in cancer genetics studies, as they are tools that are expected to connect phenotypes to genotypes, i.e. to identify subgroups of cancer patients based on the fact that they share similar gene expression patterns as well as to identify subgroups of genes that are specific to these subtypes of cancer and therefore could serve as biomarkers. In this paper we propose a new approach for identifying such relationships or biclusters between patients and gene expression profiles. This method, named biDCG, rests on two key concepts. First, it uses a new clustering technique, DCG-tree [Fushing et al, PLos One, 8, e56259 (2013)] that generates ultrametric topological spaces that capture the geometries of both the patient data set and the gene data set. Second, it optimizes the definitions of bicluster membership through an iterative two-way reclustering procedure in which patients and genes are reclustered in turn, based respectively on subsets of genes and patients defined in the previous round. We have validated biDCG on simulated and real data. Based on the simulated data we have shown that biDCG compares favorably to other biclustering techniques applied to cancer genomics data. The results on the real data sets have shown that biDCG is able to retrieve relevant biological information.
Correlations and spatial variability of soil physical properties in harvested Piedmont forests.

Soil response to timber harvest trafficking was similar for eroded soils in two locations of the Piedmont of Alabama. Pre-harvest and post-harvest data indicated compaction to be present to a depth of 40 cm as indicated by cone index measurements, with the most significant changes occurring in the upper 20 cm. The degree of spatial dependence differed among soil properties and varied by the site and the specific soil property. Significant correlations existed between individual properties (different properties for each plot) and supported previous research results in regards to the relationship between soil properties and compaction. Coregionalization was present in each site as indicated by the results for co-kriging of correlated properties and indicated that more intensively sampled properties may provide the means to predict the spatial distribution of more difficultly measured soil properties. However, it is unclear which specific conditions promote the greatest degree of compaction, and which site-soil property combinations should be evaluated to provide a better understanding of soil compaction in Piedmont soils.
Unusual Ovarian Cancer Relapse Managed by Nivolumab in a Long-term Surviving Patient with PD-L1 Mutation

case rePorT This report is approved by the Institutional Review Board of Peking Union Medical College Hospital. A 70‐year‐old female with acute abdomen referred to our hospital and received an emergency laparoscopic exploration in July 2008. Right inguinal hernia with small intestine protrusion was found, as well as ascites with peritoneal dissemination and large omental cake. Although bilateral ovaries were grossly normal, biopsy of both ovaries and peritoneal was done in addition to hernia repair. Pathology examination demonstrated serous papillary carcinoma in both ovaries. Two cycles neoadjuvant chemotherapy of taxol and carboplatin (TC, taxol 175 mg/m2, carboplatin area under the curve = 5, every 3 weeks) were added. Subsequently, a comprehensive cytoreductive surgery was performed. Surgical pathology examination established a Stage IIIc ovarian serous papillary carcinoma. The patient received another six cycles of TC chemotherapy, during which the CA125 level slopped from 1010 to normal after 2 cycles of postoperative chemotherapy. Then, she was under regular surveillance without any sign of relapse till the 7th year in 2015; a tender mass was palpated at the right sternocostal region. PET‐CT demonstrated a 3.7 cm × 4.8 cm soft‐tissue mass with high standardized uptake values (SUV) in anterior mediastinum. Thoracotomy and lower sternum resection were performed and pathology revealed poorly differentiated adenocarcinoma with immunohistochemistry compatible with ovarian cancer metastasis. Thoracic radiation was added as well as four courses of taxol chemotherapy. Platinum was omitted due to late onset allergy of carboplatin. CA125 level remained normal after the initial treatment. Seven months later, the patient noticed a fixed protuberance of 2 cm in diameter on her left forehead. Cranial magnetic resonance imaging demonstrated left parietal and frontal bone osteolytic osseous metastasis. PET/CT showed multiple nodules in both lungs with high SUV as well as the eighth posterior rib, right sacral bone, and left frontal bone, which highly indicated cancer metastasis. The patient received cranial radiation and zoledronic acids for osteolytic osseous metastasis. The whole-exome sequencing revealed CD274 (PD-L1), JAK2, and PDCD1LG2 (PD-L2) gene amplification and functional loss of p53 due to pretermination of transcription. Thus, nivolumab was administered at a dosage of 3 mg/kg every 2 weeks for seven cycles. Five months later, cranial MRI revealed regression of subcutaneous involvement on left frontal bone leaving bone erosion, and pulmonary metastases were also greatly relieved in CT examination [Figure 1]. Unusual Ovarian Cancer Relapse Managed by Nivolumab in a Long-term Surviving Patient with PD-L1 Mutation
Collisionless shockwaves formed by counter-streaming laser-produced plasmas

The interaction between two counter-streaming laser-produced plasmas is investigated using the high-power Shenguang II laser facility. The shockwaves observed in our experiment are believed to be excited by collisionless mechanisms. The dimensionless parameters calculated with the results suggest that it is possible to scale the observation to the supernova remnants using transformation and similarity criteria.
Relationship between diabetic retinopathy severity and the timespan between the endocrinopathy diagnosis and the first ophthalmic examination.

PURPOSE To investigate whether the time interval between type 2 diabetes mellitus (DM) diagnosis and the first fundoscopic examination is related with the presence and the severity of diabetic retinopathy (DR) observed. METHODS A survey of 105 type 2 DM patients referred to ophthalmologic evaluation in the "Hospital das Clinicas" (HC), University of São Paulo Medical School (USPMS). RESULTS Regarding classification of DR in the 105 patients, 15 (14.28%) did not show signs of DR, and 90 (85.72%) exhibited them on fundoscopy. Sixty patients underwent laser therapy, and 46.66% reported poor control of DM. Only 15.23% of DM patients were adequately screened for DR on the first year of their DM diagnosis. Among the 36 patients (34.30%) examined within five years of DM diagnosis, 58.33% did not present or demonstrate signs of mild DR and 22.20% of proliferative DR; 30 patients underwent an ophthalmologic examination after more than eleven years of DM diagnosis, 21.62% did not exhibit signs of DR and 59.46% were classified as proliferative DR. CONCLUSION This study showed a statistically significant relationship between the time interval from the diagnosis of type 2 DM and the first fundoscopic examination with the severity of DR.
Performance analysis of a current-fed bidirectional LLC resonant converter

Performance of a current-fed bidirectional LLC resonant converter for energy storage system in DC grid applications is analyzed and tested. The well match of the voltages on two sides of the LLC circuit is ensured by varying the duty cycle of buck-boost circuit under wide battery voltage range. Hence LLC circuit is operated like a DC transformer to improve efficiency. In the battery discharging mode, the pulse-width modulation (PWM) control is employed. While in the battery charging mode, the phase-shift modulation (PSM) and PWM control is adopted. To achieve the zero-voltage-switching (ZVS) of all the MOSFETs, a frequency feed-forward loop is introduced in the battery charging mode. Compared with conventional bidirectional LLC converter, the frequency regulation range of this converter is narrowed which is beneficial for the design of magnetic components. The operation principles are introduced, the main features such as current ripple of battery, and the zero-voltage-switching (ZVS) of the two modes are analyzed and compared with conventional solutions. A 1.6-kW prototype with a battery voltage of 160V-240V and a DC-bus voltage of 400V has been built and tested to verify the operational principle analysis.
Learning Optimal Policies from Observational Data

Choosing optimal (or at least better) policies is an important problem in domains from medicine to education to finance and many others. One approach to this problem is through controlled experiments/trials - but controlled experiments are expensive. Hence it is important to choose the best policies on the basis of observational data. This presents two difficult challenges: (i) missing counterfactuals, and (ii) selection bias. This paper presents theoretical bounds on estimation errors of counterfactuals from observational data by making connections to domain adaptation theory. It also presents a principled way of choosing optimal policies using domain adversarial neural networks. We illustrate the effectiveness of domain adversarial training together with various features of our algorithm on a semi-synthetic breast cancer dataset and a supervised UCI dataset (Statlog).
From historic books to annotated XML: Building a large multilingual diachronic corpus

This paper introduces our approach towards annotating a large heritage corpus, which spans over 100 years of alpine literature. The corpus consists of over 16.000 articles from the yearbooks of the Swiss Alpine Club, 60% of which represent German texts, 38% French, 1% Italian and the remaining 1% Swiss German and Romansh. The present work describes the inherent difficulties in processing a multilingual corpus by referring to the most challenging annotation phases such as article identification, correction of optical character recognition (OCR) errors, tokenization, and language identification. The paper aims to raise awareness for the efforts in building and annotating multilingual corpora rather than to evaluate each individual annotation phase. Keywords: multilingual corpora, cultural heritage, corpus annotation, text digitization
Physical health, lifestyle beliefs and behaviors, and mental health of entering graduate health professional students: Evidence to support screening and early intervention

Background and purpose:Little is known about the physical health, lifestyle beliefs and behaviors, and mental health among first‐year health professional graduate students. Therefore, the purpose of this study was to describe these attributes as well as to explore the relationships among them. Methods:A descriptive correlational study was conducted on the baseline data from a wellness onboarding intervention study with 93 health sciences students from seven different colleges within a large public land grant university in the Midwest United States. Findings:Nearly 40% of the sample was overweight/obese, and 19% of students had elevated total cholesterol levels. Only 44% met the recommended 30 min of exercise 5 days per week. Forty‐one percent reported elevated depressive symptoms and 28% had elevated anxiety. Four students reported suicidal ideation. Inverse relationships existed among depression/anxiety and healthy lifestyle beliefs/behaviors. Conclusions:Students entering health professional schools are at high risk for depression, anxiety, and unhealthy behaviors, which could be averted through screening and early evidence‐based interventions. Implications for practice:Assessing the physical health, lifestyle behaviors, and mental health of first‐year health sciences professional students is important to identify health problems and modifiable at‐risk behaviors so that early interventions can be implemented to improve outcomes.
Three Dimensional Quantitative Coronary Angiography Can Detect Reliably Ischemic Coronary Lesions Based on Fractional Flow Reserve

Conventional coronary angiography (CAG) has limitations in evaluating lesions producing ischemia. Three dimensional quantitative coronary angiography (3D-QCA) shows reconstructed images of CAG using computer based algorithm, the Cardio-op B system (Paieon Medical, Rosh Ha'ayin, Israel). The aim of this study was to evaluate whether 3D-QCA can reliably predict ischemia assessed by myocardial fractional flow reserve (FFR) < 0.80. 3D-QCA images were reconstructed from CAG which also were evaluated with FFR to assess ischemia. Minimal luminal diameter (MLD), percent diameter stenosis (%DS), minimal luminal area (MLA), and percent area stenosis (%AS) were obtained. The results of 3D-QCA and FFR were compared. A total of 266 patients was enrolled for the present study. FFR for all lesions ranged from 0.57 to 1.00 (0.85 ± 0.09). Measurement of MLD, %DS, MLA, and %AS all were significantly correlated with FFR (r = 0.569, 0609, 0.569, 0.670, respectively, all P < 0.001). In lesions with MLA < 4.0 mm2, %AS of more than 65.5% had a 80% sensitivity and a 83% specificity to predict FFR < 0.80 (area under curve, AUC was 0.878). 3D-QCA can reliably predict coronary lesions producing ischemia and may be used to guide therapeutic approach for coronary artery disease. Graphical Abstract
Growth and Nitrogen Uptake Kinetics in Cultured Prorocentrum donghaiense

We compared growth kinetics of Prorocentrum donghaiense cultures on different nitrogen (N) compounds including nitrate (NO3 −), ammonium (NH4 +), urea, glutamic acid (glu), dialanine (diala) and cyanate. P. donghaiense exhibited standard Monod-type growth kinetics over a range of N concentraions (0.5–500 μmol N L−1 for NO3 − and NH4 +, 0.5–50 μmol N L−1 for urea, 0.5–100 μmol N L−1 for glu and cyanate, and 0.5–200 μmol N L−1 for diala) for all of the N compounds tested. Cultures grown on glu and urea had the highest maximum growth rates (μm, 1.51±0.06 d−1 and 1.50±0.05 d−1, respectively). However, cultures grown on cyanate, NO3 −, and NH4 + had lower half saturation constants (Kμ, 0.28–0.51 μmol N L−1). N uptake kinetics were measured in NO3 −-deplete and -replete batch cultures of P. donghaiense. In NO3 −-deplete batch cultures, P. donghaiense exhibited Michaelis-Menten type uptake kinetics for NO3 −, NH4 +, urea and algal amino acids; uptake was saturated at or below 50 μmol N L−1. In NO3 −-replete batch cultures, NH4 +, urea, and algal amino acid uptake kinetics were similar to those measured in NO3 −-deplete batch cultures. Together, our results demonstrate that P. donghaiense can grow well on a variety of N sources, and exhibits similar uptake kinetics under both nutrient replete and deplete conditions. This may be an important factor facilitating their growth during bloom initiation and development in N-enriched estuaries where many algae compete for bioavailable N and the nutrient environment changes as a result of algal growth.