Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomarker Associations with Efficacy of Abiraterone Acetate and Exemestane in Postmenopausal Patients with Estrogen Receptor–Positive Metastatic Breast Cancer

Purpose: Abiraterone may suppress androgens that stimulate breast cancer growth. We conducted a biomarker analysis of circulating tumor cells (CTCs), formalin-fixed paraffin-embedded tissues (FFPETs), and serum samples from postmenopausal estrogen receptor (ER)+ breast cancer patients to identify subgroups with differential abiraterone sensitivity. Methods: Patients (randomized 1:1:1) were treated with 1,000 mg/d abiraterone acetate + 5 mg/d prednisone (AA), AA + 25 mg/d exemestane (AAE), or exemestane. The biomarker population included treated patients (n = 293). The CTC population included patients with ≥3 baseline CTCs (n = 104). Biomarker [e.g., androgen receptor (AR), ER, Ki-67, CYP17] expression was evaluated. Cox regression stratified by prior therapies in the metastatic setting (0/1 vs. 2) and setting of letrozole/anastrozole (adjuvant vs. metastatic) was used to assess biomarker associations with progression-free survival (PFS). Results: Serum testosterone and estrogen levels were lowered and progesterone increased with AA. Baseline AR or ER expression was not associated with PFS in CTCs or FFPETs for AAE versus exemestane, but dual positivity of AR and ER expression was associated with improved PFS [HR, 0.41; 95% confidence interval (CI), 0.16–1.07; P = 0.070]. For AR expression in FFPETs obtained <1 year prior to first dose (n = 67), a trend for improved PFS was noted for AAE versus exemestane (HR, 0.56; 95% CI, 0.24–1.33; P = 0.19). Conclusions: An AA pharmacodynamic effect was shown by decreased serum androgen and estrogen levels and increased progesterone. AR and ER dual expression in CTCs and newly obtained FFPETs may predict AA sensitivity. Clin Cancer Res; 22(24); 6002–9. ©2016 AACR.
Analysis of Trichosporon Isolates Obtained from the Houses of Patients with Summer-Type Hypersensitivity Pneumonitis

ABSTRACT Summer-type hypersensitivity pneumonitis (SHP) is type III or IV allergies developed by repeated inhalation of arthroconidia of Trichosporon species. We identified 105 strains obtained from the homes of 36 SHP patients by analysis of the intergenic spacer (IGS) 1 region, which is located between the 26S and 5S rRNA genes; in addition, we analyzed the IGS genotypes of the strains. Serologically, Trichosporon species are classified as serotype I, II, III, or I-III. Of the 105 strains, 43 (41.1%), 53 (50.5%), and 9 (8.6%) strains were isolated as serotypes I, II, and III, respectively. Serotype I, II, and III strains were recovered from 19 (52.8%), 29 (80.6%), and 4 (11.1%) of the 36 houses of SHP patients, respectively. No serotype I-III strains were isolated from the houses. Of 43 serotype I strains, 42 (97.7%) were identified as Trichosporon dermatis, and the remaining one was T. terricola. Of 53 serotype II strains, 37 (69.8%) were identified as T. asahii, and the remaining serotype II isolates were T. aquatile (1.9%), T. coremiiforme (7.5%), T. faecale (1.9%), T. japonicum (15.1%), and T. ovoides (3.8%). There were nine serotype III strains comprised of T. montevideense (77.8%) and T. domesticum (22.2%). Intraspecies diversity was found only in T. asahii. This microorganism also causes opportunistic infections (trichosporonosis); seven genotypes of its IGS 1 region have been identified. While the strains of T. asahii obtained from Japanese patients with trichosporonosis were genotype I, the strains from the houses of SHP patients were genotype III. Based on our analysis, we conclude that the strains that play the most significant roles in the development of SHP are T. dermatis, T. asahii genotype 3, and T. montevideense, representing serotypes I, II, and III, respectively.
Functional Characterization of ABC10α, an Essential Polypeptide Shared by All Three Forms of Eukaryotic DNA-dependent RNA Polymerases*

ABC10α is a small polypeptide shared by the three yeast RNA polymerases. Homologous polypeptides in higher eukaryotes have a zinc-binding CX 2C … CX 2C motif and a conserved basic C-terminal end. These features are also found in archaeal gene products that may encode an RNA polymerase subunit. The CX 2C … CX 2C motif is partly dispensable, since only its first cysteine is essential for growth, whereas the basic C-terminal end is critical in vivo. A mutant in the latter domain has an RNA polymerase III-specific defect and, in vitro, impairs RNA polymerase III assembly. Polymerase activity was, however, not affected in various faithful transcription assays. The mutant is suppressed by a high gene dosage of the second largest subunit of RNA polymerase III, whereas the homologous subunits of RNA polymerase I and II have aggravating effects. In a two-hybrid assay, ABC10α binds to the C-terminal half of the second largest subunit of RNA polymerase I, in a way that requires the integrity of the CX 2C … CX 2C motif. Thus, ABC10α appears to interact directly with the second largest subunit during polymerase assembly. This interaction is presumably a major rate-limiting step in assembly, since diploid cells containing only one functional gene copy for ABC10α have a partial growth defect.
Improvement of the eradication rate of Helicobacter pylori gastritis in children is by adjunction of omeprazole to a dual antibiotherapy

Aim: The possible improvement of efficacy and tolerability of a 7‐day dual antibiotherapy amoxicillin‐clarithromycin (AC) on the eradication of Helicobacter pylori (H. pylori) gastritis in children by the adjunction of omeprazole (OAC) was studied.
Epidemiology of Parkinson's Disease: A Population-Based Study in Primary Care in Italy

Background: There are no studies on prevalence, incidence and comorbidities of Parkinson's disease (PD) in the Italian population. Methods: The database of 700 Italian general practitioners (population, 923,356) was investigated. All patients with International Classification of Diseases Ninth Revision - Clinical Modification (ICD-9-CM) diagnosis of PD during the period 2002-2012 were included. Parkinsonisms were excluded. Clinical conditions preceding PD were identified through ICD-9-CM codes. The Charlson Comorbidity Index was used. PD crude and standardized prevalence and annual incidence were calculated. Crude and adjusted hazard ratios were calculated for comorbidities. Results: A total of 2,204 patients (1,140 men, 1,064 women, age 22-95 years) were included. The crude prevalence of PD was 239/100,000. Prevalence increased exponentially with age. Standardized prevalence was 233 (95% CI 232-235). One hundred ninety-four patients were newly diagnosed, giving a crude incidence of 22/100,000 and a standardized incidence of 23.1/100,000 (95% CI 22.9-23.2). Incidence increased steadily until age 75-84 years and then decreased. Older age, cardiovascular and gastrointestinal disorders, diabetes, and restless-legs syndrome were associated with increased PD risk and smoking and hypersomnia with decreased PD risk. The Charlson Comorbidity Index was associated with PD risk with a documented gradient. Conclusions: Prevalence and incidence of PD in Italy are in line with studies with the highest case ascertainment. PD risk varies with the number and type of comorbidities.
Temporal adverbials, negation and finiteness in Dutch as a second language: A scope-based account

Abstract This study investigates the acquisition of post-verbal (temporal) adverbials and post-verbal negation in L2 Dutch. It is based on previous findings for L2 French that post-verbal negation poses less of a problem for L2 learners than post-verbal adverbial placement (Hawkins, Towell, Bazergui, Second Language Research 9: 189–233, 1993; Herschensohn, Minimally raising the verb issue: 325–336, Cascadilla Press, 1998). The current data show that, at first sight, Moroccan and Turkish learners of Dutch also have fewer problems with post-verbal negation than with post-verbal adverbials. However, when a distinction is made between different types of adverbials, it seems that this holds for adverbials of position such as ‘today’ but not for adverbials of contrast such as ‘again’. To account for this difference, it is argued that different types of adverbial occupy different positions in the L2 data for reasons of scope marking. Moreover, the placement of adverbials such as ‘again’ interacts with the acquisition of finiteness marking (resulting in post-verbal placement), while there is no such interaction between adverbials such as ‘today’ and finiteness marking.
Application of a Rules-based Natural Language Parser to Critical Value Reporting in Anatomic Pathology

Critical values in anatomic pathology are rare occurrences and difficult to define with precision. Nevertheless, accrediting institutions require effective and timely communication of all critical values generated by clinical and anatomic laboratories. Provisional gating criteria for potentially critical anatomic diagnoses have been proposed, with some success in their implementation reported in the literature. Ensuring effective communication is challenging, however, making the case for programmatic implementation of a turnkey-style integrated information technology solution. To address this need, we developed a generically deployable laboratory information system-based tool, using a tiered natural language processing predicate calculus inference engine to identify qualifying cases that meet criteria for critical diagnoses but lack an indication in the electronic medical record for an appropriate clinical discussion with the ordering physician of record. Using this tool, we identified an initial cohort of 13,790 cases over a 49-month period, which were further explored by reviewing the available electronic medical record for each patient. Of these cases, 35 (0.3%) were judged to require intervention in the form of direct communication between the attending pathologist and the clinical physician of record. In 8 of the 35 cases, this intervention resulted in the conveyance of new information to the requesting physician and/or a change in the patient’s clinical plan. The very low percentage of such cases (0.058%) illustrates their rarity in daily practice, making it unlikely that manual identification/notification approaches alone can reliably manage them. The automated turnkey system was useful in avoiding missed handoffs of significant, clinically actionable diagnoses.
Adoption of Open Government Data for Commercial Service Innovation: an Inductive Case Study on Parking Open Data Services

City councils produce large amounts of data. As this data becomes available, and as information and communication technology capabilities are in place to manage and exploit this data, open government data is seen as becoming more and more valuable as a catalyst for service innovation and economic growth. Notwithstanding this, evidence of open data adoption is currently largely scattered and anecdotal. This is reflected in the lack of literature focusing on users of open data for commercial purposes. This research aims to address this gap and contributes to the IS open data services debate by proposing a model of factors perceived by an open data services business as the most relevant in explaining adoption of open government data for commercial service innovation in cities. Adopting an inductive reasoning approach through qualitative methods was critical to capture the complexity of the open data services ecosystem perceived by those reusing this data.
Mechanical and Electrical Characterisation of Individual ACA Conductor Particles

Anisotropic conductive adhesives (ACAs) consist of a polymer adhesive matrix containing fine conductive particles. The primary objective of this experimental research is to establish a clearer understanding of the effects of the bonding force on the deformation of individual ACA particles and their resulting conductivity when in contact with an appropriate metallic surface. This has been achieved through simultaneous measurements of the deformation and electrical resistance whilst applying force using a specially configured nano-indenter machine, where the "indenter", instead of being pointed, had a flat tip about 20-30 mum in diameter. The merit of using this machine is that very small forces, of the order of 100 mN, can be accurately applied to the particles to a resolution of 100 nN and the resulting deformations, of less than 6 mum, can then be recorded to a resolution of 0.1 nm. The results showed that the ACA particle deformation was nonlinear and that the force/deformation at which particle crushing occurs was affected by the load rate. The resistance was observed to decrease as the deformation increased up to the crush point at which stage it increased slightly. The voltage versus current behaviour of a deformed ACA particle was also found to be linear.
Digenean parasites of deep-sea teleosts: a review and case studies of intrageneric phylogenies

SUMMARY Studies on the digenean parasites of deep-sea (> 200 m depth) teleosts are reviewed and two case study generic phylogenies are presented based on LSU rDNA and ND1 mtDNA sequences. The phylogeny of the lepocreadiid genus Lepidapedon, the most common deep-sea digenean genus, is not clearly resolved as the two gene trees are not compatible. It can be inferred, however, that the genus has radiated in the deeper waters off the continental shelf, mainly in fishes of the gadiform family Macrouridae. Steringophorus, a fellodistomid genus, is better resolved. In this case a deep-sea radiation is also indicated, but the pattern of host-specificity is not clear, with evidence of much host-switching. Results of studies of the parasites of the macrourid fish Coryphaenoides (Nematomirus) armatus from various depths have reinforced recent views on the lack of zoned depth-related communities in the deep-sea. The diversity of deep-sea digeneans is relatively low with only 18 families (of about 60) reported. Little, or nothing, is known from most deep-sea areas and nothing from trenches and mid-ocean ridge systems.
Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment

Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM) that is strongly associated with approximately five-fold increased risk of cardiovascular mortality. CAN manifests in a spectrum of things, ranging from resting tachycardia and fixed heart rate (HR) to development of “silent” myocardial infarction. Clinical correlates or risk markers for CAN are age, DM duration, glycemic control, hypertension, and dyslipidemia (DLP), development of other microvascular complications. Established risk factors for CAN are poor glycemic control in type 1 DM and a combination of hypertension, DLP, obesity, and unsatisfactory glycemic control in type 2 DM. Symptomatic manifestations of CAN include sinus tachycardia, exercise intolerance, orthostatic hypotension (OH), abnormal blood pressure (BP) regulation, dizziness, presyncope and syncope, intraoperative cardiovascular instability, asymptomatic myocardial ischemia and infarction. Methods of CAN assessment in clinical practice include assessment of symptoms and signs, cardiovascular reflex tests based on HR and BP, short-term electrocardiography (ECG), QT interval prolongation, HR variability (24 h, classic 24 h Holter ECG), ambulatory BP monitoring, HR turbulence, baroreflex sensitivity, muscle sympathetic nerve activity, catecholamine assessment and cardiovascular sympathetic tests, heart sympathetic imaging. Although it is common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. Treatment is based on early diagnosis, life style changes, optimization of glycemic control and management of cardiovascular risk factors. Pathogenetic treatment of CAN includes: Balanced diet and physical activity; optimization of glycemic control; treatment of DLP; antioxidants, first of all α-lipoic acid (ALA), aldose reductase inhibitors, acetyl-L-carnitine; vitamins, first of all fat-soluble vitamin B1; correction of vascular endothelial dysfunction; prevention and treatment of thrombosis; in severe cases-treatment of OH. The promising methods include prescription of prostacyclin analogues, thromboxane A2 blockers and drugs that contribute into strengthening and/or normalization of Na+, K+-ATPase (phosphodiesterase inhibitor), ALA, dihomo-γ-linolenic acid (DGLA), ω-3 polyunsaturated fatty acids (ω-3 PUFAs), and the simultaneous prescription of ALA, ω-3 PUFAs and DGLA, but the future investigations are needed. Development of OH is associated with severe or advanced CAN and prescription of nonpharmacological and pharmacological, in the foreground midodrine and fludrocortisone acetate, treatment methods are necessary.
Anti-inflammatory effect of the proteasome inhibitor bortezomib on endotoxin-induced uveitis in rats.

PURPOSE We evaluated the anti-inflammatory effect of bortezomib (Velcade), a proteasome inhibitor, on endotoxin-induced uveitis (EIU) in rats and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. METHODS EIU was induced by footpad injection of LPS into Lewis rats. MG-132 (10 mg/kg), or high-dose (0.2 mg/kg) or low-dose (0.05 mg/kg) bortezomib was given 30 minutes before LPS injection in each treatment group. The rats were sacrificed 24 hours later to observe the inflammatory response in tissues. The expression levels of fractalkine, MCP-1, ICAM-1, and iNOS were evaluated by PCR and Western blot analysis. Immunohistochemical (IHC) studies were used to demonstrate the expression of pro-inflammatory mediators and nuclear factor-kappa B (NF-κB) p65 in the iris and ciliary body. The DNA-binding activity of NF-κB was evaluated using an electrophoretic mobility shift assay (EMSA). An in vitro study using RAW 264.7 cells was performed to verify the results. RESULTS Pretreatment with high-dose bortezomib significantly attenuated the inflammatory response of EIU. Reduced expression of inflammatory mediators always was observed in the high-dose bortezomib and MG-132 groups, but invariably was not noted in the low-dose bortezomib group. Decreased DNA-binding activity of NF-κB was noted in those rats pretreated with high-dose bortezomib or MG-132. In vitro study demonstrated the dose-dependent anti-inflammatory effects of bortezomib in LPS-stimulated RAW cells, consistent with the results obtained in vivo. CONCLUSIONS Bortezomib inhibits EIU, probably by inhibiting the activation of NF-κB, which in turn, down-regulates the expression of the associated inflammatory genes. Proteasome inhibition may be a potential treatment strategy for uveitis.
Applications of Family Systems Theory to the Study of Adulthood

Psychologists who study children have emphasized family processes that influence children's psychological well-being and subsequent development, but gerontologists have rarely considered the impact of the family as system in adulthood. Drawing on family systems theories, we show how between-family, within-family, and within-individual differences emerge from family interactions in adulthood. Specifically, we consider how adult behavior might be understood in terms of norms sustained by the larger family system. We present three case studies of adult families to illustrate the ways in which their shared beliefs shape emotional experiences, behavior, and conceptions of self and family in adulthood. The family, as a milieu, continues to exert influence over the day-to-day life of individual members after they are grown.
Transcription Factors VND1-VND3 Contribute to Cotyledon Xylem Vessel Formation1[OPEN]

VND1, VND2, and VND3 are required for xylem vessel element formation in the secondary veins of Arabidopsis cotyledons grown under continuous dark conditions. Arabidopsis (Arabidopsis thaliana) VASCULAR-RELATED NAC-DOMAIN1 (VND1) to VND7 encode a group of NAC domain transcription factors that function as master regulators of xylem vessel element differentiation. These transcription factors activate the transcription of genes required for secondary cell wall formation and programmed cell death, key events in xylem vessel element differentiation. Because constitutive overexpression of VND6 and VND7 induces ectopic xylem vessel element differentiation, functional studies of VND proteins have largely focused on these two proteins. Here, we report the roles of VND1, VND2, and VND3 in xylem vessel formation in cotyledons. Using our newly established in vitro system in which excised Arabidopsis cotyledons are stimulated to undergo xylem cell differentiation by cytokinin, auxin, and brassinosteroid treatment, we found that ectopic xylem vessel element differentiation required VND1, VND2, and VND3 but not VND6 or VND7. The importance of VND1, VND2, and VND3 also was indicated in vivo; in the vnd1 vnd2 vnd3 seedlings, xylem vessel element differentiation of secondary veins in cotyledons was inhibited under dark conditions. Furthermore, the light responsiveness of VND gene expression was disturbed in the vnd1 vnd2 vnd3 mutant, and vnd1 vnd2 vnd3 failed to recover lateral root development in response to the change of light conditions. These findings suggest that VND1 to VND3 have specific molecular functions, possibly linking light conditions to xylem vessel formation, during seedling development.
Cusp–core transformations induced by AGN feedback in the progenitors of cluster galaxies

ABSTRACT In a recent study (Martizzi et al. 2012), we used cosmological simulations to show thatactive galactic nuclei (AGN) feedback on the gas distribution in clusters of galaxies canbe important in determining the spatial distribution of stars and dark matter in thecentralregionsofthese systems.The hierarchicalassemblyof darkmatter, baryonsandblack holes obscures the physical mechanism behind the restructuring process. Herewe use idealized simulations to follow the response of a massive dark matter halo aswe feed the central black hole with a controlled supply of cold gas. This removes mostof the complexity taking place in the cosmological simulations that may have biasedour previous study. We conﬁrm our previous results: gas heated and expelled from thecentral regions of the halo by AGN feedback can return after cooling; repeated cyclesgenerate gravitational potential ﬂuctuations responsible for irreversible modiﬁcationsof the dark matter mass proﬁle. The main result is the expulsion of large amountsof baryons and dark matter from the central regions of the halo. According to thework presented here, outﬂow induced ﬂuctuations represent the only mechanism ableto eﬃciently create dark matter cores in clusters of galaxies.Keywords: black hole physics – cosmology:theory – cosmology:large-scalestructureof Universe – galaxies: formation – galaxies: clusters: general – methods: numerical
Atomic norm denoising-based channel estimation for massive multiuser MIMO systems

In this paper, we propose a novel channel estimation method for massive multiple-input multiple-output (MIMO) systems operating in time-division duplexing (TDD) mode. By exploiting the fact that the degrees of freedom of the physical channel matrix are smaller than the number of free parameters, the channel estimation is formulated as an atomic norm denoising problem and solved efficiently via the alternating direction method of multipliers (ADMM). Both theoretical analysis and numerical simulations demonstrate that our proposed method outperforms existing ones in terms of the channel estimation performance.