Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Strong CYP3A Inhibition and Induction on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor: Results of Drug‐Drug Interaction Studies in Patients With Advanced Solid Tumors or Lymphoma and a Physiologically Based Pharmacokinetic Analysis

At clinically relevant ixazomib concentrations, in vitro studies demonstrated that no specific cytochrome P450 (CYP) enzyme predominantly contributes to ixazomib metabolism. However, at higher than clinical concentrations, ixazomib was metabolized by multiple CYP isoforms, with the estimated relative contribution being highest for CYP3A at 42%. This multiarm phase 1 study (Clinicaltrials.gov identifier: NCT01454076) investigated the effect of the strong CYP3A inhibitors ketoconazole and clarithromycin and the strong CYP3A inducer rifampin on the pharmacokinetics of ixazomib. Eighty‐eight patients were enrolled across the 3 drug‐drug interaction studies; the ixazomib toxicity profile was consistent with previous studies. Ketoconazole and clarithromycin had no clinically meaningful effects on the pharmacokinetics of ixazomib. The geometric least‐squares mean area under the plasma concentration‐time curve from 0 to 264 hours postdose ratio (90%CI) with vs without ketoconazole coadministration was 1.09 (0.91‐1.31) and was 1.11 (0.86‐1.43) with vs without clarithromycin coadministration. Reduced plasma exposures of ixazomib were observed following coadministration with rifampin. Ixazomib area under the plasma concentration‐time curve from time 0 to the time of the last quantifiable concentration was reduced by 74% (geometric least‐squares mean ratio of 0.26 [90%CI 0.18‐0.37]), and maximum observed plasma concentration was reduced by 54% (geometric least‐squares mean ratio of 0.46 [90%CI 0.29‐0.73]) in the presence of rifampin. The clinical drug‐drug interaction study results were reconciled well by a physiologically based pharmacokinetic model that incorporated a minor contribution of CYP3A to overall ixazomib clearance and quantitatively considered the strength of induction of CYP3A and intestinal P‐glycoprotein by rifampin. On the basis of these study results, the ixazomib prescribing information recommends that patients should avoid concomitant administration of strong CYP3A inducers with ixazomib.
Schubert calculus and representations of the general linear group

We construct a canonical isomorphism between the Bethe algebra acting on a multiplicity space of a tensor product of evaluation gl_N[t]-modules and the scheme-theoretic intersection of suitable Schubert varieties. Moreover, we prove that the multiplicity space as a module over the Bethe algebra is isomorphic to the coregular representation of the scheme-theoretic intersection. In particular, this result implies the simplicity of the spectrum of the Bethe algebra for real values of evaluation parameters and the transversality of the intersection of the corresponding Schubert varieties.
Cytologic Features of Atypical Polypoid Adenomyoma of the Endometrium

BACKGROUND In 1981, Mazur reported the histologic characteristics of atypical polypoid adenomyoma (APA) of the endometrium. Although most APAs of the endometrium are considered to show benign behavior, there is a small associated risk of the development of adenocarcinoma. The histology of APA of the endometrium is well defined, but the cytologic features of the lesion have not yet been clarified. CASE A 28-year-old nulligravida with hypermenorrhea had an exophytic, polypoid mass arising from the posterior uterine wall on ultrasonography and magnetic resonance imaging. The results of endometrial smear and biopsy were normal. Transcervical total resection of the tumor was performed with a resectoscope. Frozen sections of the sample suggested APA of the endometrium, and the permanent sections confirmed the diagnosis. The tumor stump/resection plane smears revealed overlapping, highly atypical glandular cells with enlarged, hyperchromatic nuclei; squamous metaplastic cells; and abundant, spindled smooth muscle cells on a clear background, effectively reflecting the epithelial and mesenchymal cell components of the lesion. CONCLUSION Endometrial smear and biopsy are inaccurate methods for the diagnosis of APA of the endometrium because of limited sampling. Tumor stump/resection plane cytology appears to be useful for detecting APA of the endometrium.
The effect of bearing surface on risk of periprosthetic joint infection in total hip arthroplasty: A SYSTEMATIC REVIEW AND META‐ANALYSIS

Aims Periprosthetic joint infection (PJI) is a serious complication of total hip arthroplasty (THA). Different bearing surface materials have different surface properties and it has been suggested that the choice of bearing surface may influence the risk of PJI after THA. The objective of this meta‐analysis was to compare the rate of PJI between metal‐onpolyethylene (MoP), ceramic‐on‐polyethylene (CoP), and ceramic‐on‐ceramic (CoC) bearings. Patients and Methods Electronic databases (Medline, Embase, Cochrane library, Web of Science, and Cumulative Index of Nursing and Allied Health Literature) were searched for comparative randomized and observational studies that reported the incidence of PJI for different bearing surfaces. Two investigators independently reviewed studies for eligibility, evaluated risk of bias, and performed data extraction. Meta‐analysis was performed using the Mantel‐Haenzel method and random‐effects model in accordance with methods of the Cochrane group. Results Our search strategy revealed 2272 studies, of which 17 met the inclusion criteria and were analyzed. These comprised 11 randomized controlled trials and six observational studies. The overall quality of included studies was high but the observational studies were at high risk of bias due to inadequate adjustment for confounding factors. The overall cumulative incidence of PJI across all studies was 0.78% (1514/193 378). For each bearing combination, the overall incidence was as follows: MoP 0.85% (1353/158 430); CoP 0.38% (67/17 489); and CoC 0.53% (94/17 459). The meta‐analysis showed no significant difference between the three bearing combinations in terms of risk of PJI. Conclusion On the basis of the clinical studies available, there is no evidence that bearing choice influences the risk of PJI. Future research, including basic science studies and large, adequately controlled registry studies, may be helpful in determining whether implant materials play a role in determining the risk of PJI following arthroplasty surgery.
Enhanced tensile ductility in an electrodeposited nanocrystalline copper

A fully dense nanocrystalline (nc) Cu with mean grain size of 72 nm and a broad grain size distribution was synthesized by electrodeposition. Uniaxial tensile tests were done at different strain rates and room temperature. A very high strength of 1.04 G was obtained at strain rate of 0.1 s^−1. The nearly perfect plasticity with a large strain of close to 20% was displayed at specific low strain rates of 4 × 10^−5 to 10^−4 s^−1. With increasing strain rate, the nearly perfect plasticity disappeared. Strain rate sensitivity and activation volume of the nc Cu were estimated from the flow stress at a fixed strain of 1% and a strain rate change (jump) test. It was deduced from the high strain rate sensitivity exponent of 0.08 and small activation volume of 12b^3 that both dislocation and grain boundary activities would take place in this nc Cu, which explained the nearly perfect plasticity observed in the tensile test.
Edinburgh Research Explorer Detection of potentially novel paramyxovirus and coronavirus viral RNA in bats and rats in the Mekong Delta region of southern

Bats and rodents are being increasingly recognized as reservoirs of emerging zoonotic viruses. Various studies have investigated bat viruses in tropical regions, but to date there are no data regarding viruses with zoonotic potential that circulate in bat and rat populations in Viet Nam. To address this paucity of data, we sampled three bat farms and three wet markets trading in rat meat in the Mekong Delta region of southern Viet Nam. Faecal and urine samples were screened for the presence of RNA from paramyxoviruses, coronaviruses and filoviruses. Paramyxovirus RNA was detected in 4 of 248 (1%) and 11 of 222 (4.9%) bat faecal and urine samples, respectively. Coronavirus RNA was detected in 55 of 248 (22%) of bat faecal samples; filovirus RNA was not detected in any of the bat samples. Further, coronavirus RNA was detected in 12 of 270 (4.4%) of rat faecal samples; all samples tested negative for paramyxovirus. Phylogenetic analysis revealed that the bat paramyxoviruses and bat and rat coronaviruses were related to viruses circulating in bat and rodent populations globally, but showed no cross- species mixing of viruses between bat and rat populations within Viet Nam. Our study shows that potentially novel variants of paramyxoviruses and coronaviruses commonly circulate in bat and rat populations in Viet Nam. Further characterization of the viruses and additional human and animal surveillance is re-quired to evaluate the likelihood of viral spillover and to assess whether these viruses pose a risk to human health.
Clinical and Cytologic Features of Papillary Neoplasms of the Breast

OBJECTIVE To compare the cytologic features benign and malignant papillary breast lesions. STUDY DESIGN We reviewed the clinical and cytologic features in 29 cases of intraductal papilloma and 26 cases of atypical papilloma or papillary carcinoma that had been diagnosed by histologic examination. The diameter of the mass was examined as a clinical feature. The cytologic features evaluated were as follows: bloody background, row of tall columnar cells, naked bipolar nuclei, hemosiderin-laden macrophages, myoepithelial cells, single scattered atypical cells, cellularity, nuclear atypia, nuclear grade, apocrine metaplasia, eosinophilic cytoplasmic granules, papillary clusters, small papillae, cell balls and large sheets. RESULTS Of the features evaluated, the diameter of the mass, naked bipolar nuclei and cell balls differed significantly between benign and atypical or malignant papillary neoplasms. The average diameter of a benign papillary neoplasm was 1.8 cm, and that of an atypical or malignant papillary neoplasm was 2.2 cm (p = 0.042). Naked bipolar nuclei were found in 27 cases of benign papillary neoplasm (93.1%) versus 19 cases of atypical or malignant papillary neoplasm (73.1%) (p = 0.050). Cell balls were found in 14 (48.3%) and 21 (80.8%) cases, respectively (p = 0.012). All 6 cases in which cell balls were present and naked bipolar nuclei were absent proved to be atypical or malignant papillary neoplasms. Of 17 cases in which cell balls were absent and naked bipolar nuclei present, 13 (76.5%) were benign papillary neoplasms. CONCLUSION Most cytologic features overlapped in benign and atypical or malignant papillary neoplasms. Although they were not pathognomonic, naked bipolar nuclei and cell balls were cytologic features that differed significantly between benign and atypical or malignant papillary neoplasms. When papillary neoplasms of the breast are suspected in a cytologic smear, the combination of clinical examination, mammography and cytologic features should be considered to make the correct diagnosis.
Adolescent temperament dimensions as stable prospective risk and protective factors for salivary C‐reactive protein

OBJECTIVE Temperament has associations with later physical health outcomes, yet there is a dearth of research exploring the connection between temperament and mechanisms that have known associations with these health outcomes. Recent research has delineated a connection between personality and inflammation during adulthood, but this association has not yet been studied in adolescent samples. DESIGN We investigated whether stable adolescent temperament (averaged over two years), specifically effortful control and negative emotionality, provided a more robust prediction of inflammation as measured by salivary C-reactive protein (sCRP), than depressive symptoms. METHODS Temperament and depressive symptoms were measured in a sample of sixty-three adolescents (37 males) when they were approximately 12 years old (mean age = 12.30, SD = 0.69) and again when they were approximately 14 years old (mean age = 14.84, SD = 0.49). Levels of sCRP were determined approximately 7 months later (mean = 6.77, SD = 2.99) when participants were approximately 15 years old (mean age = 15.49, SD = 0.49). RESULTS Regression analyses revealed that effortful control (EC) was significantly associated with lower sCRP levels, while higher negative emotionality (NE) was significantly associated with higher sCRP levels. Furthermore, these associations were larger than those for depressive symptoms and were differentially impacted by the addition of covariates. Implications for the role of stable risk and protective factors in inflammatory processes are discussed. CONCLUSIONS These findings are the first to show associations between adolescent temperament and inflammation. Furthermore, these findings extend previous personality research to temperamental research in a younger sample of adolescents. Statement of contribution What is already known? There is a large extant literature on the association between depressive symptoms and inflammation. There is a smaller extant literature on the association between personality and inflammation. No studies have examined how adolescent temperament traits may relate to inflammation. What does this study add? Longitudinal data collection over the course of 3 years in an adolescent sample. Addresses the question of whether temperament factors relate to inflammation. Temperament provides a more robust predictor of later inflammation than depressive symptoms.
Phylogeography of Lionfishes (Pterois) Indicate Taxonomic Over Splitting and Hybrid Origin of the Invasive Pterois volitans

The lionfish is an iconic marine fish, and recently renowned for a disastrous introduction into the West Atlantic. Genetic surveys of the putative invaders (Pterois volitans and Pterois miles) in their natural Indo-Pacific range can illuminate both topics. Previous research indicated that P. volitans and P. miles are sister species that hybridize in the invasive range, but hybridization in the native range is unknown. Here, we apply mtDNA COI and 2 nuclear introns (S7 RP1 and Gpd2) from 229 lionfish including the 2 invaders and 2 closely-related taxa (44 P. miles, 91 P. volitans, 31 Pterois lunulata, and 63 Pterois russelii) from 10 locations in their native ranges. Genetic data are supplemented with key morphological characters: dorsal, anal, and pectoral fin ray counts. We observed 2 lineages (d = 4.07%, 0.89%, and 2.75% at COI, S7 RP1, and Gpd2, respectively) among the 4 putative species: an Indian Ocean lineage represented by P. miles, and a Pacific Ocean lineage represented by P. lunulata and P. russelii. All specimens of the invasive P. volitans appear to be hybrids between the Indian Ocean P. miles and a Pacific lineage encompassing P. lunulata/russelii, a conclusion supported by both genetics and morphology. The divergences between Indian and Pacific forms are within the range of species-level partitions in fishes, and we recommend retention of the names P. miles and P. russelii for Indian and Pacific forms. The hybrid origin of the Atlantic invasion invokes the possibility of heterosis as a contributing factor to invasion success.
Drying Technology in Agriculture and Food Sciences

Equilibrium moisture relations for foods and biomaterials moisture diffusivity in foods - an overview quality changes in food materials hygrothermal properties of grains quality changes during drying of food polymers physical property changes of fruits and vegetables during hot air drying spray and freeze drying of enzymes physical properties and drying rate of alfalfa principles, applications and potential of heat pump drying systems principles and applications of microwave drying innovation in drying technologies.
Violence permeating daily life: a qualitative study investigating perspectives on violence among women in Karachi, Pakistan

Background: This study explored how married women perceive situations which create family conflicts and lead to different forms of violence in urban Pakistan. In addition, it examines perceptions of consequences of violence, their adverse health effects, and how women resist violence within marital life. Methods: Five focus group discussions were conducted with 28 women in Karachi. Purposive sampling, aiming for variety in age, employment status, education, and socioeconomic status, was employed. The focus group discussions were conducted in Urdu and translated into English. Manifest and latent content analysis were applied. Results: One major theme emerged during the analysis, ie, family violence through the eyes of females. This theme was subdivided into three main categories. The first category, ie, situations provoking violence and their manifestations, elaborates on circumstances that provoke violence and situations that sustain violence. The second category, ie, actions and reactions to exposure to violence, describes consequences of ongoing violence within the family, including those that result in suicidal thoughts and actions. The final category, ie, resisting violence, describes how violence is avoided through women’s awareness and actions. Conclusion: The current study highlights how female victims of abuse are trapped in a society where violence from a partner and family members is viewed as acceptable, where divorce is unavailable to the majority, and where societal support of women is limited. There is an urgent need to raise the subject of violence against women and tackle this human rights problem at all levels of society by targeting the individual, family, community, and societal levels concurrently.
A genome‐wide linkage and association analysis of imputed insertions and deletions with cardiometabolic phenotypes in Mexican Americans: The Insulin Resistance Atherosclerosis Family Study

Insertions and deletions (INDELs) represent a significant fraction of interindividual variation in the human genome yet their contribution to phenotypes is poorly understood. To confirm the quality of imputed INDELs and investigate their roles in mediating cardiometabolic phenotypes, genome‐wide association and linkage analyses were performed for 15 phenotypes with 1,273,952 imputed INDELs in 1,024 Mexican‐origin Americans. Imputation quality was validated using whole exome sequencing with an average kappa of 0.93 in common INDELs (minor allele frequencies [MAFs] ≥ 5%). Association analysis revealed one genome‐wide significant association signal for the cholesterylester transfer protein gene (CETP) with high‐density lipoprotein levels (rs36229491, P = 3.06 × 10−12); linkage analysis identified two peaks with logarithm of the odds (LOD) > 5 (rs60560566, LOD = 5.36 with insulin sensitivity (SI) and rs5825825, LOD = 5.11 with adiponectin levels). Suggestive overlapping signals between linkage and association were observed: rs59849892 in the WSC domain containing 2 gene (WSCD2) was associated and nominally linked with SI (P = 1.17 × 10−7, LOD = 1.99). This gene has been implicated in glucose metabolism in human islet cell expression studies. In addition, rs201606363 was linked and nominally associated with low‐density lipoprotein (P = 4.73 × 10−4, LOD = 3.67), apolipoprotein B (P = 1.39 × 10−3, LOD = 4.64), and total cholesterol (P = 1.35 × 10−2, LOD = 3.80) levels. rs201606363 is an intronic variant of the UBE2F‐SCLY (where UBE2F is ubiquitin‐conjugating enzyme E2F and SCLY is selenocysteine lyase) fusion gene that may regulate cholesterol through selenium metabolism. In conclusion, these results confirm the feasibility of imputing INDELs from array‐based single nucleotide polymorphism (SNP) genotypes. Analysis of these variants using association and linkage replicated previously identified SNP signals and identified multiple novel INDEL signals. These results support the inclusion of INDELs into genetic studies to more fully interrogate the spectrum of genetic variation.
Comparative Evaluation of Polyphenol Contents and Antioxidant Activities between Ethanol Extracts of Vitex negundo and Vitex trifolia L. Leaves by Different Methods

The in vitro antioxidant potential assay between ethanolic extracts of two species from the genus Vitex (Vitex negundo L. and Vitex trifolia L.) belonging to the Lamiaceae family were evaluated. The antioxidant properties of different extracts prepared from both plant species were evaluated by different methods. DPPH scavenging, nitric oxide scavenging, and β-carotene-linoleic acid and ferrous ion chelation methods were applied. The antioxidant activities of these two species were compared to standard antioxidants such as butylated hydroxytoluene (BHT), ascorbic acid, and Ethylene diamine tetra acetic acid (EDTA). Both species of Vitex showed significant antioxidant activity in all of the tested methods. As compared to V. trifolia L. (60.87–89.99%; 40.0–226.7 μg/mL), V. negundo has been found to hold higher antioxidant activity (62.6–94.22%; IC50 = 23.5–208.3 μg/mL) in all assays. In accordance with antioxidant activity, total polyphenol contents in V. negundo possessed greater phenolic (89.71 mg GAE/g dry weight of extract) and flavonoid content (63.11 mg QE/g dry weight of extract) as compared to that of V. trifolia (77.20 mg GAE/g and 57.41 mg QE/g dry weight of extract respectively). Our study revealed the significant correlation between the antioxidant activity and total phenolic and flavonoid contents of both plant species.
Ductal carcinoma in situ of the breast: morphological and molecular features implicated in progression

The spread of mammographic screening programmes around the world, including in developing countries, has substantially contributed to the diagnosis of small non-palpable lesions, which has increased the detection rate of DCIS (ductal carcinoma in situ). DCIS is heterogeneous in several ways, such as its clinical presentation, morphology and genomic profile. Excellent outcomes have been reported; however, many questions remain unanswered. For example, which patients groups are overtreated and could instead benefit from minimal intervention and which patient groups require a more traditional multidisciplinary approach. The development of a comprehensive integrated analysis that includes the radiological, morphological and genetic aspects of DCIS is necessary to answer these questions. This review focuses on discussing the significant findings about the morphological and molecular features of DCIS and its progression that have helped to uncover the biological and genetic heterogeneity of this disease. The knowledge gained in recent years might allow the development of tailored clinical management for women with DCIS in the future.
The Green Bank Ammonia Survey: Dense Cores under Pressure in Orion A

We use data on gas temperature and velocity dispersion from the Green Bank Ammonia Survey and core masses and sizes from the James Clerk Maxwell Telescope Gould Belt Survey to estimate the virial states of dense cores within the Orion A molecular cloud. Surprisingly, we find that almost none of the dense cores are sufficiently massive to be bound when considering only the balance between self-gravity and the thermal and non-thermal motions present in the dense gas. Including the additional pressure binding imposed by the weight of the ambient molecular cloud material and additional smaller pressure terms, however, suggests that most of the dense cores are pressure-confined.