Miracle-dz/UniFAR-FTUs huggingface dataset:
Herpes Simplex Virus Type 1 Primary Envelopment: UL34 Protein Modification and the US3-UL34 Catalytic Relationship

ABSTRACT The herpes simplex virus type 1 (HSV-1) US3 kinase is likely important for primary envelopment of progeny nucleocapsids since it localizes to the nuclear envelope of infected cells and largely determines the phosphorylation state and localization of the necessary primary envelopment factor, the UL34 protein. In HEp-2 cells, the production of infectious US3 null progeny is delayed and decreased relative to that of the parental strain, HSV-1(F). Furthermore, the US3 kinase affects the morphology of primary envelopment such that in its absence, UL34 protein-containing enveloped virions accumulate within membrane-bound vesicles. These vesicles are most often found along the interior periphery of the nucleus and may be derived from the inner nuclear membrane. Since the US3 and UL34 proteins comprise a kinase-substrate pair, a reasonable hypothesis is that the US3 kinase influences these replication parameters by direct phosphorylation of the UL34 protein. For this report, recombinant viruses were constructed to determine the significance of UL34 protein phosphorylation and US3 catalytic activity on UL34 protein localization, single-step growth, and envelopment morphology in both HEp-2 and Vero cells. The data presented suggest that the significance of UL34 phosphorylation is cell type dependent and that efficient viral morphogenesis requires US3-mediated phosphorylation of an infected cell protein other than UL34.
Pap Screening and Knowledge of Risk Factors for Cervical Cancer in Chinese Women in British Columbia, Canada

Objective. Cervical cancer is a significant cause of mortality and morbidity for Chinese Canadian women, due in part to inadequate Pap screening. A community‐based survey was conducted involving 528 Chinese immigrant women residing in British Columbia, Canada, in order to identify barriers and facilitators to Pap testing. This paper addresses the relationship between knowledge level about cervical cancer risk factors and Pap screening practices. Design. Female trilingual Chinese interviewers conducted personal at‐home interviews about knowledge of cervical cancer risk factors, history of Pap screening, sociodemographic and acculturation factors. Results. The average summary score for knowledge about cervical cancer risk factors was 5.2/10, and knowledge level was significantly associated with the woman's educational level and the gender of the doctor providing usual care. Seventy‐four per cent of respondents reported ever having received a Pap test, and 56% reported having received a test within the last two years. Respondents with the highest knowledge were more likely to have ever received a Pap test (OR 6.4, 95% CI: 2.6, 15.9), and to have recently received a test (OR 3.1, 95% CI: 1.4, 6.7). Conclusion. The average knowledge level about cervical cancer risk factors is low in Chinese Canadian women, especially among those with less education and who receive their usual care from a male doctor. Knowledge of these risk factors influences Pap screening behaviour. Culturally and linguistically appropriate education interventions addressing Pap testing and risk factors for cervical cancer are needed in the Canadian Chinese community. Educational resources are also needed for their primary care givers.
Hepatocyte Growth Factor Expression in EGFR Mutant Lung Cancer with Intrinsic and Acquired Resistance to Tyrosine Kinase Inhibitors in a Japanese Cohort

Introduction: This study was performed to determine the incidence rates of resistance factors, i.e., high-level hepatocyte growth factor (HGF) expression, epidermal growth factor receptor (EGFR) T790M secondary mutation, and MET amplification, in tumors with intrinsic and acquired EGFR tyrosine kinase inhibitor (TKI) resistance in EGFR mutant lung cancer. Methods: Ninety-seven specimens from 93 EGFR mutant lung cancer patients (23 tumors with acquired resistance from 20 patients, 45 tumors with intrinsic resistance from 44 patients [nonresponders], 29 sensitive tumors from 29 patients) from 11 institutes in Japan were analyzed. HGF expression, EGFR T790M secondary mutation, and MET amplification were determined by immunohistochemistry, cycleave real-time polymerase chain reaction, and fluorescence in situ hybridization, respectively. Results: High-level HGF expression, EGFR T790M secondary mutation, and MET amplification were detected in 61, 52, and 9% of tumors with acquired resistance, respectively. High-level HGF expression was detected in 29% of tumors with intrinsic resistance (nonresponders), whereas EGFR T790M secondary mutation and MET amplification were detected in 0 and 4%, respectively. HGF expression was significantly higher in tumors with acquired resistance than in sensitive tumors (p < 0.001, Student's t test). Fifty percent of tumors with acquired resistance showed simultaneous HGF expression with EGFR T790M secondary mutation and MET amplification. Conclusions: High-level HGF expression was detected more frequently than EGFR T790M secondary mutation or MET amplification in tumors with intrinsic and acquired EGFR-TKI resistance in EGFR mutant lung cancer in Japanese patients. These observations provide a rationale for targeting HGF in EGFR-TKI resistance in EGFR mutant lung cancer.
Identification of XcpP domains that confer functionality and specificity to the Pseudomonas aeruginosa type II secretion apparatus

Gram‐negative bacteria have evolved several types of secretion mechanisms to release proteins into the extracellular medium. One such mechanism, the type II secretory system, is a widely conserved two‐step process. The first step is the translocation of signal peptide‐bearing exoproteins across the inner membrane. The second step, the translocation across the outer membrane, involves the type II secretory apparatus or secreton. The secretons are made up of 12–15 proteins (Gsp) depending on the organism. Even though the systems are conserved, hetero‐logous secretion is mostly species restricted. Moreover, components of the secreton are not systematically exchangeable, especially with distantly related microorganisms. In closely related species, two components, the GspC and GspD (secretin) family members, confer specificity for substrate recognition and/or secreton assembly. We used Pseudomonas aeruginosa as a model organism to determine which domains of XcpP (GspC member) are involved in specificity. By constructing hybrids between XcpP and OutC, the Erwinia chrysanthemi homologue, we identified a region of 35 residues that was not exchangeable. We showed that this region might influence the stability of the XcpYZ secreton subcomplex. Remarkably, XcpP and OutC have domains, coiled‐coil and PDZ, respectively, which exhibit the same function but that are structurally different. Those two domains are exchangeable and we provided evidence that they are involved in the formation of homomultimeric complexes of XcpP.
Hypertension and overweight among Turkish adolescents in a city in Aegean region of Turkey: a strong relationship in a population with a relatively low prevalence of overweight.

OBJECTIVE A school-based survey was performed in 1346 adolescents aged 15-18 years to determine the relationship between "overweight" and hypertension among adolescents in a western city in Turkey with a low prevalence of "overweight". METHODS The data were collected by a self administered questionnaire. Weight and height of adolescents were measured. US CDC pediatric anthropometric reference data were used to establish the body mass index (BMI) percentile. "At risk of overweight" (BMI-for-age and sex >or=85th, and <95th percentile) and "overweight" (BMI-for-age and sex >or=95th percentile) were defined. Hypertension (systolic and/or diastolic blood pressure that is >or=95th percentile for sex, age and height percentile) was defined according to the 4th Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (2004). The Chi-square test, Chi-square test for trend and logistic regression models were used for analysis. RESULTS Overall, prevalence of "at risk of overweight" and "overweight" were found to be 10.7% and 3.2%, respectively. About 3.5% of the adolescents were hypertensive. After adjustment for sex and age, income, family history of hypertension, the factors positively associated with hypertension were "at risk for overweight" (Odds Ratio [OR] =5.09, 95% CI: 2.57-10.07) and "overweight" (OR=7.60, 95% CI: 2.90-19.89). CONCLUSION The results of this study confirm low hypertension risk among adolescents in Manisa, which may be attributed to the low prevalence of "overweight". The relatively low cardiovascular disease risk factor profile of these adolescents needs to be encouraged through adulthood. Thus, a school program of health promotion should be established to prevent the epidemics of cardiovascular diseases in our region.
T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase

Celiac disease is an HLA‐DQ2‐associated disorder characterized by intestinal T cell responses to ingested wheat gliadins. Initial studies used gliadin that had been subjected to non‐enzymatic deamidation during pepsin / trypsin digestion to enrich for the gliadin‐specific T cells in small intestinal celiac biopsies. These T cells recognized synthetic gliadin peptides only after their deamidation in vitro by purified tissue transglutaminase (tTG). However, as these studies used a deamidated antigen for re‐stimulation prior to testing for antigen specificity, this raised the possibility that T cells specific for native epitopes had not been expanded in vitro and had thus been overlooked. To address this possibility and to look for more direct evidence that endogenous tTG mediates deamidation of gluten in the celiac lesions, we have here used a minimally deamidated chymotrypsin‐digest of gliadin to challenge biopsies and then investigated the specificity of the T cell lines derived from them. Interestingly, these T cell lines only barely responded to the chymotrypsin‐digested gliadins, but efficiently recognized the in vitro tTG‐treated variants of the same gliadins. Moreover, the addition of a tTG‐inhibitor during the gliadin challenge often resulted in T cell lines with abolished or reduced responses to deamidated gliadin. These data demonstrate that DQ2‐restricted T cells within adult celiac lesions predominantly recognize deamidated gliadin epitopes that are formed in situ by endogenous tTG.
Impact of oncology drug shortages on patient therapy: unplanned treatment changes.

PURPOSE Cancer drug shortages have increased considerably over the past 5 years, but quantitative analyses of the scope and effects are limited. We assessed the effects of drug shortages on outpatient medication use in a single New York City university hospital. METHODS We examined pharmacy records for drug shortages, as defined by the American Society of Health-System Pharmacists. We assessed outpatient records for all patients with cancer treated with infusional antineoplastic medications from April 2010 to September 2010 and April 2011 to September 2011. RESULTS Twelve medications were in shortage in 2010 and 22 in 2011. Drugs in shortage were used for 170 patients (50.8%) in 2010 and 241 patients (63.6%) in 2011 (P < .001). Of 235 patients treated in August-September 2011, there were 23(9.8%) documented therapy changes due to shortages, compared with zero changes in August-September 2010 (P < .001). Among patients treated in August-September 2010, 24 (11.4%) received paclitaxel and 19 (9.0%) received docetaxel. Among patients treated in August-September 2011, 11 (4.7%) received paclitaxel and 38 (16.2%) received docetaxel, a 69% decrease for paclitaxel and 80% increase for docetaxel from 1 year prior (P = .009, and P = .024, respectively). The estimated cost of a single treatment with paclitaxel for one patient with body-surface area 1.75 was $47.59 versus $858.39 for docetaxel, a 1,704% increase. Surveyed physicians frequently reported lower level evidence (30.4%) and increased risk of toxicity (34.8%) with alternative therapy in drug shortage cases. CONCLUSION Oncology drug shortages affected the majority of patients in our center and increased at an alarming rate. Drug shortages have substantial economic costs and mandate treatment changes that may affect efficacy and toxicity.
Regional implementation of New Zealand sport policy: new instrument, new challenges

Policies aiming to enhance sport participation and physical activity are prone to change and highly influenced by shifting government priorities and instruments. In 2009, the New Zealand Government and its agency Sport and Recreation New Zealand (SPARC) abolished programmes aimed at inducing general physical activity and in their place established Kiwisport, an initiative to get more school-age children involved in organized sport. This study analyses the impact of these changes on regional sports trusts (RSTs), as regional implementers of national sport policy and the Kiwisport initiative. Based on a process of induction from available texts (interviews with chief executives of RSTs and both public/nonpublic documents), three emerging challenges are presented and discussed. The first concerns how RSTs can fulfil Kiwisport's promises of minimal bureaucracy in the light of the limited capacities of community organizations and increasing demands from SPARC for evaluation. The second surrounds the difficulty in reconciling Kiwisport's allowance for greater RST discretion/autonomy with the demands for integrated national–regional delivery. The third challenge is with regard to creating sustainable community initiatives under conditions of depleting resources and shifting policy priorities. Findings raise fundamental questions as to how and to what extent RSTs should realign their organizations to meet central government objectives.
SEASONAL TRANSMISSION OF GASTROINTESTINAL PARASITES OF EQUIDS IN SOUTHERN LOUISIANA

Parasite-naive pony foals were used as sentinels to monitor transmission of gastrointestinal parasites of equids in Louisiana during 4 seasons of the year. Two annual periods were studied, 1988–1989 and 1992–1993. Two or 3 foals each season were turned out to graze a contaminated pasture along with resident parasitized mares and their foals. After a grazing period of 8 wk, sentinel ponies were held in a parasite-free box stall for a period of 6 wk to allow parasites to develop, thus enhancing the evaluation of hypobiotic stages. Following this holding period, necropsies were performed for complete parasite recoveries. Data show that transmission of large and small strongyles occurs during all seasons in southern Louisiana, with highest levels of transmission occurring in the winter and only minimal transmission taking place in the summer. Numbers of mucosal cyathostomes, as well as total cyathostome numbers, were highest in the winter, and luminal cyathostome numbers were highest in the spring. Transmission of Anoplocephala perfoliata and Parascaris equorum occurred during all seasons of the year, although numbers of P. equorum were reduced in spring 1989 and 1993. Gasterophilus intestinalis instars were recovered from fall and winter sentinels only. Oxyuris equi L4 were found all seasons 1 yr, but only during the fall and winter of the final year.
Spying on Your Neighbors: Fine-grained Probing of Contextual Embeddings for Information about Surrounding Words

Although models using contextual word embeddings have achieved state-of-the-art results on a host of NLP tasks, little is known about exactly what information these embeddings encode about the context words that they are understood to reflect. To address this question, we introduce a suite of probing tasks that enable fine-grained testing of contextual embeddings for encoding of information about surrounding words. We apply these tasks to examine the popular BERT, ELMo and GPT contextual encoders, and find that each of our tested information types is indeed encoded as contextual information across tokens, often with near-perfect recoverability—but the encoders vary in which features they distribute to which tokens, how nuanced their distributions are, and how robust the encoding of each feature is to distance. We discuss implications of these results for how different types of models break down and prioritize word-level context information when constructing token embeddings.
Lunasin Is Prevalent in Barley and Is Bioavailable and Bioactive in In Vivo and In Vitro Studies

Lunasin, a unique 43-amino acid peptide found in a number of seeds, has been shown to be chemopreventive in mammalian cells and in a skin cancer mouse model. To elucidate the role of cereals in cancer prevention, we report here the prevalence, bioavailability, and bioactivity of lunasin from barley. Lunasin is present in all cultivars of barley analyzed. The liver and kidney of rats fed with lunasin-enriched barley (LEB) show the presence of lunasin in Western blot. Lunasin extracted from the kidney and liver inhibits the activities of HATs (histone acetyl transferases), yGCN5 by 20% and 18% at 100 nM, and PCAF activity by 25% and 24% at 100 nM, confirming that the peptide is intact and bioactive. Purified barley lunasin localizes in the nuclei of NIH 3T3 cells. Barley lunasin added to NIH 3T3 cells in the presence of the chemical carcinogen MCA activates the expression of tumor suppressors p21 and p15 by 45% and 47%, decreases cyclin D1 by 98%, and inhibits Rb hyperphosphorylation by 45% compared with the MCA treatment alone. We conclude that lunasin is prevalent in barley, bioavailable, and bioactive and that consumption of barley could play an important role of cancer prevention in barley-consuming populations.
Monitoring bortezomib therapy in multiple myeloma: screening of cyclin D1, D2, and D3 via reliable real-time polymerase chain reaction and association with clinico-pathological features and outcome

Cyclins D1, D2, and D3 (CCND1, 2, 3) are regulated by proteasomal degradation. Their overexpression in multiple myeloma (MM) has prognostic value. We performed this pilot study to analyze a possible association between CCND1–3 overexpression and response to treatment with the proteasome inhibitor bortezomib, since a specific prognostic marker for bortezomib response has not been reported, but would be ideal to predict who benefits most from bortezomib in times of several potentially efficient therapeutic options. Bone marrow (BM) specimens of 20/47 consecutive patients were available for reliable CCND1–3 analyses by real-time PCR. With CCND1 overexpression in 9/20 patients, the risk for progression after bortezomib treatment was significantly decreased (HR 0.102, 95% CI 0.021–0.498, p = 0.0048) and progression-free survival substantially prolonged (p = 0.0011). Our study is the first to suggest that overexpressed CCND1 in MM is an independent prognostic marker associated with a more durable response to bortezomib. These preliminary results warrant a larger study.
Transcriptional analysis of genes encoding enzymes of the folate pathway in the human malaria parasite Plasmodium falciparum

Folate metabolism in Plasmodium falciparum is essential for cell growth and replication, and the target of important antimalarial agents. The pathway comprises a series of enzymes that convert GTP to derivatives of tetrahydrofolate, which are cofactors in one‐carbon transfer reactions. We investigated the expression of five of the genes encoding these enzymes by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) using a threshold detection technique. We followed changes in mRNA levels as parasites progress through the erythrocytic cell cycle and examined this process in two cloned lines of diverse origins, as well as under stress conditions, induced by either removal of important metabolites or challenge by folate enzyme inhibitors. Although conventionally regarded as performing housekeeping functions, these genes show disparate levels of and changes in expression through the cell cycle, but respond quite uniformly to folate pathway‐specific stress factors, with no evidence of feedback at the transcriptional level. Overall, the two genes involved in the thymidylate cycle (encoding dihy‐drofolate reductase–thymidylate synthase, dhfr‐ts, and serine hydroxymethyltransferase, shmt) gave the most abundant transcripts. However, only the latter showed major variation across the cell cycle, with a peak around the time of onset of DNA replication, possibly indicative of a regulatory function.
Time Dependence in Non-Autonomous Neural ODEs

Neural Ordinary Differential Equations (ODEs) are elegant reinterpretations of deep networks where continuous time can replace the discrete notion of depth, ODE solvers perform forward propagation, and the adjoint method enables efficient, constant memory backpropagation. Neural ODEs are universal approximators only when they are non-autonomous, that is, the dynamics depends explicitly on time. We propose a novel family of Neural ODEs with time-varying weights, where time-dependence is non-parametric, and the smoothness of weight trajectories can be explicitly controlled to allow a tradeoff between expressiveness and efficiency. Using this enhanced expressiveness, we outperform previous Neural ODE variants in both speed and representational capacity, ultimately outperforming standard ResNet and CNN models on select image classification and video prediction tasks.
Significant prognostic factors in patients with node-negative gastric cancer.

BACKGROUND We evaluated the influence of several clinicopathological variables on 5 year survival of patients with node-negative gastric cancer. PATIENTS AND METHODS Clinical characteristics were retrieved from the records of all patients who underwent gastric resection between 1985 and 1995 at the Department of General Surgery, Sendai National Hospital, and follow-up data were obtained from our tumor registry. Pathological characteristics were determined from a detailed review of all available histopathological slides. The results of a retrospective analysis of clinicopathological data of 339 patients having no lymph node metastasis were compared with those of 358 patients with lymph node metastasis. Univariate and multivariate analyses of patients with node-negative gastric cancer were performed to evaluate the prognostic significance of clinicopathological features (age, gender, gross type, histological type, depth of invasion and location). RESULTS The 5 year survival rate for patients with node-negative gastric cancer was 92.5%. Node-negative gastric cancers were characterized by a smaller tumor, expansive and medullary histological type, and less frequency of lymphatic invasion and vascular permeation. In multivariate analysis, the statistical significant prognostic factors were tumor size (P = 0.0185), vascular permeation (P = 0.0011) and cancer-stromal relationship (P = 0.0291). CONCLUSION Tumor size, vascular microinvasion and cancer-stromal relationship are the most reliable predictors of 5 year survival for patients with node-negative gastric cancer.