Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular and Cellular Pathobiology Distinct Patterns of Dysregulated Expression of Enzymes Involved inAndrogenSynthesis andMetabolism inMetastatic Prostate Cancer Tumors

Androgen receptor (AR) signaling persists in castration-resistant prostate carcinomas (CRPC), because of several mechanisms that include increased AR expression and intratumoral androgen metabolism. We investigated the mechanisms underlying aberrant expression of transcripts involved in androgen metabolism in CRPC. We compared gene expression profiles and DNA copy number alteration (CNA) data from 29 normal prostate tissue samples, 127 primary prostate carcinomas (PCa), and 19 metastatic PCas. Steroidogenic enzyme transcripts were evaluated by quantitative reverse transcriptase PCR in PCa cell lines and circulating tumor cells (CTC) from CRPC patients. Metastatic PCas expressed higher transcript levels for AR and several steroidogenic enzymes, including SRD5A1, SRD5A3, and AKR1C3, whereas expression of SRD5A2, CYP3A4, CYP3A5, and CYP3A7 was decreased. This aberrant expression was rarely associated with CNAs. Instead, our data suggest distinct patterns of coordinated aberrant enzyme expression. Inhibition of AR activity by itself stimulated AKR1C3 expression. The aberrant expression of the steroidogenic enzyme transcripts was detected in CTCs from CRPC patients. In conclusion, our findings identify substantial interpatient heterogeneity and distinct patterns of dysregulated expression of enzymes involved in intratumoral androgen metabolism in PCa. These steroidogenic enzymes represent targets for complete suppression of systemic and intratumoral androgen levels, an objective that is supported by the clinical efficacy of the CYP17 inhibitor abiraterone. A comprehensive AR axis–targeting approach via simultaneous, frontline enzymatic blockade, and/or transcriptional repression of several steroidogenic enzymes, in combination with GnRH analogs and potent antiandrogens, would represent a powerful future strategy for PCa management. Cancer Res; 72(23); 6142–52. 2012 AACR.
Causes of hyperglycemia and hypoglycemia in adult inpatients.

PURPOSE The underlying causes of hyperglycemia and hypoglycemia in adult medical and surgical inpatients were studied. METHODS Hyperglycemic and hypoglycemic events occurring in adult medical and surgical patients admitted between February and July 2003 to a tertiary care hospital were identified prospectively from automated daily printouts of abnormal blood glucose levels generated by the hospital laboratory. Information on the causes of a random sample of events was ascertained within 24 hours through chart review and provider and patient interviews. Narratives were presented to an expert committee to assess the causes of each event and preventability. RESULTS Eighteen of 24 hypoglycemic events and 26 of 26 hyperglycemic episodes were considered preventable. Failure to adjust antidiabetic drugs in response to decreases in oral intake and unexpected deviation from normal hospital routine were the most common factors contributing to hypoglycemia. Hyperglycemia was most often associated with an unwillingness of providers to take responsibility for diabetes management and the exclusive use of sliding-scale insulin regimens. CONCLUSION Hyperglycemia and hypoglycemia in medical and surgical inpatients were mostly related to inadequate prescribing, monitoring, and communication practices.
Local excision for more advanced rectal tumors

Over the past 20 years, local excision (LE) of T1 rectal cancer was increasingly established and represents an oncologically established technique. In contrast, the situation for T2 tumors is less clear and has only been investigated in small patient collectives. LE for T2 tumors is thus discussed controversially. Materials and Methods. In addition to our own patients with T2 rectal cancer treated locally (n=40), we have analysed the local recurrence (LR) rates after LE alone (n=124), after immediate conventional radical reoperation (n=29), after adjuvant (chemo)-radiotherapy (n=294) and those after neoadjuvant chemoradiotherapy (nCRT) (n=269) using a PubMed search. Results. LR rates of low-grade T2 tumors after R0 resection by LE alone was 19%. If additional prognostically unfavorable findings were present, the LR rate rose to 52%. By immediate radical reoperation the LR rate was decreased to 7%, whereas that after adjuvant therapy was 16%. In contrast, LE of more advanced tumors after nCRT resulted in LR rates of 9%. Discussion. LE alone of T2 rectal cancer should not be performed, and after adjuvant chemoradiotherapy the risk of developing LR was also high. In cases with unexpected T2 finding after LE, immediate conventional reoperation can represent an adequate oncological therapy, because it reveals comparable results to those obtained by primary radical resection. First results after nCRT followed by LE showed favorable results with low LR rates. If the indication for LE of T2 cancers can be extended to patients after nCRT in the future will have to be determined in prospective mutlticentre studies.
A new approach for achieving traffic-exchange localization in P2P-based content distribution

Due to the fact that P2P applications have dominantly accounted for the entire Internet traffic, how to efficiently manage P2P traffic has become increasingly important. It has been recently proposed that the underlying network information can be shared between ISPs and P2P service providers in order to achieve efficient resource utilization, with the locality-based peer selection being a specific example. Based on such collaboration, we propose a proportional traffic-exchange localization scheme for making efficient use of network resources. Our approach employs locality information in order to regulate the volume of traffic exchange between peers according to their physical distance between peers. The key objective of our approach is to further reduce both intra- and inter-autonomous system (AS) traffic compared with basic locality-based peer selection solutions. Our simulation-based results have shown that this approach is not only able to reduce a significant of inter-AS P2P traffic, but also to balance the network utilization in comparison to existing approaches.
Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Örebro, Sweden, 1993–1998

Background: Microscopic colitis, including collagenous colitis and lymphocytic colitis, mainly affects middle aged and older subjects, with a female predominance in collagenous colitis. The diseases have previously been regarded as rare. We present an epidemiological study of microscopic colitis in a well defined Swedish population. Methods: Patients were retrospectively searched for in colonoscopy reports of those who had a colonoscopy in the period 1993–1998 for non-bloody diarrhoea. All colonic mucosal biopsies were reassessed using strict diagnostic criteria. Results: Biopsies from 1018 patients were reassessed. Fifty one (45 female) collagenous colitis patients and 46 (31 female) lymphocytic colitis patients were diagnosed. Median age at diagnosis was 64 years in collagenous colitis and 59 years in lymphocytic colitis. The mean annual incidence of collagenous colitis was 4.9/105 inhabitants (95% confidence interval (CI) 3.6–6.2/105) and of lymphocytic colitis 4.4/105 inhabitants (95% CI 3.1–5.7/105). The annual incidence of collagenous colitis increased from 3.7/105 in 1993–1995 to 6.1/105 in 1996–1998 (difference 2.4/105 (95% CI −0.3–5.1/105)) whereas the incidence of lymphocytic colitis increased from 3.1/105 to 5.7/105 (difference 2.6/105 (95% CI 0.1–5.2/105)). Conclusions: The annual incidences of collagenous colitis and lymphocytic colitis are higher than considered previously and are now equal to the incidence of Crohn’s disease in Sweden, and combined rates approach the incidence of ulcerative colitis. Microscopic colitis was diagnosed in 10% of all patients with non-bloody diarrhoea referred for colonoscopy and in almost 20% of those older than 70 years.
The use of bioinformatics to identify the genomic structure of the gene that encodes neutrophil antigen NB1, CD177.

The gene encoding neutrophil alloantigen NB1, CD177, is highly homologous to a gene overexpressed in polycythemia vera neutrophils, polycythemia rubra vera-1 (PRV-1). The cDNAs of both genes have been cloned, but their genomic structure is unknown. The purpose of this study was to determine the intron-exon organization of NB1 and PRV-1 and discern if they are separate members of a homologous gene family or alleles of the same gene. GenBank's human genome sequences were probed in silico with PRV-1's 1605-nucleotide coding sequence. Searches identified two adjacent bacterial artificial chromosomes (BACs) on chromosome 19q13.2: BC338531 and BC52850. BC338531 contained sequences 100% homologous to the first 654 nucleotides of PRV-1. Comparison of coding and genomic sequences allowed us to separate this region into exons 1 through 5, interrupted by five introns. BC52850 contained sequences 95% homologous to nucleotides 413 through 1605 of PRV-1, organized into exons 4 through 9. However, the orientation of PRV-1-homologous in the first BAC was plus-plus and of the second was plus-minus, indicating they could not be portions of the same gene. The GenBank sequence of BC338531 was incomplete, creating a sequence gap in chromosome 19q13.2. Evaluation of BC338531's unfinished sequences in Joint Genome Institute public databases allowed us to complete the gap and revealed that BC338531 contained sequences 98% homologous to all nine PRV-1 exons followed by a second gene consisting of exons 9 through 4. Most likely, NB1 and PRV-1 are alleles of the same gene, CD177, and the duplication of exons 4 through 9 is a pseudo gene.
A meta‐analysis suggesting that the relationship between biodiversity and risk of zoonotic pathogen transmission is idiosyncratic

Abstract Zoonotic pathogens are significant burdens on global public health. Because they are transmitted to humans from non‐human animals, the transmission dynamics of zoonoses are necessarily influenced by the ecology of their animal hosts and vectors. The ‘dilution effect’ proposes that increased species diversity reduces disease risk, suggesting that conservation and public health initiatives can work synergistically to improve human health and wildlife biodiversity. However, the meta‐analysis that we present here indicates a weak and highly heterogeneous relationship between host biodiversity and disease. Our results suggest that disease risk is more likely a local phenomenon that relies on the specific composition of reservoir hosts and vectors, and their ecology, rather than patterns of species biodiversity.
Application of liposome encapsulation technique to improve anti-carcinoma effect of resveratrol

Aim: The promising anti-tumor effect of resveratrol (RES) has aroused much interest in recent years, but its clinical application was seriously hindered due to its poor solubility in water. The aim of this study was to improve the water solubility of RES by liposome encapsulation technique for effective tumor treatment. Methods: This study develops two liposomal formulations to solubilize RES by reverse-phase evaporation method with or without poly(ethylene glycol-2000)-grafted distearolyl phosphatidylethanolamine (DSPE-PEG2000). The effect of different formulation factors on the encapsulation efficiency (EE) and the particle sizes were investigated. These factors included the mass ratio of drug to soybean phosphatidylcholine (drug/SPC), the mass ratio of cholesterol to soybean phosphatidylcholine (chol/SPC), the volume ratio of water phase/organic phase and the microfluidization process. The drug release studies were performed in various media, simulating the desired application conditions. The cytotoxicity study was carried out by MTT assay on HeLa and Hep G2 cell lines. Results: The RES EE of 95% was obtained when using drug/SPC (1:40 mass ratio), Chol/SPC (1:10 mass ratio), water phase/oil phase (1:2 volume ratio), microfluidization process (entrance pressure 6 kpa, two times of cycle time). The addition of DSPE-PEG2000 into the formulation showed little effect on the formation and properties of RES liposome. The release of RES was pH-independent. RES liposomes and PEG-modified liposomes performed significant inhibition effects on both cells growth due to the solubilized RES. Conclusion: RES can be effectively loaded into liposomes and its anti-cancer effect was evidently improved by the application of liposome encapsulation technique.
Aliasing of Resonance Phenomena in Sampled-Data Feedback Control Design: Hazards, Modeling, and a Solution

High-performance control design for electromechanical sampled-data systems with aliased plant dynamics is investigated. Though from a theoretical viewpoint the aliasing phenomenon is automatically handled by direct sampled-data control, such an approach cannot be used in conjunction with models derived through system identification. From a practical viewpoint, aliasing is often considered as an undesirable phenomenon and a typical remedy is the increase of the sampling frequency. However, the sampling frequency is upper bounded due to physical and economical constraints and aliasing may be inevitable. Control design for plants with aliased dynamics has not received explicit attention in the literature and it is not clear how to handle this situation. In this paper, it is shown that aliased resonance phenomena can effectively be suppressed in sampled-data feedback control design without the need for increasing the sampling frequency. Furthermore, it is shown experimentally on an industrial wafer stage that ignoring aliasing during control design can have a disastrous effect on closed-loop performance. Additionally, a novel, practically feasible procedure for identification of (possibly aliased) resonance phenomena based on multirate system theory is proposed.
Transcription Factor Nkx-2.5 Induces Sodium/Iodide Symporter Gene Expression and Participates in Retinoic Acid- and Lactation-Induced Transcription in Mammary Cells

ABSTRACT The sodium/iodide symporter (NIS) is a plasma membrane protein that mediates active iodide transport in thyroid and mammary cells. It is a prerequisite for radioiodide treatment of thyroid cancer and a promising diagnostic and therapeutic tool for breast cancer. We investigated the molecular mechanisms governing NIS expression in mammary cells. Here we report that Nkx-2.5, a cardiac homeobox transcription factor that is also expressed in the thyroid primordium, is a potent inducer of the NIS promoter. By binding to two specific promoter sites (N2 and W), Nkx-2.5 induced the rNIS promoter (about 50-fold over the basal level). Interestingly, coincident with NIS expression, Nkx-2.5 mRNA and protein were present in lactating, but not virgin, mammary glands in two human breast cancer samples and in all-trans retinoic acid (tRA)-stimulated MCF-7 breast cancer cells. A cotransfected dominant-negative Nkx-2.5 mutant abolished tRA-induced endogenous NIS induction, which shows that Nkx-2.5 activity is critical for this process. Remarkably, in MCF-7 cells, Nkx-2.5 overexpression alone was sufficient to induce NIS and iodide uptake. In conclusion, Nkx-2.5 is a novel relevant transcriptional regulator of mammary NIS and could thus be exploited to manipulate NIS expression in breast cancer treatment strategies.
[Predictors of retention related factors at the initial methadone maintenance treatment clinics in Guangdong province].

OBJECTIVE To identify predictors of treatment retention problems at the two initial methadone maintenance treatment (MMT) clinics in Guangdong province, and to provide reference in reducing the rate of drop-outs. METHODS All of the patients were investigated at baseline and followed during the treatment period. Kaplan-Meier method on Survival Analysis was used to analyze retention related factors and predictors. RESULTS 509 subjects were recruited in this study with median of retention time as 108 days (95%CI: 74 - 142 days). The retention rate at 1-, 3-, 6-, 12-months were 75.9%, 52.7%, 41.6%, 30.1%, respectively. Data from Multivariate Cox Proportional Hazard Model analysis showed predictors of retention would involve factors as HIV infection state at baseline (HR = 1.241, P = 0.047), daily methadone dose (HR = 0.633, P = 0.004) and secretly using drugs during treatment period (HR = 5.345, P = 0.000). CONCLUSION The retention rates at the two initial MMT clinics in Guangdong province were low. Patients who were HIV negative at baseline but still secretly using heroine during treatment or accepted low daily average dosage of methadone, had the tendency to drop out. The results implied that retention time could be prolonged by increasing daily methadone dosage.
Tuberculosis of pancreas and peripancreatic lymph nodes in immunocompetent patients: experience from China.

AIM To determine the clinical, radiographic and laboratory characteristics, diagnostic methods, and therapeutic variables in immunocompetent patients with tuberculosis (TB) of the pancreas and peripancreatic lymph nodes. METHODS The records of 16 patients (6 male, 10 female; mean age 37 years, range 18-56 years) with tuberculosis of the pancreas and peripancreatic lymph nodes from 1983 to 2001 in the Southwest Hospital were analyzed retrospectively. In addition, 58 similar cases published in Chinese literature were reviewed and summarized. We reviewed the clinical, radiographic and laboratory findings, diagnostic methods, therapeutic approaches, and outcome in the patients. Criteria for the diagnosis of pancreatic tuberculosis were the presence of granuloma in histological sections or the presence of Mycobacterium tuberculosis DNA by polymerase chain reaction (PCR). RESULTS Predominant symptoms consisted of abdominal nodule and pain (75 %), anorexia/weight loss (69 %), malaise/weakness (64 %), fever and night sweats (50 %), back pain (38 %) and jaundice (31 %). Swelling of the head of the pancreas with heterogeneous attenuation echo was detected with ultrasound in 75 % (12/16). CT scan showed pancreatic mass with heterogeneous hypodensity focus in all patients, with calcification in 56 % (9/16) patients, and peripancreatic nodules in 38 % (6/16) patients. Anemia and lymphocytopenia were seen in 50 % (8/16) patients, and pancytopenia occurred in 13 % (2/16) patients. Hypertransaminasemia, elevated alkaline phosphatase (AP) and GGT were seen in 56 % (9/16) patients. The erythrocyte sedimentation rate (ESR) was elevated in 69 % (11/16) cases. Granulomas were found in 75 % (12/16) cases, and in 38 % (6/16) cases caseous necrosis tissue was found. Laparotomy was performed in 75 % (12/16) cases, and ultrasound-guided fine needle aspiration (FNA) was done in 63 % (10 of 16). The most commonly used combinations of medications were isoniazid/rifampin/streptomycin (63 %, n=10) and isoniazid/rifampin pyrazinamide/streptomycin or ethambutol (38 %, n=6). The duration of treatment lasted for half or one year and treatment was successful in all cases. The characteristics of 58 cases from Chinese literature were also summarized. CONCLUSION Tuberculosis of the pancreas and peripancreatic lymph nodes should be considered as a diagnostic possibility in patients presenting with a pancreatic mass, and diagnosis without laparotomy is possible if only doctors are aware of its clinical features and investigate it with appropriate modalities. Pancreatic tuberculosis can be effectively cured by antituberculous drugs.
Nitrogen control of the glnN gene that codes for GS type III, the only glutamine synthetase in the cyanobacterium Pseudanabaena sp. PCC 6903

Pseudanabaena sp. strain PCC 6903 is the first cyanobacteria lacking the typical prokaryotic glutamine synthetase type I encoded by the glnA gene. The glnN gene product, glutamine synthetase type III, is the only glutamine synthetase activity present in this cyanobacterium. Analysis of glnN expression clearly indicated a nitrogen‐dependent regulation. Pseudanabaena glnN gene expression and GSIII activity were upregulated under nitrogen starvation or using nitrate as a nitrogen source, while low levels of transcript and activity were found in ammonium‐containing medium. Primer extension analysis showed that the glnN gene promoter structure resembled that of the NtcA‐related promoters. Mobility shift assays demonstrated that Synechocystis sp. PCC 6803 NtcA protein, expressed and purified from Escherichia coli , bound to the promoter of the Pseudanabaena 6903 glnN gene. The NtcA control of the glnN gene in this cyanobacterium suggested that, in the absence of a glnA gene, NtcA took control of the only glutamine synthetase gene in a fashion similar to the way the glnA gene is governed in those cyanobacteria harbouring a glnA gene.
A spatial econometric study on the role of human capital on China's total factor productivity growth

Using Spatial Benhabib-Spiegel model, the authors construct the distance decay spatial weights matrix to study the spatial spillover effects of human capital on total factor productivity growth. It is found that the role of the human capital on the growth of total factor productivity depends on the level of human capital of the test region, the human capital of neighboring regions, as well as the technological catch-up effect considering the geographic distance of the test region. The results shows that the average level of human capital plays a positive role in promoting total factor productivity growth, besides that, the human capital of neighboring regions has positive spatial spillovers on the total factor productivity growth of the test region. In terms of idiosyncratic human capital, the spatial spillovers of different types of human capital on total factor productivity growth demonstrate significant differences. Specifically, the spatial spillover effect of human capital in primary education on total factor productivity growth is not significant, the spatial spillover effect of human capital in secondary education on total factor productivity growth shows a significant positive effect, by contrast, higher education human capital shows a negative effect. It comes to the conclusion that regions must choose a reasonable moderate level and structural human capital.
Intracellular trafficking of nucleic acids

Until recently, the attention of most researchers has focused on the first and last steps of gene transfer, namely delivery to the cell and transcription, in order to optimise transfection and gene therapy. However, over the past few years, researchers have realised that the intracellular trafficking of plasmids is more than just a ‘black box’ and is actually one of the major barriers to effective gene delivery. After entering the cytoplasm, following direct delivery or endocytosis, plasmids or other vectors must travel relatively long distances through the mesh of cytoskeletal networks before reaching the nuclear envelope. Once at the nuclear envelope, the DNA must either wait until cell division, or be specifically transported through the nuclear pore complex, in order to reach the nucleoplasm where it can be transcribed. This review focuses on recent developments in the understanding of these intracellular trafficking events as they relate to gene delivery. Hopefully, by continuing to unravel the mechanisms by which plasmids and other gene delivery vectors move throughout the cell, and by understanding the cell biology of gene transfer, superior methods of transfection and gene therapy can be developed.