Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary fibroblasts of Cockayne syndrome patients are defective in cellular repair of 8‐hydroxyguanine and 8‐hydroxyadenine resulting from oxidative stress

Cockayne syndrome (CS) is a genetic human disease with clinical symptoms that include neurodegeneration and premature aging. The disease is caused by the disruption of CSA, CSB, or some types of xeroderma pigmentosum genes. It is known that the CSB protein coded by the CS group B gene plays a role in the repair of 8‐hydroxyguanine (8‐OH‐Gua) in transcription‐coupled and non‐strand discriminating modes. Recently we reported a defect of CSB mutant cells in the repair of another oxidatively modified lesion 8‐hydroxyadenine (8‐OH‐Ade). We show here that primary fibroblasts from CS patients lack the ability to efficiently repair these particular types of oxidatively induced DNA damages. Primary fibroblasts of 11 CS patients and 6 control individuals were exposed to 2 Gy of ionizing radiation to induce oxidative DNA damage and allowed to repair the damage. DNA from cells was analyzed using liquid chromatography/isotope dilution mass spectrometry to measure the biologically important lesions 8‐OH‐Gua and 8‐OH‐Ade. After irradiation, no significant change in background levels of 8‐OH‐Gua and 8‐OH‐Ade was observed in control human cells, indicating their complete cellular repair. In contrast, cells from CS patients accumulated significant amounts of these lesions, providing evidence for a lack of DNA repair. This was supported by the observation that incision of 8‐OH‐Gua‐ or 8‐OH‐Ade‐containing oligodeoxynucleotides by whole cell extracts of fibroblasts from CS patients was deficient compared to control individuals. This study suggests that the cells from CS patients accumulate oxidatively induced specific DNA base lesions, especially after oxidative stress. A deficiency in cellular repair of oxidative DNA damage might contribute to developmental defects in CS patients.
HicA of Escherichia coli Defines a Novel Family of Translation-Independent mRNA Interferases in Bacteria and Archaea

ABSTRACT Toxin-antitoxin (TA) loci are common in free-living bacteria and archaea. TA loci encode a stable toxin that is neutralized by a metabolically unstable antitoxin. The antitoxin can be either a protein or an antisense RNA. So far, six different TA gene families, in which the antitoxins are proteins, have been identified. Recently, Makarova et al. (K. S. Makarova, N. V. Grishin, and E. V. Koonin, Bioinformatics 22:2581-2584, 2006) suggested that the hicAB loci constitute a novel TA gene family. Using the hicAB locus of Escherichia coli K-12 as a model system, we present evidence that supports this inference: expression of the small HicA protein (58 amino acids [aa]) induced cleavage in three model mRNAs and tmRNA. Concomitantly, the global rate of translation was severely reduced. Using tmRNA as a substrate, we show that HicA-induced cleavage does not require the target RNA to be translated. Expression of HicB (145 aa) prevented HicA-mediated inhibition of cell growth. These results suggest that HicB neutralizes HicA and therefore functions as an antitoxin. As with other antitoxins (RelB and MazF), HicB could resuscitate cells inhibited by HicA, indicating that ectopic production of HicA induces a bacteriostatic rather than a bactericidal condition. Nutrient starvation induced strong hicAB transcription that depended on Lon protease. Mining of 218 prokaryotic genomes revealed that hicAB loci are abundant in bacteria and archaea.
Mapping knowledge domains: Characterizing PNAS

A review of data mining and analysis techniques that can be used for the mapping of knowledge domains is given. Literature mapping techniques can be based on authors, documents, journals, words, and/or indicators. Most mapping questions are related to research assessment or to the structure and dynamics of disciplines or networks. Several mapping techniques are demonstrated on a data set comprising 20 years of papers published in PNAS. Data from a variety of sources are merged to provide unique indicators of the domain bounded by PNAS. By using funding source information and citation counts, it is shown that, on an aggregate basis, papers funded jointly by the U.S. Public Health Service (which includes the National Institutes of Health) and non-U.S. government sources outperform papers funded by other sources, including by the U.S. Public Health Service alone. Grant data from the National Institute on Aging show that, on average, papers from large grants are cited more than those from small grants, with performance increasing with grant amount. A map of the highest performing papers over the 20-year period was generated by using citation analysis. Changes and trends in the subjects of highest impact within the PNAS domain are described. Interactions between topics over the most recent 5-year period are also detailed.
Gonadotrophin‐Releasing Hormone (GnRH) Exerts Stimulatory Effects on GnRH Neurones in Intact Adult Male and Female Mice

There is substantial evidence for a role of the neuropeptide gonadotrophin‐releasing hormone (GnRH) in the regulation of GnRH neurone secretion but how this is achieved is not understood. We examined here the effects of GnRH on the electrical excitability and intracellular calcium concentration ([Ca2+]i) of GnRH neurones in intact adult male and female mice. Perforated‐patch electrophysiological recordings from GnRH‐green fluorescent protein‐tagged GnRH neurones revealed that 3 nm–3 μm GnRH evoked gradual approximately 3 mV depolarisations in membrane potential from up to 50% of GnRH neurones in male and female mice. The depolarising effect of GnRH was observed on approximately 50% of GnRH neurones throughout the oestrous cycle. However, at pro‐oestrus alone, GnRH was also found to transiently hyperpolarise approximately 30% of GnRH neurones. Both hyperpolarising and depolarising responses were maintained in the presence of tetrodotoxin. Calcium imaging studies undertaken in transgenic GnRH‐pericam mice showed that GnRH suppressed [Ca2+]i in approximately 50% of GnRH neurones in dioestrous and oestrous mice. At pro‐oestrus, 25% of GnRH neurones exhibited a suppressive [Ca2+]i response to GnRH, whereas 17% were stimulated. These results demonstrate that nm to μm concentrations of GnRH exert depolarising actions on approximately 50% of GnRH neurones in males and females throughout the oestrous cycle. This is associated with a reduction in [Ca2+]i. At pro‐oestrus, however, a further population of GnRH neurones exhibit a hyperpolarising response to GnRH. Taken together, these studies indicate that GnRH acts predominantly as a neuromodulator at the level of the GnRH cell bodies to exert a predominant excitatory influence upon GnRH neurones in intact adult male and female mice.
Millijoule 1-ps pulses from a kHz Ho:YAG regenerative amplifier seeded with a Tm, Ho-fiber laser

We demonstrate a 2090-nm 1-ps MOPA based on a Tm, Ho-fiber laser seeder and a Ho:YAG regenerative amplifier delivering 1.25-mJ pulses at a repetition rate of 1 kHz as a prospective driver laser for mid-IR frequency conversion. The output energy and the repletion rate are currently limited by the available seeder energy.
Function model of train control system for unmanned operation of urban transit system

The train control system (TCS) plays the core role to secure the safety and punctuality for railway train operation. There are various systems applied to urban transit lines which are developed differently and independently from other countries. The national standard specifications and guidelines have been established and maintained for the TCS in Korea. As the requirements of the high-efficient and economic operation of the urban transit system is getting higher, the unmanned operation of the train is moving to the limelight. Lots of systems supporting unmanned operation are being applied to the new lines such as Yongin, Busan (3rd line), Incheon (2nd line) and so on. The standard of the TCS for urban transit supports the system for unmanned operation as requirements. The function model of TCS has been established on the basis of the standard specification to analyze the requirements and behavior of the TCS. The model is also to support the test and evaluation of the system to be operated with the unmanned through the standard.
RELATIONSHIP BETWEEN R&D INVESTMENT AND HIGH-TECH EXPORTS: EMPIRICAL STUDY FROM PAKISTAN

The aim of this study is to explore the impact of R&D investment on high tech exports in Pakistan - a developing and emerging economy. To testify such relationship, data are collected from firms’ financial statements, World Bank data base and State Bank of Pakistan data source. Time span of study is consisting of 20 years from 1995 to 2014. By using ordinary least square with robust standard error, along with several macroeconomic control variables, we found significantly positive relationship between R&D investment and high the exports. According to the product life cycle theory of international trade, innovative activities help to create competitive advantage which is essential for competing in worldwide markets. The empirical results show that R&D investment creates new products, which can attract foreign customers and creating export opportunities.
Task-irrelevant alpha component analysis in motor imagery based brain computer interface

In motor imagery based BCI, the alpha rhythm shares the same frequency band with sensorimotor rhythm (SMR), and does not correlate with mental task, which contaminates the SMR recording. Independent component analysis (ICA) was applied to decompose original EEG signal into source components, and a comprehensive method was proposed to discriminate those source components by combining temporal, frequency, spatial, and class label information. Task-irrelevant alpha components were sorted out and their projections were reduced by proper bipolar electrode placement for improving the BCI performance.
Spirituality of EMTs: A Study of the Spiritual Nature of EMS Workers and Its Effects on Perceived Happiness and Prayers for Patients

Abstract Introduction: There is reason to believe that traumatic events experienced on the job make emergency medical services (EMS) workers more skeptical about their spiritual beliefs. Little is known about the spiritual lives and experiences of emergency medical technicians (EMTs). No studies have measured the responses of EMTs to the spiritual needs of their patients. Purpose: This study investigates whether EMS workers are less spiritual than the average U.S. citizen, and what effect this has on prayer for patients and perceived happiness. Methods: Data were collected in a major metropolitan EMS system from 125 EMTs and paramedics through a questionnaire about their beliefs and behaviors regarding their spirituality. Pearson product-moment correlation coefficients (r) were used to analyze variables. The religious attitudes of EMTs were compared with those of the general population as defined in the Gallup studies. Results: Ninety-one percent of the EMS workers interviewed and 94% of Gallup's sample of the general population said they believe in God. The findings on other measures in the EMT sample also were very similar to those defined in the general population. Of the EMTs, 60% said they never have doubted the existence of God. Eighty-four percent believe God still works miracles, and 80% of the EMTs believe in life after death. Eighty-seven percent of EMS workers pray; 62 % pray for their patients, and 54% pray for their coworkers. Frequency of church or synagogue attendance is positively and significantly correlated with the degree of perceived life happiness (r = 0.226, p <0.025>0.005). Frequency of prayer also is correlated positively to perceived life happiness (r = 0.182,p<0.025>0.005). Conclusion: Emergency medical services workers are interested and willing to talk about their spiritual lives. They do have more doubts about the existence of God than does the average civilian, but are just as spiritual. Those EMTs with more active spiritual lives perceive themselves as happier. The majority of EMS workers pray for their patients.
Radiofrequency ablation of liver tumors: a systematic review.

OBJECTIVES To systematically review radiofrequency ablation (RFA) for treating liver tumors. DATA SOURCES Databases were searched in July 2003. STUDY SELECTION Studies comparing RFA with other therapies for hepatocellular carcinoma (HCC) and colorectal liver metastases (CLM) plus selected case series for CLM. DATA EXTRACTION One researcher used standardized data extraction tables developed before the study, and these were checked by a second researcher. DATA SYNTHESIS For HCC, 13 comparative studies were included, 4 of which were randomized, controlled trials. For CLM, 13 studies were included, 2 of which were nonrandomized comparative studies and 11 that were case series. There did not seem to be any distinct differences in the complication rates between RFA and any of the other procedures for treatment of HCC. The local recurrence rate at 2 years showed a statistically significant benefit for RFA over percutaneous ethanol injection for treatment of HCC (6% vs 26%, 1 randomized, controlled trial). Local recurrence was reported to be more common after RFA than after laser-induced thermotherapy, and a higher recurrence rate and a shorter time to recurrence were associated with RFA compared with surgical resection (1 nonrandomized study each). For CLM, the postoperative complication rate ranged from 0% to 33% (3 case series). Survival after diagnosis was shorter in the CLM group treated with RFA than in the surgical resection group (1 nonrandomized study). The CLM local recurrence rate after RFA ranged from 4% to 55% (6 case series). CONCLUSIONS Radiofrequency ablation may be more effective than other treatments in terms of less recurrence of HCC and may be as safe, although the evidence is scant. There was not enough evidence to determine the safety or efficacy of RFA for treatment of CLM.
Targeting frameshifting in the human immunodeficiency virus

Introduction: HIV-1 uses a programmed –1 ribosomal frameshift to generate Gag-Pol, the precursor of its enzymes, when its full-length mRNA is translated by the ribosomes of the infected cells. This change in the reading frame occurs at a so-called slippery sequence that is followed by a specific secondary structure, the frameshift stimulatory signal. This signal controls the frameshift efficiency. The synthesis of HIV-1 enzymes is critical for virus replication and therefore, the –1 ribosomal frameshift could be the target of novel antiviral drugs. Areas covered: Various approaches were used to select drugs interfering with the –1 frameshift of HIV-1. These include the selection and modification of chemical compounds that specifically bind to the frameshift stimulatory signal, the use of antisense oligonucleotides targeting this signal and the selection of compounds that modulate HIV-1 frameshift, by using bicistronic reporters where the expression of the second cistron depends upon HIV-1 frameshift. Expert opinion: The most promising approach is the selection and modification of compounds specifically targeting the HIV-1 frameshift stimulatory signal. The use of antisense oligonucleotides binding to the frameshift stimulatory signal is still questionable. The use of bicistronic reporters preferentially selects compounds that modulate the frameshift by targeting the ribosomes, which is less promising.
Type VI Collagen Anchors Endothelial Basement Membranes by Interacting with Type IV Collagen*

Type VI collagen filaments are found associated with interstitial collagen fibers, around cells, and in contact with endothelial basement membranes. To identify type VI collagen binding proteins, the amino-terminal domains of the α1(VI) and α2(VI) chains and a part of the carboxyl-terminal domain of the α3(VI) chain were used as bait in a yeast two-hybrid system to screen a human placenta library. Eight persistently positive clones were identified, two coding the known matrix proteins fibronectin and basement membrane type IV collagen and the rest coding new proteins. The amino-terminal domain of α1(VI) was shown to interact with the carboxyl-terminal globular domain of type IV collagen. The specificity of this interaction was further studied using the yeast two-hybrid system in a one-on-one format and confirmed by using isolated protein domains in immunoprecipitation, affinity blots, and enzyme-linked immunosorbent assay-based binding studies. Co-distribution of type VI and type IV collagens in human muscle was demonstrated using double labeling immunofluorescent microscopy and immunoelectron microscopy. The strong interaction of type VI collagen filaments with basement membrane collagen provided a possible molecular pathogenesis for the heritable disorder Bethlem myopathy.
Noninvasive Diagnosis of Hepatocellular Carcinoma: Elaboration on Korean Liver Cancer Study Group-National Cancer Center Korea Practice Guidelines Compared with Other Guidelines and Remaining Issues

Hepatocellular carcinoma (HCC) can be diagnosed based on characteristic findings of arterial-phase enhancement and portal/delayed "washout" in cirrhotic patients. Several countries and major academic societies have proposed varying specific diagnostic criteria for HCC, largely reflecting the variable HCC prevalence in different regions and ethnic groups, as well as different practice patterns. In 2014, a new version of Korean practice guidelines for management of HCC was released by the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC). According to the KLCSG-NCC Korea practice guidelines, if the typical hallmark of HCC (i.e., hypervascularity in the arterial phase with washout in the portal or 3 min-delayed phases) is identified in a nodule ≥ 1 cm in diameter on either dynamic CT, dynamic MRI, or MRI using hepatocyte-specific contrast agent in high-risk groups, a diagnosis of HCC is established. In addition, the KLCSG-NCC Korea practice guidelines provide criteria to diagnose HCC for subcentimeter hepatic nodules according to imaging findings and tumor marker, which has not been addressed in other guidelines such as Association for the Study of Liver Diseases and European Association for the Study of the Liver. In this review, we briefly review the new HCC diagnostic criteria endorsed by the 2014 KLCSG-NCC Korea practice guidelines, in comparison with other recent guidelines; we furthermore address several remaining issues in noninvasive diagnosis of HCC, including prerequisite of sonographic demonstration of nodules, discrepancy between transitional phase and delayed phase, and implementation of ancillary features for HCC diagnosis.
The clinical use of disulfiram (Antabuse): a review.

Disulfiram is a potent alcohol-sensitizing drug, the effectiveness of which remains unproven in the treatment of alcoholism after 40 years of use. Its clinical utility is more closely associated with nonspecific, nonpharmacological factors (such as social class, patient compliance, patient personality characteristics, and treatment structure) than with its aversive biochemistry. Disulfiram is not effective as a sole alternative to a structured treatment program. Disulfiram retains a place in standard alcoholism treatment programs because clinicians have found this agent useful for selected alcoholic patients. Clinical studies and clinical lore describe these patients as older, relapse-prone, socially stable, cognitively intact, not depressed, compulsive, capable of following rules, and tolerant of dependence. Another distinctly responsive (but evasive) group is court-probated patients. These characteristics also describe patients who are well-known to have good outcomes without disulfiram, thus they do not help clinicians to select suitable patients for this medication. Consequently, this article proposes the following selection criteria: (1) patients who can tolerate a treatment relationship; (2) patients who are relapse-prone (but in treatment); (3) patients who have failed with less structured approaches; (4) patients in early abstinence who are in crisis or under severe stress; (5) patients in established recovery for whom individual or group psychotherapy is a relapse risk; and (6) patients who specifically request it. With or without disulfiram, a treatment program needs to be highly structured and predictable in order to be useful to newly recovering patients. Recovery is a process with discernible phases of development, and the provision of structure is the core of early treatment, where behavior change is more important than insight. A well-structured program will have phases through which a patient may progress. Generally speaking, disulfiram is most useful early to establish sobriety and to allow time for other support structures, such as AA, therapist-patient relationships, and new personal relationships, to take hold. Disulfiram is best given to patients with prior treatment failures, early in treatment, briefly during crises in established sobriety, or to support unusual stresses, such as psychotherapy. Prescriptions should be short-term and not allow automatic refills. It should be necessary to attend a treatment program in order to obtain them. Supervision and monitoring dramatically increase compliance. (ABSTRACT TRUNCATED AT 400 WORDS)
Development and validation of a prognostic nomogram for colorectal cancer after radical resection based on individual patient data from three large-scale phase III trials

Background Few prediction models have so far been developed and assessed for the prognosis of patients who undergo curative resection for colorectal cancer (CRC). Materials and Methods We prepared a clinical dataset including 5,530 patients who participated in three major randomized controlled trials as a training dataset and 2,263 consecutive patients who were treated at a cancer-specialized hospital as a validation dataset. All subjects underwent radical resection for CRC which was histologically diagnosed to be adenocarcinoma. The main outcomes that were predicted were the overall survival (OS) and disease free survival (DFS). The identification of the variables in this nomogram was based on a Cox regression analysis and the model performance was evaluated by Harrell's c-index. The calibration plot and its slope were also studied. For the external validation assessment, risk group stratification was employed. Results The multivariate Cox model identified variables; sex, age, pathological T and N factor, tumor location, size, lymphnode dissection, postoperative complications and adjuvant chemotherapy. The c-index was 0.72 (95% confidence interval [CI] 0.66-0.77) for the OS and 0.74 (95% CI 0.69-0.78) for the DFS. The proposed stratification in the risk groups demonstrated a significant distinction between the Kaplan–Meier curves for OS and DFS in the external validation dataset. Conclusions We established a clinically reliable nomogram to predict the OS and DFS in patients with CRC using large scale and reliable independent patient data from phase III randomized controlled trials. The external validity was also confirmed on the practical dataset.