Miracle-dz/UniFAR-FTUs huggingface dataset:
Endoscopic Submucosal Dissection Using a Novel Versatile Knife: An Animal Feasibility Study (with Video)

Background/Aims In order to reduce the procedure time and the number of accessory changes during endoscopic submucosal dissection (ESD), we developed a novel versatile knife, which has the combined advantages of several conventional knives. The aim of this study was to compare the efficacy, safety, and histological quality of ESD performed using this novel versatile knife and a combination of several conventional knives. Methods This was an in vivo animal study comparing two different modalities of ESD in mini-pigs. Completion time of each resection was documented, and the resected specimens were retrieved and evaluated for completeness. To assess the quality control of the procedures and adverse events, detailed histopathological examinations were performed. Results A total of 18 specimens were dissected by ESD safely and easily (nine specimens using the new versatile knife; nine specimens by mixing conventional knives). All resections were completed as en bloc resections. There was no significant difference in procedure time between the 2 modalities (456 seconds vs. 355 seconds, p=0.258) and cutting speed (1.983 mm2/sec vs. 1.57 mm2/sec, p=1.000). The rate of adverse events and histological quality did not statistically differ between the modalities. Conclusions ESD with a versatile knife appeared to be an easy, safe, and technically efficient method.
Down-regulation of the Antisense Mitochondrial Non-coding RNAs (ncRNAs) Is a Unique Vulnerability of Cancer Cells and a Potential Target for Cancer Therapy*

Background: Down-regulation of the antisense mitochondrial ncRNAs (ASncmtRNAs) is a general vulnerability of cancer cells. Results: Knocking down the ASncmtRNAs induces apoptosis, down-regulation of survivin, and generation of microRNAs. Conclusion: Induction of apoptosis in cancer cells is potentiated by down-regulation of survivin. Significance: The ASncmtRNAs represent a new potential therapeutic target for cancer. Hallmarks of cancer are fundamental principles involved in cancer progression. We propose an additional generalized hallmark of malignant transformation corresponding to the differential expression of a family of mitochondrial ncRNAs (ncmtRNAs) that comprises sense and antisense members, all of which contain stem-loop structures. Normal proliferating cells express sense (SncmtRNA) and antisense (ASncmtRNA) transcripts. In contrast, the ASncmtRNAs are down-regulated in tumor cells regardless of tissue of origin. Here we show that knockdown of the low copy number of the ASncmtRNAs in several tumor cell lines induces cell death by apoptosis without affecting the viability of normal cells. In addition, knockdown of ASncmtRNAs potentiates apoptotic cell death by inhibiting survivin expression, a member of the inhibitor of apoptosis (IAP) family. Down-regulation of survivin is at the translational level and is probably mediated by microRNAs generated by dicing of the double-stranded stem of the ASncmtRNAs, as suggested by evidence presented here, in which the ASncmtRNAs are bound to Dicer and knockdown of the ASncmtRNAs reduces reporter luciferase activity in a vector carrying the 3′-UTR of survivin mRNA. Taken together, down-regulation of the ASncmtRNAs constitutes a vulnerability or Achilles' heel of cancer cells, suggesting that the ASncmtRNAs are promising targets for cancer therapy.
Advanced data analysis algorithms for the time-dependent defect spectroscopy of NBTI

In order to identify the physical mechanisms behind the negative bias temperature instability (NBTI), the time-dependent defect spectroscopy (TDDS) has been recently proposed. The TDDS takes advantage of the fact that in nano-scaled devices only a handful of defects are present. As a consequence, degradation and recovery proceed in discrete steps, each of them corresponding to a charge capture or emission event. By repeatedly applying stress and recovery conditions, the TDDS analyzes the statistical properties of these discrete events. The measurement window of the TDDS is very large, but the occurrence of random telegraph noise (RTN) at certain biases/temperatures can limit its applicability. We have developed an advanced data analysis method which can also deal with data contaminated by RTN. The algorithm is based on the combination of a bootstrapping technique and cumulative sum charts. A benefit of the new method is the possibility to detect steps in a large class of different signals with a feasible amount of parameters. Moreover, de-/trapping parameters of the random telegraph noise (RTN) become accessible as well.
Sex‐specific demographic behaviours that shape human genomic variation

In the human species, the two uniparental genetic systems (mitochondrial DNA and Y chromosome) exhibit contrasting diversity patterns. It has been proposed that sex‐specific behaviours, and in particular differences in migration rate between men and women, may explain these differences. The availability of high‐density genomic data and the comparison of genetic patterns on autosomal and sex chromosomes at global and local scales allow a reassessment of the extent to which sex‐specific behaviours shape our genome. In this article, we first review studies comparing the genetic patterns at uniparental and biparental genetic systems and assess the extent to which sex‐specific migration processes explain the differences between these genetic systems. We show that differences between male and female migration rates matter, but that they are certainly not the only contributing factor. In particular, differences in effective population size between men and women are also likely to account for these differences. Then, we present and discuss three anthropological processes that may explain sex‐specific differences in effective population size and thus human genomic variation: (i) variance in reproductive success arising from, for example, polygyny; (ii) descent rules; and (iii) transmission of reproductive success.
Soluble Jagged1 Inhibits Pulmonary Hypertension by Attenuating Notch Signaling

Objective—Notch signaling has been implicated in the development of pulmonary arterial hypertension (PH) as reflected by increased expression of Notch member proteins that induce the proliferation of pulmonary arterial smooth muscle cells (PASMCs). Soluble Jagged1 (sJag1) has been shown to inhibit Notch signaling in vitro and in vivo; however, its capacity to suppress PH remains unknown. Approach and Results—Notch1, Notch3, Jagged1, and Herp2 protein were highly expressed in both the mouse model of hypoxia-induced PH and the rat model of monocrotaline-induced PH. By attenuation and reversal of multiple pathological processes that were associated with PH, adenoviral sJag1 transfection significantly reduced the proliferation and enhanced the apoptosis of PASMCs in PH, whereas vehicle had no effect. The sJag1 inhibitory effect on Notch activation is likely related to its interference with ligand-induced signaling. Importantly, the administration with adenoviral sJag1 improved the survival rate of PH rats. Furthermore, sJag1 can restore the PH-PASMCs phenotype from the dedifferentiated to the differentiated state, by giving a positive effect on the physical binding of myocardin to the CC(A/T)nGG (CArG)-containing regions of vascular smooth muscle cells–specific promoters. Conclusions—Our results demonstrated that the potential therapeutic use of the sJag1 may not only inhibit the proliferation of PASMCs but also restore the PH-PASMCs phenotype from the dedifferentiated to the differentiated state through interference with Notch–Herp2 signaling.
The exonuclease 1 Glu589Lys gene polymorphism and cancer susceptibility: evidence based on a meta-analysis.

BACKGROUND Published studies on the association between the exonuclease 1 (EXO1) Glu589Lys polymorphism and cancer susceptibility have yielded conflicting results. Thus, a meta-analysis of published studies was performed to assess the possible association. MATERIALS AND METHODS All eligible case-control studies published up to January 2013 on the association between the EXO1 Glu589Lys polymorphism and cancer susceptibility were identified by searching PubMed, Web of Science, Science Direct and hand search. Either fixed-effect or random-effect models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) using the Comprehensive Meta-Analysis software version 2.2. RESULTS A total of 4,391 cancer cases and 4,339 controls from 10 studies were included. Overall, no significant association between the EXO1 Glu589Lys polymorphism and cancer susceptibility was observed in either genetic model. However; in subgroup analyses by cancer type, a significant association between EXO1 Glu589Lys and lung cancer risk was found (Lys vs Glu: OR=1.23, 95%CI=1.07- 1.41, p heterogeneity=0.05). Further, subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians (Lys vs Glu: OR=1.42, 95%CI=1.30-1.55, p heterogeneity=0.07; Lys/Lys vs Glu/Glu: OR=1.93, 95%CI=1.20-3.12, p heterogeneity=0.01; Lys/Lys+Glu/Lys vs Glu/Glu: OR=1.52, 95%CI=1.37-1.68, p heterogeneity=0.42; Lys/Lys vs Glu/Lys+Glu/Glu: OR=1.68, 95%CI=1.07-2.65, p heterogeneity=0.02). However, significant association was absent in Caucasians. CONCLUSIONS This meta-analysis suggests, for the first time, that the EXO1 Glu589Lys polymorphism is not associated with overall cancer susceptibility, although marginal associations were found for lung cancer and Asian subgroups. Additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are needed to confirm these findings.
Molecular determinants for CRISPR RNA maturation in the Cas10–Csm complex and roles for non-Cas nucleases

Abstract CRISPR–Cas (Clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) is a prokaryotic immune system that destroys foreign nucleic acids in a sequence-specific manner using Cas nucleases guided by short RNAs (crRNAs). Staphylococcus epidermidis harbours a Type III-A CRISPR–Cas system that encodes the Cas10–Csm interference complex and crRNAs that are subjected to multiple processing steps. The final step, called maturation, involves a concerted effort between Csm3, a ruler protein in Cas10–Csm that measures six-nucleotide increments, and the activity of a nuclease(s) that remains unknown. Here, we elucidate the contributions of the Cas10–Csm complex toward maturation and explore roles of non-Cas nucleases in this process. Using genetic and biochemical approaches, we show that charged residues in Csm3 facilitate its self-assembly and dictate the extent of maturation cleavage. Additionally, acidic residues in Csm5 are required for efficient maturation, but recombinant Csm5 fails to cleave crRNAs in vitro. However, we detected cellular nucleases that co-purify with Cas10–Csm, and show that Csm5 regulates their activities through distinct mechanisms. Altogether, our results support roles for non-Cas nuclease(s) during crRNA maturation and establish a link between Type III-A CRISPR–Cas immunity and central nucleic acid metabolism.
[Pregnancy complications and pregnancy outcome in women under 18 and above 35 years old in highly industrialized urban complex of Upper Silesia].

OBJECTIVES There is a considerable effort done by many researchers towards identification factors that are responsible for increase in risk of adverse perinatal outcome. Maternal age is one of the most obvious but also one of the most difficult to proper interpretation. MATERIAL AND METHODS The authors analyzed major complications in pregnancy and labour in women under 18 above 35 years old in highly industrialized urban complex of Upper Silesia. RESULTS Extremes of reproductive age, adolescence and age above 35 years have an impact on biological, social, cultural and economic conditions that significantly affects obstetrical results. CONCLUSIONS Teenage mothers and the mothers above 35 years old are regarded to be in increased risk of instrumental delivery and caesarean section. These factors are also associated with augmented incidence of complication such as preterm labour, intrauterine growth restriction etc.
Effects of urea infusion and ruminal degradable protein concentration on microbial growth, digestibility, and fermentation in continuous culture.

The effects of urea and rumen-degradable protein (RDP) on microbial growth, digestibility, and fermentation were examined using dual-flow continuous culture. The experimental design was a 4 x 4 Latin square with a 2 x 2 factorial arrangement of treatments. Factors were urea infusion (0.4 g/L of artificial saliva) and RDP concentration, and the treatments were as follows: 1) low RDP (8% of dietary dry matter) without urea (LDNU), 2) high RDP (11% of dietary dry matter) without urea (HDNU), 3) low RDP (8% of dietary dry matter) with urea (LDU), and 4) high RDP (11% of dietary dry matter) with urea (HDU). The LDNU (i.e., negative control) and HDNU treatments were formulated to be nitrogen limiting. Results indicated that infusion of urea increased all digestibility measurements (P < 0.05), which in turn increased (P < 0.05) volatile fatty acid, NH3 nitrogen, trichloroacetic acid-soluble nitrogen, and soluble protein concentrations. Increasing dietary RDP improved dry matter and organic matter digestibility (P < 0.05) but did not alter acid detergent fiber or nonfiber carbohydrate digestibilities (P > 0.05). Isobutyrate concentration decreased (P = 0.05) with increased RDP. Increased dietary RDP increased crude protein degradation and soluble protein concentration (P < 0.05), but NH3 nitrogen, trichloroacetic acid-soluble nitrogen, and peptide nitrogen were unaffected by changing RDP levels. Microbial growth efficiency was 19.9, 24.9, 28.0, and 32.2 g N/g organic matter truly digested for LDNU, HDNU, LDU, and HDU, respectively, and was significantly improved both by urea infusion (P = 0.002) and increased RDP concentration (P = 0.021). The interactions of urea and RDP (P < 0.05) were explained by the high digestibility of neutral detergent fiber, nonstructural carbohydrate, and especially hemicellulose, with the HDNU treatment. The results of this study indicated that hemicellulose-degrading bacteria were able to effectively compete with nonstructural carbohydrate-degrading bacteria for available peptide and amino acid nitrogen. Further, the extent of protein degradation was dependent on the availability of NH3 nitrogen in the system.
Late Results of Endorectal Flap in Management of High Type Perianal Fistula

BACKGROUND Fistula-in-ano is a problematic perianal disease for physicians and patients because of its occasional difficulty in management. Due to the different types of fistulas seen in patients, careful approach is necessary to correctly choose from among the various surgical techniques. One surgical method for complex fistula is the endorectal advancement flap which has been frequently performed because of its low complication rate. METHODS This study enrolled 40 (33 males, 7 females) patients who suffered from high type fistula (greater than 30%-50% involvement of the external sphincter) as noted on digital rectal examination and endoanalsonography. Patients were seen at Shahid Faghihi Hospital, affiliated with Shiraz University of Medical Sciences, between 2007 and 2011. All enrolled patients received similar preoperational preparation. We used the jackknife operative position and determined the internal orifice of the fistula by inserting a probe, with injection of methylene blue or oxygen peroxide. Endorectal advancement flap included the mucosa, submucosa and thin portion of the muscle that completely covered the sutured internal orifice area. The external orifice was opened to adjust the external border of the external sphincter to allow for effective drainage. RESULTS All enrolled patients were followed for 36 months, which was noticeable statistically when compared with other study findings of high type fistula. The location of the external orifice, age, sex and bowel habits were not related to recurrence rate. CONCLUSION Endorectal advancement flap in selected patients who suffer from high type fistula seems to have beneficial effects with a low recurrence rate. Therefore, management of complex high type fistulas remains a challenging topic.
Role of β-Lactamase Inhibitors as Potentiators in Antimicrobial Chemotherapy Targeting Gram-Negative Bacteria

Since the discovery of penicillin, β-lactam antibiotics have commonly been used to treat bacterial infections. Unfortunately, at the same time, pathogens can develop resistance to β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems by producing β-lactamases. Therefore, a combination of β-lactam antibiotics with β-lactamase inhibitors has been a promising approach to controlling β-lactam-resistant bacteria. The discovery of novel β-lactamase inhibitors (BLIs) is essential for effectively treating antibiotic-resistant bacterial infections. Therefore, this review discusses the development of innovative inhibitors meant to enhance the activity of β-lactam antibiotics. Specifically, this review describes the classification and characteristics of different classes of β-lactamases and the synergistic mechanisms of β-lactams and BLIs. In addition, we introduce potential sources of compounds for use as novel BLIs. This provides insights into overcoming current challenges in β-lactamase-producing bacteria and designing effective treatment options in combination with BLIs.
Poverty in Russia during the Transition: An Overview

It is no surprise that the breakup of the Soviet Union and the overall demise of the planned economy have had a profound effect on the welfare of the Russian people. But the absence of reliable survey data has constrained understanding of the impact that transition has had on the distribution of income. This article draws upon several rounds of a nationally representative household survey to document the sharp increases in the incidence and severity of poverty that have occurred during the transition. The authors investigate the routes by which macroeconomic and structural developments have been transmitted through the labor market and examine the performance of an increasingly overburdened, unfocused, and inadequate system of social protection. There is no evidence to suggest that the poor have shared in Russia's emerging economic recovery, and the emergence of a core group of long-term poor appears to be a distinct possibility.
The conundrum of death, dying and organ donation

Aim: To evaluate the efficacy of oral cyclosporin A in the prevention and treatment of immune graft rejection in heavily vascularised, repeated keratoplasties with high risk for failure. Methods: 21 consecutive patients with 28 repeated corneal transplants and four quadrant vascularised recipient bed were treated with oral cyclosporin A for an average period of 12 months (range 1–41 months) and followed for an average period of 26.6 months (range 6–106 months). The average cyclosporin A blood level was 325 ng/ml (range 180–421 ng/ml). Within this group of 21 patients, another 12 regrafts were not treated with cyclosporin A and served as a control group. Results: Nine of the 28 regrafts (32%) treated with cyclosporin A remained clear. The Kaplan-Meier curve showed a constant decline in survival of the treated grafts, although the survival proportion during the first year of treatment was statistically higher for the treated group compared with the untreated group. Once immune regraft rejection occurred, the regraft failed despite treatment with cyclosporin A and extensive topical and systemic corticosteroids. Nine regrafts (32%) had immune graft rejection and all ultimately failed compared with five in the untreated regrafts (42%, p = NS). Ten other regrafts (36%) in the treatment group failed due to causes other than immune regraft rejection. Conclusions: Systemic cyclosporin A has a limited beneficial effect in preventing immune graft rejection in repeated corneal transplants in a highly vascularised corneal bed. When immune graft rejection occurs in such regrafts, the prognosis is poor despite aggressive medical treatment. Causes other than immune regraft rejection may also result in poor visual outcome in patients with clear regrafts.
Comparative Genomic Analysis of the ICESa2603 Family ICEs and Spread of erm(B)- and tet(O)-Carrying Transferable 89K-Subtype ICEs in Swine and Bovine Isolates in China

Integrative and conjugative elements (ICEs) of the ICESa2603 family have been isolated from several species of Streptococcus spp. ; however, the comparative genomic and evolutionary analyses of these particular ICEs are currently only at their initial stages. By investigating 13 ICEs of the ICESa2603 family and two ICESa2603 family-like ICEs derived from diverse hosts and locations, we have determined that ICEs comprised a backbone of 30 identical syntenic core genes and accessory genes that were restricted to the intergenic sites or the 3′-end of the non-conserved domain of core genes to maintain its function. ICESa2603 family integrase IntICESa2603 specifically recognized a 15-bp att sequence (TTATTTAAGAGTAAC) at the 3′-end of rplL, which was highly conserved in genus Streptococcus. Phylogenetic analyses suggest that extensive recombination/insertion and the occurrence of a hybrid/mosaic in the ICESa2603 family were responsible for the significant increase in ICE diversity, thereby broadening its host range. Approximately 42.5 and 38.1% of the tested Streptococcus suis and Streptococcus agalactiae clinical isolates respectively contained ICESa2603 family Type IV secretion system (T4SS) genes, and 80.5 and 62.5% of which also respectively carried intICESa2603, indicating that ICESa2603 family is widely distributed across these bacteria. Sequencing and conjugation transfer of a novel sequence type ST303 clinical S. suis isolate HB1011 demonstrated that the 89K-subtype ICESsuHB1011 retained its transferrable function, thereby conferring tetracycline and macrolide resistance.
Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation

Recurrence of hepatitis C after liver transplantation (LT) is the main cause of graft loss and retransplantation. Frequent liver biopsies are essential to follow‐up hepatitis C virus (HCV)–induced liver damage. However, liver biopsy is an invasive and expensive procedure. We evaluated prospectively the diagnostic accuracy of noninvasive measurement of liver stiffness (by transient elastography) to assess the severity of hepatitis C recurrence after LT. For this purpose, we included 124 HCV‐infected liver transplant recipients who underwent 169 liver biopsies and 129 hepatic hemodynamic studies with determination of hepatic venous pressure gradient (HVPG). Simultaneously, patients underwent measurement of liver stiffness. Liver fibrosis was mild (F0‐F1) in 96 cases (57%) and significant (F2‐F4) in 73 (43%). HVPG was normal (<6 mm Hg) in 69 cases (54%) and elevated (≥6 mm Hg) in 60 (46%). Using a liver stiffness cutoff value of 8.5 kilopascals, the sensitivity, specificity, negative predictive value, and positive predictive value for diagnosis of fibrosis ≥F2 were 90%, 81%, 79%, and 92%, respectively. The area under the curve (AUC) for diagnosis of fibrosis ≥F2, ≥F3 and F4 were 0.90, 0.93, and 0.98, respectively. There was a close direct correlation between liver stiffness and HVPG (Pearson coefficient, 0.84; P < 0.001) and the AUC for diagnosis of portal hypertension (HVPG ≥6 mm Hg) was 0.93. Importantly, none of the individuals with liver stiffness below the cutoff value had either bridging fibrosis (F3) or cirrhosis (F4) or significant portal hypertension (HVPG ≥10 mm Hg). In conclusion, determination of liver stiffness is an extremely valuable tool to assess the severity of HCV recurrence after LT and in reducing the need of follow‐up liver biopsies. Liver Transpl 12:1791‐1798, 2006. © 2006 AASLD.