Miracle-dz/UniFAR-FTUs huggingface dataset:
The Complexity of Enumeration and Reliability Problems

The class of $# P$-complete problems is a class of computationally eqivalent counting problems (defined by the author in a previous paper) that are at least as difficult as the $NP$-complete problems. Here we show, for a large number of natural counting problems for which there was no previous indication of intractability, that they belong to this class. The technique used is that of polynomial time reduction with oracles via translations that are of algebraic or arithmetic nature.
Are vaginal swabs comparable to cervical smears for human papillomavirus DNA testing?

Objective Human papillomavirus (HPV) testing is widely incorporated into cervical cancer screening strategies. Current screening requires pelvic examination for cervical sampling, which may compromise participation. The acceptance could be raised by introducing testing on vaginal swabs. We explored the interchangeability of vaginal swabs and cervical smears for HPV testing, by means of a prospective study conducted in female sex workers (FSWs). Besides, we report on the occurrence of 32 different HPV genotypes in FSW with low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion (HSIL). Methods Paired physician-collected vaginal swabs and cervical smears from 303 FSW were tested for HPV using the Abbott RealTime High-Risk HPV assay. Cervical cytology was examined on cervical smears. In case of HSIL/LSIL cytological classification (n=52), both samples were genotyped using INNO-LiPa HPV Genotyping Extra II. Results The overall prevalence of high-risk (HR)-HPV was 51%. In FSW with HSIL/LSIL cervical cytology, the sensitivity and specificity of vaginal samples for the detection of HR-HPV was 100% and 70% and for probable HR-HPV 100% and 91%. The mean number of genotypes identified in vaginal samples (mean=3.5; 95% confidence interval [CI]=2.8–4.2) was significantly higher than in cervical smear samples (mean=2.6; 95% CI=2.1–3.0) (p=0.001). The most frequently encountered HR-HPV genotypes were HPV16, 31, 51, and 52. Conclusion As our study shows that vaginal swabs are equivalent to cervical smears for the detection of (probable) HR-HPV, vaginal swabs can be used for HPV testing in cervical cancer screening strategies. Given the acceptance of vaginal sampling, this finding offers an opportunity to boost screening coverage.
Vitamin E as an Antioxidant in Female Reproductive Health

Vitamin E was first discovered in 1922 as a substance necessary for reproduction. Following this discovery, vitamin E was extensively studied, and it has become widely known as a powerful lipid-soluble antioxidant. There has been increasing interest in the role of vitamin E as an antioxidant, as it has been discovered to lower body cholesterol levels and act as an anticancer agent. Numerous studies have reported that vitamin E exhibits anti-proliferative, anti-survival, pro-apoptotic, and anti-angiogenic effects in cancer, as well as anti-inflammatory activities. There are various reports on the benefits of vitamin E on health in general. However, despite it being initially discovered as a vitamin necessary for reproduction, to date, studies relating to its effects in this area are lacking. Hence, this paper was written with the intention of providing a review of the known roles of vitamin E as an antioxidant in female reproductive health.
Warm dark matter does not do better than cold dark matter in solving small-scale inconsistencies

Over the last decade, warm dark matter (WDM) has been repeatedly proposed as an alternative scenario to the standard cold dark matter (CDM) one, potentially resolving several disagreements between the CDM model and observations on small scales. Here, we reconsider the most important CDM small-scale discrepancies in the light of recent observational constraints on WDM. As a result, we find that a conventional thermal (or thermal-like) WDM cosmology with a particle mass in agreement with Lyman-$\alpha$ is nearly indistinguishable from CDM on the relevant scales and therefore fails to alleviate any of the small-scale problems. The reason for this failure is that the power spectrum of conventional WDM falls off too rapidly. To maintain WDM as a significantly different alternative to CDM, more evolved production mechanisms leading to multiple dark matter components or a gradually decreasing small-scale power spectrum have to be considered.
The effects of downhill and uphill exercise training on osteogenesis-related factors in ovariectomy-induced bone loss

[Purpose] Recent evidence suggests that regular exercise training plays a decisive role in maintaining homeostasis and promoting muscle and skeletal formation. However, the effect of downhill exercise training on osteogenesis-related factors is not well understood. [Methods] Thus, we investigated the effect of uphill and downhill training on ovariectomy (OVX)-induced bone loss. After ovary removal, the exercise method performed included uphill (16 m/min, +15°) and downhill training (16 m/min, –15°) for 60 min/day and 5 days/week, respectively, for 8 weeks. [Results] Our results showed that both uphill and downhill training significantly decreased the body weight, total cholesterol, and creatine kinase (CK) levels in the context of OVX-induced bone loss. On the contrary, levels of an osteogenesis indicator, osteocalcin and alkaline phosphatase were elevated. Consequently, the uphill and downhill training reduced OVX- induced bone loss in the distal femoral metaphysis. Likewise, the bone microstructure in OVX-induced bone loss was enhanced upon training. In particular, the inhibition of RANKL-induced osteoclast formation and osteoclast-specific gene expression improved upon downhill training compared to uphill training. [Conclusion] These results suggest that the uphill and downhill exercise types appeared to positively affect the expression of osteogenesis-related factors along with bone density and microstructure. Particularly, the downhill training has more beneficial effects on the maintenance of homeostasis during bone formation.
Assessment of Micronutrient Status in Critically Ill Children: Challenges and Opportunities

Micronutrients refer to a group of organic vitamins and inorganic trace elements that serve many functions in metabolism. Assessment of micronutrient status in critically ill children is challenging due to many complicating factors, such as evolving metabolic demands, immature organ function, and varying methods of feeding that affect nutritional dietary intake. Determination of micronutrient status, especially in children, usually relies on a combination of biomarkers, with only a few having been established as a gold standard. Almost all micronutrients display a decrease in their serum levels in critically ill children, resulting in an increased risk of deficiency in this setting. While vitamin D deficiency is a well-known phenomenon in critical illness and can predict a higher need for intensive care, serum concentrations of many trace elements such as iron, zinc, and selenium decrease as a result of tissue redistribution in response to systemic inflammation. Despite a decrease in their levels, supplementation of micronutrients during times of severe illness has not demonstrated clear benefits in either survival advantage or reduction of adverse outcomes. For many micronutrients, the lack of large and randomized studies remains a major hindrance to critically evaluating their status and clinical significance.
Quantum weakest preconditions

We develop a notion of predicate transformer and, in particular, the weakest precondition, appropriate for quantum computation. We show that there is a Stone-type duality between the usual state-transformer semantics and the weakest precondition semantics. Rather than trying to reduce quantum computation to probabilistic programming, we develop a notion that is directly taken from concepts used in quantum computation. The proof that weakest preconditions exist for completely positive maps follows immediately from the Kraus representation theorem. As an example, we give the semantics of Selinger's language in terms of our weakest preconditions. We also cover some specific situations and exhibit an interesting link with stabilisers.
Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Background Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P = .01). Conclusions Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. Clinical Trials registration NCT02088840.
Pancreas Fat and &bgr; Cell Mass in Humans With and Without Diabetes: An Analysis in the Japanese Population

Context: The mechanisms by which &bgr; cell mass is reduced in patients with type 2 diabetes remain unclear. It has been postulated that ectopic fat deposits in the pancreas induce &bgr; cell apoptosis, leading to the development of diabetes. Objective: The aim of this study was to clarify the effects of intrapancreatic fat on &bgr; and &agr; cell mass in humans with and without diabetes. Design and Subjects: Using our tissue database, pancreas sections of 72 Japanese nondiabetic (NDM) autopsy cases and 50 diabetic and 49 age‐ and body mass index (BMI)‐matched NDM patients who underwent pancreatic surgery were analyzed. In addition to histological grading, intrapancreatic fat area (IPFA) was quantified as fractional intralobular, but not interlobular, fat area to the whole pancreas area. Results: Although IPFA was positively correlated with age and BMI, there was no significant difference in IPFA between cases with and without diabetes. Moreover, no association was found between IPFA and either &bgr; or &agr; cell area, or glycated hemoglobin. Conclusion: These findings suggest that pancreatic fat deposits have little effect on &bgr; cell mass and the development of diabetes in humans.
Hydrogen Sulfide Mitigates Myocardial Infarction via Promotion of Mitochondrial Biogenesis-Dependent M2 Polarization of Macrophages.

AIMS Macrophages are of key importance for tissue repair after myocardial infarction (MI). Hydrogen sulfide (H2S) has been shown to exert cardioprotective effects in MI. However, the mechanisms by which H2S modulates cardiac remodeling and repair post-MI remain to be clarified. RESULTS In our current study, we showed that H2S supplementation ameliorated pathological remodeling and dysfunction post-MI in wild-type (WT) and CSE KO mice, resulting in decreased infarct size and mortality, accompanied by an increase in the number of M2-polarized macrophages at the early stage of MI. Strikingly, adoptive transfer of NaHS-treated bone marrow-derived macrophages into WT and CSE KO mice with depleted macrophages also ameliorated MI-induced cardiac functional deterioration. Further mechanistic studies demonstrated that NaHS-induced M2 polarization was achieved by enhanced mitochondrial biogenesis and fatty acid oxidation. INNOVATION AND CONCLUSION Our study shows (for the first time) that H2S may have the potential as a therapeutic agent for MI via promotion of M2 macrophage polarization. Rebound Track: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16:293-296, 2012) with the following serving as open reviewers: Hideo Kimura, Chaoshu Tang, Xiaoli Tian, and Kenneth Olson. Antioxid. Redox Signal. 25, 268-281.
Partial Purification and Characterization of Cellulolytic Enzymefrom Bacillus pantothenticus Isolated from a Dumpsite

Cellulose hydrolyzing organism, Bacillus pantothenticus, was isolated from a dumpsite soil. Partial purification of the enzyme with precipitation with 60% chilled acetone and on Biogel P-100 gel filtration yielded an enzyme with specific activity of 253.50, 10.40% yield and purification fold of 2.41. The apparent Km and Vmax for Carboxymethylcellulose (CMC) hydrolysis was 1.167 mg/ml and 0.833 μg of glucose/ml/min respectively. The native molecular weight of the enzyme from B. pantothenticus was estimated as 51.48 kDa. The cellulase produced showed activity over broad range of temperature (30-70°C) with maximum activity at 60°C. The enzyme also showed activity in a wide pH range of 4-11 with optimum activity at pH 4.5. At concentration of 10 mM, KCl, MgCl2, NaCl and NiCl2 inhibited the enzyme while CoCl2 activated the enzyme. The enzyme showed highest activity with microcrystalline cellulose as substrate followed by CMC. Significant activity was also observed with organic substrates such as sugarcane bagasse, orange bagasse and corn cub. The study concluded that the cellulose enzyme obtained had suitable catalytic properties for use in biodegradation of waste and other industrial applications.
Dicer suppresses MMP-2-mediated invasion and VEGFA-induced angiogenesis and serves as a promising prognostic biomarker in human clear cell renal cell carcinoma

Dicer, a key component of the microRNA processing machinery, has been reported to exert discrepant prognostic values and biological roles in different types of cancers. Here, we investigated the function and prognostic value of Dicer in clear cell renal cell carcinoma (ccRCC). Using the retrospective ccRCC patients’ cohorts with tissue microarray (TMA), we demonstrated that Dicer expression was significantly down-regulated in ccRCC compared with renal non-tumor tissues, and negatively associated with pN status (P = 0.005), pM status (P = 0.009) and TNM stage (P =0.013). Multivariate Cox proportional hazards regression analyses showed that positive Dicer expression was an independent favorable factor for prognosis of ccRCC patients (hazard ratio (HR) = 0.709, P = 0.025 for 5-year overall survival; HR = 0.655, P = 0.008 for disease specific survival). Moreover, we found that Dicer decreased the abilities of cell migration, invasion and angiogenesis through suppressing MMP-2 and VEGFA expression. Tumor metastasis model in vivo showed much more metastatic nodules of lung in the Dicer knockdown group than the control group via increased MMP-2 expression. Our findings imply that Dicer inhibits ccRCC metastasis and may serve as promising prognostic biomarkers for ccRCC patients.
Comparison of Salmonella enterica Serovars Typhi and Typhimurium Reveals Typhoidal Serovar-Specific Responses to Bile

ABSTRACT Salmonella enterica serovars Typhi and Typhimurium cause typhoid fever and gastroenteritis, respectively. A unique feature of typhoid infection is asymptomatic carriage within the gallbladder, which is linked with S. Typhi transmission. Despite this, S. Typhi responses to bile have been poorly studied. Transcriptome sequencing (RNA-Seq) of S. Typhi Ty2 and a clinical S. Typhi isolate belonging to the globally dominant H58 lineage (strain 129-0238), as well as S. Typhimurium 14028, revealed that 249, 389, and 453 genes, respectively, were differentially expressed in the presence of 3% bile compared to control cultures lacking bile. fad genes, the actP-acs operon, and putative sialic acid uptake and metabolism genes (t1787 to t1790) were upregulated in all strains following bile exposure, which may represent adaptation to the small intestine environment. Genes within the Salmonella pathogenicity island 1 (SPI-1), those encoding a type IIII secretion system (T3SS), and motility genes were significantly upregulated in both S. Typhi strains in bile but downregulated in S. Typhimurium. Western blots of the SPI-1 proteins SipC, SipD, SopB, and SopE validated the gene expression data. Consistent with this, bile significantly increased S. Typhi HeLa cell invasion, while S. Typhimurium invasion was significantly repressed. Protein stability assays demonstrated that in S. Typhi the half-life of HilD, the dominant regulator of SPI-1, is three times longer in the presence of bile; this increase in stability was independent of the acetyltransferase Pat. Overall, we found that S. Typhi exhibits a specific response to bile, especially with regard to virulence gene expression, which could impact pathogenesis and transmission.
Comparison of phenotypic and WGS-derived antimicrobial resistance profiles of enteroaggregative Escherichia coli isolated from cases of diarrhoeal disease in England, 2015–16

Objectives Phenotypic and genotypic methods for the detection of antimicrobial resistance (AMR) in enteroaggregative Escherichia coli (EAEC) were compared and evaluated. Methods WGS data from 155 isolates of EAEC isolated between June 2015 and December 2016 were mapped to genes known to be associated with phenotypic AMR. Results Phenotypic and genotypic testing of 155 isolates against 10 antimicrobial classes resulted in a total of 25 (1.6%) discordant results of a possible 1550 isolate/antimicrobial combinations. Twenty-three of the mismatches were observed in streptomycin or sulphonamide resistance profiles. These discrepancies were associated with either insertions or truncations in the genes predicted to confer resistance, or in their promotors, rendering them non-functional, or with the presence of aadA variants associated with reduced expression. The most common resistances detected were to ampicillin (56.1%), the sulphonamides (49.7%) and trimethoprim (48.4%). The presence of CTX-M ESBL variants and/or acquired AmpC was detected in 87 of 155 (56.1%) isolates and 18 of 155 (11.6%) isolates were resistant to ciprofloxacin. Eighty-eight (56.8%) isolates were MDR. Conclusions Phenotypic and genome-derived AMR comparisons showed good correlation for EAEC. A better understanding of the role of allelic variants, specific gene combinations and promoter/attenuator mechanisms in the phenotypic manifestation will improve our ability to provide a robust interpretation of the data for surveillance purposes and, ultimately, in the clinical setting.
Meta-analysis of gene expression and integrin-associated signaling pathways in papillary renal cell carcinoma subtypes

Papillary renal cell carcinoma (PRCC) is the second most common renal cell carcinoma (RCC) that can be further subdivided into type 1 (PRCC1) and type 2 (PRCC2) RCCs based on histological and genetic features. PRCC2 is often more aggressive than PRCC1. While integrin-associated protein complexes mediate tumorigenesis and metastases in many types of cancers it is not known whether integrin-mediated signaling impacts PRCC and differs between PRCC1 and PRCC2. In this study, we combined the analysis of five PRCC gene expression datasets derived from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) by using integrative bioinformatics pipelines. We found 1475 differentially expressed genes among which 37 genes were associated with integrin pathways. In comparison with PRCC1, PRCC2 cases showed upregulated expression of α5-integrin (ITGA5) whereas the expression of α6- (ITGA6) and β8-integrins (ITGB8) was downregulated. Because PRCC2 occurs more frequently in men, the meta-analysis was extended to explore the gender effects. This analysis revealed 8 genes but none of them was related to integrin pathways suggesting that other mechanisms than integrin-mediated signaling underlie the observed gender differences in the pathogenicity of PRCC2.
The preferred nucleotide contexts of the AID/APOBEC cytidine deaminases have differential effects when mutating retrotransposon and virus sequences compared to host genes

The AID / APOBEC genes are a family of cytidine deaminases that have evolved in vertebrates, and particularly mammals, to mutate RNA and DNA at distinct preferred nucleotide contexts (or “hotspots”) on foreign genomes such as viruses and retrotransposons. These enzymes play a pivotal role in intrinsic immunity defense mechanisms, often deleteriously mutating invading retroviruses or retrotransposons and, in the case of AID, changing antibody sequences to drive affinity maturation. We investigate the strength of various hotspots on their known biological targets by evaluating the potential impact of mutations on the DNA coding sequences of these targets, and compare these results to hypothetical hotspots that did not evolve. We find that the existing AID / APOBEC hotspots have a large impact on retrotransposons and non-mammalian viruses while having a much smaller effect on vital mammalian genes, suggesting co-evolution with AID / APOBECs may have had an impact on the genomes of the viruses we analyzed. We determine that GC content appears to be a significant, but not sole, factor in resistance to deaminase activity. We discuss possible mechanisms AID and APOBEC viral targets have adopted to escape the impacts of deamination activity, including changing the GC content of the genome.
Astrocyte‐mediated infantile‐onset leukoencephalopathy mouse model

Astrocytes have recently been shown to provide physiological support for various brain functions, although little is known about their involvement in white matter integrity. Several inherited infantile‐onset leukoencephalopathies, such as Alexander disease and megalencephalic leukoencephalopathy with subcortical cysts (MLC), implicate astrocytic involvement in the formation of white matter. Several mouse models of MLC had been generated by knocking out the Mlc1 gene; however, none of those models was reported to show myelin abnormalities prior to formation of the myelin sheath. Here we generated a new Mlc1 knockout mouse and a Mlc1 overexpressing mouse, and demonstrate that astrocyte‐specific Mlc1 overexpression causes infantile‐onset abnormalities of the white matter in which astrocytic swelling followed by myelin membrane splitting are present, whereas knocking out Mlc1 does not, and only shows myelin abnormalities after 12 months of age. Biochemical analyses demonstrated that MLC1 interacts with the Na+/K+ ATPase and that overexpression of Mlc1 results in decreased activity of the astrocytic Na+/K+ pump. In contrast, no changes in Na+/K+ pump activity were observed in Mlc1 KO mice, suggesting that the reduction in Na+/K+ pump activity resulting from Mlc1 overexpression causes astrocytic swelling. Our infantile‐onset leukoencephalopathy model based on Mlc1 overexpression may provide an opportunity to further explore the roles of astrocytes in white matter development and structural integrity. We established a novel mouse model for infantile‐onset leukoencephalopathy by the overexpression of Mlc1. Mlc1 overexpression reduced activity of the astrocytic sodium pump, which may underlie white matter edema followed by myelin membrane splitting. GLIA 2016 GLIA 2017;65:150–168