Miracle-dz/UniFAR-FTUs huggingface dataset:
Probiotic properties of human lactobacilli strains to be used in the gastrointestinal tract.

AIMS The study of two human strains of Lactobacillus to be used as probiotics in the gastrointestinal tract. METHODS AND RESULTS The Lactobacillus acidophilus UO 001 and Lact. gasseri UO 002, were resistant to the gastrointestinal conditions (pH 2 and 3, presence of pepsin, pancreatin or bile salts), the resistance was enhanced in the presence of skimmed milk. Additionally, adhered to Caco-2 cells through glycoproteins in Lact. gasseri and carbohydrates in the case of Lact. acidophilus. These strains are able to inhibit the growth of certain enteropathogens: Salmonella, Listeria and Campylobacter without interfering with the normal microbiota of the gastrointestinal tract, as stated by using the mixed culture and the spot agar test. Finally, strongly adherent Lact. gasseri were found to inhibit the attachment of Escherichia coli O111 to intestinal Caco-2 cells under the condition of exclusion. CONCLUSIONS These results indicate that the two strains of Lactobacillus from human origin present important properties for survival in, and colonization of, the gastrointestinal tract, that give them potential probiotic. SIGNIFICANCE AND IMPACT OF THE STUDY Two strains of Lactobacillus isolated from human vagina of healthy premenopausal women could be promising candidates to be used in the preparation of probiotic products and for their use as health-promoting bacteria.
Sex differences in the development of kidney disease in individuals with type 1 diabetes mellitus: a contemporary analysis.

BACKGROUND Kidney disease in patients with type 1 diabetes historically has been believed to be more prevalent in men. Because recent data do not reflect this pattern, we evaluated whether a sex difference persists. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS We used 18-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study (n = 788; baseline mean age, 27 years; diabetes duration, 19 years). PREDICTOR OR FACTOR Sex and diagnosis interval (1950-1964 or 1965-1980). OUTCOMES Cumulative incidences of macroalbuminuria (albumin excretion rate >200 μg/min) and end-stage renal disease (ESRD; kidney failure, dialysis, or transplant) were evaluated at 20, 25, and 30 years of diabetes duration. To address potential survival bias, death certificate information was included in determining ESRD for those who died before baseline (n = 145). Analyses were stratified by diagnosis year (1950-1964 or 1965-1980). OTHER MEASUREMENTS Kidney disease risk factor information was available. RESULTS A significant interaction was noted between sex and diagnosis cohort for ESRD incidence by 25 (P = 0.002) and 30 (P < 0.001) years' duration. Thus, within the 1950-1964 cohort (210 men and 180 women), ESRD incidence was higher in men compared with women by 25 (30.6% vs 18.0%, respectively) and 30 (43.4% vs 24.6%, respectively) years' duration of type 1 diabetes. However, in the 1965-1980 cohort (260 men and 283 women), the incidence was higher in women (7.6% vs 13.8% by 25 years [P = 0.04] and 13.7% vs 21.0% by 30 years' duration [P = 0.09] in men vs women, respectively). Results were similar for macroalbuminuria. LIMITATIONS Study participants were not followed up from the onset of diabetes; thus, risk-factor data from that period are lacking. CONCLUSIONS Our data suggest that the male excess of type 1 diabetic kidney disease cases observed in the earlier cohort has been eliminated in the younger cohort. The reason for this dramatic change presently is unclear, but should be addressed in subsequent studies.
A Conceptual Test for Cognitively Coherent Quantum Gravity Models

In quantum gravity interpretations, the role of space- and time-related concepts is debated. Some argue that these concepts are not needed to describe physical reality at the Planck scale. Others object that an operational definition of magnitudes cannot get rid of spatiotemporal notions. We propose a “conceptual test” to assess if the mathematical content of a quantum gravity theory refers to some possibly verifiable empirical model. Given that any physical model describes the evolution of a set of measurables, these must be detectable in any empirical interpretation of a physical theory, including quantum gravity ones. Our test ultimately relies on considerations and studies concerning human cognitive limits in the discrimination of magnitudes.
Securing systems on the Internet of Things via physical properties of devices and communications

The Internet of Things (IoT) is an emerging trend that generates many new challenges in security and privacy through the interconnect of ubiquitous devices and services over the Internet. Depending on the device and its strict constraints in the IoT, one often needs to refrain from implementing costly public key cryptography to solve the key distribution problem. In this context, Physical Unclonable Functions (PUF) have been identified as a promising replacement that uses already present physical properties of the device. For encryption and authentication services, we combine this technology with Physical Key Generation (PKG) over wireless communication that leverages physical properties of the communications channel. Note that PKG uses same or similar components as PUFs, rendering the combination of both cheap compared to common public-key cryptography such as RSA or ECC. To the best of our knowledge, this is the first approach to combine both technologies to provide confidentiality and authenticity of devices for a lightweight key distribution mechanism. To demonstrate the validity and usefulness of our approach, we derive a generalized architecture for smart home systems and adopt our approach to this scenario.
Long‐term outcome in patients treated with combined heart and liver transplantation for familial amyloidotic cardiomyopathy

The amyloidogenic transthyretin (ATTR) mutation Leu111Met causes a primarily cardiac amyloidosis: Familial amyloidotic cardiomyopathy (FAC). Combined heart–liver transplantation (CHLTx) is the preferred treatment for patients with heart failure due to familial amyloidosis, but information on outcome of patients with Leu111Met mutation is limited. The aim of this study was to evaluate the long‐term outcome of CHLTx in patients with FAC.
Caspase‐11: arming the guards against bacterial infection

As a front line of defense against pathogenic microbes, our body employs a primitive, yet highly sophisticated and potent innate immune response pathway collectively referred to as the inflammasome. Innate immune cells, epithelial cells, and many other cell types are capable of detecting infection or tissue injury and mounting a coordinated molecular defense. For example, Gram‐negative bacteria are specifically detected via a surveillance mechanism that involves activation of extracellular receptors such as Toll‐like receptors (TLRs) followed by intracellular recognition and activation of pathways such as caspase‐11 (caspase‐4/5 in humans). Importantly, lipopolysaccharide (LPS), the major component of the outer membrane of Gram‐negative bacteria, is a strong trigger of these pathways. Extracellular LPS primarily stimulates TLR4, which can serve as a priming signal for expression of inflammasome components. Intracellular LPS can then trigger caspase‐11‐dependent inflammasome activation in the cytoplasm. Here, we briefly review the burgeoning caspase‐11‐dependent non‐canonical inflammasome field, focusing mainly on the innate sensing of LPS.
Phosphorylation of Serine 256 Suppresses Transactivation by FKHR (FOXO1) by Multiple Mechanisms

FKHR is a member of the FOXO subfamily of Forkhead transcription factors, which are important targets for insulin and growth factor signaling. FKHR contains three predicted protein kinase B phosphorylation sites (Thr-24, Ser-256, and Ser-319) that are conserved in other FOXO proteins. We have reported that phosphorylation of Ser-256 is critical for the ability of insulin and insulin-like growth factors to suppress transactivation by FKHR (Guo, S., Rena, G., Cichy, S., He, X., Cohen, P., and Unterman, T. (1999) J. Biol. Chem. 274, 17184–17192) and for its exclusion from the nucleus (Rena, G., Prescott, A. R., Guo, S., Cohen, P., and Unterman, T. G. (2001) Biochem. J.354, 605–612). Ser-256 is located in a basic region of the FKHR DNA binding domain where phosphorylation may have direct effects on DNA binding and/or nuclear targeting. Phosphorylation of Ser-256 may also be required for the phosphorylation of Thr-24 and Ser-319. Here, we provide the first direct evidence that basic residues in the FKHR DNA binding domain are critical for DNA binding and that Ser-256 phosphorylation alters binding activity. Ser-256 phosphorylation also is critical for regulating nuclear/cytoplasmic trafficking; however, this effect requires Thr-24/Ser-319 phosphorylation. Transient transfection studies with reporter gene constructs in 293 cells reveal that the phosphorylation of Ser-256 can inhibit the function of FKHR independent of Thr-24/Ser-319 phosphorylation. Studies with GFP1 fusion proteins indicate that Ser-256 phosphorylation is critical for nuclear exclusion of FKHR. However, this effect is disrupted when Thr-24 and Ser-319 are replaced by alanine, indicating that nuclear exclusion of FKHR also requires Thr-24/Ser-319 phosphorylation. Gel shift and fluorescence anisotropy studies reveal that basic residues at the C-terminal end of the FKHR DBD are important for DNA binding, and the introduction of a negative charge at the site of Ser-256 limits binding activity. Binding is rapid and reversible, providing an opportunity for the phosphorylation of Ser-256 and subsequent phosphorylation of Thr-24 and Ser-319 and nuclear exclusion of FKHR.
Effects of Antigen and Genetic Adjuvants on Immune Responses to Human Immunodeficiency Virus DNA Vaccines in Mice

ABSTRACT The effects of genetic adjuvants on humoral and cell-mediated immunity to two human immunodeficiency virus antigens, Env and Nef, have been examined in mice. Despite similar levels of gene expression and the same gene delivery vector, the immune responses to these two gene products differed following DNA immunization. Intramuscular immunization with a Nef expression vector plasmid generated a humoral response and antigen-specific gamma interferon (IFN-γ) production but little cytotoxic-T-lymphocyte (CTL) immunity. In contrast, immunization with an Env vector stimulated CTL activity but did not induce a high-titer antibody response. The ability to modify these antigen-specific immune responses was investigated by coinjection of DNA plasmids encoding cytokine and/or hematopoietic growth factors, interleukin-2 (IL-2), IL-12, IL-15, Flt3 ligand (FL), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Coadministration of these genes largely altered the immune responses quantitatively but not qualitatively. IL-12 induced the greatest increase in IFN-γ and immunoglobulin G responses to Nef, and GM-CSF induced the strongest IFN-γ and CTL responses to Env. A dual approach of expanding innate immunity by administering the FL gene, together with a cytokine that enhances adaptive immune responses, IL-2, IL-12, or IL-15, generated the most potent immune response at the lowest doses of Nef antigen. These findings suggest that intrinsic properties of the antigen determine the character of immune reactivity for this method of immunization and that specific combination of innate and adaptive immune cytokine genes can increase the magnitude of the response to DNA vaccines.
Beta-blocker use in severe sepsis and septic shock: a systematic review

Abstract Objective: Recent growing evidence suggests that beta-blocker treatment could improve cardiovascular dynamics and possibly the outcome of patients admitted to intensive care with severe sepsis or septic shock. Design: Systematic review. Data sources: MEDLINE and EMBASE healthcare databases. Review methods: To investigate this topic, we conducted a systematic review of the above databases up to 31 May 2015. Due to the clinical novelty of the subject, we also included non-randomized clinical studies. We focused on the impact of beta-blocker treatment on mortality, also investigating its effects on cardiovascular, immune and metabolic function. Evidence from experimental studies was reviewed as well. Results: From the initial search we selected 10 relevant clinical studies. Five prospective studies (two randomized) assessed the hemodynamic effects of the beta1-blocker esmolol. Heart rate decreased significantly in all, but the impact on other parameters differed. The imbalance between prospective studies’ size (10 to 144 patients) and the differences in their design disfavor a meta-analysis. One retrospective study showed improved hemodynamics combining metoprolol and milrinone in septic patients, and another retrospective study found no association between beta-blocker administration and mortality. We also found three case series. Twenty-one experimental studies evaluated the hemodynamic, immune and/or metabolic effects of selective and/or non-selective beta-blockers in animal models of sepsis (dogs, mice, pigs, rats, sheep), yielding conflicting results. Conclusions: Whilst there is not enough prospective data to conduct a meta-analysis, the available clinical data are promising. We discuss the ability of beta blockade to modulate sepsis-induced alterations at cardiovascular, metabolic, immunologic and coagulation levels.
Familial risk of cancer shortly after diagnosis of the first familial tumor.

BACKGROUND The diagnosis of the first cancer in a family may lead to the medical examination of the patient's relatives and the subsequent identification of additional familial cancers. If detection bias is present, familial risks could be overestimated soon after first diagnosis. METHODS We followed 1,677,722 offspring/siblings of 846,448 probands from the year of diagnosis of the first familial tumor to the diagnosis of first cancer, death, emigration, or December 31, 2002, using the Swedish Family Cancer Database. The risks of cancer among the offspring and siblings of patients with melanoma and cancers of the breast, prostate, colorectum, cervix, and lung were compared with those in the general population. Relative risks (RRs) were determined using Poisson regression, according to the time after first diagnosis. All statistical tests were two-sided. RESULTS Daughters of women with breast cancer had a statistically significantly higher relative risk of in situ breast cancer during the year of the mother's diagnosis than they did 5 or more years later (RR = 4.78, 95% confidence interval [CI] = 2.16 to 10.6, 26.6 cases per 100,000, versus RR = 1.97, 95% CI = 1.65 to 2.37, 27.2 cases per 100,000; P = .033). Daughters diagnosed the same year as their mothers were younger and were diagnosed earlier in the calendar year than daughters of women diagnosed 5 or more years after their mothers. Similarly, the risk of invasive melanoma among the offspring of individuals with invasive melanoma was higher during the year of the parent's diagnosis than it was 5 or more years afterward (RR = 8.27, 95% CI = 3.82 to 17.9, 57.0 cases per 100,000, versus RR = 3.18, 95% CI = 2.55 to 3.97, 37.6 cases per 100,000; P = .019). Sibling risks of in situ breast cancer, in situ cervical cancer, and invasive prostate cancer also decreased with time after diagnosis of the first familial tumor. CONCLUSIONS Increased surveillance may result in the earlier detection of asymptomatic familial cancers, i.e., in detection bias. The possibility of overestimated familial risks of cancer shortly after diagnosis of the first familial tumor should be considered before a patient's clinical and genetic counseling is implemented.
25-year Analysis of a Dental Undergraduate Research Training Program (BSc Dent) at the University of Manitoba Faculty of Dentistry

Research in the context of the dental school has traditionally been focused on institutional/faculty accomplishments and generating new knowledge to benefit the profession. Only recently have significant efforts been made to expand the overall research programming into the formal dental curriculum, to provide students with a baseline exposure to the research and critical thinking processes, encourage evidence-based decision-making, and stimulate interest in academic/research careers. Various approaches to curriculum reform and the establishment of multiple levels of student research opportunities are now part of the educational fabric of many dental schools worldwide. Many of the preliminary reports regarding the success and vitality of these programs have used outcomes measures and metrics that emphasize cultural changes within institutions, student research productivity, and student career preferences after graduation. However, there have not been any reports from long-standing programs (a minimum of 25 years of cumulative data) that describe dental school graduates who have had the benefit of research/training experiences during their dental education. The University of Manitoba Faculty of Dentistry initiated a BSc Dent program in 1980 that awarded a formal degree for significant research experiences taking place within the laboratories of the Faculty-based researchers and has continued to develop and expand this program. The success of the program has been demonstrated by the continued and increasing demands for entry, the academic achievements of the graduates, and the numbers of graduates who have completed advanced education/training programs or returned to the Faculty as instructors. Analysis of our long-term data validates many recent hypotheses and short-term observations regarding the benefits of dental student research programs. This information may be useful in the design and implementation of dental student research programs at other dental schools.
Extremely Radiation-Resistant Mutants of a Halophilic Archaeon with Increased Single-Stranded DNA-Binding Protein (RPA) Gene Expression

Abstract DeVeaux, L. C. , Müller, J. A. , Smith, J. R. , Petrisko, J., Wells, D. P. and DasSarma, S. Extremely Radiation-Resistant Mutants of a Halophilic Archaeon with Increased Single-Stranded DNA-Binding Protein (RPA) Gene Expression. Radiat. Res. 168, 507–514 (2007). Extremely halophilic archaea are highly resistant to multiple stressors, including radiation, desiccation and salinity. To study the basis of stress resistance and determine the maximum tolerance to ionizing radiation, we exposed cultures of the model halophile Halobacterium sp. NRC-1 to four cycles of irradiation with high doses of 18–20 MeV electrons. Two independently obtained mutants displayed an LD50 > 11 kGy, which is higher than the LD50 of the extremely radiation-resistant bacterium Deinococcus radiodurans. Whole-genome transcriptome analysis comparing the mutants to the parental wild-type strain revealed up-regulation of an operon containing two single-stranded DNA-binding protein (RPA) genes, VNG2160 (rfa3) and VNG2162, and a third gene of unknown function, VNG2163. The putative transcription start site for the rfa3 operon was mapped ∼40 bp upstream of the ATG start codon, and a classical TATA-box motif was found centered about 25 bp further upstream. We propose that RPA facilitates DNA repair machinery and/or protects repair intermediates to maximize the ionizing radiation resistance of this archaeon.
Controls on Methane Occurrences in Aquifers Overlying the Eagle Ford Shale Play, South Texas

Assessing natural vs. anthropogenic sources of methane in drinking water aquifers is a critical issue in areas of shale oil and gas production. The objective of this study was to determine controls on methane occurrences in aquifers in the Eagle Ford Shale play footprint. A total of 110 water wells were tested for dissolved light alkanes, isotopes of methane, and major ions, mostly in the eastern section of the play. Multiple aquifers were sampled with approximately 47 samples from the Carrizo‐Wilcox Aquifer (250‐1200 m depth range) and Queen City‐Sparta Aquifer (150‐900 m depth range) and 63 samples from other shallow aquifers but mostly from the Catahoula Formation (depth <150 m). Besides three shallow wells with unambiguously microbial methane, only deeper wells show significant dissolved methane (22 samples >1 mg/L, 10 samples >10 mg/L). No dissolved methane samples exhibit thermogenic characteristics that would link them unequivocally to oil and gas sourced from the Eagle Ford Shale. In particular, the well water samples contain very little or no ethane and propane (C1/C2+C3 molar ratio >453), unlike what would be expected in an oil province, but they also display relatively heavier δ13Cmethane (>−55‰) and δDmethane (>−180‰). Samples from the deeper Carrizo and Queen City aquifers are consistent with microbial methane sourced from syndepositional organic matter mixed with thermogenic methane input, most likely originating from deeper oil reservoirs and migrating through fault zones. Active oxidation of methane pushes δ13Cmethane and δDmethane toward heavier values, whereas the thermogenic gas component is enriched with methane owing to a long migration path resulting in a higher C1/C2+C3 ratio than in the local reservoirs.
Perinatal mortality in Lagos University Teaching Hospital: a five year review.

BACKGROUND An overwhelming proportion of the annual global perinatal deaths occur in developing countries. However few data on perinatal mortality are available from these countries. Reducing perinatal deaths requires adequate data that can be used to develop appropriate strategies. OBJECTIVES To determine the perinatal mortality rate at the Lagos University Teaching Hospital (LUTH), the associated risk factors and the causes of perinatal deaths; and make recommendations to help reduce perinatal mortality. METHODS A retrospective study of all deliveries in LUTH in the period between January 2002 and December 2006 was done. Data were collected on all stillbirths and early neonatal deaths. Analysis included such variables as booking status, maternal age, parity, gestational age, fetal weight and cause of perinatal death. RESULTS The perinatal mortality rate was 70.6/1000 total births. The rate was higher among unbooked patients and those with multiple pregnancies. It increased with parity after the 2nd delivery and was highest at the extremes of reproductive age groups. The commonest causes of death were antepartum haemorrhage, pre-eclampsia/eclampsia, mechanical causes, intrapartum asphyxia and prematurity. CONCLUSIONS The perinatal mortality rate in our institution is high. The causes of perinatal death are largely preventable. Urgent clinical and political actions are required to make any progress towards attaining the fourth millennium development goal (MDG4).