Miracle-dz/UniFAR-FTUs huggingface dataset:
Retrovirus‐mediated transfer of the herpes simplex virus thymidine kinase and connexin26 genes in pancreatic cells results in variable efficiency on the bystander killing: Implications for gene therapy

Currently, there is no effective treatment for pancreatic cancer and prodrug‐activating gene therapy with the herpes simplex virus thymidine kinase gene (HSV‐tk) in combination with ganciclovir (GCV) has been suggested as a candidate approach against this disease. In the present study, we have evaluated the efficacy of the HSV‐tk/GCV treatment in a panel of pancreatic tumor cells (NP‐9, NP‐18, NP‐31) and the potentiation of the cytotoxic effect in combination with the overexpression of the connexin 26 gene (Cx26). Pancreatic cells transduced with a retrovirus containing the HSV‐tk gene showed different sensitivities to GCV that seemed to be independent of HSV‐tk expression levels. The extent of the bystander effect also varied among the pancreatic tumor cells and correlated with the level of gap junction intercellular communication (GJIC). Transduction of the pancreatic tumor cells with a retrovirus carrying the connexin 26 gene resulted in high levels of connexin 26 expression and in an increase in the GJIC that correlated to an extent in the bystander effect in both NP‐9Cx26 and NP‐18Cx26 cells. Neither an increment in GJIC nor an increase in the bystander killing was detected in NP‐31Cx26. The bystander effect in NP‐18 Cx26 cells was also prevented by the long term inhibitor of GJIC, 18‐α‐glycyrrhetinic acid (AGA). Together, these results demonstrate that pancreatic tumor cells are highly different as regards the susceptibility to HSV‐tk/GCV treatment. Moreover, they indicate that overexpression of the Cx26 gene does not always correspond to an increase in GJIC although they clearly suggest the role of GJIC in mediating the bystander effect. © 2001 Wiley‐Liss, Inc.
Examining the Lived Experiences of Undergraduate Transgender Students at Four Year Institutions in the South

This qualitative, narrative study examined the lived experiences of transgender students at four-year institutions in the South. The college transition process and academic and social integration for transgender students was explored through the frameworks of Transition Theory (Schlossberg, 1995), Minority Stress Theory (Meyer, 1995; Breslow, Brewster, Velez, Wong, Geiger, & Soderstrom, 2015), and Academic and Social Integration theories (Tinto, 1975; Braxton, Hirschy, & McClendon, 2004). College climates can be challenging for transgender students, especially when campus staff and faculty are not prepared and/or aware of transgender students’ needs (Pryor, 2015). How students perceive their academic and social integration as well as how their integration was influenced by their gender identity was a key component of this study. Through a four-phase data collection process, transgender students had the opportunity to tell, share, and reflect on their experiences as transgender undergraduate students navigating the college transition, academic, and social integration processes. Through data collection and analysis, four categories emerged from participant responses: 1) Navigating Identity, 2) College Transition and Challenges, 3) Environment, Space, and Climate, and 4) Sympathizing with Others. Within each category, several sub-categories were identified as well. Institutions of higher education must recognize the ever-growing presence of transgender students on their campuses. Moreover, institutions have the opportunity and responsibility to create policies, spaces, and opportunities that allow transgender college students to have a supportive academic and social integration process.
Intrauterine contraception: incidence and factors associated with uterine perforation--a population-based study.

STUDY QUESTION What are the incidence and factors associated with uterine perforation by modern copper intrauterine device (Cu-IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS)? SUMMARY ANSWER Perforation incidence was similar to that reported in prior studies and did not vary between Cu-IUD and LNG-IUS groups. Lactation, amenorrhoea and a post-partum period of <6 months were common. WHAT IS KNOWN AND WHAT THIS PAPER ADDS The study supports findings in prior studies. The incidence rate was low and factors associated with uterine perforation were similar to those in earlier reports. DESIGN AND DATA COLLECTION METHOD: This retrospective population-based registry study included 68 patients surgically treated for uterine perforation by an intrauterine device (IUD)/intrauterine system (IUS) at clinics in the Helsinki and Uusimaa hospital district. PARTICIPANTS AND SETTING Records of 108 patients with probable uterine perforation by an IUD/IUS were analysed, leaving 68 patients treated for uterine perforation. RECRUITMENT/SAMPLING STRATEGY: Patients with diagnostic and surgical treatment codes indicating uterine perforation by an IUD/IUS between 1996 and 2009 were retrospectively selected from the Finnish National Hospital Register. DATA ANALYSIS METHOD Patients with Cu-IUDs (n = 17) and the LNG-IUS (n = 51) were analysed as one group and also compared using Mann-Whitney and chi-square tests. IUD/IUS sales numbers were used to calculate incidences. MAIN FINDINGS The overall incidence of perforation was 0.4/1000 sold devices, varying annually from 0 to 1.2/1000. The proportion of both sold and perforating LNG-IUSs increased during the study period, but perforation incidence was not affected. Demographic characteristics in the Cu-IUD and LNG-IUS groups were similar. More than half of the devices (55%) were inserted at <6 months post-partum. Breastfeeding at the time of insertion was common, comprising 32% of all patients. Moreover, of the breastfeeding women, 90% had delivered within 6 month prior to insertion. IMPLICATIONS The population-based study setting represents a good overview of patients experiencing uterine perforation with an IUD/IUS. As previously reported, the post-partum period, lactation and amenorrhoea may increase the risk of perforation. BIAS, LIMITATIONS AND GENERALIZABILITY As the study setting revealed only symptomatic patients or those attending regular follow-up, the true incidence might be somewhat higher. As there is no specific diagnostic code for uterine perforation or treatment, it is unlikely that all cases of uterine perforation can be identified in a retrospective study.
How Polarized are Citizens? Measuring Ideology from the Ground-Up

Strong evidence has been emerging that major democracies have become more politically polarized, at least according to measures based on the ideological positions of political elites. We ask: have the general public (‘citizens’) followed the same pattern? Our approach is based on unsupervised machine learning models as applied to issueposition survey data. This approach firstly indicates that coherent, latent ideologies are strongly apparent in the data, with a number of major, stable types that we label as: Liberal Centrist, Conservative Centrist, Left Anarchist and Right Anarchist. Using this framework, and a resulting measure of ‘citizen slant’, we are then able to decompose the shift in ideological positions across the population over time. Specifically, we find evidence of a ‘disappearing center’ in a range of countries with citizens shifting away from centrist ideologies into anti-establishment ‘anarchist’ ideologies over time. This trend is especially pronounced for the US.
Technical Note: A direct ray-tracing method to compute integral depth dose in pencil beam proton radiography with a multilayer ionization chamber.

PURPOSE To introduce a fast ray-tracing algorithm in pencil proton radiography (PR) with a multilayer ionization chamber (MLIC) for in vivo range error mapping. METHODS Pencil beam PR was obtained by delivering spots uniformly positioned in a square (45 × 45 mm2 field-of-view) of 9 × 9 spots capable of crossing the phantoms (210 MeV). The exit beam was collected by a MLIC to sample the integral depth dose (IDDMLIC). PRs of an electron-density and of a head phantom were acquired by moving the couch to obtain multiple 45 × 45 mm2 frames. To map the corresponding range errors, the two-dimensional set of IDDMLIC was compared with (i) the integral depth dose computed by the treatment planning system (TPS) by both analytic (IDDTPS) and Monte Carlo (IDDMC) algorithms in a volume of water simulating the MLIC at the CT, and (ii) the integral depth dose directly computed by a simple ray-tracing algorithm (IDDdirect) through the same CT data. The exact spatial position of the spot pattern was numerically adjusted testing different in-plane positions and selecting the one that minimized the range differences between IDDdirect and IDDMLIC. RESULTS Range error mapping was feasible by both the TPS and the ray-tracing methods, but very sensitive to even small misalignments. In homogeneous regions, the range errors computed by the direct ray-tracing algorithm matched the results obtained by both the analytic and the Monte Carlo algorithms. In both phantoms, lateral heterogeneities were better modeled by the ray-tracing and the Monte Carlo algorithms than by the analytic TPS computation. Accordingly, when the pencil beam crossed lateral heterogeneities, the range errors mapped by the direct algorithm matched better the Monte Carlo maps than those obtained by the analytic algorithm. Finally, the simplicity of the ray-tracing algorithm allowed to implement a prototype procedure for automated spatial alignment. CONCLUSIONS The ray-tracing algorithm can reliably replace the TPS method in MLIC PR for in vivo range verification and it can be a key component to develop software tools for spatial alignment and correction of CT calibration.
Nested Cytochrome B Polymerase Chain Reaction Diagnostics Detect Sporozoites of Hemosporidian Parasites in Peripheral Blood of Naturally Infected Birds

Abstract Some discrepancies between microscopy and PCR-based methods have been recently recorded in the diagnosis of Leucocytozoon spp. infection in naturally infected birds. To clarify this issue, blood samples from 109 yellow-whiskered greenbuls Andropadus latirostris were investigated using both the microscopic examination of blood films and a nested mitochondrial cytochrome b PCR. The overall prevalence of Leucocytozoon spp. infection was 4% after the standard microscopic examination and 17% using the PCR diagnostics. Samples from 9 randomly chosen birds that were microscopy negative, but PCR positive, were then examined microscopically by screening 2 entire blood films from each individual bird. Sporozoites of Leucocytozoon spp. were observed in 4 birds, and 1 gametocyte of the parasite was seen in each of 2 birds. We conclude that sensitive PCR-based diagnostics are able to detect extremely light parasitemias of circulating sporozoites and gametocytes of hemosporidian parasites. Because of the PCR detection of sporozoites of unknown fate in the peripheral circulation, conclusions regarding the distribution of hemosporidian lineages in wildlife should be made with caution. To be accepted as the lineages of successfully developing species of hemosporidians, such PCR-based information should be supported with the detection of blood stages of the parasites. The present study emphasizes the crucial need for a synthesis of information provided by the tools of traditional parasitology and molecular biology, particularly in field studies of blood parasites.
A Ubiquitously Expressed Human Hexacoordinate Hemoglobin*

We have identified a new human hemoglobin that we call histoglobin because it is expressed in a wide array of tissues. Histoglobin shares less than 30% identity with the other human hemoglobins, and the gene contains an intron in an unprecedented location. Spectroscopic and kinetic experiments with recombinant human histoglobin indicate that it is a hexacoordinate hemoglobin with significantly different ligand binding characteristics than the other human hexacoordinate hemoglobin, neuroglobin. In contrast to the very high oxygen affinities displayed by most hexacoordinate hemoglobins, the biophysical characteristics of histoglobin indicate that it could facilitate oxygen transport. The discovery of histoglobin demonstrates that humans, like plants, differentially express multiple hexacoordinate hemoglobins.
Long term effects of olfactory training in patients with post-infectious olfactory loss.

BACKGROUND There is evidence of the effectiveness of repeated exposure to odours on short-term olfactory function. The aim of this study was to assess the long-term effects of olfactory training. METHODS We conducted a prospective study of 111 patients with post-infectious olfactory dysfunction. Two groups of patients performed olfactory training for 16 and 56 weeks, respectively, and were compared with a control group. The training was performed twice daily using four odours (phenyl ethyl alcohol, eucalyptol, citronellal, eugenol). Olfactory testing was performed by means of the Sniffin Sticks test as a baseline assessment and then every 8 weeks for 56 weeks. Subjective ratings were performed using a visual analogue scale (0-100). RESULTS Both training groups presented significantly higher scores than the controls. The long-term group had better results than the short-term group. Short-term training patients sustained their improvement within the follow-up period. Subsets analysis showed that training patients mainly increased identification and discrimination. Subjective ratings were in accordance with the olfactory test results. CONCLUSION Long-term olfactory training seems to be associated with better results in patients with post-infectious olfactory loss than a short-term scheme. Short-term training provides sustainable results at 56 weeks follow-up assessment.
Reproducibility and clinical value of nocturnal hypotension: prospective evidence from the SAMPLE study

Objective To assess whether modifications in the night-time blood pressure fall caused by antihypertensive treatment predict the regression of end-organ damage of hypertension. Methods The analysis was performed in patients with essential hypertension and echocardiographically detected left ventricular hypertrophy involved in the SAMPLE study. For each patient, ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index were performed at the end of a 4-week wash-out pretreatment period, after 3 and 12 months of treatment with lisinopril or with lisinopril plus hydrochlorothiazide and after a final 4-week placebo period. For each ambulatory blood pressure monitoring the 24 h average, daytime average (0600–2400 h), night-time average (2400–0600 h) and day–night difference was computed. The percentages of dipper and non-dipper patients (i.e. the patients with night blood pressure falls greater and less than 10% of the daytime average, respectively) were also computed. Results The reproducibility of the day–night difference was low, both for comparison of the pretreatment and final placebo periods (n = 170) and for comparison of the third and the 12th month of treatment (n = 180). The reproducibility of the dipper–non-dipper dichotomy was also low, 35–40% of patients becoming non-dippers if they were dippers and vice versa, both with and without treatment. The changes in left ventricular mass index after 12 months of treatment were significantly (P < 0.01) related to the changes in 24 h, daytime and night-time blood pressure (r always > 0.33), but this was not the case for the treatment-induced modification of the day–night difference (r = −0.03 and −0.008 for systolic and diastolic blood pressures, respectively). Conclusions Our results show that day–night blood pressure changes and the classification of patients into dippers and non-dippers are poorly reproducible over time. It also provides the first prospective evidence that treatment-induced changes in day–night blood pressure difference are not related to treatment-induced regression of left ventricular mass index, thus having a limited clinical significance.
Human papillomavirus infection in urine samples from male renal transplant patients

Renal allograft recipients have a well‐documented increased incidence of human papillomavirus (HPV)‐related malignancies and preventive strategies should be specifically implemented. While in females the use of the Papanicolau test and HPV detection assay are used currently as a screening test for cervical cancer, no diagnostic procedures have been implemented to monitor HPV infection in males. The aim of this study was to test for HPV infection and to determine the spectrum of viral genotypes in urine samples of men with renal transplants. The study included 88 patients who underwent kidney transplantation between 1999 and 2005. HPV sequences were detected by nested PCR, using the broad‐spectrum consensus‐primer pairs MY09/MY11 and the new MGP system, and characterized by nucleotide sequence analysis. Overall, 43 (48.9%) samples were found positive for HPV sequences and the most common genotypes were HPV 16 (53.5%) and HPV 54 (9.3%) followed by HPV 6, 53, 56, 58, 66, 11, 12, 20, 45, 62, and 71, in descending order of prevalence. The majority of HPV 16 isolates were classified as European and only one as African‐1 variant on the basis of nucleotide signature present within the MGP L1 region. The high prevalence of HPV 16 among renal allograft recipients suggests that an HPV‐16‐based preventive or therapeutic vaccine may be effective for prevention or treatment of HPV‐related neoplasia in this group of immune compromised patients. J. Med. Virol. 82:1179–1185, 2010. © 2010 Wiley‐Liss, Inc.
Blood-tissue transport of exogenous albumin and immunoglobulin G in genetically analbuminemic rats.

Tracer uptake studies were carried out in adult female Nagase (NA) strain analbuminemic rats [derived from Sprague-Dawley (SD) stock] and in adult female SD controls to determine the extent to which capillary permeability to plasma proteins is altered in the absence of endogenous albumin. Accessory measurements (arterial pressure, central venous pressure, plasma and interstitial fluid protein concentrations and oncotic pressures, plasma volume, and interstitial fluid volume) confirm the report of Joles et al. [Am. J. Physiol. 257 (Renal Fluid Electrolyte Physiol. 26): F23-F28, 1989] that shows elevated plasma volumes, normal interstitial fluid volumes, nearly normal plasma oncotic pressures (due to elevated globulin concentrations), and lower interstitial fluid oncotic pressures. In skin, skeletal muscles, and heart muscle, clearances of exogenous heterologous (bovine) albumin were 20-40% higher in NA than in SD controls. In intestine, albumin clearances were 20-30% lower. In NA rats blood-to-tissue clearances of heterologous (bovine) immunoglobulin G in skin and heart were higher and in the intestine they were lower than in SD controls; however, clearances in skeletal muscles were not elevated. The differences between NA and SD are small compared with the large increases in macromolecular permeabilities reported by others for organs and single microvessels perfused with albumin-free fluids. (ABSTRACT TRUNCATED AT 250 WORDS)
A three-dimensional model for tissue deposition on complex surfaces

Biological processes are controlled by the biochemical composition and the physical properties of the environment. For example, geometrical features have been shown to influence cellular, multicellular and tissue behaviour. Moreover, the properties of these soft living materials affect their surface tension and thus, their shape. Two-dimensional (2D) models of geometry-driven growth suggest this interplay as responsible for the excellent control of tissue patterning throughout life. In this study, a digital 2D model of curvature-driven growth applicable to images from tissue culture experiments is extended to three dimensions. Artificial geometries were used to test the relevance and the precision of the simulations. The implementation of cell migration was also explored to better simulate the in vitro three-dimensional (3D) system. This model may be applied to computed tomography data, which could help in understanding to what degree surface curvature controls many biological processes such as morphogenesis, growth, bone healing, bone remodelling and implant integration.
Calcium and Weight: Clinical Studies

Data from six observational studies and three controlled trials in which calcium intake was the independent variable (and either bone mass or blood pressure the original outcome variable) have been reanalyzed to evaluate the effect of calcium intake on body weight and body fat. Analysis reveals a consistent effect of higher calcium intakes, expressed as lower body fat and/or body weight, and reduced weight gain at midlife. Similarly, studies relating nutrient intake to body composition report negative associations between calcium intake and body weight at midlife and between calcium and body fat accumulation during childhood. There is a fairly consistent effect size, with each 300 mg increment in regular calcium intake associated with ∼1 kg less body fat in children and 2.5–3.0 kg lower body weight in adults. Taken together these data suggest that increasing calcium intake by the equivalent of two dairy servings per day could reduce the risk of overweight substantially, perhaps by as much as 70 percent.
Consequences of lifetime isolated growth hormone (GH) deficiency and effects of short‐term GH treatment on bone in adults with a mutation in the GHRH‐receptor gene

Objective Growth hormone (GH) influences bone mass maintenance. However, the consequences of lifetime isolated GH deficiency (IGHD) on bone are not well established. We assessed the bone status and the effect of 6 months of GH replacement in GH‐naïve adults with IGHD due to a homozygous mutation of the GH‐releasing hormone (GHRH)‐receptor gene (GHRHR).
Noise exposure and hearing conservation practices in an industry with high incidence of workers' compensation claims for hearing loss.

BACKGROUND Washington State has experienced a striking increase in workers' compensation claims for hearing loss. METHODS This cross-sectional study examined noise exposures and hearing conservation practices in one industry with a high rate of hearing loss claims. We evaluated 10 representative foundries with personal noise dosimetry, management interviews, employee interviews, and existing audiometry. RESULTS Noise levels routinely exceeded 85 dBA. All companies were out of compliance with hearing conservation regulations. Most employees with important findings on audiograms were not aware of their findings. There was a significant positive correlation between management-interview scores and worksite-average employee-interview scores (r = 0.70, P = 0.02). CONCLUSIONS Companies where more effort is put into hearing conservation program activities can achieve a greater positive impact on employee awareness. However, there were broad deficiencies even in the better programs in this sample, suggesting that workers in this industry probably face a continuing substantial risk of occupational hearing loss.
The Climate Risk Premium

I formally analyze the marginal value of reducing greenhouse gas emissions under uncertainty about how much emissions warm the climate and under stochastic shocks to consumption growth and to the climate. I show that each source of uncertainty increases willingness to pay for emission reductions if and only if the elasticity of intertemporal substitution is less than unity. In particular, I show that the marginal effect of current emissions on future warming covaries negatively with future consumption, which increases the value of emission reductions. In a calibrated numerical simulation, the risk premium is a large percentage of the social cost of carbon emissions.