Miracle-dz/UniFAR-FTUs huggingface dataset:
The STAR protein, GLD‐1, is a translational regulator of sexual identity in Caenorhabditis elegans

The Caenorhabditis elegans sex determination gene, tra‐2, is translationally regulated by elements in the 3′‐untranslated region called TGEs. TGEs govern the translation of mRNAs in both invertebrates and vertebrates, indicating that this is a highly conserved mechanism for controlling gene activity. A factor called DRF, found in worm extracts binds the TGEs and may be a repressor of translation. Using the yeast three‐hybrid screen and RNA gel shift analysis, we have found that the protein GLD‐1, a germline‐specific protein and a member of the STAR family of RNA‐binding proteins, specifically binds to the TGEs. GLD‐1 is essential for oogenesis, and is also necessary for spermatogenesis and inhibition of germ cell proliferation. Several lines of evidence demonstrate that GLD‐1 is a translational repressor acting through the TGEs to repress tra‐2 translation. GLD‐1 can repress the translation of reporter RNAs via the TGEs both in vitro and in vivo, and is required to maintain low TRA‐2A protein levels in the germline. Genetic analysis indicates that GLD‐1 acts upstream of the TGE control. Finally, we show that endogenous GLD‐1 is a component of DRF. The conservation of the TGE control and the STAR family suggests that at least a subset of STAR proteins may work through the TGEs to control translation.
Decrease in proven ventriculitis by reducing the frequency of cerebrospinal fluid sampling from extraventricular drains.

OBJECT Ventriculitis associated with extraventricular drains (EVD) increases rates of morbidity and mortality as well as costs. Surveillance samples of CSF are taken routinely from EVD, but there is no consensus on the optimum frequency of sampling. The goal of this study was to assess whether the incidence of ventriculitis changed when CSF sampling frequency was reduced once every 3 days. METHODS After receiving institutional ethics committee approval for their project, the authors compared a prospective sample of EVD-treated patients (admitted 2008-2009) and a historical comparison group (admitted 2005-2007) at two tertiary hospital ICUs. A broad definition of ventriculitis included suspected ventriculitis (that is, treated with antibiotics for ventriculitis) and proven ventriculitis (positive CSF culture). Adult ICU patients with no preexisting neurological infection were enrolled in the study. After staff was provided with an education package, sampling of CSF was changed from daily to once every 3 days. All other management of the EVD remained unchanged. More frequent sampling was permitted if clinically indicated during the third daily sampling phase. RESULTS Two hundred seven patients were recruited during the daily sampling phase and 176 patients when sampling was reduced to once every 3 days. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was lower for the daily sampling group than for the every-3rd-day group (18.6 vs 20.3, respectively; p < 0.01), but there was no difference in mean age (47 and 45 years, respectively; p = 0.14), male or female sex (61% and 59%, respectively; p = 0.68), or median EVD duration in the ICU (4.9 and 5.8 days, respectively; p = 0.14). Most patients were admitted with subarachnoid hemorrhage (42% in the daily group and 33% in the every-3rd-day group) or traumatic head injuries (29% and 36%, respectively). The incidence of ventriculitis decreased from 17% to 11% overall and for proven ventriculitis from 10% to 3% once sampling frequency was reduced. Sampling of CSF once every 3 days was independently associated with ventriculitis (OR 0.44, 95% CI 0.22-0.88, p = 0.02). CONCLUSIONS Reducing the frequency of CSF sampling to once every 3 days was associated with a significant decrease in the incidence of ventriculitis. The authors suggest that CSF sampling should therefore be performed once every 3 days in the absence of clinical indicators of ventriculitis. Reducing frequency of CSF sampling from EVDs decreased proven ventriculitis.
Measuring cough severity: development and pilot testing of a new seven-item cough severity patient-reported outcome measure

Objective: Although chronic and subacute cough are clinically problematic and a target of therapeutic interventions, there are no validated cough severity patient-reported outcome (PRO) instruments for comprehensively evaluating cough severity in clinical trials. The Cough Severity Diary (CSD) is a simple, seven-item daily diary developed to meet this need. The objective of this study was to assess preliminary measurement characteristics in a small sample of patients with chronic or subacute cough. Methods: Thirty-nine patients (24 chronic; 15 subacute) participated in a two-week prospective pilot study. Patients completed the CSD each evening and validation instruments (cough severity visual analog scale [VAS], Leicester Cough Questionnaire [LCQ], Medical Outcomes Study 36-Item Short Form [SF-36], Work Productivity Index [WPAI], MOS Sleep Scale [MOS-SS]) at baseline, days 8 and 15, and a global rating of change at days 8 and 15. Results: Confirmatory factor analyses supported three severity subscales: frequency (three items), intensity (two items), and disruption (two items) (χ2 = 10.57 (11)). For the CSD total score, internal consistency (α) on day 1 was 0.89, and on day 8 was 0.96; reproducibility (intraclass correlation coefficients [ICC]) was 0.68 on day 1 to day 8 and 0.94 on day 8 to day 15. CSD total scores correlated with the VAS (r = 0.84, p < 0.0001), LCQ total (r =-0.62, p < 0.0001) and subscale scores (r =-0.43, p < 0.01 to -0.60, p < 0.0001), and WPAI subscale scores (r = 0.27 (ns) to 0.51, p < 0.01). No significant relationships with SF-36 or MOS-SS were found. Subacute patients showed significant improvement over time (F = 3.20, p < 0.05). Conclusions: Results suggest that the CSD is ready for further testing in larger naturalistic studies or as an exploratory endpoint in clinical trials of patients with subacute or chronic cough.
Gametic selection, developmental trajectories, and extrinsic heterogeneity in Haldane's rule

Deciphering the genetic and developmental causes of the disproportionate rarity, inviability, and sterility of hybrid males, Haldane's rule, is important for understanding the evolution of reproductive isolation between species. Moreover, extrinsic and prezygotic factors can contribute to the magnitude of intrinsic isolation experienced between species with partial reproductive compatibility. Here, we use the nematodes Caenorhabditis briggsae and C. nigoni to quantify the sensitivity of hybrid male viability to extrinsic temperature and developmental timing, and test for a role of mito‐nuclear incompatibility as a genetic cause. We demonstrate that hybrid male inviability manifests almost entirely as embryonic, not larval, arrest and is maximal at the lowest rearing temperatures, indicating an intrinsic‐by‐extrinsic interaction to hybrid inviability. Crosses using mitochondrial substitution strains that have reciprocally introgressed mitochondrial and nuclear genomes show that mito‐nuclear incompatibility is not a dominant contributor to postzygotic isolation and does not drive Haldane's rule in this system. Crosses also reveal that competitive superiority of X‐bearing sperm provides a novel means by which postmating prezygotic factors exacerbate the rarity of hybrid males. These findings highlight the important roles of gametic, developmental, and extrinsic factors in modulating the manifestation of Haldane's rule.
Emporiatric enteritis: lessons learned from U.S. students in Mexico.

In the studies reported, evidence has been presented that U.S. students traveling to Mexico represent a model for the study of travelers' diarrhea. The incidence of illness acquisition approximates that published in other studies of travelers. Natural immunity was shown to develop as students remained in Mexico presumably through repeated exposure to prevalent agents, particularly ETEC. ETEC, shigella strains and no detectable agent represented the largest groups when etiologic assessment was made. Food probably served as the important source of diarrhea particularly that due to ETEC and shigella strains. The level of bacteria isolated from food suggested that organism replication occurred due to improper temperature storage rather than to heavy initial contamination. The location of food consumption was related to degree of risk: self preparation was the safest, eating in Mexican homes the least safe and consumption of food in public restaurants was intermediate in risk. Water probably played a role in the transmission of viral infection. The risk of water contamination appeared to be highest during the rainy seasons. Finally, the antimicrobial agents TMP/SMX and TMP alone were shown to effectively prevent and treat this form of travelers' diarrhea.
MET and ERBB2 Are Coexpressed in ERBB2+ Breast Cancer and Contribute to Innate Resistance

Breast cancer displays significant intratumoral heterogeneity, which has been shown to have a substantial impact on both innate and acquired resistance to tyrosine kinase inhibitors. The heterogeneous expression of multiple receptor tyrosine kinases (RTK) in cancers supports tumor signaling robustness and plays a significant role in resistance to targeted inhibition. Recent studies have revealed interactions between the MET receptor and the ERBB receptor family in the therapeutic resistance of several cancers. In this study, the relationship between MET expression/activity and the expression/activity of the ERBB receptor family in human breast cancer was interrogated. Importantly, a significant percentage of ERBB2+ tumors coexpressing MET and ERBB2 were observed and displayed significant heterogeneity with subpopulations of cells that are MET−/ERBB2+, MET+/ERBB2−, and MET+/ERBB2+. In a MET+/ERBB2+ breast cancer cell line, MET depletion resulted in increased ERBB2 activation, and conversely, ERBB2 depletion resulted in increased MET activation. Neither EGFR nor ERBB3 compensated for MET or ERBB2 knockdown. The loss of either MET or ERBB2 led to a decrease in PI3K/AKT signaling and increased dependency on MAPK. These data show that a subset of ERBB2+ breast cancers express MET and contain MET+/ERBB2+ subpopulations. Moreover, analysis of RTK activation during ERBB2 knockdown indicated that MET signaling is a compensatory pathway of resistance. Implications: ERBB2+ breast cancers with MET+/ERBB2+ subpopulations may have an innate resistance to ERBB2 inhibition and may benefit from combined MET and ERBB2 inhibition. Mol Cancer Res; 11(9); 1112–21. ©2013 AACR.
[Family history of glaucoma and risk factors in pigmentary glaucoma. A new clinical study].

BACKGROUND Whether a family history of glaucoma (FHG) in patients with pigmentary glaucoma (PG) is a prognostical indicator, is unknown. Therefore the aim of this study was to evaluate the influence of FHG on the severity of the disease in PG and pigment dispersion syndrome (PDS). Furthermore risk factors in PG and PDS were evaluated. METHODS The findings of 207 patients with PG and PDS, who were able to give information about FHG, were evaluated (149 PG, 43 PDS with ocular hypertension (OH), 15 PDS without OH). RESULTS Significance of FHG: FHG was found in 39.1%, and in one third of the patients more than one relative had the disease. FHG was found in PG not more frequent than in PDS. Pigmentary glaucomas in advanced stages of the disease did not have a higher incidence of FHG than patients in beginning stages. Out of 207 patients with PG and PDS 71% were male and 29% female (p < 0.001). In patients with FHG the share of men was 64.2% and not significantly different to the group without FHG with 75.4%. The sex distribution in parents and grandparents having a glaucomatous disease was 1:1. RISK FACTORS The pf1p4nts with and without FHG in PDS with and without OH, PG, and within the different stages of visual field loss, showed no significant differences in risk factors, for example in maximum intraocular pressure, refraction and cup-disc ratio. Myopia: Patients with PG had a significantly higher myopia than patients with PDS (p < 0.01). The higher the myopia, the earlier the disease was diagnosed (p = 0.008). Krukenberg spindle: During miotic therapy the Krukenberg spindle decreased in the upper half of the cornea. Time of diagnosis: PG was diagnosed at a higher age compared to PDS. CONCLUSION FHG does not influence the severity of the disease in PG. Family history of glaucoma is a risk factor in patients with PG, but no prognostical indicator. Patients with FHG do not have primarily larger cup-disc ratios than patients without FHG. Myopia is a risk factor.
Investigation of Aquo and Chloro Complexes of UO(2)(2+), NpO(2)(+), Np(4+), and Pu(3+) by X-ray Absorption Fine Structure Spectroscopy.

U, Np, and Pu L(II,III)-edge X-ray absorption fine structure (XAFS) spectra were collected for the UO(2)(2+), NpO(2)(+), Np(4+), and Pu(3+) ions as a function of chloride concentration in aqueous solution. At low chloride concentration, the hydration numbers and corresponding bond lengths for the different ions are as follows: UO(2)(2+), N= 5.3, R = 2.41 Å; NpO(2)(+), N = 5.0, R = 2.50 Å; Np(4+), N = 11.2, R = 2.40 Å; Pu(3+), N = 10.2, R = 2.51 Å. As the Cl(-) concentration increases, inner-sphere Cl(-) complexation occurs, resulting in a decrease in the hydration numbers and an expansion of the actinide-oxygen (water) bond lengths. The Pu(3+) ion shows only a decrease in hydration number (40%) and no inner-sphere Cl(-) complexation for [Cl(-)] < 14 M. For concentrations up to 10-14 M Cl(-), the average Cl(-) coordination numbers and bond lengths are as follows: UO(2)(2+), N = 2.6, R = 2.73 Å; NpO(2)(+), N = 1.0, R = 2.84 Å; Np(4+), N = 2.0, R = 2.61 Å. Structural changes are observed in the near-edge spectral region as shown by significant changes in the white line intensities upon Cl(-) complexation. For ions with similar structures, i.e. Pu(3+) and Np(4+) or the actinyl ions NpO(2)(+) and UO(2)(2+), positive energy shifts are observed with increasing oxidation state. The ability to use XAFS speciation results to calculate equilibrium constants and the relationship of these results to previous studies are discussed.
Absorbent products for incontinence: 'treatment effects' and impact on quality of life.

AIM This study aimed to determine how the use and characteristics of absorbent products for incontinence impact on women's quality of life, and to examine the concept of 'treatment effects' in the context of pad use. METHOD Key pad performance characteristics were identified from the literature and focus group work. Semi-structured interviews with 99 women with light incontinence were used to investigate the impact of pad use on women's quality of life, including both positive and negative 'treatment effects', and to rank pad characteristics by their importance. RESULTS Achieving effective and discrete containment of urine was the dominant factor impacting on women's lives. Sub-themes embraced physical effects, psychological impact and social functioning. The five pad characteristics ranked most important for day time use were: 'to hold urine, to contain smell, to stay in place, discreteness, and comfort when wet. For night use discreteness was replaced by to keep skin dry'. High levels of reported anxiety were associated with perceived risk of poor pad performance, lack of discreteness and need for complex regimes for pad management. CONCLUSION Insufficient attention has been paid to the balance between the beneficial and negative treatment effects of absorbent pads to date. Existing continence-related quality of life measures are not designed for conditions where change in symptoms is not an outcome measure. The study findings provide the basis for developing a more sensitive, patient-oriented, quality of life measure for pad-users which can aid product selection, new product development and inform future evaluative comparisons between products/products and treatments. RELEVANCE TO CLINICAL PRACTICE This paper illustrates the complex influence on quality of life caused by using absorbent pads to contain incontinence. It raises awareness of the importance of careful selection of the most appropriate pad for each individual to minimize unfavourable side effects, and the need for a new quality of life measure designed for pad-users.
Modeling survival data with informative cluster size

Analysis of clustered data focusing on inference of the marginal distribution may be problematic when the risk of the outcome is related to the cluster size, termed as informative cluster size. In the absence of censoring, Hoffman et al. proposed a within‐cluster resampling method, which is asymptotically equivalent to a weighted generalized estimating equations score equation. We investigate the estimation of the marginal distribution for multivariate survival data with informative cluster size using cluster‐weighted Weibull and Cox proportional hazards models. The cluster‐weighted Cox model can be implemented using standard software. Simulation results demonstrate that the proposed methods produce unbiased parameter estimation in the presence of informative cluster size. To illustrate the proposed approach, we analyze survival data from a lymphatic filariasis study in Recife, Brazil. Copyright © 2007 John Wiley & Sons, Ltd.
Antigenic Differences Between Mycobacterium bovis Strain BCG and an Isoniazid-Resistant Mutant

The antigenicities of Mycobacterium bovis strain BCG and an isoniazid (INH) - resistant mutant were compared. Sonic extracts of heat-killed, washed bacteria were injected into rabbits, and antisera were produced (anti-BCG and anti-BCG-R). The sonic extracts were also subjected to ultracentrifugation, and test antigens were prepared from the resulting supernatants (BCG and BCG-R). The antigens were labeled with 131I, and the antisera were tested for their capacity to bind 131I-BCG and 131I-BCG-R by precipitating 131I-antigen-antibody complexes with anti-rabbit gamma globulin. Significant differences were detected between the two test antigens. Immunodiffusion studies with unabsorbed antisera and antisera absorbed with BCG and BCG-R suggested that an antigenic component in BCG is lacking or diminished in BCG-R and that anti-BCG has antibodies not found in anti-BCG-R. These quantitative and qualitative differences were confirmed by inhibition studies. Complete inhibition was achieved in all systems by both test antigens when either was added in sufficient concentration. As expected, BCG-R inhibited the binding of 131I-BCG-R by anti-BCG-R or anti-BCG (or both) to a greater extent than BCG, and BCG was a better inhibitor in an 131I-BCG-anti-BCG-R system. However, in an 131I-BCG-anti-BCG test system, BCG was the better inhibitor only at high concentrations. It was concluded that the test antigens possess different proportions of identical or cross-reacting components and that INH-sensitive organisms possess a component(s) that is diminished or absent in the INH-resistant mutant. Whether this component(s) is responsible for INH-resistance is not known.
Inflammatory bowel disease in the elderly is associated with worse outcomes: A national study of hospitalizations

Background: Inflammatory bowel disease (IBD) has a bimodal peak of incidence with ≈15% of the cases manifesting after 65 years. Previous reports on the outcomes of IBD in the elderly have been single‐center studies or have predated the use of biologics. The aim of our study was to compare outcomes of IBD‐related hospitalizations in a nationwide representative cohort of patients 65 years and older with younger patients. Methods: This was a cross‐sectional study utilizing data from the Nationwide Inpatient Sample (NIS) for the year 2004. We identified all IBD‐related hospitalizations through the presence of the appropriate ICD‐9‐CM codes for Crohn's disease, ulcerative colitis, or associated complications. We compared the differences in disease presentation as well the frequency of utilization of different interventions. We calculated the adjusted odds of mortality in older compared to the younger IBD patients using multivariate logistic regression. Results: Patients older than 65 years accounted for ≈25% of all IBD‐related hospitalizations in 2004. They were less likely to be hospitalized with fistulizing (4.0 versus 8.8%, P < 0.001) or stricturing disease (4.0 versus 5.8%, P = 0.001). Even after adjusting for comorbidity, they had higher in‐hospital mortality (odds ratio [OR] 3.91, 95% confidence interval [CI] 2.50–6.11). Older patients with fistulizing disease are more likely to undergo surgery (OR 1.55, 95% CI 1.00–2.40). Among IBD patients who underwent surgery, older patients also had a longer postoperative stay (1.73 days, 95% CI 1.04–2.21). Conclusions: Older patients with IBD‐related hospitalizations have substantial morbidity and higher mortality than younger patients. Further research is needed to better characterize the natural history and treatment outcomes in this cohort.
Is donating a kidney to a friend bad for your marriage?

Studies have shown that kidney donation to a spouse has a positive impact on marriage. This study was done to evaluate the impact on marriage when donation occurs to someone other than the spouse. Two groups of donors from our centre who donated around the same period were studied: donation to a spouse (spouse donor (SD)) or to someone other than the spouse (non‐spouse donor (ND)). A survey, the Revised Dyadic Adjustment Scale, was used to evaluate the effect of donation on the marriage. This tool consists of 14 questions that measure how satisfying and stable the relationship is. The results showed equal or better marriage scores in the ND group compared with the SD group. The NDs scored higher on two questions, one regarding agreement or disagreement on career choices (P = 0.05) and the other regarding the frequency of having stimulating exchanges of ideas with one's spouse (P = 0.02). With the highest possible total score of 69, NDs scored 53.4 and SDs scored 47.7 (P = 0.16). Scores of 47 and below indicate marital distress. In one final additional question, 97% of NDs reported ‘no change or good effect’ on the marriage, similar to 91% for SDs (P = 0.46). This is the first study to evaluate the effect of kidney donation on the state of marriage when the spouse is not the recipient. It appears that marriage is not impacted negatively when kidney donation occurs to someone other than the spouse.
Exogenous expression of claudin‐5 induces barrier properties in cultured rat brain capillary endothelial cells

Claudins are thought to be major components of tight junctions (TJs), and claudin‐5 and ‐12 are localized at TJs of the blood‐brain barrier (BBB). Claudin‐5‐deficient mice exhibit size‐selective (<800 Da) opening of the BBB. The purpose of this study was to clarify the expression levels of claudin‐5 and ‐12 in rat brain capillary endothelial cells, and to examine the ability of claudin‐5 to form TJs in cultured rat brain capillary endothelial cells (TR‐BBB). Expression of claudin‐5 mRNA in rat brain capillary fraction was 751‐fold greater than that of claudin‐12. The level of claudin‐5 mRNA in the rat brain capillary fraction (per total mRNA) was 35.6‐fold greater than that in whole brain, while the level of claudin‐12 mRNA was only 13.9% of that in whole brain, suggesting that expression of claudin‐12 mRNA is not restricted to brain capillaries. Transfection of TR‐BBB cells with the claudin‐5 gene afforded TR‐BBB/CLD5 cells, which showed no change in expression of claudin‐12 or ZO‐1, while the expressed claudin‐5 was detected at the cell–cell boundaries. The permeability surface product of [14C]inulin at a TR‐BBB/CLD5 cell monolayer was significantly smaller (P < 0.01) than that for the parental TR‐BBB cells, and the values of the permeability coefficient (Pe) were 1.14 × 10−3 and 11.6 × 10−3 cm/min, respectively. These results indicate that claudin‐5, but not claudin‐12, is predominantly expressed in brain capillaries, and plays a key role in the appearance of barrier properties of brain capillary endothelial cells. J. Cell. Physiol. 210: 81–86, 2007. © 2006 Wiley‐Liss, Inc.