Miracle-dz/UniFAR-FTUs huggingface dataset:
Localization of TGF-β type II receptor and ED-A fibronectin in normal conjunctiva and failed filtering blebs

Purpose The cytokine transforming growth factor-β (TGF-β), and the ED-A splice variant of the extracellular matrix protein fibronectin modulate wound healing and scar formation. To further elucidate their possible role in filtering bleb scarring after glaucoma surgery in human eyes in vivo, we studied the cell type specific localization of TGF-β receptors and the presence of ED-A fibronectin in sections of normal conjunctiva and scarred filtering blebs. Methods Cryosections of normal conjunctiva (four patients) and scarred filtering blebs (seven patients) were studied by double-label immunofluorescence. Antibodies against PECAM-1 and prolyl-4-hydroxylase allowed for specification of vascular endothelial cells and activated fibroblasts, respectively. TGF-β receptor type II (TGF-β-RII), α-smooth muscle actin, O-linked sialoglycoprotein, fibronectin and the ED-A fibronectin splice-variant were also detected using specific antibodies. Labeled sections were viewed with a confocal laser scanning microscope. Results Vascular endothelial cells expressed TGF-β-RII in both normal and scarred tissue. TGF-β-RII was sparsely detected in the fibroblasts of normal conjunctiva while it was strongly expressed in most fibroblasts of the scarred filtering blebs. Similarly, ED-A fibronectin was not detected in the extracellular matrix of normal conjunctiva but abundantly present in scarred filtering blebs. Conclusions Filtering bleb scarring is associated with an abundant expression of TGF-β receptors in activated fibroblasts and the deposition of the fibrogenic ED-A fibronectin splice-variant. These data support the concept of targeting TGF-β signaling to prevent scar formation after filtering glaucoma surgery.
A Speech-Enabled Fixed-Phrase Translator for Emergency Settings: Crossover Study

Background In the context of the current refugee crisis, emergency services often have to deal with patients who have no language in common with the staff. As interpreters are not always available, especially in emergency settings, medical personnel rely on alternative solutions such as machine translation, which raises reliability and data confidentiality issues, or medical fixed-phrase translators, which sometimes lack usability. A collaboration between Geneva University Hospitals and Geneva University led to the development of BabelDr, a new type of speech-enabled fixed-phrase translator. Similar to other fixed-phrase translators (such as Medibabble or UniversalDoctor), it relies on a predefined list of pretranslated sentences, but instead of searching for sentences in this list, doctors can freely ask questions. Objective This study aimed to assess if a translation tool, such as BabelDr, can be used by doctors to perform diagnostic interviews under emergency conditions and to reach a correct diagnosis. In addition, we aimed to observe how doctors interact with the system using text and speech and to investigate if speech is a useful modality in this context. Methods We conducted a crossover study in December 2017 at Geneva University Hospitals with 12 French-speaking doctors (6 doctors working at the outpatient emergency service and 6 general practitioners who also regularly work in this service). They were asked to use the BabelDr tool to diagnose two standardized Arabic-speaking patients (one male and one female). The patients received a priori list of symptoms for the condition they presented with and were instructed to provide a negative or noncommittal answer for all other symptoms during the diagnostic interview. The male patient was standardized for nephritic colic and the female, for cystitis. Doctors used BabelDr as the only means of communication with the patient and were asked to make their diagnosis at the end of the dialogue. The doctors also completed a satisfaction questionnaire. Results All doctors were able to reach the correct diagnosis based on the information collected using BabelDr. They all agreed that the system helped them reach a conclusion, even if one-half felt constrained by the tool and some considered that they could not ask enough questions to reach a diagnosis. Overall, participants used more speech than text, thus confirming that speech is an important functionality in this type of tool. There was a negative association (P=.02) between the percentage of successful speech interactions (spoken sentences sent for translation) and the number of translated text items, showing that the doctors used more text when they had no success with speech. Conclusions In emergency settings, when no interpreter is available, speech-enabled fixed-phrase translators can be a good alternative to reliably collect information from the patient.
Segregation and rearrangement of coamplified genes in different lineages of mutant cells that overproduce adenylate deaminase

Four genes encoding proteins designated as W, X, Y1, and Y2 were found previously to be amplified at different levels in a Chinese hamster fibroblast mutant line selected for overproduction of adenylate deaminase. To gain information on the molecular mechanisms responsible, we studied the levels of amplification and the structures of these four genes in several lineages of mutant cells with comparable activities of adenylate deaminase, the selected enzyme. Only the W gene was amplified in all the lines. In one line, the X, Y1, and Y2 genes were coamplified, while in others either the Y1 gene or the pair X and Y2 were coamplified. The results were consistent with linkage of all the genes--in a particular order--in an amplifiable sequence with variable endpoints. Novel joints with a nonrandom distribution were observed. We frequently detected rearranged copies of the W gene, but very few novel joints were present in the other three genes in the six highly amplified lines examined. Some of the novel joints in gene W were highly amplified; they were generated by reamplification of a rearrangement that appeared at an early selection step. In some lines, reamplification was accompanied by deletion or mass correction of preexisting units. We discuss mechanisms which might account for these observations.
Women’s experiences of ceasing to breastfeed: Australian qualitative study

Objective To investigate mothers’ infant feeding experiences (breastfeeding/formula milk feeding) with the aim of understanding how women experience cessation of exclusive breastfeeding. Design Multimethod, qualitative study; questionnaire, focus groups and interviews. Setting Northern and Southern Tasmania, Australia. Participants 127 mothers of childbearing age from a broad sociodemographic context completed a questionnaire and participated in 22 focus groups or 19 interviews across Tasmania, 2011–2013. Results Mothers view breastfeeding as ‘natural’ and ‘best’ and formula milk as ‘wrong’ and ‘unnatural’. In an effort to avoid formula and prolong exclusive breastfeeding, mothers will endure multiple issues (eg, pain, low milk supply, mastitis, public shaming) and make use of various forms of social and physical capital; resources such as father/partner support, expressing breast milk, bottles and dummies. The cessation of exclusive breastfeeding was frequently experienced as unexpected and ‘devastating’, leaving mothers with ‘breastfeeding grief’ (a prolonged sense of loss and failure). Conclusions and implications For many mothers, the cessation of exclusive breastfeeding results in lingering feelings of grief and failure making it harmful to women’s emotional well-being. Reframing breastfeeding as a family practice where fathers/partners are incorporated as breastfeeding partners has the potential to help women negotiate and prolong breastfeeding. Proactive counselling and debriefing are needed to assist women who are managing feelings of ‘breastfeeding grief’.
The Antiestrogen Tamoxifen Activates BK Channels and Stimulates Proliferation of MCF-7 Breast Cancer Cells

In the present study, we investigated the effect of the antiestrogen compound tamoxifen on BK channels by the use of the patch-clamp technique. The perfusion of 10 nM tamoxifen significantly increased the magnitude of a voltage-dependent K+ current by 22.6 ± 10.6% (n = 23). The effect of tamoxifen was always obtained in the first minute, peaked at 5.9 ± 2.2 min (n = 23), and was abolished by the perfusion of tetraethylammonium (0.5 mM), charybdotoxin (50 nM), or iberiotoxin (100 nM). The stimulatory effect of 10 nM tamoxifen was the same at low (50 nM) and high (700 nM) internal calcium concentration and was not additive to that of 17-β-estradiol (E2) or its membrane-impermeant form, β-estradiol 6-(O-carboxymethyl)oxime:bovine serum albumin. Furthermore, the effect of tamoxifen was still recorded in the presence of the selective estrogen receptor antagonist faslodex (ICI-182,780; 1 μM). At the single-channel level, tamoxifen significantly increased the open probability of the BK channel by 46.2 ± 10.1% (n = 4) without changing its unitary conductance. Moreover, we show here that the stimulation of BK channel activity by tamoxifen is involved in MCF-7 cell proliferation. Taken together, these results permitted us to identify the BK channel as the molecular target of tamoxifen that probably acts at the same extracellular molecular level as E2. The site of action of tamoxifen is probably the channel itself or the auxiliary β subunits.
Attenuation of Exercise Conditioning by Beta‐adrenergic Blockade

High levels of, β-adrenergic stimulation accompany strenuous exercise, but the possibility that β-adrenergic blockade might prevent exercise conditioning has not been adequately investigated. We studied normal, sedentary men, ages 21–35 years, before and after 5 weeks of intensive aerobic conditioning. On a double-blind protocol, eight received placebo and nine propranolol throughout the conditioning period. A high level of, β-adrenergic blockade was documented in all subjects receiving propranolol; individual mean plasma propranolol concentrations were 100–292 ng/ml. Both groups trained at comparable intensities. Graded maximal treadmill tests were performed before starting drugs or training, and were repeated 3–5 days after completing the conditioning period, when, β-adrenergic blockade was no longer present. In subjects who received placebo, training increased exercise duration (16.4 ± 1.3 to 21.2 ± 1.5 minutes [± SEMI, p < 0.01) and maximal oxygen uptake (43.6 ± 2.9 to 52.7 ± 3.2 ml/kg/min, p < 0.05). Subjects who received propranolol had only modest improvement in exercise duration (16.0 ± 0.6 to 17.3 i 0.9 minutes, p < 0.05), and no significant change in maximal oxygen uptake (40.4 ± 1.4 to 40.9 i 0.9 ml/kg/min). With training, diastolic pressure at maximal exercise decreased in subjects who received placebo (63 ± 3 to 48 ± 3 mm Hg, p < 0.05) but was unchanged in subjects who received propranolol. Training did not alter maximal heart rate in either group. Thus, high levels of f3-adrenergic blockade markedly attenuated aerobic conditioning in these normal subjects. We conclude that, β-adrenergic stimulation is essential in exercise conditioning.
Genetic diversity of Mycobacterium tuberculosis strains circulating in Botswana

Background Molecular typing of Mycobacterium tuberculosis (M.tb) isolates can inform Tuberculosis (TB) control programs on the relative proportion of transmission driving the TB epidemic. There is limited data on the M. tb genotypes that are circulating in Botswana. The aim of this study was to generate baseline data on the genetic diversity of M.tb isolates circulating in the country. Methods A total of 461 M.tb isolates received at the Botswana National Tuberculosis Reference Laboratory between March 2012 and October 2013 were included in this study. Drug susceptibility testing was conducted using the BD BACTEC MGIT 960 System. M.tb strains were genotyped using spoligotyping and spoligotype patterns were compared with existing patterns in the SITVIT Web database. A subset of drug resistant isolates which formed spoligo clusters (n = 65) was additionally genotyped with 12-loci MIRU. Factors associated with drug resistance and clustering were evaluated using logistic regression. Results Of the 461 isolates genotyped, 458 showed 108 distinct spoligotype patterns. The predominant M.tb lineages were Lineage 4 (81.9%), Lineage 2 (9%) and Lineage 1 (7.2%). The predominant spoligotype families within Lineage 4 were LAM (33%), S (14%), T (16%), X (16%). Three hundred and ninety-two (86%) isolates could be grouped into 44 clusters (2–46 isolates per cluster); giving a clustering rate of 76%. We identified 173 (37.8%) drug resistant isolates, 48 (10.5%) of these were multi-drug resistant. MIRU typing of the drug resistant isolates allowed grouping of 46 isolates into 14 clusters, giving a clustering rate of 49.2%. There was no association between age, sex, treatment category, region and clustering. Conclusions This study highlights the complexity of the TB epidemic in Botswana with multiple strains contributing to disease and provides baseline data on the population structure of M.tb strains in Botswana.
Heme catabolism in the causative agent of anthrax

A challenge common to all bacterial pathogens is to acquire nutrients from hostile host environments. Iron is an important cofactor required for essential cellular processes such as DNA repair, energy production and redox balance. Within a mammalian host, most iron is sequestered within heme, which in turn is predominantly bound by hemoglobin. While little is understood about the mechanisms by which bacterial hemophores attain heme from host‐hemoglobin, even less is known about intracellular heme processing. Bacillus anthracis, the causative agent of anthrax, displays a remarkable ability to grow in mammalian hosts. Hypothesizing this pathogen harbors robust ways to catabolize heme, we characterize two new intracellular heme‐binding proteins that are distinct from the previously described IsdG heme monooxygenase. The first of these, HmoA, binds and degrades heme, is necessary for heme detoxification and facilitates growth on heme iron sources. The second protein, HmoB, binds and degrades heme too, but is not necessary for heme utilization or virulence. The loss of both HmoA and IsdG renders B. anthracis incapable of causing anthrax disease. The additional loss of HmoB in this background increases clearance of bacilli in lungs, which is consistent with this protein being important for survival in alveolar macrophages.
NID2 and HOXA9 Promoter Hypermethylation as Biomarkers for Prevention and Early Detection in Oral Cavity Squamous Cell Carcinoma Tissues and Saliva

Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance, we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and quantitative methylation specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage design consisting of discovery and prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (κ = 0.64), HOXA9 (κ = 0.60), NID2 (κ = 0.60), and EDNRB (κ = 0.60) had a moderate to substantial agreement with clinical diagnosis in the discovery screen. HOXA9 had 68% sensitivity, 100% specificity, and a 0.81 Area Under the Curve (AUC). NID2 had 71% sensitivity, 100% specificity, and a 0.79 AUC. In the prevalence screen, HOXA9 (κ = 0.82) and NID2 (κ = 0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity, and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity, and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity, and a 0.97 AUC. In saliva, from OSCC cases and controls, HOXA9 had 75% sensitivity, 53% specificity, and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity, and a 0.73 AUC. This phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies. Cancer Prev Res; 4(7); 1061–72. ©2011 AACR.
Perceptions of Australian and Malaysian Educators in an Undergraduate Pharmacy Program on Case-based Learning

Objective. To determine the perceptions of lecturers toward case-based learning (CBL) and to elicit their feedback and opinions regarding the design of CBL sessions within the pharmacy curricula. Methods. One-on-one interviews were conducted with 10 academic staff members involved in teaching an undergraduate Bachelor of Pharmacy (BPharm) program. All sessions were audio-recorded and field notes were compiled. The recordings were transcribed, and thematic analysis of responses was performed. Results. Four key themes were identified: perceived benefits of CBL, challenges in implementing CBL within the curricula, characteristics of effective and engaging CBL, and relevance and implementation of CBL within the curriculum. Some of the specific benefits of CBL identified by participants included the applicability of knowledge learned to students’ future role as pharmacists. Participants also identified challenges such as the design of CBL cases and course time constraints. Respondents also emphasized the need for more training for facilitators in how to design cases and facilitate sessions. Conclusion. While participants identified numerous benefits of CBL, they also identified challenges to implementing this learning method within the pharmacy school curriculum. Paying careful attention to selecting facilitators and providing appropriate facilitator training, in terms of facilitation and case design, is paramount in effectively implementing CBL sessions.
Parenting differentially influences the development of boys' and girls' inhibitory control

Effortful control (EC) has important implications for children's development. While both child sex and parenting are related to child EC, and while a literature shows early sex differences in children's responses to care, interactions between care and child sex in predicting EC are not well understood. We therefore examined associations between child sex and early caregiving as predictors of children's development of a specific aspect of EC, inhibitory control (IC). A community sample of 406 three-year-old children and their caregivers completed behavioural tasks and observational measures of parenting and IC, and children were re-assessed for IC at age 5. Results showed that early care influenced change in IC over time, although caregiving was a more important influence on boys' IC than girls; specifically, differences in boys' and girls' IC at age 5 were modest when parenting was positive. The implications of a better understanding of sex differences in associations between parenting and the development of IC in early childhood are discussed. Statement of contribution What is already known on this subject? While sex differences in reactivity to early care in the development of externalizing symptoms have been explored, very little is known about such differences in children's early-emerging effortful control. What does this study add? Using a longitudinal design and independent, laboratory methods of assessing study constructs, we provide new information showing that early care appears to differentially influence boys' development of inhibitory control, a key aspect of effortful control, in early childhood.
Meta‐analysis reveals enhanced growth of marine harmful algae from temperate regions with warming and elevated CO2 levels

Elevated pCO2 and warming may promote algal growth and toxin production, and thereby possibly support the proliferation and toxicity of harmful algal blooms (HABs). Here, we tested whether empirical data support this hypothesis using a meta‐analytic approach and investigated the responses of growth rate and toxin content or toxicity of numerous marine and estuarine HAB species to elevated pCO2 and warming. Most of the available data on HAB responses towards the two tested climate change variables concern dinoflagellates, as many members of this phytoplankton group are known to cause HAB outbreaks. Toxin content and toxicity did not reveal a consistent response towards both tested climate change variables, while growth rate increased consistently with elevated pCO2. Warming also led to higher growth rates, but only for species isolated at higher latitudes. The observed gradient in temperature growth responses shows the potential for enhanced development of HABs at higher latitudes. Increases in growth rates with more CO2 may present an additional competitive advantage for HAB species, particularly as CO2 was not shown to enhance growth rate of other non‐HAB phytoplankton species. However, this may also be related to the difference in representation of dinoflagellate and diatom species in the respective HAB and non‐HAB phytoplankton groups. Since the proliferation of HAB species may strongly depend on their growth rates, our results warn for a greater potential of dinoflagellate HAB development in future coastal waters, particularly in temperate regions.
Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma

Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital‐based controls (case–control analyses), and between 17 KRAS wild‐type tumors and 61 KRAS mutated tumors (case–case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild‐type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98–11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14–0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild‐type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild‐type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen. , 60:693–703, 2019. © 2019 Wiley Periodicals, Inc.