Miracle-dz/UniFAR-FTUs huggingface dataset:
To Treat or Not to Treat: Importance of Functional Dependence in Deciding Intravenous Thrombolysis of “Mild Stroke” Patients

Intravenous thrombolysis (IVT) in patients with a low National Institutes of Health Stroke Scale (NIHSS) score of 0–5 remains controversial. IVT should be used in patients with mild but nevertheless disabling symptoms. We hypothesize that response to IVT of patients with “mild stroke” may depend on their level of functional dependence (FD) at hospital admission. The aims of our study were to investigate the effect of IVT and to explore the role of FD in influencing the response to IVT. This study was a retrospective analysis of a prospectively collected database, including 389 patients stratified into patients receiving IVT (IVT+) and not receiving IVT (IVT −) just because of mild symptoms. Barthel index (BI) at admission was used to assess FD, dividing subjects with BI score < 80 (FD+) and with BI score ≥ 80 (FD−). The efficacy endpoints were the rate of positive disability outcome (DO+) (3-month mRS score of 0 or 1), and the rate of positive functional outcome (FO+) (mRS score of zero or one, plus BI score of 95 or 100 at 3 months). At the multivariate analysis, IVT treatment was an independent predictor of DO+ (OR 3.12, 95% CI 1.34−7.27, p = 0.008) and FO+ (OR: 4.70, 95% CI 2.38−9.26, p = 0.001). However, FD+ IVT+ patients had a significantly higher prevalence of DO+ and FO+ than those FD+ IVT–. Differently, IVT treatment did not influence DO+ and FO+ in FD– patients. In FD+ patients, IVT treatment represented the strongest independent predictor of DO+ (OR 6.01, 95% CI 2.59–13.92, p = 0.001) and FO+ (OR 4.73, 95% CI 2.29–9.76, p = 0.001). In conclusion, alteplase seems to improve functional outcome in patients with “mild stroke”. However, in our experience, this beneficial effect is strongly influenced by FD at admission.
Infiltrating Mast Cell–Mediated Stimulation of Estrogen Receptor Activity in Breast Cancer Cells Promotes the Luminal Phenotype

Mast cells impact breast cancer outcome by directly affecting the phenotype of tumor cells through stimulation of the estrogen receptor pathway. Tumor growth and development is determined by both cancer cell–autonomous and microenvironmental mechanisms, including the contribution of infiltrating immune cells. Because the role of mast cells (MC) in this process is poorly characterized and even controversial, we investigated their part in breast cancer. Crossing C57BL/6 MMTV-PyMT mice, which spontaneously develop mammary carcinomas, with MC-deficient C57BL/6-KitW-sh/W-sh (Wsh) mice, showed that MCs promote tumor growth and prevent the development of basal CK5-positive areas in favor of a luminal gene program. When cocultured with breast cancer cells in vitro, MCs hindered activation of cMET, a master regulator of the basal program, and simultaneously promoted expression and activation of estrogen receptor (ESR1/ER) and its target genes (PGR, KRT8/CK8, BCL2), which are all luminal markers. Moreover, MCs reduced ERBB2/HER2 levels, whose inhibition further increased ESR1 expression. In vivo and in silico analysis of patients with breast cancer revealed a direct correlation between MC density and ESR1 expression. In mice engrafted with HER2-positive breast cancer tumors, coinjection of MCs increased tumor engraftment and outgrowth, supporting the link between MCs and increased risk of relapse in patients with breast cancer. Together, our findings support the notion that MCs influence the phenotype of breast cancer cells by stimulating a luminal phenotype and ultimately modifying the outcome of the disease. Significance: Mast cells impact breast cancer outcome by directly affecting the phenotype of tumor cells through stimulation of the estrogen receptor pathway.
Barriers and Insights in Participant Recruitment in Assisted Living Facilities

An estimated 1.2 million older adults nationwide currently reside in assisted/supportive living facilities, and research is required to continue to identify best outcomes in for their care. However, challenges exist. The aim of this paper is to address barriers and provide insights related to participant recruitment in assisted and supportive living facilities. Identified barriers included unproductive communication with reception area staff, a perceived lack of interest in research activity, and the inability of Director of Nursing (DON) to provide authorization for research activities. Recruitment insights included productive encounters with gatekeepers, establishing trust with executive administration and healthcare personnel, and research team persistence.
Low Prevalence of Celiac Disease among Patients with Functional Gastrointestinal Disorders in Latvia.

BACKGROUND AND AIMS Studies suggest that the prevalence of celiac disease (CD) is increased in individuals with functional gastrointestinal disorders (FGIDs), in particular, irritable bowel syndrome (IBS); however, the evidence is conflicting. We aimed to analyze the prevalence of CD in patients with FGIDs in Latvia. METHODS This retrospective study included patients with FGIDs, referred for a gastroenterologist consultation in a secondary gastroenterology practice unit. Patients were divided into three groups - patients only with IBS (IBS group), patients only with functional dyspepsia (FD) (FD group), patients with mixed symptoms IBS and FD (Mixed group). Patient levels of tissue transglutaminase IgA (tTG-IgA) and/or antiendomysial IgA group antibodies (EMA-IgA) were evaluated. Four duodenal biopsies were obtained and reported according to Marsh classification. Patients diagnosed or being referred for confirmation of CD were excluded from the study. RESULTS Overall, 1,833 FGIDs patients were enrolled. Celiac serology was available for 1,570 patients, duodenal histology for 582 patients, both histology and serology for 319 patients. In total, celiac seropositivity was present in 1.78% (28/1570) (3.18% in IBS group, 0.90% in FD group and 1.11% of cases in the mixed group). Fifteen patients had histopathological changes (2.58%; 15/582). Three IBS patients (2.36%) were both serology and biopsy positive. None of the FD patients had CD. CONCLUSION Prevalence of biopsy-proven CD in patients from Latvia with FGIDs was low. Routine screening for CD could be considered only among patients with IBS.
Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, in nonpregnant women

The safety and pharmacokinetics of carbetocin, a long-acting oxytocin analogue, were studied in 25 healthy nonpregnant women. The distribution and elimination half-lives of a 0.4-mg intravenous dose were found to be 5.5 ± 1.6 minutes and 41 ± 11.9 minutes, respectively. Similarly, the half-lives of a 0.8-mg intravenous dose were found to be 6.1 ± 1.2 minutes and 42.7 ± 10.6 minutes. Approximately 0.7% of the carbetocin dose was eliminated in the unchanged form by the kidney, indicating that carbetocin, like oxytocin, is eliminated primarily by nonrenal routes. Intramuscularly (IM) administered carbetocin was found to enter the circulation rapidly, with a time to peak concentration of less than 30 minutes. The absolute bioavailability of carbetocin injected IM was approximately 80%. Doses of carbetocin of 0.05 to 0.8 mg produced very few side effects. Included were transient facial flushing and mild transient tachycardia accompanied by a decrease in diastolic blood pressure. The increase in heart rate was significant (P <0.05) after the administration of 0.4- and 0.8-mg IM doses, while the decrease in diastolic blood pressure was significant after the 0.8-mg IM dose only. No clinically significant changes between predrug and postdrug chemistry values of hematology parameters were noted. (Less)
The alarmones (p)ppGpp are part of the heat shock response of Bacillus subtilis

Bacillus subtilis cells are well suited to study how bacteria sense and adapt to proteotoxic stress such as heat, since temperature fluctuations are a major challenge to soil-dwelling bacteria. Here, we show that the alarmones (p)ppGpp, well known second messengers of nutrient starvation, are also involved in the heat stress response as well as the development of thermo-resistance. Upon heat-shock, intracellular levels of (p)ppGpp rise in a rapid but transient manner. The heat-induced (p)ppGpp is primarily produced by the ribosome-associated alarmone synthetase Rel, while the small alarmone synthetases RelP and RelQ seem not to be involved. Furthermore, our study shows that the generated (p)ppGpp pulse primarily acts at the level of translation, and only specific genes are regulated at the transcriptional level. These include the down-regulation of some translation-related genes and the up-regulation of hpf, encoding the ribosome-protecting hibernation-promoting factor. In addition, the alarmones appear to interact with the activity of the stress transcription factor Spx during heat stress. Taken together, our study suggests that (p)ppGpp modulates the translational capacity at elevated temperatures and thereby allows B. subtilis cells to respond to proteotoxic stress, not only by raising the cellular repair capacity, but also by decreasing translation to concurrently reduce the protein load on the cellular protein quality control system.
Functional Alterations in Ciliogenesis-Associated Kinase 1 (CILK1) that Result from Mutations Linked to Juvenile Myoclonic Epilepsy

Ciliopathies are a group of human genetic disorders associated with mutations that give rise to the dysfunction of primary cilia. Ciliogenesis-associated kinase 1 (CILK1), formerly known as intestinal cell kinase (ICK), is a conserved serine and threonine kinase that restricts primary (non-motile) cilia formation and length. Mutations in CILK1 are associated with ciliopathies and are also linked to juvenile myoclonic epilepsy (JME). However, the effects of the JME-related mutations in CILK1 on kinase activity and CILK1 function are unknown. Here, we report that JME pathogenic mutations in the CILK1 N-terminal kinase domain abolish kinase activity, evidenced by the loss of phosphorylation of kinesin family member 3A (KIF3A) at Thr672, while JME mutations in the C-terminal non-catalytic domain (CTD) have little effect on KIF3A phosphorylation. Although CILK1 variants in the CTD retain catalytic activity, they nonetheless lose the ability to restrict cilia length and also gain function in promoting ciliogenesis. We show that wild type CILK1 predominantly localizes to the base of the primary cilium; in contrast, JME variants of CILK1 are distributed along the entire axoneme of the primary cilium. These results demonstrate that JME pathogenic mutations perturb CILK1 function and intracellular localization. These CILK1 variants affect the primary cilium, independent of CILK1 phosphorylation of KIF3A. Our findings suggest that CILK1 mutations linked to JME result in alterations of primary cilia formation and homeostasis.
Hearing loss prevalence and hearing health among school-aged children in the Canadian Arctic

Abstract Objective Hearing loss is an important health concern in Canada’s Arctic. The objective of this research was to provide information on the prevalence of childhood hearing loss in Nunavut. Design This cross-sectional study involved comprehensive audiologic assessments of school-aged children in six communities to determine overall and community-specific prevalence of hearing loss. Data were collected about hearing aid use and factors affecting use through a parent questionnaire. Study sample Assessments were completed for 644 children in kindergarten to grade 6. Results 124 (19.3%) children had hearing loss of ≥ 30 dB HL at one or more frequencies in at least one ear (93.5% conductive loss). Applying a Canadian prevalence study definition, 148 (23.5%) children had hearing loss. Tympanic membrane perforations were present in 36.8% (n = 28) of children with unilateral and 45.8% (n = 22) with bilateral loss. Conclusions The prevalence of hearing loss in Canada’s North was almost three times that reported for non-indigenous children. One in five school-aged children was found to have hearing loss that is likely to affect classroom learning and social/emotional development. A hearing health strategy tailored to this population is critically needed.
Cricket (Gryllodes sigillatus) meal fed to healthy adult dogs does not affect general health and minimally impacts apparent total tract digestibility

Abstract Insects can serve as a novel high-quality protein source for pet foods. However, there is an absence of research investigating the use of insects in pet food. The study objective was to evaluate the apparent total tract digestibility and possible health effects of diets containing graded levels of cricket (Gryllodes sigillatus) meal fed to healthy adult dogs. Thirty-two adult Beagles were randomly assigned to one of four dietary treatments: 0%, 8%, 16%, or 24% cricket meal. Dogs were fed their respective diet for a total of 29 d with a 6-d collection phase. Fecal samples were collected daily during the collection phase to measure total fecal output as well as apparent total tract digestibility for dry matter (DM), organic matter, crude protein, fat, total dietary fiber, and gross energy. Blood samples were taken prior to the study and on day 29 for hematology and chemistry profiles. Data were analyzed in a mixed model including the fixed effects of diet and sex. Total fecal output increased on both an as-is (P = 0.030) and DM basis (P = 0.024). The apparent total tract digestibility of each nutrient decreased (P < 0.001) with the increasing level of cricket meal inclusion. All blood values remained within desired reference intervals indicating healthy dogs. Slight fluctuations in blood urea nitrogen (P = 0.037) and hemoglobin (P = 0.044) levels were observed but were not considered of biological significance. Even with the decrease in digestibility with the inclusion of cricket meal, diets remained highly digestible at greater than 80% total apparent digestibility. In conclusion, crickets were demonstrated to be an acceptable ingredient for dog diets.
Antithetic population response to antibiotics in a polybacterial community

The collective response of mixed bacterial ecosystems to antibiotics can be opposite to that of single-species cultures. Much is known about the effects of antibiotics on isolated bacterial species, but their influence on polybacterial communities is less understood. Here, we study the joint response of a mixed community of nonresistant Bacillus subtilis and Escherichia coli bacteria to moderate concentrations of the β-lactam antibiotic ampicillin. We show that when the two organisms coexist, their population response to the antibiotic is opposite to that in isolation: Whereas in monoculture B. subtilis is tolerant and E. coli is sensitive to ampicillin, in coculture it is E. coli who can proliferate in the presence of the antibiotic, while B. subtilis cannot. This antithetic behavior is predicted by a mathematical model constrained only by the responses of the two species in isolation. Our results thus show that the collective response of mixed bacterial ecosystems to antibiotics can run counter to what single-species potency studies tell us about their efficacy.
Pediatric Pulmonology

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland, Australia Child Health Research Centre, The University of Queensland, South Brisbane, Queensland, Australia Queensland Paediatric Infectious Diseases Laboratory, Infection Management and Prevention Service, Children's Health Queensland, South Brisbane, Queensland, Australia School of Medicine and Infection and Immunology Division, Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia Departments of Infectious Diseases and Paediatrics, Gold Coast Health, Southport, Queensland, Australia
Splenic Gene Expression Signatures in Slow-Growing Chickens Stimulated in Ovo with Galactooligosaccharides and Challenged with Heat

Simple Summary The exposure of animals to excessive heat leads to heat stress, heat stroke, or even death. The first negative effects of heat exposure occur in the gut. The elevated temperature leads to damage in intestinal walls and shifts in the composition of intestinal microbiota. In effect, the gut content (mainly intestinal microbiota and their metabolites) leaks through compromised intestinal walls into milieu of the body. Prebiotics (e.g., GOS—galactooligosaccharides) can be used to mitigate the negative effects of the heat stress in poultry. GOS that are delivered in ovo on day 12 of egg incubation stimulates the development of healthy intestinal microbiota in a chicken embryo. Healthy intestinal microbiota enhances the barrier function of the gut and the immune system. Chickens were originally domesticated in southeast Asia and are therefore genetically adapted to handle high temperatures. However, genetic selection towards performance leads to sensitization to high ambient temperature. In this paper, we studied slow-growing chickens with a reputation for heat resistance. We used in ovo stimulation with the GOS prebiotic that was delivered in ovo to promote healthy gut microbiota. In this manner, we combine genetics and environment to describe a model of heat resistance in poultry. Abstract Galactooligosaccharides (GOS) that are delivered in ovo improve intestinal microbiota composition and mitigate the negative effects of heat stress in broiler chickens. Hubbard hybrids are slow-growing chickens with a high resistance to heat. In this paper, we determined the impact of GOS delivered in ovo on slow-growing chickens that are challenged with heat. The experiment was a 2 × 2 × 2 factorial design. On day 12 of incubation, GOS (3.5 mg/egg) was delivered into the egg (n = 300). Controls (C) were mock-injected with physiological saline (n = 300). After hatching, the GOS and C groups were split into thermal groups: thermoneutral (TN) and heat stress (HS). HS (30 °C) lasted for 14 days (days 36–50 post-hatching). The spleen (n = 8) was sampled after acute (8.5 h) and chronic (14 days) HS. The gene expression of immune-related (IL-2, IL-4, IL-6, IL-10, IL-12p40, and IL-17) and stress-related genes (HSP25, HSP90AA1, BAG3, CAT, and SOD) was detected with RT-qPCR. Chronic HS up-regulated the expression of the genes: IL-10, IL-12p40, SOD (p < 0.05), and CAT (p < 0.01). GOS delivered in ovo down-regulated IL-4 (acute p < 0.001; chronic p < 0.01), IL-12p40, CAT and SOD (chronic p < 0.05). The obtained results suggest that slow-growing hybrids are resistant to acute heat and tolerant to chronic heat, which can be supported with in ovo GOS administration.
Recombination Rate Variation and Infrequent Sex Influence Genetic Diversity in Chlamydomonas reinhardtii

Abstract Recombination confers a major evolutionary advantage by breaking up linkage disequilibrium between harmful and beneficial mutations, thereby facilitating selection. However, in species that are only periodically sexual, such as many microbial eukaryotes, the realized rate of recombination is also affected by the frequency of sex, meaning that infrequent sex can increase the effects of selection at linked sites despite high recombination rates. Despite this, the rate of sex of most facultatively sexual species is unknown. Here, we use genomewide patterns of linkage disequilibrium to infer fine-scale recombination rate variation in the genome of the facultatively sexual green alga Chlamydomonas reinhardtii. We observe recombination rate variation of up to two orders of magnitude and find evidence of recombination hotspots across the genome. Recombination rate is highest flanking genes, consistent with trends observed in other nonmammalian organisms, though intergenic recombination rates vary by intergenic tract length. We also find a positive relationship between nucleotide diversity and physical recombination rate, suggesting a widespread influence of selection at linked sites in the genome. Finally, we use estimates of the effective rate of recombination to calculate the rate of sex that occurs in natural populations, estimating a sexual cycle roughly every 840 generations. We argue that the relatively infrequent rate of sex and large effective population size creates a population genetic environment that increases the influence of selection on linked sites across the genome.
AN EVALUATION OF THE EFFECTIVENESS OF THE NATIONAL ALLIANCE OF MENTAL ILLNESS’S ENDING THE SILENCE PROGRAM

The National Alliance of Mental Illness's Ending the Silence (ETS) program focuses on the epidemic of mental illness stigma among school-aged youth. The program is targeted specifically at high school-age youth, and aims to educate, dispel myths about mental illness and instill a message of hope and recovery all while encouraging students to reduce the stigma associated with mental illness. A trained presentation team containing two people, one of whom is a young adult living with mental illness or recovered from mental illness, delivers the program. Participants (n=142) completed assessments measuring their thoughts and attitudes towards people with mental illness, as well as a mental health facts questionnaire. Data were gathered from participants before the ETS presentation, after the ETS presentation, and 6 weeks later. The assessments consisted of both qualitative and quantitative data. Content analysis of the qualitative data revealed a consistent improvement in participants' understanding and definition of mental illness. Youth reported understanding that mental illness can be a biological as well as developed illness. The majority of students (61.3%) self-reported their attitudes towards people with mental illness had become more positive after the presentation. The results of this study indicate that the Ending the Silence program is meeting its identified goals and objectives. v ACKNOWLEDGMENTS I would first like to thank my thesis chair. Dr. Lisa Sweatt for your support during the entire process. Your encouragement, patience, and guidance never wavered, and you kept me sane throughout the process. You are someone I will continue to admire the rest of my professional and academic career, and you have set a wonderful example for me to model myself after. I would also like to thank my other committee chair members, Dr. Teramoto Pedrotti and Dr. Laver for their willingness to support me during this process. Both of you are inspiring and busy and yet took the time to provide me guidance throughout the writing process. A special thank you to Dr. Laver as well for sitting in on my committee last minute and for all of your guidance through the analysis of my data. Thank you to Joe Johnson, for allowing me to evaluate the amazing work you and your team are doing with the ETS program, and thank you to the schools that allowed me to run assessments during your class time and welcomed me in so warmly. To my friends and family, thank you for being …