Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of connexin 43 in different forms of intercellular communication – gap junctions, extracellular vesicles and tunnelling nanotubes

ABSTRACT Communication is important to ensure the correct and efficient flow of information, which is required to sustain active social networks. A fine-tuned communication between cells is vital to maintain the homeostasis and function of multicellular or unicellular organisms in a community environment. Although there are different levels of complexity, intercellular communication, in prokaryotes to mammalians, can occur through secreted molecules (either soluble or encapsulated in vesicles), tubular structures connecting close cells or intercellular channels that link the cytoplasm of adjacent cells. In mammals, these different types of communication serve different purposes, may involve distinct factors and are mediated by extracellular vesicles, tunnelling nanotubes or gap junctions. Recent studies have shown that connexin 43 (Cx43, also known as GJA1), a transmembrane protein initially described as a gap junction protein, participates in all these forms of communication; this emphasizes the concept of adopting strategies to maximize the potential of available resources by reutilizing the same factor in different scenarios. In this Review, we provide an overview of the most recent advances regarding the role of Cx43 in intercellular communication mediated by extracellular vesicles, tunnelling nanotubes and gap junctions. Summary: We give an overview of the intercellular communication mechanisms involving Cx43, describing the role played by Cx43 in gap junctions, tunnelling nanotubes and extracellular vesicles.
Immunohistochemical study of receptor activator of nuclear factor kappa‐B ligand (RANK‐L) in human osteolytic bone tumors

Osteolytic bone tumors produce intercellular signaling proteins that regulate bone remodeling by altering the rates of osteoclast and osteoblast differentiation and activity. This report examines osteolytic bone tumor expression of receptor activator of nuclear factor B‐ligand (RANK‐L), a cytokine that is arguably the most critical regulator of osteoclast differentiation and activation.
Hospital safety among neurologic patients

Objective: To examine the frequency and type of adverse events (AEs) experienced by neurologic patients in hospital. Methods: This population-based, retrospective cohort study used hospital discharge abstract data for children and adults admitted to hospital from 2009 to 2015 with 1 of 9 neurologic conditions (Alzheimer disease and related dementia, brain tumor, epilepsy, motor neuron disease, multiple sclerosis, parkinsonism/Parkinson disease, spinal cord injury, traumatic brain injury, and stroke). Neurologic conditions were identified with ICD-10-CA codes. Eighteen AEs were examined with ICD-10-CA codes. The proportion of AEs was calculated, and regression analysis was used to examine factors and outcomes associated with AEs (age, sex, comorbidity, length of stay, and mortality). Results: The overall proportion of admissions associated with an AE among those with a neurologic condition was 11 per 100 admissions. Those with a spinal cord injury had the highest proportion of AEs (39.4 per 100 admissions). The most common AEs were infections and respiratory complications (32.0% and 16.7%, respectively). Age and the presence of comorbidities were associated with higher odds of an AE, while readmission was associated with lower odds of an AE. Having an AE was associated with increased length of stay and higher odds of mortality. Conclusions: This study demonstrates that neurologic patients have a high proportion of AEs in hospital. The findings provide information on the quality and safety of care for people with neurologic conditions in hospital, which can help inform future quality improvement initiatives.
Identity-level representations affect unfamiliar face matching performance in sequential but not simultaneous tasks

According to cognitive and neurological models of the face-processing system, faces are represented at two levels of abstraction. First, image-based pictorial representations code a particular instance of a face and include information that is unrelated to identity—such as lighting, pose, and expression. Second, at a more abstract level, identity-specific representations combine information from various encounters with a single face. Here we tested whether identity-level representations mediate unfamiliar face matching performance. Across three experiments we manipulated identity attributions to pairs of target images and measured the effect on subsequent identification decisions. Participants were instructed that target images were either two photos of the same person (1ID condition) or photos of two different people (2ID condition). This manipulation consistently affected performance in sequential matching: 1ID instructions improved accuracy on “match” trials and caused participants to adopt a more liberal response bias than the 2ID condition. However, this manipulation did not affect performance in simultaneous matching. We conclude that identity-level representations, generated in working memory, influence the amount of variation tolerated between images, when making identity judgements in sequential face matching.
The thin-layer agar method for direct phenotypic detection of multi- and extensively drug-resistant tuberculosis.

BACKGROUND Molecular techniques rapidly detect resistance to rifampicin (RMP) and isoniazid (INH), but do not eliminate the need for culture-based drug susceptibility testing (DST) against other drugs. The thin-layer agar (TLA) test, a non-commercial direct DST method, has demonstrated good performance for INH and RMP; however, evidence is still limited, and its applicability for DST of ofloxacin (OFX) and kanamycin (KM) is unknown. DESIGN We compared 279 TLA DST results with those of MGIT for INH and RMP, and 280 results for OFX and KM with those of the 7H11 agar proportion method, obtained from 320 smear-positive samples from 165 Georgian TB patients. Discrepancies were solved by comparison with a composite reference standard. The prevalence of multidrug-resistant tuberculosis (TB) was 30 of 164 patients (18.3%), 2 (6.7%) of whom had extensively drug-resistant TB. RESULTS TLA showed 94.7%, 98.2%, 100% and 78.9% sensitivity, respectively, for INH, RMP, OFX and KM, with 100% specificity. Average time to results was 7 days in TLA, 23 in MGIT and 49 for 7H11 agar. CONCLUSIONS In low-resource settings, TLA can be applied for the rapid detection of resistance to INH, RMP and fluoroquinolones. Further studies are necessary to improve sensitivity to KM and further assess its performance for OFX and other drugs and its applicability in field conditions.
Growth in Preterm Infants until 36 Weeks' Postmenstrual Age Is Close to Target Recommendations

Objective: To establish the determinants of weight, length and head circumference changes during their initial hospitalization in very-low-birth-weight preterm infants. Subjects/Methods: A prospective cohort study was performed. Weight z-score and percentage of target dietary intakes (TDIs) were prospectively determined daily during the first 5 weeks of life in a group of preterm infants (n = 111, birth weight <1,500 g, gestational age <34 weeks). Weight, length and head circumference at 36 weeks' postmenstrual age (PMA) were recorded. A mixed effects regression model was used to evaluate changes in weight z-score during the first 5 weeks of life. Simple Pearson correlations and stepwise logistic regression were used to determine the relationship between fetal growth, illness severity, nutritional intake and growth at 36 weeks' PMA. Results: Weight z-score decreased significantly in all infants during the first 5 weeks of life from -0.92 ± 0.66 at birth to -1.89 ± 0.65 at 5 weeks. The variation of weight z-score during the first 5 weeks of life was influenced by weight z-score at birth, energy and protein intakes and gestational age. Mean energy and protein intakes were 95.5 and 86.4% of TDIs. Weight z-score fell to -2.05 ± 0.64 at 36 weeks' PMA. Birth weight z-score was significantly correlated with weight z-score at 36 weeks (R2 = 0.71; p < 0.001). Severity of illness influenced the weight z-score at 36 weeks. Conclusion: Despite achieving a protein and energy intake close to the described target intake, the rate of growth in our infants was lower than indicated by the intrauterine growth curve. Lower gestational age, lower birth weight and severe illness had a negative effect on growth.
Epidemiology of Respiratory Infections in Young Children: Insights from the New Vaccine Surveillance Network

Background: The New Vaccine Surveillance Network, funded by the Centers for Disease Control and Prevention, was established to provide longitudinal data to help measure the impact of vaccines that decrease the burden of acute respiratory illness in children younger than 5 years of age. Currently 140,000 children younger than 5 years of age, nearly 1% of the U.S. population, are under surveillance in 3 urban counties, which include Nashville, TN, Rochester, NY, and Cincinnati, OH. Prospective, active, population-based surveillance of children hospitalized with respiratory symptoms or fever began in 2000, and outpatient surveillance began in 2002 in selected winter months. Results: During the first year of surveillance, the admission rate for acute respiratory illness/fever in children younger than 5 years of age in the surveillance areas was 180 per 10,000 children. In 61% of these hospitalizations, a respiratory virus was identified. Respiratory syncytial viruses, influenza viruses and parainfluenza viruses were identified in 30%, and other respiratory viruses were identified in 36%. Approximately one-third of children hospitalized had identified high risk conditions, primarily asthma (24%). About one-half of the children hospitalized were younger than 6 months of age. Polymerase chain reaction doubled the diagnostic yield of culture for respiratory syncytial viruses, influenza and parainfluenza virus combined. Preliminary data on influenza admissions during the 4 years indicated considerable variation in admission rates by season and site. Annually the mean admission rates during the study period were 43 per 10,000 children younger than 6 months of age, 9 per 10,000 children 6–23 months of age and 4 per 10,000 children 24–59 months of age. Conclusion: These data provide ongoing surveillance of hospitalizations and other medically attended visits for respiratory viral illness in children younger than 5 years of age. Evaluation of influenza vaccine effectiveness, the epidemiology of respiratory viruses in children and the impact of the pediatric influenza vaccination program are in progress.
Clinical and organizational factors associated with feeding tube use among nursing home residents with advanced cognitive impairment.

CONTEXT Empiric data and expert opinion suggest that use of feeding tubes is not beneficial for older persons with advanced dementia. Previous research has shown a 10-fold variation in this practice across the United States. OBJECTIVE To identify the facility and resident characteristics associated with feeding tube use among US nursing homes residents with severe cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of all residents with advanced cognitive impairment who had Minimum Data Set assessments within 60 days of April 1, 1999, (N = 186,835) and who resided in Medicare- or Medicaid-certified US nursing homes. Main Outcomes Measures Facility and resident characteristics described in the 1999 On-line Survey Certification of Automated Records and the 1999 Minimum Data Set. Multivariate analysis using generalized estimating equations determined the facility and resident factors independently associated with feeding tube use. RESULTS Thirty-four percent of residents with advanced cognitive impairment had feeding tubes (N = 63,101). Resident characteristics associated with a greater likelihood of feeding tube use included younger age, nonwhite race, male sex, divorced marital status, lack of advance directives, a recent decline in functional status, and no diagnosis of Alzheimer disease. Controlling for these patient factors, residents living in facilities that were for profit (adjusted odds ratio [OR], 1.09; 95% confidence interval [CI], 1.06-1.12); located in an urban area (OR, 1.14; 95% CI, 1.11-1.16); having more than 100 beds (OR, 1.04; 95% CI, 1.01-1.07); and lacking a special dementia care unit (OR, 1.11; 95% CI, 1.07-1.15) had a higher likelihood of having a feeding tube. Additionally, feeding tube use was more likely among residents living in facilities that had a smaller proportion of residents with do-not-resuscitate orders, had a higher prevalence of nonwhite residents, and lacked a nurse practitioner or physician assistant on staff. CONCLUSIONS More than one third of severely cognitively impaired residents in US nursing homes have feeding tubes. Feeding tube use is independently associated with both the residents' clinical characteristics and the nursing homes' fiscal, organizational, and demographic features.
Deletion of Open Reading Frame UL26 from the Human Cytomegalovirus Genome Results in Reduced Viral Growth, Which Involves Impaired Stability of Viral Particles

ABSTRACT We previously showed that open reading frame (ORF) UL26 of human cytomegalovirus, a member of the US22 multigene family of betaherpesviruses, encodes a novel tegument protein, which is imported into cells in the course of viral infection. Moreover, we demonstrated that pUL26 contains a strong transcriptional activation domain and is capable of stimulating the major immediate-early (IE) enhancer-promoter. Since this suggested an important function of pUL26 during the initiation of the viral replicative cycle, we sought to ascertain the relevance of pUL26 by construction of a viral deletion mutant lacking the UL26 ORF using the bacterial artificial chromosome mutagenesis procedure. The resulting deletion virus was verified by PCR, enzyme restriction, and Southern blot analyses. After infection of human foreskin fibroblasts, the UL26 deletion mutant showed a small-plaque phenotype and replicated to significantly lower titers than wild-type or revertant virus. In particular, we noticed a striking decrease of infectious titers 7 days postinfection in a multistep growth experiment, whereas the release of viral DNA from infected cells was not impaired. A further investigation of this aspect revealed a significantly diminished stability of viral particles derived from the UL26 deletion mutant. Consistent with this, we observed that the tegument composition of the deletion mutant deviates from that of the wild-type virus. We therefore hypothesize that pUL26 plays a role not only in the onset of IE gene transcription but also in the assembly of the viral tegument layer in a stable and correct manner.
Role of antifibrotic cytokine interferon-gamma in the prevention of postlaminectomy peridural fibrosis in rats.

OBJECTIVE Extensive peridural fibrosis after spinal surgery may be the underlying cause of failed-back syndrome in some cases. There is increasing evidence that generation of specific cytokine patterns by immune and structural cells and interactions among these cells mediate many of the key events involved in fibrogenesis. Interferon-gamma (IFN-gamma) has several potential antifibrotic actions, including inhibition of fibroblast proliferation and collagen deposition, promotion of fibroblast apoptosis, and inhibition of production and action of the fibrogenic cytokine, transforming growth factor-beta. We conducted a study to determine the effectiveness of IFN-gamma in preventing postlaminectomy peridural fibrosis in rats. To the best of our knowledge, this is the first study testing immunotherapy in peridural fibrosis. Type 2 cytokine hypothesis of fibrogenesis is emphasized. METHODS Laminectomies were performed in 30 rats. We administered 2000 U/d IFN-gamma, 20,000 U/d IFN-gamma, or 0.2 ml/d saline to the laminectomy site through a silicone catheter for 3 days in blinded fashion. The amount of scar tissue, fibroblast density, inflammatory cell density, arachnoidal involvement, and bone regeneration were analyzed histologically. RESULTS Histopathological examination showed a significantly reduced amount of scar tissue and fibroblast density in the low-dose IFN-gamma group compared with the control and high-dose IFN-gamma groups. A significant increase was detected in inflammatory cell density in the high-dose IFN-gamma group compared with the control and low-dose IFN-gamma groups. CONCLUSION Cytokines play a critical role in wound healing, tissue repair, and fibrogenesis. This study suggests that topical application of low-dose IFN-gamma is an effective and safe method of preventing peridural fibrosis, but further studies with different doses, durations, and intervals are required to achieve better results.
Satellite chlorophyll fluorescence measurements reveal large‐scale decoupling of photosynthesis and greenness dynamics in boreal evergreen forests

Mid‐to‐high latitude forests play an important role in the terrestrial carbon cycle, but the representation of photosynthesis in boreal forests by current modelling and observational methods is still challenging. In particular, the applicability of existing satellite‐based proxies of greenness to indicate photosynthetic activity is hindered by small annual changes in green biomass of the often evergreen tree population and by the confounding effects of background materials such as snow. As an alternative, satellite measurements of sun‐induced chlorophyll fluorescence (SIF) can be used as a direct proxy of photosynthetic activity. In this study, the start and end of the photosynthetically active season of the main boreal forests are analysed using spaceborne SIF measurements retrieved from the GOME‐2 instrument and compared to that of green biomass, proxied by vegetation indices including the Enhanced Vegetation Index (EVI) derived from MODIS data. We find that photosynthesis and greenness show a similar seasonality in deciduous forests. In high‐latitude evergreen needleleaf forests, however, the length of the photosynthetically active period indicated by SIF is up to 6 weeks longer than the green biomass changing period proxied by EVI, with SIF showing a start‐of‐season of approximately 1 month earlier than EVI. On average, the photosynthetic spring recovery as signalled by SIF occurs as soon as air temperatures exceed the freezing point (2–3 °C) and when the snow on the ground has not yet completely melted. These findings are supported by model data of gross primary production and a number of other studies which evaluated in situ observations of CO2 fluxes, meteorology and the physiological state of the needles. Our results demonstrate the sensitivity of space‐based SIF measurements to light‐use efficiency of boreal forests and their potential for an unbiased detection of photosynthetic activity even under the challenging conditions interposed by evergreen boreal ecosystems.
Conceptual overlap between moral norms and anticipated regret in the prediction of intention: Implications for theory of planned behaviour research

Moral norms and anticipated regret are widely used extensions to the theory of planned behaviour, yet there is some evidence to suggest that these constructs may conceptually overlap as predictors of intention. Two health-related behaviours with distinct moral implications (Study 1: organ donation registration, N = 352 and Study 2: condom usage, N = 1815) were therefore examined to ascertain whether moral norms and anticipated regret are indeed conceptually distinct. While evidence consistent with conceptual overlap was identified in Study 1, the evidence for such overlap in Study 2 was more ambiguous. In Study 3, a meta-analysis of existing literature revealed that the relationship between moral norms and anticipated regret was moderated by the extent of the moral implications arising from the behaviour under examination. Taken together, these findings suggest that conceptual overlap between moral norms and anticipated regret is more likely to occur among behaviours with obvious moral implications. Researchers wishing to examine the predictive utility of moral norms and anticipated regret among such behaviours would therefore be advised to aggregate these measures to form a composite variable (personal norms).
Treatment with all-trans-retinoic acid decreases levels of endogenous TGF-beta(1) in the mesenchyme of the developing mouse inner ear.

BACKGROUND Previous studies have shown that in utero exposure of the mouse embryo to high doses of all-trans-retinoic acid (atRA) produces defects of the developing inner ear and its surrounding cartilaginous capsule, while exposure of cultured periotic mesenchyme plus otic epithelium to high doses of exogenous atRA results in an inhibition of otic capsule chondrogenesis. METHODS In this study, we examine the effects of atRA exposure on the endogenous expression of transforming growth factor-beta(1) (TGF-beta(1)), a signaling molecule that mediates the epithelial-mesenchymal interactions that guide the development of the capsule of the inner ear. RESULTS Our results demonstrate a marked reduction in immunostaining for TGF-beta(1) in the periotic mesenchyme of atRA-exposed embryos of age E10.5 and E12 days in comparison with control specimens. Consistent with these in vivo findings, high-density cultures of E10.5 periotic mesenchyme plus otic epithelium, treated with doses of atRA that suppress chondrogenesis, showed significantly decreased levels of TGF-beta(1), as compared with TGF-beta(1) levels in untreated control cultures. Furthermore, we demonstrate a rescue of cultured periotic mesenchyme plus otic epithelium from atRA-induced chondrogenic suppression by supplementation of cultures with excess TGF-beta(1). CONCLUSIONS Our results support the hypothesis that TGF-beta(1) plays a role in mechanisms of atRA teratogenicity during inner ear development.
Long-term Oral Application of 5-Bromo-2-Deoxyuridine Does Not Reliably Label Proliferating Immune Cells in the LEW Rat

To study the lifespan of immune cell populations in the LEW rat, 5-bromo-2-deoxyuridine (BrdU) was administered in the drinking water. After 12 weeks, the epithelium of gut and skin was completely BrdU+. In contrast, thymus, bone marrow, and germinal centers of Peyer's patches contained only a few BrdU+ cells, although most should have been labeled during this time. The lack of labeling was due neither to obvious toxic effects of BrdU on these organs nor to insufficient detection of incorporated BrdU. Analysis of the kinetic pattern of the appearance of BrdU+ cells in bone marrow, blood, spleen, and lymph nodes over 12 weeks revealed that the dosage of BrdU initially was high enough to label the proliferating cells in the bone marrow, but then became too low, although the BrdU uptake of the rats was similar over the entire time. This indicates that in the LEW rat the metabolism of orally applied BrdU changes over time, leading to a reduction in the amount of BrdU available for incorporation into the DNA below a level necessary for labeling all proliferating cells. This effect appears to be species- and strain-dependent, and should be considered when the BrdU technique is used. (J Histochem Cytochem 45:393–401, 1997)