Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of synovial B cell survival in rheumatoid arthritis by vascular cell adhesion molecule 1 (CD106) expressed on fibroblast-like synoviocytes.

OBJECTIVE B lymphocytes accumulate in the inflamed joints of patients with rheumatoid arthritis (RA) and are responsible for production of high amounts of (auto)-antibodies. The aim of this study was to determine the capacity of fibroblast-like synoviocytes (FLS) to contribute to the accumulation of synovial fluid (SF) B cells by extending their life span. METHODS Highly purified SF B cells were cultured with FLS in the presence or absence of blocking antibodies directed against cell adhesion molecules, and cell viability was determined after various time intervals by trypan blue, annexin V, propidium iodide, or Hoechst staining. Phenotypic characterization of peripheral blood and SF B cells and FLS was carried out by flow cytometry. RESULTS Synovial B cells, which consist predominantly of memory B cells and plasma cells (PC), undergo spontaneous cell death by apoptosis upon removal from their in vivo environment, despite expression of Bcl-2. Coculture with FLS rescued synovial B cells from apoptosis in a cell contact-dependent manner. Blocking studies using monoclonal antibodies demonstrated a role for the molecular interaction of SF B cells with vascular cell adhesion molecule 1 (VCAM-1; CD106) in FLS-induced survival. The ability of FLS to induce SF B cell survival was not related to the rheumatoid origin since FLS from non-RA patients had similar properties. CONCLUSION These findings indicate a crucial role for FLS in the survival of synovial B cells at the site of inflammation in RA through the interaction with VCAM-1 expressed on FLS. Consequently, memory B cells and PC accumulation arise and persist not only as a result of maturation and recruitment of these cells, but also by active prevention from cell death by the microenvironment.
Assessment of an iPad Loan Program in an Academic Medical Library: A Case Study

An academic medical library expanded its iPad loan service to multiple campus libraries and conducted an assessment of the service. iPads loaded with medical and educational apps were loaned for two-week checkouts from five library campus locations. Device circulation statistics were tracked and users were invited to complete an online survey about their experience. Data were gathered and analyzed for 11 months. The assessment informed the library on how best to adapt the service, including what resources to add to the iPads, and the decision to move devices to campuses with more frequent usage.
Laboratory simulations show diabatic heating drives cumulus-cloud evolution and entrainment

Clouds are the largest source of uncertainty in climate science, and remain a weak link in modeling tropical circulation. A major challenge is to establish connections between particulate microphysics and macroscale turbulent dynamics in cumulus clouds. Here we address the issue from the latter standpoint. First we show how to create bench-scale flows that reproduce a variety of cumulus-cloud forms (including two genera and three species), and track complete cloud life cycles—e.g., from a “cauliflower” congestus to a dissipating fractus. The flow model used is a transient plume with volumetric diabatic heating scaled dynamically to simulate latent-heat release from phase changes in clouds. Laser-based diagnostics of steady plumes reveal Riehl–Malkus type protected cores. They also show that, unlike the constancy implied by early self-similar plume models, the diabatic heating raises the Taylor entrainment coefficient just above cloud base, depressing it at higher levels. This behavior is consistent with cloud-dilution rates found in recent numerical simulations of steady deep convection, and with aircraft-based observations of homogeneous mixing in clouds. In-cloud diabatic heating thus emerges as the key driver in cloud development, and could well provide a major link between microphysics and cloud-scale dynamics.
The Emergence of Glycopeptide-Resistant Enterococcus faecium in a University Hospital in Southwestern Greece

Background: Enterococci and especially glycopeptide-resistant strains (GRE) are widely distributed in the hospital environment, by acquiring resistance determinants and virulence factors. Methods: The study included 48 GRE isolated during a 1-year period from different inpatients in a tertiary hospital in southwestern Greece. Antibiotic susceptibility was determined by the Etest, and the presence of resistance and virulence genes was shown by PCR. Clonal types were identified by pulsed-field gel electrophoresis of SmaI DNA digests. Results: All GRE were multi-resistant of the VanA phenotype, verified by the detection of the gene by PCR. Two major clones were distributed in all hospital wards. The majority of the strains (46 of 48) harbored the esp gene, while 27 GRE expressed also the gelE and/or as genes. Conclusions: The spread of two clones expressing the vanA gene and virulence factors were responsible for the emergence of GRE in the University Hospital of Patras.
Changes in Choroidal Thickness After Panretinal Photocoagulation for Diabetic Retinopathy: A 12-Week Longitudinal Study.

PURPOSE To investigate the longitudinal changes in choroidal thickness of the eyes of diabetic retinopathy patients during 12 weeks after panretinal photocoagulation (PRP). METHODS This prospective, comparative study included 46 eyes undergoing four-session PRP. At baseline and 1, 4, 8, and 12 weeks after completion of the PRP treatments, subfoveal choroidal thickness (SFCT) was measured by using enhanced depth imaging optical coherence tomography. Also measured were central macular thickness (CMT) and best-corrected visual acuity (BCVA). RESULTS The mean SFCT at baseline was 309 ± 77 μm, changing to 323 ± 78 μm, 315 ± 75 μm, 299 ± 68 μm, and 289 ± 71 μm at 1, 4, 8, and 12 weeks, respectively. This constituted a statistically significant increase at 1 week and a significant decrease at 12 weeks. The mean baseline CMT was 294 ± 92 μm, which increased significantly 1 week after PRP to 344 ± 123 μm, remaining higher at 4 weeks (340 ± 117 μm) and 8 weeks (318 ± 100 μm), but subsiding to baseline at 12 weeks (311 ± 96 μm). The mean BCVA at baseline and the last visit were 0.63 ± 0.28 logMAR and 0.53 ± 0.42 logMAR, respectively. There was no significant difference in BCVA between eyes with and without central-involved diabetic macular edema at all time points. Compared with the baseline, the mean BCVA dropped at 1 week and 4 weeks but recovered by 12 weeks. CONCLUSIONS Choroidal thickness decreased 12 weeks after PRP, suggesting that PRP may reduce choroidal vascular permeability or cause atrophy of choroidal vessels over a 12-week period.
CIRCADIAN RHYTHMICITY OF CORTISOL AND BODY TEMPERATURE: MORNINGNESS-EVENINGNESS EFFECTS

The purpose of this study was to describe and compare the circadian rhythm of body temperature and cortisol, as well as self-reported clock times of sleep onset and offset on weekdays and weekends in 19 healthy adult “larks” (morning chronotypes) and “owls” (evening chronotypes), defined by the Horne and Östberg questionnaire. Day-active subjects entered the General Clinical Research Center, where blood was sampled every 2h over 38h for later analysis for cortisol concentration by enzyme immunoassay. Rectal body temperature was measured continuously. Lights were turned off at 22:30 for sleep and turned on at 06:00, when subjects were awakened. The acrophases (peak times) of the cortisol and temperature rhythms occurred 55 minutes (P ≤.05) and 68 minutes (P <.01), respectively, earlier in the morningness group. The amplitude of the cortisol rhythm was lower in the eveningness than in the morningness group (P = n.s.). Subject groups differed on all indices of habitual and preferred timing of sleep and work weekdays and weekends (P =. 05–.001). (Chronobiology International, 18(2), 249–261, 2001)
Pharmacogenetics of Immunosuppressants: Progress, Pitfalls and Promises

Most of the immunosuppressants used in organ transplantation are characterized by a narrow therapeutic index, whereby underdosing is associated with increased risk of rejection episodes and overdosing may exacerbate drug‐related toxicity. Pharmacogenetics—complementary to pharmacokinetics—holds the potential to allow individualized dosing of immunosuppressive agents to optimize their therapeutic actions while minimizing adverse effects. Most of the studies have focused on polymorphisms of genes involved in drug metabolism and distribution, but as of now, only thiopurine‐S‐methyltransferase and cytochrome P 450 3A5 genotypes appear to have sufficiently large influence to have potentialities in guiding drug dosing. This may reflect the fact that available information from other polymorphisms derives almost exclusively from retrospective observations or from studies with important methodological biases. Active investigations aimed at identifying allelic variants of gene encoding for the pharmacologic targets are now ongoing. Recent studies have demonstrated that also donor genotype may play a significant role in immunosuppressive drug pharmacokinetics and pharmacodynamics. As one of the main future tasks, it is mandatory to develop mathematical models able to incorporate multiple gene polymorphisms with pharmacokinetic data and other critical information, providing algorithms able to individualize the best immunosuppressive therapy for each patient before transplantation.
Dietary Health Does Affect Histological Age Assessment: An Evaluation of the Stout and Paine (1992) Age Estimation Equation Using Secondary Osteons from the Rib *

ABSTRACT: An age at death estimation equation that uses rib histological variables presented by Stout and Paine was used to evaluate a skeletal population of individuals with a known age at death and cause of death from either malnutrition or the niacin deficiency disease pellagra. The sample was comprised of 26 autopsied black South Africans. Histological analysis of mounted thin sections involved the microscopic measurement of cortical area and a count of the number of intact and fragmentary secondary osteons for the entire cross‐section of the rib. Rib osteon population density values were then calculated for each case. It was found that this equation under‐aged individuals on average by 29.2 years. Overall, secondary osteon size and Haversian canals tended to be larger than expected, while cortical bone area was less when compared with a control population. The implications of these findings are critical given that many of the skeletal remains examined by forensic anthropologists come from marginalized backgrounds, including malnutrition. This research suggests that measurements based on healthy cases may not be useful in an analysis of individuals with poor diet and health. It is argued that new standards for histological age assessment methods need to be created that account for variation in the health status of individuals examined by forensic anthropologists.
Phosphorylation state of postsynaptic density proteins

The postsynaptic density (PSD) is an electron‐dense structure located at the synaptic contacts between neurons. Its considerable complexity includes cytoskeletal and scaffold proteins, receptors, ion channels and signaling molecules, in line with the role of PSDs in signal transduction and processing. The phosphorylation state of components of the PSD is central to synaptic transmission and is known to play a role in synaptic plasticity, learning and memory. The presence of a range of kinases and phosphatases in the PSD defines potential key players in this context. However, the substrates that these enzymes target have not been fully identified to date. We analyzed the protein composition of purified PSD samples from adult mouse brains by strong cation exchange chromatography fractionation of a tryptic digest followed by nano‐reverse phase liquid chromatography coupled with electrospray ionization–quadrupole time of flight tandem mass spectrometry. This led to the identification of 244 proteins. To gain an insight into the phosphoproteome of the PSD we then purified phosphorylated tryptic peptides by immobilized metal ion affinity chromatography. This approach for the specific enrichment of phosphopeptides resulted in the identification of 42 phosphoproteins in the PSD preparation, 39 of which are known PSD components. Here we present a total of 83 in vivo phosphorylation sites.
Examining Young Recreational Sportswomen's Intentions to Engage in Sun-Protective Behavior: The Role of Group and Image Norms

Researchers examined the sun-protective intentions and behavior of young, Caucasian, Australian sportswomen aged between 17 and 35 years (N = 100). The study adopted a 2 x 2 experimental design, comparing group norms (supportive vs. non-supportive) and image norms (tanned vs. pale) related to sun protection and taking into account group identification with friends and peers in the sport. While no significant findings emerged involving image norms, regression analyses revealed a significant two-way interaction for group norm x identification on recreational sportswomen's intentions to engage in sun protection in the next fortnight. Participants identifying strongly with their group had stronger intentions to engage in sun protection when exposed to a norm reflecting fellow recreational sportswomen engaging in sun-protective actions in comparison to those exposed to a non-supportive group. In addition, while prior intentions to engage in sun protection were not significantly related to sun-protection behavior, post-manipulation intentions after exposure to the sun-protective information that was provided were significantly related to follow-up behavior. Overall, the findings supported the importance of group-based social influences, rather than tanned media images, on sun-protective decisions among young recreational sportswomen and provided a targeted source for intervention strategies encouraging sun safety among this at-risk group for repeated sun exposure.
Basement membrane-dependent modification of phenotype and gene expression in human retinal pigment epithelial ARPE-19 cells.

PURPOSE To use porcine lens capsule (PLC) as basement membrane for ARPE-19 cells and to characterize its effects on cell differentiation and gene expression. METHODS Postconfluent cultures of ARPE-19 cells were established on either porous polyester filters or PLC membranes and characterized by electron microscopy, immunocytochemistry, and transepithelial electrical resistance measurements. Metabolic activity was assessed by measuring phagocytosis of rod outer segments. mRNA populations of ARPE-19 cells grown on polyester and PLC membranes were compared by suppressive subtractive hybridization. Differentially regulated messages were subsequently identified by DNA sequencing and their altered expression confirmed by Northern or virtual Northern blot analysis. RESULTS Culture of ARPE-19 cells on PLC membrane induced the formation of apical microvilli and the ability to phagocytose rod outer segments. These culture conditions also led to enhanced junctional distribution of ZO-1 and occludin, the formation of polarized membrane domains, and a significant increase in transepithelial resistance. Gene expression was significantly altered by growth on PLC membranes and 29 differentially expressed transcripts were identified. CONCLUSIONS Culture of ARPE-19 cells on PLC membranes resulted in a more differentiated phenotype and in expression of a specific set of transcripts encoding protein products that may affect epithelial differentiation, polarity and survival.
Lamotrigine Augmentation Strategy for Patients with Treatment-Resistant Depression

Abstract Objective: To investigate if lamotrigine added to an antidepressant regimen reduces the symptoms of major depression in treatment-resistant patients. Introduction: Charts were retrospectively reviewed for 34 patients (36–63 years of age) with major depressive disorder who received lamotrigine augmentation to the antidepressant regimen for treatment-resistant depression (TRD). Data collection occurred at baseline and at an average of 30 (Time 2), 78 (Time 3), 167 (Time 6), and 356 days (Time 12), thereafter, using a “Medication Visit by MD” scale for collection of target symptom data at each timepoint. Results: Following the addition of lamotrigine to the antidepressant regimen (mean dose of 43, 63, and 113 mg/day for Time 3, Time 6, and Time 12, respectively), a statistically significant reduction of scores was shown as early as Time 2 for target symptoms of depressed mood, loss of interest, anxiety, irritability, (low) energy, and cognitive impairment. The difference from baseline remained statistically significant at Time 3, Time 6, and Time 12 (with the exception of irritability, which was not statistically significant at Time 6). “Patient's response” also reflected statistically significant improvement at each time period compared with baseline. The most common side effect reported and reason for discontinuation was tiredness. Discussion: Because TRD is a clinical condition that can present with severe and disabling symptoms, many clinicians are faced with an urgent need to find relief for their patients. Trying to achieve symptom improvement in a timely manner during a medication change can be challenging and difficult. This can be managed by an augmentation strategy using a psychotropic add-on to an existing medication regimen. Our results show the benefits of lamotrigine augmentation to an antidepressant regimen. Prospective, controlled clinical trials with larger sample size are needed to confirm our results. Conclusion: In this retrospective chart review, augmentation with lamotrigine was a tolerable and efficacious strategy for treating patients with TRD.
C-Terminal Signal Sequence Promotes Virulence Factor Secretion in Mycobacterium tuberculosis

Mycobacterium tuberculosis uses the ESX-1/Snm system [early secreted antigen 6 kilodaltons (ESAT-6) system 1/secretion in mycobacteria] to deliver virulence factors into host macrophages during infection. Despite its essential role in virulence, the mechanism of ESX-1 secretion is unclear. We found that the unstructured C terminus of the CFP-10 substrate was recognized by Rv3871, a cytosolic component of the ESX-1 system that itself interacts with the membrane protein Rv3870. Point mutations in the signal that abolished binding of CFP-10 to Rv3871 prevented secretion of the CFP-10 (culture filtrate protein, 10 kilodaltons)/ESAT-6 virulence factor complex. Attachment of the signal to yeast ubiquitin was sufficient for secretion from M. tuberculosis cells, demonstrating that this ESX-1 signal is portable.
Sustainable Soil Management Practices: Adoption and Its Impact on Farm Income in Ramechhap District, Nepal

This study was carried out to assess the impact of sustainable soil management (SSM) practices in relation to technology adoption and farm income in Ramechhap district of Nepal in 2015. Total 120 sample households were taken (60 SSM practices adopters and 60 non-adopters) using random sampling technique. Primary data were collected through face-to-face interview, focus group discussion, direct observation and key informant interview to gauge the impact using with-without SSM project intervention approach. Descriptive statistics along with independent t-test, chi square test, Probit and income function multi-regression models were used for data analysis. From the cost-benefit analysis, in tomato production, all the variables were found to be significantly different except cost of planting materials. The gross margin, gross income and B: C ratio were also found to be significantly different in tomato production by SSM practices adoption. In beans, potato and cauliflower production, most of the variables were found to be significantly different. The results revealed that, farm income was higher in adopters by significant margin whereas the income from services and remittance was higher in non-adopters than adopters. Probit model revealed that type of family and trainings received were found statistically and positively significant on SSM practices adoption whereas education of household head had negative impact. Income function multi-regression model showed that SSM adoption, male of the respondent, education of the household head and farm size have positively significant on farm income whereas nuclear family type was negatively determinate on farm income. Among the variables, SSM practices adoption was major determinate factor on farm income. If farmer adopted SSM practices, farm income would be about 198 percent higher than among non-adopters. SSM technology has identified an environmentally friendly and improved rural farmers’ income in a sustainable manner in Nepal.
Assessment of Fluorescent In Situ Hybridization and PCR-Based Methods for Rapid Identification of Burkholderia cepacia Complex Organisms Directly from Sputum Samples

ABSTRACT Several species within the Burkholderia cepacia complex (BCC) have emerged as significant opportunistic pathogens of patients with cystic fibrosis (CF). BCC infection is typically associated with a poor clinical prognosis and decreased survival. These factors, combined with the existence of highly transmissible epidemic strains, have resulted in strict segregation of BCC- and non-BCC-infected patients to minimize cross infection. Accurate and rapid diagnosis of infections is essential to enable appropriate patient management. However, the rapidly evolving taxonomy of BCC poses a considerable challenge to diagnostics. In the present study, we assessed a commercially available fluorescent in situ hybridization (FISH) assay (seaFAST Cystic Fibrosis I kit) and a novel rRNA gene-based PCR assay for the rapid identification of BCC-positive sputa, irrespective of the BCC species. We report that, while the FISH assay fails to identify all BCC species, it does identify the majority of species, including the two most clinically relevant species, B. multivorans and B. cenocepacia. The sensitivity of the assay applied to sputum was limited by nonspecific background fluorescence. While sputum processing was optimized to minimize background, the resulting sensitivity for BCC detection was 8 × 105 CFU/ml. In contrast, the novel PCR assay reported herein exhibits 100% sensitivity and specificity for all BCC species and can detect 104 CFU/ml when applied to sputum. This novel rRNA gene-based assay is currently the most sensitive BCC-specific PCR assay for the detection of BCC direct from clinical samples and as such is a valuable addition to the field of BCC diagnostics.