Miracle-dz/UniFAR-FTUs huggingface dataset:
Clonal analysis of a human antibody response. II. Sequences of the VH genes of human IgM, IgG, and IgA to rabies virus reveal preferential utilization of VHIII segments and somatic hypermutation.

The construction of mAb-producing cell lines has been instrumental in dissecting the fine specificities and genetic makeup of murine antibodies to exogenous and self Ag. The analysis of the genetic composition of human antibody responses has been hampered by the difficulty in generating human mAb of predetermined class and specificity. Using B lymphocytes from three healthy subjects vaccinated with inactivated rabies virus vaccine, we generated nine human mAb binding to rabies virus and analyzed the genes encoding their VH regions. Six mAb (five IgG1 and one IgA1) were monoreactive and displayed high affinities for rabies virus Ag. The remaining three mAb (IgM) were polyreactive and displayed lower affinities for rabies virus Ag. Seven mAb (3 IgG1, the IgA1, and the three IgM) utilized VH gene segments of the VHIII family. The remaining two IgG1 mAb utilized gene segments of the VHI and VHIV families. Of the seven expressed VHIII family genes, three were similar to the germline VH26c gene, two to the germline 22-2B gene, one to the germline H11 gene, and one to the germline 8-1B gene. The expressed VHI and VHIV genes displayed sequences similar to those of the germline hv1263 and V71-4 genes, respectively. The VH genes of all but one mAb (mAb55) resembled those that are predominantly expressed by C mu + clones in human fetal liver libraries. When compared with known germline sequences, the VH genes of the rabies virus-binding mAb displayed variable numbers of nucleotide differences. That such differences resulted from a process of somatic hypermutation was formally demonstrated (by analyzing DNA from polymorphonuclear neutrophil of the same subject whose B lymphocytes were used for the mAb generation) in the case of the VH gene of the high affinity (anti-rabies virus glycoprotein) IgG1 mAb57 that has been shown to efficiently neutralize the virus in vitro and in vivo. The distribution, mainly within the complementarity determining regions, and the high replacement-to-silent ratio of the mutations, were consistent with the hypothesis that the mAb57-producing cell clone underwent a process of Ag-driven affinity maturation through clonal selection. The D gene segments of the rabies virus-selected mAb were heterogeneous and, in most cases, flanked by significant N segment additions. The JH segment utilization was unbalanced and reminiscent of those of the adult and fetus. Four mAb utilized JH4, two JH6, two JH3, and one JH5; no mAb utilized JH1 or JH2 genes. (ABSTRACT TRUNCATED AT 400 WORDS)
Sedation in the intensive care unit: a systematic review.

CONTEXT Sedation has become an integral part of critical care practice in minimizing patient discomfort; however, sedatives have adverse effects and the potential to prolong mechanical ventilation, which may increase health care costs. OBJECTIVE To determine which form of sedation is associated with optimal sedation, the shortest time to extubation, and length of intensive care unit (ICU) stay. DATA SOURCES A key word search of MEDLINE, EMBASE, and the Cochrane Collaboration databases and hand searches of 6 anesthesiology journals from 1980 to June 1998. Experts and industry representatives were contacted, personal files were searched, and reference lists of relevant primary and review articles were reviewed. STUDY SELECTION Studies included were randomized controlled trials enrolling adult patients receiving mechanical ventilation and requiring short-term or long-term sedation. At least 2 sedative agents had to be compared and the quality of sedation, time to extubation, or length of ICU stay analyzed. DATA EXTRACTION Data on population, intervention, outcome, and methodological quality were extracted in duplicate by 2 of 3 investigators using 8 validity criteria. DATA SYNTHESIS Of 49 identified randomized controlled trials, 32 met our selection criteria; 20 studied short-term sedation and 14, long-term sedation. Of these, 20 compared propofol with midazolam. Most trials were not double-blind and did not report or standardize important cointerventions. Propofol provides at least as effective sedation as midazolam and results in a faster time to extubation, with an increased risk of hypotension and higher cost. Insufficient data exist to determine effect on length of stay in the ICU. Isoflurane demonstrated some advantages over midazolam, and ketamine had a more favorable hemodynamic profile than fentanyl in patients with head injuries. CONCLUSION Considering the widespread use of sedation for critically ill patients, more large, high-quality, randomized controlled trials of the effectiveness of different agents for short-term and long-term sedation are warranted.
Altered luteinizing hormone and prolactin responses to excitatory amino acids during lactation.

We have used excitatory amino acids as tools to elucidate changes in hypothalamic function associated with lactation, focusing on the regulation of luteinizing hormone (LH) and prolactin secretion. In these studies, we have compared the responsiveness to NMA (N-methyl-D,L-aspartate), an agonist for the N-methyl-D-aspartate (NMDA) receptor, with that of kainate, an agonist for another type of glutamate receptor, the kainate receptor. To address the issue of the permeability of the blood-brain barrier to either NMA or kainate, systemic and central administration of the drugs were compared. Four injections of either drug were administered at 10-min intervals to cycling or lactating rats suckling 8 pups. All of these treatment significantly stimulated LH secretion in cycling rats. However, neither systemic injections of NMA (40 mg/kg) or kainate (2.5-3.5 mg/kg), nor third-ventricular administration of NMA (2 micrograms/2 microliters) or kainate (0.2-0.3 micrograms/2 microliters) stimulated LH secretion during lactation. In contrast, LH responses to NMA were observed in lactating animals suckling 2 pups. These data demonstrate that the intensity of the suckling stimulus determines the degree of gonadotropin-releasing hormone (GnRH) neuronal inhibition during lactation. Recovery of the LH response to NMA in animals suckling 8 pups was not observed after treatment with RU 486 to block the effects of progesterone. Thus, the elevated levels of progesterone during lactation do not appear to play a role in inhibiting GnRH neuronal responsiveness. Removal of the 8-pup suckling stimulus for 24 h also did not restore the LH response to NMA. However, treatment with RU 486 and removal of the suckling stimulus for 24 h did restore LH responses to NMA, suggesting that progesterone may play a role in prolonging the recovery of GnRH neuronal responsiveness. The prolactin responses to NMA and kainate changed with the reproductive state of the animal and the site of administration. Central injections of either drug stimulated prolactin release in both cycling and lactating animals. In contrast, whereas systemic administration of NMA stimulated prolactin secretion in cycling animals, kainate had no effect. In the lactating animals, systemic administration of either drug inhibited prolactin secretion. Thus, the difference in the prolactin responses to systemic administration of the drugs may not only be due to a difference in the distribution of kainate and NMDA receptors but also to the steady state level of activity of the prolactin-releasing and -inhibiting factors which is determined by the reproductive state of the animal. (ABSTRACT TRUNCATED AT 400 WORDS)
Understanding the relationship among resources, social media use and hotel performance

Purpose The purpose of this study is to understand the use of social networking sites (SNSs) by hotels. Specifically, drawn upon a resource and capability-based perspective, this study addresses two research questions: (1) the relationship between a hotel’s resources and its use of Twitter and (2) the relationship between the use of Twitter by hotels and their RevPAR. Design/methodology/approach The research data include the hotel chain scales, Twitter user profiles and Twitter activities of the hotel parent companies in the USA and the hotels’ RevPAR. To more clearly understand the effect of the use of SNSs, the study uses two dimensions: electronic word-of-mouth and customer engagement. The two dimensions of the hotels’ Twitter use are calculated based on the data extracted from their Twitter user profiles and historical tweets. For a practical purpose, a social media index (SMI), which combines electronic word-of-mouth and the customer engagement score, was used to determine the overall level of Twitter use by hotels. Findings For RQ1, the results indicate there is a positive association between a hotel’s resources and Twitter use. For RQ2, this study shows there is also a positive association between Twitter use by hotels and their RevPAR. Practical implications Twitter use appears to be associated with hotels’ resources. In turn, Twitter use is positively associated with hotel RevPAR. Thus, hotels should look at Twitter as a potential strategic tool for business operation and attempt to increase their ability to leverage Twitter (and other SNSs) for organizational goals (e.g. sales, promotion, customer service). Originality/value To the authors’ knowledge, this is the first study empirically investigating the use of SNSs by hotels with the data drawn from actual firm-generated content (e.g. tweets, retweets) and hotels’ user profile information from Twitter.
Vesicle fusion in protein transport through the Golgi in vitro does not involve long-lived prefusion intermediates. A reassessment of the kinetics of transport as measured by glycosylation.

The well-characterized cell-free assay measuring protein transport between compartments of the Golgi [Balch, W. E. , Dunphy, W. G. , Braell, W. A. , & Rothman, J. E. (1984) Cell 39, 405-416] utilizes glycosylation of a glycoprotein to mark movement of that protein from one Golgi compartment to the next. Glycosylation had been thought to occur immediately after vesicles carrying the glycoprotein fuse with their transport target. Therefore, the kinetics of glycosylation were taken to reflect the kinetics of vesicle fusion. We previously isolated and raised monoclonal antibodies against a protein (the prefusion operating protein, POP) which is required in this assay at a step after vesicles have apparently been formed and interacted with the target membranes, but long before glycosylation takes place. This was therefore presumed to be a reaction involving targeted but unfused vesicles. Here we report that POP is identical to uridine monophosphokinase, as revealed by molecular cloning. We show that POP is not active in transport per se but instead enhances the glycosylation used to mark transport. This indicated that, contrary to previous assumptions, glycosylation might lag significantly behind vesicle fusion. We directly show this to be true. This alters the interpretation of several earlier studies. In particular, the previously reported existence of a late, prefusion intermediate, the "NEM-resistant intermediate", can be seen to be due to effects on glycosylation and not indicative of true fusion events.
Safety Practice and Professional Exposure to Blood and Blood‐Containing Materials in Serbian Health Care Workers

Safety Practice and Professional Exposure to Blood and Blood‐Containing Materials in Serbian Health Care Workers: Aleksandra Jovic‐Vranes, et al. Institute of Social Medicine, Medical School University of Belgrade, Servia and Montenegro—Safety practice is an important element of workplace safety and quality of health care. To investigate the safety practice and professional exposure to blood and blood‐containing materials during a one‐year period among Health Care Workers (HCWs) in Serbia. Cross‐sectional study of 1559 Serbian HCWs using a self‐administered questionnaire. Mantel‐Haenszel statistics and multiple logistic regression analysis were used in statistical analysis. Fifty‐nine percent (921) of HCWs had skin contact with patients blood, followed by 51% (791) with needle stick injuries, 38% (599) with cuts from sharp instruments, and 34% with contact of eye and other mucosa with patient's blood. Nurses reported professional exposure more often than others. Safety practices consisted of using appropriate barriers (gloves, mask, glasses) in all procedures with patients and were used by 58%, 23%, and 4% of HCWs, respectively. Doctors protected themselves more regularly than others. Hospital protocols for post exposure prophylaxis and safety disposal of medical waste are not common in Serbian health care settings. Safety practices in use were having hospital guidelines for safety practice in hospitals [odds ratio (OR)=1.58, 95% confidence interval (CI)=1.14–2.19], carrying out some form of intervention with risks of infection (OR=3.76, 95% CI=2.57–5.51), and HCWs aware of the professional risk of acquiring infection (OR=1.48, 95% CI=1.28–1.79). This study indicates that emphasis on work practice, attire, disposal systems and education strategies, should be employed to reduce professional exposure to blood and blood containing materials among HCWs in Serbia.
A study on the immunomodulation of polysaccharopeptide through the TLR4-TIRAP/MAL-MyD88 signaling pathway in PBMCs from breast cancer patients

Abstract Context: Polysaccharopeptide (PSP), isolated from the Coriolus versicolor COV-1 strain, has been widely used as an immunoadjuvant for cancer immunotherapy. Objective: The present study was undertaken to examine the role of PSP on the TLR4-TIRAP/MAL-MyD88 signaling pathway in peripheral blood mononuclear cells (PBMCs) from breast cancer patients. Methods: For blockade of TLR4, cells were cultured with or without PSP and anti-TLR4 for 24 h, and then the mRNA and proteins (IL-12, IL-6, and TNF-α) levels in each group were detected by Q-PCR and ELISA. Meanwhile, Q-PCR and western blot analysis were used to detect the expression of TLR4-TIRAP/MAL-MyD88 pathway genes and proteins under the regulation of PSP. Results: As anticipated, the transcription and expression of genes (IL-12 and TNF-α) in the anti-TLR4 group were significantly downregulated compared with the control group, while genes (IL-12, IL-6 and TNF-α) in the PSP group were significantly upregulated. Moreover, the mRNA levels in the PSP+anti-TLR4 group were significantly upregulated compared with the anti-TLR4 group. The results of ELISA were as the same as Q-PCR. Genes, kinase phosphorylation levels and proteins in the TLR4 pathway were significantly upregulated by PSP. Conclusions: Collectively, our study revealed that PSP has an immunoregulatory effect through regulation of the TLR4-TIRAP/MAL-MyD88 signaling pathway.
Molecular characterization and genotypic antimicrobial resistance analysis of Campylobacter jejuni and Campylobacter coli isolated from broiler flocks in northern Italy

Genetic variability and genotypic antimicrobial resistance (AMR) of Campylobacter jejuni and Campylobacter coli from commercial broiler farms were investigated in this study. Campylobacter isolates were genetically characterized by random amplified polymorphic DNA (RAPD)-polymerase chain reaction (PCR) and flaA-SVR and flaB-SVR sequence-based typing. Eight RAPD types were identified in C. jejuni and three in C. coli, while 16 fla profiles were detected among all isolates. Further, 13 flaA-SVR and 13 flaB-SVR alleles were identified. Both typing methods detected a high level of genetic diversity, but fla-SVR typing showed a higher discriminatory power. Indeed, Simpson's index of fla typing (D=0.920) was higher than that of RAPD typing (D=0.814). Moreover, the association of flaA-SVR and flaB-SVR sequence analysis showed a higher discriminatory power compared with the sequence analysis of single loci. Isolates were also analysed by the mismatch amplification mutation assay PCR test and the detection of cmeB gene to determine the occurrence of genetic determinants of AMR to macrolides and fluoroquinolones and multidrug resistance. The A2074C and A2075G mutations in the 23S rRNA gene, the C257T mutation in the gyrA gene, and the cmeB gene were higher in C. coli (19.0%, 67.0%, 100.0% and 100.0%, respectively) than in C. jejuni (0.0%, 3.1%, 48.3% and 48.3%, respectively). This study showed a high degree of genetic diversity and a high prevalence of genetic determinants of macrolide resistance, fluoroquinolone resistance and multidrug resistance among C. jejuni and C. coli isolates from Italian commercial broiler farms.
Human papilloma virus types in the oral and cervical mucosa of HIV-positive South African women prior to antiretroviral therapy.

BACKGROUND To evaluate the prevalence of human papilloma virus (HPV) infection and types in the oral and cervix mucosa of treatment-naïve HIV-1-positive women with CD4 counts less than 300 cells per ml with no HPV-associated oral lesions. METHODS Oral epithelium was harvested from the buccal mucosa and lateral borders of the tongue and cervical samples were collected from the endocervical area of 30 women, 22-64 years old. Cytobrush Plus cell collectors were used for sampling both anatomical areas. Genital pathology, obstetric and gynaecological history, co-morbid disease, hormone therapy, sexual behavior and smoking history were assessed via physical examination and clinical interviews. Special investigations included cervical Papanicolau smears, CD4 counts and HIV-1 viral loads. The linear array HPV test was used to determine HPV genotypes present in the specimens. RESULTS Oral HPV were identified in 20% (n = 6) of the patients, of which two had infection with two HPV types. Genital HPV was found in 96.7% (n = 29) of the women, of which only 14 had cytological abnormalities on Papanicolau smear. Infection with multiple HPV types were present in 93.1% (n = 27) of the patients, with an average of four HPV types per individual. CONCLUSIONS South African HIV-positive women with CD4 counts less than 300 cells per ml have a significant risk of cervical HPV strains and multiple strain infection of the cervix. The prevalence of HPV in normal oral mucosa was low but high-risk types were present. Limited correlation between oral HPV types and those identified in the cervical mucosa was found.
What Drives Policy Attention to Climate Change in China? An Empirical Analysis through the Lens of People’s Daily

Addressing climate change requires sustained effort from all levels of society. Garnering and maintaining the attention of policy elites can be optimized through understanding what drives their attention to climate change. This study goes beyond the focus on democratic regimes to unravel the dynamics of attention to climate change in China. To do this, this study analyzed the content of articles published in People’s Daily from 1985 to 2013. Drawing upon the information processing theory of policy dynamics, we used the time-series regression to examine the effects of information flows of different types on attention to climate change. We found that events such as important international conferences on climate change, domestic attention to environmental issues other than climate change, and pressure from abroad have a significant influence on attention to climate change in China. In addition, these factors were found to have different effects over time, which has received little attention to date.
Effect of Experimental Diabetic Retinopathy on the Non-Image-Forming Visual System

Diabetic retinopathy is a leading cause of blindness. Intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin, are involved in non-image-forming visual responses such as photoentrainment of circadian rhythms and pupilary light reflex. Since several reports indicate that retinal ganglion cells are affected by diabetes, we investigated the non-image-forming visual system in an advanced stage of experimental diabetes in rats induced by streptozotocin. After 15 wks of diabetes induction, clear alterations in the visual function were observed and all animals developed mature cataracts. At this time point, concomitantly with a significant decrease in the number of Brn3a(+) retinal ganglion cells, no differences in the number of melanopsin-containing cells, melanopsin levels, and retinal projections to the suprachiasmatic nuclei and the olivary pretectal nucleus were observed. At high light intensity, afferent pupil light reflex appears to be conserved in diabetic animals. After 15 wks of diabetes induction, a significant decrease in light-induced c-Fos expression in the suprachiasmatic nuclei was found. In diabetic animals, the locomotor activity pattern was conserved, although a delay in the time needed for re-entrainment after a phase delay was observed. In diabetic animals, lensectomy reversed the alterations in c-Fos expression and in the locomotor activity rhythm. These results suggest that the neuronal substrate of the non-image-forming visual system remained largely unaffected at advanced stages of diabetes, and that lensectomy, a relatively easy and safe surgery, could partially restore circadian alterations induced by diabetes. (Author correspondence: ruthr@fmed.uba.ar)
Impact of De Novo Everolimus-Based Immunosuppression on Incisional Complications in Heart Transplantation

Background. The mammalian target of rapamycin inhibitor sirolimus has been associated with an increased incidence of wound-healing complications after de novo heart transplantation. To evaluate the possibility of a similar association for everolimus, we performed a risk-factor analysis to compare the incidence of incision-related wound complications for everolimus with that of other adjunctive drugs. Methods. Safety data from 1009 heart transplant recipients (n=214, receiving azathioprine; n=84, mycophenolate mofetil (MMF); n=711, everolimus) were reviewed in a post hoc analysis from three randomized, multicenter studies—B253 (n=634), A2403 (n=199), and A2411 (n=176)—in which de novo patients received fixed-dose or concentration-controlled everolimus (target trough, 3–8 ng/mL), azathioprine, or MMF with standard- or reduced-exposure cyclosporine A. Incisional complications were analyzed for incidence, type, and severity up to day 90 posttransplant. Results. Incisional-complication events occurred in 25 (11.7%) azathioprine, six (7.2%) MMF, and 87 (12.3%) everolimus patients. Serious incisional complications were more frequent with everolimus (6.9%) compared with azathioprine (4.2%; P=0.197) or MMF (1.2%; P=0.051). In a univariate analysis, patient sex, body mass index (BMI), and diabetes were associated with incisional complications. Only BMI was significantly associated with incisional complications in the subsequent multivariate analysis, with the odds of an incisional-complication event increasing by 12.9% for every 1 kg/m2 increase in BMI (P<0.001). Conclusions. The incidence of incisional complications with everolimus was generally low, although numerically higher compared with MMF. Our analyses provided no strong evidence that everolimus is an independent risk factor for incisional complications. After de novo heart transplantation, patients with a high BMI are at higher risk of incision-related wound complications.