Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic Activation and Carcinogenesis of Tobacco-Specific Nitrosamine N’-Nitrosonornicotine (NNN): A Density Function Theory and Molecular Docking Study

N’-nitrosonornicotine (NNN) is one of the tobacco-specific nitrosamines (TSNAs) that exists widely in smoke and smokeless tobacco products. NNN can induce tumors in various laboratory animal models and has been identified by International Agency for Research on Cancer (IARC) as a human carcinogen. Metabolic activation of NNN is primarily initiated by cytochrome P450 enzymes (CYP450s) via 2′-hydroxylation or 5′-hydroxylation. Subsequently, the hydroxylating intermediates undergo spontaneous decomposition to generate diazohydroxides, which can be further converted to alkyldiazonium ions, followed by attacking DNA to form various DNA damages, such as pyridyloxobutyl (POB)-DNA adducts and pyridyl-N-pyrrolidinyl (py-py)-DNA adducts. If not repaired correctly, these lesions would lead to tumor formation. In the present study, we performed density functional theory (DFT) computations and molecular docking studies to understand the mechanism of metabolic activation and carcinogenesis of NNN. DFT calculations were performed to explore the 2′- or 5′- hydroxylation reaction of (R)-NNN and (S)-NNN. The results indicated that NNN catalyzed by the ferric porphyrin (Compound I, Cpd I) at the active center of CYP450 included two steps, hydrogen abstraction and rebound reactions. The free energy barriers of the 2′- and 5′-hydroxylation of NNN are 9.82/8.44 kcal/mol (R/S) and 7.99/9.19 kcal/mol (R/S), respectively, suggesting that the 2′-(S) and 5′-(R) pathways have a slight advantage. The free energy barriers of the decomposition occurred at the 2′-position and 5′-position of NNN are 18.04/18.02 kcal/mol (R/S) and 18.33/19.53 kcal/mol (R/S), respectively. Moreover, we calculated the alkylation reactions occurred at ten DNA base sites induced by the 2′-hydroxylation product of NNN, generating the free energy barriers ranging from 0.86 to 4.72 kcal/mol, which indicated that these reactions occurred easily. The docking study showed that (S)-NNN had better affinity with CYP450s than that of (R)-NNN, which was consistent with the experimental results. Overall, the combined results of the DFT calculations and the docking obtained in this study provide an insight into the understanding of the carcinogenesis of NNN and other TSNAs.
Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors

Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins.
Hodgkin's Lymphoma survivors' intentions to follow survivorship care plans

The purpose of this study was to determine the attitudes, perceived subjective norms, and perceived behavioral control that Hodgkin’s Lymphoma (HL) survivors had towards survivorship care plans (SCPs) and how those factors impact their intentions to follow a care plan. Participants were HL survivors who had completed treatment. An online self-reporting questionnaire was used to assess demographics and questions related to HL survivor’s attitudes, behavioral intention, perceived subjective norms, and perceived behavioral control. Frequency analysis and correlations were used to describe the participants and their attitudes, perceived subjective norms, and behavioral control in relation to participants’ intentions to follow a SCP. Significant correlations were noted between HL survivors’ intentions to follow a SCP for five years and the attitudes helpful and easy. Perceived behavioral control was noted to be a predictor of intention to follow a SCP. Cancer doctors recommended 32.7 percent of participants to follow a SCP for HL. Almost 60 percent of participants were not currently following a SCP at the time of completing the online questionnaire. Although participants had positive attitudes toward SCPs, attitudes were not found as a predictor of intention. Future research should focus on survivors’ intentions to follow a SCP before, during, and after the survivors follow a SCP to better understand how intentions change. HODGKIN’S LYMPHOMA SURVIVORS’ INTENTIONS iii
Benefits of a Psychosocial Intervention on Positive Affect and Posttraumatic Growth for Chinese American Breast Cancer Survivors: A Pilot Study

Abstract Breast cancer survivors report persistent psychological and physical symptoms, which affect their quality of life and may challenge the recovery process. Due to social, cultural, and linguistic barriers, culturally sensitive care is largely unavailable for Chinese Americans, and their psychological needs are not often addressed. We aimed to investigate whether the Joy Luck Academy (JLA), a psychosocial intervention providing both information and peer support, was associated with positive adjustment among Chinese American breast cancer survivors. Thirty-nine Chinese American breast cancer survivors participated in a pilot psychosocial intervention. The educational materials and lectures were delivered in the participants’ native language of Chinese. All of the educators and mentors shared the same linguistic and cultural background with the participants. The program utilized a community-based participatory research (CBPR) approach to further enhance the cultural sensitivity of the intervention. Participants’ post-traumatic growth and positive affect were assessed before and after the intervention. The JLA showed an improvement in positive affect, and they had a greater appreciation for life. The intervention was found to be feasible, well-accepted, and beneficial for this population. Chinese American breast cancer survivors reported improved psychological health after attending the intervention. These findings encourage the development and implementation of psychosocial interventions for Chinese breast cancer survivors. Similar programs could be integrated into other ethnic or cultural communities.
The State of Cardiovascular Developmental Biology is Strong — Honoring Dr. Roger Markwald and his Seminal Contributions to the Field

In August 2017, the Cardiovascular Developmental Biology Center (CDBC), together with the “Department of Regenerative Medicine and Cell Biology (RMCB) at the Medical University of South Carolina (MUSC), organized their 13th Annual CDBC Symposium. During this special event, which was organized in collaboration with The Anatomical Record, the unique and important contributions of Dr. Roger Markwald (known to all of us as Roger) to the field of cardiovascular research were celebrated. Fifteen leading investigators in the field presented their ideas and reported results of their studies to an audience that included many familiar faces from Roger's past and present. This group consisted of established investigators from around the world as well as young and upcoming scientists from local institutions. In their presentations, the platform speakers emphasized the significance of Roger's scientific contributions and advice to their professional development and career. In this Special Issue of The Anatomical Record, we assembled a collection of invited papers written by several attendees of the symposium. The issue also contains a number of articles written by colleagues who, for one reason or the other, were not able to attend the meeting, but expressed their desire to contribute to this special “festschrift” of The Anatomical Record in honor and recognition of Roger's amazing career. Anat Rec, 302:14–18, 2019. © 2018 Wiley Periodicals, Inc.
Early Seroreversion After 2 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus–Positive Patients: Incidence and Associated Factors

Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)‐positive patients. Incidence of and associated factors with early seroreversion (loss of seroresponse) among HIV‐positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV‐positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case‐control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow‐up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow‐up of 611 days. In a case‐control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio [aOR], 1.703; 95% confidence interval [CI], 1.292‐2.323, per 10‐kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067‐7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020‐0.154) and 0.837 (95% CI, 0.704‐0.979, per 100‐cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two‐dose HAV vaccination occurred in 3.9% of HIV‐positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV‐positive adults with predictors of early seroreversion.
Characteristics of Campylobacter, Salmonella Infections and Acute Gastroenteritis in Older Adults in Australia, Canada, and the United States.

Background The early detection of enteric infections in older adults is challenging because typical signs and symptoms of disease may be less common, absent, or overlooked. Understanding illness characteristics of enteric infections among older adults could improve the timeliness and accuracy of clinical diagnoses, thereby improving patient outcomes and increasing cases reported to surveillance. Methods This study describes illness characteristics (percentage reporting bloody diarrhea, fever, vomiting, abdominal pain, percentage hospitalized, duration of hospitalization, and duration of illness) among older adults (≥65 years) with acute gastroenteritis and culture-confirmed Campylobacter and nontyphoidal Salmonella infections in Australia, Canada, and the United States, and compares these characteristics with those among younger adults (25-64 years) and children (<5 years, 5-24 years). Results A significant negative correlation was found between all symptoms and increasing age group, except for bloody diarrhea in cases of acute gastroenteritis. Adults ≥85 years old reported bloody diarrhea in only 9% of nontyphoidal Salmonella and 4% of Campylobacter infections, compared with 59% and 55% among children aged <5 years. Conversely, a greater percentage of older adults (≥65) than younger persons (<5, 5-24, 25-64) reported being hospitalized, with an increasing linear relationship in age groups 65 years and older. Conclusions Although older adults are more likely to have severe illness and be hospitalized, this study found that the proportion of persons reporting symptoms typically associated with enteric infections decreases with age. These findings have implications for clinical recognition and treatment of gastrointestinal illness, as well as for public health research.
Push and pull factors of nurses' intention to leave.

AIM To expand knowledge about the predictive factors of nurses' intention to leave their job and consequently to turnover. BACKGROUND Nurse turnover is costly and negatively influences quality of care. Understanding the association between intention to leave and modifiable features of hospital organisation may inform strategies to reduce turnover. METHODS A cross-sectional survey of 3,667 medical and surgical nurses was conducted in Italy. Measures included intention to leave; work environment; burnout; job satisfaction; and missed care using the RN4CAST instruments. Descriptive, logistic regression analysis was used. RESULTS Due to job dissatisfaction, 35.5% of the nurses intended to leave their current job, and of these, 33.1%, the nursing profession. Push factors included the following: understaffing, emotional exhaustion, poor patient safety, performing non-nursing care and being male. Pull factors included the following: positive perception of quality and safety of care, and performing core nursing activities. CONCLUSION The present study expands knowledge about the predictive factors of nurses' intention to leave their job and consequently to turnover, which is one of today's major issues contributing to the shortage of nurses. IMPLICATIONS FOR NURSING MANAGEMENT Nurses' intention to leave their job is the consequence of a poor work environment, characterized by factors such as understaffing and performance of non-nursing activities.
Immunity and Inflammation in Atherosclerosis

There is now overwhelming experimental and clinical evidence that atherosclerosis is a chronic inflammatory disease. Lessons from genome-wide association studies, advanced in vivo imaging techniques, transgenic lineage tracing mice, and clinical interventional studies have shown that both innate and adaptive immune mechanisms can accelerate or curb atherosclerosis. Here, we summarize and discuss the pathogenesis of atherosclerosis with a focus on adaptive immunity. We discuss some limitations of animal models and the need for models that are tailored to better translate to human atherosclerosis and ultimately progress in prevention and treatment.
The Translation of Graphemes in Anime in Its Original and Fansubbed Versions

Anime, Japanese animation, is massive, with “60% of the animation in the world made in Japan” (Goto-Jones 2009, 3). Anime occasionally makes an innovative use of graphemes on screen, but this has not been studied so far. This study, then, describes and analyses how graphemes have been translated in anime, presenting a series of cases, but concentrating on three particular releases: Gurren Lagann, Kill la Kill, and Tōkyō Godfathers, products that feature a frequent and innovative use of graphemes in its anime. These graphemes are categorised into two types: (1) the ones that are part of the original anime and (2) the graphemes added in fansubbed anime. Much anime is fansubbed (subtitled by fans), and these fans are not constrained by the industry’s rules, meaning that they have complete liberty in subtitling, allowing for really creative forms of subtitling. Even if this freedom can sometimes be taken to the extreme—with subtitles covering the entire screen—fansubs have shown creative subtitling solutions, specially in the case of graphemes that cover a great part of the screen. After describing and analysing these graphemes and how they have been subtitled, this article concludes that, even if fansubs can frequently be excessive, they are at the fore of creativity, and present better solutions than official subtitles in the translation of graphemes in anime.
Sequential intrathecal injection of fentanyl and hyperbaric bupivacaine at different rates: does it make a difference? A randomized controlled trial

Background Previous studies have shown that sequential intrathecal injection of fentanyl and hyperbaric bupivacaine for cesarean section (CS) anesthesia provides a superior anesthetic effect than use of bupivacaine alone, and prolongs postoperative analgesia. Herein, we investigated whether rapid intrathecal injection of fentanyl followed by slow injection of hyperbaric bupivacaine affects the duration of postoperative analgesia, the effectiveness of anesthesia, and hemodynamic status. Methods Fifty-six parturients with American Society of Anesthesiologists physical status I or II, aged 18–40 years, and scheduled to undergo elective CS were randomly assigned to 2 groups of 28 patients each. The normal sequential group received sequential intrathecal injections of fentanyl and hyperbaric bupivacaine at the same rate, each with a 5 ml syringe. The rapid sequential group received a rapid intrathecal injection of fentanyl with an insulin syringe, followed by a slow injection of hyperbaric bupivacaine with a 5 ml syringe. The onset of sensory block, the timing of the first rescue analgesia, the doses of rescue analgesics, the degree of postoperative pain, the onset and duration of motor block, the incidence and duration of hypotension, and spinal anesthesia-related complications were recorded. Results While both approaches had comparable spinal anesthesia-related complications, incidence and duration of hypotension, and doses of ephedrine, the rapid sequential group exhibited a more rapid onset of sensory block, a higher sensory level, and more prolonged postoperative analgesia. Conclusions Rapid sequential injection of fentanyl and hyperbaric bupivacaine produced superior anesthesia and more prolonged postoperative analgesia than sequential injections of both at the same rate.
Conclusiveness of Cochrane Reviews in physiotherapy: a systematic search and analytical review

Numerous Cochrane Reviews (CRs) in the field of physiotherapy have been published, but their conclusiveness has not been investigated. The purpose of this study was to provide an overview and describe the conclusiveness of evidence from CRs regarding physiotherapy. We conducted a systematic search using the Cochrane Database of Systematic Reviews in the Cochrane Library from 2008 through 2017 in the field of physiotherapy, the Physical Rehabilitation Evidence Database, and the CRs list on the Cochrane Rehabilitation website. Reviewers extracted the following data: year of publication, editorial group, number of articles meeting the criteria, number of patients enrolled, conclusiveness, and need for additional studies. Linear regression was used to determine whether the percentage of conclusive reviews was affected by the year of publication. Reviewers found 283 CRs in the field of physiotherapy, and only 16 (5.7%) of which were conclusive. The number of trials and participants enrolled in conclusive reviews were significantly higher than those in inconclusive reviews (P < 0.001). The percentage of conclusive reviews was significantly correlated with year of publication (P = 0.03). Almost all reviews recognized the need for additional studies. Most CRs in physiotherapy are inconclusive, and most emphasize the need for further research. The ability of a Cochrane Review to reach a conclusion is affected by the cumulative patient sample size and number of trials included in the analysis.
Examining diabetic heel ulcers through an ecological lens: microbial community dynamics associated with healing and infection

Purpose. While some micro‐organisms, such as Staphylococcus aureus, are clearly implicated in causing tissue damage in diabetic foot ulcers (DFUs), our knowledge of the contribution of the entire microbiome to clinical outcomes is limited. We profiled the microbiome of a longitudinal sample series of 28 people with diabetes and DFUs of the heel in an attempt to better characterize the relationship between healing, infection and the microbiome. Methodology. In total, 237 samples were analysed from 28 DFUs, collected at fortnightly intervals for 6 months or until healing. Microbiome profiles were generated by 16S rRNA gene sequence analysis, supplemented by targeted nanopore sequencing. Result/Key findings. DFUs which failed to heal during the study period (20/28, 71.4 %) were more likely to be persistently colonized with a heterogeneous community of micro‐organisms including anaerobes and Enterobacteriaceae (log‐likelihood ratio 9.56, P=0.008). During clinically apparent infection, a reduction in the diversity of micro‐organisms in a DFU was often observed due to expansion of one or two taxa, with recovery in diversity at resolution. Modelling of the predicted species interactions in a single DFU with high diversity indicated that networks of metabolic interactions may exist that contribute to the formation of stable communities. Conclusion. Longitudinal profiling is an essential tool for improving our understanding of the microbiology of chronic wounds, as community dynamics associated with clinical events can only be identified by examining changes over multiple time points. The development of complex communities, particularly involving Enterobacteriaceae and strict anaerobes, may be contributing to poor outcomes in DFUs and requires further investigation.
Evidence of reduced viremia, pathogenicity and vector competence in a re‐emerging European strain of bluetongue virus serotype 8 in sheep

The outbreak of bluetongue virus (BTV) serotype 8 (BTV-8) during 2006-2009 in Europe was the most costly epidemic of the virus in recorded history. In 2015, a BTV-8 strain re-emerged in France which has continued to circulate since then. To examine anecdotal reports of reduced pathogenicity and transmission efficiency, we investigated the infection kinetics of a 2007 UK BTV-8 strain alongside the re-emerging BTV-8 strain isolated from France in 2017. Two groups of eight BTV-naïve British mule sheep were inoculated with 5.75 log10TCID50 ml−1 of either BTV-8 strain. BTV RNA was detected by 2 dpi in both groups with peak viremia occurring between 5-9 dpi. A significantly greater amount of BTV RNA was detected in sheep infected with the 2007 strain (6.0-8.8 log10 genome copies mL−1) than the re-emerging BTV-8 strain (2.9-7.9 log10 genome copies mL−1). All infected sheep developed BTV-specific antibodies by 9 dpi. BTV was isolated from 2 dpi to 12 dpi for 2007 BTV-8-inoculated sheep and from 5 to 10 dpi for sheep inoculated with the remerging BTV-8. In Culicoides sonorensis feeding on the sheep over the period 7-12 dpi, vector competence was significantly higher for the 2007 strain than the re-emerging strain. Both the proportion of animals showing moderate (as opposed to mild or no) clinical disease (6/8 vs 1/8) and the overall clinical scores (median 5.25 vs 3) were significantly higher in sheep infected with the 2007 strain, compared to those infected with the re-emerging strain. However, one sheep infected with the re-emerging strain was euthanized at 16 dpi having developed severe lameness. This highlights the potential of the re-emerging BTV-8 to still cause illness in naïve ruminants with concurrent costs to the livestock industry. Summary The re-emerging Bluetongue virus serotype 8 still presents a threat to naïve ruminants in Europe despite reduced virulence