bluuebunny/crossref_metadata_2025_split huggingface dataset:
PC-10 Classical HLA alleles are associated with prevalent and persistent cervical high-risk HPV infection in African women
Authors: Adebamowo Sally , Adeyemo Adebowale , Adebamowo Clement 
Published: April 2019

Background:
Persistent cervical high-risk human papillomavirus (hrHPV) infection is a necessary cause of cervical cancer. However, the genetic factors underlying its risk are not well understood. We hypothesized that immunogenetic variation plays a role in hrHPV infection and persistence. Therefore, we conducted a study of classical HLA alleles and their association with hrHPV infection and persistence.

Methods:
We characterized HPV infection using SPF25/LiPA10 in Nigerian women at baseline and at 6 months follow-up visits in 2014. hrHPV infection was prevalent if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was performed with the Illumina Multi-Ethnic Genotyping Array. Classical HLA alleles were imputed from genotypes in the MHC region using the HLA genotype imputation with attribute bagging (HIBAG) algorithm. HLA association tests were conducted under additive genetic models. P values were adjusted for multiple comparisons with the false discovery rate (FDR) method.

Results:
The mean (±SD) age of the study participants was 38 (±8) years, 48% (247/517) were HIV negative, 24% (125/517) were hrHPV positive at baseline and 10% (51/517) had persistent hrHPV infections. In multivariate regression models adjusted for age, HIV status and the first principal component, DQA1*01:02 (OR 1.46; 95% CI: 1.07 to 1.97; P = 0.03). and DQA1*02:01 (OR 1.89; 95% CI: 1.12 to 3.15; P = 0.03) were positively associated with prevalent but not persistent hrHPV infections, while DQA1*05:01 was negatively associated with prevalent hrHPV (OR 0.45; 95% CI: 0.24 to 0.85; P = 0.03) but positively associated with persistent cervical hrHPV infections (OR 2.46; 95% CI: 1.27 to 4.77; P = 0.04). Four haplotypes (A*30:01 - DQA1*05:01, B*07:02 - C*07:02, B*07:02 - DQA1*05:01 and C*07:02 - DQA1*05:01) were significantly associated with prevalent cervical hrHPV infections and several haplotypes that included the DQA1*05:01 allelic variant (including B*15:10 - DQA1*05:01, DQA1*05:01 - DQB1*02:01 and DQA1*05:01 - DRB1*03:01) were significantly associated with persistent cervical hrHPV infections. Six amino acids located on the DQA1 gene were associated with prevalent but not persistent cervical hrHPV infections.

Conclusions:
This study, the first to investigate the association between HLA alleles and persistent hrHPV risk in African women, has identified important risk alleles that merit further study. Our findings provide new insights into risk factors for hrHPV infection in women of African ancestry.
PC-12 Bone marrow microenvironment-induced miR-300 expression impairs natural killer cell proliferation and anti-tumor activity
Authors: Trotta Rosanna , Silvestri Giovannino , Stramucci Lorenzo , Marcucci Guido , Guimond Martin , Fan Xiaoxuanfan , Baer Maria , Perrotti Danila 
Published: April 2019

Natural killer (NK) cells mediate immune responses against cancer; however, NK cell quantitative and functional defects are features of cancers including chronic myelogenous leukemia (CML). As increased numbers of activated NK cells were found in CML patients in treatment-free remission, the understanding of the molecular events inhibiting NK proliferation and function may lead to the development of NK cell-based therapies against drug-resistant cancer stem cells.
Because altered miRNA expression and inactivation of the protein phosphatase 2A (PP2A) tumor suppressor are also features of cancer, and SET-dependent PP2A inhibition is essential for NK cell function, we hypothesized that increased expression of miR-300, a miRNA with anti-proliferative activity, found inhibited in CML and targeting the PP2A inhibitor SET, accounts for impaired NK cell proliferation/activity.
An initial analysis revealed that miR-300 levels were significantly higher in peripheral blood (PB) CD56+CD3-NK cells from CML patients at diagnosis compared to healthy individuals. As NK cell activity is regulated by the bone marrow microenvironment (BMM), we evaluated whether hypoxic conditions and/or cell-to-cell interaction influence NK cell proliferation and cytotoxic activity by modulating miR-300 intracellular levels.
A marked and significant increase in miR-300 expression was detected in NK-92 and primary CD56+CD3-NK cells exposed to low O2 levels or cultured in the presence of conditioned medium (CM) or exosomes isolated from BM-derived primary mesenchymal stromal (MSC) and HS-5 MSC cells. As expected, increased miR-300 levels correlated with decreased SET levels and markedly reduced NK cell number. Interestingly, miR-300-induced growth inhibition was rescued in NK cells treated with CM/exosomes from HS-5 cells expressing an anti-miR-300 lentivirus. Notably, qRT-PCR indicated that miR-300 was contained in MSC exosomes. Functionally, exposure to MSCs (CM or exosomes) inhibited NK cell IL-12/IL-18-induced IFN-γ production and cytotoxic activity against K562 CML-BC cells in a miR-300-dependent manner. Accordingly, miR-300 lentiviruses and/or CpG-miR-300 oligonucleotides inhibited SET expression, reduced proliferation and suppressed spontaneous cytotoxicity of NK-92 and/or primary NK cells, likely through reactivation of PP2A.
Because BM hypoxic conditions and MSCs significantly contribute to decreased NK cell number and cytotoxic activity through upregulation of miR-300, its genetic or pharmacologic inhibition may result in reactivation of NK cell activity against leukemic stem/progenitor cells.
PF-2 Hepatitis B virus and risk factors among HIV+ and HIV− Nigerian men who have sex with men
Authors: Adeyemi Olusegun , Crowell Trevor , Peel Shelia , Ndembi Nicaise , Shutt Ashley , Baral Stefan , Charurat Man , Nowak Rebecca 
Published: April 2019

Introduction:
Despite the advent of hepatitis B virus infection (HBV) vaccine since 1982, HBV prevalence among men who have sex with men (MSM) ranges between 8% and 18%, differing by population settings and geographic regions of Nigeria. Because of shared risk factors for viral acquisition, HBV is more common in HIV infected individuals and MSM are 2–4 times more likely to be infected with HBV as compared to the general population. We conducted a cross sectional study to estimate the prevalence and risk factors of HBV among HIV-infected and HIV-uninfected MSM.

Methods:
From March 2013 to December 2017, the TRUST/RV368 study recruited MSM into HIV care and treatment services in Abuja and Lagos, Nigeria using respondent driven sampling. Men were screened for Hepatitis B surface antigen using ELISA and confirmed to have active infection with PCR detection of HBV DNA. All participants with HBV and HIV diagnoses at baseline were included in the analysis (n = 717). Differences in demographics and behavioral characteristics were compared using Pearson χ2 test for categorical outcomes. Bivariate and multivariable analyses were conducted using logistic regression models.

Results:
Median age was 24 years (Inter quartile range: 21–27) and the prevalence of HBV was similar between the HIV uninfected and HIV-infected (9% vs 10%, P = 0.60). Among the HIV-infected, prevalence was higher for those not on an ART regimen with anti-HBV activity (tenofovir, lamivudine, or emtricitabine) as compared to those with anti-HBV regimen (11% vs 5%), although not statistically significant (P = 0.12). In the multivariable analysis, HIV infection status was not associated with HBV prevalence (OR = 1.1, 95% CI: 0.6 to 2.0). Any condomless sex at last anal intercourse was associated with a 2-fold higher odds of HBV as compared to those always using condoms (OR = 2.3, 95% CI: 1.3 to 3.5). Those self-reporting as homosexual as compared to bisexual trended towards a higher odds of HBV (OR = 1.5, 95% CI: 0.9 to 2.5). Age, access to health care, concurrent STIs, receptive partnerships, and concurrency were not associated with HBV.

Conclusions:
HBV prevalence was modest in this high risk population and did not differ by HIV status. This lower than expected prevalence may be attributed to ART with anti-HBV activity. Although condomless sex continues to elevate the risk of HBV, reinforcing the need to increase communication and education on HBV and its potential complications.
PG-3 Assessment of internationally-available diagnostic test kits for their suitability to meet manufacturers' claims
Authors: Constantine Niel , Abouhmada Ahmed , Athwal Bhavneet , Saleh Ebtehal 
Published: April 2019

Background:
Diagnostic test kits are used throughout the world as a primary measure to protect the blood supply and provide diagnosis to save lives. The US government purchases large numbers of HIV, syphilis, hepatitis, and other varieties of test kits from a number of manufacturers at considerable expense, and expects them to perform adequately when provided to countries.

Objective:
To assess a large number and variety of rapid test kits, purchased for many countries, to determine if they meet the claims of the manufacturers.

Methods:
From September 2010 through July 2018, a total of 1502 lots of rapid test kits from 16 manufacturers, representing 11 different types of tests from 26 countries, were received for evaluation at the IHV. The performance of each test kit was assessed for performance characteristics using panels of sera (n = 30–160) that included positives (n = 20–80), and negatives (n = 20–80). Greater than 1 false positive or false negative result constituted failure.

Results:
Of the 1502 rapid test kit lots, 1491 (99.3%) successfully passed the evaluation. Of the 11 lots from 5 manufacturers that did not pass, 3 lots were found to produce high background that interfered with reading, 2 lots performed inadequately with high-temperature testing, 4 lots gave 2 false-positive results, and 2 lots gave 2 false-negative results. In one case, the failure resulted in cessation of bulk purchase of test kits by the US Government and removal from WHO's e-catalogue. In another case, the manufacturer acknowledged that their internal lot release results indicated a less than usual level and that it was subsequently addressed.

Conclusions:
In our evaluation of a large number and variety of rapid test kit lots from 16 manufacturers that were sent to or targeted for 26 countries, nearly all performed as expected and met the manufacturers' claims. An evaluation system for the monitoring of test kit performance is essential to identify test kits that may not meet manufacturers' claims.
PG-8 Characterization of pre exposure prophylaxis (PrEP) cascade among Nigerian MSM
Authors: Omari Habib , Ayande Dorcas , Ndo-Ndombi Teclaire , Nowak Rebecca , Crowell Trevor , Baral Stefan , Ndembi Nicaise , Charurat Man 
Published: April 2019

Introduction:
With an estimated HIV incidence of 15.4/100 person years, Nigerian men who have sex with men (MSM) account for one of the highest HIV incidence among members of key populations. Proven HIV biomedical intervention such as Pre exposure Prophylaxis (PrEP) will potentially decrease new HIV infections and likely benefit MSM in this setting. Here we characterize engagement in the HIV PrEP cascade and assess factors associated with PrEP initiation among Nigerian MSM.

Methods:
The TRUST/RV368 cohort employs respondent-driven-sampling (RDS) to recruit MSM into HIV/STI prevention and treatment services in Abuja and Lagos, Nigeria. HIV negative MSM at the Abuja site who completed a survey instrument on awareness and willingness to use PrEP were approached by telephone for PrEP initiation. Follow-up visits were one month after enrollment and quarterly thereafter. Bivariate logistic regression models were used to assess factors associated with PrEP initiation.

Results:
Between March 2013 and July 2018, 428 HIV negative MSM completed the survey instrument on awareness and willingness to use PrEP. Of these, 13 (3%) seroconverted during their initial follow up prior to PrEP initiation and were excluded, and the remaining 415 were included in these analyses. Participants had a median age of 25 (interquartile range [IQR]: 22–29) years. Among 415 HIV negative, 250 (60%) were successfully contacted, 144 (35%) screened and 133 (32%) initiated PrEP (Figure 1). Younger MSM, [≤19 years vs ≥ 25 years (OR 0.6; 95% CI 0.4 to 0.9)] and religion, (Muslims vs. Christians, (OR 0.5; 95% CI 0.3 to 0.9) were associated with decreased odds of PrEP initiation. Exposure to HIV education such as receiving information on HIV prevention in the past 12-months was associated with increased odds of PrEP initiation, (OR 1.7; 95% CI 1.1 to 2.7).

Conclusions:
Engagement in PrEP in this population is relatively low with younger individuals less likely to engage in PrEP. Reinforcing HIV prevention education and facilitating young MSM to engage in PrEP programs is critical in order to prevent onward HIV transmission.
PG-9 Predictors of final HIV status outcome for HIV-exposed infants at 18 months of age in 10 Nigerian states
Authors: Adelekan Babatunde , Harry-Erin Abidemi , Sam-Agudu Nadia , Okposo Martha , Ndembi Nicaise , Mensah Charles , Dakum Patrick , Aliyu Ahmad 
Published: April 2019

Introduction:
There were an estimated 37,000 new child HIV infections in Nigeria in 2016, the highest globally. For Nigeria, 6 week and final mother-to-child transmission of HIV (MTCT) rates are estimated at 13.1% and 23.0%, respectively. The UNAIDS has targeted final MTCT rates of <2% and <5% among non-breastfeeding and breastfeeding infants, respectively. Data on 18-month final outcomes among HIV-Exposed Infants (HEI) in Nigeria is scarce. We evaluated for predictors of HIV status among HEI at 18 months of life in 10 Nigerian states.

Methods:
This retrospective, cross-sectional study collected data from 96 PEPFAR-supported health facilities supported by the Institute of Human Virology Nigeria in 10 Nigerian states between October 2014 and September 2015. Only HEI with a first DNA PCR result at ≥4–6 weeks, and a rapid HIV antibody test result at ≥18 months of age were included. Data including residence, birth weight, breastfeeding status, and maternal ART access were collected for analysis. Multivariate logistic regression (adjusted odds ratios [aORs] evaluated for predictors of HIV test positivity at 18 months.

Results:
A total of 2405 HEI from the 96 facilities were included in the study. Median birthweight was 3 kg (IQR 1.2–6.1), and at final testing was 10 kg (IQR 5.5–15). Of the 2405 HEI negative at first DNA PCR test and tested at ≥18 months, 68 (2.8%) were positive. After a minimum of 18 months of age, 51 (75%) of the 68 HIV-positive infants were alive on ART; 7 (10%) had died, 4 (6%) were lost to follow-up and 6 (9%) had transferred out to other facilities for care. Infant birth weight of ≥2.5 kg (AOR 0.40, P = 0.009), urban residence (OR 0.45, P = 0.008) and exclusive breastfeeding (OR 0.04, P < 0.001) protected against MTCT; maternal non-initiation/utilization of antenatal/in-labor ART (OR 9.59, P < 0.001) correlated with MTCT.

Conclusions:
The final HIV positivity rate of 2.8% in our cohort is lower than the national estimates, which is encouraging. However, this should be interpreted with caution: the HIV status of HEI seen at the study facilities who did not present for early and/or final testing was not available and thus not evaluated. Nevertheless, supported by our findings, we recommend strengthening universal maternal access to ART, ideally in the pre-conception and prenatal stages. This should be prioritized especially for rural women living with HIV. Furthermore, our findings correlate with the nationally-recommended 6-months of exclusive infant breastfeeding. We acknowledge that data from non-presenting HEI are also needed to devise interventions for universal uptake of early and final HIV testing. We expect that as Option B plus is scaled up in Nigeria, more women would access and be maintained on ART through their first and subsequent pregnancies, thereby reducing the gaps in maternal-infant HIV service uptake.
From Tramadol to Methadone
Authors: Friedrichsdorf Stefan J. 
Published: April 2019

Background:
More than 15,000 children die annually in the United States due to an underlying life-limiting disease and the majority of those children experience distressing symptoms, which are not adequately relieved, such as pain and dyspnea. Multimodal analgesia, that is multiple agents, interventions, rehabilitation, psychological modalities, and integrative (nonpharmacologic) therapies, act synergistically for more effective pediatric pain and symptom control with fewer side effects than a single analgesic or modality. However, opioids, such as morphine, fentanyl, hydromorphone, oxycodone, and methadone (in the United Kingdom: diamorphine) remain the mainstay medication to effectively treat pain and dyspnea in children with serious illness.

Methods:
This article reviews commonly used opioids in Pediatric Palliative Care, which a special emphasis on 2 potentially particularly effective multimechanistic opioids: tramadol and methadone.

Results:
Methadone, due to its multimechanistic action profile, is possibly among the most effective and most underutilized opioid analgesics in children with severe unrelieved pain at end of life. However, methadone should not be prescribed by those unfamiliar with its use: Its effects should be closely monitored for several days, particularly when it is first started and after any dose changes.

Conclusions:
Tramadol appears to play a key role in treating episodes of inconsolability in children with progressive neurologic, metabolic, or chromosomally based condition with impairment of the central nervous system. However, the recent 2017 United States Food and Drug Administration (FDA) warning against pediatric use of tramadol does not seem to be based on clinical evidence, and therefore puts children at risk for unrelieved pain or increased respiratory depression.
Blood Loss of Posterior Lumbar Interbody Fusion on Lumbar Stenosis in Patients With Rheumatoid Arthritis
Authors: Xu Shuai , Liang Yan , Wang Jing , Yu Guanjie , Guo Chen , Zhu Zhenqi , Liu Haiying 
Published: April 2019

Study Design.
Case–control study.

Objective.
To compare intraoperative bleeding, drainage, and hidden blood loss (HBL) of posterior lumbar interbody fusion (PLIF) on lumbar spinal stenosis (LSS) in patients with rheumatoid arthritis (RA) and non-RA and identify the risk factors of HBL with RA.

Summary of Background Data.
Exploration on PLIF on LSS and HBL has been reported before while the comparison on total blood loss (TBL), especially HBL of PLIF or PLF on LSS between patients with RA and without RA has not been studied.

Methods.
Sixty-one patients diagnosed LSS with RA (RA group) and 87 matched patients without RA (NRA group) were enrolled and demographic characteristics, RA-related parameters, operation and blood loss information were extracted. Intraoperative blood loss, drainage, and HBL were primary outcomes and secondary measures included operation time, hematocrit (Hct) and hemoglobin (Hb), the number of anemia and blood transfusion.

Results.
There was no statistical difference in total blood loss (TBL), intraoperative blood loss, and postoperative drainage while HBL and the proportion of HBL in TBL were lower in NRA group (P < 0.001 and P = 0.012, respectively). Stratified analysis based on the number of surgical levels suggested HBL and the proportion of HBL in NRA group was superior in long-segment surgery (>2 segments). The secondary outcomes showed the change of Hct was lower in NRA group (P = 0.021) but not the reduction of Hb. In addition, there was no significant difference in neoformative and grade-aggravated anemia, as well as the number of allogeneic blood transfusion and operation time showed Steinbroker classification, disease-modifying anti-rheumatic drugs (DMARDs), hange of Hb and allogeneic blood transfusion were risk factors for HBL with RA.

Conclusion.
There was no difference in TBL, intraoperative bleeding, and operation time, but HBL were higher in RA patients particularly in long-segmental operation. Steinbroker classification, DMARDs, the change of Hb, and allogeneic blood transfusion were independent risk factors for HBL in RA patients.

Level of Evidence: 3
Risk and Prognostic Factors of Low Back Pain
Authors: Halonen Jaana I. , Shiri Rahman , Magnusson Hanson Linda L. , Lallukka Tea 
Published: April 2019

Study Design.
Prospective longitudinal cohort study.

Objective.
To determine the associations for workload and health-related factors with incident and recurrent low back pain (LBP), and to determine the mediating role of health-related factors in associations between physical workload factors and incident LBP.

Summary of Background Data.
It is not known whether the risk factors for the development of LBP are also prognostic factors for recurrence of LBP and whether the associations between physical workload and incident LBP are mediated by health-related factors. We used data from the Swedish Longitudinal Occupational Survey of Health study. Those responding to any two subsequent surveys in 2010 to 2016 were included for the main analyses (N = 17,962). Information on occupational lifting, working in twisted positions, weight/height, smoking, physical activity, depressive symptoms, and sleep problems were self-reported. Incident LBP was defined as pain limiting daily activities in the preceding three months in participants free from LBP at baseline. Recurrent LBP was defined as having LBP both at baseline and follow-up. For the mediation analyses, those responding to three subsequent surveys were included (N = 3516).

Methods.
Main associations were determined using generalized estimating equation models for repeated measures data. Mediation was examined with counterfactual mediation analysis.

Results.
All risk factors at baseline but smoking and physical activity were associated with incident LBP after adjustment for confounders. The strongest associations were observed for working in twisted positions (risk ratio  = 1.52, 95% CI 1.37, 1.70) and occupational lifting (risk ratio  = 1.52, 95% CI 1.32, 1.74). These associations were not mediated by health-related factors. The studied factors did not have meaningful effects on recurrent LBP.

Conclusion.
The findings suggest that workload and health-related factors have stronger effects on the development than on the recurrence or progression of LBP, and that health-related factors do not mediate associations between workload factors and incident LBP.

Level of Evidence: 3