bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of expert rule bases, logistic regression, and non-linear machine learning techniques for predicting response to antiretroviral treatment
Authors: Prosperi Mattia CF , Altmann Andre , Rosen-Zvi Michal , Aharoni Ehud , Borgulya Gabor , Bazso Fulop , Sönnerborg Anders , Schülter Eugen , Struck Daniel , Ulivi Giovanni , Vandamme Anne-Mieke , Vercauteren Jurgen , Zazzi Maurizio 
Published: April 2022

Background The extreme flexibility of the HIV type-1 (HIV-1) genome makes it challenging to build the ideal antiretroviral treatment regimen. Interpretation of HIV-1 genotypic drug resistance is evolving from rule-based systems guided by expert opinion to data-driven engines developed through machine learning methods. Methods The aim of the study was to investigate linear and non-linear statistical learning models for classifying short-term virological outcome of antiretroviral treatment. To optimize the model, different feature selection methods were considered. Robust extra-sample error estimation and different loss functions were used to assess model performance. The results were compared with widely used rule-based genotypic interpretation systems (Stanford HIVdb, Rega and ANRS). Results A set of 3,143 treatment change episodes were extracted from the EuResist database. The dataset included patient demographics, treatment history and viral genotypes. A logistic regression model using high order interaction variables performed better than rule-based genotypic interpretation systems (accuracy 75.63% versus 71.74–73.89%, area under the receiver operating characteristic curve [AUC] 0.76 versus 0.68–0.70) and was equivalent to a random forest model (accuracy 76.16%, AUC 0.77). However, when rule-based genotypic interpretation systems were coupled with additional patient attributes, and the combination was provided as input to the logistic regression model, the performance increased significantly, becoming comparable to the fully data-driven methods. Conclusions Patient-derived supplementary features significantly improved the accuracy of the prediction of response to treatment, both with rule-based and data-driven interpretation systems. Fully data-driven models derived from large-scale data sources show promise as antiretroviral treatment decision support tools.
Rapid decrease of wild-type hepatitis C virus on telaprevir treatment
Authors: Adiwijaya Bambang S , Hare Brian , Caron Paul R , Randle John CR , Neumann Avidan U , Reesink Hendrik W , Zeuzem Stefan , Herrmann Eva 
Published: April 2022

Background Telaprevir (TVR) is a hepatitis C virus (HCV) NS3.4A protease inhibitor that has exhibited antiviral activity in patients with HCV genotype 1 infection. The viral dynamics in patients dosed with TVR were compared with those reported for patients treated with interferon (IFN). Methods The dynamics of wild-type HCV genotype 1 in patients dosed with TVR monotherapy ( n=36) and TVR plus pegylated interferon (PEG-IFN)-α2a ( n=8) were quantified using a biphasic viral dynamic model. Results Patients dosed with either TVR monotherapy or TVR plus PEG-IFN-α2a had median first and second phase decreases of 12 per day and 1.1 per day, respectively. The second phase decrease was approximately 10-fold higher than reported values for IFN-based treatments ( P<0.0001). Patients dosed with TVR plus PEG-IFN-α2a had a median remaining viral production after blockage (1-ε) of -2.37 log10. In patients dosed with TVR mono-therapy, increased TVR dosage of the same schedule was related to better blockage. Conclusions These results suggested that TVR-based regimens for chronic HCV infection will lead to an early and more rapid viral decrease that could potentially result in higher sustained viral response rates as well as offer the potential for a reduced duration of treatment.
Incidence rate and risk factors for loss to follow-up in HIV-infected patients from five French clinical centres in Northern France – January 1997 to December 2006
Authors: Ndiaye Bakhao , Ould-Kaci Karim , Salleron Julia , Bataille Pierre , Bonnevie Frederique , Choisy Philippe , Cochonat Karine , Fontier Clotilde , Guerroumi Habib , Ajana Faiza , Chaud Pascal , Yazdanpanah Yazdan 
Published: April 2022

Background Our goal was to determine the incidence rate and risk factors for loss to follow-up (LTFU) of HIV-infected patients in Northern France. Methods We estimated the incidence rate of LTFU in 1,007 HIV-infected patients under care from January 1997 to December 2006. We then investigated potential risk factors for LTFU at inclusion and during follow-up. Results The incidence of LTFU was estimated to be 3.5 per 100 person-years. Risk factors for LTFU at enrolment in a multivariate Cox model were age <30 years (hazard ratio [HR] 1.66 versus >40 years, 95% confidence interval [CI] 1.04–2.64), transmission by injection drug use (HR 5.26 versus men who have sex with men, 95% CI 2.90– 9.52), no phone number provided (HR 5.4, 95% CI 3.6–8.2), no primary care physician (HR 2.10, 95% CI 1.25–3.52) and sub-Saharan African origin (HR 2.09, 95% CI 1.36–3.22). Patients with CD4+ T-cell counts <200 cells/mm3 (HR 0.49 versus ≥350 cells/mm3, 95% CI 0.32– 0.76) and 200– 349 cells/mm3 at baseline (HR 0.63 versus ≥350 cells/mm3, 95% CI 0.41–0.98) had a decreased risk of LTFU. During follow-up, the risk of LTFU increased when the most recent CD4+ T-cell count was <200 cells/ mm3 (HR 2.06, 95% CI 1.16–3.66), the patient was not on highly active antiretroviral therapy (HAART; HR 4.20, 95% CI 2.66–6.61) and the patient was on HAART but had a detectable viral load (HR 1.92, 95% CI 1.19–3.01). Conclusions Our findings will help clinicians recognize patients who require additional support for retention in care, including younger patients, injection drug users, people of sub-Saharan African origin, patients who are healthier at enrolment and patients who do not adhere to HAART during follow-up.
HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme
Authors: Orrell Catherine , Walensky Rochelle P , Losina Elena , Pitt Jennifer , Freedberg Kenneth A , Wood Robin 
Published: April 2022

Background This study aimed to evaluate HIV type-1 (HIV-1) drug resistance pretreatment and in those failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in South Africa. Methods This was an observational cohort. Genotypic resistance testing was performed on treatment-naive individuals and those failing first-line ART (confirmed HIV-1 RNA>1,000 copies/ml) from public sector clinics in Cape Town (2002–2007). Resistance profiles and mutations relative to timing of known virological failure were examined. Results In total, 230 patients (120 treatment-naive and 110 with virological failure) were included: 98% had clade C virus. Among treatment-naive patients, prevalence of primary resistance was 2.5% (95% confidence interval 0.0–5.3). Three patients had one significant reverse transcriptase mutation: K65R, Y181C and G190A. Among treatment-experienced patients, 95 (86%) individuals had therapy-limiting NNRTI mutations, including K103N (55%), V106M (31%) and Y181C (9%). The M184V mutation was the most common mutation, found in 86 (78%) patients. In total, 10 (9%) patients had the K65R mutation. More individuals tended to develop thymidine analogue mutations when sampling occurred after 6 months of detected therapy failure (10/31 [32%] individuals) compared with those who had genotyping before 6 months (15/79 [19%] patients; P=0.246). Conclusions Prevalence of primary resistance in a sample of ART-naive clade C HIV-1-infected individuals in South Africa was low during the study period. Patients failing first-line ART most often developed resistance to NNRTIs and nucleoside reverse transcriptase inhibitors, the two drug classes used in first-line therapy. Viral load monitoring in this setting is crucial and individual genotypes in those failing first-line therapy should be considered.
Effect of rifampicin-based antitubercular therapy and the cytochrome P450 2B6 516G>T polymorphism on efavirenz concentrations in adults in South Africa
Authors: Cohen Karen , Grant Alison , Dandara Collet , McIlleron Helen , Pemba Lindiwe , Fielding Katherine , Charalombous Salome , Churchyard Gavin , Smith Peter , Maartens Gary 
Published: April 2022

Background Rifampicin induces expression of the cytochrome P450 isoenzyme 2B6 (CYP2B6), which metabolizes efavirenz. The CYP2B6 516G>T polymorphism impairs efavirenz metabolism and occurs more commonly in Africans than in Caucasians. We explored the effect of rifampicin-based antitubercular therapy and the 516G>T polymorphism on efavirenz concentrations in HIV- infected patients in South Africa. Methods Between-patient and within-patient comparisons were made of mid-dosing interval efavirenz plasma concentrations in adults on antiretroviral therapy including efavirenz 600 mg daily, with and without antitubercular therapy. Results There were 142 participants (40 were on antitubercular therapy and 102 were controls), the mean weight was 66 kg. Median efavirenz concentration was 2.4 mg/l (interquartile range [IQR] 1.3–3.1) and 1.8 mg/l (IQR 1.4–4.4) in participants on antitubercular therapy and controls, respectively ( P=0.734). Paired efavirenz concentrations during and after antitubercular therapy in 17 participants were also similar ( P=0.113). Genotyping results were 60 (49%) G/G homozygotes, 46 (38%) G/T heterozygotes and 16 (13%) T/T homozygotes. In a multivariate logistic regression model adjusted for sex, weight and concomitant antitubercular therapy, the 516G>T polymorphism was strongly associated with high (>4 mg/l) efavirenz concentrations: odds ratio (OR) 4.4 (95% confidence interval [CI] 1.3–14.9) for G/T versus G/G and 31.1 (95% CI 6.6–146.6) for T/T versus G/G. High efavirenz concentrations were associated with severe sleep disturbance ( P=0.048). Low (<1 mg/l) efavirenz concentrations were associated with virological failure (OR 12.5, 95% CI 2.7–57.3). Conclusions Efavirenz can be used together with rifampicin-based antitubercular therapy without dose adjustment in this population. The 516G>T polymorphism occurred commonly and was associated with high efavirenz concentrations.
Short-term randomized proof-of-principle trial of TMC278 in patients with HIV type-1 who have previously failed antiretroviral therapy
Authors: Arastéh Keikawus , Rieger Armin , Yeni Patrick , Pozniak Anton , Boogaerts Griet , van Heeswijk Rolf , de Béthune Marie-Pierre , Peeters Monika , Woodfall Brian 
Published: April 2022

Background In vitro, TMC278, an investigational next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), has shown activity against wild-type and NNRTI-resistant HIV type-1 (HIV-1) and a higher genetic barrier to the development of resistance than efavirenz or nevirapine. This Phase II open-label trial evaluated the short-term (7-day) antiviral activity of TMC278 administered at three different doses replacing either the protease inhibitor (PI) or NNRTI of an ongoing failing treatment regimen in HIV-1-infected patients. Methods A total of 36 patients on failing antiretroviral therapy containing either an NNRTI or a PI (with evidence of ≥1 NNRTI resistance-associated mutation at screening for the PI group) and plasma viral load (VL)>1,000 copies/ml were randomized to one of three once-daily TMC278 doses (25 mg, 50 mg or 150 mg) for 7 days, while continuing NRTIs used at screening. The primary efficacy parameter was the change on day 8 in log10 plasma VL from baseline. Results On day 8, median (min, max) changes from baseline in plasma VL were -0.87 (-2.3, 0.0), -0.95 (-1.8, 0.4) and -0.66 (-1.3, -0.2) log10 copies/ml for the 25 mg, 50 mg and 150 mg once-daily TMC278 groups, respectively ( P<0.001–<0.01). Overall, the median change from baseline was -1.19 log10 copies/ml in the PI-substituted therapy group and -0.71 log10 copies/ml in the NNRTI-substituted therapy group. TMC278 was generally safe and well tolerated with no apparent differences in safety among the three dose groups. Conclusions Once-daily TMC278 showed significant antiviral activity against HIV-1 in treatment-experienced patients with NNRTI failure and/or resistance, and was generally safe and well tolerated.
Prevention of cytomegalovirus disease using preemptive treatment after solid organ transplant in patients at high risk for cytomegalovirus infection
Authors: BenMarzouk-Hidalgo Omar Jesus , Cordero Elisa , Martín-Peña Almudena , García-Prado Elena , Gentil Miguel Angel , Gomez-Bravo Miguel Angel , Barrera-Pulido Lydia , Cisneros Jose Miguel , Perez-Romero Pilar 
Published: April 2022

Background The use of pre-emptive or prophylactic treatment to control cytomegalovirus (CMV) replication after solid organ transplant (SOT) remains controversial. The aim of this study was to evaluate whether administration of pre-emptive treatment to control viral replication guided by a highly sensitive diagnostic tool is an effective approach for preventing CMV disease, even in high-risk transplant recipients. Methods Plasma samples from eight SOT patients were tested using antigenaemia and real-time PCR (RT-PCR) assays. Pre-emptive treatment was administered guided by RT-PCR when viral load values were >1,000 copies/ml. Results All patients developed episodes of CMV infection, but none of them developed CMV disease or indirect effects. No patient in this study died or experienced graft rejection. Treatment was needed in 10 replication episodes. At the end of treatment, four had undetectable levels and the other six were cleared 3 weeks later. In 42.6% of tested samples RT-PCR was more sensitive for detecting viral infection. Conclusions Pre-emptive monitoring of SOT patients at high risk for CMV infection protected patients from developing CMV disease during the first 6 months after transplant. The use of this sensitive method for guiding pre-emptive treatment diminished viral load early enough that it did not have consequences for patient health.
Zidovudine Resensitization and Dual HIV-1 Resistance to Zidovudine and Lamivudine in the Delta Lamivudine Roll-Over Study
Authors: Masquelier B , Descamps D , Carrière I , Ferchal F , Collin G , Denayrolles M , Ruffault A , Chanzy B , Izopet J , Buffet-Janvresse C , Schmitt MP , Race E , Fleury HJA , Aboulker JP , Yeni P , Brun-Vézinet F 
Published: April 2022

Objective To study zidovudine resensitization and dual resistance to zidovudine/lamivudine in HIV-1 isolates from nucleoside reverse transcriptase (RT) inhibitor-experienced patients during selective pressure exerted by zidovudine/lamivudine combination therapy. Design and methods HIV-1 isolates from 29 patients receiving zidovudine/lamivudine combination therapy in the Delta roll-over study were analysed at entry and during a 1 year follow-up period for phenotypic susceptibility to zidovudine and lamivudine in the ANRS PBMC assay. The RT gene from codon 20 to 230 and at codon 333 was analysed by nucleotide sequencing of the corresponding isolates. Results HIV-1 isolates from 23 of the 29 patients were phenotypically resistant to zidovudine at baseline; 61% of these patients showed significant zidovudine resensitization during follow-up. The zidovudine IC50 value correlated positively with log10 plasma HIV-1 RNA ( P=0.02) and negatively with the CD4 cell count ( P=0.004). Zidovudine resensitization (related to acquisition of the M184V mutation) was transient, with evolution towards dual resistance to zidovudine and lamivudine in 20 of the 29 patients. The phenotype of certain dually resistant isolates coincided with the emergence of multiple mutations in the 5’ part of the RT gene. Conclusions M184V-mediated zidovudine resensitization of HIV-1 is transient in most patients who are given zidovudine/lamivudine combination therapy when zidovudine resistance has already emerged. The subsequent evolution towards dual phenotypic resistance to zidovudine/lamivudine corresponds to complex genotypic profiles.
Risk Factors of Frailty in Patients with Distal Radius Fractures
Authors: Kang Jeong-Hyun , Hong Seok Woo 
Published: April 2022

Aim The aim of this study was to determine risk factors for the incidence of frailty in patients with distal radius fractures (DRFs). Methods In total, 116 patients (mean age, 66.3 ± 7.7 years) with DRFs were recruited. The participants were categorized into two groups, “frail” and “non-frail,” according to the presence or absence of frailty, respectively. The areal bone mineral densities (aBMDs) of the total hip, femoral neck, and lumbar spine were measured using dual-energy x-ray absorptiometry. The participants’ levels of resilience, depression, anxiety, nutritional intake, oral health-related quality of life, and social support were evaluated by self-reported questionnaires. The participants’ grip strength, gait speed, number of teeth present in their oral cavities, circumference of their upper arms and calves, and serum levels of vitamin D were also assessed. Results The participants in the “frail” group seemed to have lower aBMDs and muscle function and mass than those in the “non-frail” group. There were significant differences in grip strength, calf circumference, gait speed, and aBMD of the total hip, femoral neck, and lumbar spine between the groups. There were also significant differences in the levels of resilience and depression between the groups. A multivariate logistic regression analyses demonstrated that levels of sarcopenia, malnutritional status, and aBMDs of the total hip and femoral neck had significant relationships with the development of frailty in patients with DRFs. Conclusions An interdisciplinary approach involving the management of osteoporosis, sarcopenia, oral health, social relationships, and psychological support would be required for the proper management of DRF patients in preventing frailty.
Comparative study on molecular epidemiology of measles H1 outbreak and sporadic cases in Shandong Province, 2013–2019
Authors: Wang Suting , Wang Changyin , Liu Xiaodong , Liu Yao , Xiong Ping , Tao Zexin , Chen Meng , Xu Qing , Zhang Li , Xu Aiqiang 
Published: April 2022

AbstractBackgroundMeasles caused by measles virus (MeV) is a highly contagious viral disease which has also been associated with complications including pneumonia, myocarditis, encephalitis, and subacute sclerosing panencephalitis. The current study isolated 33 strains belonging to 2 groups, outbreak and sporadic strains, in 13 cities of Shandong province, China from 2013 to 2019. Comparison of genetic characterization among 15 outbreak strains and 18 sporadic strains was performed by analyzing nucleotide sequences of the C-terminal region of N protein gene (N-450).ResultsAll 33 stains belonged to genotype H1. The outbreak strains and sporadic strains distributed crossly in phylogenetic tree. Sequences alignment revealed some interesting G to A transversion which changed the amino acids on genomic sites 1317, 1422, and 1543. The nucleotide and amino acid similarities among outbreak isolates were 98–100% (0–10 nucleotide variations) and 97.7–100%, respectively; They were 97.3–100% and 96.6–100%, respectively for sporadic isolates. Evolutionary genetics analysis revealed that the mean evolution rates of outbreak and sporadic isolates were 1.26 N 10− 3and 1.48 N 10− 3substitutions per site per year separately, which were similar with corresponding data before 2012. Local transmission analysis suggested that there were three transmission chains in this study, two of them originated from Japan. Outbreak cases and sporadic cases emerged alternatively and were reciprocal causation on the transmission chains.ConclusionsOur study investigated the phylogeny and evolutional genetics of MeV during a 7-year surveillance, and compared epidemic and genetic characteristics of outbreak strains and sporadic strains. These results underscore the importance of evolutionary study alongside with sporadic cases in discovering and tracing possible outbreaks, especially in the stage of measles elimination.
The microbiomes of the eyelid and buccal area of patients with uveitic glaucoma
Authors: Shin Jong Hoon , Lee Ji-Woong , Lim Su-Ho , Yoon Byung Woo , Lee Young , Seo Je Hyun 
Published: April 2022

AbstractBackgroundThe microbiome could trigger inflammation leading to epigenetic changes and is involved in the pathophysiology of eye diseases; however, its effect on uveitic glaucoma (UG) has not been fully investigated. This study analysed the differences in eyelid and buccal microbiomes in patients with UG using next-generation sequencing.MethodsThe eyelid and buccal specimens of 34 UG and 25 control patients were collected. The taxonomic composition of the microbiome was obtained via 16S ribosomal DNA sequencing. Diversity and differential gene expression analyses (DEG) determined taxon differences between the microbiomes of UG and control groups.ResultsIn both the eyelid and buccal microbiomes, alpha-diversity was lower in UG patients than controls, while beta-diversity in patients with UG was higher than in controls. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment ofPaenibacillusandDermacoccus(p-value, 1.31e−6and 1.55e−7, respectively) and depletion ofMorganellaandLactococcus(p-value, 6.26e−12and 2.55e−6, respectively) in patients with UG. In the buccal microbiome, taxa such asLactococcuswas significantly depleted (p-value, 1.31e−17), whereasFaecalibacteriumwas enriched in patients with UG (p-value, 6.12e−8).ConclusionsThe eyelid and buccal microbiomes in patients with UG differ from controls, which raises concerns surrounding environmental influences on the pathogenesis of UG. The reducedLactococcusin the eyelid and buccal area suggest that microbiota dysbiosis is associated with UG.
Changes in professional commitment of undergraduate nurse students before and after internship: a longitudinal study
Authors: Zhao Ling , Su Yinhua , Jiang Na , Zhou Fanhua , Liao Li , Liu Yannan 
Published: April 2022

Abstract
Background
Experiencing internship shapes nursing students’ professional commitment and aggravates its changes. However, few studies have been investigated how this changes empirically.

Objectives
The aims of this study are to investigate (a) what are the changes of professional commitment of nursing students before and after the internship? (b) Which of multiple independent variables is the strongest predictor?

Methods
A longitudinal study was conducted with 996 senior undergraduate nursing students (ready to enter clinical practice) in the China universities. The survey was conducted in the spring of 2015 and autumn of 2016. The data were collected by a paper-and-pencil questionnaire. The instruments used included Professional Commitment Scale and Perceived Stress Scale. Analysis of paired t-test and linear regression analysis were performed on the data.

Results
Nursing students showed lower professional commitment (2.79 ± 0.36) than they were (2.92 ± 0.36) before internship. Socio-demographic variables, pre-internship professional commitment and stress perceived during internship predicted 40.1% of the variance in the post-internship commitment.

Discussion
These data summarize the nursing students’ professional commitment changes and the main influential factors that contribute to post-internship professional commitment of undergraduate nursing student. The findings are timely, which indicate that senior nursing students’ professional commitment can be increased by enhancing pre-internship commitment and reducing students’ stress levels during internship.