bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rescue Monotherapy in Lamivudine-Resistant Hepatitis B e Antigen-Positive Chronic Hepatitis B: Adefovir versus Entecavir
Authors: Lee Jung Min , Kim Hyung Joon , Park Jun Yong , Lee Chun Kyon , Kim Do Young , Kim Ja Kyung , Lee Hyun Woong , Paik Yong Han , Lee Kwan Sik , Han Kwang-Hyub , Chon Chae Yoon , Hong Sun Pyo , Nguyen Tin , Ahn Sang Hoon 
Published: April 2022

Background The efficacy of adefovir dipivoxil (ADV) or entecavir (ETV) rescue monotherapy has not been directly compared in hepatitis B e antigen (HBeAg)- positive patients with lamivudine (3TC)-resistant chronic hepatitis B (CHB). We compared the efficacy of ADV and ETV rescue monotherapy in HBeAg-positive patients with confirmed genotypic 3TC resistance. Methods A total of 160 HBeAg-positive patients with confirmed 3TC resistance underwent switch therapy (91 ADV and 59 ETV). Parameters assessed included alanine aminotransferase (ALT) normalization, HBeAg serocon-version, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower detection limit <300 copies/ml), virological breakthrough and initial virological response (IVR) at 3 (IVR-3) and 6 (IVR-6) months. Results Following 52 weeks of treatment in the ADV and ETV groups, serum HBV DNA became undetectable in 25 (27.5%) and 21 (35.6%; P=0.292) patients, ALT normalization occurred in 67/78 (85.9%) and 43/47 (91.5%; P=0.351), HBeAg seroconversion in 4 (4.4%) and 1 (1.7%; P=1.000), IVR-3 in 19 (20.9%) and 18 (30.5%), IVR-6 in 40 (44.0%) and 25 (42.4%) and virological breakthrough in 2 (2.2%) and 1 (1.7%; P=1.000) patients, respectively. Conclusions ADV and ETV revealed comparable efficacy after 52 weeks of treatment in HBeAg-positive patients with 3TC resistance. Undetectable HBV DNA in serum following 52 weeks of treatment was predictable with IVR-3 and IVR-6 in both groups.
Inhibition of Epstein–Barr virus replication by small interfering RNA targeting the Epstein–Barr virus protease gene
Authors: Larrat Sylvie , Morand Patrice , Bas Ariane , Vigne Solenne , Crance Jean-Marc , Boyer Véronique , Nicod Sandrine , Grossi Laurence , Buisson Marlyse , Burmeister Wim P , Seigneurin Jean-Marie , Germi Raphaële 
Published: April 2022

Background The Epstein–Barr virus (EBV) protease (PR), coded by the BVRF2 gene, is essential for the maturation of the viral capsid and viral DNA packaging during the late stage of the EBV lytic cycle. Like the other herpesvirus serine PRs, EBV PR could be a target for the inhibition of EBV replication. To date, no data have been reported on the inhibition of EBV PR messenger RNA (mRNA) by small interfering RNA (siRNA). Methods In this study, siRNAs targeting EBV PR were delivered to the epithelial 293 cell line stably transfected with the complete B95-8 EBV episome. EBV DNA and PR mRNA were quantified by real-time PCR in cells and supernatant, protein expression was assessed by immunoblotting, and production of EBV infectious particles in the culture medium was measured by Raji cell superinfection. Results The EBV PR mRNA within the cells was reduced by 73%, the PR protein by 35% and the amount of virus in the cell supernatant was drastically decreased by 86% or 95%, depending on the method. Conclusions The strong effect of the siRNA targeting EBV PR on EBV replication attests to the crucial role played by EBV PR in the production of infectious particles and suggests that targeting this enzyme can be a new strategy against EBV-associated diseases where virus replication occurs.
Combination of baseline parameters and on-treatment hepatitis B virus DNA levels to start and continue patients with lamivudine therapy
Authors: Yuen Man-Fung , Fung James , Seto Wai-Kay , Wong Danny Ka-Ho , Yuen John Chi-Hang , Lai Ching-Lung 
Published: April 2022

Background This study aimed to identify the baseline hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT) levels and on-treatment HBV DNA levels for favourable outcome in patients receiving 5-year lamivudine. Methods Virological, serological and biochemical parameters were assessed in 74 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients at year 5 of therapy. Results Patients with baseline HBV DNA levels <9 log10 copies/ml and ALT≥2x the upper limit of normal (ULN) had a significantly higher chance of HBV DNA suppression to <4 log10 copies/ml (76.5%) and HBeAg seroconversion (82.4%), and a lower chance of YMDD mutations (35.3%) compared with patients with HBV DNA<9 log10 copies/ml and ALT<2xULN and patients with HBV DNA≥9 log10 copies/ml (all P<0.05). All patients with these two baseline parameters plus week 4 HBV DNA<4 log10 copies/ml achieved HBV DNA<35 copies/ml, HBeAg seroconversion and ALT normalization without YMDD mutations at year 5. When these two baseline parameters were combined with week 24 HBV DNA<3 log10 copies/ml, 60%, 80% and 90% of patients had HBV DNA<35 copies/ml, <3 log10 copies/ml and <4 log10 copies/ml, respectively at year 5. Overall, 90% of patients had HBeAg seroconversion and only 10% had YMDD mutations. Conclusions For HBeAg-positive patients with baseline HBV DNA<9 log10 copies/ml and ALT≥2xULN, lamivudine could be initiated. For those with HBV DNA<4 log10 copies/ml at week 4 or <3 log10 copies/ml at week 24, continuation of lamivudine treatment would be more likely to result in a good long-term response.
Cytomegalovirus resistance in solid organ transplant recipients treated with intravenous ganciclovir or oral valganciclovir
Authors: Boivin Guy , Goyette Nathalie , Rollag Halvor , Jardine Alan G , Pescovitz Mark D , Asberg Anders , Ives Jane , Hartmann Anders , Humar Atul 
Published: April 2022

Background The rate of cytomegalovirus (CMV) mutations conferring ganciclovir resistance was assessed in a trial comparing intravenous ganciclovir and oral valganciclovir for treatment of CMV disease in solid organ transplant (SOT) recipients. Methods Viral genes ( UL97 and UL54) conferring ganciclovir resistance were amplified and sequenced from blood samples collected at days 0 (before therapy), 21 (end of induction) and 49 (end of maintenance). Results The overall risk of developing a confirmed or probable ganciclovir resistance mutation during treatment was similar for patients treated with ganciclovir (2.3%) and valganciclovir (3.6%; P=0.51). A persistent viral load at day 21 was associated with a significant risk of ganciclovir resistance by day 49 (odds ratio 11.83; P=0.022). In multivariate analyses, presence of a confirmed ganciclovir resistance mutation was independently associated with virological failure (viral load ≥600 copies/ml) at days 21 and 49. One-third (3/9) of patients with confirmed CMV resistance mutations had recurrent CMV disease. The plasma half-life of confirmed ganciclovir-resistant UL97 mutants was significantly longer than that of wild-type strains, polymorphic variants and strains with mutations of unknown significance ( P=0.045). Multiple UL54 mutations of unknown significance were found in clinical strains. Viral kinetic analysis of these latter strains revealed no effect (negative or positive) on in vivo viral fitness. Conclusions Treatment with oral valganciclovir or intravenous ganciclovir results in similar and low rates of resistance mutations in SOT recipients. Patients with drug-resistant CMV strains often have virological failure and might have unfavourable clinical outcomes.
Dried Fluid Spots for HIV Type-1 Viral Load and Resistance Genotyping: A Systematic Review
Authors: Hamers Raph L , Smit Pieter W , Stevens Wendy , Schuurman Rob , Rinke de Wit Tobias F 
Published: April 2022

Background Dried spots on filter paper made of whole blood (dried blood spots; DBS), plasma (dried plasma spots; DPS) or serum (dried serum spots) hold promise as an affordable and practical alternative specimen source to liquid plasma for HIV type-1 (HIV-1) viral load determination and drug resistance genotyping in the context of the rapidly expanding access to antiretroviral therapy (ART) for HIV-1-infected individuals in low- and middle-income countries. This report reviews the current evidence for their utility. Methods We systematically searched the English language literature published before 2009 on Medline, the websites of the World Health Organization and US Centers for Disease Control and Prevention, abstracts presented at relevant international conferences and references from relevant articles. Results Data indicate that HIV-1 viral load determination and resistance genotyping from DBS and DPS is feasible, yielding comparable test performances, even after storage. Limitations include reduced analytical sensitivity resulting from small analyte volumes (approximately 3.5 log10 copies/ ml at 50 ml sample volume), nucleic acid degradation under extreme environmental conditions, impaired efficiency of nucleic acid extraction, potential interference of archived proviral DNA in genotypes obtained from DBS and the excision of spots from the filters in high-volume testing. Conclusions This technology offers the advantages of a stable specimen matrix, ease of sample collection and shipment. The current sensitivity in drug resistance testing is appropriate for public health surveillance among pretreatment populations. However, consistently improved analytical sensitivity is needed for their routine application in the therapeutic monitoring of individuals receiving ART, particularly at the onset of treatment failure.
Management of Antiretroviral Therapy for HIV Infection: Modelling when to Change Therapy
Authors: D'Amato Rebecca M , D'Aquila Richard T , Wein Lawrence M 
Published: April 2022

Objective To evaluate four strategies for monitoring plasma HIV RNA levels and/or resistance genotypes to decide when to change antiretroviral therapy. The strategies include: (i) 1997 guidelines recommending a therapy switch when plasma RNA exceeds a threshold level; (ii) a viral load policy, using a fixed increase in viral load as the trigger; (iii) a genotype policy, requiring a smaller viral rebound than (ii) and detection of genotypic resistance before switching; and (iv) a proactive policy, switching drug regimens at a predetermined time if viral load has not rebounded. Design and setting A Monte Carlo simulation tracks patients’ viral loads and presence of opportunistic infection during therapy. The model uses clinical and virological data and statistical variation in patient parameters for the evaluation of therapeutic strategies. Main outcome measures: To determine which strategies minimize viral rebound detection delay while maintaining a low (prespecified) probability of switching therapy before rebound. Results 1997 Guidelines and the viral load policy create lengthy delays in detection of rebound, particularly when patients are drug-naive and the detection limit of the viral load assay is 500 copies/ml. A detection limit of 20 copies/ml decreases this delay substantially. Genotyping achieves only minor additional delay reductions. Of the strategies tested, the proactive policy leads to the shortest delays. Conclusions This model indicates that prolonged periods may be required for viral load to rebound to detectable levels following prolonged suppression. Proactive switching produces the best outcome in our model because it may reduce the duration of viral replication under pressure of a failing regimen before detection of viral rebound. This strategy should be evaluated in clinical trials.
Comparison of Once and Twice Daily Dosing of Didanosine in Combination with Stavudine for the Treatment of HIV-1 Infection
Authors: Monno Laura , Cargnel Antonietta , Soranzo Maria Luisa , Chirianni Antonio , Ferraro Teresa , Di Stefano Mariantonietta , Angarano Gioacchino ,   the AI 454-146 Team
Published: April 2022

Objective To compare the antiviral activity, safety and tolerability of didanosine dosed once and twice daily when administered in combination with stavudine dosed twice daily in human immunodeficiency virus type 1 (HIV-1)-infected individuals with little or no previous exposure to antiretroviral drugs. Design Comparative, multicentre, randomized, open-label, short-term study. Patients and Methods Eighty-four HIV-1-infected adults with qualifying baseline CD4 cell counts of 200 to 500 cells/mm3 were included in the study. Of these, 43 patients received once daily didanosine plus twice daily stavudine (group A) and 41 subjects received twice daily didanosine plus twice daily stavudine (group B). The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens of variations in plasma HIV-1 RNA levels from baseline over the first 12 weeks of therapy. Plasma HIV-1 RNA levels, CD4 cell counts and adverse events were monitored. Results: At week 12, median HIV-1 RNA variations were –1.18 log10 copies/ml in group A and –0.88 log10 copies/ml in group B. For patients who were followed up to week 24, median variations of HIV-1 RNA levels from baseline were –1.21 log10 copies/ml in group A and –0.78 log10 copies/ml in group B. The TAD between the two treatment groups for variations from baseline plasma HIV-1 RNA levels over the first 12 weeks was 0.10 log10 copies/ml (95% confidence interval, –0.19 to 0.40), indicating equivalence. Conclusion Once daily didanosine plus twice daily stavudine and twice daily didanosine plus twice daily stavudine are equally effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts. Both regimens are safe and well tolerated.
The analysis on the seismic behavior of L-shaped prefabricated special-shaped CFST with rectangular multi-cell columns
Authors: Wang Lai , Cui Wenbin , Liu Su , Chen Huirong , Chen Haitao 
Published: April 2022

In this paper, a prefabricated special-shaped concrete-filled steel tube (CFST) with rectangular multi-cell column has been subjected to low cyclic reversed loading experiment and finite element (FE) parameter analysis. A total of three full-scale L-shaped specimens were tested under constant axial compression load and transverse cyclic load. The main variable in the experiment was the direction of loading. The results show that the failure mode of the special-shaped column specimen is compression-bending failure. Within 300 mm of the bottom of the column, the steel tube bulges or even cracks, the concrete powder fells and fails to exit the work. Among them, the L-135° specimen has the highest peak bearing capacity while the L-0° specimen has better ductility. The main variables of FE parametric analysis are axial compression ratio, concrete grade, steel tube thickness and loading angle. The analysis results show that the lower axial compression ratio and higher concrete grade are conducive to the improvement of bearing capacity. As the thickness of the steel tube increases, the peak bearing capacity and displacement of the specimen increases but the ductility decreases. The special-shaped column model has better seismic behavior when loaded along various loading angles. The peak bearing capacity of the special-shaped column specimen loaded at 135° is consistent with the test results and compared with the L-45° specimen, its bearing capacity is increased by up to 62.04%, which has better comprehensive seismic behavior.
Characteristics of indoor human-induced particle resuspension under different ventilation conditions
Authors: Sun Zenan , Zheng Shuihua , Fu Yueyao , Chai Min 
Published: April 2022

This study performed a series of experiments to study the characteristics of human-induced particle resuspension under different ventilation conditions. Four modes of supplied airspeed were evaluated: no wind, low wind (2.742 m/s), medium wind (3.849 m/s) and high wind (4.422 m/s). Results show that the steady-state particle concentration can be approximated as a linear function of the airspeed. Human walking and ventilation conditions can have a significant and coupling role in particle behaviours. In particular, human walking provides initial energy for resuspension by disturbing the local fields, and thus increases the resuspension, especially for large particles of 5–10 μm in size. The wind has two competitive effects, that is, supplying energy to keep particles suspended and pushing the particles downward, and the latter becomes dominant when the airspeed was too high. Consequently, intermediate airspeeds can intensify the effect of human walking, and introduce higher peaks of particle concentration in the human-walking stages. As for the particle number density, similar conclusions can be drawn that the effect of ventilation conditions is more pronounced on small particles less than 1 μm while that of human walking is on large particles. This work lays a foundation for revealing the particle resuspension mechanism.
Personal and complex: The needs and experiences related to technology use for people living with dementia
Authors: Liddle Jacki , Worthy Peter , Frost Dennis , Taylor Eileen , Taylor Dubhglas , Beleno Ron , Angus Daniel , Wiles Janet , Angwin Anthony ,   The Florence Project Living Experience Expert Reference Group
Published: April 2022

Background With increasing focus on living well with dementia, technology has been identified as having potential benefits for safety, independence and wellbeing. Despite a large growth in specialised technology development, there has been limited uptake. There is a need to understand the current use and needs related to technology for people living with dementia and their care partners (informal carers). Methods As part of a participatory design study, a qualitative inquiry into technology experiences and needs was undertaken within an interpretive description approach. A cross-disciplinary team including living experience experts (people living with dementia, unpaid care partners) was involved. Semi-structured interviews, including sharing technology locations and supports, were conducted, audio-recorded and transcribed. Key aspects of the technology use experience were constructed. Findings Thirteen people living with dementia and 21 care partners participated in the study. Two core aspects of technology use were identified: Lots of moving parts: the complex context, and A technology cycle: the use and non-use. The findings indicated that the context involved an individual configuration of multiple factors including the user, their technology identity, their supporters, the technology and the environment. The experience is underpinned by shifting foundations created by constantly changing technologies and user characteristics. The cycle of use and non-use identified the processes required to maintain technology engagement. Conclusion The use of technology for people living with dementia is complex and personal. Future technology development, policies and practices need to consider this complexity and the effort required to keep using technology to realise the benefits.
Percutaneous mechanical thrombectomy in the management of early acute superior mesenteric artery embolism
Authors: Yu Zuanbiao , Wang Shuyuan , Lang Dehai , Yin Xiaoliang , Lin Zuodong , Hu Songjie , Wang Di , Xu Qiyang , Hu Jiangnan 
Published: April 2022

Purpose This study was performed to summarize our experience in the management of early-stage acute superior mesenteric artery embolism (ASMAE) by percutaneous mechanical thrombectomy (PMT). Methods The clinical data of 12 patients with early-stage ASMAE treated by PMT in our institution from November 2019 to September 2021 were retrospectively analyzed. The patients had no obvious evidence of bowel infarction as shown by peritoneal puncture and computed tomography angiography. Thrombectomy of the superior mesenteric artery was performed using a 6F AngioJet catheter. Results The emboli were completely removed in 10 (83.3%) patients. Six patients were treated only by the AngioJet device. The other six patients underwent combined treatment with a 6F multipurpose drainage catheter after PMT, including one patient who underwent simultaneous stent implantation. Two patients showed no significant improvement in their symptoms after the operation; one was found to have intestinal necrosis and underwent resection by exploratory laparotomy, and the other died of septic shock 3 days after PMT (further intervention had been discontinued because of complications with multiple underlying diseases). No other PMT-related complications occurred. Only one patient was found to have a pseudoaneurysm of the superior mesenteric artery 1 week after PMT and underwent resection by exploratory laparotomy. The 11 surviving patients were smoothly discharged from the hospital after their symptoms were relieved. At a mean follow-up of 13.2 months, computed tomography angiography showed smooth patency of the superior mesenteric artery. No patients developed serious symptoms during follow-up. Conclusions PMT by the AngioJet device is a minimally invasive, safe, and effective technique to remove ASMAE. Early application of PMT can avoid acute intestinal necrosis. Combining the AngioJet device with a 6F multipurpose drainage catheter might be more helpful to remove residual emboli.
Pre-Operative Medications as a Predictor for Post-Operative Complications Following Geriatric Hip Fracture Surgery
Authors: McDonald Christopher L. , Cohen Brian H. , Medina Pérez Giancarlo , Modest Jacob M. , Kuris Eren O. , Born Christopher 
Published: April 2022

Background Fragility hip fractures are a common orthopedic injury seen in Emergency Departments, with variable outcomes that can range from average to devastating. Currently, few reliable metrics to predict which patients will suffer post-operative complications exist. The aim of this study was to determine if the number and type of pre-operative medications can help predict post-operative complications. Methods A prospectively collected database of hip fracture patients was retrospectively reviewed. Patients with isolated greater trochanteric fractures, periprosthetic fractures, or re-fractures were excluded. Pre-operative baseline characteristics as well as number and type of post-operative complications were reviewed. Any complication within 6 months of surgery and complications that could be directly attributable to the surgical procedure within 2 years of surgery were examined. Major complications (return to the operating room, deep infection, pulmonary, cardiac, and hematologic) and minor medical complications were assessed. A multivariate regression model was performed to identify independent risk factors. Results Three-hundred ninety-one patients were included. A majority were aged 80–90 and female, and lived at home prior to presentation. Overall, 33.7% of patients suffered a complication within a 2-year follow-up period. Mortality rates were 5.4%, 10.0%, and 14.9% over 30 days, 1 year, and 2 years, respectively. After assessing this relationship while controlling for age, sex, injury type, pre-operative residence, ambulatory status, ASA score, and CCI score, the relationship remained significant for both an increased number of complications ( P = .048) and a higher likelihood of having a complication ( P = .008). Cardiovascular ( P = .003), pulmonary ( P = .001), gout ( P = .002), or diabetes ( P = .042) medications were associated with a higher likelihood for experiencing a complication. Conclusions Our study suggests that there is a strong and linear relationship between the number and type of pre-operative medications taken and risk of post-operative complications. This exists for up to 8 medications, at which point further increase does not contribute to an increased risk of complication. This relationship exists even after controlling for confounding variables and can be used by surgeons to better counsel patients and families regarding their specific risk for suffering perioperative complications.