bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-infected patients
Authors: Soria Alessandro , Porten Klaudia , Fampou-Toundji Jean-Calvin , Galli Laura , Mougnutou Rose , Buard Vincent , Kfutwah Anfumbom , Vessière Aurelia , Rousset Dominique , Teck Roger , Calmy Alexandra , Ciaff Laura , Lazzarin Adriano , Gianotti Nicola 
Published: April 2022

Background The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring. Methods Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped. Results Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure ( P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count ≤50 cells/ mm3 at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm3 (2.10 versus 0.56; P<0.0001; and 1.65 versus 0.76; P=0.005, respectively). A baseline CD4+ T-cell count ≤50 cells/mm3 predicted ≥1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [CI] 2.20-32.14), ≥1 NNRTI mutation (AOR 4.25, 95% CI 1.36-15.48), ≥1 thymidine analogue mutation (AOR 8.45, 95% CI 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% CI 1.49-32.29) and etravirine (AOR 4.72, 95% CI 1.53-15.70). Conclusions Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.
HIV Type-1 Transmission Dynamics in Recent Seroconverters: Relationship with Transmission of drug Resistance and Viral Diversity
Authors: Recordon-Pinson Patricia , Anies Guerric , Bruyand Mathias , Neau Didier , Morlat Philippe , Pellegrin Jean-Luc , Groppi Alexis , Thiébaut Rodolphe , Dabis François , Fleury Hervé , Masquelier Bernard ,   the ANRS CO3 Aquitaine Cohort
Published: April 2022

Background HIV type-1 (HIV-1) has been shown to be frequently transmitted by acutely infected patients. We investigated the relationship between the dynamics of HIV-1 transmission within recently infected patients, the HIV-1 variability and the transmission of antiretroviral drug resistance. Methods We included patients infected between 1996 and 2006, with a plasma sample obtained <18 months after seroconversion and prior to antiretroviral therapy initiation. Reverse transcriptase (RT) and protease sequences were determined by direct population sequencing from plasma samples. Genotypic resistance was interpreted with the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales 2006 algorithm and International AIDS Society–USA list. Phylogenetic analysis (neighbour-joining and maximum likelihood methods) of RT sequences was used to determine the HIV-1 subtype and the interrelationship between sequences. Results Genotypic resistance was detected in 37/263 (14.1%) patients. Patients were infected by HIV-1 clade B in 222 (84%) cases and with non-B subtypes in 41 (16%). A total of 80 (30.4%) RT sequences were segregated in 24 clusters with bootstrap values >98% for 22 clusters. The frequency of grouping in clusters was higher within B sequences compared with non-B sequences (35.1% versus 4.9%; P<2.10-4). Drug-resistant isolates were retrieved in only 3 clusters, but the prevalence of resistance in clustering viruses (10/80, 12.5%) was not different than in isolated sequences. Conclusions The segregation into clusters suggested frequent forward transmission events in patients infected with HIV-1 subtype B, including the possibility of transmission of drug-resistant isolates. These findings warrant increasing prevention efforts and serological screening in the at-risk populations.
Adefovir dipivoxil resistance patterns in patients with lamivudine-resistant chronic hepatitis B
Authors: Santantonio Teresa , Fasano Massimo , Durantel Sandra , Barraud Luc , Heichen Manuela , Guastadisegni Angela , Pastore Giuseppe , Zoulim Fabien 
Published: April 2022

Background Lamivudine (3TC)-resistant chronic hepatitis B patients demonstrated a higher rate of adefovir dipivoxil (ADV) resistance compared with nucleoside-naive patients. This study describes ADV mutation patterns in 3TC-resistant patients treated with ADV+3TC or ADV monotherapy, investigating whether mutations selected during 3TC therapy predispose to ADV resistance. Risk factors for ADV resistance were also evaluated. Methods A total of 60 3TC-experienced patients were treated with (or switched to) ADV monotherapy (30 patients) or ADV+3TC combination therapy (30 patients), and followed for at least 12 months. In all patients the hepatitis B virus reverse transcriptase (RT) region was amplified and directly sequenced before initiating ADV. The RT sequence was reevaluated for virological breakthrough patients and phenotypic analysis was performed for several patients. Results In total, 14 (23%) patients showed virological breakthrough (10/30 on ADV monotherapy and 4/30 on ADV+3TC). ADV resistance mutations (rtA181V/T and rtN236T) were detected alone or in combination for 11/14 patients, whereas novel substitutions were present in 3 patients. Before ADV treatment, apart from 3TC resistance signature mutations, additional changes were found, including the rtA181T mutation, which was already present in 2/14 ADV-resistant patients. Conclusions Although most patients showed virological breakthrough because of the well known rtA181V/T and rtN236T substitutions, more complex patterns were also found. ADV monotherapy, dose reduction and suboptimal virological response after 48 weeks of therapy were significantly associated with ADV resistance.
Kinetics of Productive and Latent HIV Infection in Lymphatic Tissue and Peripheral Blood during Triple-Drug Combination Therapy with or without Additional Interleukin-2
Authors: Stellbrink Hans-Jürgen , Hufert Frank T , Tenner-Racz Klara , Lauer Johannes , Schneider Claus , Albrecht Helmut , Racz Paul , van Lunzen Jan 
Published: April 2022

Objective To study decay rates of productively and latently infected cells in peripheral blood and lymph nodes during triple antiretroviral therapy and the possible impact of interleukin-2 (IL-2) on viral kinetics. Methods: In this non-randomized study, nine antiretro-viral-naive HIV-positive patients received either saquinavir hard gel capsules 2400 mg three times daily (group I; four patients) or saquinavir soft gel capsules 1200 mg three times daily and IL-2 (group II), in both cases together with two nucleoside analogues. Plasma viraemia and lymphocyte subsets were analysed. Axillary lymph nodes were excised before and after 12 weeks of therapy. Lymph node sections were examined by in situ hybridization for HIV RNA, and productively infected cells were counted. Infection rates of FACS-sorted CD3, CD4 lymph node and peripheral blood mononuclear cells were determined by nested DNA PCR. Results Baseline plasma HIV RNA levels ranged from <25 to >1x106 copies/ml and remained undetectable throughout the study in one patient in group I. Plasma viraemia became undetectable after 3 months in four patients (three in group I). Productively infected cells were markedly reduced in the follow-up lymph node specimens. HIV DNA-positive CD4 T cells were reduced in lymphoid tissue and peripheral blood in all six evaluable patients. There were no significant differences between the groups in the clearance rates of plasma virus and of HIV DNA-positive cells. Conclusions Combined antiretroviral therapy rapidly suppressed active HIV replication in plasma and lymphoid tissue. Latently infected cells were cleared at a slower rate. Viral clearance did not appear to be markedly affected by additional IL-2 therapy.
Evaluation of Mixtures of Wild-Type HIV-1 and HIV-1 with Resistance Point Mutations against Reverse Transcriptase Inhibitors
Authors: Villahermosa María Luisa , Contreras Gerardo , Pérez-Alvarez Lucía , Bru Francisco , Medrano Leandro , Delgado Elena , Colomo Concha , Thomson Miguel , Nájera Rafael 
Published: April 2022

The presence of resistance-related mutations in 185 serial proviral DNA samples from 108 HIV-infected patients was monitored using the line probe assay (LiPA). The proportions of wild-type and mutant virus in each sample were determined. Subsequent samples from the same patient were analysed. Resistance mutations were detected in 58 of 108 patients studied (53.7%), 53 of 73 (72.6%) treated with antivirals and 5 of 35 (14.2%) untreated. The mutations were against zidovudine (51), lamivudine (1), zidovudine and lamivudine (4), zidovudine and zalcitabine (1) and zidovudine and didanosine (1). Among the 58 patients with resistant virus, 168 related mutations were observed: 161 to zidovudine (90 in codon 70, 25 in codon 41 and 46 in codon 215), 5 to lamivudine (codon 184), 1 to zalcitabine (codon 69) and 1 to didanosine (codon 74). Mixtures of wild-type and resistant mutants were detected in 76 of 90 (84.4%) mutated at codon 70, 28 of 46 (60.8%) mutated at codon 215 and in 21 of 25 (84%) mutated at codon 41. The mutations at codon 184 were mixtures of wild-type and resistant in 4 of 5 samples. The agreement between LiPA and sequencing was 96.5%. LiPA was more sensitive for the detection of mutants that were present at low frequency. The analysis of sequential samples from the same patient allowed evaluation of the dynamics of appearance of the resistant mutants.
Quality of Life Outcomes of Saquinavir, Zalcitabine and Combination Saquinavir plus Zalcitabine Therapy for Adults with Advanced HIV Infection with CD4 Counts between 50 and 300 Cells/mm3
Authors: Revicki Dennis A , Swartz Cassandra , Wu Albert W , Haubrich Richard , Collier Ann C 
Published: April 2022

Background Benefits in patient health-related quality of life (HRQL) have not yet been demonstrated for combination antiretroviral therapy with protease inhibitors and nucleoside analogues. This double-blind study evaluated zalcitabine or saquinavir monotherapy and combination saquinavir plus zalcitabine therapy on HRQL of human immunodeficiency virus (HIV)-infected adults. Methods 940 HIV-infected patients (CD4 counts 50–300 cells/mm3) who had discontinued zidovudine therapy (for intolerance or treatment failure) were randomized to one of three regimens: zalcitabine 0.75 mg every 8 h; saquinavir 600 mg every 8 h; or combination zalcitabine 0.75 mg plus saquinavir 600 mg every 8 hours. HRQL was measured at baseline, 24 and 48 weeks using the Medical Outcome Study HIV Health Survey (MOS-HIV). The primary endpoints were the physical and mental health summary scores (PHS; MHS) of the MOS-HIV as well as a global visual analogue scale (VAS) score. Results After 24 weeks, the zalcitabine-treated patients demonstrated significantly greater decreases in PHS scores (-4.4±0.6; saquinavir: -1.3±0.6; zalcitabine plus saquinavir: -1.7±0.6; P<0.0001) and MHS scores (-2.2±0.5; saquinavir: -1.0±0.5; zalcitabine plus saquinavir: -0.5±0.5; P=0.032) compared to saquinavir and zalcitabine plus saquinavir treated patients. No differences were observed on the VAS ( P=0.172). Nine of 10 MOS-HIV subscales demonstrated results consistent with the primary endpoints. After 48 weeks, a statistically significant difference between the saquinavir-treated groups and the zalcitabine monotherapy group was observed for PHS scores (zalcitabine: -5.8±0.6; saquinavir: -4.1±0.6; zalcitabine plus saquinavir: -3.5±0.6; P=0.014). Conclusions Saquinavir monotherapy and combination saquinavir plus zalcitabine demonstrated a benefit in HRQL relative to zalcitabine monotherapy in patients with prior zidovudine therapy. The HRQL findings are concordant with improved survival and reduced clinical progression of HIV infection found in this study.
Long-term friction performance monitoring of sliding layer in China railway track system Ⅱ slab track on bridge superstructure
Authors: Li Shunlong , Wang Dedao , Lin Chao , Wang Senrong 
Published: April 2022

The sliding layer is an important component of the China Railway Track System (CRTS) Ⅱ slab track on bridges, and its friction performance has a significant influence on the intensity of track–bridge interaction (TBI). However, the friction performance deterioration of this sliding layer under actual repeated abrasion and harsh environmental conditions is difficult to grasp since structural health monitoring implementation into in-service high-speed railway tracks is extremely hard to be permitted and only limited valuable monitoring datasets are available at present. In this study, the friction performance degradation of the sliding layer was therefore investigated using long-term monitoring data from a multi-span simply supported box girder bridge. First, the friction-induced strain in the base plate was decoupled using the monitored strain at the fixing point and mid-span based on mechanical properties of TBI. Then, structural health monitoring and finite element analysis both indicated an approximately linear relationship between the decoupled friction-induced strain and the temperature of the investigated bridge under certain circumstances. Furthermore, the correspondence between the slope of this linear relationship and the friction coefficient was modelled. Finally, the friction coefficients of the sliding layers on target spans were identified using 4 years of monitoring data and the established correspondence model to analyse the statistical characteristics and degradation performance of the layers. This investigation of the friction performance degradation of the sliding layer in the CRTS II slab track system provides guidance for future maintenance and replacement decision making.
Low-Dose Gamma Radiation Modulates Liver and Testis Tissues Response to Acute Whole Body Irradiation
Authors: Abdel-Aziz Nahed , Haroun Riham A.-H. , Mohamed Hebatallah E. 
Published: April 2022

Aim This work aims to investigate whether the pre-exposure to low dose/low dose rate (40 mGy, 2.2 mGy/hour) γ-radiation as a priming dose can produce a protective effect against the subsequent high one (4 Gy, .425 Gy/minute). Methods Rats were divided into Group I (control), Group II (L); exposed to 40 mGy, Group III (H); exposed to 4 Gy, and Group IV (L+H); exposed to 40 mGy 24 hours before the exposure to 4Gy. The molecular and biochemical changes related to oxidative stress, DNA damage, apoptosis, and mitochondrial activity in the liver and testis were studied 4 hours after irradiation. Results Exposure to 40 mGy before 4 Gy induced a significant increase in the levels of Nrf2, Nrf2 mRNA, TAC, and mitochondrial complexes I & II accompanied by a significant decrease in the levels of LPO, 8-OHdG, DNA fragmentation, TNF-α, caspase-3, and caspase-3 mRNA compared with H group. Conclusion Exposure to low-dose γ-radiation before a high dose provides protective mechanisms that allow the body to survive better after exposure to a subsequent high one via reducing the oxidative stress, DNA damage, and apoptosis-induced early after irradiation. However, further studies are required to identify the long-term effects of this low dose.
Contemporary management and time to revascularization in upper extremity arterial injury
Authors: Chipman Amanda M , Ottochian Marcus , Ricaurte Daniel , Gunter Grahya , DuBose Joseph J , Stonko David P , Feliciano David V , Scalea Thomas M , Morrison Jonathan 
Published: April 2022

Introduction Upper extremity arterial injury is associated with significant morbidity and mortality for trauma patients, but there is a paucity of data to guide the clinician in the management of these injuries. The goals of this review were to characterize the demographics, presentation, clinical management, and outcomes, and to evaluate how time to intervention associates with outcomes in trauma patients with upper extremity vascular injuries. Methods The National Trauma Data Bank (NTDB) Research Data Set for the years 2007–2016 was queried in order to identify adult patients (age ≥ 18) with an upper extremity arterial injury. Patients with brachiocephalic, subclavian, axillary, or brachial artery injury using the 1998 and 2005 versions of the Abbreviated Injury Scale were included. Patients with non-survivable injuries to the brain, traumatic amputation, or other major arterial injuries to the torso or lower extremities were excluded. Results The data from 7908 patients with upper extremity arterial injuries was reviewed. Of those, 5407 (68.4%) underwent repair of the injured artery. The median Injury Severity Score (ISS) was 10 (IQR = 7–18), and 7.7% of patients had a severe ISS (≥ 25). Median time to repair was 120 min (IQR = 60–240 min). Management was open repair in 52.3%, endovascular repair in 7.3%, and combined open and endovascular repairs in 8.8%; amputation occurred in 1.8% and non-operative management was used in 31.6% of patients. Blunt mechanism of injury, crush injury, concomitant fractures/dislocations, and nerve injuries were associated with amputation, whereas simultaneous venous injury was not. There was a significant decrease in the rate of amputation when patients undergoing surgical revascularization did so within 90 min of injury (P = 0.007). Conclusion Injuries to arteries of the upper extremity are managed with open repair, endovascular repair, and, rarely, amputation. Expeditious transport to the operating room for revascularization is the key for limb salvage.
Multilateralism and public support for drone strikes
Authors: Lushenko Paul , Raman Shyam , Kreps Sarah 
Published: April 2022

The use of armed drones has emerged as a principal counterterrorism tool for western militaries, especially France and the United States. While France submits its strikes to the United Nations for approval, the United States typically does not. Does this difference matter for public support and perceptions of legitimacy? To better understand these dynamics, we fielded original survey experiments across nationally representative samples in France and the United States totaling in over 1800 respondents. Our results reflect that international approval is associated with both higher public support and greater perceived legitimacy for a strike. Further, we find that respondents emphasize international law as the basis for support and legitimacy, suggesting a cross-national belief in multilateralism for normative rather than strictly instrumental reasons. These relationships are moderated by the identity of the country conducting a hypothetical strike, implying both an “othering” effect and the emergence of distinct models of strikes across countries that deserve more study amid the ongoing proliferation of armed drones. Video Abstract: https://www.youtube.com/watch?v=YevyaKThae0
Editing TINF2 as a potential therapeutic approach to restore telomere length in dyskeratosis congenita
Authors: Choo Seunga , Lorbeer Franziska K. , Regalado Samuel G. , Short Sarah B. , Wu Shannon , Rieser Gabrielle , Bertuch Alison A. , Hockemeyer Dirk 
Published: April 2022

Abstract
Mutations in the TINF2 gene, encoding the shelterin protein TIN2, cause telomere shortening and the inherited bone marrow (BM) failure syndrome dyskeratosis congenita (DC). A lack of suitable model systems limits the mechanistic understanding of telomere shortening in the stem cells and thus hinders the development of treatment options for BM failure. Here, we endogenously introduced TIN2-DC mutations in human embryonic stem cells (hESCs) and human hematopoietic stem and progenitor cells (HSPCs) to dissect the disease mechanism and identify a gene-editing strategy that rescued the disease phenotypes. The hESCs with the T284R disease mutation exhibited the short telomere phenotype observed in DC patients. Yet, telomeres in mutant hESCs did not trigger DNA damage responses at telomeres or show exacerbated telomere shortening when differentiated into telomerase-negative cells. Disruption of the mutant TINF2 allele by introducing a frameshift mutation in exon 2 restored telomere length in stem cells and the replicative potential of differentiated cells. Similarly, we introduced TIN2-DC disease variants in human HSPCs to assess the changes in telomere length and proliferative capacity. Lastly, we showed that editing at exon 2 of TINF2 that restored telomere length in hESCs could be generated in TINF2-DC patient HSPCs. Our study demonstrates a simple genetic intervention that rescues the TIN2-DC disease phenotype in stem cells and provides a versatile platform to assess the efficacy of potential therapeutic approaches in vivo.
Microwave complex permittivity and anisotropy of conifer wood chips vs moisture content: experiments and modeling
Authors: Rönnow D. , Ottosson P. , Andersson D. 
Published: April 2022

AbstractThe complex microwave permittivity—including anisotropy- of wood chips of softwood has been measured for different moisture contents in the band 0.75 to 2.5 GHz using an ultra-wide band radio transmission technique. The real and imaginary parts increase monotonically with moisture content. The wood chips are oriented by gravity, which gives anisotropic permittivity. The anisotropy ratio of the real part increases from 1.1 to 1.6 with moisture content from 0 to 120%. The anisotropy ratio of the imaginary part is around 2.5 at all moisture contents. Effective medium models were used to model the permittivity. The Bruggeman, and two versions of the Maxwell Garnett model gave good results at low moisture content (below the fiber saturation point). Above the fiber saturation point only the Bruggeman model gave results in agreement with experiments. The difference in model performance suggests that the free water does not follow the wood chips geometry.