bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co‐infected patients from Western Africa
Authors: Boyd A. , Moh R. , Maylin S. , Abdou Chekaraou M. , Mahjoub N. , Gabillard D. , Anglaret X. , Eholié S. P. , Delaugerre C. , Danel C. , Zoulim F. , Lacombe K. ,   for the ANRS 12240 VarBVA study
Published: April 2018

SummaryThe nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)‐infected patients. Whether this mutation affects the therapeutic course of HIV‐HBV co‐infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)‐naïve HIV‐HBV co‐infected patients from Côte d'Ivoire, initiating ARV‐treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV‐DNA, hepatitis B “e” antigen (HBeAg) seroclearance (in HBeAg‐positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV‐initiation, median HBV‐DNA was 6.04 log10 copies/mL (IQR = 3.70‐7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg‐negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24‐36). Cumulative proportion of undetectable HBV‐DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV‐DNA levels and anti‐HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti‐HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.
Serum NGAL can act as an early renal safety biomarker during long‐term nucleos(t)ide analogue antiviral therapy in chronic hepatitis B
Authors: Carey I. , Byrne R. , Childs K. , Horner M. , Bruce M. , Wang B. , Dusheiko G. , Agarwal K. 
Published: April 2018

SummaryTubular renal toxicity is a side‐effect of long‐term therapy with nucleos(t)ide analogue(s) (NA) in chronic hepatitis B (CHB). There are no established surrogate markers in plasma of early NA‐related toxicity. Neutrophil gelatinase‐associated lipocalin (NGAL) is a protein produced by tubular cells following renal damage. We aimed therefore to retrospectively compare conventional renal markers (estimated glomerular filtration rates (eGFR) and urinary protein/creatinine ratio uPCR) with a sensitive biomarker (NGAL) in CHB patients on long‐term NA therapy and assess the ability of new markers to predict NA‐related renal toxicity (new onset of nonalbumin proteinuria). A total of 192 naïve CHB patients (median age 41 years, 78% males, 25% HBeAg+, 35% cirrhosis) were NA treated for at least 5 years (median 8.34 years, range 5.54‐11.1 years). The eGFR and uPCR were compared at baseline and last clinical visit with serum NGAL concentrations measured by ELISA at same time‐points and assessed according to the presence/absence of nonalbumin proteinuria at last visit. While baseline and last visit eGFR were similar (median:78 vs 84 mL/min), serum NGAL concentrations increased during therapy (median:9.4 vs 16.4 ng/mL, P < .05). The proportion of patients with proteinuria (uPCR > 15) increased between baseline and last visit (4.6% vs 21.4%, P < .05), with 30 (16%) patients having de novo nonalbumin proteinuria at last visit. High baseline NGAL concentrations were exclusive to patients with de novo nonalbumin proteinuria (median:31.7 vs 7.8 ng/mL, P < .01) and baseline NGAL levels >25 mg/mL were predictive of nonalbumin proteinuria at last visit (AUROC = 0.813). In conclusion, serum NGAL can act as a surrogate marker of early renal injury (de novo nonalbumin proteinuria) in CHB on long‐term NA therapy.
Early development of de novo hepatocellular carcinoma after direct‐acting agent therapy: Comparison with pegylated interferon‐based therapy in chronic hepatitis C patients
Authors: Yoo S. H. , Kwon J. H. , Nam S. W. , Kim H. Y. , Kim C. W. , You C. R. , Choi S. W. , Cho S. H. , Han J.‐Y. , Song D. S. , Chang U. I. , Yang J. M. , Lee H. L. , Lee S. W. , Han N. I. , Kim S.‐H. , Song M. J. , Hwang S. , Sung P. S. , Jang J. W. , Bae S. H. , Choi J. Y. , Yoon S. K. 
Published: April 2018

SummaryPatients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct‐acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct‐acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct‐acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct‐acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child‐Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha‐fetoprotein level >9.5 ng/mL at the time of end‐of‐treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768‐2882.473) and in patients treated with direct‐acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417‐1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct‐acting antivirals and was associated with the serum alpha‐fetoprotein level at the time of end‐of‐treatment response.
Clinical findings and diagnostic procedures in 270 small ruminants with obstructive urolithiasis
Authors: Riedi Anna‐Katharina , Knubben‐Schweizer Gabriela , Meylan Mireille 
Published: April 2018

BackgroundDetails of the clinical signs of obstructive urolithiasis in male small ruminants have not been documented in a large population.ObjectiveTo describe the clinical presentation and diagnostic procedures in a large group of small ruminants with urolithiasis.AnimalsTwo hundred and seventy small ruminants (158 sheep and 112 goats).MethodsRetrospective study of 270 cases identified based on clinical records.Results81.2% affected goats were castrated and 91.7% sheep were intact males; 65.5% of the animals had been sick ≤2 days before referral. Common abnormalities included dysuria (93.6%), indigestion (84.4%), reduced general state of health (79.5%), signs of pain (73%), increased heart and respiratory rates (53.6% and 39.1%), and azotemia (89.4%). Blood urea nitrogen (BUN) and creatinine concentrations were strongly correlated (r2 = 0.81). Hypochloremia (52.2%), hyponatremia (43.3%), hypophosphatemia (52.4%), and abnormal potassium concentrations (26.2% hypokalemia and 24.5% hyperkalemia) were the most common serum electrolyte imbalances. Packed cell volume (PCV), plasma proteins, potassium, BUN, and creatinine concentrations were significantly increased in animals with uroperitoneum. Ultrasonography allowed for confirmation of diagnosis in 83.9% of the cases (135/161 with sufficient available information), uroliths were visible on 34 of 56 plain radiographs.Conclusions and Clinical ImportanceOur study confirmed that clinical and ultrasonographic examinations are sufficient to diagnose urolithiasis. Clinical signs can be divided into an early stage with discrete unspecific clinical signs, a painful stage with frequent straining, expression of pain and moderately reduced general condition, and an advanced stage with a markedly reduced general condition and eventually recumbency.
Revisiting the first report of temperature‐dependent sex determination in a vertebrate, the African redhead agama
Authors: Steele A. L. , Wibbels T. , Warner D. A. 
Published: April 2018

AbstractVertebrates display a wide variety of sex‐determining mechanisms (SDMs). IdentifyingSDMs for different taxa is important for understanding the origins and phylogenetic history of sex‐determining mechanisms. Temperature‐dependent sex determination (TSD) is found in several vertebrate and invertebrate species, and has been studied most extensively in reptiles. The initial discovery ofTSDwas in a lizard, the African redhead agama (Agama agama), over 50 years ago. The original study ofA. agamaused only two incubation temperature treatments and had a small sample size, thus it could not fully characterize the pattern ofTSDin this species. The goal of this study is to revisit this research to better characterize the pattern ofTSD. We also assessed the effect of fluctuating incubation temperatures on offspring sex ratio to provide insight into how variation in offspring sex ratio is produced under natural conditions. After incubating eggs across six constant temperature treatments, we demonstrated that females are produced at relatively cool temperatures and males at warmer temperatures (30°C); fluctuating thermal regimes showed this same pattern. However, some females are again produced at even warmer temperatures, resulting in relatively balanced sex ratios toward the end of the sex‐determining reaction norm. Though the shape of the sex‐determining reaction norm shown here is unusual, it shows some similarities to that of other agamid lizards. Future studies that explore the diversity ofTSDreaction norms and underlying physiological mechanisms will provide new insights into the evolution ofTSD.
Shorter hepatitis B immunoglobulin administration is not associated to hepatitis B virus recurrence when receiving combined prophylaxis after liver transplantation
Authors: Lens Sabela , García‐Eliz María , Fernández Inmaculada , Castells Lluis , Bonacci Martin , Mas Antoni , Crespo Gonzalo , Buti María , Prieto Martín , Forns Xavier 
Published: April 2018

AbstractBackground & AimsThe combination of hepatitis B immunoglobulin and a nucleos(t)ide analogues has markedly reduced the rate of hepatitis B virus recurrence after liver transplantation; however, the optimal duration of hepatitis B immunoglobulin has not been clarified. This lack of consensus perpetuates the use of different strategies. The aim of this study was to evaluate the risk factors associated to hepatitis B virus recurrence after liver transplantation in a large cohort of patients under different hepatitis B immunoglobulin regimens.MethodsRetrospective multicentre analysis of hepatitis B virus‐related liver transplantation recipients receiving combined prophylaxis (hepatitis B immunoglobulin + nucleos(t)ide analogues). The strategy of short‐term hepatitis B immunoglobulin was compared to lifelong administration. Hepatitis B virus recurrence was defined as positive HBsAg after liver transplantation.ResultsThree hundred and thirty‐eight patients were analysed. After a median follow‐up period of 72 months, 37 patients (11%) developed hepatitis B virus recurrence. Hepatocellular carcinoma recurrence and lamivudine resistance after liver transplantation were the only factors independently associated to hepatitis B virus recurrence (HR 5.4 [2.3‐12] and 9.3 [4.2‐20] respectively P < .001). HBsAg reappearance after hepatitis B virus recurrence was transient (16 patients), persistent (15) or alternant (6). The hepatitis B immunoglobulin regimen did not have an impact on the rate or evolution of hepatitis B virus recurrence. Overall, patient survival was good and not influenced by hepatitis B virus recurrence (82% at 5 years). Fulminant liver failure, hepatitis C coinfection or hepatocellular carcinoma at liver transplantation were independent risk factors for lower survival.ConclusionsLiver transplantation is an effective treatment for hepatitis B virus‐related liver disease. Since the introduction of combined prophylaxis the rate of hepatitis B virus recurrence is very low. However, lifelong hepatitis B immunoglobulin administration does not seem necessary to reduce hepatitis B virus recurrence.
Hepatitis E seroprevalence in the Americas: A systematic review and meta‐analysis
Authors: Horvatits Thomas , Ozga Ann‐Kathrin , Westhölter Dirk , Hartl Johannes , Manthey Carolin F. , Lütgehetmann Marc , Rauch Geraldine , Kriston Levente , Lohse Ansgar W. , Bendall Richard , Wedemeyer Heiner , Dalton Harry R. , Pischke Sven 
Published: April 2018

AbstractBackground & AimsWhile hepatitis E virus infections are a relevant topic in Europe, knowledge about epidemiology of hepatitis E virus infections in the USA and Latin America is still limited. Aim of this study was to estimate anti‐hepatitis E virus IgG seroprevalence in the Americas and to assess whether low socioeconomic status is associated with hepatitis E virus exposure.MethodsWe performed a systematic review and meta‐analysis. Literature search was performed in PubMed for articles published 01/1994‐12/2016. Prevalence was estimated using a mixed‐effects model and reported in line with PRISMA reporting guidelines.ResultsSeroprevalence was significantly higher in the USA than in Latin America, independently of assay, patient cohort, methodological quality or study year (OR: 1.82 (1.06‐3.08), P = .03). Patients in the USA had a more than doubled estimated seroprevalence (up to 9%, confidence interval 5%‐15.6%) than those in Brazil (up to 4.2%, confidence interval 2.4%‐7.1%; OR: 2.27 (1.25‐4.13); P = .007) and Mixed Caribbean (up to 1%, OR: 8.33 (1.15‐81.61); P = .04). A comparison with published data from Europe demonstrated that anti‐hepatitis E virus seroprevalence in the USA and Europe did not differ significantly (OR: 1.33 (0.81‐2.19), P = .25), while rate in South America was significantly lower than that in Europe (OR: 0.67 (0.45‐0.98), P = .04).ConclusionsHepatitis E virus is common in the USA. Surprisingly, the risk of hepatitis E virus exposure was low in many South American countries. Seroprevalence did not differ significantly between Europe and the USA. Hence, hepatitis E virus is not limited to countries with low sanitary standards, and a higher socioeconomic status does not protect populations from hepatitis E virus exposure.
A Nonballasted Rail Track Slab Crack Identification Method Using a Level‐Set‐Based Active Contour Model
Authors: Ai Chengbo , Qiu Shi , Xu Guiyang , Zhang Allen , Wang Kelvin C.P. 
Published: April 2018

AbstractThe nonballasted rail tracks have been extensively applied in the new high‐speed railway system development in China, that is, the China Railway Track System (CRTS). However, many defects have been identified during the operation of the CRTS, among which concrete slab crack is recognized as one of the most common, yet critical defects that require accurate identification and timely maintenance attention. Because of the unique outlook of the cracks in nonballasted rail track slabs captured in the survey imagery, direct adaptations of the existing crack extraction methods show dramatically degraded performance. A new automatic crack identification method is developed in this study by employing a region‐based active contour framework with the intensity cluster energy. The proposed method embodies three major contributions, including (1) a heavy penalization energy component that could effectively avoid both under‐ and overevolutions; (2) a multiphase level‐set function that effectively evolves the contours generated with different intensity clusters; and (3) a two‐step implementation of the framework that significantly improves the efficiency. The experimental test evaluates the performance of the proposed method using the data collected on high‐speed rail tracks in Hebei Province, China. The proposed method accurately identifies more than 93.0% of digitized cracks in different crack patterns and challenging backgrounds using a data set consisting of 1,500 synthetic images and 150 actual images. In addition, it shows promising performance in comparison with other popular state‐of‐the‐art crack detection algorithms in terms of accuracy and computational efficiency. The proposed method has demonstrated the promising capacity to support a reliable and efficient nonballasted rail track crack identification and to facilitate the subsequent maintenance cost‐effectively.
Increased flexibility in the use of exogenous lipoic acid by Staphylococcus aureus
Authors: Laczkovich Irina , Teoh Wei Ping , Flury Sarah , Grayczyk James P. , Zorzoli Azul , Alonzo Francis 
Published: April 2018

SummaryLipoic acid is a cofactor required for intermediary metabolism that is either synthesized de novo or acquired from environmental sources. The bacterial pathogen Staphylococcus aureus encodes enzymes required for de novo biosynthesis, but also encodes two ligases, LplA1 and LplA2, that are sufficient for lipoic acid salvage during infection. S. aureus also encodes two H proteins, GcvH of the glycine cleavage system and the homologous GcvH‐L encoded in an operon with LplA2. GcvH is a recognized conduit for lipoyl transfer to α‐ketoacid dehydrogenase E2 subunits, while the function of GcvH‐L remains unclear. The potential to produce two ligases and two H proteins is an unusual characteristic of S. aureus that is unlike most other Gram positive Firmicutes and might allude to an expanded pathway of lipoic acid acquisition in this microorganism. Here, we demonstrate that LplA1 and LplA2 facilitate lipoic acid salvage by differentially targeting lipoyl domain‐containing proteins; LplA1 targets H proteins and LplA2 targets α‐ketoacid dehydrogenase E2 subunits. Furthermore, GcvH and GcvH‐L both facilitate lipoyl relay to E2 subunits. Altogether, these studies identify an expanded mode of lipoic acid salvage used by S. aureus and more broadly underscore the importance of bacterial adaptations when faced with nutritional limitation.
Heat shock transcription factor 3 regulates plant immune response through modulation of salicylic acid accumulation and signalling in cassava
Authors: Wei Yunxie , Liu Guoyin , Chang Yanli , He Chaozu , Shi Haitao 
Published: April 2018

SummaryAs the terminal components of signal transduction, heat stress transcription factors (Hsfs) mediate the activation of multiple genes responsive to various stresses. However, the information and functional analysis are very limited in non‐model plants, especially in cassava (Manihot esculenta), one of the most important crops in tropical areas. In this study, 32 MeHsfs were identified from the cassava genome; the evolutionary tree, gene structures and motifs were also analysed. Gene expression analysis found that MeHsfs were commonly regulated by Xanthomonas axonopodis pv. manihotis (Xam). Amongst these MeHsfs, MeHsf3 was specifically located in the cell nucleus and showed transcriptionally activated activity on heat stress elements (HSEs). Through transient expression in Nicotiana benthamiana leaves and virus‐induced gene silencing (VIGS) in cassava, we identified the essential role of MeHsf3 in plant disease resistance, by regulating the transcripts of Enhanced Disease Susceptibility 1 (EDS1) and pathogen‐related gene 4 (PR4). Notably, as regulators of defence susceptibility, MeEDS1 and MePR4 were identified as direct targets of MeHsf3. Moreover, the disease sensitivity of MeHsf3‐ and MeEDS1‐silenced plants could be restored by exogenous salicylic acid (SA) treatment. Taken together, this study highlights the involvement of MeHsf3 in defence resistance through the transcriptional activation of MeEDS1 and MePR4.
Towards the automated identification of Chrysomya blow flies from wing images
Authors: Macleod N. , Hall M. J. R. , Wardhana A. H. 
Published: April 2018

AbstractThe Old World screwworm fly (OWSF), Chrysomya bezziana (Diptera: Calliphoridae), is an important agent of traumatic myiasis and, as such, a major human and animal health problem. In the implementation of OWSF control operations, it is important to determine the geographical origins of such disease‐causing species in order to establish whether they derive from endemic or invading populations. Gross morphological and molecular studies have demonstrated the existence of two distinct lineages of this species, one African and the other Asian. Wing morphometry is known to be of substantial assistance in identifying the geographical origin of individuals because it provides diagnostic markers that complement molecular diagnostics. However, placement of the landmarks used in traditional geometric morphometric analysis can be time‐consuming and subject to error caused by operator subjectivity. Here we report results of an image‐based approach to geometric morphometric analysis for delivering wing‐based identifications. Our results indicate that this approach can produce identifications that are practically indistinguishable from more traditional landmark‐based results. In addition, we demonstrate that the direct analysis of digital wing images can be used to discriminate between three Chrysomya species of veterinary and forensic importance and between C. bezziana genders.
Transcription factor WRKY22 promotes aluminum tolerance via activation of OsFRDL4 expression and enhancement of citrate secretion in rice (Oryza sativa)
Authors: Li Ge Zi , Wang Zhan Qi , Yokosho Kengo , Ding Bing , Fan Wei , Gong Qiao Qiao , Li Gui Xin , Wu Yun Rong , Yang Jian Li , Ma Jian Feng , Zheng Shao Jian 
Published: April 2018

Summary

Whilst WRKY transcription factors are known to be involved in diverse plant responses to biotic stresses, their involvement in abiotic stress tolerance is poorly understood. OsFRDL4, encoding a citrate transporter, has been reported to be regulated by ALUMINUM (Al) RESISTANCE TRANSCRIPTION FACTOR 1 (ART1) in rice, but whether it is also regulated by other transcription factors is unknown.

We define the role of OsWRKY22 in response to Al stress in rice by using mutation and transgenic complementation assays, and characterize the regulation of OsFRDL4 by OsWRKY22 via yeas one‐hybrid, electrophoretic mobility shift assay and ChIP‐quantitative PCR.

We demonstrate that loss of OsWRKY22 function conferred by the oswrky22 T‐DNA insertion allele causes enhanced sensitivity to Al stress, and a reduction in Al‐induced citrate secretion. We next show that OsWRKY22 is localized in the nucleus, functions as a transcriptional activator and is able to bind to the promoter of OsFRDL4 via W‐box elements. Finally, we find that both OsFRDL4 expression and Al‐induced citrate secretion are significantly lower in art1 oswrky22 double mutants than in the respective single mutants.

We conclude that OsWRKY22 promotes Al‐induced increases in OsFRDL4 expression, thus enhancing Al‐induced citrate secretion and Al tolerance in rice.