bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic engineering of Rhodococcus jostii RHA1 for production of pyridine-dicarboxylic acids from lignin
Authors: Spence Edward M. , Calvo-Bado Leonides , Mines Paul , Bugg Timothy D. H. 
Published: January 2021

AbstractGenetic modification of Rhodococcus jostii RHA1 was carried out in order to optimise the production of pyridine-2,4-dicarboxylic acid and pyridine-2,5-dicarboxylic acid bioproducts from lignin or lignocellulose breakdown, via insertion of either the Sphingobium SYK-6 ligAB genes or Paenibacillus praA gene respectively. Insertion of inducible plasmid pTipQC2 expression vector containing either ligAB or praA genes into a ΔpcaHG R. jostii RHA1 gene deletion strain gave 2–threefold higher titres of PDCA production from lignocellulose (200–287 mg/L), compared to plasmid expression in wild-type R. jostii RHA1. The ligAB genes were inserted in place of the chromosomal pcaHG genes encoding protocatechuate 3,4-dioxygenase, under the control of inducible Picl or PnitA promoters, or a constitutive Ptpc5 promoter, producing 2,4-PDCA products using either wheat straw lignocellulose or commercial soda lignin as carbon source. Insertion of Amycolatopsis sp. 75iv2 dyp2 gene on a pTipQC2 expression plasmid led to enhanced titres of 2,4-PDCA products, due to enhanced rate of lignin degradation. Growth in minimal media containing wheat straw lignocellulose led to the production of 2,4-PDCA in 330 mg/L titre in 40 h, with > tenfold enhanced productivity, compared with plasmid-based expression of ligAB genes in wild-type R. jostii RHA1. Production of 2,4-PDCA was also observed using several different polymeric lignins as carbon sources, and a titre of 240 mg/L was observed using a commercially available soda lignin as feedstock.
Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017–2018
Authors: Gansané Adama , Moriarty Leah F. , Ménard Didier , Yerbanga Isidore , Ouedraogo Esperance , Sondo Paul , Kinda Rene , Tarama Casimir , Soulama Edwige , Tapsoba Madou , Kangoye David , Compaore Cheick Said , Badolo Ousmane , Dao Blami , Tchwenko Samuel , Tinto Halidou , Valea Innocent 
Published: January 2021

Abstract
Background
The World Health Organization recommends regularly assessing the efficacy of artemisinin-based combination therapy (ACT), which is a critical tool in the fight against malaria. This study evaluated the efficacy of two artemisinin-based combinations recommended to treat uncomplicated Plasmodium falciparum malaria in Burkina Faso in three sites: Niangoloko, Nanoro, and Gourcy.

Methods
This was a two-arm randomized control trial of the efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Children aged 6–59 months old were monitored for 42 days. The primary outcomes of the study were uncorrected and PCR-corrected efficacies to day 28 for AL and 42 for DP. Molecular markers of resistance to artemisinin derivatives and partner drugs were also analysed.

Results
Of 720 children enrolled, 672 reached study endpoints at day 28, 333 in the AL arm and 339 in the DP arm. PCR-corrected 28-day per protocol efficacy in the AL arm was 74% (64–83%) in Nanoro, 76% (66–83%) in Gourcy, and 92% (84–96%) in Niangoloko. The PCR-corrected 42-day per protocol efficacy in the DP arm was 84% (75–89%) in Gourcy, 89% (81–94%) in Nanoro, and 97% (92–99%) in Niangoloko.
No Pfk13 mutation previously associated with artemisinin-resistance was observed. No statistically significant association was found between treatment outcome and presence of the 86Y mutation in the Pfmdr1 gene. There was also no association observed between treatment outcome and Pfpm2 or Pfmdr1 copy number variation.

Conclusion
The results of this study indicate evidence of inadequate efficacy of AL at day 28 and DP at day 42 in the same two sites. A change of first-line ACT may be warranted in Burkina Faso.
Trial Registry Pan African Clinical Trial Registry Identifier: PACTR201708002499311.
Date of registration: 8/3/2017
https://pactr.samrc.ac.za/Search.aspx
Houston hurricane Harvey health (Houston-3H) study: assessment of allergic symptoms and stress after hurricane Harvey flooding
Authors: Oluyomi Abiodun O. , Panthagani Kristen , Sotelo Jesus , Gu Xiangjun , Armstrong Georgina , Luo Dan Na , Hoffman Kristi L. , Rohlman Diana , Tidwell Lane , Hamilton Winifred J. , Symanski Elaine , Anderson Kimberly , Petrosino Joseph F. , Walker Cheryl Lyn , Bondy Melissa 
Published: January 2021

AbstractBackgroundIn August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey’s landfall.MethodsThe Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 unique participants from four sites across Harris County at two times: within approximately 1-month of Harvey (T1,n = 206) and approximately 12-months after Harvey (T2,n = 266), including 125 individuals who participated at both time points. Using a self-administered questionnaire, participants reported details on demographics, flood-related exposures, and health outcomes, including allergic symptoms and stress.ResultsThe majority of participants reported hurricane-related flooding in their homes at T1 (79.1%) and T2 (87.2%) and experienced at least one allergic symptom after the hurricane (79.4% at T1 and 68.4% at T2). In general, flood-exposed individuals were at increased risk of upper respiratory tract allergic symptoms, reported at both the T1 and T2 time points, with exposures to dirty water and mold associated with increased risk of multiple allergic symptoms. The mean stress score of study participants at T1 was 8.0 ± 2.1 and at T2, 5.1 ± 3.2, on a 0–10 scale. Participants who experienced specific flood-related exposures reported higher stress scores when compared with their counterparts, especially 1 year after Harvey. Also, a supplementary paired-samples analysis showed that reports of wheezing, shortness of breath, and skin rash did not change between T1 and T2, though other conditions were less commonly reported at T2.ConclusionThese initial Houston-3H findings demonstrate that flooding experiences that occurred as a consequence of Hurricane Harvey had lasting impacts on the health of Houstonians up to 1 year after the hurricane.
Few-layer graphene induces both primary and secondary genotoxicity in epithelial barrier models in vitro
Authors: Burgum Michael J. , Clift Martin J. D. , Evans Stephen J. , Hondow Nicole , Tarat Afshin , Jenkins Gareth J. , Doak Shareen H. 
Published: January 2021

Abstract
Background
Toxicological evaluation of engineered nanomaterials (ENMs) is essential for occupational health and safety, particularly where bulk manufactured ENMs such as few-layer graphene (FLG) are concerned. Additionally, there is a necessity to develop advanced in vitro models when testing ENMs to provide a physiologically relevant alternative to invasive animal experimentation. The aim of this study was to determine the genotoxicity of non-functionalised (neutral), amine- and carboxyl-functionalised FLG upon both human-transformed type-I (TT1) alveolar epithelial cell monocultures, as well as co-cultures of TT1 and differentiated THP-1 monocytes (d.THP-1 (macrophages)).

Results
In monocultures, TT1 and d.THP-1 macrophages showed a statistically significant (p < 0.05) cytotoxic response with each ENM following 24-h exposures. Monoculture genotoxicity measured by the in vitro cytokinesis blocked micronucleus (CBMN) assay revealed significant (p < 0.05) micronuclei induction at 8 µg/ml for amine- and carboxyl-FLG. Transmission electron microscopy (TEM) revealed ENMs were internalised by TT1 cells within membrane-bound vesicles. In the co-cultures, ENMs induced genotoxicity in the absence of cytotoxic effects. Co-cultures pre-exposed to 1.5 mM N-acetylcysteine (NAC), showed baseline levels of micronuclei induction, indicating that the genotoxicity observed was driven by oxidative stress.

Conclusions
Therefore, FLG genotoxicity when examined in monocultures, results in primary-indirect DNA damage; whereas co-cultured cells reveal secondary mechanisms of DNA damage.
Modular vaccine platform based on the norovirus-like particle
Authors: Lampinen Vili , Heinimäki Suvi , Laitinen Olli H. , Pesu Marko , Hankaniemi Minna M. , Blazevic Vesna , Hytönen Vesa P. 
Published: January 2021

Abstract
Background
Virus-like particle (VLP) vaccines have recently emerged as a safe and effective alternative to conventional vaccine technologies. The strong immunogenic effects of VLPs can be harnessed for making vaccines against any pathogen by decorating VLPs with antigens from the pathogen. Producing the antigenic pathogen fragments and the VLP platform separately makes vaccine development rapid and convenient. Here we decorated the norovirus-like particle with two conserved influenza antigens and tested for the immunogenicity of the vaccine candidates in BALB/c mice.

Results
SpyTagged noro-VLP was expressed with high efficiency in insect cells and purified using industrially scalable methods. Like the native noro-VLP, SpyTagged noro-VLP is stable for months when refrigerated in a physiological buffer. The conserved influenza antigens were produced separately as SpyCatcher fusions in E. coli before covalent conjugation on the surface of noro-VLP. The noro-VLP had a high adjuvant effect, inducing high titers of antibody production against the antigens presented on its surface.

Conclusions
The modular noro-VLP vaccine platform presented here offers a rapid, convenient and safe method to present various soluble protein antigens to the immune system for vaccination and antibody production purposes.
Fusion expression of nanobodies specific for the insecticide fipronil on magnetosomes in Magnetospirillum gryphiswaldense MSR-1
Authors: Wu Sha , Ma Fengfei , He Jinxin , Li Qing X. , Hammock Bruce D. , Tian Jiesheng , Xu Ting 
Published: January 2021

Abstract
Background
Magnetic nanoparticles such as magnetosomes modified with antibodies allow a high probability of their interaction with targets of interest. Magnetosomes biomineralized by magnetotactic bacteria are in homogeneous nanoscale size and have crystallographic structure, and high thermal and colloidal stability. Camelidae derived nanobodies (Nbs) are small in size, thermal stable, highly water soluble, easy to produce, and fusible with magnetosomes. We aimed to functionalize Nb-magnetosomes for the analysis of the insecticide fipronil.

Results
Three recombinant magnetotactic bacteria (CF, CF+ , and CFFF) biomineralizing magnetosomes with different abundance of Nbs displayed on the surface were constructed. Compared to magnetosomes from the wild type Magnetospirillum gryphiswaldense MSR-1, all of the Nb-magnetosomes biosynthesized by strains CF, CF+ , and CFFF showed a detectable level of binding capability to fipronil-horseradish peroxidase (H2-HRP), but none of them recognized free fipronil. The Nb-magnetosomes from CFFF were oxidized with H2O2 or a glutathione mixture consisting of reduced glutathione and oxidized glutathione in vitro and their binding affinity to H2-HRP was decreased, whereas that to free fipronil was enhanced. The magnetosomes treated with the glutathione mixture were employed to develop an enzyme-linked immunosorbent assay for the detection of fipronil in water samples, with average recoveries in a range of 78–101%.

Conclusions
The economical and environmental-friendly Nb-magnetosomes biomineralized by the bacterial strain MSR-1 can be potentially applied to nanobody-based immunoassays for the detection of fipronil or nanobody-based assays in general.
More evidence or stronger political will: exploring the feasibility of needle and syringe programs in Ukrainian prisons
Authors: Dmitrieva Alexandra , Stepanov Vladimir , Svyrydova Kateryna , Lukash Ievgeniia-Galyna , Doltu Svetlana , Golichenko Mikhail , Kalivoshko Valeriy , Khanyukov Evgeniy , Kosmukhamedova Zhannat , Torkunov Oleh , Zagrebelnyi Oleksii 
Published: January 2021

AbstractIntroductionIn 2007, the World Health Organization (WHO) recommended for prison authorities to introduce prison needle and syringe programs (PNSP) if they have any evidence that injecting drug use is taking place in prisons. This article presents descriptive evidence that injecting drug use takes place in Ukrainian prisons, it discusses how (denial of) access to injection equipment is regulated in the current system and what changes should be considered in order to implement PNSP.BackgroundUkrainian prisons still live by the laws and policies adopted in the Soviet Union. Besides laws and regulations, these legacies are replicated through the organization and infrastructure of the prison’s physical space, and through “carceral collectivism” as a specific form of living and behaving. Inviolability of the prison order over time helps the prison staff to normalize and routinely rationalize punishment enforcement as a power “over” prisoners, but not a power “for” achieving a specific goal.MethodsThe Participatory Action Research approach was used as a way of involving different actors in the study’s working group and research process. The data were gathered through 160 semi-structured interviews with prison health care workers, guards, people who inject drugs (PWID) who served one or several terms and other informants.ResultsThe “expertise” in drug use among prisoners demonstrated by prison staff tells us two things—they admit that injecting use takes place in prisons, and that the surveillance of prisoner behavior has been carried out constantly since the very beginning as a core function of control. The communal living conditions and prison collectivism may not only produce and reproduce a criminal subculture but, using the same mechanisms, produce and reproduce drug use in prison. The “political will” incorporated into prison laws and policies is essential for the revision of outdated legacies and making PNSP implementation feasible.ConclusionPNSP implementation is not just a question of having evidence of injecting drug use in the hands of prison authorities. For PNSP to be feasible in the prison environment, there is a need for specific changes to transition from one historical period and political leadership to another. And, thus, to make PNSP work requires making power work for change, and not just for reproducing the power itself.
Individual and structural correlates of willingness for intravenous buprenorphine treatment among people who inject sublingual buprenorphine in France
Authors: Mezaache Salim , Carrieri Patrizia , Briand-Madrid Laélia , Laporte Virginie , Morel Alain , Rojas Castro Daniela , Roux Perrine 
Published: January 2021

Abstract
Background
Some people do not benefit from oral administration of opioid agonist treatment, and an intravenous (IV) formulation may be more suitable. Our objective was to evaluate the willingness of people who regularly inject sublingual buprenorphine to receive IV buprenorphine as a prescribed treatment, and to examine related correlates.

Methods
We performed a secondary analysis of data from the cross-sectional study PrebupIV, conducted in France in 2015 among 557 people who inject opioids. The study comprised questionnaires completed either face to face or online and community-based workshops. We only included participants who reported buprenorphine as their main injected drug (n = 209). Willingness to receive IV buprenorphine treatment was measured on a scale from 0 to 10. Ordinal logistic regression identified correlates of willingness. Artworks and testimonies from participants in the workshops were also used to illustrate correlates of willingness.

Results
Among the 209 participants, the mean score (SD) for willingness to receive IV buprenorphine was 8.0 (2.8). Multivariate analysis showed that participants who reported using non-prescribed buprenorphine (AOR = 4.82, p = 0.019), a higher daily dosage of buprenorphine (AOR (for 1 mg) = 1.05, p = 0.043), and a higher number of complications due to injection (AOR = 2.28, p = 0.037), were more willing to receive IV buprenorphine treatment.

Conclusions
Willingness to initiate IV buprenorphine treatment was high among people who regularly inject sublingual buprenorphine. A prescribed IV formulation could attract and retain more people into care and reduce harms associated with the injection of buprenorphine tablets.
Identification of potential CpG sites for oral squamous cell carcinoma diagnosis via integrated analysis of DNA methylation and gene expression
Authors: Chen Le , Wang Dong 
Published: January 2021

Abstract
Background
Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the oral carcinomas and has a high fatality rate. This study aimed to identify potentially diagnostic biomarkers of OSCC through integrated analysis of DNA methylation and gene expression profiles.

Methods
The DNA methylation profiles of OSCC patients from The Cancer Genome Atlas (TCGA) were analyzed to screen patients with CpG island methylator phenotype (CIMP) and investigate the relationship between CIMP and survival probability of OSCC patients. Differential methylation and expression analyses of the paired OSCC tumor and paracancerous samples from TCGA were performed. Logistic regression model was established, and the accuracy of this diagnostic model for OSCC was evaluated in validation sets from Gene Expression Omnibus (GEO).

Results
OSCC patients with CIMP had lower survival probability than those without CIMP. The cg02860732 and cg04342955 were determined as candidate diagnostic methylation sites for OSCC. Logistic regression model was established based on cg02860732 and cg04342955 showed relatively high diagnostic accuracy in OSCC.

Conclusions
A diagnostic model for OSCC was identified based on the methylation sites cg02860732 and cg04342955, which might be favorable for the diagnosis of OSCC.
Accuracy of the end-expiratory lung volume measured by the modified nitrogen washout/washin technique: a bench study
Authors: Berger-Estilita Joana , Haenggi Matthias , Ott Daniel , Berger David 
Published: January 2021

Abstract
Background
The functional residual capacity (FRC) determines the oxygenating capacity of the lung and is heavily affected in the clinical context of the acute respiratory distress syndrome. Nitrogen-wash-in/wash-out methods have been used to measure FRC. These methods have rarely been validated against exactly known volumes. The aim of the study was to assess the accuracy and precision of the N2 washout/washin method in measuring FRC, by comparing it with set volumes in a lung simulator.

Methods
We conducted a diagnostic bench study in the Intensive Care Unit and Radiology Department of a tertiary hospital in Switzerland. Using a fully controllable high fidelity lung simulator (TestChest®), we set the functional residual capacity at 1500 ml, 2000 ml and 2500 ml and connected to the GE Carestation respirator, which includes the nitrogen washout/washin technique (INview™ tool). FRC was then set to vary by different levels of PEEP (5, 8, 12 and 15 cmH2O). The main outcome measures were bias and precision of the TestChest® when compared to the results from the washout/washin technique, according to the results of a Bland Altman Analysis. We verified our findings with volumetric computed tomography.

Results
One hundred and thirty-five nitrogen-wash-in/wash-out measurements were taken at three levels of FIO2 (0.4, 0.5, 0.6). The CT volumetry reproduced the set end-expiratory volumes at the Simulator with a bias of 4 ml. The nitrogen-wash-in/wash-out method had a bias of 603 ml with acceptable limits of agreement (95% CI 252 to − 953 ml). Changes were detected with a concordance rate of 97%.

Conclusions
We conclude that the TestChest® simulator is an accurate simulation tool, concerning the simulation of lung volumes. The nitrogen wash-in/wash out method correlated positively with FRC changes, despite a relatively large bias in absolute measurements. The reference volumes in the lung simulator verified with CT volumetry were very close to their expected values. The reason for the bias could not be determined.
Activation of MC1R with BMS-470539 attenuates neuroinflammation via cAMP/PKA/Nurr1 pathway after neonatal hypoxic-ischemic brain injury in rats
Authors: Yu Shufeng , Doycheva Desislava Met , Gamdzyk Marcin , Yang Yijun , Lenahan Cameron , Li Gaigai , Li Dujuan , Lian Lifei , Tang Jiping , Lu Jun , Zhang John H. 
Published: January 2021

AbstractBackgroundMicroglia-mediated neuroinflammation plays a crucial role in the pathogenesis of hypoxic-ischemic (HI)-induced brain injury. Activation of melanocortin-1 receptor (MC1R) has been shown to exert anti-inflammatory and neuroprotective effects in several neurological diseases. In the present study, we have explored the role of MC1R activation on neuroinflammation and the potential underlying mechanisms after neonatal hypoxic-ischemic brain injury in rats.MethodsA total of 169 post-natal day 10 unsexed rat pups were used. HI was induced by right common carotid artery ligation followed by 2.5 h of hypoxia. BMS-470539, a specific selective MC1R agonist, was administered intranasally at 1 h after HI induction. To elucidate the potential underlying mechanism, MC1R CRISPR KO plasmid or Nurr1 CRISPR KO plasmid was administered via intracerebroventricular injection at 48 h before HI induction. Percent brain infarct area, short- and long-term neurobehavioral tests, Nissl staining, immunofluorescence staining, and Western blot were conducted.ResultsThe expression levels of MC1R and Nurr1 increased over time post-HI. MC1R and Nurr1 were expressed on microglia at 48 h post-HI. Activation of MC1R with BMS-470539 significantly reduced the percent infarct area, brain atrophy, and inflammation, and improved short- and long-term neurological deficits at 48 h and 28 days post-HI. MC1R activation increased the expression of CD206 (a microglial M2 marker) and reduced the expression of MPO. Moreover, activation of MC1R with BMS-470539 significantly increased the expression levels of MC1R, cAMP, p-PKA, and Nurr1, while downregulating the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-1β) at 48 h post-HI. However, knockout of MC1R or Nurr1 by specific CRISPR reversed the neuroprotective effects of MC1R activation post-HI.ConclusionsOur study demonstrated that activation of MC1R with BMS-470539 attenuated neuroinflammation, and improved neurological deficits after neonatal hypoxic-ischemic brain injury in rats. Such anti-inflammatory and neuroprotective effects were mediated, at least in part, via the cAMP/PKA/Nurr1 signaling pathway. Therefore, MC1R activation might be a promising therapeutic target for infants with hypoxic-ischemic encephalopathy (HIE).