bluuebunny/crossref_metadata_2025_split huggingface dataset:
MEN1 silencing aggravates tumorigenic potential of AR-independent prostate cancer cells through nuclear translocation and activation of JunD and β-catenin
Authors: Luo Yakun , Vlaeminck-Guillem Virginie , Baron Silvère , Dallel Sarah , Zhang Chang Xian , Le Romancer Muriel 
Published: August 2021

Abstract
Background
Recent studies highlighted the increased frequency of AR-low or -negative prostate cancers (PCas) and the importance of AR-independent mechanisms in driving metastatic castration-resistant PCa (mCRPC) development and progression. Several previous studies have highlighted the involvement of the MEN1 gene in PCa. In the current study, we focused on its role specifically in AR-independent PCa cells.

Methods
Cell tumorigenic features were evaluated by proliferation assay, foci formation, colony formation in soft agar, wound healing assay and xenograft experiments in mice. Quantitative RT-PCR, Western blot and immunostaining were performed to determine the expression of different factors in human PCa lines. Different ChIP-qPCR-based assays were carried out to dissect the action of JunD and β-catenin.

Results
We found that MEN1 silencing in AR-independent cell lines, DU145 and PC3, resulted in an increase in anchorage independence and cell migration, accompanied by sustained MYC expression. By searching for factors known to positively regulate MYC expression and play a relevant role in PCa development and progression, we uncovered that MEN1-KD triggered the nuclear translocation of JunD and β-catenin. ChIP and 3C analyses further demonstrated that MEN1-KD led to, on the one hand, augmented binding of JunD to the MYC 5′ enhancer and increased formation of loop structure, and on the other hand, increased binding of β-catenin to the MYC promoter. Moreover, the expression of several molecular markers of EMT, including E-cadherin, BMI1, Twist1 and HIF-1α, was altered in MEN1-KD DU145 and PC3 cells. In addition, analyses using cultured cells and PC3-GFP xenografts in mice demonstrated that JunD and β-catenin are necessary for the altered tumorigenic potential triggered by MEN1 inactivation in AR-independent PCa cells. Finally, we observed a significant negative clinical correlation between MEN1 and CTNNB1 mRNA expression in primary PCa and mCRPC datasets.

Conclusions
Our current work highlights an unrecognized oncosuppressive role for menin specifically in AR-independent PCa cells, through the activation of JunD and β-catenin pathways.
Accessory enzymes of hypercellulolytic Penicillium funiculosum facilitate complete saccharification of sugarcane bagasse
Authors: Ogunyewo Olusola A. , Upadhyay Pooja , Rajacharya Girish H. , Okereke Omoaruemike E. , Faas Laura , Gómez Leonardo D. , McQueen-Mason Simon J. , Yazdani Syed Shams 
Published: August 2021

Abstract
Background
Sugarcane bagasse (SCB) is an abundant feedstock for second-generation bioethanol production. This complex biomass requires an array of carbohydrate active enzymes (CAZymes), mostly from filamentous fungi, for its deconstruction to monomeric sugars for the production of value-added fuels and chemicals. In this study, we evaluated the repertoire of proteins in the secretome of a catabolite repressor-deficient strain of Penicillium funiculosum, PfMig188, in response to SCB induction and examined their role in the saccharification of SCB.

Results
A systematic approach was developed for the cultivation of the fungus with the aim of producing and understanding arrays of enzymes tailored for saccharification of SCB. To achieve this, the fungus was grown in media supplemented with different concentrations of pretreated SCB (0–45 g/L). The profile of secreted proteins was characterized by enzyme activity assays and liquid chromatography–tandem mass spectrometry (LC–MS/MS). A total of 280 proteins were identified in the secretome of PfMig188, 46% of them being clearly identified as CAZymes. Modulation of the cultivation media with SCB up to 15 g/L led to sequential enhancement in the secretion of hemicellulases and cell wall-modifying enzymes, including endo-β-1,3(4)-glucanase (GH16), endo-α-1,3-glucanase (GH71), xylanase (GH30), β-xylosidase (GH5), β-1,3-galactosidase (GH43) and cutinase (CE5). There was ~ 122% and 60% increases in β-xylosidase and cutinase activities, respectively. There was also a 36% increase in activities towards mixed-linked glucans. Induction of these enzymes in the secretome improved the saccharification performance to 98% (~ 20% increase over control), suggesting their synergy with core cellulases in accessing the recalcitrant region of SCB.

Conclusion
Our findings provide an insight into the enzyme system of PfMig188 for degradation of complex biomass such as SCB and highlight the importance of adding SCB to the culture medium to optimize the secretion of enzymes specific for the saccharification of sugarcane bagasse.
Optimized DNA-based identification of Toxocara spp. eggs in soil and sand samples
Authors: Jarosz Wojciech , Durant Jean-Francois , Irenge Leonid Mwana Wa Bene , Fogt-Wyrwas Renata , Mizgajska-Wiktor Hanna , Gala Jean-Luc 
Published: August 2021

AbstractBackgroundToxocara canisandToxocara catiare globally distributed roundworms and causative agents of human toxocariasis, via ingestion ofToxocaraeggs. Control ofToxocarainfections is constrained by a lack of sensitive methods for screening of animal faeces and environmental samples potentially contaminated byToxocaraeggs. In this work, a pre-analytical method for efficient extraction of DNA fromToxocaraeggs in environmental samples was set up using our previously validatedT.canis- andT.cati-specific quantitative real-time polymerase chain reaction (qPCR). For this purpose, the influence of different methods for egg lysis, DNA extraction and purification for removal of PCR inhibitors were assessed on environmental samples.MethodsTo select the best egg disruption method, six protocols were compared on pureT.canisegg suspensions, including enzymatic lysis and thermal or mechanical disruption. Based on the selected best method, an analytical workflow was set up to compare two DNA extraction methods (FastDNA™ SPIN Kit for Soil versus DNeasy®PowerMax®Soil Kit) with an optional dilution and/or clean-up (Agencourt®AMPure®) step. This workflow was evaluated on 10-g soil and 10-g sand samples spiked with egg suspensions ofT.canis(tenfold dilutions of 104eggs in triplicate). The capacity of the different methods, used alone or in combination, to increase the ratio of positive tests was assessed. The resulting optimal workflow for processing spiked soil samples was then tested on environmental soil samples and compared with the conventional flotation-centrifugation and microscopic examination ofToxocaraeggs.ResultsThe most effective DNA extraction method forToxocaraeggs in soil samples consisted in the combination of mechanical lysis of eggs using beads, followed by DNA extraction with the DNeasy®PowerMax®Soil Kit, and completed with an additional DNA clean-up step with AMPure®beads and a sample DNA dilution (1:10). This workflow exhibited a limit of detection of 4 and 46T.caniseggs in 10-g sand and 10-g soil samples, respectively.ConclusionsThe pre-analytical flow process developed here combined with qPCR represents an improved, potentially automatable, and cost-effective method for the surveillance ofToxocaracontamination in the environment.Graphical Abstract
Dirofilaria immitis and Dirofilaria repens in mosquitoes from Corsica Island, France
Authors: Younes Laidoudi , Barré-Cardi Hélène , Bedjaoui Samia , Ayhan Nazli , Varloud Marie , Mediannikov Oleg , Otranto Domenico , Davoust Bernard 
Published: August 2021

Abstract
Background
Dirofilaria immitis and Dirofilaria repens are the main causative agents of heartworm disease and subcutaneous dirofilariasis in domestic and wild canids, respectively. Both pathogens have zoonotic potential and are transmitted by mosquitoes. The present study aimed to determine the transmission period, prevalence and diversity of Dirofilaria spp. vectors from endemic areas of Corsica (France).

Methods
A monthly point data model based on average temperature recorded by four meteorological stations during 2017 was used to calculate the Dirofilaria transmission period. From June to September 2017, female mosquitoes (n = 1802) were captured using Biogents® Sentinel 2 traps lured with carbon dioxide and BG-Lure™ or octanol. Mosquitoes were identified to species level, pooled accordingly, and screened using multiplex real-time qPCR to detect D. immitis and D. repens.

Results
The monthly point data model showed the possible transmission of Dirofilaria spp. from the third week in May to the last week in October in the studied area. Mosquitoes were identified as Ochlerotatus caspius (n = 1432), Aedes albopictus (n = 199), Culex pipiens sensu lato (n = 165) and Aedes vexans (n = 6) and were grouped into 109 pools (from 1 to 27 specimens, mean 11.4 ± 0.7), of which 16 scored positive for Dirofilaria spp. (i.e., n = 13; estimated infection rate [EIR] = 1.1% for D. immitis and n = 3; EIR = 0.2% for D. repens). Specifically, 6 (i.e., EIR = 3.8%) of 15 pools of Ae. albopictus were positive for D. immitis, 2 of 14 of Cx. pipiens s.l. were positive for D. immitis and D. repens, respectively, and 8 of 77 pools of Oc. caspius were positive for D. immitis (i.e., n = 6; EIR = 0.4%) and D. repens (i.e., 2; EIR = 0.1%). The highest mosquito infection rate was recorded in July (EIR = 2.5%), then in June (EIR = 1.3%) and September (EIR = 0.6%).

Conclusions
The data suggest that both Dirofilaria species are endemic and occur possibly in sympatry in the studied area in Corsica, highlighting the need to implement preventive chemoprophylaxis and vector control strategies to reduce the risk of these filarioids in dog and human populations.

Graphical Abstract
Wolbachia prevalence in the vector species Culex pipiens and Culex torrentium in a Sindbis virus-endemic region of Sweden
Authors: Bergman Alexander , Hesson Jenny C. 
Published: August 2021

Abstract
Background
Wolbachia pipientis are endosymbiotic bacteria present in a large proportion of terrestrial arthropods. The species is known to sometimes affect the ability of its host to transmit vector-borne pathogens. Central Sweden is endemic for Sindbis virus (SINV), where it is mainly transmitted by the vector species Culex pipiens and Culex torrentium, with the latter established as the main vector. In this study we investigated the Wolbachia prevalence in these two vector species in a region highly endemic for SINV.

Methods
Culex mosquitoes were collected using CDC light traps baited with carbon dioxide over 9 years at 50 collection sites across the River Dalälven floodplains in central Sweden. Mosquito genus was determined morphologically, while a molecular method was used for reliable species determination. The presence of Wolbachia was determined through PCR using general primers targeting the wsp gene and sequencing of selected samples.

Results
In total, 676 Cx. pipiens and 293 Cx. torrentium were tested for Wolbachia. The prevalence of Wolbachia in Cx. pipiens was 97% (95% CI 94.8–97.6%), while only 0.7% (95% CI 0.19–2.45%) in Cx. torrentium. The two Cx. torrentium mosquitoes that were infected with Wolbachia carried different types of the bacteria.

Conclusions
The main vector of SINV in the investigated endemic region, Cx. torrentium, was seldom infected with Wolbachia, while it was highly prevalent in the secondary vector, Cx. pipiens. The presence of Wolbachia could potentially have an impact on the vector competence of these two species. Furthermore, the detection of Wolbachia in Cx. torrentium could indicate horizontal transmission of the endosymbiont between arthropods of different species.

Graphical abstract
The mechanism of Annexin A1 to modulate TRPV1 and nociception in dorsal root ganglion neurons
Authors: Zhang Yufen , Ma Sehui , Ke Xiao , Yi Yao , Yu Hongyan , Yu Dian , Li Qiang , Shang You , Lu Youming , Pei Lei 
Published: August 2021

Abstract
Background
Annexin A1 (ANXA1) exerts anti-nociceptive effect through ANXA1 receptor formyl peptide receptor 2 (FPR2/ALX (receptor for lipoxin A4), FPR2) at the dorsal root ganglia (DRG) level. However, the mechanisms remain elucidated. By using radiant heat, hot/cold plate, tail flick, von Frey, and Randall-Selitto tests to detect nociception in intact and chemical (capsaicin, menthol, mustard oil, formalin or CFA) injected AnxA1 conditional knockout (AnxA1−/−) mice, applying calcium imaging and patch clamp recordings in cultured DRG neurons to measure neuronal excitability, conducting immunofluorescence and western blotting to detect the protein levels of TRPV1, FPR2 and its downstream molecules, and performing double immunofluorescence and co-immunoprecipitation to investigate the interaction between Calmodulin (CaM) and TRPV1; we aim to uncover the molecular and cellular mechanisms of ANXA1’s role in antinociception.

Results
AnxA1−/− mice exhibited significant sensitivity to noxious heat (mean ± SD, 6.2 ± 1.0 s vs. 9.9 ± 1.6 s in Hargreaves test; 13.6 ± 1.5 s vs. 19.0 ± 1.9 s in hot plate test; n = 8; P < 0.001), capsaicin (101.0 ± 15.3 vs. 76.2 ± 10.9; n = 8; P < 0.01), formalin (early phase: 169.5 ± 32.8 s vs. 76.0 ± 21.9 s; n = 8; P < 0.05; late phase: 444.6 ± 40.1 s vs. 320.4 ± 33.6 s; n = 8; P < 0.01) and CFA (3.5 ± 0.8 s vs. 5.9 ± 1.4 s; n = 8; P < 0.01). In addition, we found significantly increased capsaicin induced Ca2+ response, TRPV1 currents and neuronal firing in AnxA1 deficient DRG neurons. Furthermore, ANXA1 mimic peptide Ac2-26 robustly increased intracellular Ca2+, inhibited TRPV1 current, activated PLCβ and promoted CaM-TRPV1 interaction. And these effects of Ac2-26 could be attenuated by FPR2 antagonist Boc2.

Conclusions
Selective deletion of AnxA1 in DRG neurons enhances TRPV1 sensitivity and deteriorates noxious heat or capsaicin induced nociception, while ANXA1 mimic peptide Ac2-26 desensitizes TRPV1 via FPR2 and the downstream PLCβ-Ca2+-CaM signal. This study may provide possible target for developing new analgesic drugs in inflammatory pain.
Quality of selected anti-retroviral medicines: Tanzania Mainland market as a case study
Authors: Mziray Sophia , Maganda Betty A. , Mwamwitwa Kissa , Fimbo Adam M. , Kisenge Seth , Sambu Gerald , Mwalwisi Yonah H. , Bitegeko Adonis , Alphonce Emmanuel , Khea Akida , Shewiyo Danstan H. , Kaale Eliangiringa 
Published: August 2021

Abstract
Background
Antiretroviral drugs (ARVs) have significantly reduced morbidity, mortality and improved the quality of life of people living with HIV infection. Poor quality ARVs may result in harmful consequences such as adverse drug reactions, treatment failure and development of drug resistant strains and sometimes death, which in turn may undermine the healthcare delivery system. To ensure optimal treatment outcomes, medicines quality control must be undertaken regularly. This study was aimed at evaluating the quality of ARVs circulating on the Tanzania Mainland market.

Methods
This was a survey study. ARVs samples were collected in 20 regions of Tanzania Mainland, between 2012 and 2018. All sampled ARVs were subjected to screening testing using the Global Pharma Health Fund® Mini-Lab kits. Sampled ARV’s that failed screening test or yielded doubtful results and 10 % (10 %) of all that complied with the screening test requirements were selected for full quality control testing. Quality control testing was conducted at the Tanzania Medicines and Medical Devices Authority (TMDA) laboratory a World Health Organisation prequalified. Samples collected from the medicine distribution outlets were also, subjected to product information review.

Results
A total of 2,630 samples were collected, of which 83.7 % (2200/2630) were from port of entry (POEs). All sampled ARVs were screened and conformed to the specifications, except of the fixed dose combination (FDC) lopinavir/ritonavir 0.27 % (7/2630) and lamivudine/zidovudine/nevirapine 0.27 % (7/2630) that failed the disintegration test. Out of the 100 samples selected for full quality control testing, 3 % of them failed to comply with the specifications, of which FDC stavudine/lamivudine/nevirapine failed disintegration and assay tests 2 % (2/100) and 1 % (1/100), respectively. Samples failing the assay test had low content of stavudine (86.6 %) versus specification limits (90 -110 %). Out of the 430 samples which were subjected to product information review, 25.6 % (110/430) failed to comply with the TMDA packaging and labelling requirements.

Conclusions
The quality of majority of ARVs circulating on the Tanzania Mainland market was good, even so, significant deficiencies on labelling and packaging were observed. These results call for continuous monitoring of quality of medicines circulating on the Tanzania Mainland market.
Joint effusion, anteroposterior stability, muscle strength and degree of patellofemoral osteoarthritis significantly impact outcome following revision ACL reconstruction
Authors: Andrä Kathleen , Kayaalp Enes , Prill Robert , Irlenbusch Lars , Liesaus Eckehard , Trommer Tilo , Ullmann Peter , Becker Roland 
Published: August 2021

Abstract
Purpose: Effusion, impaired muscle function and knee instability are considered as some of the most important factors effecting outcome following anterior cruciate ligament reconstruction (ACL-R) but the impact on revision ACL-R remains unclear. It was hypothesized that these factors will significantly worsen clinical outcome following revision ACL-R.

Methods
Seventy knees (13 female and 57 male) were followed retrospectively after revision ACL-R at a mean follow-up of 47.8 ± 20.7 months. Clinical examination was based on the International Knee Documentation Evaluation Form-2000 (IKDC), Tegner activity scale. Instrumented measurement of anterior tibial translation was performed using the Rolimeter® (DJO Global, Freiburg, Germany). Bilateral circumference of the thigh was measured 10 and 20 cm proximal to the medial joint space. Cartilage was assessed according to Outerbridge classification during both primary and revision ACL-R.

Results
Tegner activity scale decreased significantly from 7.8 ± 1.4 points at primary ACL-R to 7 ± 1.8 points at revision ACL-R, and 5.8 ± 1.7 points at the time of follow up (p < 0.001). Joint effusion (r = − 0.47, p < 0.01) and side to side differences in single leg hop test (r = − 0.48, p < 0.1) significantly correlated with inferior outcome. Cartilage lesions were found in 67% of the patients at the time of revision ACL-R compared to 38% at the time of primary ACL-R. According to the IKDC classification A was graded in three patients (4.3%), B in 35 (50%), C in 29 (41.4%) and D in three (4.3%). Joint effusion was measured in 35% of patients at the time of follow-up. Degeneration at the patellofemoral compartment of > grad 2 was responsible for IKDC grade C and D (p = 0.035). Instrumented anteroposterior site-to-site difference of ≥3 mm showed significant impact on clinical outcome (p < 0.019).

Conclusion
The study has shown that chronic effusion, quadriceps dysfunction, cartilage lesions especially at the patellofemoral compartment and side to side difference in anteroposterior stability significantly influences patient outcome after revision ACL-R. These factors require special attention when predicting patient’s outcome.

Level of evidence
Level-IV, case-controlled study.
Multimodal phantoms for clinical PET/MRI
Authors: Lennie Eve , Tsoumpas Charalampos , Sourbron Steven 
Published: August 2021

AbstractPhantoms are commonly used throughout medical imaging and medical physics for a multitude of applications, the designs of which vary between modalities and clinical or research requirements. Within positron emission tomography (PET) and nuclear medicine, phantoms have a well-established role in the validation of imaging protocols so as to reduce the administration of radioisotope to volunteers. Similarly, phantoms are used within magnetic resonance imaging (MRI) to perform quality assurance on clinical scanners, and gel-based phantoms have a longstanding use within the MRI research community as tissue equivalent phantoms. In recent years, combined PET/MRI scanners for simultaneous acquisition have entered both research and clinical use. This review explores the designs and applications of phantom work within the field of simultaneous acquisition PET/MRI as published over the period of a decade. Common themes in the design, manufacture and materials used within phantoms are identified and the solutions they provided to research in PET/MRI are summarised. Finally, the challenges remaining in creating multimodal phantoms for use with simultaneous acquisition PET/MRI are discussed. No phantoms currently exist commercially that have been designed and optimised for simultaneous PET/MRI acquisition. Subsequently, commercially available PET and nuclear medicine phantoms are often utilised, with CT-based attenuation maps substituted for MR-based attenuation maps due to the lack of MR visibility in phantom housing. Tissue equivalent and anthropomorphic phantoms are often developed by research groups in-house and provide customisable alternatives to overcome barriers such as MR-based attenuation correction, or to address specific areas of study such as motion correction. Further work to characterise materials and manufacture methods used in phantom design would facilitate the ability to reproduce phantoms across sites.
Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report
Authors: Jimbo Hikari , Horimoto Yoshiya , Okazaki Misato , Ishizuka Yumiko , Kido Hidenori , Saito Mitsue 
Published: August 2021

Abstract
Background
Pegfilgrastim is a modified version of granulocyte-colony stimulating factor (G-CSF), with a polyethylene glycol (PEG) that prolongs its half-life in peripheral blood. It is prophylactically administered during chemotherapy to prevent severe febrile neutropenia. G-CSF-related aortitis is a rare side effect but reports of this disease have been increasing in recent years, probably due to PEGylation. Herein, we report a case who developed pegfilgrastim-induced aortitis, localized to the right subclavian artery, during adjuvant chemotherapy. Her condition recovered without the use of steroids.

Case presentation
A 58-year-old woman was diagnosed with invasive ductal carcinoma of the left breast. She had a medical history of contralateral breast cancer and pyelonephritis. Following curative surgery for her left breast cancer, she received adjuvant chemotherapy. Two days after the first course of dose-dense paclitaxel, pegfilgrastim was used as planned. Eight days after the administration of pegfilgrastim, she developed a high fever of 38 °C and visited the emergency outpatient clinic 3 days after. Blood tests revealed an increased inflammatory response, and contrast-enhanced computed tomography (CT) revealed a wall thickening of the subclavian artery, suggesting aortitis caused by pegfilgrastim. She was hospitalized on day 15 when CRP increased to 21.5 mg/dL and the high fever continued. Blood and urine culture tests were negative throughout. Pegfilgrastim-induced aortitis was suspected and she was observed without the use of steroids. Seven days later, her fever abated. A contrast-enhanced CT scan on day 26 showed the subclavian artery wall thickening had disappeared. The patient continues to be afebrile and is currently on weekly paclitaxel without use of G-CSF.

Conclusions
The onset of this disease is known to usually occur within 2 weeks after the first pegfilgrastim administration. Aortitis localized to the subclavian artery is relatively rare with the most frequent site being the aortic arch. Clinicians should be aware of the timing and location of onset of this disease.