bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-fat diet impairs ferroptosis and promotes cancer invasiveness via downregulating tumor suppressor ACSL4 in lung adenocarcinoma
Authors: Zhang Yixiang , Li Songyu , Li Fengzhou , Lv Changsheng , Yang Qing-kai 
Published: May 2021

Abstract
Background
Long-chain acyl-CoA synthetase-4 (ACSL4) is involved in fatty acid metabolism, and aberrant ACSL4 expression could be either tumorigenic or tumor-suppressive in different tumor types. However, the function and clinical significance of ACSL4 in lung adenocarcinoma remain elusive.

Results
ACSL4 was frequently downregulated in lung adenocarcinoma when analyzing both the TCGA database and the validation samples, and the lower ACSL4 expression was correlated with a worse prognosis. Using gene set enrichment analysis, we found that high ACSL4 expression was frequently associated with the oxidative stress pathway, especially ferroptosis-related proteins. In vitro functional studies showed that knockdown of ACSL4 increased tumor survival/invasiveness and inhibited ferroptosis, while ACSL4 overexpression exhibited the opposite effects. Moreover, high-fat treatment could also inhibit erastin-induced ferroptosis by affecting ACSL4 expression. The anti-tumor effects of ferroptosis inducers and the anti-ferroptosis effects of the high-fat diet were further validated using the mouse xenograft model.

Conclusions
ACSL4 plays a tumor-suppressive role in lung adenocarcinoma by suppressing tumor survival/invasiveness and promoting ferroptosis. Our study provided a theoretical reference for the application of ferroptotic inducers and dietary guidance for lung adenocarcinoma patients.
Improvements of the productivity and saccharification efficiency of the cellulolytic β-glucosidase D2-BGL in Pichia pastoris via directed evolution
Authors: Kao Mu-Rong , Yu Su-May , Ho Tuan-H ua David 
Published: May 2021

Abstract
Background
β-Glucosidases are essential for cellulose hydrolysis by catalyzing the final cellulolytic degradation of cello-oligomers and cellobiose to glucose. D2-BGL is a fungal glycoside hydrolase family 3 (GH3) β-glucosidase isolated from Chaetomella raphigera with high substrate affinity, and is an efficient β-glucosidase supplement to Trichoderma reesei cellulase mixtures for the saccharification of lignocellulosic biomass.

Results
We have carried out error-prone PCR to further increase catalytic efficiency of wild-type (WT) D2-BGL. Three mutants, each with substitution of two amino acids on D2-BGL, exhibited increased activity in a preliminary mutant screening in Saccharomyces cerevisiae. Effects of single amino acid replacements on catalysis efficiency and enzyme production have been investigated by subsequent expression in Pichia pastoris. Substitution F256M resulted in enhancing the tolerance to substrate inhibition and specific activity, and substitution D224G resulted in increasing the production of recombinant enzyme. The best D2-BGL mutant generated, Mut M, was constructed by combining beneficial mutations D224G, F256M and Y260D. Expression of Mut M in Pichia pastoris resulted in 2.7-fold higher production of recombinant protein, higher Vmax and greater substrate inhibition tolerance towards cellobiose relative to wild-type enzyme. Surprisingly, Mut M overexpression induced the ER unfolded protein response to a level lower than that with WT D2 overexpression in P. pastoris. When combined with the T. reesei cellulase preparation Celluclast 1.5L, Mut M hydrolyzed acid-pretreated sugarcane bagasse more efficiently than WT D2.

Conclusions
D2-BGL mutant Mut M was generated successfully by following directed evolution approach. Mut M carries three mutations that are not reported in other directed evolution studies of GH3 β-glucosidases, and this mutant exhibited greater tolerance to substrate inhibition and higher Vmax than wild-type enzyme. Besides the enhanced specific activity, Mut M also exhibited a higher protein titer than WT D2 when it was overexpressed in P. pastoris. Our study demonstrates that both catalytic efficiency and productivity of a cellulolytic enzyme can be enhanced via protein engineering.
Polysaccharide utilization loci-driven enzyme discovery reveals BD-FAE: a bifunctional feruloyl and acetyl xylan esterase active on complex natural xylans
Authors: Hameleers Lisanne , Penttinen Leena , Ikonen Martina , Jaillot Léa , Fauré Régis , Terrapon Nicolas , Deuss Peter J. , Hakulinen Nina , Master Emma R. , Jurak Edita 
Published: May 2021

AbstractBackgroundNowadays there is a strong trend towards a circular economy using lignocellulosic biowaste for the production of biofuels and other bio-based products. The use of enzymes at several stages of the production process (e.g., saccharification) can offer a sustainable route due to avoidance of harsh chemicals and high temperatures. For novel enzyme discovery, physically linked gene clusters targeting carbohydrate degradation in bacteria, polysaccharide utilization loci (PULs), are recognized ‘treasure troves’ in the era of exponentially growing numbers of sequenced genomes.ResultsWe determined the biochemical properties and structure of a protein of unknown function (PUF) encoded within PULs of metagenomes from beaver droppings and moose rumen enriched on poplar hydrolysate. The corresponding novel bifunctional carbohydrate esterase (CE), now named BD-FAE, displayed feruloyl esterase (FAE) and acetyl esterase activity on simple, synthetic substrates. Whereas acetyl xylan esterase (AcXE) activity was detected on acetylated glucuronoxylan from birchwood, only FAE activity was observed on acetylated and feruloylated xylooligosaccharides from corn fiber. The genomic contexts of 200 homologs of BD-FAE revealed that the 33 closest homologs appear in PULs likely involved in xylan breakdown, while the more distant homologs were found either in alginate-targeting PULs or else outside PUL contexts. Although the BD-FAE structure adopts a typical α/β-hydrolase fold with a catalytic triad (Ser-Asp-His), it is distinct from other biochemically characterized CEs.ConclusionsThe bifunctional CE, BD-FAE, represents a new candidate for biomass processing given its capacity to remove ferulic acid and acetic acid from natural corn and birchwood xylan substrates, respectively. Its detailed biochemical characterization and solved crystal structure add to the toolbox of enzymes for biomass valorization as well as structural information to inform the classification of new CEs.
Data management plan for a community-level study of the hidden burden of cutaneous leishmaniasis in Colombia
Authors: Oviedo Sarmiento Oscar Javier , Castro María del Mar , Lerma Yenifer Orobio , Bernal Leonardo Vargas , Navarro Andrés , Alexander Neal D. E. 
Published: May 2021

Abstract
Objectives
Cutaneous leishmaniasis is a vector-borne parasitic disease whose lasting scars can cause stigmatization and depressive symptoms. It is endemic in remote rural areas and its incidence is under-reported, while the effectiveness, as opposed to efficacy, of its treatments is largely unknown. Here we present the data management plan (DMP) of a project which includes mHealth tools to address these knowledge gaps in Colombia. The objectives of the DMP are to specify the tools and procedures for data collection, data transfer, data entry, creation of analysis dataset, monitoring and archiving.

Results
The DMP includes data from two mobile apps: one implements a clinical prediction rule, and the other is for follow-up and treatment of confirmed cases. A desktop interface integrates these data and facilitates their linkage with other sources which include routine surveillance as well as paper and electronic case report forms. Multiple user and programming interfaces are used, as well as multiple relational and non-relational database engines. This DMP describes the successful integration of heterogeneous data sources and technologies. However the complexity of the project meant that the DMP took longer to develop than expected. We describe lessons learned which could be useful for future mHealth projects.
Giant hamartomatous polyp of the uterine cervix with heterologous mesenchymal tissue in a child: a case report
Authors: Esmat Esmatullah , Malakzai Haider Ali , Haidari Mujtaba , Haidary Ahmed Maseh , Baha Merwaise , Abdul-Ghafar Jamshid 
Published: May 2021

Abstract
Background
Polyps of the uterine cervix are one of the most common benign hyperplastic lesions occurring in the female genital tract that usually arise from the endocervical canal and are believed to be the result of reactive changes due to long-standing chronic inflammation, multiparty, and foreign bodies. Cervical polyps are usually small in size (less than 4 cm) that are commonly found in adult women; however, a few cases of giant polyps and the rare occurrence of these lesions in children have also been reported. Heterotopias and malignant transformation in cervical polyps are considered to be very rare.

Case presentation
We present the case of a 10-year-old Afghan girl with a giant pedunculated mass protruding out of the uterine cervix that was accompanied by abdominal pain and mass sensation. The mass was completely excised by surgical intervention and the specimen was submitted for histopathological evaluation. Upon gross and microscopic examination, the characteristic findings of a hamartomatous polyp with heterologous mesenchymal tissue in the form of mature cartilage were seen. To the best of our knowledge, this is the first case of a giant (17.5 cm) hamartomatous polyp of the uterine cervix in this age group.

Conclusion
Giant hamartomatous cervical polyps rarely occur in patients below 10 years of age. The majority of these lesions are benign; however, a few cases with malignant transformation are also reported, which demands elaborate investigations into the etiopathogenesis and nature of the lesions.
Impact of dexamethasone on the incidence of ventilator-associated pneumonia and blood stream infections in COVID-19 patients requiring invasive mechanical ventilation: a multicenter retrospective study
Authors: Gragueb-Chatti Ines , Lopez Alexandre , Hamidi Dany , Guervilly Christophe , Loundou Anderson , Daviet Florence , Cassir Nadim , Papazian Laurent , Forel Jean-Marie , Leone Marc , Dellamonica Jean , Hraiech Sami 
Published: May 2021

Abstract
Background
Dexamethasone decreases mortality in patients with severe coronavirus disease 2019 (COVID-19) and has become the standard of care during the second wave of pandemic. Dexamethasone is an immunosuppressive treatment potentially increasing the risk of secondary hospital acquired infections in critically ill patients. We conducted an observational retrospective study in three French intensive care units (ICUs) comparing the first and second waves of pandemic to investigate the role of dexamethasone in the occurrence of ventilator-associated pneumonia (VAP) and blood stream infections (BSI). Patients admitted from March to November 2020 with a documented COVID-19 and requiring mechanical ventilation (MV) for ≥ 48 h were included. The main study outcomes were the incidence of VAP and BSI according to the use of dexamethasone. Secondary outcomes were the ventilator-free days (VFD) at day-28 and day-60, ICU and hospital length of stay and mortality.

Results
Among the 151 patients included, 84 received dexamethasone, all but one during the second wave. VAP occurred in 63% of patients treated with dexamethasone (DEXA+) and 57% in those not receiving dexamethasone (DEXA−) (p = 0.43). The cumulative incidence of VAP, considering death, duration of MV and late immunosuppression as competing factors was not different between groups (p = 0.59). A multivariate analysis did not identify dexamethasone as an independent risk factor for VAP occurrence. The occurrence of BSI was not different between groups (29 vs. 30%; p = 0.86). DEXA+ patients had more VFD at day-28 (9 (0–21) vs. 0 (0–11) days; p = 0.009) and a reduced ICU length of stay (20 (11–44) vs. 32 (17–46) days; p = 0.01). Mortality did not differ between groups.

Conclusions
In this cohort of COVID-19 patients requiring invasive MV, dexamethasone was not associated with an increased incidence of VAP or BSI. Dexamethasone might not explain the high rates of VAP and BSI observed in critically ill COVID-19 patients.
Nitrogen uptake strategies of mature conifers in Northeastern China, illustrated by the 15N natural abundance method
Authors: Zhou Xulun , Wang Ang , Hobbie Erik A. , Zhu Feifei , Wang Xueyan , Li Yinghua , Fang Yunting 
Published: May 2021

Abstract

Background
Conifers partition different N forms from soil, including ammonium, nitrate, and dissolved organic N (DON), to sustain plant growth. Previous studies focused on inorganic N sources and specific amino acid forms using 15N labelling, but knowledge of the contribution of DON to mature conifers’ N uptake is still scarce. Here, we quantified the contribution of different N forms (DON vs. NH4+ vs. NO3−) to total N uptake, based on 15N natural abundance of plant and soil available N, in four mature conifers (Pinus koraiensis, Pinus sylvestris, Picea koraiensis, and Larix olgensis).

Results
DON contributed 31%, 29%, 28%, and 24% to total N uptake by Larix olgensis, Picea koraiensis, Pinus koraiensis, and Pinus sylvestris, respectively, whereas nitrate contributed 42 to 52% and ammonium contributed 19 to 29% of total N uptake for these four coniferous species.

Conclusions
Our results suggested that all four conifers could take up a relatively large proportion of nitrate, while DON was also an important N source for the four conifers. Given that DON was the dominant N form in study soil, such uptake pattern of conifers could be an adaptive strategy for plants to compete for the limited available N sources from soil so as to promote conifer growth and maintain species coexistence.
Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches
Authors: Shakya Sajina , Gromovsky Anthony D. , Hale James S. , Knudsen Arnon M. , Prager Briana , Wallace Lisa C. , Penalva Luiz O. F. , Brown H. Alex , Kristensen Bjarne W. , Rich Jeremy N. , Lathia Justin D. , Brown J. Mark , Hubert Christopher G. 
Published: May 2021

AbstractGlioblastoma (GBM) displays marked cellular and metabolic heterogeneity that varies among cellular microenvironments within a tumor. Metabolic targeting has long been advocated as a therapy against many tumors including GBM, but how lipid metabolism is altered to suit different microenvironmental conditions and whether cancer stem cells (CSCs) have altered lipid metabolism are outstanding questions in the field. We interrogated gene expression in separate microenvironments of GBM organoid models that mimic the transition between nutrient-rich and nutrient-poor pseudopalisading/perinecrotic tumor zones using spatial-capture RNA-sequencing. We revealed a striking difference in lipid processing gene expression and total lipid content between diverse cell populations from the same patient, with lipid enrichment in hypoxic organoid cores and also in perinecrotic and pseudopalisading regions of primary patient tumors. This was accompanied by regionally restricted upregulation of hypoxia-inducible lipid droplet-associated (HILPDA) gene expression in organoid cores and pseudopalisading regions of clinical GBM specimens, but not lower-grade brain tumors. CSCs have low lipid droplet accumulation compared to non-CSCs in organoid models and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. Targeted lipidomic analysis of multiple patient-derived models revealed a significant shift in lipid metabolism between GBM CSCs and non-CSCs, suggesting that lipid levels may not be simply a product of the microenvironment but also may be a reflection of cellular state. CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs, but had significantly increased polyunsaturated fatty acid production due to high fatty acid desaturase (FADS1/2) expression which was essential to maintain CSC viability and self-renewal. Our data demonstrate spatially and hierarchically distinct lipid metabolism phenotypes occur clinically in the majority of patients, can be recapitulated in laboratory models, and may represent therapeutic targets for GBM.
Estimation of renal perfusion based on measurement of rubidium-82 clearance by PET/CT scanning in healthy subjects
Authors: Langaa Stine Sundgaard , Lauridsen Thomas Guldager , Mose Frank Holden , Fynbo Claire Anne , Theil Jørn , Bech Jesper Nørgaard 
Published: May 2021

Abstract
Background
Changes in renal blood flow (RBF) may play a pathophysiological role in hypertension and kidney disease. However, RBF determination in humans has proven difficult. We aimed to confirm the feasibility of RBF estimation based on positron emission tomography/computed tomography (PET/CT) and rubidium-82 (82Rb) using the abdominal aorta as input function in a 1-tissue compartment model.

Methods
Eighteen healthy subjects underwent two dynamic 82Rb PET/CT scans in two different fields of view (FOV). FOV-A included the left ventricular blood pool (LVBP), the abdominal aorta (AA) and the majority of the kidneys. FOV-B included AA and the kidneys in their entirety. In FOV-A, an input function was derived from LVBP and from AA, in FOV-B from AA. One-tissue compartmental modelling was performed using tissue time activity curves generated from volumes of interest (VOI) contouring the kidneys, where the renal clearance of 82Rb is represented by the K1 kinetic parameter. Total clearance for both kidneys was calculated by multiplying the K1 values with the volume of VOIs used for analysis. Intra-assay coefficients of variation and inter-observer variation were calculated.

Results
For both kidneys, K1 values derived from AA did not differ significantly from values obtained from LVBP, neither were significant differences seen between AA in FOV-A and AA in FOV-B, nor between the right and left kidneys. For both kidneys, the intra-assay coefficients of variation were low (~ 5%) for both input functions. The measured K1 of 2.80 ml/min/cm3 translates to a total clearance for both kidneys of 766 ml/min/1.73 m2.

Conclusion
Measurement of renal perfusion based on PET/CT and 82Rb using AA as input function in a 1-tissue compartment model is feasible in a single FOV. Based on previous studies showing 82Rb to be primarily present in plasma, the measured K1 clearance values are most likely representative of effective renal plasma flow (ERPF) rather than estimated RBF values, but as the accurate calculation of total clearance/flow is very much dependent on the analysed volume, a standardised definition for the employed renal volumes is needed to allow for proper comparison with standard ERPF and RBF reference methods.
Review of menopausal palpitations measures
Authors: Sheng Ying , Carpenter Janet S. , Elomba Charles D. , Alwine Jennifer S. , Yue Min , Pike Caitlin A. , Chen Chen X. , Tisdale James E. 
Published: May 2021

AbstractPalpitations are reported commonly by women around the time of menopause as skipped, missed, irregular, and/or exaggerated heartbeats or heart pounding. However, much less is known about palpitations than other menopausal symptoms such as vasomotor symptoms. The objective of this review was to integrate evidence on menopausal palpitations measures. Keyword searching was done in PubMed, CINAHL, and PsycINFO for English-language, descriptive articles containing data on menopause and palpitations and meeting other pre-specified inclusion criteria. Of 670 articles, 110 met inclusion criteria and were included in the review. Results showed that 11 different measures were used across articles, with variability within and between measures. Inconsistencies in the wording of measurement items, recall periods, and response options were observed even when standardized measures were used. Most measures were limited to assessing symptom presence and severity. Findings suggest that efforts should be undertaken to (1) standardize conceptual and operational definitions of menopausal palpitations and (2) develop a patient-friendly, conceptually clear, psychometrically sound measure of menopausal palpitations.
Influence of low-level laser therapy on implant stability in implants placed in healed sites: a randomized controlled trial
Authors: Kinalski Mateus de Azevedo , Agostini Bernardo Antonio , Bergoli Cesar Dalmolin , dos Santos Mateus Bertolini Fernandes 
Published: May 2021

Abstract
Background
The present study aims to assess the influence of low-level laser therapy (LLLT) on stability in implants placed in healed sites.

Material and methods
The present study followed the SPIRIT statement and is reported according to CONSORT. Patients were randomly allocated to LLLT or control groups. LLLT consisted in the application of 808-nm GaAlA laser applied before the preparation of the implant bed and after suturing (80 seconds; 11J/cm2). Implant stability quotient (ISQ) and the distance between the implant platform to the alveolar bone crest (millimeters) were assessed at implant placement (T0) and the abutment selection phase (4–6 months, Ta).

Results
A total of 64 implants were placed in 33 patients. The insertion torque ranged from 10 to 70 N.cm (mean 43.23; SD ±16.82). The T0 ISQ ranged from 18 to 95.5 (mean 61.7; SD ±18.23) and the crestal bone radiographic distance was 2.03 mm (SD±1.27). At Ta, the ISQ ranged from 39 to 90 (mean 64.2; SD±9.84), and the mean crestal bone radiographic loss was 1.70mm (SD±1.65). However, no differences were observed when LLLT and control groups were compared with ISQ difference (Ta–T0; p=0.598) or radiographical peri-implant alterations (p=0.531).

Conclusion
LLLT did not influence the implant stability in implants placed in healed sites compared to a control group.

Trial registration
ReBEC, RBR-35TNJ7. Registered May 23, 2018