bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational profiling of micro-dissected pre-malignant lesions from archived specimens
Authors: Nachmanson Daniela , Steward Joseph , Yao Huazhen , Officer Adam , Jeong Eliza , O’Keefe Thomas J. , Hasteh Farnaz , Jepsen Kristen , Hirst Gillian L. , Esserman Laura J. , Borowsky Alexander D. , Harismendy Olivier 
Published: November 2020

Abstract
Background
Systematic cancer screening has led to the increased detection of pre-malignant lesions (PMLs). The absence of reliable prognostic markers has led mostly to over treatment resulting in potentially unnecessary stress, or insufficient treatment and avoidable progression. Importantly, most mutational profiling studies have relied on PML synchronous to invasive cancer, or performed in patients without outcome information, hence limiting their utility for biomarker discovery. The limitations in comprehensive mutational profiling of PMLs are in large part due to the significant technical and methodological challenges: most PML specimens are small, fixed in formalin and paraffin embedded (FFPE) and lack matching normal DNA.

Methods
Using test DNA from a highly degraded FFPE specimen, multiple targeted sequencing approaches were evaluated, varying DNA input amount (3–200 ng), library preparation strategy (BE: Blunt-End, SS: Single-Strand, AT: A-Tailing) and target size (whole exome vs. cancer gene panel). Variants in high-input DNA from FFPE and mirrored frozen specimens were used for PML-specific variant calling training and testing, respectively. The resulting approach was applied to profile and compare multiple regions micro-dissected (mean area 5 mm2) from 3 breast ductal carcinoma in situ (DCIS).

Results
Using low-input FFPE DNA, BE and SS libraries resulted in 4.9 and 3.7 increase over AT libraries in the fraction of whole exome covered at 20x (BE:87%, SS:63%, AT:17%). Compared to high-confidence somatic mutations from frozen specimens, PML-specific variant filtering increased recall (BE:85%, SS:80%, AT:75%) and precision (BE:93%, SS:91%, AT:84%) to levels expected from sampling variation. Copy number alterations were consistent across all tested approaches and only impacted by the design of the capture probe-set. Applied to DNA extracted from 9 micro-dissected regions (8 PML, 1 normal epithelium), the approach achieved comparable performance, illustrated the data adequacy to identify candidate driver events (GATA3 mutations, ERBB2 or FGFR1 gains, TP53 loss) and measure intra-lesion genetic heterogeneity.

Conclusion
Alternate experimental and analytical strategies increased the accuracy of DNA sequencing from archived micro-dissected PML regions, supporting the deeper molecular characterization of early cancer lesions and achieving a critical milestone in the development of biology-informed prognostic markers and precision chemo-prevention strategies.
Lower serum 25-hydroxycholecalciferol is associated with depressive symptoms in older adults in Southern Brazil
Authors: Ceolin Gilciane , Matsuo Luísa Harumi , Confortin Susana Cararo , D’Orsi Eleonora , Rieger Débora Kurrle , Moreira Júlia Dubois 
Published: November 2020

AbstractBackgroundOlder adults are one of the most susceptible populations to depression, especially those living in low- and middle-income countries. As well, they are also considering a risk group for vitamin D deficiency. Low serum vitamin D has been associated with an increased risk of brain neuropsychiatry disorders. We aimed to investigate the association between serum 25-hydroxycholecalciferol concentrations and depressive symptoms in adults aged 60 years and over from southern Brazil.MethodsA cross-sectional analysis was performed using data collected during 2013–2014 from the populational-based longitudinal EpiFloripa Aging Study (n = 1197). Serum 25-hydroxycholecalciferol concentrations were analyzed and classified according to the Endocrine Society reference values [sufficiency (≥ 30 ng/mL), insufficiency (21–29 ng/mL), and deficiency (≤ 20 ng/mL)]. Depressive symptoms were evaluated using the Geriatric Depression Scale (15-item GDS). Logistic regression was performed to assess depressive symptoms in each vitamin D category. The analysis was adjusted for sex, age, skin color, family income, leisure-time physical activities, social or religious groups attendance, morbidities, cognitive impairment, and dependence in activities of daily living.ResultsA total of 557 participants with complete data for exposure and outcome were enrolled in the analysis. Most of the sample participants were female (63.1%), age-range 60–69 years (42.2%), white skin color (85.1%), and vitamin D serum level samples were collected in autumn (50.7%). Depressive symptoms were present in 15.8% of the participants, and the prevalence was higher in individuals classified as deficient in vitamin D (23.2, 95% confidence interval [CI] = 15.6;32.9) and insufficiency (17.2, 95%CI = 11.0;25.9). The crude analysis showed that vitamin D deficient participants had 3.08 (CI = 1.53;6.20) times higher odds to present depressive symptoms compared to vitamin D sufficiency. After adjusting, the association was maintained [OR 2.27 (95%CI = 1.05;4.94).ConclusionsSerum 25-hydroxycholecalciferol deficiency was positively associated with depressive symptoms in older adults from southern Brazil.
Cytoplasm protein GFAP magnetic beads construction and application as cell separation target for brain tumors
Authors: Zhao Yang , Jiang Feng , Wang Qinhua , Wang Baocheng , Han Yipeng , Yang Jian , Wang Jiajia , Wang Kai , Ao Junping , Guo Xunxiang , Liang Xiaofei , Ma Jie 
Published: November 2020

Abstract
Background
It is very important to develop a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function, for which the detection of circulating tumor cells (CTCs) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTCs separation target, a cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposome beads (IMLs). The validation and efficiency of this system in capturing CTCs for brain tumors were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed.

Results
Our data show that CTCs can be successfully isolated from CSF and blood samples from 32 children with brain tumors. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. The higher the CTCs number is, the more possibly the patient will suffer from poor prognosis. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTCs was consistent with that of tumor tissue.

Conclusions
The results indicated that GFAP-IML CTCs isolation system, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique may play a significant role in the clinical diagnosis and drug evaluation of brain tumors.
Effect of silica-coated magnetic nanoparticles on rigidity sensing of human embryonic kidney cells
Authors: Ketebo Abdurazak Aman , Shin Tae Hwan , Jun Myeongjun , Lee Gwang , Park Sungsu 
Published: November 2020

AbstractBackgroundNanoparticles (NPs) can enter cells and cause cellular dysfunction. For example, reactive oxygen species generated by NPs can damage the cytoskeleton and impair cellular adhesion properties. Previously, we reported that cell spreading and protrusion structures such as lamellipodia and filopodia was reduced when cells are treated with silica-coated magnetic nanoparticles incorporating rhodamine B isothiocyanate (MNPs@SiO2(RITC)), even at 0.1 μg/μL. These protruded structures are involved in a cell’s rigidity sensing, but how these NPs affect rigidity sensing is unknown.ResultsHere, we report that the rigidity sensing of human embryonic kidney (HEK293) cells was impaired even at 0.1 μg/μL of MNPs@SiO2(RITC). At this concentration, cells were unable to discern the stiffness difference between soft (5 kPa) and rigid (2 MPa) flat surfaces. The impairment of rigidity sensing was further supported by observing the disappearance of locally contracted elastomeric submicron pillars (900 nm in diameter, 2 μm in height, 24.21 nN/μm in stiffnessk) under MNPs@SiO2(RITC) treated cells. A decrease in the phosphorylation of paxillin, which is involved in focal adhesion dynamics, may cause cells to be insensitive to stiffness differences when they are treated with MNPs@SiO2(RITC).ConclusionsOur results suggest that NPs may impair the rigidity sensing of cells even at low concentrations, thereby affecting cell adhesion and spreading.
Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis
Authors: Chen Mei , Yang Nan , Lechner Judith , Toth Levente , Hogg Ruth , Silvestri Giuliana , Chakravarthy Usha , Xu Heping 
Published: November 2020

Abstract
Background
Previously, we and others have reported higher populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients’ responsiveness to anti-VEGF therapy.

Results
One hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 healthy controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r = 0.29, P = 0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r = 0.34, p = 0.0007) but not in healthy controls (r = 0.057, p = 0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients’ responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls.

Conclusions
Our results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.
An anti-CD6 monoclonal antibody (itolizumab) reduces circulating IL-6 in severe COVID-19 elderly patients
Authors: Saavedra Danay , Añé-Kourí Ana Laura , Sánchez Naivy , Filgueira Lázaro Manuel , Betancourt Julio , Herrera Carlos , Manso Leniel , Chávez Elibet , Caballero Armando , Hidalgo Carlos , Lorenzo Geydi , Cepeda Meylan , Valenzuela Carmen , Ramos Mayra , León Kalet , Mazorra Zaima , Crombet Tania 
Published: November 2020

Abstract
Background
Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around the world has been placed. In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities have been the most risky population. Although most patients present a mild to moderate disease, some have developed severe symptoms. One of the possible mechanisms underlying rapid disease progression is a cytokine storm, in which interleukin (IL) -6 seems to be a major mediator. Itolizumab is a humanized recombinant anti-CD6 monoclonal antibody (MAb), with the ability of reducing serum interferon gamma (INF-γ), tumour necrosis factor alpha (TNFα) and IL-6. Based on these previous results in patients with psoriasis and rheumatoid arthritis, an expanded access clinical trial was approved by the Cuban regulatory agency for COVID-19 critically, severely and moderately ill patients.

Results
We show here a short kinetic of IL-6 serum concentration in the first 24 COVID-19 patients treated with itolizumab. Most of patients were elderly with multiple comorbidities. We found that with one itolizumab dose, the circulating IL-6 decreased in critically and severely ill patients, whereas in moderately ill patients the values didn’t rise as compared to their low baseline levels.

Conclusion
These findings suggest that itolizumab could be an attractive therapeutic option to decrease the negative outcome of the cytokine storm in COVID-19 patients.

Trial registration
CECMED IIC RD-EC 179, RPCEC00000311. Registered 4 May 2020 - Retrospectively registered, http://rpcec.sld.cu/ensayos/RPCEC00000311-Sp or http://rpcec.sld.cu/trials/RPCEC00000311-En
First report of Plum bark necrosis stem pitting-associated virus infecting grapevine in China
Authors: Yang Yang , Sun Yifan , Li Qingliang , Wu Yufeng , Wang Deya 
Published: November 2020

Abstract
Background
Virus disease is one of the main diseases in grapevine, and there has been no report on Plum bark necrosis and stem pitting-associated virus infecting grapevine in China.

Objective
The leaf samples of grapevine cultivar 'Cabernet Gernischt' were collected from Shandong province, which the leaves suffered from viral-like symptoms with spotting and crinkle.

Methods
Small RNA-seq combined with reverse transcription PCR (RT-PCR) were performed to detect the potential viruses in these field samples. Phylogenetic tree was constructed using the neighbor joining method in MEGA 5.1

Conclusions
This is the first report of PBNSPaV infecting grapevine in China, contributing to a better understanding of the epidemiology and host range distribution of this pathogen.
Poor sensitivity of "AccuPower SARS-CoV-2 real time RT-PCR kit (Bioneer, South Korea)"
Authors: Freire-Paspuel Byron , Garcia-Bereguiain Miguel Angel 
Published: November 2020

Abstract
Background
Several molecular kits are available for SARS-CoV-2 diagnosis, mostly lacking of proper clinical evaluation due to the emergency caused by COVID19 pandemia, particularly at developing countries like Ecuador.

Objective
We carried out an evaluation of the clinical performance of "AccuPower SARS-CoV-2 Real Time RT-PCR kit" (Bioneer, South Korea) for SARS-CoV-2 diagnosis using 2019-nCoV CDC EUA kit (IDT, USA) as a gold standard.

Results
48 clinical specimens were included on the study, 38 tested SARS-CoV-2 positive and 10 SARS-CoV-2 negative for 2019-nCoV CDC EUA kit. For "AccuPower SARS-CoV-2 Real Time RT-PCR kit", only 30 were SARS-CoV-2 positive, indicating a low clinical performance with sensitivity of 78.9%. Moreover, the limit of detection for "AccuPower SARS-CoV-2 Real Time RT-PCR kit" was estimated to be higher than 40,000 viral RNA copies/mL of sample.

Conclusions
Proper clinical performance evaluation studies from government agencies at developing countries should be mandatory prior to clinical use authorization of SARS-CoV-2 diagnosis kits, particularly when those kits lack of either FDA or its country of origin clinical use authorization, to prevent the distribution of low quality products that may have a negative impact of COVID19 surveillance at developing countries.
Estimated prevalence of mucopolysaccharidoses from population-based exomes and genomes
Authors: Borges Pâmella , Pasqualim Gabriela , Giugliani Roberto , Vairo Filippo , Matte Ursula 
Published: November 2020

Abstract
Background
In this study, the prevalence of different types of mucopolysaccharidoses (MPS) was estimated based on data from the exome aggregation consortium (ExAC) and the genome aggregation database (gnomAD). The population-based allele frequencies were used to identify potential disease-causing variants on each gene related to MPS I to IX (except MPS II).

Methods
We evaluated the canonical transcripts and excluded homozygous, intronic, 3′, and 5′ UTR variants. Frameshift and in-frame insertions and deletions were evaluated using the SIFT Indel tool. Splice variants were evaluated using SpliceAI and Human Splice Finder 3.0 (HSF). Loss-of-function single nucleotide variants in coding regions were classified as potentially pathogenic, while synonymous variants outside the exon–intron boundaries were deemed non-pathogenic. Missense variants were evaluated by five in silico prediction tools, and only those predicted to be damaging by at least three different algorithms were considered disease-causing.

Results
The combined frequencies of selected variants (ranged from 127 in GNS to 259 in IDUA) were used to calculate prevalence based on Hardy–Weinberg's equilibrium. The maximum estimated prevalence ranged from 0.46 per 100,000 for MPSIIID to 7.1 per 100,000 for MPS I. Overall, the estimated prevalence of all types of MPS was higher than what has been published in the literature. This difference may be due to misdiagnoses and/or underdiagnoses, especially of the attenuated forms of MPS. However, overestimation of the number of disease-causing variants by in silico predictors cannot be ruled out. Even so, the disease prevalences are similar to those reported in diagnosis-based prevalence studies.

Conclusion
We report on an approach to estimate the prevalence of different types of MPS based on publicly available population-based genomic data, which may help health systems to be better prepared to deal with these conditions and provide support to initiatives on diagnosis and management of MPS.
Promoting the co-utilisation of glucose and xylose in lignocellulosic ethanol fermentations using a data-driven feed-back controller
Authors: Lopez Pau Cabaneros , Abeykoon Udugama Isuru , Thomsen Sune Tjalfe , Bayer Christoph , Junicke Helena , Gernaey Krist V. 
Published: November 2020

Abstract
Background
The diauxic growth of Saccharomyces cerevisiae on glucose and xylose during cellulose-to-ethanol processes extends the duration of the fermentation and reduces productivity. Despite the remarkable advances in strain engineering, the co-consumption of glucose and xylose is still limited due to catabolite repression. This work addresses this challenge by developing a closed-loop controller that is capable of maintaining the glucose concentration at a steady set-point during fed-batch fermentation. The suggested controller uses a data-driven model to measure the concentration of glucose from ‘real-time’ spectroscopic data. The concentration of glucose is then automatically controlled using a control scheme that consists of a proportional, integral, differential (PID) algorithm and a supervisory layer that manipulates the feed-rates to the reactor accounting for the changing dynamics of fermentation.

Results
The PID parameters and the supervisory layer were progressively improved throughout four fed-batch lignocellulosic-to-ethanol fermentations to attain a robust controller able of maintaining the glucose concentration at the pre-defined set-points. The results showed an increased co-consumption of glucose and xylose that resulted in volumetric productivities that are 20–33% higher than the reference batch processes. It was also observed that fermentations operated at a glucose concentration of 10 g/L were faster than those operated at 4 g/L, indicating that there is an optimal glucose concentration that maximises the overall productivity.

Conclusions
Promoting the simultaneous consumption of glucose and xylose in S. cerevisiae is critical to increase the productivity of lignocellulosic ethanol processes, but also challenging due to the strong catabolite repression of glucose on the uptake of xylose. Operating the fermentation at low concentrations of glucose allows reducing the effects of the catabolite repression to promote the co-consumption of the two carbon sources. However, S. cerevisiae is very sensitive to changes in the glucose concentration and deviations from a set-point result in notable productivity losses. The controller structure developed and implemented in this work illustrates how combining data-driven measurements of the glucose concentration and a robust yet effective PID-based supervisory control allowed tight control of the concentration of glucose to adjust it to the metabolic requirements of the cell culture that can unlock tangible gains in productivities.
Evaluating the impact of biannual school-based and community-wide treatment on urogenital schistosomiasis in Niger
Authors: Phillips Anna E. , Tohon Zilahatou , Dhanani Neerav A. , Sofo Boubacar , Gnandou Issa , Sidikou Boubacar , Noma Adamou Garba , Madougou Bassirou , Alto Oumarou , Sebangou Hannatou , Halilou Kader M. , Andia Roumanatou , Garba Amadou , Fenwick Alan , Hamidou Amina A. 
Published: November 2020

Abstract
Background
The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinated a five-year study implemented in several countries, including Niger, to provide an evidence-base for programmatic decisions regarding cost-effective approaches to preventive chemotherapy for schistosomiasis control.

Methods
This was a cluster-randomised trial investigating six possible combinations of annual or biannual community-wide treatment (CWT), school-based treatment (SBT), and holidays from mass treatment over four years. The most intense arm involved two years of annual CWT followed by 2 years of biannual CWT, while the least intensive arm involved one year of annual SBT followed by a year without treatment and two more years of annual SBT. The primary outcome of interest was prevalence and intensity of Schistosoma haematobium among 100 children aged 9–12 years sampled each year. In addition, 100 children aged 5–8 years in their first year of school and 50 adults (aged 20–55 years) were tested in the first and final fifth year of the study.

Results
In total, data were collected from 167,500 individuals across 225 villages in nine districts within the Niger River valley, Western Niger. Overall, the prevalence of S. haematobium decreased from baseline to Year 5 across all study arms. The relative reduction of prevalence was greater in biannual compared with annual treatment across all arms; however, the only significant difference was seen in areas with a high starting prevalence. Although adults were not targeted for treatment in SBT arms, a statistically significant decrease in prevalence among adults was seen in moderate prevalence areas receiving biannual (10.7% to 4.8%) SBT (P < 0.001). Adults tested in the annual SBT group also showed a decrease in prevalence between Year 1 and Year 5 (12.2% to 11.0%), but this difference was not significant.

Conclusions
These findings are an important consideration for schistosomiasis control programmes that are considering elimination and support the idea that scaling up the frequency of treatment rounds, particularly in areas of low prevalence, will not eliminate schistosomiasis. Interestingly, the finding that prevalence decreased among adults in SBT arms suggests that transmission in the community can be reduced, even where only school children are being treated, which could have logistical and cost-saving implications for the national control programmes.

Graphical Abstract