bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microaerobic metabolism of lactate and propionate enhances vitamin B12 production in Propionibacterium freudenreichii
Authors: Dank Alexander , Biel Gabriela , Abee Tjakko , Smid Eddy J. 
Published: October 2022

Abstract
Background
Propionibacterium freudenreichii is used in biotechnological applications to produce vitamin B12. Although cultured mainly in anaerobic conditions, microaerobic conditions can greatly enhance biomass formation in P. freudenreichii. Since B12 yields may be coupled to biomass formation, microaerobic conditions show great potential for increasing B12 yields in P. freudenreichii.

Results
Here we show biomass formation increases 2.7 times for P. freudenreichii grown in microaerobic conditions on lactate versus anaerobic conditions (1.87 g/L vs 0.70 g/L). Consumption of lactate in microaerobic conditions resulted first in production of pyruvate, propionate and acetate. When lactate was depleted, pyruvate and propionate were oxidised with a concomitant sixfold increase in the B12 titer compared to anaerobic conditions, showing potential for propionate and pyruvate as carbon sources for B12 production. Consequently, a fed-batch reactor with anaerobically precultured lactate-grown cells was fed propionate in microaerobic conditions resulting in biomass increase and production of B12. Vitamin yields increased from 0.3 $$\mu g$$

μ
g

B12 per mmol lactate in anaerobic conditions to 2.4 $$\mu g$$

μ
g

B12 per mmol lactate and 8.4 $$\mu g$$

μ
g

B12 per mmol propionate in microaerobic conditions. Yield per cell dry weight (CDW) increased from 41 $$\mu g$$

μ
g

per g CDW in anaerobic conditions on lactate to 92 $$\mu g$$

μ
g

per g CDW on lactate and 184 $$\mu g$$

μ
g

per g CDW on propionate in microaerobic conditions.

Conclusions
Here we have shown both B12 yield per substrate and per CDW were highest on cells oxidising propionate in microaerobic conditions, showing the potential of propionate for biotechnological production of vitamin B12 by P. freudenreichii.
Lipid production from lignocellulosic biomass using an engineered Yarrowia lipolytica strain
Authors: Drzymała-Kapinos Katarzyna , Mirończuk Aleksandra M. , Dobrowolski Adam 
Published: October 2022

Abstract
Background
The utilization of industrial wastes as feedstock in microbial-based processes is a one of the high-potential approach for the development of sustainable, environmentally beneficial and valuable bioproduction, inter alia, lipids. Rye straw hydrolysate, a possible renewable carbon source for bioconversion, contains a large amount of xylose, inaccessible to the wild-type Yarrowia lipolytica strains. Although these oleaginous yeasts possesses all crucial genes for xylose utilization, it is necessary to induce their metabolic pathway for efficient growth on xylose and mixed sugars from agricultural wastes. Either way, biotechnological production of single cell oils (SCO) from lignocellulosic hydrolysate requires yeast genome modification or adaptation to a suboptimal environment.

Results
The presented Y. lipolytica strain was developed using minimal genome modification—overexpression of endogenous xylitol dehydrogenase (XDH) and xylulose kinase (XK) genes was sufficient to allow yeast to grow on xylose as a sole carbon source. Diacylglycerol acyltransferase (DGA1) expression remained stable and provided lipid overproduction. Obtained an engineered Y.lipolytica strain produced 5.51 g/L biomass and 2.19 g/L lipids from nitrogen-supplemented rye straw hydrolysate, which represents an increase of 64% and an almost 10 times higher level, respectively, compared to the wild type (WT) strain. Glucose and xylose were depleted after 120 h of fermentation. No increase in byproducts such as xylitol was observed.

Conclusions
Xylose-rich rye straw hydrolysate was exploited efficiently for the benefit of production of lipids. This study indicates that it is possible to fine-tune a newly strain with as minimally genetic changes as possible by adjusting to an unfavorable environment, thus limiting multi-level genome modification. It is documented here the use of Y. lipolytica as a microbial cell factory for lipid synthesis from rye straw hydrolysate as a low-cost feedstock.
Molecular subtypes based on cuproptosis-related genes and tumor microenvironment infiltration characterization in ovarian cancer
Authors: Zhang Jingjing , Lu Miao , Xu Haoya , Ren Fang , Zhu Liancheng 
Published: October 2022

Abstract
Background
Cuproptosis (copper death) is a recently found cell death type produced by copper iron; nonetheless, the properties of cuproptosis molecular subtypes and possible involvement of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) in ovarian cancer (OC) remain unknown.

Methods
CRG changes were characterized at the genomic and transcriptional levels in 656 OC samples, and their expression patterns were investigated using three different datasets.

Results
We identified three distinct molecular subtypes, and discovered that variations in molecular subtypes were linked to patient prognosis, TME cell infiltration characteristics, malignancy, and immune-related pathways. Then, in order to predict overall survival (OS), we created a risk score and tested its predictive potential in OC patients. As a result, we created a very accurate nomogram to increase risk score clinical applicability. Better OS, younger age, early stage, and immune activity were all associated with a low risk score. The hallmarks of a high-risk score are older age, advanced stage, immunosuppression, and a bad prognosis. Furthermore, risk score was linked to immune checkpoint expression (including PD-L1, CTLA4), targeted therapy gene expression (PARP, PDGFRA), cancer stem cell (CSC), chemotherapy and targeted medication sensitivity.

Conclusions
Our comprehensive analysis of CRGs in OC showed their potential role in TME, clinicopathological characteristics, chemotherapy and targeted drug screening and prognosis. These discoveries could help us better understand CRGs in OC, as well as pave the path for novel ways to assess prognosis and design more effective immunotherapy strategies.
Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018
Authors: Guerra Angela Patricia , Olivera Mario Javier , Cortés Liliana Jazmín , Chenet Stella M. , Macedo de Oliveira Alexandre , Lucchi Naomi W. 
Published: October 2022

Abstract
Background
Resistance to anti-malarial drugs is associated with polymorphisms in target genes and surveillance for these molecular markers is important to detect the emergence of mutations associated with drug resistance and signal recovering sensitivity to anti-malarials previously used.

Methods
The presence of polymorphisms in genes associated with Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated by Sanger sequencing, in 85 P. falciparum day of enrollment samples from a therapeutic efficacy study of artemether–lumefantrine conducted in 2018–2019 in Quibdo, Colombia. Samples were genotyped to assess mutations in pfcrt (codons 72–76), pfdhfr (codons 51, 59, 108, and 164), and pfdhps genes (codons 436, 437, 540, and 581). Further, the genetic diversity of infections using seven neutral microsatellites (NMSs) (C2M34, C3M69, Poly α, TA1, TA109, 2490, and PfPK2) was assessed.

Results
All isolates carried mutant alleles for pfcrt (K76T and N75E), and for pfdhfr (N51I and S108N), while for pfdhps, mutations were observed only for codon A437G (32/73, 43.8%). Fifty samples (58.8%) showed a complete neutral microsatellites (NMS) profile. The low mean number of alleles (2 ± 0.57) per locus and mean expected heterozygosity (0.17 ± 0.03) showed a reduced genetic diversity. NMS multilocus genotypes (MMG) were built and nine MMG were identified.

Conclusions
Overall, these findings confirm the fixation of chloroquine and pyrimethamine-resistant alleles already described in the literature, implying that these drugs are not currently appropriate for use in Colombia. In contrast, mutations in the pfdhps gene were only observed at codon 437, an indication that full resistance to sulfadoxine has not been achieved in Choco. MMGs found matched the clonal lineage E variant 1 previously reported in northwestern Colombia.
New insight into the role of lipid metabolism-related proteins in rheumatic heart valve disease
Authors: Xie Ting , Chen Xuan , Liu Cong , Cai Xingjiu , Xiang Mei , Liu Shiwu , Li Ruzheng , Lin Zhichuan , Liu Debing , Dong Ming , Chen Xinzhong , Zou Minghui , Qiao Ping 
Published: October 2022

Abstract
Purpose
The aim of this study was to determine the expression of lipid metabolism-related proteins in rheumatic heart valve disease (RHVD).

Methods
This retrospective study involved a total of 20 cases of moderate or severe rheumatic mitral valve stenosis and 4 cases of mitral regurgitation due to secondary causes from September 2018 to September 2021. The patients enrolled included 12 males and 12 females who underwent surgical excision of the mitral valve at the cardiac surgery department of Hainan General Hospital. The samples of mitral valve were collected during surgery treatment as the study group, and mitral valves collected from patients with ischemic heart disease were allocated into the control group. Hematoxylin–eosin (HE), oil red staining and immunohistochemical (IHC) staining were conducted to compare the expression of lipid metabolism-related proteins (ATP-binding cassette transporter A1 and acyl-coenzyme A: cholesterol acyltransferase-1), and real-time polymerase chain reaction (RT–PCR) was applied to compare the mRNA levels of ABCA1, ACAT1, and the inflammatory cytokines TNF-α, IL-10, and MCP-1.

Results
In general, the rheumatic mitral valve showed leaflet thickening along with border adhesions and visible yellow fats. Oil red O staining also revealed the abovementioned results as well as fat cells. Both ABCA1 and ACAT1 were expressed in the rheumatic mitral valve via IHC, whereas only ACAT1 showed a faint level of expression in the ischemic mitral valve with no expression of ABCA1. In addition, compared with the ischemic mitral valve, RT-PCT showed increased mRNA expression levels of ABCA1, ACAT1, and the inflammatory cytokines TNF-α, IL-10, and MCP-1 (P < 0.05). After dividing the RMs into two groups for RT–PCR, we found that the higher the expression of ABCA1 and ACAT1 was, the lower the relative expression of inflammatory factors.

Conclusion
This study showed that adipose tissue, adipose cells, and lipid transport-related proteins were expressed strongly in the rheumatic mitral valve, suggesting that adipose tissue formation might be one of the important pathways in the pathology of rheumatic heart disease. In addition, adipose tissue and adipocytes were also involved in the inflammatory process. These data provide new insight into pathological mechanisms in rheumatic heart disease.
MICALL2 as a substrate of ubiquitinase TRIM21 regulates tumorigenesis of colorectal cancer
Authors: Wen Pushuai , Wang Huade , Li Yi , Sui Xinyao , Hou Zhijuan , Guo Xiaoyan , Xue Wanying , Liu Dahua , Wang Yu , Gao Jing 
Published: October 2022

AbstractBackgroundMolecule interacting with CasL-like protein 2 (MICALL2) is believed to regulate cytoskeleton dynamics, tight junction formation, and neurite outgrowth. However, its biological role and the underlying mechanism in colorectal cancer (CRC) remain largely elusive.MethodsqRT-PCR, Western blotting and immunohistochemistry assays were used to detect the expression levels of different genes. Next, mass spectrometry, co-immunoprecipitation and immunofluorescence staining were used to detect the interactions of proteins. Furthermore, MTT assay, colony formation assay, wound-healing assays and xenograft tumor models were performed to demonstrate the functions of MICALL2 in CRC. In addition, transcriptome sequencing and Western blotting were conducted to verify the mechanism of MICALL2 in CRC.ResultsWe found that both mRNA and protein levels of MICALL2 are up-regulated in colorectal cancer tissues compared with non-tumor tissues and that its overexpression is closely correlated with poor prognosis. Ubiquitin E3 ligase Tripartite motif-containing protein 21 (TRIM21) mediated MICALL2 ubiquitination and proteasome-dependent degradation, negatively correlated with MICALL2 levels, and reversely regulated the tumorigenic activity of MICALL2 in CRC. Functional studies confirmed that MICALL2 promoted colorectal cancer cell growth and migration via the Wnt/β-catenin signaling pathway.ConclusionsAs a substrate of ubiquitinase TRIM21, MICALL2 enhances the growth and migration of colorectal cancer cells and activates the Wnt/β-catenin signaling pathway.
ANCA-associated vasculitis with cardiac valve vegetations in two teenage males: two case reports and a literature review
Authors: Theisen Alexandra , Phillips Carrie L. , Rodriguez Martha 
Published: October 2022

Abstract
Background
Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis is a term used to describe systemic vasculitides that affect small and medium-sized blood vessels. Granulomatosis with Polyangiitis (GPA), a type of ANCA-associated vasculitis (AAV), is rare in children with an estimated prevalence of 3–4 per million, and even more rare is the manifestation of cardiac abnormalities secondary to ANCA-associated vasculitis in the pediatric population.

Case presentation
We discuss the cases of two teenage males who presented with cardiac valvular lesions secondary to GPA in addition to sinus, pulmonary, renal, and cutaneous involvement. These findings of cardiac valvular abnormalities in GPA have rarely been described in the literature in pediatrics. Both patients were treated with rituximab, high-dose methylprednisolone, and therapeutic plasma exchange and showed improvement in their disease manifestations.

Conclusions
A review of the literature revealed only five pediatric cases of ANCA-associated vasculitis with cardiac manifestations, and interestingly, three of the five had valvular involvement. Subsequent valvular involvement makes obtaining the diagnosis of ANCA-Associated Vasculitis difficult due to concern for underlying infectious endocarditis and can lead to misdiagnosis given the rarity of cardiac involvement in ANCA-associated vasculitis. Routine echocardiogram is not always completed in newly diagnosed AAV, yet cardiac involvement can lead to severe consequences as was seen with our first patient in the form of thromboembolic stroke. We discuss the importance of keeping AAV on the differential when cardiac lesions are present as well as the importance of regular cardiac screening in newly diagnosed patients with AAV, as it is a major factor of cardiac morbidity and mortality in the adult population and can contribute substantially to management decisions.
Targeted medical examinations for workers exposed to fumigants
Authors: Aribou Zeenathnisa Mougammadou , Ng Wee Tong 
Published: October 2022

AbstractFumigants are gaseous pesticides or biocides which eradicate pests by suffocation or poisoning. Worker exposure to fumigants is mainly via inhalation, followed by dermal contact and ingestion, leading to various acute and chronic health effects. Implementation of appropriate workplace controls such as adequate ventilation, training and personal protective equipment ensure that exposure to fumigants are kept to the lowest level as practically possible. In addition, routine medical examinations also allow for doctors to identify and manage possible exposure to fumigants and ascertain workers’ fitness to work.While management guidelines after an acute exposure to such fumigants is clear and consistent, the guidelines on routine medical examination for fumigators is sparse. Components of the medical examinations vary according to the fumigant, workers are exposed to and its chronic health effects. Hence, this paper highlights the health hazards of commonly utilised fumigants; Methyl Bromide, Hydrogen Cyanide, Hydrogen Phosphide and Sulfuryl Fluoride; and outlines the guidance for routine medical examinations for exposed fumigators.
A safety study of intraoperative radiation therapy following stereotactic body radiation therapy and multi-agent chemotherapy in the treatment of localized pancreatic adenocarcinoma: study protocol of a phase I trial
Authors: Reddy Abhinav V. , Hill Colin S. , Zheng Lei , He Jin , Narang Amol K. 
Published: October 2022

Abstract
Background
Localized pancreatic adenocarcinoma carries a poor prognosis even after aggressive therapy. Up to 40% of patients may develop locoregional disease as the first site of failure. As such, there may be a role for intensification of local therapy such as radiation therapy. Radiation dose escalation for pancreatic cancer is limited by proximity of the tumor to the duodenum. However, the duodenum is removed during Whipple procedure, allowing the opportunity to dose escalate with intraoperative radiation therapy (IORT). Although prior studies have shown potential benefit of IORT in pancreatic cancer, these studies did not utilize ablative doses (biologically effective dose [BED10] > 100 Gy). Furthermore, the optimal radiation target volume in this setting is unclear. There has been increased interest in a “Triangle Volume” (TV), bordered by the celiac axis, superior mesenteric artery, common hepatic artery, portal vein, and superior mesenteric vein. Dissection of this area, has been advocated for by surgeons from Heidelberg as it contains extra-pancreatic perineural and lymphatic tracts, which may harbor microscopic disease at risk of mediating local failure. Interestingly, a recent analysis from our institution indicated that nearly all local failures occur in the TV. Therefore, the purpose of this protocol is to evaluate the safety of delivering an ablative radiation dose to the TV with IORT following neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT).

Methods
Patients with non-metastatic pancreatic adenocarcinoma centered in the head or neck of the pancreas will be enrolled. Following treatment with multi-agent neoadjuvant chemotherapy, patients will undergo SBRT (40 Gy/5 fractions) followed by IORT (15 Gy/1 fraction) to the TV during the Whipple procedure. The primary objective is acute (< 90 days) toxicity after IORT measured by Clavien-Dindo classification. Secondary objectives include late (> 90 days) toxicity after IORT measured by Clavien-Dindo classification, overall survival, local progression-free survival, distant metastasis-free survival, and progression-free survival.

Discussion
If the results show that delivering an ablative radiation dose to the TV with IORT after neoadjuvant chemotherapy and SBRT is safe and feasible, it warrants further investigation in a phase II trial to evaluate efficacy of this approach.
Trial Registration This study was registered at ClinicalTrials.gov on 12/2/2021 (NCT05141513). https://clinicaltrials.gov/ct2/show/NCT05141513
Alterations of bacteriome, mycobiome and metabolome characteristics in PCOS patients with normal/overweight individuals
Authors: Yin Guoshu , Chen Fu , Chen Guishan , Yang Xiaoping , Huang Qingxia , Chen Lan , Chen Minjie , Zhang Weichun , Ou Miaoqiong , Cao Man , Lin Hong , Chen Man , Xu Hongzhi , Ren Jianlin , Chen Yongsong , Chen Zhangran 
Published: October 2022

AbstractTo characterize the gut bacteriome, mycobiome and serum metabolome profiles in polycystic ovary syndrome (PCOS) patients with normal/overweight individuals and evaluate a potential microbiota-related diagnostic method development for PCOS, 16S rRNA and ITS2 gene sequencing using 88 fecal samples and 87 metabolome analysis from serum samples are conducted and PCOS classifiers based on multiomics markers are constructed. There are significant bacterial, fungal community and metabolite differences among PCOS patients and healthy volunteers with normal/overweight individuals. Healthy individuals with overweight/obesity display less abnormal metabolism than PCOS patients and uniquely higher abundance of the fungal genus Mortierella. Nine bacterial genera, 4 predicted pathways, 11 fungal genera and top 30 metabolites are screened out which distinguish PCOS from healthy controls, with AUCs of 0.84, 0.64, 0.85 and 1, respectively. The metabolite-derived model is more accurate than the microbe-based model in discriminating normal BMI PCOS (PCOS-LB) from normal BMI healthy (Healthy-LB), PCOS-HB from Healthy-HB. Featured bacteria, fungi, predicted pathways and serum metabolites display higher associations with free androgen index (FAI) in the cooccurrence network. In conclusion, our data reveal that hyperandrogenemia plays a central role in the dysbiosis of intestinal microecology and the change in metabolic status in patients with PCOS and that its effect exceeds the role of BMI. Healthy women with high BMI showed unique microbiota and metabolic features.The priority of predictive models in discriminating PCOS from healthy status in this study were serum metabolites, fungal taxa and bacterial taxa.
scTAM-seq enables targeted high-confidence analysis of DNA methylation in single cells
Authors: Bianchi Agostina , Scherer Michael , Zaurin Roser , Quililan Kimberly , Velten Lars , Beekman Renée 
Published: October 2022

AbstractSingle-cell DNA methylation profiling currently suffers from excessive noise and/or limited cellular throughput. We developed scTAM-seq, a targeted bisulfite-free method for profiling up to 650 CpGs in up to 10,000 cells per experiment, with a dropout rate as low as 7%. We demonstrate that scTAM-seq can resolve DNA methylation dynamics across B-cell differentiation in blood and bone marrow, identifying intermediate differentiation states that were previously masked. scTAM-seq additionally queries surface-protein expression, thus enabling integration of single-cell DNA methylation information with cell atlas data. In summary, scTAM-seq is a high-throughput, high-confidence method for analyzing DNA methylation at single-CpG resolution across thousands of single cells.