bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal trends in enrollees’ employment and student status after Medicaid expansion
Authors: Tipirneni Renuka , Kieffer Edith C. , Ayanian John Z. , Patel Minal R. , Kirch Matthias A. , Luster Jamie E. , Karmakar Monita , Goold Susan D. 
Published: February 2022

Abstract
Background
Medicaid community engagement requirements previously received federal approval in 12 states, despite limited data on their impact on enrollees’ employment-related activities. Our objective was to assess longitudinal changes in enrollees’ employment and student status after implementation of Michigan’s Medicaid expansion.

Methods
Longitudinal telephone survey of Michigan Medicaid expansion enrollees in 2016 (response rate [RR] = 53.7%), 2017 (RR = 83.4%), and 2018 (N = 2,608, RR = 89.4%) serially assessing self-reported employment or student status. Survey responses were benchmarked against statewide changes in assessed similar low-income adults in the U.S. Census Bureau Current Population Survey. We used mixed models with individual random effects to assess changes in the proportion of enrollees who were employed or students by year.

Results
Most respondents had incomes < 100% FPL (61.7% with 0–35% of the federal poverty level [FPL], 22.9% with 36–99% FPL, and 15.4% with 100–133% FPL), 89.3% had at least a high school diploma/equivalent, and they ranged in age (39.6% age 19–34, 34.5% age 35–50, 25.9% age 51–64). Employment or student status increased significantly among Michigan Medicaid expansion respondents, from 54.5% in 2016 to 61.4% in 2018 (P < 0.001), including among those with a chronic condition (47.8% to 53.8%, P < 0.001) or mental health/substance use disorder (48.5% to 56.0%, P < 0.001). In contrast, the statewide proportion of low-income non-elderly adults who were employed or students did not change significantly (from 42.7% in 2016 to 46.0% in 2018, P = 0.57).

Conclusions
Medicaid expansion, absent a community engagement requirement, was associated with increased employment and related activities. The role of Medicaid in providing safety-net coverage to individuals during times of economic stress is likely to grow.
Residential care staff are the key to quality of health care for adults with profound intellectual and multiple disabilities in Sweden
Authors: Matérne Marie , Holmefur Marie 
Published: February 2022

Abstract
Background

People with profound intellectual and multiple disabilities (PIMD) have combined severe intellectual and physical disability and need extensive health care support. They cannot communicate by spoken language and need around the clock support. The health care for people with PIMD is typically provided by a number of different health care services in collaboration with residential care staff and their managers. The quality of health care for people with PIMD are important due to their limited ability to communicate their needs. The aim of this study was to explore residential care staff and manager’s experiences and views of health care services for adults with PIMD.

Methods
Thirteen semi-structured interviews with residential care staff (n = 7) and managers (n = 6) were conducted and analysed using qualitative content analysis.

Results
The informants expressed a variety of experiences, under the theme was Quality of health care is enhanced through residential care staff. The theme was comprised of four subthemes: (1) Individually tailored support promotes quality, (2) Accessibility requires adaptation and prioritization by healthcare providers, (3) Disability competence promotes quality and safety and (4) Complex collaboration conditions between the person with PIMD, residential care staff and disability health care.

Conclusions
The residential care staff create quality of care in their role as representatives for adults with PIMD. The care situation is complex and requires adequate competence in the disability, the individual’s needs and adaptations to ensure quality of health care. It is also important to build collaboration with other services that are involved in the care of people with PIMD.
Antemortem diagnosis of anomalous origin of the left coronary artery from the pulmonary artery in a dog
Authors: Takamura Kazuki , Chen Ayaka , Ono Shin , Uechi Masami 
Published: February 2022

AbstractBackgroundIn both humans and animals, anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary artery anomaly. In veterinary medicine, ALCAPA is reported to be discovered only during autopsy or necropsy, and diagnostic methods and prognosis remain poorly understood in dogs.Case presentationA 6-month-old Kaninchen Dachshund was diagnosed with functional mitral valve regurgitation and ALCAPA. Echocardiography identified anomalous vessels in the left ventricular wall and abnormal origin of the left coronary artery from the pulmonary artery.Further evaluation with coronary computed tomographic angiography demonstrated the left coronary artery arising from the posterior aspect of the main pulmonary artery together with the characteristic findings of ALCAPA. The right coronary artery was found to be dilated and tortuous. Furthermore, dilated coronary collateral arteries within the ventricular septum and along the epicardial surface were observed. The dog underwent surgery, but the origin of the anomalous artery could not be ligated, and it died from pulmonary edema 5 months after surgery.ConclusionAnomalous origin of the left coronary artery from the pulmonary artery is overlooked in clinical practice due to its rarity. Coronary computed tomographic angiography was useful to definitively diagnose ALCAPA in a low-invasive manner. Antemortem diagnosis of ALCAPA was shown to be possible in dogs for the first time, and presence of unexplained mitral valve regurgitation should raise concern to this anomaly.
GeneTerpret: a customizable multilayer approach to genomic variant prioritization and interpretation
Authors: Manshaei Roozbeh , DeLong Sean , Andric Veronica , Joshi Esha , Okello John B. A. , Dhir Priya , Somerville Cherith , Farncombe Kirsten M. , Kalbfleisch Kelsey , Jobling Rebekah K. , Scherer Stephen W. , Kim Raymond H. , Hosseini S. Mohsen 
Published: February 2022

Abstract
Background
Variant interpretation is the main bottleneck in medical genomic sequencing efforts. This usually involves genome analysts manually searching through a multitude of independent databases, often with the aid of several, mostly independent, computational tools. To streamline variant interpretation, we developed the GeneTerpret platform which collates data from current interpretation tools and databases, and applies a phenotype-driven query to categorize the variants identified in the genome(s). The platform assigns quantitative validity scores to genes by query and assembly of the genotype–phenotype data, sequence homology, molecular interactions, expression data, and animal models. It also uses the American College of Medical Genetics and Genomics (ACMG) criteria to categorize variants into five tiers of pathogenicity. The final output is a prioritized list of potentially causal variants/genes.

Results
We tested GeneTerpret by comparing its performance to expert-curated genes (ClinGen’s gene-validity database) and variant pathogenicity reports (DECIPHER database). Output from GeneTerpret was 97.2% and 83.5% concordant with the expert-curated sources, respectively. Additionally, similar concordance was observed when GeneTerpret’s performance was compared with our internal expert-interpreted clinical datasets.

Conclusions
GeneTerpret is a flexible platform designed to streamline the genome interpretation process, through a unique interface, with improved ease, speed and accuracy. This modular and customizable system allows the user to tailor the component-programs in the analysis process to their preference. GeneTerpret is available online at https://geneterpret.com.
The association between regional transcriptome profiles and lung volumes in response to mechanical ventilation and lung injury
Authors: Song Yong , Yen Seiha , Preissner Melissa , Bennett Ellen , Dubsky Stephen , Fouras Andreas , Dargaville Peter A. , Zosky Graeme R. 
Published: February 2022

AbstractBackgroundLung inhomogeneity plays a pivotal role in the development of ventilator-induced lung injury (VILI), particularly in the context of pre-existing lung injury. The mechanisms that underlie this interaction are poorly understood. We aimed to elucidate the regional transcriptomic response to mechanical ventilation (MV), with or without pre-existing lung injury, and link this to the regional lung volume response to MV.MethodsAdult female BALB/c mice were randomly assigned into one of four groups: Saline, MV, lipopolysaccharide (LPS) or LPS/MV. Lung volumes (tidal volume, Vt; end-expiratory volume, EEV) were measured at baseline or after 2 h of ventilation using four-dimensional computed tomography (4DCT). Regional lung tissue samples corresponding to specific imaging regions were analysed for the transcriptome response by RNA-Seq. Bioinformatics analyses were conducted and the regional expression of dysregulated gene clusters was then correlated with the lung volume response.ResultsMV in the absence of pre-existing lung injury was associated with regional variations in tidal stretch. The addition of LPS also caused regional increases in EEV. We identified 345, 141 and 184 region-specific differentially expressed genes in response to MV, LPS and LPS/MV, respectively. Amongst these candidate genes, up-regulation of genes related to immune responses were positively correlated with increased regional tidal stretch in the MV group, while dysregulation of genes associated with endothelial barrier related pathways were associated with increased regional EEV and Vt when MV was combined with LPS. Further protein–protein interaction analysis led to the identification of two protein clusters representing the PI3K/Akt and MEK/ERK signalling hubs which may explain the interaction between MV and LPS exposure.ConclusionThe biological pathways associated with lung volume inhomogeneity during MV, and MV in the presence of pre-existing inflammation, differed. MV related tidal stretch induced up-regulation of immune response genes, while LPS combined with MV disrupted PI3K/Akt and MEK/ERK signalling.
Altering the fatty acid profile of Yarrowia lipolytica to mimic cocoa butter by genetic engineering of desaturases
Authors: Konzock Oliver , Matsushita Yuika , Zaghen Simone , Sako Aboubakar , Norbeck Joakim 
Published: February 2022

Abstract
Background
Demand for Cocoa butter is steadily increasing, but the supply of cocoa beans is naturally limited and under threat from global warming. One route to meeting the future demand for cocoa butter equivalent (CBE) could be to utilize microbial cell factories such as the oleaginous yeast Yarrowia lipolytica.

Results
The main goal was to achieve triacyl-glycerol (TAG) storage lipids in Y. lipolytica mimicking cocoa butter. This was accomplished by replacing the native Δ9 fatty acid desaturase (Ole1p) with homologs from other species and changing the expression of both Ole1p and the Δ12 fatty acid desaturase (Fad2p). We thereby abolished the palmitoleic acid and reduced the linoleic acid content in TAG, while the oleic acid content was reduced to approximately 40 percent of the total fatty acids. The proportion of fatty acids in TAG changed dramatically over time during growth, and the fatty acid composition of TAG, free fatty acids and phospholipids was found to be very different.

Conclusions
We show that the fatty acid profile in the TAG of Y. lipolytica can be altered to mimic cocoa butter. We also demonstrate that a wide range of fatty acid profiles can be achieved while maintaining good growth and high lipid accumulation, which, together with the ability of Y. lipolytica to utilize a wide variety of carbon sources, opens up the path toward sustainable production of CBE and other food oils.
Metabolic engineering of Rhodotorula toruloides IFO0880 improves C16 and C18 fatty alcohol production from synthetic media
Authors: Schultz J. Carl , Mishra Shekhar , Gaither Emily , Mejia Andrea , Dinh Hoang , Maranas Costas , Zhao Huimin 
Published: February 2022

Abstract
Background
The oleaginous, carotenogenic yeast Rhodotorula toruloides has been increasingly explored as a platform organism for the production of terpenoids and fatty acid derivatives. Fatty alcohols, a fatty acid derivative widely used in the production of detergents and surfactants, can be produced microbially with the expression of a heterologous fatty acyl-CoA reductase. Due to its high lipid production, R. toruloides has high potential for fatty alcohol production, and in this study several metabolic engineering approaches were investigated to improve the titer of this product.

Results
Fatty acyl-CoA reductase from Marinobacter aqueolei was co-expressed with SpCas9 in R. toruloides IFO0880 and a panel of gene overexpressions and Cas9-mediated gene deletions were explored to increase the fatty alcohol production. Two overexpression targets (ACL1 and ACC1, improving cytosolic acetyl-CoA and malonyl-CoA production, respectively) and two deletion targets (the acyltransferases DGA1 and LRO1) resulted in significant (1.8 to 4.4-fold) increases to the fatty alcohol titer in culture tubes. Combinatorial exploration of these modifications in bioreactor fermentation culminated in a 3.7 g/L fatty alcohol titer in the LRO1Δ mutant. As LRO1 deletion was not found to be beneficial for fatty alcohol production in other yeasts, a lipidomic comparison of the DGA1 and LRO1 knockout mutants was performed, finding that DGA1 is the primary acyltransferase responsible for triacylglyceride production in R. toruloides, while LRO1 disruption simultaneously improved fatty alcohol production, increased diacylglyceride and triacylglyceride production, and increased glucose consumption.

Conclusions
The fatty alcohol titer of fatty acyl-CoA reductase-expressing R. toruloides was significantly improved through the deletion of LRO1, or the deletion of DGA1 combined with overexpression of ACC1 and ACL1. Disruption of LRO1 surprisingly increased both lipid and fatty alcohol production, creating a possible avenue for future study of the lipid metabolism of this yeast.
MeCP2 confers 5-fluorouracil resistance in gastric cancer via upregulating the NOX4/PKM2 pathway
Authors: Qin Yannan , Ma Xiaoping , Guo Chen , Cai Shuang , Ma Hailin , Zhao Lingyu 
Published: February 2022

Abstract
Background
Increasing evidence suggests that aberrant methylation is involved in 5-fluorouracil (5-FU) resistance in gastric cancer (GC). Our previous work has identified that Methyl-CpG binding protein 2 (MeCP2) promotes GC progression by binding to the methylation sites of promoter regions of specific genes to affect the downstream signaling pathways. However, the function and molecular mechanisms of MeCP2 in GC 5-FU resistance remain unclear.

Methods
We detected the expression of MeCP2 in 5-FU-resistant GC cells and examined cell behaviors when MeCP2 was silenced. The molecular mechanisms were explored through chromatin immunoprecipitation (ChIP)-qRT-PCR, luciferase reporter assay, clinical tissue samples analysis, and in vivo tumorigenicity assay.

Results
MeCP2 was up-regulated in 5-FU-resistant GC cells. Knockdown of MeCP2 enhanced the sensitivity of the cells to 5-FU. Moreover, MeCP2 promoted NOX4 transcription in the cells by binding to the promoter of NOX4. Silencing NOX4 rescued the inductive effect of MeCP2 overexpression on 5-FU sensitivity of GC cells and reduced the expression of NOX4 and PKM2 in MeCP2 overexpressed 5-FU-resistant GC cells. In addition, our in vivo experiments demonstrated that MeCP2 knockdown enhanced 5-FU sensitivity in tumors.

Conclusion
MeCP2 confers 5-FU resistance in GC cells via upregulating the NOX4/PKM2 pathway, which may lead to a promising therapeutic strategy for GC.
Differences in stem cell marker and osteopontin expression in primary and recurrent glioblastoma
Authors: Polat Bülent , Wohlleben Gisela , Kosmala Rebekka , Lisowski Dominik , Mantel Frederick , Lewitzki Victor , Löhr Mario , Blum Robert , Herud Petra , Flentje Michael , Monoranu Camelia-Maria 
Published: February 2022

Abstract
Background
Despite of a multimodal approach, recurrences can hardly be prevented in glioblastoma. This may be in part due to so called glioma stem cells. However, there is no established marker to identify these stem cells.

Methods
Paired samples from glioma patients were analyzed by immunohistochemistry for expression of the following stem cell markers: CD133, Musashi, Nanog, Nestin, octamer-binding transcription factor 4 (Oct4), and sex determining region Y-box 2 (Sox2). In addition, the expression of osteopontin (OPN) was investigated. The relative number of positively stained cells was determined. By means of Kaplan–Meier analysis, a possible association with overall survival by marker expression was investigated.

Results
Sixty tissue samples from 30 patients (17 male, 13 female) were available for analysis. For Nestin, Musashi and OPN a significant increase was seen. There was also an increase (not significant) for CD133 and Oct4. Patients with mutated Isocitrate Dehydrogenase-1/2 (IDH-1/2) status had a reduced expression for CD133 and Nestin in their recurrent tumors. Significant correlations were seen for CD133 and Nanog between OPN in the primary and recurrent tumor and between CD133 and Nestin in recurrent tumors. By confocal imaging we could demonstrate a co-expression of CD133 and Nestin within recurrent glioma cells. Patients with high CD133 expression had a worse prognosis (22.6 vs 41.1 months, p = 0.013). A similar trend was seen for elevated Nestin levels (24.9 vs 41.1 months, p = 0.08).

Conclusions
Most of the evaluated markers showed an increased expression in their recurrent tumor. CD133 and Nestin were associated with survival and are candidate markers for further clinical investigation.
HOXA7 promotes the metastasis of KRAS mutant colorectal cancer by regulating myeloid-derived suppressor cells
Authors: Dang Yunzhi , Yu Jiao , Zhao Shuhong , Cao Ximing , Wang Qing 
Published: February 2022

Abstract
Background
KRAS mutation accounts for 30–50% of human colorectal cancer (CRC) cases. Due to the scarcity of effective treatment options, KRAS mutant CRC is difficult to treat in the clinic. Metastasis is still the major cause of the high mortality associated with KRAS mutant CRC, but the exact mechanism remains unclear. Here, we report a unique function of Homeobox 7 (HOXA7) in driving KRAS mutant CRC metastasis and explore therapeutic strategies for subpopulations of patients with this disease.

Methods
The expression of HOXA7 in a human CRC cohort was measured by immunohistochemistry. The function of HOXA7 in KRAS mutant CRC metastasis was analyzed with the cecum orthotopic model.

Results
Elevated HOXA7 expression was positively correlated with lymph node metastasis, distant metastasis, poor tumor differentiation, high TNM stage, and poor prognosis in CRC patients. Furthermore, HOXA7 was an independent prognostic marker in KRAS mutant CRC patients (P < 0.001) but not in KRAS wild-type CRC patients (P = 0.575). Overexpression of HOXA7 improved the ability of KRAS mutant CT26 cells to metastasize and simultaneously promoted the infiltration of myeloid-derived suppressor cells (MDSCs). When MDSC infiltration was blocked by a CXCR2 inhibitor, the metastasis rate of CT26 cells was markedly suppressed. The combination of the CXCR2 inhibitor SB265610 and programmed death-ligand 1 antibody (anti-PD-L1) could largely inhibit the metastasis of KRAS mutant CRC.

Conclusions
HOXA7 overexpression upregulated CXCL1 expression, which promoted MDSC infiltration. Interruption of this loop might provide a promising treatment strategy for HOXA7-mediated KRAS mutant CRC metastasis.
Malaria prevalence and performance of diagnostic tests among patients hospitalized with acute undifferentiated fever in Zanzibar
Authors: Onken Annette , Haanshuus Christel Gill , Miraji Mohammed Khamis , Marijani Msafiri , Kibwana Kibwana Omar , Abeid Khamis Ali , Mørch Kristine , Reimers Marianne , Langeland Nina , Müller Fredrik , Jenum Pål A. , Blomberg Bjørn 
Published: February 2022

Abstract
Background
Control efforts in Zanzibar reduced the burden of malaria substantially from 2000 to 2015, but re-emergence of falciparum malaria has been observed lately. This study evaluated the prevalence of malaria and performance of routine diagnostic tests among hospitalized fever patients in a 1.5 years period in 2015 and 2016.

Methods
From March 2015 to October 2016, paediatric and adult patients hospitalized with acute undifferentiated fever at Mnazi Mmoja Hospital, Zanzibar were included. The malaria prevalence, and performance of rapid diagnostic test (RDT) and microscopy, were assessed using polymerase chain reaction (PCR) as gold standard.

Results
The malaria prevalence was 9% (63/731). Children under 5 years old had lower malaria prevalence (5%, 14/260) than older children (15%, 20/131, p = 0.001) and persons aged 16 to 30 years (13%, 15/119, p = 0.02), but not different from persons over 30 years old (6%, 14/217, p = 0.7). All cases had Plasmodium falciparum infection, except for one case of Plasmodium ovale. Ten malaria patients had no history of visiting mainland Tanzania. The RDT had a sensitivity of 64% (36/56) and a specificity of 98% (561/575), and microscopy had a sensitivity of 50% (18/36) and a specificity of 99% (251/254), compared to PCR. The malaria parasitaemia was lower in patients with false negative results on RDT (median 7 × 103 copies/µL, interquartile range [IQR] 2 × 103 – 8 × 104, p = 0.002) and microscopy (median 9 × 103 copies/µL, IQR 8 × 102 – 7 × 104, p = 0.006) compared to those with true positive RDT (median 2 × 105 copies/µL, IQR 3 × 104 – 5 × 105) and microscopy (median 2 × 105 copies/µL, IQR 6 × 104 – 5 × 105).

Conclusions
The study emphasizes that malaria was a frequent cause of febrile illness in hospitalized patients in Zanzibar in the years 2015-2016, particularly among school age children and young adults. We found evidence of autochthonous malaria transmission in Zanzibar. Compared to PCR, both RDT and microscopy had low sensitivity, and false negative results were associated with low parasitaemia. While low parasitaemia identified only by PCR in a semi-immune individual could be coincidental and without clinical relevance, clinicians should be aware of the risk of false negative results on routine tests.