bluuebunny/crossref_metadata_2025 huggingface dataset:
Marginalization in the Medical Encounter: Ostomy Patients Experience of Perceived Stigmatizing Sentiments from Medical Clinicians
Authors: Miller Leslie Riggle , Peck B. Mitchell
Published: April 2022

Introduction

Ostomy 1 stigma negatively impacts the health of people with an ostomy and contributes to a lower quality of life and health outcomes.

Objective

To assess whether participants experience perceived stigmatizing sentiments (SS) from medical clinicians at the time of their ostomy procedure.

Methods

Using a nonprobability sample of 312 persons with an ostomy, we conducted a retrospective descriptive study. We measured SS as patients’ self-reports of verbal and non-verbal communication from clinicians that were perceived to be negative and may contribute to ostomy stigma. We used thematic analyses to analyze open-ended written comments.

Results

Findings indicate that ostomy patients experience stigmatizing sentiments from their medical clinician before and after surgery. Sixteen percent of patients reported a SS, such as clinicians stating feelings of disgust, showing visible signs of disgust, or treating patients negatively regarding the ostomy.

Conclusion

The perceived treatment that this patient cohort experienced in healthcare likely contributes to ostomy stigmatization and may impact ostomy patients’ psychosocial adjustment. Future research should examine the specific consequences of perceived stigmatizing sentiments from medical clinicians.
Mask Refusal Backlash: The Politicization of Face Masks in the American Public Sphere during the Early Stages of the COVID-19 Pandemic
Authors: Scoville Caleb , McCumber Andrew , Amironesei Razvan , Jeon June
Published: April 2022

This research shows how face masks took on discursive political significance during the early stages of the coronavirus disease 2019 pandemic in the United States. The authors argue that political divisions over masks cannot be understood by looking to partisan differences in mask-wearing behaviors alone. Instead, they show how the mask became a political symbol enrolled into patterns of affective polarization. This study relies on qualitative and computational analyses of opinion articles ( n = 7,970) and supplemental analyses of Twitter data, the transcripts of major news networks, and longitudinal survey data. First, the authors show that antimask discourse was consistently marginal and that backlash against mask refusal came to prominence and did not decline even as masking behaviors normalized and partly depolarized. Second, they show that backlash against mask refusal, rather than mask refusal itself, was the primary way masks were discussed in relation to national electoral, governmental, and partisan themes.
Different Trends in Marriage and Fertility Behavior for Roman Catholics, German Protestants, and Women without Religious Affiliation in West Germany: An Analysis of Five Birth Cohorts Based on the German General Social Survey
Authors: Schulz Sonja
Published: April 2022

In this visualization, the author shows that cohort changes in the propensity to get married and bear a child are different for Roman Catholics, German Protestants, and religiously unaffiliated West German women. The data are from the German General Social Survey—Cumulation 1980–2018. Calculations are based on the life-table method (Kaplan-Meier estimates). In general, demographic changes toward a lower tendency to get married and to bear a child start among the religiously unaffiliated and diffuse to the Christian groups over time, with the Catholics being most resistant to change. The different time trends in demographic behavior translate into increasing differences between religious groups across time, which are most pronounced in the cohort born from 1960 to 1969, and tend to decrease again thereafter.
Book review: John Stratton Hawley, Christian Lee Novetzke and Swapna Sharma (eds.), Bhakti and Power: Debating India’s Religion of the Heart
Authors: Jacobsen Knut A.
Published: April 2022

John Stratton Hawley, Christian Lee Novetzke and Swapna Sharma (eds.), Bhakti and Power: Debating India’s Religion of the Heart. Hyderabad: Orient Blackswan, 2019, xi+255 pp. ISBN: 9789352876211.
Book review: K. S. Chalam, Political Economy of Caste in India
Authors: Pankaj Ashok
Published: April 2022

K. S. Chalam, Political Economy of Caste in India. New Delhi: SAGE Publications, 2020, 274 pp., ₹1250. ISBN 978-93-5388-407-9.
Is There a Relationship Between Vascularity and Echogenicity of Thyroid Lobes in Ultrasonography With BMI? A Large Retrospective Cohort Study
Authors: Sobhani Sahar , Kalantari Forough , Rasoul Zakavi Seyed , Shafiei Susan , Ebrahimi Miandehi Elahe , Eslami Saeed , Aghaee Atena
Published: April 2022

Objective:

The aim of this study was to investigate the relationship between sonographic vascularity and echogenicity of the thyroid lobes, compared with a participant’s body mass index (BMI).

Materials and Methods:

A total of 3722 participations, with varied BMI, were included in the study. For all the participants, the thyroid-stimulating hormone (TSH) was measured, as well as thyroid volume, sonographic echogenicity, and vascularity were recorded. A multiple regression analysis was performed to assess the relationship between the sonographic vascularity and echogenicity, of thyroid lobes, compared with the participants’ BMI.

Results:

The serum TSH values were significantly higher in patients with a BMI > 25 kg/m². The sonographic vascularity and volume of thyroid lobes were positively correlated the participants’ BMI ( P < .005). Sonographic heterogenicity of the left thyroid lobe, right thyroid lobe, and the isthmus were positively associated with BMI ( P < .005). However, the hyper/hypoechogenicity did not demonstrate any significant correlation with BMI ( P > .005).

Conclusion:

Based on the findings of this study, it was concluded that thyroid volumes may have a significant positive relationship with BMI. In overweight participants (i.e., BMI more than 25), thyroid echogenicity was more heterogeneous and their thyroid lobes were more hypovascular.
Magnetite as a provenance and exploration tool for metamorphosed base-metal sulfide deposits in the Stollberg ore field, Bergslagen, Sweden
Authors: Frank Katherine S. , Spry Paul G. , O'Brien Joshua J. , Koenig Alan , Allen Rodney L. , Jansson Nils
Published: April 2022

Magnetite is a common mineral in the Paleoproterozoic Stollberg Zn–Pb–Ag plus magnetite ore field (~6.6 Mt of production), which occurs in 1.9 Ga metamorphosed felsic and mafic rocks. Mineralisation at Stollberg consists of magnetite bodies and massive to semi-massive sphalerite–galena and pyrrhotite (with subordinate pyrite, chalcopyrite, arsenopyrite and magnetite) hosted by metavolcanic rocks and skarn. Magnetite occurs in sulfides, skarn, amphibolite and altered metamorphosed rhyolitic ash–siltstone that consists of garnet–biotite, quartz–garnet–pyroxene, gedrite–albite, and sericitic rocks. Magnetite probably formed from hydrothermal ore-bearing fluids (~250–400°C) that replaced limestone and rhyolitic ash–siltstone, and subsequently recrystallised during metamorphism. The composition of magnetite from these rock types was measured using electron microprobe analysis and LA–ICP–MS. Utilisation of discrimination plots (Ca+Al+Mn vs. Ti+V, Ni/(Cr+Mn) vs. Ti+V, and trace-element variation diagrams (median concentration of Mg, Al, Ti, V, Co, Mn, Zn and Ga) suggest that the composition of magnetite in sulfides from the Stollberg ore field more closely resembles that from skarns found elsewhere rather than previously published compositions of magnetite in metamorphosed volcanogenic massive sulfide deposits. Although the variation diagrams show that magnetite compositions from various rock types have similar patterns, principal component analyses and element–element variation diagrams indicate that its composition from the same rock type in different sulfide deposits can be distinguished. This suggests that bulk-rock composition also has a strong influence on magnetite composition. Principal component analyses also show that magnetite in sulfides has a distinctive compositional signature which allows it to be a prospective pathfinder mineral for sulfide deposits in the Stollberg ore field.
Prediction of clinical outcome in CLL based on recurrent gene mutations, CLL-IPI variables, and (para)clinical data
Authors: Parviz Mehdi , Brieghel Christian , Agius Rudi , Niemann Carsten U.
Published: April 2022

A highly variable clinical course, immune dysfunction, and a complex genetic blueprint pose challenges for treatment decisions and the management of risk of infection in patients with chronic lymphocytic leukemia (CLL). In recent years, the use of machine learning (ML) technologies has made it possible to attempt to untangle such heterogeneous disease entities. In this study, using 3 classes of variables (international prognostic index for CLL [CLL-IPI] variables, baseline [para]clinical data, and data on recurrent gene mutations), we built ML predictive models to identify the individual risk of 4 clinical outcomes: death, treatment, infection, and the combined outcome of treatment or infection. Using the predictive models, we assessed to what extent the different classes of variables are predictive of the 4 different outcomes, within both a short-term 2-year outlook and a long-term 5-year outlook after CLL diagnosis. By adding the baseline (para)clinical data to CLL-IPI variables, predictive performance was improved, whereas no further improvement was observed when including the data on recurrent genetic mutations. We discovered 2 main clusters of variables predictive of treatment and infection. Further emphasizing the high mortality resulting from infection in CLL, we found a close similarity between variables predictive of infection in the short-term outlook and those predictive of death in the long-term outlook. We conclude that at the time of CLL diagnosis, routine (para)clinical data are more predictive of patient outcome than recurrent mutations. Future studies on modeling genetics and clinical outcome should always consider the inclusion of several (para)clinical data to improve performance.
MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis
Authors: Peng Zongqing , Ouyang Xinhua , Wang Yexing , Fan Qiming
Published: April 2022

Background

Hepatocellular carcinoma (HCC) is a common malignancy. Long non-coding RNAs (lncRNAs) partake in the progression of HCC. However, the role of lncRNA MAPKAPK5-AS1 in the development of HCC has not been fully clarified.

Methods

RNA sequencing data and quantitative real-time polymerase chain reaction (qRT-PCR) were adopted to analyze MAPKAPK5-AS1, miR-429 and ZEB1 mRNA expressions in HCC tissues and cell lines. Western blot was used to detect ZEB1, E-cadherin and N-cadherin protein expressions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and flow cytometry assays were adopted to analyze the effects of MAPKAPK5-AS1 on cell proliferation, migration, invasion and apoptosis. Besides, luciferase reporter assay was used to detect the targeting relationship between miR-429 and MAPKAPK5-AS1 or ZEB1 3’UTR. The xenograft tumor mouse models were used to explore the effect of MAPKAPK5-AS1 on lung metastasis of HCC cells.

Results

MAPKAPK5-AS1 and ZEB1 expressions were up-regulated in HCC tissues, and miR-429 expression is down-regulated in HCC tissues. MAPKAPK5-AS1 knockdown could significantly impede HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), as well as promote cell apoptosis. MAPKAPK5-AS1 overexpression could enhance L02 cell proliferation, migration, invasion and EMT, and inhibit cell apoptosis. MiR-429 was validated to be the target of MAPKAPK5-AS1, and miR-429 inhibitors could partially offset the effects of knocking down MAPKAPK5-AS1 on HCC cells. MAPKAPK5-AS1 could positively regulate ZEB1 expression through repressing miR-429. Moreover, fewer lung metastatic nodules were observed in the lung tissues of nude mice when the MAPKAPK5-AS1 was knocked down in HCC cells.

Conclusion

MAPKAPK5-AS1 can adsorb miR-429 to promote ZEB1 expression to participate in the development of HCC.
Development of a questionnaire to evaluate female fertility care in pediatric oncology, a TREL initiative
Authors: van der Perk M. E. Madeleine , Stukaitė-Ruibienė Eglė , Bumbulienė Žana , Vaitkevičienė Goda Elizabeta , Bos Annelies M. E. , van den Heuvel-Eibrink Marry M. , Rascon Jelena
Published: April 2022

Background

Currently the five-year survival of childhood cancer is up to 80% due to improved treatment modalities. However, the majority of childhood cancer survivors develop late effects including infertility. Survivors describe infertility as an important and life-altering late effect. Fertility preservation options are becoming available to pre- and postpubertal patients diagnosed with childhood cancer and fertility care is now an important aspect in cancer treatment. The use of fertility preservation options depends on the quality of counseling on this important and delicate issue. The aim of this manuscript is to present a questionnaire to determine the impact of fertility counseling in patients suffering from childhood cancer, to improve fertility care and evaluate what patients and their parents or guardians consider good fertility care.

Methods

Within the framework of the EU-Horizon 2020 TREL project, a fertility care evaluation questionnaire used in the Netherlands was made applicable for international multi-center use. The questionnaire to be used at least also in Lithuania, incorporates patients’ views on fertility care to further improve the quality of fertility care and counseling. Results evaluate fertility care and will be used to improve current fertility care in a national specialized pediatric oncology center in the Netherlands and a pediatric oncology center in Lithuania.

Conclusion

An oncofertility-care-evaluation questionnaire has been developed for pediatric oncology patients and their families specifically. Results of this questionnaire may contribute to enhancement of fertility care in pediatric oncology in wider settings and thus improve quality of life of childhood cancer patients and survivors.
Lipid emulsion-induced hypertension post resection of pediatric neuroblastoma: a case report and literature review
Authors: Yuan Lihua , Li Tao , Yuan Lijuan , Chen Feng , Qiu Jinchun , Ji Xing
Published: April 2022

Background

Parenteral Nutrition (PN) is preferred when patient is unable to eat. Most clinically widely used lipid emulsion is now attracting more attention in its stability and adverse reactions. We report here the first case of lipid emulsions caused hypertension.

Case presentation

A 1.5 years old girl was diagnosed with neuroblastoma and underwent chemotherapy subsequently followed by resection surgery. She received PN for nutritional support after surgery. with the initiation of PN, this patient developed hypertension. Possible causes of hypertension were evaluated. After the discontinuation of lipid emulsions in PN, her hypertensive symptoms ceased. The lipid emulsion was therefore considered as the cause of her hypertension.

Conclusions

The pathogenesis of hypertension caused by fatty milk is possibly associated with increased production of reactive oxygen species, increased oxidative stress and vasoconstriction.
Assessment of psychometric properties of the modified experiences of teaching–learning questionnaire in Iranian nursing students
Authors: Hosseini Mohammadali , Jalali Amir , Salari Nader
Published: April 2022

Background

Universities are in charge of training, educating, and preparing students for their future. Teaching and learning methods have a profound role in fulfilling this responsibility by universities. Examining teaching–learning experiences needs a proper tool to collect the information needed. The aim of this study was to collect validity evidence of the modified experiences of teaching–learning questionnaire (ETLQ) in Iranian nursing students.

Methods

The validation process was started by securing the required permissions from the designer of the tool. Then the tool was translated into Farsi using forward–backward method. After preparing a Farsi version of the tool, the content, response process, and internal structure assessment were checked and supported using qualified methods. To examine internal structure, Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were conducted for three sections of the scale with the participation of 278 nursing students. To examine the reliability of the tool, test–retest method was used and internal correlation was examined using Cronbach’s alpha.

Results

The EFA and CFA results confirmed the tool with three domains, seven factors and 33 items. The R2-index of the model was obtained equal to 0.99, which indicates that 99% of the changes in teaching–learning experiences are explained by the tool (33 items). The main indices in CFA were higher than 0.9, which indicates the goodness of fit of the model. Pearson correlation between the items and the subscales was significantly and directly related to the whole scale. Moreover, with Cronbach’s alpha equal to 0.944 and test–retest result equal to 0.88, reliability of the Farsi version of modified ETLQ was supported.

Conclusion

The results showed that the Farsi version of modified ETLQ had acceptable and applied indices to measure teaching–learning experiences in nursing students. The tool can be used as a valid tool in different fields of education in medical sciences.
RETRACTED ARTICLE: A thematic analysis of system wide learning from first wave Covid-19 in the East of England
Authors: Jackson Carolyn , Manley Kim , Webster Jonathan , Hardy Sally
Published: April 2022

Background

The Covid-19 pandemic has created an unprecedented challenge for health and social care systems globally. There is an urgent need for research on experiences of COVID-19 at different levels of health systems, including lessons from professional, organisational and local system responses, that can be used to inform managerial and policy responses.

Methods

This paper presents the findings from a thematic analysis of front-line staff experiences working across the Norfolk and Waveney integrated care system (ICS) in the East of England during April and October 2020 to address the question “What are the experiences and perceptions of partner organisations and practitioners at multiple levels of the health system in responding to COVID-19 during the first wave of the pandemic?” This question was posed to learn from how practitioners, interdependent partner organisations and the system experienced the pandemic and responded. 176 interview transcripts derived from one to one and focus group interviews, meeting notes and feedback from a “We Care Together” Instagram campaign were submitted for qualitative thematic analysis to an external research team at a regional University commissioned to undertake an independent evaluation. Three phases of qualitative analysis were systematically undertaken to derive the findings.

Findings

Thirty-one themes were distilled highlighting lessons learned from things that went well compared with those that did not; challenges compared with the celebrations and outcomes; learning and insights gained; impact on role; and system headlines. The analysis supported the ICS to inform and capitalise on system wide learning for integration, improvement and innovations in patient and care home resident safety, and staff wellbeing to deal with successive waves of the pandemic as well as prioritising workforce development priorities as part of its People Plan.

Conclusions

The findings contribute to a growing body of knowledge about what impact the pandemic has had on health and social care systems and front-line practitioners globally. It is important to understand the impact at all three levels of the system (micro, meso and macro) as it is the meso and macro system levels that ultimately impact front line staff experiences and the ability to deliver person centered safe and effective care in any context. The paper presents implications for future workforce and health services policy, practice innovation and research.
Adding rituximab to chemotherapy for diffuse large B-cell lymphoma patients in Indonesia: a cost utility and budget impact analysis
Authors: Putri Septiara , Setiawan Ery , Saldi Siti Rizny F. , Khoe Levina Chandra , Sari Euis Ratna , Megraini Amila , Nadjib Mardiati , Sastroasmoro Sudigdo , Armansyah Armansyah
Published: April 2022

Background

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been used to treat patients with diffuse large B-cell lymphoma (DLBCL) under National Health Insurance (NHI) scheme in Indonesia. This study aims to estimate its cost-effectiveness and budget impact.

Methods

We conducted a cost utility analysis using Markov model over a lifetime horizon, from a societal perspective. Clinical evidence was derived from published clinical trials. Direct medical costs were gathered from hospital data. Direct non-medical costs, indirect costs, and utility data were primarily gathered by interviewing the patients. We applied 3% discount rate for both costs and effect. All monetary data are converted into USD (1 USD = IDR 14,000, 2019). Probabilistic sensitivity analysis was performed. In addition, from a payer perspective, budget impact analysis was estimated using price reduction scenarios.

Results

The incremental cost-effectiveness ratio (ICER) of R-CHOP was USD 4674/LYG and 9280/QALY. If we refer to the threshold three times the GDP per capita (USD 11,538), R-CHOP could thus be determined as a cost-effective therapy. Its significant health benefit has contributed to the considerable ICER result. Although the R-CHOP has been considered a cost-effective intervention, the financial consequence of R-CHOP if remain in benefit package under National Health Insurance (NHI) system in Indonesia is considerably substantial, approximately USD 35.00 million with 75% price reduction scenario.

Conclusions

As a favorable treatment for DLBCL, R-CHOP ensures value for money in Indonesia. Budget impact analysis provides results which can be used as further consideration for decision-makers in matters related to benefit packages.
Phylogenomic approaches untangle early divergences and complex diversifications of the olive plant family
Authors: Dong Wenpan , Li Enze , Liu Yanlei , Xu Chao , Wang Yushuang , Liu Kangjia , Cui Xingyong , Sun Jiahui , Suo Zhili , Zhang Zhixiang , Wen Jun , Zhou Shiliang
Published: April 2022

Background

Deep-branching phylogenetic relationships are often difficult to resolve because phylogenetic signals are obscured by the long history and complexity of evolutionary processes, such as ancient introgression/hybridization, polyploidization, and incomplete lineage sorting (ILS). Phylogenomics has been effective in providing information for resolving both deep- and shallow-scale relationships across all branches of the tree of life. The olive family (Oleaceae) is composed of 25 genera classified into five tribes with tribe Oleeae consisting of four subtribes. Previous phylogenetic analyses showed that ILS and/or hybridization led to phylogenetic incongruence in the family. It was essential to distinguish phylogenetic signal conflicts, and explore mechanisms for the uncertainties concerning relationships of the olive family, especially at the deep-branching nodes.

Results

We used the whole plastid genome and nuclear single nucleotide polymorphism (SNP) data to infer the phylogenetic relationships and to assess the variation and rates among the main clades of the olive family. We also used 2608 and 1865 orthologous nuclear genes to infer the deep-branching relationships among tribes of Oleaceae and subtribes of tribe Oleeae, respectively. Concatenated and coalescence trees based on the plastid genome, nuclear SNPs and multiple nuclear genes suggest events of ILS and/or ancient introgression during the diversification of Oleaceae. Additionally, there was extreme heterogeneity in the substitution rates across the tribes. Furthermore, our results supported that introgression/hybridization, rather than ILS, is the main factor for phylogenetic discordance among the five tribes of Oleaceae. The tribe Oleeae is supported to have originated via ancient hybridization and polyploidy, and its most likely parentages are the ancestral lineage of Jasmineae or its sister group, which is a “ghost lineage,” and Forsythieae. However, ILS and ancient introgression are mainly responsible for the phylogenetic discordance among the four subtribes of tribe Oleeae.

Conclusions

This study showcases that using multiple sequence datasets (plastid genomes, nuclear SNPs and thousands of nuclear genes) and diverse phylogenomic methods such as data partition, heterogeneous models, quantifying introgression via branch lengths (QuIBL) analysis, and species network analysis can facilitate untangling long and complex evolutionary processes of ancient introgression, paleopolyploidization, and ILS.
Comprehensive analysis of prognostic value and immune infiltration of CXC chemokines in pancreatic cancer
Authors: Jing Yanhua , Wang Fengjiao , Zhang Ke , Chen Zhen
Published: April 2022

Background

The prognosis of pancreatic cancer is poor, with a 5-year survival rate of less than 10%. Studies have shown that chemokines in the tumour microenvironment are often altered, which is associated with immune infiltration and the prognosis and survival of pancreatic cancer patients.

Methods

Multiomics and bioinformatics tools were used to clarify CXC chemokine expression and its role in the pancreatic ductal adenocarcinoma (PDAC) immune microenvironment.

Results

Most CXC chemokines were upregulated in pancreatic cancer and correlated with patient prognosis. CXC chemokines can activate cancer-related signalling pathways and affect immune infiltration. Furthermore, most CXC chemokines were significantly correlated with the abundance of macrophages, neutrophils and dendritic cells. CXCL5 was selected as a hub gene, and a variety of immune checkpoints, including PD-1/PD-L1 and CTLA-4, were identified.

Conclusion

Our study provides novel insights into CXC chemokine expression and its role in the PDAC immune microenvironment. These results can provide more data about prognostic biomarkers and therapeutic targets of PDAC.
Genotypic and phenotypic diversity among Komagataella species reveals a hidden pathway for xylose utilization
Authors: Heistinger Lina , Dohm Juliane C. , Paes Barbara G. , Koizar Daniel , Troyer Christina , Ata Özge , Steininger-Mairinger Teresa , Mattanovich Diethard
Published: April 2022

Background

The yeast genusKomagataellacurrently consists of seven methylotrophic species isolated from tree environments. Well-characterized strains ofK. phaffiiandK. pastorisare important hosts for biotechnological applications, but the potential of other species from the genus remains largely unexplored. In this study, we characterized 25 natural isolates from all seven describedKomagataellaspecies to identify interesting traits and provide a comprehensive overview of the genotypic and phenotypic diversity available within this genus.

Results

Growth tests on different carbon sources and in the presence of stressors at two different temperatures allowed us to identify strains with differences in tolerance to high pH, high temperature, and growth on xylose. AsKomagataellaspecies are generally not considered xylose-utilizing yeasts, xylose assimilation was characterized in detail. Growth assays, enzyme activity measurements and13C labeling confirmed the ability ofK. phaffiito utilize D-xylose via the oxidoreductase pathway. In addition, we performed long-read whole-genome sequencing to generate genome assemblies of allKomagataellaspecies type strains and additionalK. phaffiiandK. pastorisisolates for comparative analysis. All sequenced genomes have a similar size and share 83–99% average sequence identity. Genome structure analysis showed thatK. pastorisandK. ulmishare the same rearrangements in difference toK. phaffii, while the genome structure ofK. kurtzmaniiis similar toK. phaffii. The genomes of the other, more distant species showed a larger number of structural differences. Moreover, we used the newly assembled genomes to identify putative orthologs of important xylose-related genes in the differentKomagataellaspecies.

Conclusions

By characterizing the phenotypes of 25 naturalKomagataellaisolates, we could identify strains with improved growth on different relevant carbon sources and stress conditions. Our data on the phenotypic and genotypic diversity will provide the basis for the use of so-far neglectedKomagataellastrains with interesting characteristics and the elucidation of the genetic determinants of improved growth and stress tolerance for targeted strain improvement.
Human neural stem cell-derived extracellular vesicles protect against Parkinson’s disease pathologies
Authors: Lee Eun Ji , Choi Yoori , Lee Hong J. , Hwang Do Won , Lee Dong Soo
Published: April 2022

Background

Neural stem cells (NSCs) have the ability to generate a variety of functional neural cell types and have a high potential for neuronal cell regeneration and recovery. Thus, they been recognized as the best source of cell therapy for neurodegenerative diseases, such as Parkinson’s disease (PD). Owing to the possibility of paracrine effect-based therapeutic mechanisms and easier clinical accessibility, extracellular vesicles (EVs), which possess very similar bio-functional components from their cellular origin, have emerged as potential alternatives in regenerative medicine.

Material and methods

EVs were isolated from human fibroblast (HFF) and human NSC (F3 cells). The supernatant of the cells was concentrated by a tangential flow filtration (TFF) system. Then, the final EVs were isolated using a total EV isolation kit.

Results

In this study, we demonstrate the potential protective effect of human NSC-derived EVs, showing the prevention of PD pathologies in 6-hydroxydopamine (6-OHDA)-induced in vitro and in vivo mouse models. Human NSC and F3 cell (F3)-derived EVs reduced the intracellular reactive oxygen species (ROS) and associated apoptotic pathways. In addition, F3-derived EVs induced downregulation of pro-inflammatory factors and significantly decreased 6-OHDA-induced dopaminergic neuronal loss in vivo. F3 specific microRNAs (miRNAs) such as hsa-mir-182-5p, hsa-mir-183-5p, hsa-mir-9, and hsa-let-7, which are involved in cell differentiation, neurotrophic function, and immune modulation, were found in F3-derived EVs.

Conclusions

We report that human NSC-derived EVs show an effective neuroprotective property in an in vitro transwell system and in a PD model. The EVs clearly decreased ROS and pro-inflammatory cytokines. Taken together, these results indicate that NSC-derived EVs could potentially help prevent the neuropathology and progression of PD.

Graphical Abstract
TMT-based proteomics analysis of the cerebral cortex of TauT knockout rats
Authors: Xia Yiming , Huang Xiaoling , Mo Lidong , Wang Chen , Fan Weijia , Huang Huiling
Published: April 2022

Background

Taurine serves a variety of nutritional and physiological roles, and it is mostly transported in cells via taurine transporter (TauT). The effect of taurine transporter in cerebral cortex is still unknown. We employed TMT label-based proteomics to find differences in proteins in the cerebral cortex of TauT knockout rats in this investigation. The goal of this research was to see how TauT deletion affected protein alterations in brain tissue and to see if there was a new research area for TauT.

Methods

The cerebral cortex of TauT knockout rats and wild-type control rats were analyzed using TMT-based proteomics, and differentially expressed proteins were analyzed by bioinformatics analysis means such as GO and KEGG, the association between the proteins was found by PPI, and biologically significant and interesting proteins were selected for verification by WB and immunohistochemistry.

Results

There were total of 8275 proteins found, but only 35 differentially expressed proteins were identified (27 up-regulated and 8 down-regulated), and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological pathways and functional classification of the proteins. The results show that these differentially expressed proteins are mainly enriched in lysine degradation, cell cycle, chronic myeloid leukemia, and longevity regulating pathways-multiple species, renal cell carcinoma, pathways in cancer, etc. To verify the proteomic data, we analyzed the expression of Annexin6 and Pik3r2 by western blotting and immunofluorescence. The results are consistent with proteomics, which proves the reliability of our proteomics data.

Conclusion

Through TMT-based proteomics, we have a comprehensive understanding of the effect of TauT knockout on the changes of other proteins in the cerebral cortex, providing new evidence for further understanding the function of TauT.
The need for uniform and coordinated practices involving centrally manufactured cell therapies
Authors: Stroncek David , Dinh Anh , Rai Herleen , Zhang Nan , Somerville Rob , Panch Sandhya
Published: April 2022

Cellular therapies have become an important part of clinical care. The treatment of patients with cell therapies often involves the collection of autologous cells at the medical center treating the patient, the shipment of these cells to a centralized manufacturing site, and the return of the cryopreserved clinical cell therapy to the medical center treating the patient for storage until infusion. As this activity grows, cell processing laboratories at many academic medical centers are involved with many different autologous products manufactured by several different centralized laboratories. The handling of these products by medical center-based cell therapy laboratories is complicated and resource-intensive since each centralized manufacturing laboratory has unique methods for labeling, storing, shipping, receiving, thawing, and infusing the cells. The field would benefit from the development of more uniform practices. The development of a coordinating center similar to those established to facilitate the collection, shipping, and transplantation of hematopoietic stem cells from unrelated donors would also be beneficial. In summary, the wide range of practices involved with labeling, shipping, freezing, thawing, and infusing centrally manufactured autologous cellular therapies lack efficiency and consistency and puts patients at risk. More uniform practices are needed.
Identification of molecular subtypes and a novel prognostic model of diffuse large B-cell lymphoma based on a metabolism-associated gene signature
Authors: He Jing , Chen Ziwei , Xue Qingfeng , Sun Pingping , Wang Yuan , Zhu Cindy , Shi Wenyu
Published: April 2022

Background

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in adults. Metabolic reprogramming in tumors is closely related to the immune microenvironment. This study aimed to explore the interactions between metabolism-associated genes (MAGs) and DLBCL prognosis and their potential associations with the immune microenvironment.

Methods

Gene expression and clinical data on DLBCL patients were obtained from the GEO database. Metabolism-associated molecular subtypes were identified by consensus clustering. A prognostic risk model containing 14 MAGs was established using Lasso-Cox regression in the GEO training cohort. It was then validated in the GEO internal testing cohort and TCGA external validation cohort. GO, KEGG and GSVA were used to explore the differences in enriched pathways between high- and low-risk groups. ESTIMATE, CIBERSORT, and ssGSEA analyses were used to assess the immune microenvironment. Finally, WGCNA analysis was used to identify two hub genes among the 14 model MAGs, and they were preliminarily verified in our tissue microarray (TMA) using multiple fluorescence immunohistochemistry (mIHC).

Results

Consensus clustering divided DLBCL patients into two metabolic subtypes with significant differences in prognosis and the immune microenvironment. Poor prognosis was associated with an immunosuppressive microenvironment. A prognostic risk model was constructed based on 14 MAGs and it was used to classify the patients into two risk groups; the high-risk group had poorer prognosis and an immunosuppressive microenvironment characterized by low immune score, low immune status, high abundance of immunosuppressive cells, and high expression of immune checkpoints. Cox regression, ROC curve analysis, and a nomogram indicated that the risk model was an independent prognostic factor and had a better prognostic value than the International Prognostic Index (IPI) score. The risk model underwent multiple validations and the verification of the two hub genes in TMA indicated consistent results with the bioinformatics analyses.

Conclusions

The molecular subtypes and a risk model based on MAGs proposed in our study are both promising prognostic classifications in DLBCL, which may provide novel insights for developing accurate targeted cancer therapies.
Effect of GOAL-Directed ANalgesia using ANI (Analgesia/Nociception Index) during general anesthesia on immediate postoperative pain and intraoperative hemodynamics in adult patients (GOALDAN study): a study protocol for randomized, controlled, multicenter trial
Authors: Michalot Adrien , Bazin Jean-Étienne , Richebé Philippe , Allaouchiche Bernard , Boselli Emmanuel
Published: April 2022

Background

Severe postoperative pain remains a major problem that is seen in 20 to 40% of patients. The Analgesia/Nociception Index (ANI) is a 0–100 index reflecting the relative parasympathetic activity allowing for intraoperative analgesia monitoring. We have previously shown that an ANI value < 50 immediately before extubation may predict the occurrence of immediate postoperative pain with good performance. We hypothesized that GOAL-Directed ANalgesia may provide reduced immediate postoperative pain and optimized intraoperative remifentanil administration (GOLDAN study).

Methods

The GOALDAN study is an international, multicenter, simple-blind, parallel, prospective, randomized, controlled, two-armed trial. Patients are randomly assigned in a 1:1 ratio in the control group or in the experimental group. Patients will be randomly allocated to either the intervention group (ANI) or the control group (standard care only). In the ANI group, the administration of remifentanil will be goal-directed targeting a 50–80 ANI range, with a prophylactic injection of morphine immediately after extubation if the case of ANI < 50. Our primary objective was to determine whether the prophylactic administration of morphine at the end of the procedure in patients at risk of immediate postoperative pain (ANI < 50 immediately before extubation) could reduce the incidence of the latter by 50% in the post-anesthetic care unit. Our secondary objective was to determine whether the intraoperative use of goal-directed analgesia with an ANI target of 50 to 80 could improve intraoperative hemodynamics and postoperative outcome.

Discussion

Because of the paucity of well-conducted trials, the authors believe that a randomized-controlled trial will improve the evidence for using analgesia monitoring during general anesthesia and strengthen current recommendations for intraoperative analgesia management.

Trial registration

ClinicalTrials.govNCT03618082. Registered on 7 August 2018
Highly efficient biosynthesis of β-caryophyllene with a new sesquiterpene synthase from tobacco
Authors: Cheng Tao , Zhang Kai , Guo Jing , Yang Qing , Li Yiting , Xian Mo , Zhang Rubing
Published: April 2022

Background

β-Caryophyllene, a kind of bicyclic sesquiterpene, is mainly used as a spice in the food and cosmetic industries. Furthermore, it also has significant value in the pharmaceutical industry and is now considered to be used as a new fuel. As a chemical energy heterotrophic microorganism, Escherichia coli can produce a large amount of acetyl-CoA through aerobic respiration, and acetyl-CoA is the common precursor substance in the biosynthesis of all terpenoids. Therefore, E. coli has the potential to be a cell factory to produce terpenoids.

Results

A new gene of β-caryophyllene synthase (TPS7) was found by analyzing the genome of Nicotiana tabacum L. using bioinformatics methods. The gene was overexpressed in engineered E. coli with a heterogeneous mevalonate (MVA) pathway to build a recombinant strain CAR1. Subsequent cultivation experiments in shake flask of engineered strain CAR1 verified that 16.1 mg/L β-caryophyllene was detected from the fermentation broth in the shake flask after induction for 24 h with IPTG. The toxic by-product of farnesyl acetate was detected during the process, and CAR1 showed a heavily cellular accumulation of product. We constructed an engineered strain CAR2, in which the downstream genes of the MVA pathway were integrated into the E. coli chromosome, successfully increasing β-caryophyllene production to 100.3 mg/L. The highest production of β-caryophyllene during the fed-batch fermentation was 4319 mg/L. Then we employed in situ extraction fermentation to successfully increase the production of β-caryophyllene by 20% to 5142 mg/L.

Conclusion

A new sesquiterpene synthase, TPS7, from tobacco was found to be able to produce β-caryophyllene with high efficiency. Based on this, an engineered E. coli was constructed to produce a much higher concentration of β-caryophyllene than the previous studies. During the fermentation process, we observed that β-caryophyllene tends to accumulate in intracellular space, which will eventually influence the activity of engineered E. coli. As a result, we solved this by metabolism regulation and in situ extractive fermentation.
Improving the reproducibility and integrity of research: what can different stakeholders contribute?
Authors: Macleod Malcolm ,   the University of Edinburgh Research Strategy Group
Published: April 2022

Increasing awareness of problems with the reproducibility and integrity of research led the UK Parliament Science and Technology Committee to launch, in July 2021, an inquiry into reproducibility and research integrity. We recognise at least four potential reasons why attempts to replicate a research finding may be unsuccessful: false positive statistical analyses, low generalisability of findings, suboptimal study designs (research integrity), and deliberate malfeasance (researcher integrity). It is important to make a distinction between the contributions of research integrity and of researcher integrity to the reproducibility crisis. While the impact of an individual instance of compromised researcher integrity is substantial, the aggregate impact of more prevalent problems with research integrity is likely much greater. The research community will be most efficient when failed replication efforts are never due to issues of research integrity or of researcher integrity, as this would allow focus on the scientific reasons for why two apparently similar experiments should reach different conclusions. We discuss the role of funders, institutions and government in addressing the “reproducibility crisis” before considering which interventions might have a positive impact on academia’s approach to reproducible research, and a possible role for a committee on research integrity.
Multilinear strongly singular integral operators on non-homogeneous metric measure spaces
Authors: Wang Hailian , Xie Rulong
Published: April 2022

Let $(X,d,\mu )$
(
X
,
d
,
μ
)
be a non-homogeneous metric measure space satisfying the geometrically and upper doubling measure conditions. In this paper, the boundedness in Lebesgue spaces for multilinear strongly singular integral operators on non-homogeneous metric measure spaces is proved. As an application, the boundedness in Morrey spaces for multilinear strongly singular integral operators is also obtained.
Barriers of artificial intelligence implementation in the diagnosis of obstructive sleep apnea
Authors: Brennan Hannah L. , Kirby Simon D.
Published: April 2022

Background

Obstructive sleep apnea is a common clinical condition and has a significant impact on the health of patients if untreated. The current diagnostic gold standard for obstructive sleep apnea is polysomnography, which is labor intensive, requires specialists to utilize, expensive, and has accessibility challenges. There are also challenges with awareness and identification of obstructive sleep apnea in the primary care setting. Artificial intelligence systems offer the opportunity for a new diagnostic approach that addresses the limitations of polysomnography and ultimately benefits patients by streamlining the diagnostic expedition.

Main body

The purpose of this project is to elucidate the barriers that exist in the implementation of artificial intelligence systems into the diagnostic context of obstructive sleep apnea. It is essential to understand these challenges in order to proactively create solutions and establish an efficient adoption of this new technology. The literature regarding the evolution of the diagnosis of obstructive sleep apnea, the role of artificial intelligence in the diagnosis, and the barriers in artificial intelligence implementation was reviewed and analyzed.

Conclusion

The barriers identified were categorized into different themes including technology, data, regulation, human resources, education, and culture. Many of these challenges are ubiquitous across artificial intelligence implementation in any medical diagnostic setting. Future research directions include developing solutions to the barriers presented in this project.

Graphical abstract
Optimal timing of introducing mobilization therapy for ICU patients with sepsis
Authors: Liu Keibun , Shibata Junichiro , Fukuchi Kiyoyasu , Takahashi Kunihiko , Sonoo Tomohiro , Ogura Takayuki , Goto Tadahiro
Published: April 2022

Background

For patients admitted to the intensive care unit (ICU) with sepsis, mobilization therapy during ICU stay can improve their outcomes during and after the ICU stay. However, little is known about the optimal timing of introducing mobilization therapy.

Methods

This is a retrospective cohort study using data from a tertiary medical center in Japan during 2013–2017. We included patients aged ≥ 18 years who were admitted to the ICU with sepsis based on the Sepsis-3 criteria. We defined early mobilization (EM) as the rehabilitation at the level of sitting on the edge of the bed or more within the first 3 days of the patients’ ICU stay. Patients were divided into the EM and non-EM groups. The primary outcomes were in-hospital mortality and ambulatory dependence at hospital discharge. We estimated the effects of EM by stabilized inverse probability weighting (sIPW). We then tested alternative definitions of EM by changing the cutoff in days to mobilization by 1-day increments from 2 to 7 days to investigate the optimal timing of mobilization.

Results

Our study sample consisted of a total of 296 septic patients, including 96 patients in the EM group and 200 patients in the non-EM group. In the sIPW model, the adjusted OR for in-hospital mortality in the EM group compared to the non-EM group was 0.22 [95% CI 0.06–0.88], and the adjusted OR for ambulatory dependence at the hospital discharge was 0.24 [95% CI 0.09–0.61]. When alternative definitions of EM were tested, patients who achieved mobilization within the first 2–4 days of their ICU stays had better outcomes.

Conclusions

Achieving mobilization within the first 3 days of ICU stay was significantly associated with better outcomes. Patients with sepsis might benefit most from achieving mobilization within 2–4 days. Further studies are warranted to validate the findings.