bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria
Authors: Jagannathan Prasanna , Ty Maureen , Sun Shenghuan , Callaway Perri , Rek John , Dantzler Kathleen , Ploeg Kattria van der , Nideffer Jason , Hu Zicheng , Klemm Sandy , Greenleaf William , Donato Michele , Tukwasibwe Stephen , Arinaitwe Emmanuel , Nankya Felistas , Musinguzi Kenneth , Andrew Dean , Parte Lauren de la , Mori Diego , Takahashi Saki , Rodriguez-Barraquer Isabel , Greenhouse Bryan , Blish Catherine , Utz Paul , Khatri Purvesh , Dorsey Grant , Kamya Moses , Boyle Michelle , Feeney Margaret , Ssewanyana Isaac 
Published: November 2022

Abstract
Natural Killer (NK) cells likely play an important role in immunity to malaria, but whether repeated malaria modifies the NK cell response remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56neg population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56dim NK cells, including decreased expression of PLZF and the Fc receptor g chain, increased histone methylation, and increased protein expression of LAG-3, KIR and LILRB1. CD56neg NK cells were highly functional, displaying greater antibody dependent cellular cytotoxicity than CD56dim NK cells, and higher frequencies of these cells were associated with protection against symptomatic malaria and high parasite densities. Importantly, following marked reductions in malaria transmission, frequencies of these cells rapidly declined, suggesting that continuous exposure to malaria is required to maintain this modified, adaptive-like NK cell subset.
CENPF Knockdown Inhibits Adriamycin Chemoresistance In Triple Negative Breast Cancer Mediated By Rb-E2F1 Axis
Authors: Wang Depeng , Xu Wei , Huang Minghua , Ma Wei , Liu Yulu , Zhou Xingchen , Yang Qingrui , Mu Kun 
Published: November 2022

Abstract
Background:
Frequent developed resistance leads to early relapse and short survival in Triple-negative breast cancer (TNBC). Targeting DNA damage response (DDR) has become an effective strategy for overcoming TNBC chemoresistance. CENPF (centromere protein) is a key regulator of cell cycle progression, but its role in TNBC chemotherapy resistance remains unclear.
Methods:
We Used bioinformatics, immunohistochemical staining and real-time quantitative PCR analysis to explore the expression of CENPF in triple negative breast cancer tissues and cells. Then, we analyze the relationship between CENPF expression with clinicopathological parameters and survival prognosis of patients. The effects of CENPF on the proliferation, apoptosis, cycle, and drug sensitivity of triple negative breast cancer cells were detected in vitro. The chemoresistance mechanisms of CENPF in TNBC cells was evaluated by immunoblotting, immunofluorescence co-localization, and co-immunoprecipitation .
Results:
Here we found CENPF, highly expressed in TNBC, is associated with poor prognosis in patients receiving chemotherapy. And in vitro CENPF knockdown significantly increased adriamycin (ADR)-induced cytotoxicity in MDA-MB-231 and its ADR-resistant strains (MDA-MB-231/ADR). Then we demonstrated that CENPF targets Chk1-mediated G2/M phase arrest and binds to Rb for competing with E2F1 in TNBC. Collectively Considering crucial role of E2F1 in DNA damage response and DNA repair, a novel mechanism for CENPF to regulate Rb-E2F1 axis will provide new horizons to finally overcome chemotherapy resistance in TNBC.
Conclusion:
CENPF binds to Rb for competing with E2F1 and promotes Chk1 expression through the Rb/E2F1 axis to enhance chemoresistance to doxorubicin in TNBC.
Distinct immunoreactions after microwave ablation of primary tumor with different heating parameters in VX2 tumor model
Authors: Qian Mengjia , Lyu Jin , Da Xia , Zhu Chunhua , Wang Guozhu , Fang Yuan , Xu Jin 
Published: November 2022

AbstractBackground Thermal ablations of solid tumors in situ can activate the immune system and produce a specific immune response against tumor. Microwave ablation (MWA) with different parameters can ablate tumors with similar sizes and cause different local inflammatory effects. Our aim was to determine whether MWA of primary tumor in different energy modes can induce different immunological effects. Methods Seventy rabbits with VX2 tumors implanted subcutaneously underneath the right second nipple were treated with high-power MWA (40W×1 minute), low-power MWA (20W×2 minutes), surgical resection, or left without treatment as control. Survival time was evaluated by log-rank test. On day 14 after ablation, immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses. Besides, the cytokine patterns were also identified from enzyme-linked immunosorbent assay. Results Tumor eradication was achieved completely in MWA groups as proven by nicotinamide adenine dinucleotide diapforase (NADH-diaphorase) staining. The rabbits in the control group showed significantly more pulmonary metastases and poorer survival than the three treatment groups; however, no significant difference was observed among three treatment groups. MWA groups induced more intratumoral and systemic CD4+and CD8+T cells than the control group. MWA caused more systemic CD4+T cells than operation. High-power MWA induced more intratumoral CD4+and CD8+T cells and systemic CD4+T cells than low-power MWA. MWA induced increased levels of IL-2, IL-12 and decreased levels of IL-4, IL-6, IL-10 compared with control group. Importantly, a significant higher level of serum IL-12 was found in high-power MWA than that in low-power MWA group. Conclusions High-power MWA induced enhanced Th1-type immune response in comparison to low-power MWA. High-power MWA may be selected for the treatment of solid tumors, although future studies are still needed to confirm our results.
High Cell Density Cultivation (HCDC) of E. coli with Intensive Multiple Sequential Batches Together with
Fed-Batch at Cell Level (FBC) Superior to the Fed-Batch Technique
Authors: Chamsart Saethawat 
Published: November 2022

Abstract
High cell density cultivation (HCDC) is a technique that was developed and used in the cultivation of various microorganisms. Escherichia coli is the most prominent in the bacterial group and popular at the industrial scale for the production of bio-products. The HCDC conducted with the Fed-Batch modes is complicated. In this study, we developed a batch production medium (BPM), a minimal defined medium for industrial utilization with the potential use of dextrin at high concentrations as the major carbon source. Dextrin prevents cell cultivation system from the Crabtree effect due to its gradual hydrolysis to release glucose and gradual assimilation into E. coli cells like Fed-Batch at Cell Level (FBC). Yeast extract was added into the BPM to enhance cell growth. It was operated using 5-L bioreactors with the aerobic batch cultivation at high concentrations of dextrin, i.e., 90 g/L to achieve high-cell-density concentration at a high production rate superior to the Fed-Batch technique. Further, the Intensive Multiple Sequential Batch (IMFB) technique was developed to achieve a high yield at a high productivity. The maximum values of cell biomass, x; specific growth rate; yield coefficient, Yx/s; productivity, rx; and efficiency (Ef) were 46.31 g/L, 0.54 h-1, 0.55 g/g, 3.86 g/L/h and 98%, respectively. The results showed that cell cultivations and growth kinetics, biochemical engineering mass balances, and design of impeller speeds using fluid dynamics in the 5-L bioreactor of aerobic batch cell cultivation for the production of E. coli cell biomass a high-density concentration using dextrin to control the FBC at a high titer can be used for the scale-up of industrial bioreactors.
Innovation in healthcare: leadership perceptions about the innovation characteristics of artificial intelligence- a qualitative interview study with healthcare leaders in Sweden
Authors: Neher Margit , Petersson Lena , Nygren Jens , Svedberg Petra , Larsson Ingrid , Nilsen Per 
Published: November 2022

Abstract
Background
There are substantial challenges in the implementation of intelligence (AI) applications in healthcare. This study aimed to provide an insight into implementation preconditions by exploring the perceptions of leaders and managers in Swedish healthcare concerning the intervention characteristics of AI as an innovation to be implemented into their organization.
Methods
The study had a deductive qualitative design, using constructs from the domain of intervention characteristics in the Consolidated Framework for Implementation Research (CFIR). Interviews were conducted with 26 leaders in healthcare.
Results
The participants perceived that AI could provide relative advantages in solutions for the management of care, for clinical decision-support and for early detection of disease and disease risk. The development of AI in the organization itself was perceived as the main current intervention source. The evidence strength behind AI-technology was questioned by the participants, who highlighted a lack of transparency and potential quality and safety risks. Although the participants perceived AI to be superior for humans in terms of effectiveness and precision in the analysis of medical imaging, they expressed uncertainty about the adaptability and trialability of AI in other clinical environments. The participants perceived that user and end-user views on design quality and packaging would impact implementation at all levels. Complexities such as the characteristics of the technology, the lack of consensus about AI as a concept, and the need for many implementation strategies to achieve potentially transformative practice change were spoken of, and the participants also expressed uncertainty about the costs involved in AI-implementation.
Conclusion
The leaders saw the potential of the technology and its use in practice, but also perceived that AI’s opacity limits its evidence strength, and that there was a high level of complexity both in AI itself and in introducing it in healthcare practice. More research is needed about the perceptions of AI implementation in other stakeholder groups and about outcomes from the implementation of AI in real-world situations. New theories, models and frameworks may need to be developed to meet the challenges related to the implementation of AI.
An African Perspective on the Water-Energy-Food Nexus
Authors: Simpson Gareth , Jewitt Graham P.W. , Mabhaudhi Tafadzwanashe , Badenhorst Jessica 
Published: November 2022

Abstract
There is a need to address resource security and distributional justice in developing countries. People need water, energy, and food to sustain their livelihoods and to achieve sustainable development. The interactions between these resource sectors form the crux of water-energy-food (WEF) nexus assessments. In this study, we have utilised the WEF Nexus Index to analyse 54 African nations for whom sufficient data was available in 2019. The results for several countries were analysed to illustrate the opportunities and constraints for future development. The analysis demonstrates that, for many African countries, policies that undergird investments in energy supply projects are needed to unlock available freshwater resources to meet their food requirements. Such projects can be utilised to enhance the ability of farmers to manage water through drought-proofing rainfed agriculture, an increase in irrigation development, or both. WEF nexus-based studies, policies, and projects must be focussed on the direct and indirect achievement of SDGs 1, 2, 6, 7, and 13, both in terms of access and availability, to ensure distributional justice, especially in the African context. Such actions, combined with broad public participation, can have a ripple effect on other SDGs such as SDGs 5, 10, and 17, thereby reducing inequalities and building partnerships to attain these aspirational goals. The assessment of Africa’s relatively low scores in terms of the WEF Nexus Index does not represent a negative narrative. Instead, it provides an entry point to understanding the underlying challenges, through which more detailed analyses can lead to identified solutions and policies. Many African countries are trapped in an environment that could be termed a ‘poverty-unemployment-inequality nexus’ (due to the interlinkages that exist between these ‘wicked’ problems). The WEF Nexus Index provides high-level insights into these opportunities.
IL-6 up-regulates the expression of IL-6R through JAK2/STAT3 signaling pathway to promote HCC progression
Authors: Song Li , Xu Ruyue , Cai Wenpeng , Liang Jiaojiao , Cao Niandie , Gao Jiafeng , Tang Xiaolong 
Published: November 2022

Abstract
Background

The progression of hepatocellular carcinoma (HCC) involves multi-factor, multi-step interactions. It has been reported that the high expression of interleukin-6 receptor (IL-6R) plays an important role in the occurrence and development of tumors, but the regulation mechamismof IL-6R expression and its function in HCC have not been adequately reported.

Methods

Western Blot was used to evaluate the phosphorylation of key kinases in JAK2/STAT3 pathway and the protein expression levels of related proliferative molecules, migration molecules and apoptotic molecules. The anti-apoptosis, migration and proliferation abilities of cells of each group were analyzed using JC-1 measures cell apoptosis, EdU method to detect cell apoptosis, clone formation experiment and Transwell.

Result

The expression of IL-6R in HCC cells (HepG2, Huh7 and SK-Hep1) was higher than that in normal hepatocytes (THLE-2 and THLE-5), and the protein expression of IL-6R was relatively highest in SK-Hep1 and relatively lowest in HepG2. Compared with the HepG2IL − 6 cell line, the protein levels of apoptotic molecules c-Caspase7 and c-Caspase3 were lower, while the protein levels of proliferative molecules p-P70S6K and migration molecules MMP9 and MMP2 were higher, showing stronger anti-apoptosis, proliferation and migration abilities. Compared with SK-Hep1 in SK-Hep1TCZ and SK-Hep1IL − 6R−, the protein levels of apoptotic molecules c-Caspase7 and c-Caspase3 were higher, while the protein levels of proliferative molecules p-P70S6K and migration molecules MMP9 and MMP2 were lower. It showed strong apoptotic ability and low proliferation and migration ability. Interestingly, IL-6 up-regulated the expression of IL-6R by activating JAK2/STAT3 signaling pathway. The expression of IL-6R protein was also down-regulated after lentivirus knockdown of STAT3. In subcutaneous tumor-bearing experiments in nude mice, compared with SK-Hep1 group, the up-regulation of IL-6R expression after JAK2/STAT3 signaling pathway activation by IL-6 in SK-Hep1IL − 6 group significantly improved the tumor growth ability. However, the expression of IL-6R protein was down-regulated and the terminal tumor volume was significantly down-regulated in the lentiviral STAT3 knockdown group, which inhibited the tumor growth ability.

Conclusions

The results showed that IL-6 regulated the transcription of IL-6R through the activation of JAK2/STAT3 signaling pathway, thereby promoting the progression of HCC. The result are expected to provide experimental basis for IL-6R as a potential therapeutic target for HCC.
Assessment of Students’ Earthquake Risk Perception on Their Metacognition in Weija-gbawe Municipality, Ghana.
Authors: Kwang Moses Abamoah , Osman Adams , Adu-Boahen Kofi 
Published: November 2022

Abstract
Most studies on metacognition have devoted attention to self-awareness, learning process and outcome. However, there is a paucity of literature on how earthquake risk perception affects students’ metacognition. This study assessed Senior High School (SHS) students’ earthquake risk perception and its effects on their metacognition in the Weija-Gbawe Municipality, Ghana. The study used a questionnaire collect data from 219 students proportionally from three (3) SHS (Ansong Senior High School, Pentecost Vocational Training Institute, and Royals Senior High Schools). Data processing and analysis techniques employed were exploratory and confirmatory factor analysis, the Kruskal-Wallis test, and path analysis. Results showed a high earthquake risk perception among students. Also, students' risk perception had statistical significance effects on the metacognition especially for younger students. The study recommends that the National Disaster Management Organisation (NADMO) and Ghana Education Service to offer counselling sessions for students and earthquake disaster risk sensitisation programmes for students.
Do symptoms moderate the association between participation and executive function outcomes among people with schizophrenia?
Authors: Kaizerman-Dinerman Alona , Roe David , Demeter Naor , Josman Naomi 
Published: November 2022

Abstract
Background: Literature explains participation limitations among people with schizophrenia through the context of metacognitive limitations, specifically in symptoms and in executive functions (EF). Research has shown mixed results regarding associations between symptoms and participation, reporting association with negative symptoms, positive symptoms, or only metacognitive limitations. The aim of this study was to deepen understanding of the symptoms’ impact on participation among people with schizophrenia.
Methods: Forty-three participants with schizophrenia received 8 group sessions of focused metacognitive intervention (MCG) aimed at promoting participation by focusing on EF components (e.g., analyzing individual cognitive strategy use). Three measures were administered: the Positive and Negative Syndrome Scale (PANSS) to evaluate symptoms, the Weekly Calendar Planning Assessment (WCPA) to assess EF, and the Activity Card Sort (ACS) to measure participation at the baseline and 12 weeks following completion of the intervention. Scores were compared to a matched control group of 41 people with schizophrenia who instead received treatment as usual. The role of PANSS as moderator was examined using multiple hierarchical regressions, entering interactions between the PANSS scores and WCPA change scores in the final regression step.
Results: Relationships were not significant for participants with high PANSS scores. A positive relationship existed between change in WCPA and change in ACS for participants with low PANSS scores.
Conclusions: These results demonstrate that low PANSS scores moderate the association between EF and participation and highlight the importance of symptoms as a predictor of participation following the MCG intervention.
Synergistic effects of selenium and silicon mitigate arsenic toxicity in plant (Oryza sativa L.) and human model (keratinocyte HaCaT cells lines) systems
Authors: Kumar Amit , Gupta Kiran , Baker Abu , Srivast Sudhakar , Singh Pradyumna Kumar , Khan Shahebraj , Ansari Mohammad Israil 
Published: November 2022

AbstractArsenic (As) is a toxic element for plants, animals and humans. The mitigation of As stress has been achieved via selenium (Se) and silica (Si) supplementations. However, the effects of combined application of Se and Si against As stress are not known. The present study was conducted on a plant (rice;Oryza sativaL.) and human model (keratinocyte HaCaT cell lines) systems to evaluate the effects of Se (0.5 and 1 mg L− 1) and Si (10 and 30 mg L− 1) against As (4 mg L− 1). The rice plants, grown hydroponically for 7 d in various treatments, showed reduction in As accumulation in As + Se/Si/Se + Si treatments in comparison to As treated plants. The reduction in As accumulation in root and shoot was 57% and 64%, respectively in As + Se + Si treatment. The increase in enzymatic antioxidant system (SOD, APX, GPx, GR and GST) along with decrease in oxidative stress markers (MDA, DHA, ASC and H2O2) in As + Se + Si treatment as compared to As treatment signified elevated tolerance of rice plants to As stress. The cytotoxicity amelioration by Se + Si supply was also seen in HaCaT cells exposed to As in terms of cell viability and As-induced shrinking and apoptosis. In conclusion, the results demonstrated that an optimum combination of Se and Si can be effectively used to mitigate As toxicity in plants and possibly humans also.
A randomised study of rituximab and belimumab sequential therapy in PR3 ANCAassociated vasculitis (COMBIVAS): design of the study protocol
Authors: McClure Mark Edward , Gopaluni Seerapani , Wason James , Henderson Robert B , Maurik Andre Van , Savage Caroline , Pusey Charles , Salama Alan , Lyons Paul A. , Lee Jacinta , Mynard Kim , Jayne David , Jones Rachel 
Published: November 2022

Abstract
Background. Sequential B cell targeted immunotherapy with BAFF antagonism (belimumab) and B cell depletion (rituximab) and may enhance B cell targeting in ANCA-associated vasculitis (AAV) through several mechanisms.
Study Design. COMBIVAS is a randomised, double blind, placebo-controlled trial designed to assess the mechanistic effects of sequential therapy of belimumab and rituximab in patients with active PR3-AAV. The recruitment target is 30 patients who meet the criteria for inclusion in the per protocol analysis. Thirty-six participants have been randomised to one of two treatment groups in a 1:1 ratio; either rituximab plus belimumab or rituximab plus placebo (both groups with the same tapering corticosteroid regimen) and recruitment is now closed (final patient enrolled March 2021). For each patient, the trial will last for two years comprising a 12-month treatment period followed by a 12-month follow-up period.
Participants. Participants have been recruited from five of seven UK trial sites. Eligibility criteria were age ³18 years, a diagnosis of AAV with active disease (newly diagnosed or relapsing disease), along with a concurrent positive test for PR3-ANCA by ELISA.
Interventions. Rituximab 1000mg was administered by intravenous infusions on Day 8 and Day 22. Weekly subcutaneous injections of 200mg belimumab or placebo were initiated a week before rituximab on Day 1 and then weekly through to Week 51. All participants received a relatively low prednisolone (20 mg/day) starting dose from Day 1 followed by a protocol-specified corticosteroid taper aiming for complete cessation by 3 months.
Outcomes. The primary endpoint of this study is time to PR3 ANCA negativity. Key secondary outcomes include change from baseline in naïve, transitional, memory, plasmablast B cell subsets (by flow cytometry) in blood at Months 3, 12, 18 and 24, time to clinical remission, time to relapse, and incidence of serious adverse events. Exploratory biomarker assessments include assessment of B cell receptor clonality, B cell and T cell functional assays, whole blood transcriptomic analysis and urinary lymphocyte and proteomic analysis. Inguinal lymph node and nasal mucosal biopsies have been performed on a subgroup of patients at baseline and Month 3.
Discussion. This experimental medicine study provides a unique opportunity to gain detailed insights into the immunological mechanisms of belimumab-rituximab sequential therapy across multiple body compartments in the setting of AAV. Trial status. The final patient was recruited in March 2021. Last subject last visit will be March 2023.
ClinicalTrials.gov Identifier: NCT03967925, May 30, 2019.