bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematical analysis reveals a strong cancer relevance of CREB1-regulated genes
Authors: Zheng Tianyu , Huang Jinrong , Xiang Xi , Li Siyuan , Yu Jiaying , Qu Kunli , Xu Zhe , Han Peng , Dong Zhanying , Liu Yang , Xu Fengping , Yang Huanming , Jäättelä Marja , Luo Yonglun , Liu Bin 
Published: October 2021

AbstractThe transcription factor cyclic-AMP response element-binding protein 1 (CREB1) responds to cAMP level and controls the expression of target genes, which regulates nutrition partitioning. The promoters of CREB1-targeted genes responsive to cAMP have been extensively investigated and characterized with the presence of both cAMP response element and TATA box. Compelling evidence demonstrates that CREB1 also plays an essential role in promoting tumor development. However, only very few genes required for cell survival, proliferation and migration are known to be constitutively regulated by CREB1 in tumors. Their promoters mostly do not harbor any cAMP response element. Thus, it is very likely that CREB1 regulates the expressions of distinct sets of target genes in normal tissues and tumors. The whole gene network constitutively regulated by CREB1 in tumors has remained unrevealed. Here, we employ a systematical and integrative approach to decipher this gene network in the context of both tissue cultured cancer cells and patient samples. We combine transcriptomic, Rank-Rank Hypergeometric Overlap, and Chipseq analysis, to define and characterize CREB1-regulated genes in a multidimensional fashion. A strong cancer relevance of those top-ranked targets, which meet the most stringent criteria, is eventually verified by overall survival analysis of cancer patients. These findings strongly suggest the importance of genes constitutively regulated by CREB1 for their implicative involvement in promoting tumorigenesis.
Molecular surveillance for polymorphisms associated with artemisinin-based combination therapy resistance in Plasmodium falciparum isolates collected in Mozambique, 2018
Authors: Chidimatembue Arlindo , Svigel Samaly S. , Mayor Alfredo , Aíde Pedro , Nhama Abel , Nhamussua Lídia , Nhacolo Arsénio , Bassat Quique , Salvador Crizólgo , Enosse Sónia , Saifodine Abuchahama , De Carvalho Eva , Candrinho Baltazar , Zulliger Rose , Goldman Ira , Udhayakumar Venkatachalam , Lucchi Naomi W. , Halsey Eric S. , Macete Eusébio 
Published: October 2021

Abstract
Background
Due to the threat of emerging anti-malarial resistance, the World Health Organization recommends incorporating surveillance for molecular markers of anti-malarial resistance into routine therapeutic efficacy studies (TESs). In 2018, a TES of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) was conducted in Mozambique, and the prevalence of polymorphisms in the pfk13, pfcrt, and pfmdr1 genes associated with drug resistance was investigated.

Methods
Children aged 6–59 months were enrolled in four study sites. Blood was collected and dried on filter paper from participants who developed fever within 28 days of initial malaria treatment. All samples were first screened for Plasmodium falciparum using a multiplex real-time PCR assay, and polymorphisms in the pfk13, pfcrt, and pfmdr1 genes were investigated by Sanger sequencing.

Results
No pfk13 mutations, associated with artemisinin partial resistance, were observed. The only pfcrt haplotype observed was the wild type CVMNK (codons 72–76), associated with chloroquine sensitivity. Polymorphisms in pfmdr1 were only observed at codon 184, with the mutant 184F in 43/109 (39.4%) of the samples, wild type Y184 in 42/109 (38.5%), and mixed 184F/Y in 24/109 (22.0%). All samples possessed N86 and D1246 at these two codons.

Conclusion
In 2018, no markers of artemisinin resistance were documented. Molecular surveillance should continue to monitor the prevalence of these markers to inform decisions on malaria treatment in Mozambique.
Catalytic core–shell nanoparticles with self-supplied calcium and H2O2 to enable combinational tumor inhibition
Authors: Kong Hanjing , Fang Chao , Chu Qiang , Hu Zefeng , Fu Yike , Han Gaorong , Li Xiang , Zhou Yi 
Published: October 2021

AbstractNanoparticles, presenting catalytic activity to induce intracellular oxidative species, have been extensively explored for tumor treatment, but suffer daunting challenges in the limited intracellular H2O2 and thus suppressed therapeutic efficacy. Here in this study, a type of composite nanoparticles, consisting CaO2 core and Co-ferrocene shell, is designed and synthesized for combinational tumor treatment. The findings indicate that CaO2 core can be hydrolyzed to produce large amounts of H2O2 and calcium ions at the acidic tumor sites. Meanwhile, Co-ferrocene shell acts as an excellent Fenton catalyst, inducing considerable ROS generation following its reaction with H2O2. Excessive cellular oxidative stress triggers agitated calcium accumulation in addition to the calcium ions released from the particles. The combined effect of intracellular ROS and calcium overload causes significant tumor inhibition both in vitro and in vivo.
Nanoselenium transformation and inhibition of cadmium accumulation by regulating the lignin biosynthetic pathway and plant hormone signal transduction in pepper plants
Authors: Li Dong , Zhou Chunran , Ma Jinling , Wu Yangliu , Kang Lu , An Quanshun , Zhang Jingbang , Deng Kailin , Li Jia-Qi , Pan Canping 
Published: October 2021

AbstractSelenium (Se) can promote the growth and resistance of agricultural crops as fertilizers, while the role of nano-selenium (nano-Se) against Cd remains unclear in pepper plants (Capsicum annuum L.). Biofortification with nano-Se observably restored Cd stress by decreasing the level of Cd in plant tissues and boosting the accumulation in biomass. The Se compounds transformed by nano-Se were primarily in the form of SeMet and MeSeCys in pepper tissues. Differential metabolites and the genes of plant signal transduction and lignin biosynthesis were measured by employing transcriptomics and determining target metabolites. The number of lignin-related genes (PAL, CAD, 4CL, and COMT) and contents of metabolites (sinapyl alcohol, phenylalanine, p-coumaryl alcohol, caffeyl alcohol, and coniferaldehyde) were remarkably enhanced by treatment with Cd1Se0.2, thus, maintaining the integrity of cell walls in the roots. It also enhanced signal transduction by plant hormones and responsive resistance by inducing the biosynthesis of genes (BZR1, LOX3, and NCDE1) and metabolites (brassinolide, abscisic acid, and jasmonic acid) in the roots and leaves. In general, this study can enable a better understanding of the protective mechanism of nano-Se in improving the capacity of plants to resist environmental stress.
Community health workers at the dawn of a new era: 5. Roles and tasks
Authors: Glenton Claire , Javadi Dena , Perry Henry B. 
Published: October 2021

Abstract
Background
This is the fifth of our 11-paper supplement on “Community Health Workers at the Dawn of a New Era.” When planning new community health worker (CHW) roles or expanding existing roles, programme planners need to analyse global and local research evidence and evidence-based guidance on the effectiveness and safety of relevant tasks performed by CHWs.

Methods
In this paper, we explore key areas of consideration when selecting roles and tasks; present current knowledge regarding these issues; and suggest how decision-makers could consider these issues when assigning tasks in their setting. This paper draws on the chapter “Community Health Worker Roles and Tasks” in Developing and Strengthening Community Health Worker Programs at Scale: A Reference Guide and Case Studies for Program Managers and Policymakers, as well as on a recently published compendium of 29 case studies of national CHW programmes and on recently published literature pertaining to roles and tasks of CHWs.

Results
This paper provides a list of questions that aim to help programme planners think about important issues when determining CHW roles and tasks in their setting. Planners need to assess whether the recommended roles and tasks are considered acceptable and appropriate by their target population and by the CHWs themselves and those who support them. Planners also need to think about the practical and organizational implications of each task for their particular setting with regard to training requirements, health systems support, work location, workload, and programme costs.

Conclusion
When planning CHW roles and tasks, planners, programme implementers, and policy-makers should draw from global guidance and research evidence, but they also need to engage with the experiences, needs, and concerns of local communities and health workers. By drawing from both sources of information, they will stand a better chance of developing programmes that are effective in achieving their goals while remaining acceptable to those affected by them, feasible to implement, and sustainable over time.
Community health workers at the dawn of a new era: 11. CHWs leading the way to “Health for All”
Authors: Perry Henry B. , Chowdhury Mushtaque , Were Miriam , LeBan Karen , Crigler Lauren , Lewin Simon , Musoke David , Kok Maryse , Scott Kerry , Ballard Madeleine , Hodgins Steve 
Published: October 2021

AbstractBackgroundThis is the concluding paper of our 11-paper supplement, “Community health workers at the dawn of a new era”.MethodsWe relied on our collective experience, an extensive body of literature about community health workers (CHWs), and the other papers in this supplement to identify the most pressing challenges facing CHW programmes and approaches for strengthening CHW programmes.ResultsCHWs are increasingly being recognized as a critical resource for achieving national and global health goals. These goals include achieving the health-related Sustainable Development Goals of Universal Health Coverage, ending preventable child and maternal deaths, and making a major contribution to the control of HIV, tuberculosis, malaria, and noncommunicable diseases. CHWs can also play a critical role in responding to current and future pandemics. For these reasons, we argue that CHWs are now at the dawn of a new era. While CHW programmes have long been an underfunded afterthought, they are now front and centre as the emerging foundation of health systems. Despite this increased attention, CHW programmes continue to face the same pressing challenges: inadequate financing, lack of supplies and commodities, low compensation of CHWs, and inadequate supervision. We outline approaches for strengthening CHW programmes, arguing that their enormous potential will only be realized when investment and health system support matches rhetoric. Rigorous monitoring, evaluation, and implementation research are also needed to enable CHW programmes to continuously improve their quality and effectiveness.ConclusionA marked increase in sustainable funding for CHW programmes is needed, and this will require increased domestic political support for prioritizing CHW programmes as economies grow and additional health-related funding becomes available. The paradigm shift called for here will be an important step in accelerating progress in achieving current global health goals and in reaching the goal of Health for All.
Community health workers at the dawn of a new era: 9. CHWs’ relationships with the health system and communities
Authors: LeBan Karen , Kok Maryse , Perry Henry B. 
Published: October 2021

Abstract
Background
This is the ninth paper in our series, “Community Health Workers at the Dawn of a New Era”. Community health workers (CHWs) are in an intermediary position between the health system and the community. While this position provides CHWs with a good platform to improve community health, a major challenge in large-scale CHW programmes is the need for CHWs to establish and maintain beneficial relationships with both sets of actors, who may have different expectations and needs. This paper focuses on the quality of CHW relationships with actors at the local level of the national health system and with communities.

Methods
The authors conducted a selective review of journal articles and the grey literature, including case study findings in the 2020 book Health for the People: National CHW Programs from Afghanistan to Zimbabwe. They also drew upon their experience working with CHW programmes.

Results
The space where CHWs form relationships with the health system and the community has various inherent strengths and tensions that can enable or constrain the quality of these relationships. Important elements are role clarity for all actors, working referral systems, and functioning supply chains. CHWs need good interpersonal communication skills, good community engagement skills, and the opportunity to participate in community-based organizations. Communities need to have a realistic understanding of the CHW programme, to be involved in a transparent process for selecting CHWs, and to have the opportunity to participate in the CHW programme. Support and interaction between CHWs and other health workers are essential, as is positive engagement with community members, groups, and leaders.

Conclusion
To be successful, large-scale CHW programmes need well-designed, effective support from the health system, productive interactions between CHWs and health system staff, and support and engagement of the community. This requires health sector leadership from national to local levels, support from local government, and partnerships with community organizations. Large-scale CHW programmes should be designed to enable local flexibility in adjusting to the local community context.
Management of HIV-2 resistance to antiretroviral therapy in a HIV-1/HIV-2/HBV co-infected patient
Authors: Cardoso Margarida , Vasconcelos Joana , Baptista Teresa , Diogo Isabel , Gonçalves Fátima , Mansinho Kamal , Gomes Perpétua 
Published: October 2021

Abstract
Background
The current standard of care is to start antiretroviral therapy in all patients diagnosed with HIV-1, as for HIV-2 current DHHS guideline suggests ART for HIV-2 as soon as diagnosis is established, although this practice is not universal, for instance, in Portugal there are specific criteria to start treatment.

Case presentation
We present a case of a man, chronically infected with HIV-1, HIV-2 and hepatitis B virus who developed resistance to HIV-2 while maintaining HIV-1 under control. 6 years after starting antiretroviral therapy he had his first virologic failure. We performed HIV-2 resistance tests that revealed high-grade resistance to all nucleoside reverse-transcriptase inhibitors except tenofovir and to all protease inhibitors except darunavir. After a decade of permanent poor adherence to therapy he developed resistance to both tenofovir and darunavir. We put together a new regiment with tenofovir alafenamide + emtricitabine + dolutegravir + maraviroc and nowadays he is with undetectable HIV-1 and HIV-2 viral loads.

Conclusions
This shows the importance of having access to HIV-2 viral load determination and HIV-2 resistance testing.
The standardization of clinical ethics consultation and technique’s “long encirclement” of humanity: a response to Brummett and Muaygil
Authors: Parks Benjamin N. , Mason Jordan 
Published: October 2021

AbstractIn their recent article, Brummett and Muaygil reject Bishop et al.’s framing of the debate over standardization in clinical ethics consultation (CEC) “as one between pro-credentialing procedural and anti-credentialing phenomenological,” claiming that this framing “amounts to a false dichotomy between two extreme approaches to CEC.” Instead of accepting proceduralism and phenomenology as a binary, Brummett and Muaygil propose that these two views should be seen as the extreme ends of a spectrum upon which CEC should be done. However, as evidenced by several inconsistencies within their article, they have failed to fully appreciate the concern animating Bishop et al.’s proposal. Additionally, because of this failure, they do not seem to realize that credentialing ethicists for CEC will only create different problems in Saudi Arabia even as it possibly solves some of the current problems they identify. In this commentary, we highlight and clarify Brummet and Muaygil’s five misunderstandings of Bishop et al. This leads us to conclude that while they claim to be advocating a middle way between proceduralism and phenomenology, in fact they would like for us to standardize another proceduralism, albeit one that incorporates some of the “qualitative” values of American bioethics.
Personalized analysis of minimal residual cancer cells in peritoneal lavage fluid predicts peritoneal dissemination of gastric cancer
Authors: Zhao Dongbing , Yue Pinli , Wang Tongbo , Wang Pei , Song Qianqian , Wang Jingjing , Jiao Yuchen 
Published: October 2021

AbstractPeritoneal dissemination (PD) is a major type of gastric cancer (GC) recurrence and leads to rapid death. Current approaches cannot precisely determine which patients are at high risk of PD to provide early intervention. In this study, we developed a technology to detect minimal residual cancer cells in peritoneal lavage fluid (PLF) samples with a personalized assay profiling tumor-specific mutations. In a prospective cohort of 104 GC patients, the technology detected all the cases that developed PD with 100% sensitivity and 85% specificity. The minimal residual cancer cells in PLF were associated with a significantly increased risk of PD (HR = 145.13; 95% CI 20.20–18,435.79; p < 0.001), which was the strongest independent predictor over pathologic diagnosis and cytological diagnosis. In pathologically high-risk (pT4) patients, the PLF mutation profiling model exhibited a greater specificity of 91% and a positive predictive value of 88% while retaining a sensitivity of 100%. This approach may help in the postsurgical management of GC patients by detecting PD far before metastatic lesions grow to a significant size detectable by conventional methods such as MRI and CT scanning.
Differences between intrinsic and acquired nucleoside analogue resistance in acute myeloid leukaemia cells
Authors: Rothenburger Tamara , Thomas Dominique , Schreiber Yannick , Wratil Paul R. , Pflantz Tamara , Knecht Kirsten , Digianantonio Katie , Temple Joshua , Schneider Constanze , Baldauf Hanna-Mari , McLaughlin Katie-May , Rothweiler Florian , Bilen Berna , Farmand Samira , Bojkova Denisa , Costa Rui , Ferreirós Nerea , Geisslinger Gerd , Oellerich Thomas , Xiong Yong , Keppler Oliver T. , Wass Mark N. , Michaelis Martin , Cinatl Jindrich 
Published: October 2021

Abstract
Background
SAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage of their triphosphorylated forms. Hence, SAMHD1 inhibitors are promising candidates for the sensitisation of leukaemia cells to nucleoside analogue-based therapy. Here, we investigated the effects of the cytosine analogue CNDAC, which has been proposed to be a SAMHD1 inhibitor, in the context of SAMHD1.

Methods
CNDAC was tested in 13 acute myeloid leukaemia (AML) cell lines, in 26 acute lymphoblastic leukaemia (ALL) cell lines, ten AML sublines adapted to various antileukaemic drugs, 24 single cell-derived clonal AML sublines, and primary leukaemic blasts from 24 AML patients. Moreover, 24 CNDAC-resistant sublines of the AML cell lines HL-60 and PL-21 were established. The SAMHD1 gene was disrupted using CRISPR/Cas9 and SAMHD1 depleted using RNAi, and the viral Vpx protein. Forced DCK expression was achieved by lentiviral transduction. SAMHD1 promoter methylation was determined by PCR after treatment of genomic DNA with the methylation-sensitive HpaII endonuclease. Nucleoside (analogue) triphosphate levels were determined by LC-MS/MS. CNDAC interaction with SAMHD1 was analysed by an enzymatic assay and by crystallisation.

Results
Although the cytosine analogue CNDAC was anticipated to inhibit SAMHD1, SAMHD1 mediated intrinsic CNDAC resistance in leukaemia cells. Accordingly, SAMHD1 depletion increased CNDAC triphosphate (CNDAC-TP) levels and CNDAC toxicity. Enzymatic assays and crystallisation studies confirmed CNDAC-TP to be a SAMHD1 substrate. In 24 CNDAC-adapted acute myeloid leukaemia (AML) sublines, resistance was driven by DCK (catalyses initial nucleoside phosphorylation) loss. CNDAC-adapted sublines displayed cross-resistance only to other DCK substrates (e.g. cytarabine, decitabine). Cell lines adapted to drugs not affected by DCK or SAMHD1 remained CNDAC sensitive. In cytarabine-adapted AML cells, increased SAMHD1 and reduced DCK levels contributed to cytarabine and CNDAC resistance.

Conclusion
Intrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. The lack of cross-resistance between SAMHD1/ DCK substrates and non-substrates provides scope for next-line therapies after treatment failure.
Under-nutrition and associated factors among children on ART in Southern Ethiopia: a facility-based cross-sectional study
Authors: Tiruneh Chalie Marew , Walle Belete Gelaw , Emiru Tigabu Desie , Tibebu Nigusie Selomon , Abate Moges Wubneh , Nigat Adane Birhanu , Belete Amsalu , Alem Eyasu , Lankrew Tadele , Eshetu Kirubel 
Published: October 2021

Abstract
Background
Malnutrition is very common in HIV-infected individuals. Even though data from different settings are necessary to tackle it, pieces of evidence are limited especially in the case of the nutritional status of HIV-infected children. Hence, this study aims to assess the nutritional status and associated factors among children on antiretroviral therapy.

Methods
An institutional-based cross-sectional study was conducted among 383 HIV-positive children in Southern Ethiopia. Data were collected using an interviewer-administered questionnaire and anthropometry measurement. Data were coded and entered into Epi-Data Version 3.1 and analyzed using SPSS Version 25. Bi-variable and multi-variable binary logistic regression models were used to identify factors associated with nutritional status and variables with p-values <0.05 in multi-variable logistic regression were considered as statistically significant.

Results
The prevalence of wasting among HIV-positive children in Southern Ethiopiaselected Hospitals was 36.3% (95% CI, 31.6–41.0) while stunting on the same study population was 5.5% (95% CI, 3.4–7.8). Rural residence, lack of maternal education, low CD4 counts (< 500), using an unprotected water source, having a non-biological mother and recurrent oral lesion were significantly associated with wasting. Furthermore, history of hospital admission, recurrent oral lesion, low CD4 counts (< 500), advanced WHO clinical stage were statically associated with stunting with p-value < 0.05.

Conclusion
This study found that the prevalence of under-nutrition among HIV-positive children in Ethiopia was significantly high. Therefore, timely identification and monitoring of nutritional problems should be necessary to enhance the effectiveness of ART treatment and to prevent further related complications.