bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives of stakeholders of the free maternity services for mothers in western Kenya: lessons for universal health coverage
Authors: Ochieng Beverly Marion , Kaseje Margaret , Kaseje Dan Clement Owino , Oria Kevin , Magadi Monica 
Published: February 2022

Abstract
Background
The strategic aim of universal health coverage (UHC) is to ensure that everyone can use health services they need without risk of financial hardship. Linda Mama (Taking care of the mother) initiative focuses on the most vulnerable women, newborns and infants in offering free health services. Financial risk protection is one element in the package of measures that provides overall social protection, as well as protection against severe financial difficulties in the event of pregnancy, childbirth, neonatal and perinatal health care for mothers and their children.

Purpose
The aim of this study was to find out the extent of awareness, and involvement among managers, service providers and consumers of Linda mama supported services and benefits of the initiative from the perspectives of consumers, providers and managers.

Methods
We carried out cross sectional study in four sub counties in western Kenya: Rachuonyo East, Nyando, Nyakach, and Alego Usonga. We used qualitative techniques to collect data from purposively selected Linda Mama project implementors, managers, service providers and service consumers. We used key informant interview guides to collect data from a total of thirty six managers, nine from each Sub -County and focus group discussion tools to collect data from sixteen groups of service consumers attending either antenatal or post-natal clinics, four from each sub county, selecting two groups from antenatal and two from postnatal clinics in each sub county. Data analysis was based on thematic content analysis.

Findings
Managers and service providers were well aware of the initiative and were involved in it. Participation in Linda Mama, either in providing or using, seemed to be more prominent among managers and service providers. Routine household visits by community health volunteers to sensitize mothers and community engagement was core to the initiative. The managers and providers of services displayed profound awareness of how requiring identification cards and telephone numbers had the potential to undermine equity by excluding those in greater need of care such as under-age pregnant adolescents. Maternity and mother child health services improved as a result of the funds received by health facilities. Linda Mama reimbursements helped to purchase drug and reduced workload in the facility by hiring extra hands.

Conclusion
The initiative seems to have influenced attitudes on health facility delivery through: Partnership among key stakeholders and highlighting the need for enhanced partnership with the communities. It enhanced the capacity of health facilities to deliver high quality comprehensive, essential care package and easing economic burden.
Castration-resistant prostate cancer patient presenting with whole genome doubling with CDK-12 mutation
Authors: Baba Yuto , Kosaka Takeo , Kobayashi Hiroaki , Nakamura Kohei , Mikami Shuji , Nishihara Hiroshi , Nakanishi Makoto , Oya Mototsugu 
Published: February 2022

Abstract
Background
The use of whole-genome sequencing in clinical practice has revealed variable genomic characteristics across cancer types, one of which is whole-genome doubling (WGD), which describes the duplication of a complete set of chromosomes. Yet it is relatively rare in prostate cancer and no such case has ever been reported in Japanese patients.

Case presentation
A 54-year-old patient with prostatic adenocarcinoma with bone and lymph node metastases was started on androgen-deprivation therapy. As the prostate cancer turned castration-resistant, multimodal therapies including taxane- and platinum-based chemotherapy, androgen-receptor antagonist inhibitors, radiotherapy and radium-233 were introduced. Good controls of serum prostate-specific antigen (PSA) level and bone metastases were achieved for more than 13 years since after the initial treatment. During the treatment, a metastatic lymph node biopsy was performed to confirm the tumor histology, and spinal decompression surgery were performed for spinal compression due to lumber vertebral metastases. The immunohistochemical analysis identified PSA and androgen receptor positive tumor cells in both metastatic lesions, while no variable cancer cells were detected in the prostate on second biopsy. Whole-genome sequencing was performed on the biopsied metastatic lymph node in search for another possible treatment and it revealed that the tumor had WGD and CDK12 mutation. The WGD-positive tumor cells contained large and polymorphic nucleus, presumably reflecting on the ploidy abnormality of the chromosomes.

Conclusions
This report is the first case of a Japanese patient presenting with WGD, who survived more than 13 years with multimodal chemotherapies and radiotherapies.
Macular pigment-enriched oil production from genome-edited microalgae
Authors: Song Inhwa , Kim Sunbin , Kim Jongrae , Oh Hyeonjun , Jang Junhwan , Jeong Su Jin , Baek Kwangryul , Shin Weon-Sun , Sim Sang Jun , Jin EonSeon 
Published: February 2022

Abstract
Background
The photosynthetic microorganism Chlamydomonas reinhardtii has been approved as generally recognized as safe (GRAS) recently, this can excessively produce carotenoid pigments and fatty acids. Zeaxanthin epoxidase (ZEP), which converts zeaxanthin to violaxanthin, and ADP-glucose pyrophosphorylase (AGP). These are key regulating genes for the xanthophyll and starch pathways in C. reinhardtii respectively. In this study, to produce macular pigment-enriched microalgal oil, we attempted to edit the AGP gene as an additional knock-out target in the zep mutant as a parental strain.

Results
Using a sequential CRISPR-Cas9 RNP-mediated knock-out method, we generated double knock-out mutants (dZAs), in which both the ZEP and AGP genes were deleted. In dZA1, lutein (2.93 ± 0.22 mg g−1 DCW: dried cell weight), zeaxanthin (3.12 ± 0.30 mg g−1 DCW), and lipids (450.09 ± 25.48 mg g−1 DCW) were highly accumulated in N-deprivation condition. Optimization of the culture medium and process made it possible to produce pigments and oil via one-step cultivation. This optimization process enabled dZAs to achieve 81% higher oil productivity along with similar macular pigment productivity, than the conventional two-step process. The hexane/isopropanol extraction method was developed for the use of macular pigment-enriched microalgal oil for food. As a result, 196 ± 20.1 mg g−1 DCW of edible microalgal oil containing 8.42 ± 0.92 mg g−1 lutein of oil and 7.69 ± 1.03 mg g−1 zeaxanthin of oil was produced.

Conclusion
Our research showed that lipids and pigments are simultaneously induced in the dZA strain. Since dZAs are generated by introducing pre-assembled sgRNA and Cas9-protein into cells, antibiotic resistance genes or selective markers are not inserted into the genome of dZA, which is advantageous for applying dZA mutant to food. Therefore, the enriched macular pigment oil extracted from improved strains (dZAs) can be further applied to various food products and nutraceuticals.
District-led malaria surveillance and response as an effective way to manage malaria upsurges following the withdrawal of indoor residual spraying: a case study from Nwoya District, northern Uganda
Authors: Nuwa Anthony , Oola Janet , Obonyo Sam Okot , Feldman Mitra , Karungi Shirah , Kertho Edmound , Odong David Salandini , Kimera Isaac , Magumba Godfrey , Beinomugisha Geofrey , Chitty Alexandra , Tibenderana James , Opigo Jimmy , Abwaimo Francis 
Published: February 2022

Abstract
Background
Malaria remains the number one cause of morbidity and mortality in Uganda. In 2009, the United States President’s Malaria Initiative (PMI) funded an indoor residual spraying (IRS) project in 10 mid-northern districts, resulting in marked reductions in malaria prevalence over 5 years, from 62.5 percent to 7.2 percent. When the project ended and IRS withdrawn, malaria prevalence increased exponentially to pre-IRS level of 63 percent in 2016 and was characterized by frequent life-threatening upsurges that were exacerbated by a weak national led malaria surveillance system with delayed and piece meal responses. Malaria Consortium, in collaboration with Nwoya district local government implemented a district led malaria surveillance and response system. This study was conducted to compare the impact of District led and national led surveillance and response systems on overall malaria burden in two sub-counties in Nwoya district, Northern Uganda.

Methods
The assessment was conducted between week 41 of 2018 and week 10 of 2019 in Anaka and Alero sub counties following the shift from the national to district led malaria surveillance and response system. A district multi-sectoral malaria response taskforce team, known as the District Malaria Surveillance and Response Team (DMSRT), was formed by the Nwoya District Health Team (DHT). The DMSRT was trained and equipped with new surveillance tools for early detection of and response to malaria upsurges within the district, and were mandated to develop a costed district specific malaria response plan.

Results
All (18) targeted health facilities provided weekly malaria reports and continuously updated the malaria normal channel graphs. There was an overall reduction in weekly new malaria cases from 12.9 in week 41 of 2018 to 6.2 cases in week 10 of 2019. Malaria positivity rates (TPR) for Alero and Anaka sub-counties reduced from 76.0 percent and 69.3 percent at week 42 of 2018 to 28 percent and 30.3 percent, respectively at week 10 of 2019.

Conclusions
Malaria surveillance and response, with precisely targeted multipronged activities, when led and implemented by local district health authorities is an effective, efficient, and sustainable approach to prevent malaria upsurges and associated morbidity and mortality.
Knowledge and social beliefs of malaria and prevention strategies among itinerant Nomadic Arabs, Fulanis and Dagazada groups in Chad: a mixed method study
Authors: Moukénet Azoukalné , Honoré Beackgoubé , Smith Helen , Moundiné Kebféné , Djonkamla Wang-Mbe , Richardson Sol , Dormbaye Makido , Ngarasta Ngarkodje , Seck Ibrahima 
Published: February 2022

Abstract
Background
Nomadic populations in Chad are at increased risk of contracting malaria because of their lifestyle. Being highly mobile they are often excluded from disease control programmes, and access to preventive measures and treatment is more difficult. Effective malaria control interventions take account of local modes of transmission, patterns of care-seeking behaviour and community perceptions of cause and prevention practices. There is currently little information about malaria knowledge and perceptions among nomadic groups in Chad, or their awareness of malaria control interventions and this study sought to address this knowledge gap.

Methods
A mixed methods study, including a cross-sectional survey with men and women (n = 78) to determine the level of knowledge and use of malaria prevention strategies among Arabs, Peuls and Dagazada nomadic groups. Three focus group discussions were conducted with women to explore their representation of malaria and knowledge of preventive methods. Key informant interviews were held with leaders of nomadic groups (n = 6) to understand perception of malaria risk among itinerant communities.

Results
Nomads are aware of the risk of malaria, recognize the symptoms and have local explanations for the disease. Reported use of preventive interventions such as Seasonal Malaria Chemoprevention (SMC) for children and Intermittent Preventive Treatment (IPT) of malaria in pregnancy was very low. However, 42.3% of respondents reported owning at least one LLIN and 60% said they slept under an LLIN the night before the survey. In case of a malaria episode, nomads seek clinicians, informal drug sellers in the street or market for self-medication, or traditional medicine depending on their financial means. Interviews with nomad leaders and discussions with women provide key themes on: (i) social representation of malaria risk and (ii) social representation of malaria and (iii) perspectives on malaria prevention and (iv) malaria treatment practices.

Conclusion
The nomadic groups included in this study are aware of risk of malaria and their level of exposure. Local interpretations of the cause of malaria could be addressed through tailored and appropriate health education. Except for LLINs, malaria prevention interventions are not well known or used. Financial barriers lowered access to both mosquito nets and malaria treatment. Reducing the barriers highlighted in this study will improve access to the healthcare system for nomadic groups, and increase the opportunity to create awareness of and improve uptake of SMC and IPT among women and children.
Human placental exosomes induce maternal systemic immune tolerance by reprogramming circulating monocytes
Authors: Bai Kunfeng , Lee Cheuk-Lun , Liu Xiaofeng , Li Jianlin , Cao Dandan , Zhang Li , Hu Duanlin , Li Hong , Hou Yanqing , Xu Yue , Kan Anita S. Y. , Cheung Ka-Wang , Ng Ernest H. Y. , Yeung William S. B. , Chiu Philip C. N. 
Published: February 2022

Abstract
Background
The maternal immune system needs to tolerate the semi-allogeneic fetus in pregnancy. The adaptation occurs locally at the maternal–fetal interface as well as systemically through the maternal circulation. Failure to tolerate the paternal antigens may result in pregnancy complications, such as pregnancy loss and pre-eclampsia. However, the mechanism that regulates maternal immune tolerance, especially at the systemic level, is still an enigma. Here we report that the first-trimester placenta-derived exosomes (pEXOs) contribute to maternal immune tolerance by reprogramming the circulating monocytes.

Results
pEXOs predominantly target monocytes and pEXO-educated monocytes exhibit an immunosuppressive phenotype as demonstrated by reduced expression of marker genes for monocyte activation, T-cell activation and antigen-process/presentation at the transcriptomic level. They also have a greater propensity towards M2 polarization when compared to the monocytes without pEXO treatment. The inclusion of pEXOs in a monocyte-T-cell coculture model significantly reduces proliferation of the T helper cells and cytotoxic T cells and elevates the expansion of regulatory T cells. By integrating the microRNAome of pEXO and the transcriptomes of pEXO-educated monocytes as well as various immune cell functional assays, we demonstrate that the pEXO-derived microRNA miR-29a-3p promotes the expression of programmed cell death ligand-1, a well-known surface receptor that suppresses the adaptive immune system, by down-regulation of phosphatase and tensin homolog in monocytes.

Conclusions
This is the first report to show how human pEXO directly regulates monocyte functions and its molecular mechanism during early pregnancy. The results uncover the importance of pEXO in regulating the maternal systemic immune response during early pregnancy by reprogramming circulating monocytes. The study provides the basis for understanding the regulation of maternal immune tolerance to the fetal allograft.

Graphical Abstract
Zinc-metal–organic frameworks with tunable UV diffuse-reflectance as sunscreens
Authors: Xiao Jisheng , Li Haishan , Zhao Wanling , Cai Chengyuan , You Tingting , Wang Zhenyu , Wang Mengling , Zeng Feng , Cheng Jinmei , Li Jiaxin , Duan Xiaopin 
Published: February 2022

Abstract
Background
UV exposure continues to induce many health issues, though commercial sunscreens are available. Novel UV filters with high safety and efficacy are urgently needed. Metal–organic frameworks (MOFs) could be a suitable platform for UV filter development, due to their tunable optical, electrical, and photoelectric properties by precise controlled synthesis.

Results
Herein, four zinc-based MOFs with various bandgap energies were chose to investigate their optical behaviors and evaluate their possibility as sunscreens. Zeolitic imidazolate framework-8 (ZIF-8) was found to possess the highest and widest UV reflectance, thereby protecting against sunburn and DNA damage on mouse skin and even achieving a comparable or higher anti-UV efficacy relative to the commercially available UV filters, TiO2 or ZnO, on pig skin, a model that correlates well with human skin. Also, ZIF-8 exerted appealing characteristics for topical skin use with low radical production, low skin penetration, low toxicity, high transparency, and high stability.

Conclusion
These results confirmed ZIF-8 could potentially be a safe and effective sunscreen surrogate for human, and MOFs could be a novel source to develop more effective and safe UV filters.

Graphical Abstract
Self-oxygenation mesoporous MnO2 nanoparticles with ultra-high drug loading capacity for targeted arteriosclerosis therapy
Authors: Sun Weidong , Xu Yiyan , Yao Ye , Yue Jie , Wu Zhen , Li Haocheng , Shen Guanghui , Liao Yan , Wang Haiyang , Zhou Wenhu 
Published: February 2022

AbstractAtherosclerosis (AS) is a leading cause of vascular diseases that severely threats the human health due to the lack of efficient therapeutic methods. During the development and progress of AS, macrophages play critical roles, which are polarized into pro-inflammatory M1 phenotype to excrete abundant cytokines and overproduce reactive oxygen species (ROS), and take up excess amount of lipid to form foam cells. In this work, we developed a MnO2-based nanomedicine to re-educate macrophages for targeting AS therapy. The MnO2 was one-pot synthesized under mild condition, showing intrinsic catalase-mimic activity for self-oxygenation by using endogenous H2O2 as substrate. Moreover, the mesoporous structure as well as the abundant metal coordination sites in MnO2 structure facilitated the loading of an anti-AS drug of curcumin (Cur), achieving extraordinarily high drug loading capacity of 54%. Cur displayed a broad spectrum of anti-oxidant and anti-inflammatory capabilities to repolarize M1 macrophages into M2 phenotype, and the catalytic MnO2 recovered the function of lipid efflux transporter to remove lipid from cells by suppressing HIF-1α. Collectively, the nanocarrier and the payload drug functioned as an all-active nanoplatform to synergistically alleviate the syndromes of AS. In ApoE−/− mice model, the nanosystem could significantly prolong the circulation half-life of Cur by sixfold, and enhance drug accumulation in atherosclerotic lesion by 3.5-fold after intravenous injection by virtue of surface hyaluronic acid (HA) modification. As a result, a robust anti-AS efficacy was achieved as evidenced by the decrease of atherosclerotic lesion, plaque area, lipid level.
Graphical Abstract
Hierarchical functional nanoparticles boost osteoarthritis therapy by utilizing joint-resident mesenchymal stem cells
Authors: Lu Yao , Chen Jieli , Li Lihua , Cao Yumei , Zhao Yang , Nie Xiaoyu , Ding Changhai 
Published: February 2022

AbstractUtilization of joint-resident mesenchymal stem cells (MSC) to repair articular cartilage is a promising strategy in osteoarthritis (OA) therapy but remains a considerable research challenge. Here, hierarchical targeting and microenvironment responsive peptide functionalized nanoparticles (NPs) are used to achieve cartilage repair in situ. Ultrasmall copper oxide (CuO) NPs are conjugated with type 2 collagen and MSC dual-targeting peptide (designated WPV) with a matrix metalloproteinase 2 (MMP-2)-sensitive sequence as a spacer to achieve hierarchical targeting. Guided by this peptide, WPV-CuO NPs initially penetrate cartilage and subsequently expose the inner MSC-targeted peptide to attract MSCs through MMP-2 clearance. CuO further promotes chondrogenesis of MSCs. In an anterior cruciate ligament transection rat model, intraarticular injection of WPV-CuO NPs induces significant reduction of cartilage destruction. The therapeutic mechanism involves inhibition of the PI3K/AKT/mTOR pathway, as determined via transcriptome analysis. In conclusion, a novel therapeutic strategy for OA has been successfully developed based on localized MSC recruitment and cartilage repair without transplantation of exogenous cells or growth factors.
Graphical Abstract
Evaluation of an alternative heterotopic transplantation model for ovarian tissue to test pharmaceuticals improvements for fertility restoration
Authors: Terren Carmen , Bindels Jules , Nisolle Michelle , Noël Agnès , Munaut Carine 
Published: February 2022

Abstract
Background
Ovarian tissue cryopreservation and transplantation (OTCTP) is currently the main option available to preserve fertility in prepubertal patients undergoing aggressive cancer therapy treatments. However, a major limitation of OTCTP is follicle loss after transplantation. The mouse is a model of choice for studying ovarian function and follicle development after ovarian tissue grafting in vivo. In these mouse models, ovarian tissue or ovaries can be transplanted to different sites. Our aim was to evaluate a new alternative to heterotopic transplantation models that could be useful to test pharmaceutical improvement for ovarian grafts after OTCTP.

Methods
Slow frozen murine whole ovaries were transplanted into the mouse ears (between the external ear skin layer and the cartilage). Ovarian transplants were recovered after 3, 14 or 21 days. Grafts were analyzed by immunohistochemistry and follicle density analyses were performed.

Results
An increase of ovarian vascularization (CD31 and Dextran-FITC positive staining), as well as cellular proliferation (Ki67 staining) were observed 3 weeks after transplantation in comparison to 3 days. Fibrosis density, evaluated after Van Gieson staining, decreased 3 weeks after transplantation. Furthermore, transplantation of cryopreserved ovaries into ovariectomized mice favored follicle activation compared to transplantation into non-ovariectomized mice.

Conclusion
The present study indicates that surgical tissue insertion in the highly vascularized murine ear is an effective model for ovarian grafting. This model could be helpful in research to test pharmaceutical strategies to improve the function and survival of cryopreserved and transplanted ovarian tissue.