bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of community case management of malaria in malaria endemic counties of western Kenya: are community health volunteers up to the task in diagnosing malaria?
Authors: Marita Enock , Langat Bernard , Kinyari Teresa , Igunza Patrick , Apat Donald , Kimori Josephat , Carter Jane , Kiplimo Richard , Muhula Samuel 
Published: March 2022

Abstract
Background
Community case management of malaria (CCMm) is an equity-focused strategy that complements and extends the reach of health services by providing timely and effective management of malaria to populations with limited access to facility-based healthcare. In Kenya, CCMm involves the use of malaria rapid diagnostic tests (RDT) and treatment of confirmed uncomplicated malaria cases with artemether lumefantrine (AL) by community health volunteers (CHVs). The test positivity rate (TPR) from CCMm reports collected by the Ministry of Health in 2018 was two-fold compared to facility-based reports for the same period. This necessitated the need to evaluate the performance of CHVs in conducting malaria RDTs.

Methods
The study was conducted in four counties within the malaria-endemic lake zone in Kenya with a malaria prevalence in 2018 of 27%; the national prevalence of malaria was 8%. Multi-stage cluster sampling and random selection were used. Results from 200 malaria RDTs performed by CHVs were compared with test results obtained by experienced medical laboratory technicians (MLT) performing the same test under the same conditions. Blood slides prepared by the MLTs were examined microscopically as a back-up check of the results. A Kappa score was calculated to assess level of agreement. Sensitivity, specificity, and positive and negative predictive values were calculated to determine diagnostic accuracy.

Results
The median age of CHVs was 46 (IQR: 38, 52) with a range (26–73) years. Females were 72% of the CHVs. Test positivity rates were 42% and 41% for MLTs and CHVs respectively. The kappa score was 0.89, indicating an almost perfect agreement in RDT results between CHVs and MLTs. The overall sensitivity and specificity between the CHVs and MLTs were 95.0% (95% CI 87.7, 98.6) and 94.0% (95% CI 88.0, 97.5), respectively.

Conclusion
Engaging CHVs to diagnose malaria cases under the CCMm strategy yielded results which compared well with the results of qualified experienced laboratory personnel. CHVs can reliably continue to offer malaria diagnosis using RDTs in the community setting.
Quantification of the dynamics of antibody response to malaria to inform sero-surveillance in pregnant women
Authors: Dharmaratne A. D. V. Tharkeshi T. , Dini Saber , O’Flaherty Katherine , Price David J. , Beeson James , McGready Rose , Nosten Francois , Fowkes Freya J. I. , Simpson Julie A. , Zaloumis Sophie G. 
Published: March 2022

AbstractBackgroundMalaria remains a major public health threat and tools sensitive to detect infections in low malaria transmission areas are needed to progress elimination efforts. Pregnant women are particularly vulnerable to malaria infections. Throughout pregnancy they access routine antenatal care, presenting a unique sentinel population to apply novel sero-surveillance tools to measure malaria transmission. The aim of this study was to quantify the dynamic antibody responses to multiple antigens during pregnancy so as to identify a single or multiple antibody response of exposure to malaria in pregnancy.MethodsThis study involved a secondary analysis of antibody responses to six parasite antigens [five commonly studied merozoite antigens and the variant surface antigen 2-chondroitin sulphate A (VAR2CSA), a pregnancy-specific erythrocytic antigen] measured by enzyme-linked immunosorbent assay (ELISA) over the gestation period until delivery (median of 7 measurements/woman) in 250 pregnant women who attended antenatal clinics located at the Thai-Myanmar border. A multivariate mixture linear mixed model was used to cluster the pregnant women into groups that have similar longitudinal antibody responses to all six antigens over the gestational period using a Bayesian approach. The variable-specific entropy was calculated to identify the antibody responses that have the highest influence on the classification of the women into clusters, and subsequent agreement with grouping of women based on exposure to malaria during pregnancy.ResultsOf the 250 pregnant women, 135 had aPlasmodiuminfection detected by light microscopy during pregnancy (39%Plasmodium falciparumonly, 33%Plasmodium vivaxonly and 28% mixed/other species), defined as cases. The antibody responses to all six antigens accurately identified the women who did not have a malaria infection detected during pregnancy (93%, 107/115 controls). Antibody responses toP. falciparummerozoite surface protein 3 (PfMSP3) andP. vivaxapical membrane antigen 1 (PvAMA1) were the least dynamic. Antibody responses to the antigensP. falciparumapical membrane antigen 1 (PfAMA1) andPfVAR2CSA were able to identify the majority of the cases more accurately (63%, 85/135).ConclusionThese findings suggest that the combination of antibodies,PfAMA1 andPfVAR2CSA, may be useful for sero-surveillance of malaria infections in pregnant women, particularly in low malaria transmission settings. Further investigation of other antibody markers is warranted considering these antibodies combined only detected 63% of the malaria infections during pregnancy.
Super-resolution imaging of Douglas fir xylem cell wall nanostructure using SRRF microscopy
Authors: Donaldson Lloyd A. 
Published: March 2022

AbstractBackgroundThe nanostructure of plant cell walls is of significant biological and technological interest, but methods suited to imaging cell walls at the nanoscale while maintaining the natural water-saturated state are limited. Light microscopy allows imaging of wet cell walls but with spatial resolution limited to the micro-scale. Most super-resolution techniques require expensive hardware and/or special stains so are less applicable to some applications such as autofluorescence imaging of plant tissues.ResultsA protocol was developed for super-resolution imaging of xylem cell walls using super-resolution radial fluctuations (SRRF) microscopy combined with confocal fluorescence imaging (CLSM). We compared lignin autofluorescence imaging with acriflavin or rhodamine B staining. The SRRF technique allows imaging of wet or dry tissue with moderate improvement in resolution for autofluorescence and acriflavin staining, and a large improvement for rhodamine B staining, achieving sub 100 nm resolution based on comparison with measurements from electron microscopy. Rhodamine B staining, which represents a convolution of lignin staining and cell wall accessibility, provided remarkable new details of cell wall structural features including both circumferential and radial lamellae demonstrating nanoscale variations in lignification and cell wall porosity within secondary cell walls.ConclusionsSRRF microscopy can be combined with confocal fluorescence microscopy to provide nanoscale imaging of plant cell walls using conventional stains or autofluorescence in either the wet or dry state.
LncRNA HOTAIR facilitates proliferation and represses apoptosis of retinoblastoma cells through the miR-20b-5p/RRM2/PI3K/AKT axis
Authors: Fu Ke , Zhang Ke , Zhang Xiaoyu 
Published: March 2022

Abstract
Purpose
Retinoblastoma (RB) represents an adolescent eye malignancy. Long non-coding RNA (LncRNA) HOTAIR shows aberrant expression in many malignancies. This research investigated the mechanism of HOTAIR in RB.

Methods
Normal retinal cell lines (ARPE-19 and RPE-1) and RB cell lines (ORB50, Y79, HXO-RB44, and WERI-RB) were selected for detection of HOTAIR expression by qRT-PCR. sh-HOTAIR was delivered into Y79 and HXO-RB44 cells. Cell-cycle distribution, proliferation, and apoptosis were detected by CCK-8 assay and flow cytometry. Binding relationships among HOTAIR, miR-20b-5p, and RRM2 were confirmed using dual-luciferase assay. Roles of miR-20b-5p and RRM2 in RB cell-cycle distribution, proliferation, and apoptosis were ascertained by functional rescue experiments. Murine model of xenograft tumor was established, followed by detection of tumor growth and counting of Ki67-positive cells. Expressions of proliferation- and apoptosis-associated proteins and PI3K/AKT pathway-related proteins were determined by Western blot.

Results
HOTAIR was elevated in RB cells relative to that in normal retinal cells and showed relatively high expression in Y79 and HXO-RB44 cells. sh-HOTAIR induced RB cell-cycle arrest, restrained proliferation, and strengthened apoptosis. HOTAIR functioned as the ceRNA of miR-20b-5p and targeted RRM2. RB cells had poorly-expressed miR-20b-5p and highly-expressed RRM2. miR-20b-5p downregulation or RRM2 overexpression facilitated RB cell-cycle and proliferation, suppressed apoptosis, and reversed the protective effect of sh-HOTAIR on RB. sh-HOTAIR reduced tumor growth and Ki67-positive cells in vivo and inactivated PI3K/AKT pathway.

Conclusion
LncRNA HOTAIR upregulated RRM2 by competitively binding to miR-20b-5p and activated PI3K/AKT pathway, thereby facilitating proliferation and repressing apoptosis of RB cells.
Heterogeneous clinical features in Cockayne syndrome patients and siblings carrying the same CSA mutations
Authors: Chikhaoui Asma , Kraoua Ichraf , Calmels Nadège , Bouchoucha Sami , Obringer Cathy , Zayoud Khouloud , Montagne Benjamin , M’rad Ridha , Abdelhak Sonia , Laugel Vincent , Ricchetti Miria , Turki Ilhem , Yacoub-Youssef Houda 
Published: March 2022

Abstract
Background
Cockayne syndrome (CS) is a rare autosomal recessive disorder caused by mutations in ERCC6/CSB or ERCC8/CSA that participate in the transcription-coupled nucleotide excision repair (TC-NER) of UV-induced DNA damage. CS patients display a large heterogeneity of clinical symptoms and severities, the reason of which is not fully understood, and that cannot be anticipated in the diagnostic phase. In addition, little data is available for affected siblings, and this disease is largely undiagnosed in North Africa.

Methods
We report here the clinical description as well as genetic and functional characterization of eight Tunisian CS patients, including siblings. These patients, who belonged to six unrelated families, underwent complete clinical examination and biochemical analyses. Sanger sequencing was performed for the recurrent mutation in five families, and targeted gene sequencing was done for one patient of the sixth family. We also performed Recovery RNA Synthesis (RRS) to confirm the functional impairment of DNA repair in patient-derived fibroblasts.

Results
Six out of eight patients carried a homozygous indel mutation (c.598_600delinsAA) in exon 7 of ERCC8, and displayed a variable clinical spectrum including between siblings sharing the same mutation. The other two patients were siblings who carried a homozygous splice-site variant in ERCC8 (c.843+1G>C). This last pair presented more severe clinical manifestations, which are rarely associated with CSA mutations, leading to gastrostomy and hepatic damage. Impaired TC-NER was confirmed by RRS in six tested patients.

Conclusions
This study provides the first deep characterization of case series of CS patients carrying CSA mutations in North Africa. These mutations have been described only in this region and in the Middle-East. We also provide the largest characterization of multiple unrelated patients, as well as siblings, carrying the same mutation, providing a framework for dissecting elusive genotype–phenotype correlations in CS.
Treating rare diseases with the cinema: Can popular movies enhance public understanding of rare diseases?
Authors: Domaradzki Jan 
Published: March 2022

AbstractBackgroundRare diseases (RDs) constitute an important public health issue. However, although public awareness campaigns focus on the improvement of undergraduate and postgraduate education, also popular culture may serve as an educational tool in this field. This study aims to analyse how rare genetic diseases are depicted in popular movies.MethodsTwenty popular movies on RDs were analysed quantitatively. The main categories included in the coding frame were: disease, patient, physician/scientist and psychosocial issuses related to RDs.ResultsThe majority of movies do not contain adequate scientific information on RDs. Consequently, their cinematic image is either inaccurate or simplified. However, the cinema does take up some important topics in the field of RDs and highlight their ethical, psychosocial, legal or economic dimension: the diagnostic and therapeutic odyssey, the role of RD patients’ advocacy groups in the production of scientific knowledge, the problem of orphan drugs, the stigmatisation of and discrimination against RD patients, and the impact of diagnosis on one’s concept of self and parents’ feelings of guilt.ConclusionAlthough popular movies mostly focus on RD patients’ problems of daily living and rarely describe clinical aspects of RDs, they do have an educational potential. Thus, movies can help to raise the public’s awareness on the psychospocial and economic problems faced by RD patients and their families.
Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease
Authors: Bairamian Diane , Sha Sha , Rolhion Nathalie , Sokol Harry , Dorothée Guillaume , Lemere Cynthia A. , Krantic Slavica 
Published: March 2022

Abstract
Background
The implication of gut microbiota in the control of brain functions in health and disease is a novel, currently emerging concept. Accumulating data suggest that the gut microbiota exert its action at least in part by modulating neuroinflammation. Given the link between neuroinflammatory changes and neuronal activity, it is plausible that gut microbiota may affect neuronal functions indirectly by impacting microglia, a key player in neuroinflammation. Indeed, increasing evidence suggests that interplay between microglia and synaptic dysfunction may involve microbiota, among other factors. In addition to these indirect microglia-dependent actions of microbiota on neuronal activity, it has been recently recognized that microbiota could also affect neuronal activity directly by stimulation of the vagus nerve.

Main messages
The putative mechanisms of the indirect and direct impact of microbiota on neuronal activity are discussed by focusing on Alzheimer’s disease, one of the most studied neurodegenerative disorders and the prime cause of dementia worldwide. More specifically, the mechanisms of microbiota-mediated microglial alterations are discussed in the context of the peripheral and central inflammation cross-talk. Next, we highlight the role of microbiota in the regulation of humoral mediators of peripheral immunity and their impact on vagus nerve stimulation. Finally, we address whether and how microbiota perturbations could affect synaptic neurotransmission and downstream cognitive dysfunction.

Conclusions
There is strong increasing evidence supporting a role for the gut microbiome in the pathogenesis of Alzheimer’s disease, including effects on synaptic dysfunction and neuroinflammation, which contribute to cognitive decline. Putative early intervention strategies based on microbiota modulation appear therapeutically promising for Alzheimer’s disease but still require further investigation.
Alzheimer’s disease – the journey of a healthy brain into organ failure
Authors: Golde Todd E. 
Published: March 2022

AbstractAs the most common dementia, Alzheimer’s disease (AD) exacts an immense personal, societal, and economic toll. AD was first described at the neuropathological level in the early 1900s. Today, we have mechanistic insight into select aspects of AD pathogenesis and have the ability to clinically detect and diagnose AD and underlying AD pathologies in living patients. These insights demonstrate that AD is a complex, insidious, degenerative proteinopathy triggered by Aβ aggregate formation. Over time Aβ pathology drives neurofibrillary tangle (NFT) pathology, dysfunction of virtually all cell types in the brain, and ultimately, overt neurodegeneration. Yet, large gaps in our knowledge of AD pathophysiology and huge unmet medical need remain. Though we largely conceptualize AD as a disease of aging, heritable and non-heritable factors impact brain physiology, either continuously or at specific time points during the lifespan, and thereby alter risk for devolvement of AD. Herein, I describe the lifelong journey of a healthy brain from birth to death with AD, while acknowledging the many knowledge gaps that remain regarding our understanding of AD pathogenesis. To ensure the current lexicon surrounding AD changes from inevitable, incurable, and poorly manageable to a lexicon of preventable, curable, and manageable we must address these knowledge gaps, develop therapies that have a bigger impact on clinical symptoms or progression of disease and use these interventions at the appropriate stage of disease.
Promising practices for the monitoring and evaluation of gender-based violence risk mitigation interventions in humanitarian response: a multi-methods study
Authors: Sharma Vandana , Ausubel Emily , Heckman Christine , Rastogi Sonia , Kelly Jocelyn T. D. 
Published: March 2022

AbstractBackgroundRisks of gender-based violence (GBV) are exacerbated in humanitarian crises. GBV risk mitigation interventions aim to reduce exposure to GBV and ensure that humanitarian response actions and services themselves do not cause harm or increase the risk of violence. The 2015 IASC Guidelines for Integrating Gender-Based Violence Interventions in Humanitarian Action (‘GBV Guidelines’) are a globally endorsed resource that provides comprehensive guidance for all humanitarian actors and sectors on GBV risk mitigation. While uptake of GBV risk mitigation approaches across multiple humanitarian sectors has occurred, there is limited understanding of how to monitor and evaluate GBV risk mitigation interventions.MethodsA multi-methods study was conducted in 2019 to identify promising practices for the monitoring and evaluation (M&E) of GBV risk mitigation interventions in non-GBV sectors and to develop a set of illustrative case examples. The study included a comprehensive desk review of 145 articles, documents and resources from the published and grey literature, as well as 11 in-depth interviews and five focus group discussions with humanitarian practitioners. Using Dedoose software and a codebook developed a priori, qualitative data were transcribed and coded and a content analysis was conducted. Excerpts focusing on promising practices from the qualitative data and the desk review were analyzed together and grouped by thematic area. Similar promising practices were combined and consolidated to create a final list, and case examples were identified.ResultsCurrent promising practices for M&E of GBV risk mitigation activities in the following categories are described: (1) Coordination and collaboration, (2) Designing M&E approaches and tools for GBV risk mitigation activities, (3) Contextualization, (4) Developing and selecting indicators, (5) Data collection, (6) Data analysis and use of findings, (7) Potential safety concerns for affected populations and staff, and (8) Staff capacity and engagement. These are supplemented with seven diverse case examples to illustrate application of the promising practices using real-world examples.ConclusionThis paper highlights current promising practices for M&E of GBV risk mitigation interventions in humanitarian response. Further application of these practices—alongside ongoing documentation of emerging approaches—will be critical to ensuring that GBV risk mitigation interventions are more rigorously tested with the aim of building the evidence base on the effectiveness of different GBV risk mitigation interventions within specific humanitarian sectors.
Targeting CRABP-II overcomes pancreatic cancer drug resistance by reversing lipid raft cholesterol accumulation and AKT survival signaling
Authors: Yu Shuiliang , Wang Lei , Che Danian , Zhang Mei , Li Ming , Naito Mikihiko , Xin Wei , Zhou Lan 
Published: March 2022

Abstract
Background
Resistance to standard therapy is a major reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Developing novel therapy to overcome PDAC drug-resistance is urgently needed. CRABP-II was highly expressed in all PDAC but not expressed in normal pancreatic tissues and chronic pancreatitis. CRABP-II was shown to promote PDAC migration and metastasis while its potential role in promoting PDAC drug-resistance was not known.

Methods
A paired cohort of human primary and relapsing PDAC tissues was assessed for CRABP-II expression by immunohistochemistry. CRISPR/cas9 gene editing was used to establish CRABP-II knockout cell lines and MTT assays were performed to assess gemcitabine sensitivity in vitro. Cleaved caspase-3/PARP blots and Annexin V staining were conducted to detect cell apoptosis. Gene expression microarray, Q-PCR, western blots, Co-IP and RNA-IP were used to study the molecular function of CRABP-II. Sucrose gradient ultracentrifugation was applied to isolate lipid rafts and LC–MS-MS was used to assess cholesterol content. Both subcutaneous CDX models and orthotopic PDX models were established to examine the efficacy of SNIPER-11 and the synergistic effect between SNIPER-11 and gemcitabine in vivo.

Results
A higher expression of CRABP-II was found in relapsing PDAC tissue and was associated with poor prognosis. Gemcitabine-resistant cell lines exhibited increased level of CRABP-II, while CRABP-II knockout resensitized PDAC cells to gemcitabine. Mechanistically, aberrant expression of CRABP-II increased the stability of SREBP-1c mRNA through cooperation with HuR and upregulated the downstream genes of SREBP-1c to favor cholesterol uptake and accumulation in lipid rafts. Increased lipid raft cholesterol accumulation facilitated ATK survival signaling and PDAC drug resistance. The small compound SNIPER-11 treatment effectively induced CRABP-II protein degradation, induced apoptosis, and suppressed tumor growth. Combination of SNIPER-11 and gemcitabine significantly reduced the lipid raft cholesterol content in CDX/PDX and profoundly inhibited tumor progression.

Conclusions
These findings identified CRABP-II as a novel regulator of cholesterol metabolism and suggested that CRABP-II is a selective target for overcoming PDAC drug resistance.
miR-3189-targeted GLUT3 repression by HDAC2 knockdown inhibits glioblastoma tumorigenesis through regulating glucose metabolism and proliferation
Authors: Kwak Sungmin , Park Seung-Ho , Kim Sung-Hak , Sung Gi-Jun , Song Ji-Hye , Jeong Ji-Hoon , Kim Hyunhee , Ha Chang Hoon , Kim Seong Who , Choi Kyung-Chul 
Published: March 2022

Abstract
Background
Epigenetic regulations frequently appear in Glioblastoma (GBM) and are highly associated with metabolic alterations. Especially, Histone deacetylases (HDACs) correlates with the regulation of tumorigenesis and cell metabolism in GBM progression, and HDAC inhibitors report to have therapeutic efficacy in GBM and other neurological diseases; however, GBM prevention and therapy by HDAC inhibition lacks a mechanism in the focus of metabolic reprogramming.

Methods
HDAC2 highly express in GBM and is analyzed in TCGA/GEPIA databases. Therefore, HDAC2 knockdown affects GBM cell death. Analysis of RNA sequencing and qRT-PCR reveals that miR-3189 increases and GLUT3 decreases by HDAC2 knockdown. GBM tumorigenesis also examines by using in vivo orthotopic xenograft tumor models. The metabolism change in HDAC2 knockdown GBM cells measures by glucose uptake, lactate production, and OCR/ECAR analysis, indicating that HDAC2 knockdown induces GBM cell death by inhibiting GLUT3.

Results
Notably, GLUT3 was suppressed by increasing miR-3189, demonstrating that miR-3189-mediated GLUT3 inhibition shows an anti-tumorigenic effect and cell death by regulating glucose metabolism in HDAC2 knockdown GBM.

Conclusions
Our findings will demonstrate the central role of HDAC2 in GBM tumorigenesis through the reprogramming of glucose metabolism by controlling miR-3189-inhibited GLUT3 expression, providing a potential new therapeutic strategy for GBM treatment.