Foresight and trade-off analyses : tools for science strategy development in agriculture and food systems research

Foresight and trade-off analyses offer organizations such as CGIAR an opportunity to better prepare for alternative futures through adaptive research strategy and management. This essay introduces a set of papers that explore foresight and trade-off analyses within the context of the major reforms now occurring in the CGIAR. We tease out lessons not only for One CGIAR, but also for international development research organizations more broadly.Publisher PDFPeer reviewe

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures.Genetics of disease, diagnosis and treatmen

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures

The Cost of Maternal Complications and Its Associated Factors Among Mothers Attending Public Hospitals in Harari Region and Dire Dawa City Administration, Eastern Ethiopia: An Institution-Based Cross-Sectional Study

Samrawit Shawel,1 Behailu Hawulte Ayele,1 Yadeta Dessie,1 Abera Kenay Tura,2 Gimaye Dinsa,1,3 Abainash Tekola,1 Miheret Mandefro,1 Awoke Masrie,1 Aklilu Tamire,1 Obsan Kassa Tefasa1 1School of Public Health, Haramaya University, Harar, Ethiopia; 2School of Nursing and Midwifery, Haramaya University, Harar, Ethiopia; 3School of Population and Public Health, University of British Columbia, Vancouver, CanadaCorrespondence: Samrawit Shawel, Tel +251 913 705 953, Email [email protected]: Pregnant women face high costs for health-care services despite being advertised as free. These costs include non-medical expenses, lost productivity, difficulties caring for family members, and long-term financial impact from complications. Limited research has been done on the cost burden of maternal services and complications, despite numerous studies on maternal health service provision. This is notable considering the government’s claim of providing free maternal health-care services.Methods: A cross-sectional study was conducted in July (1– 30) 2022 among 425 randomly selected mothers in Harari and Dire Dawa City, Eastern Ethiopia. Data were collected through structured questionnaires and medical record reviews. The collected data was entered into Epi-Data version 3.02 and analyzed using STATA version 14.0 after data cleaning. Descriptive statistics and linear regression analysis were used to examine the data, ensuring assumptions of linearity, independence, homoscedasticity, and normality were met. The correlation coefficient was used to assess the strength of the association.Results: The median cost of maternal complications was around 4250 ETB (81.3 USD; IQR = 2900– 5833.3), factors that predicted cost were monthly family income of ≥ 3001 birr (β=1.13; 95% CI: 1.00, 1.26), distance from hospital (β=0.73; 95% CI = 0.64– 0.83), being admitted for less than 4 days (β=0.60; 95% CI = 0.53– 0.69), accompanied by relatives besides their husbands (β=1.93; 95% CI = 1.52– 2.46), caesarian sections delivery (β=1.17; 95% CI = 1.04– 1.31), and giving birth to a normal baby (β=0.86; 95% CI = 0.77– 0.97).Conclusion: Maternal complications incur significant costs, with factors such as family income, travel time, hospital stay, caregiver presence, mode of delivery, and neonatal outcome predicting these costs. The Ethiopian health system should address the additional expenses faced by mothers with complications and their caregivers.Keywords: direct cost, indirect cost, medical-cost, maternal complication, Eastern Ethiopi

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice

Neural cultures derived from Huntington’s disease (HD) patient-derived induced pluripotent stem cells were used for ‘omics’ analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation. We observed a strong correlation between HD-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysregulated pathways, led to amelioration of expanded polyglutamine repeat-associated phenotypes in neural cells and of cognitive impairment and synaptic pathology in HD model R6/2 mice. These data suggest that mutant huntingtin impairs neurodevelopmental pathways that could disrupt synaptic homeostasis and increase vulnerability to the pathologic consequence of expanded polyglutamine repeats over time