Bellmunt risk score as a survival predictor in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: The prognosis of metastatic castration-resistant prostate cancer (mCRPC) is influenced by numerous individual factors. Despite various proposed prognostic models, the clinical application of these remains limited, probably due to complexity. Our study aimed to evaluate the predictive value of the Bellmunt risk score, which is well-known for urothelial carcinoma and easily assessed, in mCRPC patients. METHODS: The Bellmunt risk score was calculated from three risk factors (Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥1, serum hemoglobin <10 g/dL, presence of liver metastases) in 125 patients who received first-line mCRPC treatment between 2005 and 2023. In addition, a modified score was established (one point each for hemoglobin <10 g/dL and the presence of liver metastases added to the ECOG PS). Associations with overall survival (OS) under first- and second-line therapy were tested using Cox regression analyzes, log-rank tests, concordance index (C-index) and time-dependent receiver operating characteristic. RESULTS: There is a significant correlation between the level of the Bellmunt risk score and shorter OS (hazard ratio: 3.23, 95% confidence interval: 2.06-5.05; log-rank p < 0.001; C-index: 0.724). The semi-quantitative modified risk score showed even better prognostic discrimination (log-rank p < 0.001, C-index: 0.764). The score and its dynamics were also predictive in the second-line setting (log-rank p < 0.001 and = 0.01; C-index: 0.742 and 0.595). CONCLUSIONS: The Bellmunt risk score is easy to assess and provides useful prognostic information in mCRPC, and can support physicians in their treatment decisions.

Unraveling Axonal Transcriptional Landscapes: Insights from iPSC-Derived Cortical Neurons and Implications for Motor Neuron Degeneration.

Neuronal function and pathology are deeply influenced by the distinct molecular profiles of the axon and soma. Traditional studies have often overlooked these differences due to the technical challenges of compartment specific analysis. In this study, we employ a robust RNA-sequencing (RNA-seq) approach, using microfluidic devices, to generate high-quality axonal transcriptomes from iPSC-derived cortical neurons (CNs). We achieve high specificity of axonal fractions, ensuring sample purity without contamination. Comparative analysis revealed a unique and specific transcriptional landscape in axonal compartments, characterized by diverse transcript types, including protein-coding mRNAs, ribosomal proteins (RPs), mitochondrial-encoded RNAs, and long non-coding RNAs (lncRNAs). Previous works have reported the existence of transcription factors (TFs) in the axon. Here, we detect a subset of previously unreported TFs specific to the axon and indicative of their active participation in transcriptional regulation. To investigate transcripts and pathways essential for central motor neuron (MN) degeneration and maintenance we analyzed KIF1C-knockout (KO) CNs, modeling hereditary spastic paraplegia (HSP), a disorder associated with prominent length-dependent degeneration of central MN axons. We found that several key factors crucial for survival and health were absent in KIF1C-KO axons, highlighting a possible role of these also in other neurodegenerative diseases. Taken together, this study underscores the utility of microfluidic devices in studying compartment-specific transcriptomics in human neuronal models and reveals complex molecular dynamics of axonal biology. The impact of KIF1C on the axonal transcriptome not only deepens our understanding of MN diseases but also presents a promising avenue for exploration of compartment specific disease mechanisms.

Vitamin D3 deficiency and osteopenia in spastic paraplegia type 5 indicate impaired bone homeostasis.

Hereditary spastic paraplegia type 5 (SPG5) is an autosomal recessively inherited movement disorder characterized by progressive spastic gait disturbance and afferent ataxia. SPG5 is caused by bi-allelic loss of function mutations in CYP7B1 resulting in accumulation of the oxysterols 25-hydroxycholesterol and 27-hydroxycholesterol in serum and cerebrospinal fluid of SPG5 patients. An effect of 27- hydroxycholesterol via the estrogen and liver X receptors was previously shown on bone homeostasis. This study analyzed bone homeostasis and osteopenia in 14 SPG5 patients as a non-motor feature leading to a potential increased risk for bone fractures. T-Scores in CT bone density measurements were reduced, indicating osteopenia in SPG5 patients. Further, we analyzed various metabolites of bone homeostasis by ELISA in serum samples of these patients. We identified a lack of vitamin D3 metabolites (Calcidiol and Calcitriol), an increase in Sclerostin as a bone formation/mineralization inhibiting factor, and a decrease in cross-linked N-telopeptide of type I collagen (NTX), a marker indicating reduced bone resorption. As statin treatment has been found to lower oxysterol levels, we evaluated its effect in samples of the STOP-SPG5 trial and found atorvastatin to normalize the increased sclerostin levels. In summary, our study identified osteopenia as a non-motor feature in SPG5 and suggests the need for vitamin D3 substitution in SPG5 patients. Sclerostin may be considered a therapeutic target and biomarker in upcoming therapeutical trials in SPG5.

Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEEs) are a heterogenous group of epilepsies in which altered brain development leads to developmental delay and seizures, with the epileptic activity further negatively impacting neurodevelopment. Identifying the underlying cause of DEEs is essential for progress toward precision therapies. Here we describe a group of individuals with biallelic variants in DENND5A and determine that variant type is correlated with disease severity. We demonstrate that DENND5A interacts with MUPP1 and PALS1, components of the Crumbs apical polarity complex, which is required for both neural progenitor cell identity and the ability of these stem cells to divide symmetrically. Induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division during neural induction and have an inherent propensity to differentiate into neurons, and transgenic DENND5A mice, with phenotypes like the human syndrome, have an increased number of neurons in the adult subventricular zone. Disruption of symmetric cell division following loss of DENND5A results from misalignment of the mitotic spindle in apical neural progenitors. A subset of DENND5A is localized to centrosomes, which define the spindle poles during mitosis. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state and ultimately shortening the period of neurogenesis. This study provides a mechanism behind DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families.

Delayed symptomatic renal arteriovenous fistula in a 24 years old male following renal biopsy.

We report a case of a 24-year-old male with a history of kidney biopsy at young age due to chronic renal dysfunction and challenging hypertension, who presented with flank pain and hematuria. Initial imaging suggested renal pelvis enlargement, but MRI revealed a massive renal arteriovenous malformation (AVM). Angiographic embolization was abandoned due to extensive effluent flow, followed by successful surgical resection preserving healthy kidney tissue. This case underscores the importance of considering renal AVMs in the differential diagnosis of young patients with gross hematuria or refractory hypertension to prevent complications and improve patient outcomes.

Clinical implications of AGR2 in primary prostate cancer: Results from a large-scale study.

Human anterior gradient-2 (AGR2) has been implicated in carcinogenesis of various solid tumours, but the expression data in prostate cancer are contradictory regarding its prognostic value. The objective of this study is to evaluate the expression of AGR2 in a large prostate cancer cohort and to correlate it with clinicopathological data. AGR2 protein expression was analysed immunohistochemically in 1023 well-characterized prostate cancer samples with a validated antibody. AGR2 expression levels in carcinomas were compared with matched tissue samples of adjacent normal glands. AGR2 expression levels were dichotomized and tested for statistical significance. Increased AGR2 expression was found in 93.5% of prostate cancer cases. AGR2 levels were significantly higher in prostate cancer compared with normal prostate tissue. A gradual loss of AGR2 expression was associated with increasing tumour grade (ISUP), and AGR2 expression is inversely related to patient survival, however, multivariable significance is not achieved. AGR2 is clearly upregulated in the majority of prostate cancer cases, yet a true diagnostic value appears unlikely. In spite of the negative correlation of AGR2 expression with increasing tumour grade, no independent prognostic significance was found in this large-scale study.

Multiple taxa inoculants of arbuscular mycorrhizal fungi enhanced colonization frequency, biomass production, and water use efficiency of cassava (Manihot esculenta).

Increasing water use efficiency (WUE) in crops is critical to maintaining agricultural production under climate change-exacerbated drought. One of these approaches may consist of leveraging on the beneficial interactions between crops and arbuscular mycorrhizal fungi (AMF). In this study, we investigated how inoculation with AMF from three different taxa (Claroideoglomus etunicatum (T1), Gigaspora margarita (T2), and Rhizophagus irregularis (T3)) and their combination (T123) and a non-inoculated "control" treatment in a greenhouse could achieve increased biomass production and water use efficiency in cassava under three levels of water availability (100% PC, 60%-moderate stress, and 30%-severe stress). Whereas T1 and T2 resulted in a lower growth rate for the plants than the control, T123 enhanced cassava height and the number of petioles and leaves. T123 and T3 increased the total plant dry biomass in comparison with uninoculated plants by 30% and 26%, respectively. The T123 and plants inoculated with T3 significantly increased cassava above-ground biomass by 19% as compared to T1 (8.68 ± 2.44 g) and T2 (8.68 ± 2.44 g) inoculated plants. T123 resulted in higher WUE, which was validated by the leaf carbon (δ13C) isotopic signature, significantly outperforming cassava with T1 and T2, yet there was no difference between the control and T3. Overall, this study demonstrated that the use of multiple AMF from different taxa can increase cassava growth and WUE under greenhouse conditions.

Depletion of the m6A demethylases FTO and ALKBH5 impairs growth and metastatic capacity through EMT phenotype change in clear cell renal cell carcinoma.

BACKGROUND: N6-methyladenosine (m6A) is one of the most common RNA modifications in eukaryotes and has effects on RNA structure and stability. Recent studies have shown that m6A methylation is involved in human carcinogenesis. In the present study, we investigated the effects of m6A demethylases FTO and ALKBH5 on renal cell carcinoma (RCC) cell lines. METHODS: The epithelial-mesenchymal in vitro knockdowns of FTO and ALKBH5 induced by antisense oligonucleotides (LNA-GapmeR system) were established in RCC cell lines. Their effects on migration and proliferation were investigated subsequently. The influence of FTO and ALKBH5 knockdown on key epithelial-mesenchymal transition (EMT) genes was analyzed. RESULTS: Inactivation of FTO and ALKBH5 resulted in decreased proliferation and motility in all cell lines examined (ACHN, Caki-1, 769-P). Vimentin (VIM) was downregulated after the knockdown of FTO and ALKBH5, indicating an EMT switch. CONCLUSIONS: Knockdown of the m6A erasers FTO and ALKBH5 inhibits the malignant potential in the cell cultures studied by means of an EMT switch.

TR-FRET-Based Immunoassay to Measure Ataxin-2 as a Target Engagement Marker in Spinocerebellar Ataxia Type 2.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease, which belongs to the trinucleotide repeat disease group with a CAG repeat expansion in exon 1 of the ATXN2 gene resulting in an ataxin-2 protein with an expanded polyglutamine (polyQ)-stretch. The disease is late manifesting leading to early death. Today, therapeutic interventions to cure the disease or even to decelerate disease progression are not available yet. Furthermore, primary readout parameter for disease progression and therapeutic intervention studies are limited. Thus, there is an urgent need for quantifiable molecular biomarkers such as ataxin-2 becoming even more important due to numerous potential protein-lowering therapeutic intervention strategies. The aim of this study was to establish a sensitive technique to measure the amount of soluble polyQ-expanded ataxin-2 in human biofluids to evaluate ataxin-2 protein levels as prognostic and/or therapeutic biomarker in SCA2. Time-resolved fluorescence energy transfer (TR-FRET) was used to establish a polyQ-expanded ataxin-2-specific immunoassay. Two different ataxin-2 antibodies and two different polyQ-binding antibodies were validated in three different concentrations and tested in cellular and animal tissue as well as in human cell lines, comparing different buffer conditions to evaluate the best assay conditions. We established a TR-FRET-based immunoassay for soluble polyQ-expanded ataxin-2 and validated measurements in human cell lines including iPSC-derived cortical neurons. Additionally, our immunoassay was sensitive enough to monitor small ataxin-2 expression changes by siRNA or starvation treatment. We successfully established the first sensitive ataxin-2 immunoassay to measure specifically soluble polyQ-expanded ataxin-2 in human biomaterials.

Generation of a heterozygous and a homozygous CSF1R knockout line from iPSC using CRISPR/Cas9.

Mutations in Colony-stimulating factor 1 receptor (CSF1R) lead to CSF1R-related leukoencephalopathy, also known as Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rapidly progressing neurodegenerative disease with severe cognitive and motor impairment. In this study, a homozygous and a heterozygous CSF1R knockout induced pluripotent stem cell (iPSC) line were generated by CRISPR/Cas9-based gene editing. These in vitro models will provide a helpful tool for investigating the still largely unknown pathophysiology of CSF1R-related leukoencephalopathy.

Impact of patient nationality on the severity of early side effects after radiotherapy.

BACKGROUND: Major demographical changes in Germany commenced in the 1960s. Ongoing humanitarian crises in the Ukraine with subsequent immigration will have also long-range effects on national provision of cancer treatment. Ensuring the best possible outcomes for each cancer patient undergoing radiotherapy requires the prediction and prevention of unfavorable side effects. Given that recent research has primarily focused on clinical outcome indicators solely, less is known regarding sociodemographic predictors of therapeutic outcomes, such as patient nationality. Here, we investigated whether the severity of early side effects after radiotherapy are associated with patient nationality and other sociodemographic and clinical characteristics. METHODS: Out of 9187 patients treated at a German university medical center between 2017 and 2021, 178 German and 178 non-German patients were selected for matched-pair analysis based on diagnostic and demographic criteria. For all 356 patients, data on side effects from follow-up care after radiotherapy were collected. RESULTS: Non-German patients were more likely to have severe side effects than German patients. Side effect severity was also associated with tumor entity, concomitant therapy, body mass index, and age. CONCLUSION: Foreign cancer patients are at higher risk of experiencing severe side effects of radiotherapy, suggesting a need to develop and implement targeted preventive measures for these patients. Further research investigating factors predicting the occurrence of radiotherapy side effects, including other sociodemographic characteristics, is needed to better personalize therapy regimens for cancer.

Effective splicing restoration of a deep-intronic ABCA4 variant in cone photoreceptor precursor cells by CRISPR/SpCas9 approaches.

Stargardt disease is an autosomal recessively inherited retinal disorder commonly caused by pathogenic variants in the ABCA4 gene encoding the ATP-binding cassette subfamily A member 4 (ABCA4) protein. Several deep-intronic variants in ABCA4 have been classified as disease causing. By strengthening a cryptic splice site, deep-intronic variant c.5197-557G>T induces the inclusion of a 188-bp intronic sequence in the mature mRNA, resulting in a premature termination codon. Here, we report the design and evaluation of three CRISPR-Cas9 approaches implementing Streptococcus pyogenes Cas9 (single and dual guide RNA) or Streptococcus pyogenes Cas9 nickase (dual guide RNA) for their potential to correct c.5197-557G>T-induced aberrant splicing in minigene splicing assays and patient-derived cone photoreceptor precursor cells. The different strategies were able to rescue correct splicing by up to 83% and increase the overall correctly spliced transcripts by 1.8-fold, demonstrating the successful CRISPR-Cas9-mediated rescue in patient-derived photoreceptor precursor cells of an ABCA4 splicing defect. The results provide initial evidence of possible permanent splicing correction for Stargardt disease, expanding the therapeutic toolbox to counteract deep-intronic pathogenic variants in ABCA4.

Towards Personalized Allele-Specific Antisense Oligonucleotide Therapies for Toxic Gain-of-Function Neurodegenerative Diseases.

Antisense oligonucleotides (ASOs) are single-stranded nucleic acid strings that can be used to selectively modify protein synthesis by binding complementary (pre-)mRNA sequences. By specific arrangements of DNA and RNA into a chain of nucleic acids and additional modifications of the backbone, sugar, and base, the specificity and functionality of the designed ASOs can be adjusted. Thereby cellular uptake, toxicity, and nuclease resistance, as well as binding affinity and specificity to its target (pre-)mRNA, can be modified. Several neurodegenerative diseases are caused by autosomal dominant toxic gain-of-function mutations, which lead to toxic protein products driving disease progression. ASOs targeting such mutations-or even more comprehensively, associated variants, such as single nucleotide polymorphisms (SNPs)-promise a selective degradation of the mutant (pre-)mRNA while sparing the wild type allele. By this approach, protein expression from the wild type strand is preserved, and side effects from an unselective knockdown of both alleles can be prevented. This makes allele-specific targeting strategies a focus for future personalized therapies. Here, we provide an overview of current strategies to develop personalized, allele-specific ASO therapies for the treatment of neurodegenerative diseases, such Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3/MJD).

Cassava-maize intercropping systems in southern Nigeria: Radiation use efficiency, soil moisture dynamics, and yields of component crops.

Efficient utilization of incident solar radiation and rainwater conservation in rain-fed smallholder cropping systems require the development and adoption of cropping systems with high resource use efficiency. Due to the popularity of cassava-maize intercropping and the food security and economic importance of both crops in Nigeria, we investigated options to improve interception of photosynthetically active radiation (IPAR), radiation use efficiency (RUE), soil moisture retention, and yields of cassava and maize in cassava-maize intercropping systems in 8 on-farm researcher-managed multi-location trials between 2017 and 2019 in different agro-ecologies of southern Nigeria. Treatments were a combination of (1) maize planting density (low density at 20,000 maize plants ha-1 versus high density at 40,000 maize plants ha-1, intercropped with 12,500 cassava plants ha-1); (2) fertilizer application and management targeting either the maize crop (90 kg N, 20 kg P and 37 kg K ha-1) or the cassava crop (75 kg N, 20 kg P and 90 kg K ha-1), compared with control without fertilizer application. Cassava and maize development parameters were highest in the maize fertilizer regime, resulting in the highest IPAR at high maize density. The combined intercrop biomass yield was highest at high maize density in the maize fertilizer regime. Without fertilizer application, RUE was highest at low maize density. However, the application of the maize fertilizer regime at high maize density resulted in the highest RUE, soil moisture content, and maize grain yield. Cassava storage root yield was higher in the cassava fertilizer regime than in the maize fertilizer regime. We conclude that improved IPAR, RUE, soil moisture retention, and grain yield on nutrient-limited soils of southern Nigeria, or in similar environments, can be achieved by intercropping 40,000 maize plants ha-1 with 12,500 cassava plants ha-1 and managing the system with the maize fertilizer regime. However, for higher cassava storage root yield, the system should be managed with the cassava fertilizer regime.

KPNB1 modulates the Machado-Joseph disease protein ataxin-3 through activation of the mitochondrial protease CLPP.

Machado-Joseph disease (MJD) is characterized by a pathological expansion of the polyglutamine (polyQ) tract within the ataxin-3 protein. Despite its primarily cytoplasmic localization, polyQ-expanded ataxin-3 accumulates in the nucleus and forms intranuclear aggregates in the affected neurons. Due to these histopathological hallmarks, the nucleocytoplasmic transport machinery has garnered attention as an important disease relevant mechanism. Here, we report on MJD cell model-based analysis of the nuclear transport receptor karyopherin subunit beta-1 (KPNB1) and its implications in the molecular pathogenesis of MJD. Although directly interacting with both wild-type and polyQ-expanded ataxin-3, modulating KPNB1 did not alter the intracellular localization of ataxin-3. Instead, overexpression of KPNB1 reduced ataxin-3 protein levels and the aggregate load, thereby improving cell viability. On the other hand, its knockdown and inhibition resulted in the accumulation of soluble and insoluble ataxin-3. Interestingly, the reduction of ataxin-3 was apparently based on protein fragmentation independent of the classical MJD-associated proteolytic pathways. Label-free quantitative proteomics and knockdown experiments identified mitochondrial protease CLPP as a potential mediator of the ataxin-3-degrading effect induced by KPNB1. We confirmed reduction of KPNB1 protein levels in MJD by analyzing two MJD transgenic mouse models and induced pluripotent stem cells (iPSCs) derived from MJD patients. Our results reveal a yet undescribed regulatory function of KPNB1 in controlling the turnover of ataxin-3, thereby highlighting a new potential target of therapeutic value for MJD.

CD103+ Tissue Resident T-Lymphocytes Accumulate in Lung Metastases and Are Correlated with Poor Prognosis in ccRCC.

Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor with variable responses to immune checkpoint therapy. The significance of the immune cell infiltrate in distant metastases, their association with the immune infiltrate in the primary tumors and their impact on prognosis are poorly described. We hypothesized that specific subtypes of immune cells may be involved in the control of metastases and may have an impact on the prognosis of ccRCC. We analyzed the immune microenvironment in ccRCC primary tumors with distant metastases, paired distant metastases and non-metastasized ccRCC (n = 25 each group) by immunohistochemistry. Confirmatory analyses for CD8+ and CD103+ cells were performed in a large ccRCC cohort (n = 241) using a TCGA-KIRC data set (ITGAE/CD103). High immune cell infiltration in primary ccRCC tumors was significantly correlated with the development of distant tumor metastasis (p < 0.05). A high density of CD103+ cells in ccRCC was more frequent in poorly differentiated tumors (p < 0.001). ccRCCs showed high levels of ITGAE/CD103 compared with adjacent non-neoplastic tissue. A higher density of CD103+ cells and a higher ITGAE/CD103 expression were significantly correlated with poor overall survival in ccRCC (log rank p < 0.05). Our results show a major prognostic value of the immune pattern, in particular CD103+ cell infiltration in ccRCC, and highlight the importance of the tumor immune microenvironment.

Spatial variability and environmental drivers of cassava-arbuscular mycorrhiza fungi (AMF) associations across Southern Nigeria.

Cassava, forming starch-rich, tuberous roots, is an important staple crop in smallholder farming systems in sub-Saharan Africa. Its relatively good tolerance to drought and nutrient-poor soils may be partly attributed to the crop's association with arbuscular mycorrhiza fungi (AMF). Yet insights into AMF-community composition and richness of cassava, and knowledge of its environmental drivers are still limited. Here, we sampled 60 cassava fields across three major cassava-growing agro-ecological zones in Nigeria and used a DNA meta-barcoding approach to quantify large-scale spatial variation and evaluate the effects of soil characteristics and common agricultural practices on AMF community composition, richness and Shannon diversity. We identified 515 AMF operational taxonomic units (OTUs), dominated by Glomus, with large variation across agro-ecological zones, and with soil pH explaining most of the variation in AMF community composition. High levels of soil available phosphorus reduced OTU richness without affecting Shannon diversity. Long fallow periods (> 5 years) reduced AMF richness compared with short fallows, whereas both zero tillage and tractor tillage reduced AMF diversity compared with hoe tillage. This study reveals that the symbiotic relationship between cassava and AMF is strongly influenced by soil characteristics and agricultural management and that it is possible to adjust cassava cultivation practices to modify AMF diversity and community structure.

Allele-specific targeting of mutant ataxin-3 by antisense oligonucleotides in SCA3-iPSC-derived neurons.

Spinocerebellar ataxia type 3 (SCA3) is caused by an expanded polyglutamine stretch in ataxin-3. While wild-type ataxin-3 has important functions, e.g., as a deubiquitinase, downregulation of mutant ataxin-3 is likely to slow down the course of this fatal disease. We established a screening platform with human neurons of patients and controls derived from induced pluripotent stem cells to test antisense oligonucleotides (ASOs) for their effects on ataxin-3 expression. We identified an ASO that suppressed mutant and wild-type ataxin-3 levels by >90% after a singular treatment. Next, we screened pairs of ASOs designed to selectively target the mutant or the wild-type allele by taking advantage of a SNP (c.987G > C) in ATXN3 that is present in most SCA3 patients. We found ASOmut4 to reduce levels of mutant ataxin-3 by 80% after 10 days while leaving expression of wild-type ataxin-3 largely unaffected. In a long-term study we proved this effect to last for about 4 weeks after a single treatment without signs of neurotoxicity. This study provides proof of principle that allele-specific lowering of poly(Q)-expanded ataxin-3 by selective ASOs is feasible and long lasting, with sparing of wild-type ataxin-3 expression in a human cell culture model that is genetically identical to SCA3 patients.

Increasing cassava root yield on farmers' fields in Nigeria through appropriate weed management.

Weed competition is the major biological stress affecting cassava production in smallholder farms in West and Central Africa, where yields are low compared with those in Asia and Latin America. Options for improved weed management are crucial in increasing productivity. Selected pre- and post-emergence herbicides, integrated with appropriate tillage and plant spacing, were tested in 96 sites in four locations in Nigeria, 24 in 2016 and 72 in 2017. Trials were split plots with six pre-emergence herbicides and no post-emergence treatment as main plots. Subplot treatments were four post-emergence herbicides, weeding with a motorized rotary weeder, short- and long-handled hoes, and no post-emergence weed control, i.e., regardless of pre-emergence treatments. Indaziflam-based treatments, irrespective of post-emergence treatment, and flumioxazin + pyroxasulfone applied pre-emergence followed by one weeding with a long-handled hoe provided >80% control of major broadleaf and grass weeds. Compared with herbicide use, farmer control practices (53%) were not efficient in controlling weeds. The highest root yield was produced where (1) s-metolachlor was combined with atrazine, and one weeding with a long-handled hoe or clethodim with lactofen, and (2) indaziflam + isoxaflutole was combined with glyphosate. An increase in root yield from 3.41 to 14.2 t ha-1 and from 3.0 to 11.99 t ha-1 was obtained where herbicides were used compared with farmers' practice and manual hoe weeding. Our results showed that integrating good agronomic practices with safe and effective use of appropriate herbicides can result in root yield >20 t ha-1. i.e., twice the national average root yield of 8-12 t ha-1, with >50% net profit. The use of appropriate herbicides can reduce the amount of manual labor required and improve livelihoods, specifically for women and children. Smallholder cassava farmers would require continuous training on the safe use and handling of herbicides to improve efficiency and prevent adverse effects on humans and the environment.

Developing recommendations for increased productivity in cassava-maize intercropping systems in Southern Nigeria.

Cassava-maize intercropping is a common practice among smallholder farmers in Southern Nigeria. It provides food security and early access to income from the maize component. However, yields of both crops are commonly low in farmers' fields. Multi-locational trials were conducted in Southern Nigeria in 2016 and 2017 to investigate options to increase productivity and profitability through increased cassava and maize plant densities and fertilizer application. Trials with 4 and 6 treatments in 2016 and 2017, respectively were established on 126 farmers' fields over two seasons with a set of different designs, including combinations of two levels of crop density and three levels of fertilizer rates. The maize crop was tested at low density (LM) with 20,000 plants ha-1 versus high density (HM) with 40,000 plants ha-1. For cassava, low density (LC) had had 10,000 plants ha-1 versus the high density (HC) with 12,500 plants ha-1.; The fertilizer application followed a regime favouring either the maize crop (FM: 90 kg N, 20 kg P and 37 kg K ha-1) or the cassava crop (FC: 75 kg N, 20 kg P and 90 kg K ha-1), next to control without fertilizer application (F0). Higher maize density (HM) increased marketable maize cob yield by 14 % (3700 cobs ha-1) in the first cycle and by 8% (2100 cobs ha-1) in the second cycle, relative to the LM treatment. Across both cropping cycles, fertilizer application increased cob yield by 15 % (5000 cobs ha-1) and 19 % (6700 cobs ha-1) in the FC and FM regime, respectively. Cassava storage root yield increased by 16 % (4 Mg ha-1) due to increased cassava plant density, and by 14 % (4 Mg ha-1) due to fertilizer application (i.e., with both fertilizer regimes) but only in the first cropping cycle. In the second cycle, increased maize plant density (HM) reduced cassava storage root yield by 7% (1.5 Mg ha-1) relative to the LM treatment. However, the negative effect of high maize density on storage root yield was counteracted by fertilizer application. Fresh storage root yield increased by 8% (2 Mg ha-1) in both fertilizer regimes compared to the control without fertilizer application. Responses to fertilizer by cassava and maize varied between fields. Positive responses tended to decline with increasing yields in the control treatment. The average value-to-cost ratio (VCR) of fertilizer use for the FM regime was 3.6 and higher than for the FC regime (VCR = 1.6), resulting from higher maize yields when FM than when FC was applied. Revenue generated by maize constituted 84-91% of the total revenue of the cropping system. The highest profits were achieved with the FM regime when both cassava and maize were grown at high density. However, fertilizer application was not always advisable as 34 % of farmers did not realize a profit. For higher yields and profitability, fertilizer recommendations should be targeted to responsive fields based on soil fertility knowledge.