A survey of carboplatin desensitization therapy in Japan: A multicenter retrospective study.

INTRODUCTION: Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. METHODS: Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. RESULTS: This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre-existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620-18,282) mg, and the mean number of doses was 14 (4-63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. CONCLUSION: Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

MucoUp® as a spacer in brachytherapy for uterine cervical cancer: A first-in-human experience.

We first used MucoUp®, a hyaluronic acid used in endoscopic resection, as a spacer in brachytherapy. In five cervical cancer patients, MucoUp® insertion increased a 90% dose of the high-risk CTV to over 80 Gy while decreasing the dose of organs at risk. No related adverse events were observed.

Application of Trehalose Mitigates Short-Styled Flowers in Solanaceous Crops.

Trehalose is a disaccharide and is often foliar applied by farmers aiming at increasing stress resistance or crop production. However, the physiological effect of exogenously applied trehalose on crops remains obscure. Here, we explored the effect of foliar trehalose application on style length of solanaceous crops, Solanum melongena and S. lycopersicum. Trehalose application promotes pistil to stamen ratio by gaining style length. Another disaccharide consisting of two glucose molecules, maltose, showed the same effect on style length of S. lycopersicum, while monosaccharide glucose did not. Trehalose is found to affect style length through uptake via roots or interaction with rhizosphere but not through absorption by shoots in S. lycopersicum. Our study suggests that yield improvement of solanaceous crops by trehalose application under stressed conditions is brought about by suppression of the occurrence of short-styled flowers. This study suggests that trehalose holds potential to act as a plant biostimulant in preventing short-styled flowers in solanaceous crops.

Plant Hormonomics: A Key Tool for Deep Physiological Phenotyping to Improve Crop Productivity.

Agriculture is particularly vulnerable to climate change. To cope with the risks posed by climate-related stressors to agricultural production, global population growth, and changes in food preferences, it is imperative to develop new climate-smart crop varieties with increased yield and environmental resilience. Molecular genetics and genomic analyses have revealed that allelic variations in genes involved in phytohormone-mediated growth regulation have greatly improved productivity in major crops. Plant science has remarkably advanced our understanding of the molecular basis of various phytohormone-mediated events in plant life. These findings provide essential information for improving the productivity of crops growing in changing climates. In this review, we highlight the recent advances in plant hormonomics (multiple phytohormone profiling) and discuss its application to crop improvement. We present plant hormonomics as a key tool for deep physiological phenotyping, focusing on representative plant growth regulators associated with the improvement of crop productivity. Specifically, we review advanced methodologies in plant hormonomics, highlighting mass spectrometry- and nanosensor-based plant hormone profiling techniques. We also discuss the applications of plant hormonomics in crop improvement through breeding and agricultural management practices.

Exome-wide variation in a diverse barley panel reveals genetic associations with ten agronomic traits in Eastern landraces.

Barley (Hordeum vulgare ssp. vulgare) is one of the first crops to be domesticated and is adapted to a wide range of environments. Worldwide barley germplasm collections possess valuable allelic variations that could further improve barley productivity. Although barley genomics has offered a global picture of allelic variation among varieties and its association with various agronomic traits, polymorphisms from East Asian varieties remain scarce. In this study, we analyze exome polymorphisms in a panel of 274 barley varieties collected worldwide, including 137 varieties from East Asian countries and Ethiopia. We reveal the underlying population structure and conduct genome-wide association studies for 10 agronomic traits. Moreover, we examin genome-wide associations for traits related to grain size such as awn length and glume length. Our results demonstrate the value of diverse barley germplasm panels containing Eastern varieties, highlighting their distinct genomic signatures relative to Western subpopulations.

FE UPTAKE-INDUCING PEPTIDE1 maintains Fe translocation by controlling Fe deficiency response genes in the vascular tissue of Arabidopsis.

FE UPTAKE-INDUCING PEPTIDE1 (FEP1), also named IRON MAN3 (IMA3) is a short peptide involved in the iron deficiency response in Arabidopsis thaliana. Recent studies uncovered its molecular function, but its physiological function in the systemic Fe response is not fully understood. To explore the physiological function of FEP1 in iron homoeostasis, we performed a transcriptome analysis using the FEP1 loss-of-function mutant fep1-1 and a transgenic line with oestrogen-inducible expression of FEP1. We determined that FEP1 specifically regulates several iron deficiency-responsive genes, indicating that FEP1 participates in iron translocation rather than iron uptake in roots. The iron concentration in xylem sap under iron-deficient conditions was lower in the fep1-1 mutant and higher in FEP1-induced transgenic plants compared with the wild type (WT). Perls staining revealed a greater accumulation of iron in the cortex of fep1-1 roots than in the WT root cortex, although total iron levels in roots were comparable in the two genotypes. Moreover, the fep1-1 mutation partially suppressed the iron overaccumulation phenotype in the leaves of the oligopeptide transporter3-2 (opt3-2) mutant. These data suggest that FEP1 plays a pivotal role in iron movement and in maintaining the iron quota in vascular tissues in Arabidopsis.

A case of a large solitary fibrous tumor arising from the retroperitoneum resected completely using an intra-aortic balloon.

Solitary fibrous tumors (SFTs) are rare mesenchymal cell-derived tumors that can cause substantial bleeding during surgery due to hyper-vascularization. We report a case of a large retroperitoneal SFT resected completely using an intra-aortic balloon. A 71-year-old female with a history of type 2 diabetes mellitus presented with a tumor that was diagnosed as an insulin-like growth factor-II-producing benign SFT using computed tomography-guided biopsy. The tumor had grown from 6 to 20 cm in diameter within 4 years, with concurrent and severe hypoglycemia. Preoperative computed tomography findings showed substantial blood flow toward the tumor. The retroperitoneal tumor was observed to be widely attached. Substantial hemorrhaging during tumor resection was observed despite vascular embolism. We inflated the intra-aortic balloon for 45 min and resected the tumor completely. In conclusion, large SFT resection requires preoperative tumor blood flow evaluation and preparation of both a vascular embolism and an intra-aortic balloon.

PARN-like Proteins Regulate Gene Expression in Land Plant Mitochondria by Modulating mRNA Polyadenylation.

Mitochondria have their own double-stranded DNA genomes and systems to regulate transcription, mRNA processing, and translation. These systems differ from those operating in the host cell, and among eukaryotes. In recent decades, studies have revealed several plant-specific features of mitochondrial gene regulation. The polyadenylation status of mRNA is critical for its stability and translation in mitochondria. In this short review, I focus on recent advances in understanding the mechanisms regulating mRNA polyadenylation in plant mitochondria, including the role of poly(A)-specific ribonuclease-like proteins (PARNs). Accumulating evidence suggests that plant mitochondria have unique regulatory systems for mRNA poly(A) status and that PARNs play pivotal roles in these systems.

Susceptibility of subregions of prefrontal cortex and corpus callosum to damage by high-dose oxytocin-induced labor in male neonatal mice.

Induction and augmentation of labor is one of the most common obstetrical interventions. However, this intervention is not free of risks and could cause adverse events, such as hyperactive uterine contraction, uterine rupture, and amniotic-fluid embolism. Our previous study using a new animal model showed that labor induced with high-dose oxytocin (OXT) in pregnant mice resulted in massive cell death in selective brain regions, specifically in male offspring. The affected brain regions included the prefrontal cortex (PFC), but a detailed study in the PFC subregions has not been performed. In this study, we induced labor in mice using high-dose OXT and investigated neonatal brain damage in detail in the PFC using light and electron microscopy. We found that TUNEL-positive or pyknotic nuclei and Iba-1-positive microglial cells were detected more abundantly in infralimbic (IL) and prelimbic (PL) cortex of the ventromedial PFC (vmPFC) in male pups delivered by OXT-induced labor than in the control male pups. These Iba-1-positive microglial cells were engulfing dying cells. Additionally, we also noticed that in the forceps minor (FMI) of the corpus callosum (CC), the number of TUNEL-positive or pyknotic nuclei and Iba-1-positive microglial cells were largely increased and Iba-1-positive microglial cells phagocytosed massive dying cells in male pups delivered by high-dose OXT-induced labor. In conclusion, IL and PL of the vmPFC and FMI of the CC, were susceptible to brain damage in male neonates after high-dose OXT-induced labor.

A report on the 73th Annual Congress of the Japan Society of Obstetrics and Gynecology International Workshop for Junior Fellows: Risk-reducing surgery for hereditary breast and ovarian cancer.

At the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, young doctors from Japan and South Korea made presentations on the present condition of risk-reducing surgery for hereditary breast and ovarian cancer (RRSO) in their respective country. RRSO was insured in Japan in April 2020, whereas in South Korea, it was insured 7 years earlier in 2013. In Japan, certification criteria have been set for facilities that perform RRSO, and the number of facilities is increasing, but regional disparities still exist in its distribution. The number of gBRCA1/2 testing facilities is larger, and the cost is more affordable in South Korea than in Japan. Additionally, South Korea provides genetic counseling to a wider range of relatives compared to Japan. In the future, as the indications for the gBRCA1/2 test have expanded as a companion diagnostic for the use of PARP inhibitors, it is expected that the number of candidates for the gBRCA1/2 mutation test and RRSO will increase in Japan. It is important to increase the number of BRCA tests while maintaining the quality of genetic counseling in order to provide adequate information on BRCA mutations and RRSO for patients to support their decision. For the development of hereditary breast and ovarian cancer (HBOC) medical care, it is necessary to publish a nationwide database in Japan and continue to analyze and discuss the data based on the results.

Genetic Elucidation for Response of Flowering Time to Ambient Temperatures in Asian Rice Cultivars.

Climate resilience of crops is critical for global food security. Understanding the genetic basis of plant responses to ambient environmental changes is key to developing resilient crops. To detect genetic factors that set flowering time according to seasonal temperature conditions, we evaluated differences of flowering time over years by using chromosome segment substitution lines (CSSLs) derived from japonica rice cultivars "Koshihikari" × "Khao Nam Jen", each with different robustness of flowering time to environmental fluctuations. The difference of flowering times in 9 years' field tests was large in "Khao Nam Jen" (36.7 days) but small in "Koshihikari" (9.9 days). Part of this difference was explained by two QTLs. A CSSL with a "Khao Nam Jen" segment on chromosome 11 showed 28.0 days' difference; this QTL would encode a novel flowering-time gene. Another CSSL with a segment from "Khao Nam Jen" in the region around Hd16 on chromosome 3 showed 23.4 days" difference. A near-isogenic line (NIL) for Hd16 showed 21.6 days' difference, suggesting Hd16 as a candidate for this QTL. RNA-seq analysis showed differential expression of several flowering-time genes between early and late flowering seasons. Low-temperature treatment at panicle initiation stage significantly delayed flowering in the CSSL and NIL compared with "Koshihikari". Our results unravel the molecular control of flowering time under ambient temperature fluctuations.

Temperature-dependent fasciation mutants provide a link between mitochondrial RNA processing and lateral root morphogenesis.

Although mechanisms that activate organogenesis in plants are well established, much less is known about the subsequent fine-tuning of cell proliferation, which is crucial for creating properly structured and sized organs. Here we show, through analysis of temperature-dependent fasciation (TDF) mutants of Arabidopsis, root redifferentiation defective 1 (rrd1), rrd2, and root initiation defective 4 (rid4), that mitochondrial RNA processing is required for limiting cell division during early lateral root (LR) organogenesis. These mutants formed abnormally broadened (i.e. fasciated) LRs under high-temperature conditions due to extra cell division. All TDF proteins localized to mitochondria, where they were found to participate in RNA processing: RRD1 in mRNA deadenylation, and RRD2 and RID4 in mRNA editing. Further analysis suggested that LR fasciation in the TDF mutants is triggered by reactive oxygen species generation caused by defective mitochondrial respiration. Our findings provide novel clues for the physiological significance of mitochondrial activities in plant organogenesis.

Nondestructive measurements of depth distribution of carrier lifetimes in 4H-SiC thick epitaxial layers using time-resolved free carrier absorption with intersectional lights.

To achieve low on-state and switching losses simultaneously in SiC bipolar devices, the depth distribution of the carrier lifetime within the voltage blocking layer and the techniques used for observing the carrier lifetime distribution are important considerations. We developed a measurement system of the time-resolved free carrier absorption with intersectional lights (IL-TRFCA) for the nondestructive measurements of the depth distribution of the carrier lifetime in 4H-SiC thick epilayers. To confirm the reliability of the measurement results, we also performed TRFCA measurements to the cross section of the samples. As a result, although the lifetimes are underestimated owing to an inevitable diffusion of the carriers from the measurement region, the system was able to observe a carrier lifetime distribution up to a depth of 250 µm. Our IL-TRFCA system demonstrated a depth resolution of ∼10 µm, which is the best resolution among previously reported nondestructive measurement techniques. We consider the proposed system to be useful for the development of SiC bipolar devices.

The barley pan-genome reveals the hidden legacy of mutation breeding.

Genetic diversity is key to crop improvement. Owing to pervasive genomic structural variation, a single reference genome assembly cannot capture the full complement of sequence diversity of a crop species (known as the 'pan-genome'1). Multiple high-quality sequence assemblies are an indispensable component of a pan-genome infrastructure. Barley (Hordeum vulgare L.) is an important cereal crop with a long history of cultivation that is adapted to a wide range of agro-climatic conditions2. Here we report the construction of chromosome-scale sequence assemblies for the genotypes of 20 varieties of barley-comprising landraces, cultivars and a wild barley-that were selected as representatives of global barley diversity. We catalogued genomic presence/absence variants and explored the use of structural variants for quantitative genetic analysis through whole-genome shotgun sequencing of 300 gene bank accessions. We discovered abundant large inversion polymorphisms and analysed in detail two inversions that are frequently found in current elite barley germplasm; one is probably the product of mutation breeding and the other is tightly linked to a locus that is involved in the expansion of geographical range. This first-generation barley pan-genome makes previously hidden genetic variation accessible to genetic studies and breeding.

BdWRKY38 is required for the incompatible interaction of Brachypodium distachyon with the necrotrophic fungus Rhizoctonia solani.

Rhizoctonia solani is a soil-borne necrotrophic fungus that causes sheath blight in grasses. The basal resistance of compatible interactions between R. solani and rice is known to be modulated by some WRKY transcription factors (TFs). However, genes and defense responses involved in incompatible interaction with R. solani remain unexplored, because no such interactions are known in any host plants. Recently, we demonstrated that Bd3-1, an accession of the model grass Brachypodium distachyon, is resistant to R. solani and, upon inoculation with the fungus, undergoes rapid induction of genes responsive to the phytohormone salicylic acid (SA) that encode the WRKY TFs BdWRKY38 and BdWRKY44. Here, we show that endogenous SA and these WRKY TFs positively regulate this accession-specific R. solani resistance. In contrast to a susceptible accession (Bd21), the infection process in the resistant accessions Bd3-1 and Tek-3 was suppressed at early stages before the development of fungal biomass and infection machinery. A comparative transcriptome analysis during pathogen infection revealed that putative WRKY-dependent defense genes were induced faster in the resistant accessions than in Bd21. A gene regulatory network (GRN) analysis based on the transcriptome dataset demonstrated that BdWRKY38 was a GRN hub connected to many target genes specifically in resistant accessions, whereas BdWRKY44 was shared in the GRNs of all three accessions. Moreover, overexpression of BdWRKY38 increased R. solani resistance in Bd21. Our findings demonstrate that these resistant accessions can activate an incompatible host response to R. solani, and BdWRKY38 regulates this response by mediating SA signaling.

Decoding Plant-Environment Interactions That Influence Crop Agronomic Traits.

To ensure food security in the face of increasing global demand due to population growth and progressive urbanization, it will be crucial to integrate emerging technologies in multiple disciplines to accelerate overall throughput of gene discovery and crop breeding. Plant agronomic traits often appear during the plants' later growth stages due to the cumulative effects of their lifetime interactions with the environment. Therefore, decoding plant-environment interactions by elucidating plants' temporal physiological responses to environmental changes throughout their lifespans will facilitate the identification of genetic and environmental factors, timing and pathways that influence complex end-point agronomic traits, such as yield. Here, we discuss the expected role of the life-course approach to monitoring plant and crop health status in improving crop productivity by enhancing the understanding of plant-environment interactions. We review recent advances in analytical technologies for monitoring health status in plants based on multi-omics analyses and strategies for integrating heterogeneous datasets from multiple omics areas to identify informative factors associated with traits of interest. In addition, we showcase emerging phenomics techniques that enable the noninvasive and continuous monitoring of plant growth by various means, including three-dimensional phenotyping, plant root phenotyping, implantable/injectable sensors and affordable phenotyping devices. Finally, we present an integrated review of analytical technologies and applications for monitoring plant growth, developed across disciplines, such as plant science, data science and sensors and Internet-of-things technologies, to improve plant productivity.

Life-Course Monitoring of Endogenous Phytohormone Levels under Field Conditions Reveals Diversity of Physiological States among Barley Accessions.

Agronomically important traits often develop during the later stages of crop growth as consequences of various plant-environment interactions. Therefore, the temporal physiological states that change and accumulate during the crop's life course can significantly affect the eventual phenotypic differences in agronomic traits among crop varieties. Thus, to improve productivity, it is important to elucidate the associations between temporal physiological responses during the growth of different crop varieties and their agronomic traits. However, data representing the dynamics and diversity of physiological states in plants grown under field conditions are sparse. In this study, we quantified the endogenous levels of five phytohormones - auxin, cytokinins (CKs), ABA, jasmonate and salicylic acid - in the leaves of eight diverse barley (Hordeum vulgare) accessions grown under field conditions sampled weekly over their life course to assess the ongoing fluctuations in hormone levels in the different accessions under field growth conditions. Notably, we observed enormous changes over time in the development-related plant hormones, such as auxin and CKs. Using 3' RNA-seq-based transcriptome data from the same samples, we investigated the expression of barley genes orthologous to known hormone-related genes of Arabidopsis throughout the life course. These data illustrated the dynamics and diversity of the physiological states of these field-grown barley accessions. Together, our findings provide new insights into plant-environment interactions, highlighting that there is cultivar diversity in physiological responses during growth under field conditions.

Regulation of the Poly(A) Status of Mitochondrial mRNA by Poly(A)-Specific Ribonuclease Is Conserved among Land Plants.

Regulation of the stability and the quality of mitochondrial RNA is essential for the maintenance of mitochondrial and cellular functions in eukaryotes. We have previously reported that the eukaryotic poly(A)-specific ribonuclease (PARN) and the prokaryotic poly(A) polymerase encoded by AHG2 and AGS1, respectively, coordinately regulate the poly(A) status and the stability of mitochondrial mRNA in Arabidopsis. Mitochondrial function of PARN has not been reported in any other eukaryotes. To know how much this PARN-based mitochondrial mRNA regulation is conserved among plants, we studied the AHG2 and AGS1 counterparts of the liverwort, Marchantia polymorpha, a member of basal land plant lineage. We found that M. polymorpha has one ortholog each for AHG2 and AGS1, named MpAHG2 and MpAGS1, respectively. Their Citrine-fused proteins were detected in mitochondria of the liverwort. Molecular genetic analysis showed that MpAHG2 is essential and functionally interacts with MpAGS1 as observed in Arabidopsis. A recombinant MpAHG2 protein had a deadenylase activity in vitro. Overexpression of MpAGS1 and the reduced expression of MpAHG2 caused an accumulation of polyadenylated Mpcox1 mRNA. Furthermore, MpAHG2 suppressed Arabidopsis ahg2-1 mutant phenotype. These results suggest that the PARN-based mitochondrial mRNA regulatory system is conserved in land plants.

Hormonal and transcriptional analyses of fruit development and ripening in different varieties of black pepper (Piper nigrum).

Black pepper (Piper nigrum L.) is one of the most popular and oldest spices in the world with culinary uses and various pharmacological properties. In order to satisfy the growing worldwide demand for black pepper, improved productivity of pepper is highly desirable. A primary constraint in black pepper production is the non-synchronous nature of flower development and non-uniform fruit ripening within a spike. The uneven ripening of pepper berries results in a high labour requirement for selective harvesting contributes to low productivity and affects the quality of the pepper products. In Malaysia, there are a few recommended varieties for black pepper planting, each having some limitations in addition to the useful characteristics. Therefore, a comparative study of different black pepper varieties will provide a better understanding of the mechanisms regulates fruit development and ripening. Plant hormones are known to influence the fruit development process and their roles in black pepper flower and fruit development were inferred based on the probe-based gene expression analysis and the quantification of the multiple plant hormones using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). In this study, jasmonic acid and salicylic acid were found to play roles in flowering and fruit setting, whereas auxin, gibberellin and cytokinins are important for fruit growth. Abscisic acid has positive role in fruit maturation and ripening in the development process. Distinct pattern of plant hormones related gene expression profiles with the hormones accumulation profiles suggested a complex network of regulation is involved in the signaling process and crosstalk between plant hormones was another layer of regulation in the black pepper fruit development mechanisms. The current study provides clues to help in elucidating the timing of the action of each specific plant hormone during fruit development and ripening which could be applied to enhance our ability to control the ripening process, leading to improving procedures for the production and post-harvest handling of pepper fruits.