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PURPOSE To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2. PATIENTS AND METHODS Patients with recurrent UCS with HER2 immunohistochemistry scores ≥1+ previously treated with chemotherapy were included. Patients were assigned to the HER2-high (immunohistochemistry score ≥2+; n = 22) or low (immunohistochemistry score of 1+; n = 10) groups for primary and exploratory analyses, respectively. Trastuzumab deruxtecan 6.4 or 5.4 mg/kg was administered intravenously once every 3 weeks until unacceptable toxicity or disease progression. Dose modification was based on the updated recommended phase II dose for breast cancer to be 5.4 mg/kg. The primary end point was the objective response rate by central review in the HER2-high group. Secondary end points included the overall response rate (ORR) in the HER2-high group by investigator assessment, ORR in the HER2-low group, progression-free survival (PFS), overall survival (OS), and safety. RESULTS The ORR by central review in the HER2-high and HER2-low groups were 54.5% (95% CI, 32.2 to 75.6) and 70.0% (95% CI, 34.8 to 93.3) and those by investigator assessments were 68.2% and 60.0%, respectively. The median PFS and OS in the HER2-high and HER2-low groups were 6.2 and 13.3 months and 6.7 months and not reached, respectively. Grade ≥ 3 adverse events occurred in 20 patients (61%). Grades 1-2 and 3 pneumonitis/interstitial lung disease occurred in eight (24%) and one (3%) patient, respectively. CONCLUSION Trastuzumab deruxtecan has efficacy in patients with UCS, regardless of HER2 status. The safety profile was generally consistent with that previously reported. Toxicities were manageable with appropriate monitoring and treatment.

We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum‐resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open‐label, phase II trial (JGOG3023), patients were randomized 1:1 to a single‐agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m2 administered intravenously], topotecan [1.25 mg/m2 intravenously], paclitaxel [80 mg/m2 intravenously], or gemcitabine [1000 mg/m2 intravenously]) or single‐agent chemotherapy + bevacizumab (15 mg/m2 intravenously). The primary endpoint was investigator‐assessed progression‐free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator‐assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32‐0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38‐1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment‐related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification., We evaluated chemotherapy ± bevacizumab for platinum‐resistant recurrent ovarian cancer previously treated with bevacizumab. The results of this phase II study demonstrate the efficacy and manageable toxicity of continuing bevacizumab beyond progressive disease in patients with platinum‐resistant recurrent ovarian cancer previously treated with bevacizumab for front‐line or platinum‐sensitive recurrent ovarian cancer.

Hemorrhage and organ injury have been frequently reported as complications associated with trocar puncture in laparoscopic surgery. This report presents a case of delayed intestinal necrosis due to mesenteric injury. A 76-year-old woman who had a history of distal gastrectomy and adrenal insufficiency was diagnosed with stage IA endometrial cancer. We performed laparoscopic total hysterectomy and bilateral salpingo-oophorectomy. The upper abdominal wall and mesentery were adhered, and bleeding from the mesentery was noted during the first trocar puncture of the umbilical region, resulting in ligation and hemostasis. Abdominal pain and fever developed on the third postoperative day, and contrast-enhanced computed tomography demonstrated transverse colon perforation. Emergency laparotomy showed necrosis in the proximal transverse colon and a defect in the marginal artery. Mesenteric injury can lead to delayed intestinal necrosis without intraoperative macroscopic findings. In laparoscopic cases where adhesion is expected, trocar placement should be carefully considered.

Maize grain hardness influences storage pest resistance, a key characteristic valued by smallholder farmers. The structural changes in the endosperm determine grain hardness and are influenced by agronomic practices. The purpose of this study was to establish whether supply of calcium and magnesium based fertilizers can alter physicochemical properties of local and hybrid maize varieties and reduce the infestation by larger grain borer (Prostephanus truncatus (Coleoptera: Bostrichidae)) during storage. Two local and one hybrid maize varieties commonly grown by smallholder farmers in Malawi were cultivated under three fertilizer treatments (NPK (nitrogen, phosphorous, potassium), NPK plus gypsum, and NPK plus dolomite). After harvest, the grains were classified into flint and dent types, followed by P. truncatus infestation and determination of their physicochemical properties. The addition of gypsum and dolomite fertilizers led to higher levels of amylose, total zein and β-14 zein, traits associated with kernel hardness, compared to the application of NPK fertilizer. Moreover, local maize varieties showed higher resistance to P. truncatus infestation, hardness and biochemical properties associated with hardness (total zein, α-19 and β-14 zein, starch lysophosphatidylcholine, and non-starch free fatty acid) compared to hybrid variety. Our study suggests the potential for utilizing Ca and Mg nutrition in maize to improve kernel hardness, thus adoption of gypsum and dolomite by smallholder farmers may be beneficial against P. truncatus during storage.

Grain size is an important agronomic trait that influences the yield and end-use quality of bread wheat (Triticum aestivum L.). We conducted quantitative trait loci (QTL) analysis using recombinant inbred lines derived from a cross of a semi-dwarf modern variety with large grains (Zenkoujikomugi: Zen) and a landrace with small grains (Chinese Spring: CS). Grain size was evaluated as grain length (GL), grain width (GW), grain thickness (GT), and thousand-grain weight (TGW) under two environmental conditions. A major QTL (QGl.obu-4B) associated with GL was detected in both environments near the Rht-B1 locus for the semi-dwarf trait on chromosome 4B, despite Zen and CS having the same Rht-B1a allele. No QTL for GW was found in the QGl.obu-4B region, and QTLs for GT and TGW was detected in only one environment. To validate the effect of QGl.obu-4B, we developed two backcrossed populations in the CS and Zen genetic backgrounds. The Zen-derived allele conferred larger GL, GW, and GT, resulting in greater TGW (13.7% increase compared to the CS-derived allele) in the CS background. In contrast, the QGl.obu-4B effect was smaller in the Zen background, and the Zen-derived allele increased TGW by only 7.0%. The QTL was located within the 168-Mbp region tightly linked to the Rht-B1 locus. Further characterization and fine-mapping of QGl.obu-4B will facilitate the use of this allele by marker-assisted selection in wheat breeding programs.

Some studies have shown increased risks of preterm birth, low birth weight, and cesarean delivery after oncologic treatment; others have shown the opposite. We evaluated the outcomes of pregnancies and deliveries of patients who underwent fertility-preserving surgery (FSS) for early-stage epithelial ovarian cancer (EOC) and examined their perinatal prognosis. This retrospective study included women with a history of stage IA or IC ovarian cancer reported in our previous study. The primary outcome was preterm birth after cancer diagnosis was considered. Secondary outcomes were neonatal morbidity and severe maternal morbidity. Thirty-one children were born to 25 women who had undergone FSS. The mean number of weeks at delivery was 38.7 ± 0.7, and the mean birth weight of infants was 3021 ± 160 g. With respect to pregnancy outcomes, 5 patients had preterm labor and 26 had full-term labor. The delivery mode was vaginal delivery in 18 patients and cesarean delivery in 13. Complications during pregnancy included placenta previa (one case) and pelvic abscess (one case). Except for three preterm infants with low birth weight, there were no other perinatal abnormalities. Pregnancy after fertility preservation in EOC has an excellent perinatal prognosis, although the cesarean delivery rate is high.

Uterine carcinosarcoma (UCS) is an uncommon and highly aggressive tumor. There is no HER2 testing protocol for UCS despite the development of HER2 antibody conjugates. We aimed to elucidate histopathological HER2 expression details in UCS, to compare HER2 scores between ASCO/CAP criteria for gastric and breast cancer, and to propose requirements for HER2 testing for UCS. Eighty-nine specimens from 84 patients with metastatic/recurrent UCS were prospectively collected from May 2018 to July 2020. We performed HER2 immunohistochemistry (IHC) for 89 specimens and FISH for 44 specimens. HER2 expression details and HER2 score were evaluated according to the latest ASCO/CAP criteria for gastric (2016) and breast cancer (2018). HER2 IHC scores according to the gastric cancer criteria were 0 in 31 cases (35%), 1+ in 26 (29%), 2+ in 22 (25%), and 3+ in 10 cases (11%) of the 89 specimens. A lateral/basolateral membranous staining pattern was observed in 28/32 (88%) specimens with HER2 scores of 2+/3+. HER2 intratumoral heterogeneity was identified in 28/32 (88%) of the specimens with HER2 scores of 2+/3+. The overall concordance rate of HER2 score was 70% between the gastric and breast criteria. FISH revealed HER2 gene amplification in 10/44 (23%) specimens containing only lateral/basolateral membranous staining pattern. Based on the histopathological features of HER2 expression in UCS, a scoring system that accepts lateral/basolateral staining patterns should be applied. Furthermore, we proposed specific requirements for UCS testing, including specimen selection, scoring system, and calculating the proportion of HER2-positive cells.

The dynamic behavior of a machine tool is affected by the forces applied to the structure. However, cutting processes have been analyzed considering the linear systems in most of the studies so far. In this study, a machine tool structure was excited by using an electromagnetic shaker and the force-dependant frequency response characteristics were measured. Based on the measured result, the nonlinear characteristics of the machine tool structure was identified, and a machine tool with the nonlinear characteristics was mathematically reproduced, which enabled to analyse the nonlinear frequency response characteristics and simulate cutting processes.

Epicotyl length (ECL) of adzuki bean (Vigna angularis) affects the efficiency of mechanized weeding and harvest. The present study investigated the genetic factors controlling ECL. An F2 population derived from a cross between the breeding line 'Tokei1121' (T1121, long epicotyls) and the cultivar 'Erimo167' (common epicotyls) was phenotyped for ECL and genotyped using simple sequence repeats (SSRs) and single-nucleotide polymorphism (SNP) markers. A molecular linkage map was generated and fifty-two segregating markers, including 27 SSRs and 25 SNPs, were located on seven linkage groups (LGs) at a LOD threshold value of 3.0. Four quantitative trait loci (QTLs) for ECL, with LOD scores of 4.0, 3.4, 4.8 and 6.4, were identified on LGs 2, 4, 7 and 10, respectively; together, these four QTLs accounted for 49.3% of the phenotypic variance. The segregation patterns observed in F5 residual heterozygous lines at qECL10 revealed that a single recessive gene derived from T1121 contributed to the longer ECL phenotype. Using five insertion and deletion markers, this gene was fine mapped to a ~255 kb region near the end of LG10. These findings will facilitate marker-assisted selection for breeding in the adzuki bean and contribute to an understanding of the mechanisms associated with epicotyl elongation.

In early 1995, Crispian Scully telephoned Newell Johnson and said he wanted to start a completely new journal in our field motivated, perhaps, by not being able to place every piece of his extraordinary personal output of the art [yes art] and science of oral medicine and pathology. Newell was initially sceptical because it was, even then, a struggle for ordinary mortals to keep up with the literature. Crispian was always hard to say no to, indeed a couple of years earlier he had done the same thing on creation of Oral Oncology.

The aim of this study was to establish the attributes of kernel type based on kernel hardness and its interrelationship with maize endosperm chemical components, which are essential during storage. Three local varieties and one hybrid variety commonly grown by smallholder farmers in central Malawi were used. For storage experiment, the maize samples were infested with Prostephanus truncatus, larger grain borer (LGB) for eight weeks. Due to the high propensity of maize to cross-pollinate, the kernels were classified into flint and dent kernels to establish the physicochemical properties of the kernel type and variety independently. Local variety (L-3) exhibited the lowest number and weight of damaged grains and the highest adult LGB cadavers. Local variety, L-1 and L-3 had significantly the highest proportion of flint kernels type. Moreover, flint kernels of local varieties showed significantly the highest hardness, and the highest content of protein, total zein, α-zein and zinc (p < 0.05). Furthermore, hardness was significantly and positively correlated with total zein and 14 kDa β-zein content (p < 0.05). Zein in the endosperm, particularly 19 and 22 kDa α-zein mainly contributed to distinct hardness of the local varieties hence may contribute to physical barrier of the kernels against storage pests. Key words: Maize, local variety, kernel type, hardness, chemical properties, larger grain borer.

Objectives Certain human leucocyte antigen (HLA)-B alleles (protective alleles) associate with durable immune control of HIV-1, but with substantial heterogeneity in the level of control. It remains elusive whether viral factors including Nef-mediated immune evasion function diminish protective allele effect on viral control. Design The naturally occurring non-Ser variant at position 9 of HIV-1 subtype C Nef has recently exhibited an association with enhanced HLA-B downregulation function and decreased susceptibility to recognition by CD8 T cells. We therefore hypothesized this Nef genotype leads to diminished immune control mediated by protective HLA alleles. Methods Nef sequences were isolated from HIV-1 subtype C-infected patients harboring protective alleles and several Nef functions including downregulation of HLA-A, HLA-B, CD4, and SERINC5 were examined. Association between Nef non-Ser9 and plasma viral load was examined in two independent South African and Botswanan treatment-naive cohorts. Results Nef clones isolated from protective allele individuals encoding Nef non-Ser9 variant exhibited greater ability to downregulate HLA-B when compared with the Ser9 variant, while other Nef functions including HLA-A, CD4, and SERINC5 downregulation activity were unaltered. By analyzing a cohort of South African participants chronically infected with subtype C HIV-1, Nef non-Ser9 associated with higher plasma viral load in patients harboring protective alleles. Corroboratively, the Nef non-Ser9 correlated with higher plasma viral load in an independent cohort in Botswana. Conclusion Taken together, our study identifies the Nef genotype, non-Ser9 that subverts host immune control in HIV-1 subtype C infection.

ObjectiveFinancial toxicity is a financial burden of cancer care itself, which leads to worse quality of life and higher mortality and is considered an adverse effect. The COmprehensive Score for financial Toxicity (COST) tool is a patient-reported outcome measurement used to evaluate financial toxicity. We aimed to validate the internal consistency and reproducibility of the COST tool in patients with gynecologic cancer.MethodsIn this multicenter study covering the period April 2019 to July 2021, using the COST tool in Japan, patients diagnosed with ovarian, cervical, or endometrial cancer receiving systemic anti-cancer drug therapy for more than 2 months were eligible. Patients with no out-of-pocket costs for direct medical costs were excluded. The patients answered the initial test and a retest, which was completed from 2 to 14 days after the initial test. Internal consistency and reproducibility were assessed using Cronbach’s alpha and intraclass correlation coefficient (ICC), respectively. Cronbach’s alpha ≥0.8 indicates good internal consistency, and ICC ≥0.8 is highly reliable.ResultsA total of 112 patients (ovarian: 50, cervical: 26, endometrial: 36) responded to the initial test, and 89 patients answered the retest from 2 to 14 days after the initial test. The median patient age was 58 (range, 28–78) years. The median COST score was 19. Cronbach’s alpha showed good internal consistency at 0.83 (95% CI 0.78 to 0.87). The ICC at 0.850 (95% CI 0.777 to 0.900) showed high reliability.ConclusionsThe COST tool has good internal consistency and reliable reproducibility in patients with gynecologic cancer in Japan. The COST tool quantifies financial toxicity in the insurance system, where patients have limited out-of-pocket direct medical costs. The results support the use of the COST tool in patients with gynecologic cancer.