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INTRODUCTION: While selective dorsal rhizotomy (SDR) was originally described as a multilevel approach, single-level approaches are now popularized. Conus localization is beneficial for operative planning in single-level selective dorsal rhizotomy. Our approach to SDR involves minimal exposure for a single-level laminoplasty, preserving one attached interspinous ligament. Pre-operative conus localization is required for this tailored approach to determine the laminoplasty level and dictate rostral or caudal division of the superior spinus ligament. While rapid MRI sequences have been popularized for pediatric cranial imaging, its utility for spinal imagining is less well-described, and specific application for conus localization has not been reported. OBJECTIVE: Illustrate that rapid MRI without sedation is sufficient to identify conus level for tailored single-level laminoplasty SDR. MATERIAL AND METHODS: Patients undergoing SDR from 2014 to 2022 at one institution were reviewed for type of pre-operative MRI (rapid vs full), conus level, procedural time for MRI, and radiology report. The typical rapid MRI has four sequences utilizing single-shot technique (scout, sagittal T2, axial T2, and axial T1) that typically take less than 1 min each of acquisition time, with non-single-shot sequences added periodically in cooperative patients. To include time for patient positioning, pre-scan shimming, procedural incidentals, and other patient-specific variations, MRI procedure length was recorded as documented in the electronic medical record. RESULTS: N = 100 patients had documentation of an MRI for pre-operative imaging. Seventy-nine of these had a rapid MRI, and 21 required a full MRI with anesthesia for their treatment plan. Mean total procedure time for rapid MRI was 21.5 min (median 17). Mean procedure time for MRI under general anesthesia was 91.2 min (median 94). Of patients with rapid MRI imaging, 2/79 had an ambiguous conus level (1 from motion artifact, 1 from spinal hardware) vs 1/21 with a full MRI under anesthesia (due to spinal hardware). CONCLUSION: Rapid spinal MRI without sedation can be used for conus localization in a pediatric population. This may be routinely used as pre-operative imaging for a single-level approach to selective dorsal rhizotomy, without sedation or intubation procedures.

Abstract Background Climate change and the growing demand for agricultural water threaten global food security. Understanding water use characteristics of major crops from leaf to field scale is critical, particularly for identifying crop varieties with enhanced water-use efficiency (WUE) and stress tolerance. Traditional methods to assess WUE are either by gas exchange measurements at the leaf level or labor-intensive manual pot weighing at the whole-plant level, both of which have limited throughput. Results Here, we developed a microcontroller-based low-cost system that integrates pot weighing, automated water supply, and real-time monitoring of plant water consumption via Wi-Fi. We validated the system using major crops (rice soybean, maize) under diverse stress conditions (salt, waterlogging, drought). Salt-tolerant rice maintained higher water consumption and growth under salinity than salt-sensitive rice. Waterlogged soybean exhibited reduced water use and growth. Long-term experiments revealed significant WUE differences between rice varieties and morphological adaptations represented by altered shoot-to-root ratios under constant drought conditions in maize. Conclusions We demonstrate that the system can be used for varietal differences between major crops in their response to drought, waterlogging, and salinity stress. This system enables high-throughput, long-term evaluation of water use characteristics, facilitating the selection and development of water-saving and stress-tolerant crop varieties.

Abstract Background The copy number status (CNS) of the survival motor neuron (SMN) gene may influence the risk and prognosis of amyotrophic lateral sclerosis (ALS) and lower motor neuron diseases (LMND) other than spinal muscular atrophy (SMA). However, previous studies of this association, mainly from Europe, have yielded controversial results, suggesting possible regional differences. Here, we investigated the effect of the SMN gene in Japanese patients with ALS and LMND. Methods We examined the SMN copy numbers and clinical histories of 487 Japanese patients with sporadic ALS (281 men; mean age at onset 61.5 years), 50 with adult LMND (50 men; mean age at onset 58.4 years) and 399 Japanese controls (171 men; mean age 62.2 years). Patients with pathogenic mutations in ALS-causing genes were excluded. SMN1 and SMN2 copy numbers were determined using the droplet digital polymerase chain reaction. Results The frequency of a copy number of one for the SMN2 gene was higher in patients with ALS (38.0%) than in healthy controls (30.8%) (odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.04–1.82, p

Abstract In cancer genome analysis, identifying pathogenic alterations and assessing their effects on oncogenic processes is important. Although whole exome sequencing (WES) can effectively detect such changes, driver alterations could not be identified in 27.8% of the cases, according to a previous study. The objectives of the present study were to evaluate the utility of whole genome sequencing (WGS) and clarify its differences with WES in terms of driver alteration detection. For this purpose, WGS analysis was conducted on 177 driverless WES samples, selected from 5,480 fresh frozen samples derived from 5,140 Japanese patients with cancer. These samples were selected as primary tumor, both WES and transcriptome profiling were performed, estimated tumor content of ≥ 30%, and no driver alterations were identified by WES. WGS identified driver and likely driver alterations in 68.4 and 22.6% of the samples, respectively. The most frequent alteration type was oncogene amplification, followed by tumor suppressor gene deletion and small variants located outside the coding region. In the remaining 9.0% of samples, no such signals were identified; therefore, further investigations are required. The current study clearly demonstrated the role and utility of WGS in identifying genomic alterations that contribute to tumorigenesis.

Background: Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review the existing literature, and elucidate its clinicopathological characteristics, including the potential therapeutic targets. Methods: We retrospectively reviewed the pathological diagnoses of 501 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLAs. Results: Among the 501 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52–76 years old, and the initial FIGO stages were IC1 (two cases) and IIIB (one case). All the cases exhibited HRP, pMMR, PD-L1 negativity (CPS < 1), and low HER2 expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. The MLAs frequently exhibited KRAS mutations (90%, 38/42), with a recurrence rate of 39% (26/67). Conclusion: MLAs accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. The literature also reported a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA.

Abstract Background Primary lateral sclerosis (PLS) is an extremely rare condition; therefore, to date no clinical studies have been conducted. The Primary Lateral Sclerosis Functional Rating Scale (PLSFRS) was developed in the United States of America. The PLSFRS is a crucial assessment scale for international collaborative research and future clinical trials for PLS. It is useful for evaluating medical conditions through face-to-face assessments and telephone interviews such as when a face-to-face assessment is not possible due to disasters or the burden of hospital visits. This study assessed the reliability and consistency of in-person and telephone interviews using the Japanese version of the PLSFRS. Methods We enrolled 19 Japanese patients who met the specific criteria for inclusion at the six collaborating institutions. The PLSFRS assessments were performed by two evaluators at defined time points and analyzed for intra-rater and inter-rater reliability and consistency between the in-person and telephone interviews. Results The Japanese version of the PLSFRS was developed by a specialized company and translator, and modified to consider the Japanese lifestyle through a consensus among motor neuron specialists. The quadratic-weighted kappa coefficients for the intra-rater and the inter-rater agreement were substantial (intra-rater: 0.691-1.000, inter-rater: 0.634-1.000). Moreover, the intraclass correlation coefficient for the PLSFRS total score was 0.997 (95% confidence interval, 0.992–0.999). Conclusions This study provides results regarding the Japanese version of the PLSFRS intra-rater and inter-rater reliability and consistency between in-person and telephone interviews.

Abstract Background Stereotactic irradiation has become the mainstay treatment for brain metastases (BM), and whole-brain radiotherapy (WBRT) is often used for symptom palliation. However, the survival time of patients with BM undergoing palliative WBRT (pWBRT) is limited, making it difficult to select patients who should receive treatment. Methods We collected patient data from 2016 to 2022 at the Shizuoka Cancer Center and retrospectively analyzed the factors related to survival time. Overall survival (OS) was defined as the survival time after WBRT. Results A total of 301 patients (median age, 66 years) who underwent pWBRT were included. The primary cancers were lung, breast, gastrointestinal tract, and other cancers in 203 (67%), 38 (13%), 33 (11%), and 27 (9%) patients, respectively. Median OS of all patients was 4.1 months. In the multivariate analysis, male sex (hazard ratio [HR]:1.4), Karnofsky Performance Status (KPS) ≤ 60 (HR:1.7), presence of extracranial metastasis (ECM) (HR:1.6), neutrophil-lymphocyte ratio (NLR) ≥ 5 (HR:1.6), and lactate dehydrogenase (LDH) ≥ upper limit of normal (ULN) (HR:1.3) were significantly associated with shorter OS (all P

Abstract While certain human hepatitis B virus-targeting nucleoside analogs (NAs) serve as crucial anti-HBV drugs, HBV yet remains to be a major global health threat. E-CFCP is a 4′-modified and fluoromethylenated NA that exhibits potent antiviral activity against both wild-type and drug-resistant HBVs but less potent against human immunodeficiency virus type-1 (HIV-1). Here, we show that HIV-1 with HBV-associated amino acid substitutions introduced into the RT’s dNTP-binding site (N-site) is highly susceptible to E-CFCP. We determined the X-ray structures of HBV-associated HIV-1 RT mutants complexed with DNA:E-CFCP-triphosphate (E-CFCP-TP). The structures revealed that exocyclic fluoromethylene pushes the Met184 sidechain backward, and the resultant enlarged hydrophobic pocket accommodates both the fluoromethylene and 4′-cyano moiety of E-CFCP. Structural comparison with the DNA:dGTP/entecavir-triphosphate complex also indicated that the cyclopentene moiety of the bound E-CFCP-TP is slightly skewed and deviated. This positioning partly corresponds to that of the bound dNTP observed in the HIV-1 RT mutant with drug-resistant mutations F160M/M184V, resulting in the attenuation of the structural effects of F160M/M184V substitutions. These results expand our knowledge of the interactions between NAs and the RT N-site and should help further design antiviral NAs against both HIV-1 and HBV.

Abstract Background Platinum chemotherapy is the cornerstone of treatment for high‐grade serous ovarian cancer (HGSOC); however, validated biomarkers that can accurately predict platinum response are lacking. Based on their roles in the underlying pathophysiology, circulating microRNAs are potential, noninvasive biomarkers in cancer. In the present study, we aimed to evaluate the circulating miRNA profiles of patients with HGSOC and to assess their potential utility as biomarkers to predict platinum response. Methods Pretreatment serum samples collected from patients who received platinum chemotherapy for Stage III–IV HGSOC between 2008 and 2016 were analyzed using miRNA microarray. LASSO logistic regression analysis was used to construct predictive models for treatment‐free interval of platinum (TFIp). Results The median follow‐up was 54.6 (range, 3.5–144.1) months. The comprehensive analysis of 2588 miRNAs was performed in serum samples of 153 eligible patients, and predictive models were constructed using a combination of circulating miRNAs with an area under the receiver operating characteristic curve of 0.944 for TFIp >1 month, 0.637 for TFIp ≥6 months, 0.705 for TFIp ≥12 months, and 0.938 for TFIp ≥36 months. Each predictive model provided a significant TFIp classification (p = 0.001 in TFIp >1 month, p = 0.013 in TFIp ≥6 months, p

Lenvatinib plus pembrolizumab (LP) therapy is currently used in patients with advanced or recurrent endometrial cancer. However, patients with uterine carcinosarcoma (UCS) were not included in the KEYNOTE-775, and the efficacy of LP therapy for patients with UCS in clinical practice remains unclear. We administered LP therapy to five patients with UCS. We aimed to report our clinical experience with LP therapy in these patients and investigate the genomic characteristics of those who responded to LP therapy.We retrospectively reviewed patients with UCS (n = 5) who underwent LP therapy at our hospital from January 2019 to December 2023. Efficacy was assessed using the response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Safety was evaluated in terms of adverse events.The median age was 65 (55–78) years, and the mismatch repair status was proficient in all of the patients. One patient had stage II disease, and four had stage III. The median number of LP therapy courses was 8 (1–35). The overall response rate was 40%. None of the patients experienced adverse events that were grade 3 or higher. The median follow-up duration was 9 (1–26) months, median progression-free survival was 9.1 (0.16 to NA) months, and median overall survival was 10.2 (1.41 to NA) months.LP therapy may be effective for patients with UCS. As this report was based on a limited number of patients, more cases are required to investigate the efficacy of LP therapy in patients with UCS.

Abstract The incidence of vulvar carcinoma varies by race; however, it is a rare disease, and its genomic profiles remain largely unknown. This study examined the characteristics of vulvar squamous cell carcinoma (VSCC) in Japanese patients, focusing on genomic profiles and potential racial disparities. The study included two Japanese groups: the National Cancer Center Hospital (NCCH) group comprised 19 patients diagnosed between 2015 and 2023, and the Center for Cancer Genomics and Advanced Therapeutics group comprised 29 patients diagnosed between 2019 and 2022. Somatic mutations were identified by targeted or panel sequencing, and TP53 was identified as the most common mutation (52–81%), followed by HRAS (7–26%), CDKN2A (21–24%), and PIK3CA (5–10%). The mutation frequencies, except for TP53, were similar to those of Caucasian cohorts. In the NCCH group, 16 patients of HPV-independent tumors were identified by immunohistochemistry and genotyping. Univariate analysis revealed that TP53-mutated patients were associated with a poor prognosis (log-rank test, P = 0.089). Japanese VSCC mutations resembled those of Caucasian vulvar carcinomas, and TP53 mutations predicted prognosis regardless of ethnicity. The present findings suggest potential molecular-targeted therapies for select VSCC patients.

Vulvar intestinal adenocarcinoma is a rare malignancy. The most significant predictor of advanced vulvar cancer is achieving complete resection, although determining the optimal treatment for this rare histologic type remains uncertain. We report the case of a 63-year-old woman with a primary vulvar tumor suspected of having rectal invasion and inguinal lymph node metastases based on preoperative magnetic resonance imaging and computed tomography scans. To achieve complete resection of stage IIIC intestinal-type vulvar adenocarcinoma, we performed a laparoscopic posterior pelvic exenteration (PPE) and radical vulvectomy, along with bilateral inguinal lymph node dissection. This case report highlights the use of a novel hybrid procedure that combines laparoscopic PPE with radical vulvectomy and bilateral inguinal lymph node dissection for vulvar adenocarcinoma of the intestinal type. Laparoscopic PPE can be considered a minimally invasive approach for vulvar tumor when complete resection is achievable with an appropriate safety margin.

A Japanese female in her 20 s with a history of self-induced vomiting was diagnosed with severe renal failure and referred to our department. She was extremely lean, with a body mass index of 9.6 kg/m2. Computed tomography showed increased brightness of the entire renal parenchyma; renal biopsy demonstrated prominent calcium deposition in the Bowman’s capsule and tubulointerstitial areas accompanied by collapsed glomeruli, severe interstitial fibrosis and tubular atrophy. Although the diagnosis was nephrocalcinosis, no underlying conditions were found. Despite the management of chronic kidney disease-mineral bone disorder and nutritional therapy, the patient developed uremia and initiated maintenance hemodialysis approximately two years after the first visit. Kidney disorders are commonly observed in patients with eating disorders and may occasionally lead to end-stage kidney disease. However, detailed investigations are few, especially regarding the histopathological conditions of these patients, and the precise mechanisms remain unclear. Nephrocalcinosis can cause end-stage kidney disease if extensive, as observed in the present case.

ObjectiveThe present study aimed to compare the effectiveness and reliability of quantified superb microvascular imaging (qSMI) and quantified contrast-enhanced ultrasonography (qCEUS) in assessing vascularization in both operable and non-operable uterine cervical cancer.MethodsA case-control study included 64 patients with pathology-proven and untreated cervical cancer, who underwent transvaginal ultrasonography combined with qSMI and qCEUS between January 2022 and June 2023. SMI results were quantified as the vascular index (VI), which were compared to 12 quantitative parameters of CEUS calculated with time-intensity curves (TIC).ResultsAccording to FIGO staging and different treatment regimens, 64 patients with cervical cancer were divided into operable group (IA ~ IIA, n = 19) and non-operable group (IIB ~ IV, n = 45). In comparison to the operable group, the non-operable group showed significantly higher values in VI, peak intensity (PI), area under the curve (AUC), wash-in area (iAUC), wash-out area (oAUC), wash-in rate (WiR), mean intensity (Mean Int), and standard deviation (STD) (all P < 0.05). VI demonstrated strong correlations with CEUS parameters, notably PI (r = 0.854, P < 0.001) and AUC (r = 0.635, P < 0.001). Furthermore, VI showed a better predictive performance for treatment-group assignment than qCEUS parameters, with an 80.7% accuracy, 64.4% sensitivity and 89.5% specificity.ConclusionBoth qSMI and qCEUS exhibit significant and comparable utility in detecting microvascular hyperplasia and predicting treatment-group assignments in cervical cancer. Furthermore, qSMI may offer added convenience in implementation.

Background and Objectives: Cerclage cable fixation with 2 mm multiple-braided cables for displaced acetabular fractures has shown good midterm functional and radiographic outcomes. We retrospectively evaluated the clinical and radiographic outcomes of cerclage cable fixations over ten years. Materials and Methods: We extracted data for patients who underwent cerclage cable fixation for acetabular fractures at a single institution from 2007 to 2012. We adopted this procedure for acetabulum fractures with posterior column fractures. Postoperative reduction quality, complications, reoperations, and Japanese Orthopedic Association (JOA) hip objective functional scores were analyzed. Postoperative reduction quality was classified using plain radiography and computed tomography. Results: We evaluated nine patients with a mean follow-up period of 14.1 ± 2.6 years (range: 10.8–18.1 years). The mean age was 47.1 ± 15.5 years old (range: 28–74 years); the mean injury severity score was 13.6 ± 4.7 (range: 9–22). The most frequent type of fracture was a both-column fracture. Anatomical reduction quality was achieved in five cases. Four patients had hip osteoarthritis at the last follow-up; among them, one patient had worsening hip arthritis > 5 years after surgery, and one patient developed osteoarthritis > 10 years after surgery. Their postoperative reduction quality was worse than their anatomical reduction quality, and both engaged in physical labor. None of the patients underwent revision total hip arthroplasty. The mean JOA hip score was 90.9 ± 7.9 (range: 74–100); seven patients scored >90 at the last follow-up. Conclusions: Cerclage cable fixation showed satisfactory postoperative reductions and favorable long-term clinical outcomes. Long-term follow-up might be necessary for patients whose postoperative reduction is not anatomical to detect late occurrence of hip osteoarthritis, even if osteoarthritis is not evident during short-term follow-up periods.

Background Patients with Parkinson's disease have a high dislocation rate after total hip arthroplasty (THA). This study describes a case with severe Parkinson's disease who developed rapidly destructive coxarthrosis (RDC) and underwent THA using a dual mobility cup after a levodopa‐carbidopa intestinal gel (LCIG) infusion. Case presentation The patient is a 59‐year‐old female with a ten‐year history of Parkinson's disease, which was first treated with oral levodopa. The patient developed RDC of the right hip joint. However, THA was difficult owing to Parkinson's disease and its treatment side effects, such as wearing‐off, dyskinesia, and freezing of the gait, Thus, LCIG was initiated, and improvement in wearing‐off and dyskinesia was observed. Two months after the LCIG therapy, the disease was controlled well. THA was subsequently performed using a dual mobility cup to prevent postoperative dislocation. Postoperatively, LCIG therapy was continuously administered to carefully manage the disease, which was controlled well with no increase in wearing‐off and dyskinesia after surgery. At 1 year after surgery, the walking speed, stride length, and the Harris hip score improved compared to preoperatively. The UPDRS III motor score improved to eight without signs of wearing‐off or dyskinesia. The Hoehn‐Yahr scale was II in the “on” period and remained unchanged 1 year after surgery. The patient could walk without a cane and had satisfactory functional outcomes. Conclusion This case proved that LCIG treatment performed preoperatively, followed by THA using a dual mobility cup, and strict management of Parkinson's disease could result in a satisfactory clinical course without recurrence of wearing‐off and dyskinesia. Similar procedures may benefit other patients with Parkinson's disease who have previously been deemed unsuitable for THA.

Abstract Introduction Pegfilgrastim is indicated to decrease the incidence of chemotherapy‐induced febrile neutropenia. It is the first granulocyte‐colony stimulating factor approved for prophylactic use regardless of carcinoma type and is marketed in Japan as G‐LASTA (Kyowa Kirin Co., Ltd., Tokyo, Japan). MD‐110 is a biosimilar of pegfilgrastim. This phase III, multicenter, open‐label, single‐arm study investigated the efficacy and safety of MD‐110 in early‐stage breast cancer patients receiving neoadjuvant or adjuvant myelosuppressive chemotherapy. Methods A total of 101 patients received the study drug. Each patient received docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 (TC) for four cycles on day 1 of each cycle. MD‐110 (3.6 mg) was administered subcutaneously on day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 (days with absolute neutrophil count < 500/mm3). The safety endpoints were adverse events and the presence of antidrug antibodies. Results The mean (SD) duration of severe neutropenia for MD‐110 was 0.2 (0.4) days. The upper limit of the two‐sided 95% confidence interval for the mean duration of severe neutropenia was 0.2 days, below the predefined threshold of 3.0 days. The incidence of febrile neutropenia, the secondary efficacy endpoint, was 6.9% (7/101). Adverse events, occurring in more than 50% of patients, were alopecia, constipation, and malaise, which are common side effects of TC chemotherapy. Antidrug antibodies were negative in all patients. Conclusion MD‐110 was effective against chemotherapy‐induced neutropenia. No additional safety concern, compared with the originator, was observed in patients with breast cancer receiving TC chemotherapy.(JapicCTI‐205230).

Abstract SARS-CoV-2-BA.4/5-adapted-bivalent-BNT162b2-vaccine (bvBNT), developed in response to the recent emergence of immune-evasive Omicron-variants, has been given to individuals who completed at least 2-doses of the monovalent-BNT162b2-vaccine (mvBNT). In the present cohort study, we evaluated neutralization-titers (NT50s) against Wuhan-strain (SCoV2Wuhan) and Omicron-sublineages including BA.2/BA.5/BQ.1.1/XBB/XBB.1.5, and vaccine-elicited S1-binding-IgG in sera from participants-vaccinated with 5th-bvBNT following 4th-mvBNT. The 5th-bvBNT-dose elicited good protective-activity against SCoV2Wuhan with geometric-mean (gMean)-NT50 of 1966–2091, higher than the peak-values post-4th-mvBNT with no statistical significance, and favorable neutralization-activity against not only BA.5 but also BA.2, with ~ 3.2-/~ 2.2-fold greater gMean-NT50 compared to the peak-values post-4th-mvBNT-dose, in participants with or without risk factors. However, neutralization-activity of sera post-5th-bvBNT-dose was low against BQ.1.1/XBB/XBB.1.5. Interestingly, participants receiving bvBNT following breakthrough (BT) infection during Omicron-wave had significantly enhanced neutralization-activity against SCoV2Wuhan/BA.2/BA.5 with ~ 4.6-/~ 6.3-/~ 8.1-fold greater gMean-NT50, respectively, compared to uninfected participants receiving bvBNT. Sera from BT-infected-participants receiving bvBNT had enhanced neutralization-activity against BQ.1.1/XBB/XBB.1.5 by ~ 3.8-fold compared to those from the same participants post-4th-mvBNT-dose, and had enhanced gMean-NT50 ~ 5.4-fold greater compared to those of uninfected-participants’ sera post-bvBNT. These results suggest that repeated stimulation brought about by exposure to BA.5’s-Spike elicit favorable cross-neutralization-activity against various SARS-CoV-2-variants.