Extraction of local structure differences in silica based on unsupervised learning.

Silica exhibits a rich phase diagram with numerous stable structures existing at different temperature and pressure conditions, including its glassy form. In large-scale atomistic simulations, due to the small energy difference, several phases may coexist. While, in terms of long-range order, there are clear differences between these phases, their short- or medium-range structural properties are similar for many phases, thus making it difficult to detect the structural differences. In this study, a methodology based on unsupervised learning is proposed to detect the differences in local structures between eight phases of silica, using atomic models prepared by molecular dynamics (MD) simulations. A combination of two-step locality preserving projections (TS-LPP) and locally averaged atomic fingerprints (LAAF) descriptor was employed to find a low-dimensional space in which the differences among all the phases can be detected. From the distance between each structure in the found low-dimensional space, the similarity between the structures can be discussed and subtle local changes in the structures can be detected. Using the obtained low-dimensional space, the ß-α transition in quartz at a low temperature was analyzed, as well as the structural evolution during the melt-quench process starting from α-quartz. The proper differentiation and ease of visualization make the present methodology promising for improving the analysis of the structure and properties of glasses, where subtle differences in structure appear due to differences in the temperature and pressure conditions at which they were synthesized.

Clonal origin and genomic diversity in Lynch syndrome-associated endometrial cancer with multiple synchronous tumors: Identification of the pathogenicity of MLH1 p.L582H.

Lynch syndrome-associated endometrial cancer patients often present multiple synchronous tumors and this assessment can affect treatment strategies. We present a case of a 27-year-old woman with tumors in the uterine corpus, cervix, and ovaries who was diagnosed with endometrial cancer and exhibited cervical invasion and ovarian metastasis. Her family history suggested Lynch syndrome, and genetic testing identified a variant of uncertain significance, MLH1 p.L582H. We conducted immunohistochemical staining, microsatellite instability analysis, and Sanger sequencing for Lynch syndrome-associated cancers in three generations of the family and identified consistent MLH1 loss. Whole-exome sequencing for the corpus, cervical, and ovarian tumors of the proband identified a copy-neutral loss of heterozygosity (LOH) occurring at the MLH1 position in all tumors. This indicated that the germline variant and the copy-neutral LOH led to biallelic loss of MLH1 and was the cause of cancer initiation. All tumors shared a portion of somatic mutations with high mutant allele frequencies, suggesting a common clonal origin. There were no mutations shared only between the cervix and ovary samples. The profiles of mutant allele frequencies shared between the corpus and cervix or ovary indicated that two different subclones originating from the corpus independently metastasized to the cervix or ovary. Additionally, all tumors presented unique mutations in endometrial cancer-associated genes such as ARID1A and PIK3CA. In conclusion, we demonstrated clonal origin and genomic diversity in a Lynch syndrome-associated endometrial cancer, suggesting the importance of evaluating multiple sites in Lynch syndrome patients with synchronous tumors.

Lung cancer detection in perioperative patients' exhaled breath with nanomechanical sensor array.

INTRODUCTION: Breath analysis using a chemical sensor array combined with machine learning algorithms may be applicable for detecting and screening lung cancer. In this study, we examined whether perioperative breath analysis can predict the presence of lung cancer using a Membrane-type Surface stress Sensor (MSS) array and machine learning. METHODS: Patients who underwent lung cancer surgery at an academic medical center, Japan, between November 2018 and November 2019 were included. Exhaled breaths were collected just before surgery and about one month after surgery, and analyzed using an MSS array. The array had 12 channels with various receptor materials and provided 12 waveforms from a single exhaled breath sample. Boxplots of the perioperative changes in the expiratory waveforms of each channel were generated and Mann-Whitney U test were performed. An optimal lung cancer prediction model was created and validated using machine learning. RESULTS: Sixty-six patients were enrolled of whom 57 were included in the analysis. Through the comprehensive analysis of the entire dataset, a prototype model for predicting lung cancer was created from the combination of array five channels. The optimal accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 0.809, 0.830, 0.807, 0.806, and 0.812, respectively. CONCLUSION: Breath analysis with MSS and machine learning with careful control of both samples and measurement conditions provided a lung cancer prediction model, demonstrating its capacity for non-invasive screening of lung cancer.

Trends in endometrial carcinoma: experience of a single institute for four decades.

OBJECTIVE: To determine the current prognosis of endometrial carcinoma in Japan by analyzing long-term trends in endometrial carcinoma at our hospital. METHODS: We divided 1463 patients with endometrial carcinoma who visited our hospital between 1984 and 2022 into group 1984-1991, group 1992-1999, group 2000-2006, group 2007-2014 and group 2015-2022. Trends were determined using the Jonckheere-Terpstra and Cochran-Armitage tests. Data were analyzed using Cox regression analysis. RESULTS: When group 2015-2022 was used as a reference in the univariate analysis, the hazard ratios for the other groups were <1. In particular, the hazard ratio for group 2007-2014 was 0.65 (95% confidence interval, 0.47-0.90, P = 0.009), suggesting that the prognosis of group 2015-2022 was worse than that of group 2007-2014 and seemed to be the worst among all prognoses. In multivariate analysis, the hazard ratios for each group were 1.38, 1.42, 1.88, 1.16 and 1, respectively; the group with the worst prognosis changed from group 2015-2022 to group 2000-2006 (hazard ratio, 1.88; 95% confidence interval, 1.27-2.78, P = 0.001). Age and the rate of non-endometrioid carcinoma exhibited significantly increasing trends (P < 0.001 and P < 0.001, respectively), as did the rates of serous and mixed carcinomas (P = 0.001 and 0.024, respectively). The rates of non-endometrioid carcinoma, serous carcinoma and mixed carcinoma were 19.0%, 5.5% and 3.1% in group 2007-2014 and 28.2%, 10.8% and 4.6% in group 2015-2022, respectively. CONCLUSIONS: The increasing rates of non-endometrioid carcinoma-especially serous and mixed carcinoma-may be associated with the worsening prognosis of endometrial carcinoma at our institution. Careful monitoring is needed to confirm whether this phenomenon is observed throughout Japan.

Rapidly growing intramuscular lipoma: a unique entity of benign lipomas in children.

This report presents a case of an intramuscular lipoma observed in the left back of a healthy female toddler. It was resected after 3 months of observation because of rapid enlargement, raising suspicion of malignancy. Histopathological examination confirmed a diagnosis of intramuscular lipoma without malignant and blastemal components. Intramuscular lipomas are benign neoplasms that mostly appear as a rapidly growing tumour. Several hypotheses regarding the pathogenesis of this characteristic growth pattern have been proposed, including atrophy of the surrounding muscle, reactive adipocytic neoformation and multiple contractive interactions between the lipoma and the surrounding muscle.

Refractory ovarian squamous cell carcinoma arising from a seromucinous borderline tumor with squamous overgrowth: A case report.

Ovarian squamous cell carcinoma (SCC) is rare, and most cases arise from ovarian teratomas. Herein, we present a case of ovarian SCC arising from an ovarian seromucinous borderline tumor (SMBT) with squamous overgrowth. A 71-year-old woman an underwent emergency laparotomy due to the rupture of a right ovarian tumor suspected to be a borderline or malignant tumor. We performed a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy. The postoperative diagnosis was stage IC3 ovarian SCC arising from the SMBT with a squamous overgrowth. Subsequently, she underwent six cycles of combination therapy comprising paclitaxel and carboplatin. Two months after the last chemotherapy treatment, she presented with back pain. A CT scan showed a 14 mm pelvic tumor affecting the ureter, leading to right hydronephrosis. The patient underwent tumor resection and ureteroureterostomy. The pathological diagnosis was keratinizing SCC, representing ovarian cancer recurrence. Eight months after the removal of the recurrent tumor, we found a 35 mm recurrent pelvic tumor causing right hydronephrosis. Additionally, a 20 mm pleural dissemination was identified. Comprehensive genome profiling of recurrent tumor revealed genomic abnormalities in TP53, ARID1A, PTEN, PIK3R1, and CDKN2A/2B. Regarding immunotherapy biomarkers, the microsatellite instability test result was negative, the tumor mutation burden was low, and PD-L1 was highly expressed. The patient was referred to another hospital for participation in an immunotherapy clinical trial for ovarian SCC. This case indicates that refractory ovarian SCC can arise from SMBT. Further evaluation of additional cases is required to identify the molecular biological characteristics of ovarian SCC.

SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma.

BRCA1/2 mutations are robust biomarkers for platinum-based chemotherapy in epithelial ovarian cancers. However, BRCA1/2 mutations in clear cell ovarian carcinoma (CCC) are less frequent compared with high-grade serous ovarian cancer (HGSC). The discovery of biomarkers that can be applied to CCC is an unmet need in chemotherapy. Schlafen 11 (SLFN11) has attracted attention as a novel sensitizer for DNA-damaging agents including platinum. In this study, we investigated the utility of SLFN11 in HGSC and CCC for platinum-based chemotherapy. SLFN11 expression was analyzed retrospectively by IHC across 326 ovarian cancer samples. The clinicopathologic significance of SLFN11 expression was analyzed across 57 advanced HGSC as a discovery set, 96 advanced HGSC as a validation set, and 57 advanced CCC cases, all of whom received platinum-based chemotherapy. BRCA1/2 mutation was analyzed using targeted-gene sequencing. In the HGSC cohort, the SLFN11-positive and BRCA mutation group showed significantly longer whereas the SLFN11-negative and BRCA wild-type group showed significantly shorter progression-free survival and overall survival. Moreover, SLFN11-positive HGSC shrunk significantly better than SLFN11-negative HGSC after neoadjuvant chemotherapy. Comparable results were obtained with CCC but without consideration of BRCA1/2 mutation due to a small population. Multivariate analysis identified SLFN11 as an independent factor for better survival in HGSC and CCC. The SLFN11-dependent sensitivity to platinum and PARP inhibitors were validated with genetically modified non-HGSC ovarian cancer cell lines. Our study reveals that SLFN11 predicts platinum sensitivity in HGSC and CCC independently of BRCA1/2 mutation status, indicating that SLFN11 assessment can guide treatment selection in HGSC and CCC.

Endometrial Cancer with and without Endometriosis: Clinicopathological Differences.

Endometriosis is known to be associated with an increased risk of endometrioid and clear cell ovarian cancer. However, the association between endometriosis and endometrial cancer is controversial. Therefore, we retrospectively analyzed the medical records of women with endometrial cancer who had undergone surgery at our institution to evaluate the clinicopathological relationship between endometrial cancer and endometriosis. The study included 720 women pathologically diagnosed with endometrial cancer at our hospital between 2000 and 2020. The participants were allocated to two groups of patients with endometrial cancer: patients with endometriosis (n = 101) and patients without endometriosis (n = 619). Endometrial cancer patients with endometriosis were significantly younger (median age 54.0 vs. 58.0; p = 0.002). In addition, endometrial cancer patients with endometriosis had fewer pregnancies and deliveries (median pregnancy 1.58 vs. 1.99; p = 0.019, median delivery 1.25 vs. 1.56; p = 0.012). The percentage of patients classified as stage IA was significantly higher in those with endometrial cancer with endometriosis (68.3% vs. 56.4%; p = 0.029). In the analysis of synchronous ovarian cancer, the percentage of dual primary cancer was higher in patients with endometriosis (14.9% vs. 1.6%; p < 0.001). The association of young-onset early-stage endometrial cancer with endometriosis is an important finding that cannot be ignored clinically.

Revealing factors influencing polymer degradation with rank-based machine learning.

The efficient treatment of polymer waste is a major challenge for marine sustainability. It is useful to reveal the factors that dominate the degradability of polymer materials for developing polymer materials in the future. The small number of available datasets on degradability and the diversity of their experimental means and conditions hinder large-scale analysis. In this study, we have developed a platform for evaluating the degradability of polymers that is suitable for such data, using a rank-based machine learning technique based on RankSVM. We then made a ranking model to evaluate the degradability of polymers, integrating three datasets on the degradability of polymers that are measured by different means and conditions. Analysis of this ranking model with a decision tree revealed factors that dominate the degradability of polymers.

External Esophageal Stenting Technique in Palliation for Tracheal Agenesis in a Case of Esophageal Lung: A Lesson Learned from the Experience for Tracheomalacia.

Tracheal agenesis (TA) is a rare congenital anomaly with an incidence of 1 per 50,000 newborns. It appears at birth with severe respiratory distress, cyanosis, and inaudible crying. Prompt esophageal intubation and long-term management of the esophageal airway are essential to overcome this catastrophic condition. In the long-term management, external stenting of the esophageal airway has been reported as promising to support the fragile esophageal wall; this technique was taken from the surgery for tracheomalacia. We experienced a case of an infant with tracheal agenesis whose respiratory status was stabilized after external esophageal stenting. The stenting was performed based on a lesson learned in the extensive experience in the surgical treatment for tracheomalacia, and the surgical techniques for successful stenting are herein described.

A retrospective study of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers.

OBJECTIVES: Although the Pipelle endometrial biopsy is widely performed as a practical and minimally invasive test for endometrial disease(s), its effectiveness in ovarian cancer has not been explored. The aim of the present study was to evaluate the results of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers. METHODS: A pre-treatment Pipelle-endometrial biopsy was performed in 90 patients with ovarian, fallopian tube, or peritoneal cancers between January 2014 and November 2021. We retrospectively analysed the association between the results of Pipelle endometrial biopsy and clinicopathological data. Moreover, we evaluated their impact on the following treatment in advanced cases initially treated with chemotherapy. RESULTS: The sensitivity and false-negative rates for Pipelle endometrial biopsy were 25/90 (27.8%) and 65/90 (72.2%) in all patients, respectively, and 23/56 (41.0%) and 33/56 (58.9%) in cases with advanced disease (stages III and IV), respectively. Pipelle-positive endometrial biopsy-positive (Pipelle-positive) was not observed in 29 patients with clinical stage I disease, and Pipelle-positive patients exhibited significantly more high-grade serous carcinomas, and positive peritoneal, endometrial, and cervical cytologies than Pipelle-endometrial biopsy-negative cases. Surgical pathology was confirmed in 23 Pipelle-positive patients, and 17/23 (74.0%) had the same diagnosis as that for Pipelle endometrial biopsy. Conversely, 6/23 (26.0%) patients exhibited a minor diagnostic discrepancy between Pipelle endometrial biopsy and surgical pathology. Nineteen of the 38 (50.0%) patients initially treated with chemotherapy were identified as Pipelle-positive, contributing to a prompt histological diagnosis and pre-treatment tumour sampling. Companion diagnostic tests were performed using Pipelle endometrial biopsy samples from 4 inoperable patients. CONCLUSION: Although the positive rate of Pipelle endometrial biopsy in ovarian, fallopian tube, and peritoneal cancers is low, Pipelle endometrial biopsy may enable prompt histological diagnosis and initiation of chemotherapy while collecting tumour tissue for genetic testing in some cases with advanced disease.

The effectiveness of pre-treatment Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers remains unclear. This study demonstrated that Pipelle endometrial biopsy may enable prompt histological diagnosis and initiation of chemotherapy while collecting tumour tissue for genetic testing in some cases with advanced disease. This was a single-centre, retrospective study; as such, the effectiveness of Pipelle endometrial biopsy should be evaluated in larger prospective studies, including comparisons with other tumour sampling methods.

Mapping stress inside living cells by atomic force microscopy in response to environmental stimuli.

The response of cells to environmental stimuli, under either physiological or pathological conditions, plays a key role in determining cell fate toward either adaptive survival or controlled death. The efficiency of such a feedback mechanism is closely related to the most challenging human diseases, including cancer. Since cellular responses are implemented through physical forces exerted on intracellular components, more detailed knowledge of force distribution through modern imaging techniques is needed to ensure a mechanistic understanding of these forces. In this work, we mapped these intracellular forces at a whole-cell scale and with submicron resolution to correlate intracellular force distribution to the cytoskeletal structures. Furthermore, we visualized dynamic mechanical responses of the cells adapting to environmental modulations in situ. Such task was achieved by using an informatics-assisted atomic force microscope (AFM) indentation technique where a key step was Markov-chain Monte Carlo optimization to search for both the models used to fit indentation force-displacement curves and probe geometry descriptors. We demonstrated force dynamics within cytoskeleton, as well as nucleoskeleton in living cells which were subjected to mechanical state modulation: myosin motor inhibition, micro-compression stimulation and geometrical confinement manipulation. Our results highlight the alteration in the intracellular prestress to attenuate environmental stimuli; to involve in cellular survival against mechanical signal-initiated death during cancer growth and metastasis; and to initiate cell migration.

Koopmans' Theorem-Compliant Long-Range Corrected (KTLC) Density Functional Mediated by Black-Box Optimization and Data-Driven Prediction for Organic Molecules.

Density functional theory (DFT) is a significant computational tool that has substantially influenced chemistry, physics, and materials science. DFT necessitates parametrized approximation for determining an expected value. Hence, to predict the properties of a given molecule using DFT, appropriate parameters of the functional should be set for each molecule. Herein, we optimize the parameters of range-separated functionals (LC-BLYP and CAM-B3LYP) via Bayesian optimization (BO) to satisfy Koopmans' theorem. Our results demonstrate the effectiveness of the BO in optimizing functional parameters. Particularly, Koopmans' theorem-compliant LC-BLYP (KTLC-BLYP) shows results comparable to the experimental UV-absorption values. Furthermore, we prepared an optimized parameter dataset of KTLC-BLYP for over 3000 molecules through BO for satisfying Koopmans' theorem. We have developed a machine learning model on this dataset to predict the parameters of the LC-BLYP functional for a given molecule. The prediction model automatically predicts the appropriate parameters for a given molecule and calculates the corresponding values. The approach in this paper would be useful to develop new functionals and to update the previously developed functionals.

Uptake and Outcomes of Neoadjuvant Chemotherapy Among US Patients With Less Common Epithelial Ovarian Carcinomas.

Importance: Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade serous carcinomas. The use and outcomes of NACT in less common epithelial carcinomas are understudied. Objective: To investigate the uptake and survival outcomes in treatment with NACT for less common histologic subtypes of epithelial ovarian cancer. Design, Setting, and Participants: A retrospective cohort study and systematic literature review with meta-analysis was conducted using the National Cancer Database from 2006 to 2017 and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2006 to 2019. Data analysis was performed from July 2022 to April 2023. The evaluation included patients with stage III to IV ovarian cancer with clear cell, mucinous, or low-grade serous histologic subtypes who received multimodal treatment with surgery and chemotherapy. Exposures: Exposure assignment per the sequence of treatment: primary debulking surgery (PDS) followed by chemotherapy (PDS group) or NACT followed by interval surgery (NACT group). Main Outcomes and Measures: Temporal trends and characteristics of NACT use were assessed using multivariable analysis, and overall survival (OS) was assessed with the inverse probability of treatment weighting propensity score. Results: A total of 3880 patients were examined in the National Cancer Database including 1829 women (median age, 56 [IQR, 49-63] years) with clear cell, 1156 women (median age, 53 [IQR, 42-64] years) with low-grade serous, and 895 women (median age, 57 [IQR, 48-66] years) with mucinous carcinomas. NACT use increased in patients with clear cell (from 10.2% to 16.2%, 58.8% relative increase; P < .001 for trend) or low-grade serous (from 7.7% to 14.2%, 84.4% relative increase; P = .007 for trend) carcinoma during the study period. This association remained consistent in multivariable analysis. NACT use also increased, but nonsignificantly, in mucinous carcinomas (from 8.6% to 13.9%, 61.6% relative increase; P = .07 for trend). Across the 3 histologic subtypes, older age and stage IV disease were independently associated with NACT use. In a propensity score-weighted model, the NACT and PDS groups had comparable OS for clear cell (4-year rates, 31.4% vs 37.7%; hazard ratio [HR], 1.12; 95% CI, 0.95-1.33) and mucinous (27.0% vs 26.7%; HR, 0.90; 95% CI, 0.68-1.19) carcinomas. For patients with low-grade serous carcinoma, NACT was associated with decreased OS compared with PDS (4-year rates, 56.4% vs 81.0%; HR, 2.12; 95% CI, 1.55-2.90). Increasing NACT use and histologic subtype-specific survival association were also found in the Surveillance, Epidemiology, and End Results Program cohort (n = 1447). A meta-analysis of 4 studies, including the current study, observed similar OS associations for clear cell (HR, 1.13; 95% CI, 0.96-1.34; 2 studies), mucinous (HR, 0.93; 95% CI, 0.71-1.21; 2 studies), and low-grade serous (HR, 2.11; 95% CI, 1.63-2.74; 3 studies) carcinomas. Conclusions and Relevance: Despite the lack of data on outcomes of NACT among patients with less common carcinomas, this study noted that NACT use for advanced disease has gradually increased in the US. Primary chemotherapy for advanced-stage, low-grade serous ovarian cancer may be associated with worse survival compared with PDS.

Determination of hyper-parameters in the atomic descriptors for efficient and robust molecular dynamics simulations with machine learning forces.

The atomic descriptors used in machine learning to predict forces are often high dimensional. In general, by retrieving a significant amount of structural information from these descriptors, accurate force predictions can be achieved. On the other hand, to acquire higher robustness for transferability without overfitting, sufficient reduction of descriptors should be necessary. In this study, we propose a method to automatically determine hyperparameters in the atomic descriptors, aiming to obtain accurate machine learning forces while using a small number of descriptors. Our method focuses on identifying an appropriate threshold cut-off for the variance value of the descriptor components. To demonstrate the effectiveness of our method, we apply it to crystalline, liquid, and amorphous structures in SiO2, SiGe, and Si systems. By using both conventional two-body descriptors and our introduced split-type three-body descriptors, we demonstrate that our method can provide machine learning forces that enable efficient and robust molecular dynamics simulations.

The Junction Between the Peristaltic and Non-peristaltic Bowel (Shore Break) is Found in the Transition Zone in Hirschsprung's Disease.

BACKGROUND: The junction between the peristaltic and non-peristaltic bowel, which is named the "shore break" (SB), observed on endoscopy is thought to be the boundary between normal and abnormal motility in Hirschsprung's disease (HD). The transition zone (TZ), which is the histopathological border, does not have normal motility and should be resected. This study aimed to evaluate the histopathological findings of the SB and determine the association between the SB and TZ. METHODS: A retrospective review of surgical specimens of patients with HD who underwent preoperative SB marking was conducted. The TZ was defined if nerve hypertrophy, myenteric hypoganglionosis, or partial circumferential aganglionosis was detected. RESULTS: Ten patients (9 boys and 1 girl) were studied. The median age at surgery was 30 days. The median distance from the anal verge to the marked SB site was 14 cm. No patients manifested any obstructive symptoms resulting from a residual TZ bowel. In eight patients, nerve hypertrophy was identified at the proximal margin and at the SB. Myenteric hypoganglionosis was identified in three patients at the proximal margin and SB. Partial circumferential aganglionosis was identified at the SB in two patients. As a result, in all patients, the pull-through site and SB site had histopathological features indicating TZ. CONCLUSIONS: The SB is located in the TZ. Our results suggest that the proximal part of the TZ has normal motility and that functional border points may be present in the TZ. LEVEL OF EVIDENCE: IV.

Congenital diaphragmatic hernia survival in an English regional ECMO center.

Introduction: Congenital diaphragmatic hernia (CDH) remains a cause of neonatal death. Our aims are to describe contemporary rates of survival and the variables associated with this outcome, contrasting these with our study of two decades earlier and recent reports. Materials and methods: A retrospective review of all infants diagnosed in a regional center between January 2000 and December 2020 was performed. The outcome of interest was survival. Possible explanatory variables included side of defect, use of complex ventilatory or hemodynamic strategies (inhaled nitric oxide (iNO), high-frequency oscillatory ventilation (HFOV), extracorporeal membrane oxygenation (ECMO), and Prostin), presence of antenatal diagnosis, associated anomalies, birth weight, and gestation. Temporal changes were studied by measuring outcomes in each of four consecutive 63-month periods. Results: A total of 225 cases were diagnosed. Survival was 60% (134 of 225). Postnatal survival was 68% (134 of 198 liveborn), and postrepair survival was 84% (134 of 159 who survived to repair). Diagnosis was made antenatally in 66% of cases. Variables associated with mortality were the need for complex ventilatory strategies (iNO, HFOV, Prostin, and ECMO), antenatal diagnosis, right-sided defects, use of patch repair, associated anomalies, birth weight, and gestation. Survival has improved from our report of a prior decade and did not vary during the study period. Postnatal survival has improved despite fewer terminations. On multivariate analysis, the need for complex ventilation was the strongest predictor of death (OR=50, 95% CI 13 to 224, p<0.0001), and associated anomalies ceased to be predictive. Conclusions: Survival has improved from our earlier report, despite reduced numbers of terminations. This may be related to increased use of complex ventilatory strategies.

Successful treatment of advanced squamous cell carcinoma arising from mature cystic teratoma of the ovary with homologous recombination deficiency: A case report.

INTRODUCTION AND IMPORTANCE: Squamous cell carcinoma (SCC) arising from mature cystic teratoma of the ovary (MCT-SCC) has a poor prognosis at advanced stages. Although the relationship between homologous recombination deficiency (HRD) and platinum-based chemotherapy sensitivity or poly (ADP ribose) polymerase (PARP) inhibitor efficacy in epithelial ovarian cancer has been demonstrated in clinical trials, the significance of HRD status in MCT-SCC has not previously been described. CASE PRESENTATION: A 73-year-old woman underwent emergency laparotomy due to ovarian tumor rupture. The ovarian tumor was strongly adherent to the surrounding pelvic organs and could not be completely resected. The postoperative diagnosis was stage IIIB MCT-SCC (pT3bNXM0) of the left ovary. After surgery, we conducted the myChoice CDx. The genomic instability (GI) score of 87 was remarkably high, and there was no BRCA1/2 pathogenic mutation. After six courses of combination therapy with paclitaxel and carboplatin, the residual tumors had shrunk by 73 %. We performed interval debulking surgery (IDS), and the residual tumors were completely resected. Subsequently, the patient underwent two courses of the combination of paclitaxel, carboplatin, and bevacizumab, followed by maintenance therapy with olaparib and bevacizumab. Twelve months after IDS, no recurrence has been observed. CLINICAL DISCUSSION: The present case suggests that there are some HRD cases among MCT-SCC patients and that IDS and maintenance therapy with PARP inhibitors may be effective in such cases, as in epithelial ovarian cancer. CONCLUSION: Although the frequency of HRD-positive status in MCT-SCC remains unknown, HRD testing may provide appropriate treatment options for advanced MCT-SCC.

Quantum Annealing Designs Nonhemolytic Antimicrobial Peptides in a Discrete Latent Space.

Increasing the variety of antimicrobial peptides is crucial in meeting the global challenge of multi-drug-resistant bacterial pathogens. While several deep-learning-based peptide design pipelines are reported, they may not be optimal in data efficiency. High efficiency requires a well-compressed latent space, where optimization is likely to fail due to numerous local minima. We present a multi-objective peptide design pipeline based on a discrete latent space and D-Wave quantum annealer with the aim of solving the local minima problem. To achieve multi-objective optimization, multiple peptide properties are encoded into a score using non-dominated sorting. Our pipeline is applied to design therapeutic peptides that are antimicrobial and non-hemolytic at the same time. From 200 000 peptides designed by our pipeline, four peptides proceeded to wet-lab validation. Three of them showed high anti-microbial activity, and two are non-hemolytic. Our results demonstrate how quantum-based optimizers can be taken advantage of in real-world medical studies.

Falciform ligament hernia: combination of key CT findings.

A male patient in his early 90s with no history of abdominal surgery was referred to us for abdominal pain and vomiting. An abdominal computed tomography (CT) demonstrated dilated small bowel with a double beak sign and poorly enhanced wall, which indicated a closed-loop obstruction that leads to strangulation. A closed-loop bowel was located in front of the anterior and medial segments of the liver and to the right of the round ligament of the liver on axial images. Sagittal images revealed that the round ligament has deviated downward and 2 adjacent narrowed intestines were located at its cranial side. These CT findings suggested the hernia orifice was in the falciform ligament. Emergency surgery for highly suspected bowel ischemia revealed the falciform ligament hernia. A combination of the CT findings played a key role, including the double beak sign, the location of the closed-loop small bowel, and the downward deviation of the round ligament, although preoperative CT diagnosis of falciform ligament hernia is a diagnostic challenge.