Artificial intelligence-based histopathological subtyping of high-grade serous ovarian cancer.

Four subtypes of ovarian high-grade serous carcinoma (HGSC) have previously been identified, each with different prognoses and drug sensitivities. However, the accuracy of the classification depended on the assessor's experience. This study aimed to develop a universal algorithm for HGSC-subtype classification using deep learning techniques. An artificial intelligence (AI)-based classification algorithm, which replicates the consensus diagnosis of pathologists, was formulated to analyze the morphological patterns and tumor-infiltrating lymphocyte counts for each tile extracted from whole slide images of ovarian HGSC available in The Cancer Genome Atlas (TCGA) dataset. The accuracy of the algorithm was determined using the validation set from the Japanese Gynecologic Oncology Group 3022A1 (JGOG3022A1) and Kindai and Kyoto University (Kindai/Kyoto) cohorts. The algorithm classified the four HGSC-subtypes with mean accuracies of 0.933, 0.910, and 0.862 for the TCGA, JGOG3022A1, and Kindai/Kyoto cohorts, respectively. To compare Mesenchymal Transition (MT) with non-MT groups, overall survival analysis was performed in the TCGA dataset. The AI-based prediction of HGSC-subtype classification in TCGA cases showed that the MT group had a worse prognosis than the non-MT group (p = 0.017). Furthermore, Cox proportional hazard regression analysis identified AI-based MT subtype classification prediction as a contributing factor along with residual disease after surgery, stage, and age. In conclusion, a robust AI-based HGSC-subtype classification algorithm was established using virtual slides of ovarian HGSC.

Chronic Encapsulated Intracerebral Hematoma after Carbon Ion Therapy for Chordoma Mimicking Malignant Glioma: A Case Report.

Chronic encapsulated intracerebral hematoma is a rare type of intracerebral hemorrhage. Reportedly, it is associated with vascular malformations, including arteriovenous malformations, cavernous hemangiomas, microaneurysms, and venous malformations. Recently, an association between chronic encapsulated intracerebral hematoma and stereotactic radiosurgery for arteriovenous malformations has been reported. In general, as the hematoma enlarges, symptoms progress slowly. In this report, we present a case of a 50-year-old woman who had undergone clivus chordoma resection and carbon ion therapy for the clivus respectively 27 and 20 years before developing chronic encapsulated intracerebral hematoma with rapidly progressing disturbance of consciousness. She was referred to our hospital because of difficulty walking due to left hemiparesis. Head computed tomography and magnetic resonance imaging showed a cystic lesion in the right temporal lobe with perifocal edema. On the second day of hospitalization, the patient's consciousness worsened. We suspected a malignant glioma and performed an emergency craniotomy; however, the pathological diagnosis was chronic encapsulated intracerebral hematoma. After the rehabilitation therapy, the patient became ambulatory and was discharged. To the date of reporting, the patient remained recurrence-free. Chronic encapsulated intracerebral hematoma may be due to invasive craniotomy or carbon ion therapy. It usually progresses slowly; however, in some cases, such as this one, it may cause rapid deterioration of consciousness.

CatSper mediates not only chemotactic behavior but also the motility of ascidian sperm.

Introduction: Sperm motility, including chemotactic behavior, is regulated by changes in the intracellular Ca2+ concentration, and the sperm-specific Ca2+ channel CatSper has been shown to play an important role in the regulation of intracellular Ca2+. In particular, in mammals, CatSper is the only functional Ca2+ channel in the sperm, and mice deficient in the genes comprising the pore region of the Ca2+ channel are infertile due to the inhibition of sperm hyperactivation. CatSper is also thought to be involved in sea urchin chemotaxis. In contrast, in ascidian Ciona intestinalis, SAAF, a sperm attractant, interacts with Ca2+/ATPase, a Ca2+ pump. Although the existence of CatSper genes has been reported, it is not clear whether CatSper is a functional Ca2+ channel in sperm. Results: We showed that CatSper is present in the sperm flagella of C. intestinalis as in mammalian species, although a small level of gene expression was found in other tissues. The spermatozoa of CatSper3 KO animals were significantly less motile, and some motile sperms did not show any chemotactic behavior. These results suggest that CatSper plays an important role in ascidians and mammals, and is involved in spermatogenesis and basic motility mechanisms.

Alkyl-C60 liquid electrets as deformable mechanoelectric generators.

Special attention is being paid to the potential applicability of various soft electronics in deformable/wearable devices. These devices must be constantly connected to energy sources to ensure their uninterrupted operation. Electrets, which are capable of retaining quasi-permanent electric charges inside or on the surface of materials, are expected to be a battery-less power source. Here, we present a strategy for harvesting the charges in alkyl-C60 liquids. Suitable substitution of bulky yet flexible branched long-alkyl chains generated C60-mono-adducts and regioisomeric bis-adducts as room-temperature solvent-free liquids. These alkyl-C60 liquids were negatively poled by the corona-discharging and soaked in nylon fabric. The liquid of the C60 bis-adduct exhibited better charge retention in comparison to the liquid of the C60 mono-adduct. This suggests that the bulky long-alkyl chains provided proper insulation for the C60 core and charge trapping in the liquid. This charge-trapping behaviour and the inherent fluidity of the alkyl-C60 liquids enabled their fabrication into deformable mechanoelectric generator (MEG) devices. The MEG exhibited applicability as a deformable micropower source or vibration sensor by generating output voltage pulses even under folded/twisted/rolled conditions. The alkylated-liquid-based MEGs worked at frequencies similar to human body motion, showing promising potential for body motion sensors and healthcare applications.

Poor Treatment Outcomes of Locally Advanced Cervical Adenocarcinoma of Human Papilloma Virus Independent Type, Represented by Gastric Type Adenocarcinoma: A Multi-Center Retrospective Study (Sankai Gynecology Study Group).

The revised World Health Organization classification of cervical cancer divides adenocarcinomas into human papillomavirus-associated (HPVa) and -independent (HPVi) types; the HPVi type is represented by the gastric type. The treatment outcomes of locally advanced adenocarcinoma (LaAC), based on this classification, are understudied. We investigated the outcomes of patients with HPVa and HPVi LaACs. Data for all consecutive patients with stage IB3 to IIIC1 adenocarcinoma who received treatment at 12 institutions throughout Japan between 2004 and 2009 were retrieved to analyze progression-free and overall survival. Central pathological review classified 103 and 48 patients as having HPVa and HPVi tumors, respectively. Usual- (84%) and gastric- (90%) type adenocarcinomas were the most frequent subtypes. Surgery was the primary treatment strategy for most patients. Progression-free and overall survival of patients with HPVi were worse than those of patients with HPVa (p = 0.009 and 0.032, respectively). Subgroup analysis by stage showed that progression-free survival was significantly different for stage IIB. The current surgical treatment strategy for LaACs is less effective for HPVi tumors than for HPVa tumors, especially those in stage IIB.

Spawning-Induced pH Increase Activates Sperm Attraction and Fertilization Abilities in Eggs of the Ascidian, Phallusia philippinensis and Ciona intestinalis.

In Phlebobranchiata ascidians, oocytes and spermatozoa are stored in the oviduct and spermiduct, respectively, until spawning occurs. Gametes in the gonoducts are mature and fertilizable; however, it was found that the gametes of the ascidians Phallusia philippinensis and Ciona intestinalis could not undergo fertilization in the gonoductal fluids. The body fluids of the ascidians, especially in the gonoducts, were much more acidic (pH 5.5-6.8) than seawater (pH 8.2), and the fertilization rate was low under such acidic conditions. Hence, we examined the effect of pH on gametes. Pre-incubation of gonoductal eggs at pH 8.2 prior to insemination increased fertilization rates, even when insemination was performed under low pH conditions. Furthermore, an increase in ambient pH induced an increase in the intracellular pH of the eggs. It was also found that an increase in ambient pH triggered the release of sperm attractants from the egg and is therefore necessary for sperm chemotaxis. Hence, acidic conditions in the gonoductal fluids keep the gametes, especially eggs, infertile, and the release of eggs into seawater upon spawning induces an increase in ambient pH, which enables egg fertilization.

Helicobacter pylori-negative Gastric Adenocarcinoma Mimicking Verrucous Gastritis in the Antrum: A Case Report and Literature Review.

A 46-year-old man was referred to our hospital for the examination of a flat elevated lesion with an erosion-like depression, located on the greater curvature of the antrum. Endoscopic submucosal dissection was performed. Histological findings of the resected specimen demonstrated a well-differentiated tubular adenocarcinoma with a diameter of 12 mm. No atrophy was observed in the tumor-adjacent mucosa. Serum Helicobacter pylori antibody estimation and 13C-urea breath tests yielded negative results. Immunohistochemical staining was positive for both gastric mucin and intestinal mucin. The final diagnosis was well-differentiated tubular adenocarcinoma with a gastrointestinal phenotype that originated in mucosa uninfected by H. pylori.

Development of wearable multi-lead ECG measurement device using cubic flocked electrode.

This paper describes the fabrication and fundamental evaluation of the cubic flocked electrode (CFE), which is a dry electrode that is fabricated using electrostatic flocking technology. The development of a wearable multi-lead electrocardiogram (ECG) measurement device using the CFE is also reported. To enable the measurement of ECG signals with sufficient quality for medical applications, the occurrence of motion artifacts (MAs) is the most important problem to be overcome. Therefore, it is necessary to stabilize the contact between the patient's skin and the dry electrode. Because the CFE developed in this work offers both contact stability and flexibility, it is expected to enable ECG measurements with low MA levels. In this study, it is demonstrated that the number of MAs caused by respiration can be reduced when the CFE contact is made at a contact pressure of approximately 500 Pa using MA evaluation equipment that was developed in-house. Additionally, a wearable multi-lead ECG is designed and fabricated based on this contact pressure (500 Pa). The results of the demonstration experiment show that the ECG measurements are successful to the same extent as a conventional medical device.

A novel role for ATP2B in ascidians: Ascidian-specific mutations in ATP2B contribute to sperm chemotaxis.

Sperm chemotaxis, in which sperms are attracted to conspecific eggs via species-specific attractants, plays an important role in fertilization. This phenomenon has been observed in various animals and species-specific sperm attractants have been reported in some species. However, the mechanisms involved in the reception and recognition of the species-specific attractant by the sperms is poorly studied. Previously, we found that the plasma membrane-type Ca2+ /ATPase (PMCA) is the receptor for the sperm-activating and -attracting factor (SAAF) in the ascidian Ciona intestinalis. To determine the role of PMCA in species-specific sperm chemotaxis, we identified the amino acid sequences of PMCAs derived from six Phlebobranchia species. The testis-specific splice variant of PMCA was found to be present in all the species investigated and the ascidian-specific sequence was detected near the 3'-terminus. Moreover, dN/dS analysis revealed that the extracellular loops 1, 2, and 4 in ascidian PMCA underwent a positive selection. These findings suggest that PMCA recognizes the species-specific structure of SAAF at the extracellular loops 1, 2, and 4, and its testis-specific C-terminal region is involved in the activation and chemotaxis of ascidian sperms.

DATSURYOKU Sensor-A Capacitive-Sensor-Based Belt for Predicting Muscle Tension: Preliminary Results.

Excessive muscle tension is implicitly caused by inactivity or tension in daily activities, and it results in increased joint stiffness and vibration, and thus, poor performance, failure, and injury in sports. Therefore, the routine measurement of muscle tension is important. However, a co-contraction observed in excessive muscle tension cannot be easily detected because it does not appear in motion owing to the counteracting muscle tension, and it cannot be measured by conventional motion capture systems. Therefore, we focused on the physiological characteristics of muscle, that is, the increase in muscle belly cross-sectional area during activity and softening during relaxation. Furthermore, we measured muscle tension, especially co-contraction and relaxation, using a DATSURYOKU sensor, which measures the circumference of the applied part. The experiments showed high interclass correlation between muscle activities and circumference across maximal voluntary co-contractions of the thigh muscles and squats. Moreover, the circumference sensor can measure passive muscle deformation that does not appear in muscle activities. Therefore, the DATSURYOKU sensor showed the potential to routinely measure muscle tension and relaxation, thus avoiding the risk of failure and injury owing to excessive muscle tension and can contribute to the realization of preemptive medicine by measuring daily changes.

Identification of an antibacterial polypeptide in mouse seminal vesicle secretions.

In both men and women, pathogenic bacteria enter the reproductive tract and cause harmful symptoms. Intrauterine and oviductal inflammation after copulation may have severe effects, such as infertility, implantation failure, oviduct obstruction, and robust life-threatening bacterial infection. Human seminal plasma is considered to be protective against bacterial infection. Among its components, Semenogelin-I/-II proteins are digested to function as bactericidal factors; however, their sequences are not conserved in mammals. Therefore, alternative antibacterial (bactericidal and/or bacteriostatic) systems may exist across mammals. In this study, we examined the antibacterial activity in the seminal plasma of mice lacking a gene cluster encoding Semenogelin-I/-II counterparts. Even in the absence of the majority of seminal proteins, antibacterial activity remained in the seminal plasma. Moreover, a combination of gel chromatography and liquid chromatography coupled with tandem mass spectrometry revealed that the prostate and testis expressed 4 protein as a novel antibacterial (specifically, bacteriostatic) protein, the sequence of which is broadly conserved across mammals. Our results provide the first evidence of a bacteriostatic protein that is widely present in the mammalian seminal plasma.

Pathological eradication of recurrent metastatic renal cell carcinoma with sarcomatoid component by nivolumab plus ipilimumab combination therapy.

Although immuno-oncology combination therapy with nivolumab plus ipilimumab has recently shown a notable antitumor effect for first-line metastatic renal cell carcinoma, the eradication of the disease is extremely rare. Moreover, conventional treatments for renal cell carcinoma show little efficacy in the case of a poor prognostic pathological feature of sarcomatoid dedifferentiation. We report a case of pathological eradication of recurrent metastatic renal cell carcinoma with sarcomatoid component after laparoscopic radical nephrectomy by nivolumab plus ipilimumab combination therapy. A 57-year-old male patient received four cycles of nivolumab plus ipilimumab and thirty cycles of nivolumab for local recurrence and liver metastasis after laparoscopic radical nephrectomy for T3a renal cell carcinoma with sarcomatoid component. He underwent partial hepatectomy for the remaining small hepatic lesion after immuno-oncology therapy. Pathology of the surgical specimen showed no viable cancer cells. The patient was alive with no evidence of disease a year after partial hepatectomy. Our case encourages clinicians to achieve a second cure for patients with recurrent metastatic renal cell carcinoma after radical nephrectomy even though the resected kidney pathology showed sarcomatoid component.

Does the Rainbow Trout Ovarian Fluid Promote the Spermatozoon on Its Way to the Egg?

The fertilization of freshwater fish occurs in an environment that may negatively affect the gametes; therefore, the specific mechanisms triggering the encounters of gametes would be highly expedient. The egg and ovarian fluid are likely the major sources of these triggers, which we confirmed here for rainbow trout (Oncorhynchus mykiss). The ovarian fluid affected significantly spermatozoa performance: it supported high velocity for a longer period and changed the motility pattern from tumbling in water to straightforward moving in the ovarian fluid. Rainbow trout ovarian fluid induced a trapping chemotaxis-like effect on activated male gametes, and this effect depended on the properties of the activating medium. The interaction of the spermatozoa with the attracting agents was accompanied by the "turn-and-run" behavior involving asymmetric flagellar beating and Ca2+ concentration bursts in the bent flagellum segment, which are characteristic of the chemotactic response. Ovarian fluid created the optimal environment for rainbow trout spermatozoa performance, and the individual peculiarities of the egg (ovarian fluid)-sperm interaction reflect the specific features of the spawning process in this species.

HER2-positive breast cancer in a germline BRCA1 gene large deletion carrier.

A majority of breast cancer (BC) molecular subtype in BRCA1 variants carriers is triple-negative type. In contrast, human epidermal growth factor 2 (HER2)-positive BC among carriers of BRCA1 variants is rarely reported. A 42-year-old woman who previously received adjuvant endocrine therapy against left BC developed a left BC relapse and a right new primary BC. Her mother had BC and ovary cancer, and her cousin had BC. Genetic testing revealed a pathogenic large deletion of exons 1-8 in BRCA1. She was diagnosed with hereditary breast and ovary cancer and underwent bilateral mastectomy. The molecular subtypes of her right and left primary BC were HER2-enriched type and luminal-HER2 type, respectively. After completion of adjuvant therapy for right BC, risk-reducing salpingo-oophorectomy (RRSO) is planned. The present case makes us consider the frequency of BRCA1 large rearrangements in Japanese, the association between HER2 amplification and BRCA1 variants, and the optimal timing of RRSO in patients receiving adjuvant therapy for BC.

Kulikovia alborostrata and Kulikovia fulva comb. nov. (Nemertea: Heteronemertea) are Sister Species with Prezygotic Isolating Barriers.

The heteronemertean Kulikovia alborostrata (Takakura, 1898) was originally described as Lineus alborostratus based on material from Misaki, Japan. Although this species was regarded as consisting of two color variants, purple and brown-yellow, the identity of these variants has never been examined based on topotypes. In this study, we performed a multi-locus phylogeny reconstruction, species delimitation analyses, and cross-fertilization experiments to examine the species status of Takakura's original taxon concept consisting of these color variants. Our results suggest that the purple type is identical to Lineus alborostratus Takakura, 1898 auct. (currently Kulikovia alborostrata), whereas the brown-yellow type is conspecific with Lineus fulvus Iwata, 1954, originally established from Hokkaido. These two species appear to have a sister-taxon relationship and are reproductively isolated from each other by prezygotic mechanisms involving gamete incompatibility, minimally separated with 2.8% (16S rRNA) and 14.4% (COI) uncorrected p-distances. We propose that the purple type be considered as representing the true identity of the nominal species Lineus alborostratus (currently assigned to the genus Kulikovia) to maintain the common usage of the name. Although Takakura's type material is not extant, we consider that neotypification is unnecessary in this case because no taxonomic/nomenclatural confusion persists. We also propose to transfer Lineus fulvus to yield Kulikovia fulva comb. nov.

Electrical Characterization of a Double-Layered Conductive Pattern with Different Crack Configurations for Durable E-Textiles.

For the conductive patterns of electronic textiles (e-textiles), it is still challenging to maintain low electrical resistance, even under large or cyclic tensile deformation. This study investigated a double-layered pattern with different crack configurations as a possible solution. Patterns with single crack growth exhibit a low initial resistance and resistance change rate. In contrast, patterns with multiple crack growth maintain their conductivity under deformation, where electrical failure occurs in those with single crack growth. We considered that a double-layered structure could combine the electrical characteristics of patterns with single and multiple crack growths. In this study, each layer was theoretically designed to control the crack configuration. Then, meandering copper patterns, silver ink patterns, and their double layers were fabricated on textiles as patterns with single and multiple crack growths and double-layered patterns, respectively. Their resistance changes under the single (large) and cyclic tensile deformations were characterized. The results confirmed that the double-layered patterns maintained the lowest resistance at the high elongation rate and cycle. The resistance change rates of the meandering copper and silver ink patterns were constant, and changed monotonically against the elongation rate/cycle, respectively. In contrast, the change rate of the double-layered patterns varied considerably when electrical failure occurred in the copper layer. The change rate after the failure was much higher than that before the failure, and on the same order as that of the silver ink patterns.

Human Semenogelin 1 Promotes Sperm Survival in the Mouse Female Reproductive Tract.

Semenogelin 1 (SEMG1), a main component of human seminal plasma, is a multi-functional protein involved in the regulation of sperm motility and fertility. SEMG1 is orthologous to mouse seminal vesicle secretion 2 (SVS2), required for sperm survival in the female reproductive tract after copulation; however, its in vivo function remains unclear. In this study, we addressed this issue by examining the effect of recombinant SEMG1 on intrauterine mouse sperm survival. SEMG1 caused a dose-dependent decrease in mouse sperm motility, similar to its effect on human sperm, but SVS2 had no effect on mouse sperm motility. Mouse epididymal sperm in the presence of 100 µM SEMG1, a concentration that does not affect mouse sperm motility, were injected into the mouse uterus (intrauterine insemination, IUI). IUI combined with SEMG1 significantly increased the survival rate of intrauterine mouse sperm. The effect of SEMG1 on intrauterine sperm survival was comparable with that of SVS2. For clinical applications, three potentially sperm-protecting polypeptides that are easy to handle were designed from SEMG1, but their individual use was unable to mimic the ability of SEMG1. Our results indicate that SEMG1 has potential clinical applications for effective IUI and thereby for safe, simple, and effective internal fertilization.

Mucosa-associated lymphoid tissue (MALT) lymphoma developing in ectopic mediastinal thyroid tissue: a case report.

BACKGROUND: Normally located in the neck, ectopic mediastinal thyroid tissue consists of very rare ectopic thyroid tissue that does not connect to the thyroid gland. A patient with mucosa-associated lymphoid tissue (MALT) lymphoma that has developed in mediastinal thyroid tissue, to our best knowledge, has not been previously reported. CASE PRESENTATION: A 67-year-old woman presented with a superior mediastinal mass that was revealed by chest computed tomography (CT), an optional examination she hoped, during a medical checkup. Contrast-enhanced CT scan performed in our hospital for close examination confirmed the presence of a 2 × 1.3 cm poorly enhanced mass anterior to the trachea during the arterial phase. Magnetic resonance imaging depicted low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. I-131 meta-iodobenzylguanidine did not accumulate in the mass. Serum levels of interleukin-2 receptor, catecholamine, and anti-acetylcholine receptor antibody were within the normal range. The mass was resected through a transverse neck incision for the diagnosis and treatment. The histopathological diagnosis of the specimen was ectopic mediastinal thyroid tissue associated with MALT lymphoma and chronic thyroiditis. Immunoglobulin heavy chain class switch recombination was identified. Fine-needle aspiration biopsy of the cervical thyroid showed chronic thyroiditis but not lymphoma. The patient's postoperative thyroid function was normal. To date, the patient's recovery has been uneventful, and she is being monitored without further treatment. CONCLUSION: We treated the patient with MALT lymphoma that developed in ectopic mediastinal thyroid tissue. This novel case illustrates a new differential diagnosis associated with ectopic mediastinal thyroid tissue.

Resistance Reduction of Conductive Patterns Printed on Textile by Curing Shrinkage of Passivation Layers.

Directly printing conductive ink on textiles is simple and compatible with the conventional electronics manufacturing process. However, the conductive patterns thus formed often show high initial resistance and significant resistance increase due to tensile deformation. Achieving conductive patterns with low initial resistance and reduced deformation-induced resistance increase is a significant challenge in the field of electronic textiles (e-textiles). In this study, the passivation layers printed on conductive patterns, which are necessary for practical use, were examined as a possible solution. Specifically, the reduction of the initial resistance and deformation-induced resistance increase, caused by the curing shrinkage of passivation layers, were theoretically and experimentally investigated. In the theoretical analysis, to clarify the mechanism of the reduction of deformation-induced resistance increase, crack propagation in conductive patterns was analyzed. In the experiments, conductive patterns with and without shrinking passivation layers (polydimethylsiloxane) cured at temperatures of 20-120 °C were prepared, and the initial resistances and resistance increases due to cyclic tensile and washing in each case were compared. As a result, the initial resistance was reduced further by the formation of shrinking passivation layers cured at higher temperatures, and reduced to 0.45 times when the curing temperature was 120 °C. The cyclic tensile and washing tests confirmed a 0.48 and a 0.011 times reduction of resistance change rate after the 100th elongation cycle (10% in elongation rate) and the 10th washing cycle, respectively, by comparing the samples with and without shrinking passivation layers cured at 120 °C.

Electronic Component Mounting for Durable E-Textiles: Direct Soldering of Components onto Textile-Based Deeply Permeated Conductive Patterns.

For the improvement of the performance and function of electronic textiles (e-textiles), methods for electronic component mounting of textile circuits with electrical and mechanical durability are necessary. This manuscript presents a component mounting method for durable e-textiles, with a simpler implementation and increased compatibility with conventional electronics manufacturing processes. In this process, conductive patterns are directly formed on a textile by the printing of conductive ink with deep permeation and, then, components are directly soldered on the patterns. The stiffness of patterns is enhanced by the deep permeation, and the enhancement prevents electrical and mechanical breakages due to the stress concentration between the pattern and solder. This allows components to be directly mounting on textile circuits with electrical and mechanical durability. In this study, a chip resistor was soldered on printed patterns with different permeation depths, and the durability of the samples were evaluated by measuring the variation in resistance based on cyclic tensile tests and shear tests. The experiments confirmed that the durability was improved by the deep permeation, and that the samples with solder and deep permeation exhibited superior durability as compared with the samples based on commercially available elastic conductive adhesives for component mounting. In addition, a radio circuit was fabricated on a textile to demonstrate that various types of components can be mounted based on the proposed methods.