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Introduction Transverse testicular ectopia is a rare anomaly in which both testes descend toward the same side of the hemiscrotum. Case presentation A 35‐year‐old man presented with right inguinal enlargement. Computed tomography showed a normal testis in the right hemiscrotum and a 58 mm heterogeneous mass in the right inguinal area. No testis was observed in the left hemiscrotum. The vascular structures extended from the right inguinal mass to the left renal vein. Consequently, the left testicular tumor was diagnosed as transverse testicular ectopia, and a left orchiectomy was performed. The histological diagnosis was seminoma stage pT2. Furthermore, left para‐aortic lymph node metastasis developed 10 months postoperatively. A complete response was obtained after systemic chemotherapy. Conclusion Awareness of seminomas in transverse testicular ectopia could facilitate appropriate diagnosis and treatment. Furthermore, the location of the lymph node metastasis indicated that the ectopic testis could have originated from the left side.

Abstract We report a case of severe Aicardi–Goutières syndrome caused by a novel homozygous RNASEH2B intronic variant, NC_000013.10(NM_024570.4):c.65-13G > A p.Glu22Valfs*5. The patient was born with pseudo-TORCH symptoms, including intracranial calcification, cataracts, and hepatosplenomegaly. Furthermore, the patient exhibited profound intellectual impairment and died at 14 months due to aspiration pneumonia accompanied by interstitial lung abnormalities. The severity of the patient’s symptoms underscores the critical role of the C-terminal region of RNase H2B.

Abstract Background Prostate ductal adenocarcinoma, a rare histology observed in 0.4–0.8% of all prostate cancers, is treated similarly to acinar adenocarcinoma but tends to have a higher likelihood of metastasis, recurrence, and poorer prognosis. Case presentation A 73-year-old Asian-Japanese male presented with gross hematuria, with investigations revealing a prostate ductal adenocarcinoma. Subsequent radical prostatectomy indicated a Gleason score of 8 with no lymph node metastasis. Despite initial prostate-specific antigen level reductions post-prostatectomy and salvage radiation therapy due to recurring elevated prostate-specific antigen levels, no recurrence was evident until 13 years later. A tumor in the anterior urethra was identified as metastasis of his prostate ductal adenocarcinoma. Conclusion This report presents an uncommon case of prostate ductal adenocarcinoma exhibiting a late recurrence in the anterior urethra 13 years post-radical prostatectomy.

A cavity-based X-ray free-electron laser (CBXFEL) is a possible future direction in the development of fully coherent X-ray sources. CBXFELs consist of a low-emittance electron source, a magnet system with several undulators and chicanes, and an X-ray cavity. The X-ray cavity stores and circulates X-ray pulses for repeated FEL interactions with electron pulses until the FEL reaches saturation. CBXFEL cavities require low-loss wavefront-preserving optical components: near-100%-reflectivity X-ray diamond Bragg-reflecting crystals, outcoupling devices such as thin diamond membranes or X-ray gratings, and aberration-free focusing elements. In the framework of the collaborative CBXFEL research and development project of Argonne National Laboratory, SLAC National Accelerator Laboratory and SPring-8, we report here the design, manufacturing and characterization of X-ray optical components for the CBXFEL cavity, which include high-reflectivity diamond crystal mirrors, a diamond drumhead crystal with thin membranes, beryllium refractive lenses and channel-cut Si monochromators. All the designed optical components have been fully characterized at the Advanced Photon Source to demonstrate their suitability for the CBXFEL cavity application.

Abstract We report on the feasibility of Fourier transform holography in the hard X-ray regime using a Free Electron Laser source. Our study shows successful single and multi-pulse holographic reconstructions of the nanostructures. We observe beam-induced heating of the sample exposed to the intense X-ray pulses leading to reduced visibility of the holographic reconstructions. Furthermore, we extended our study exploring the feasibility of recording holographic reconstructions with hard X-ray split-and-delay optics. Our study paves the way towards studying dynamics at sub-nanosecond timescales and atomic lengthscales.

Abstract A intermediate multidomain state and large crystallographic tilting of 1.78° for the (hh0)pc planes of a (001)pc-oriented single-domain Mn-doped BiFeO3 (BFMO) thin film were found when an electric field was applied along the [110]pc direction. The anomalous crystallographic tilting was caused by ferroelastic domain switching of the 109° domain switching. In addition, ferroelastic domain switching occurred via an intermediate multidomain state. To investigate these switching dynamics under an electric field, we used in situ fluorescent X-ray induced Kossel line pattern measurements with synchrotron radiation. In addition, in situ inverse X-ray fluorescence holography (XFH) experiments revealed that atomic displacement occurred under an applied electric field. We attributed the atomic displacement to crystallographic tilting induced by a converse piezoelectric effect. Our findings provide important insights for the design of piezoelectric and ferroelectric materials and devices.

Evaporable indano[60]fullerene ketone (FIDO) was converted to indano[60]fullerene thioketone (FIDS) in high yield by using Lawesson's reagent. Three compounds with different substituents in para position were successfully converted to the corresponding thioketones, showing that the reaction tolerates compounds with electron-donating and electron-withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives (FIDO, FIDS, C60) as electron-acceptors were compared, and the open-circuit voltage with FIDS was 0.16 V higher than that with C60.

Abstract Mitochondrial diseases are mainly caused by dysfunction of mitochondrial respiratory chain complexes and have a variety of genetic variants or phenotypes. There are only a few approved treatments, and fundamental therapies are yet to be developed. Leigh syndrome (LS) is the most severe type of progressive encephalopathy. We previously reported that apomorphine, an anti- “off” agent for Parkinson’s disease, has cell-protective activity in patient-derived skin fibroblasts in addition to strong dopamine agonist effect. We obtained 26 apomorphine analogs, synthesized 20 apomorphine derivatives, and determined their anti-cell death effect, dopamine agonist activity, and effects on the mitochondrial function. We found three novel apomorphine derivatives with an active hydroxy group at position 11 of the aporphine framework, with a high anti-cell death effect without emetic dopamine agonist activity. These synthetic aporphine alkaloids are potent therapeutics for mitochondrial diseases without emetic side effects and have the potential to overcome the low bioavailability of apomorphine. Moreover, they have high anti-ferroptotic activity and therefore have potential as a therapeutic agent for diseases related to ferroptosis.

Introduction Low‐grade fibromyxoid sarcoma is an uncommon deep‐seated soft‐tissue sarcoma that occurs rarely in young adults and children. Although surgical resection provides a long‐term prognosis, late local recurrence and metastasis may occur. Case presentation A 44‐year‐old woman with no prior medical history presented with breathing and abdominal discomfort. Contrast‐enhanced computed tomography scan revealed a retroperitoneal tumor protruding into the thoracic cavity and pleural effusion on the left side. Tumor biopsy revealed sarcoma. We performed complete resection of the tumor along with part of the diaphragm and replaced the diaphragm with a prosthetic patch. Histopathologic findings indicated low‐grade fibromyxoid sarcoma. The patient experienced no postoperative complications and received no adjuvant therapy. Furthermore, she survived 4 years after surgery without recurrence. Conclusion Complete surgical resection is effective for low‐grade fibromyxoid sarcoma; therefore, it is important to plan appropriately for complete resection when biopsy reveals malignant findings.

Introduction Inflammatory myofibroblastic tumors are difficult to diagnose because of the lack of specific indicators. We describe a diagnostically challenging case of an inflammatory myofibroblastic tumor primary to the peritoneum. Case presentation The patient was a 25‐year‐old male who presented at our hospital with lower abdominal pain. Computed tomography revealed a mass lesion 80 mm in diameter just above the bladder. This was suspected to be a bleeding tumor of the urachus. Since malignancy could not be ruled out, surgery was planned. This revealed a fragile tumor arising from the peritoneum. Following its removal, the tumor was diagnosed by histopathological analysis as an inflammatory myofibroblastic tumor. Conclusion We describe a case of inflammatory myofibroblastic tumor primary to the peritoneum diagnosed by histopathology. Inflammatory myofibroblastic tumor should be considered in the differential diagnosis of abdominal wall and anterior bladder tumors.

Abstract Ancillary service provision and peak shaving (PS) play essential roles in the current day‐to‐day power system operation, which is challenged by the increasing renewable generation penetration. Providing these critical services using classical approaches such as peak load generators has been limited due to high operational costs and environmental impacts. The use of battery energy storage systems (BESS) is another popular method that is limited by high initial investment costs and high degradation rates. In this work, a novel approach to utilize industrial loads and BESS to provide multiple power system services in different stages is proposed. Industrial loads such as aluminium crushers are known for their intensive electricity consumption. Nevertheless, when applied in frequency regulation (FR), they perform poorly due to their discrete nature in operation. This drawback and the aforementioned BESS shortcomings are addressed by combining on‐site BESS with plant machinery to provide FR services and recover BESS related costs. Later, depending on the optimal capacity distribution, BESS usage is extended into the energy arbitrage market to provide PS services. This approach resulted in higher earnings for participating customers and network operators, as well as in less CO2 emissions, and minimal BESS degradations. An Australian case study of the South West Interconnected System, along with Worsley Alumina refinery data of Western Australia has been used to showcase the model performances.

Abstract Background For patients with nonischemic dilated cardiomyopathy (NIDCM), the indications for and results of mitral surgery remain controversial. We reviewed a strategy of mitral repair and replacement for clinically relevant secondary mitral regurgitation (MR) in patients with NIDCM. Methods We retrospectively reviewed 65 patients with advanced NIDCM (LVEF

Autosomal dominant optic atrophy (DOA) is a progressive form of blindness caused by degeneration of retinal ganglion cells and their axons, mainly caused by mutations in the OPA1 mitochondrial dynamin like GTPase (OPA1) gene. OPA1 encodes a dynamin-like GTPase present in the mitochondrial inner membrane. When associated with OPA1 mutations, DOA can present not only ocular symptoms but also multi-organ symptoms (DOA plus). DOA plus often results from point mutations in the GTPase domain, which are assumed to have dominant-negative effects. However, the presence of mutations in the GTPase domain does not always result in DOA plus. Therefore, an experimental system to distinguish between DOA and DOA plus is needed. In this study, we found that loss-of-function mutations of the dOPA1 gene in Drosophila can imitate the pathology of optic nerve degeneration observed in DOA. We successfully rescued this degeneration by expressing the human OPA1 (hOPA1) gene, indicating that hOPA1 is functionally interchangeable with dOPA1 in the fly system. However, mutations previously identified did not ameliorate the dOPA1 deficiency phenotype. By expressing both WT and DOA plus mutant hOPA1 forms in the optic nerve of dOPA1 mutants, we observed that DOA plus mutations suppressed the rescue, facilitating the distinction between loss-of-function and dominant-negative mutations in hOPA1. This fly model aids in distinguishing DOA from DOA plus and guides initial hOPA1 mutation treatment strategies.

Anastomosis of the prosthetic graft to the double-barreled aorta with intimal flap fenestration is a useful technique in surgery for chronic aortic dissection. Conversely, anastomosis to the false lumen's outer wall is prone to complications such as pseudoaneurysms, but little is known about the technique of reinforcing the double-barreled aorta. In this report, we describe a surgical case of chronic aortic dissection in which an H-shaped prosthetic graft was sutured to both aortic lumens, including the intimal flap, to prevent complications at the anastomosis site.

Diet therapy is one of the most important treatments for people with type 2 diabetes (T2D). However, dietary restrictions due to diet therapy may reduce quality of life (QOL). This cross-sectional study aimed to investigate the association between diabetes diet-related QOL and dietary fiber intake in 238 people with T2D. The Diabetes Diet-related Quality of Life–Revised version (DDRQOL-9-R) and the brief-type self-administered diet history questionnaire were used to evaluate diabetes diet-related QOL and nutritional intake, respectively. Higher scores of each DDRQOL-9-R subscale means greater satisfaction with diet, perceived merits of diet therapy, and lower burden of diet therapy, which indicates good QOL. The median scores for perceived merits of diet therapy, satisfaction with diet, and burden of diet therapy were 58.3 [41.7–75.0], 75.0 [66.7–91.7], and 66.7 [50.0–75.0] points, respectively. HbA1c levels in people with high perceived merits of diet therapy (7.3 [6.7–7.8] vs. 7.5 [7.1–8.2] %, p = 0.007) and people with high satisfaction with diet (7.3 [6.8–7.8] vs. 7.5 [7.1–8.4] %, p = 0.010) were lower than those without. Dietary fiber intake was higher in people with high perceived merits of diet therapy (11.6 [8.8–16.7] vs. 10.0 [7.9–13.8] g/day, p = 0.010), high satisfaction with diet (11.4 [8.8–16.1] vs. 9.7 [7.8–13.2] g/day, p = 0.007), and low burden of diet therapy (11.8 [8.7–16.5] vs. 9.7 [7.8–12.6] g/day, p = 0.004) than in those without. Dietary fiber intake was related to perceived merits of diet therapy (Odds ratio [OR]1.07 [95%CI: 1.00–1.15], p = 0.049), burden of diet therapy (OR 0.90 [95%CI: 0.82–0.98], p = 0.022), and satisfaction with diet (OR 1.18 [95%CI: 1.09–1.27], p < 0.001) after adjusting for covariates. Dietary fiber intake is associated with diabetes diet-related QOL in people with T2D.

Abstract In this study, we investigated the composition of free amino acids and lactate (Lac) in polychaetes in river estuaries and inner bays using chromatographic techniques. Both l-amino acids and d-amino acids (d-asparagine, d-alanine (d-Ala), d-serine, d-aspartic acid, and d-proline (d-Pro)) were detected, indicating that polychaetes contain some d-amino acids. Some polychaete species exhibited notable amino acid levels, such as glycine in Capitellidae sp. and Thelepus sp., d-Pro in Glycera sp., and β-Ala in Scoletoma nipponica and Scoletoma sp.. High d-Lac levels were detected in Tylorrhynchus osawai and Hediste diadroma, (691 and 797 μmol/100 g-wet, respectively), with the d-form exceeding 98%. T. osawai was dominant in the upper tidal-sensitive zone, wherein other organisms were less abundant because of low salinity (3–8 PSU). Seasonal differences in the concentrations of components in T. osawai were observed, particularly a significant increase in d-Lac in the reproductive period. Notably, the d-Lac concentrations of T. osawai were higher upstream than downstream. Thus, d-Lac might be involved in strategies underlying adaptations to low salinity and reproductive activity. These results suggest that both the d-form of Lac and amino acids may play certain physiological roles in the life of polychaetes.

Abstract Purpose The NY‐ESO‐1 antigen is highly immunogenic and often spontaneously induces an immune response in patients with cancer. We conducted a large‐scale multicenter cohort study to investigate the utility of serum NY‐ESO‐1 and p53 antibodies as predictive markers for the postoperative recurrence of gastric cancer. Here, we examined the usefulness of pre‐treatment NY‐ESO‐1 and p53 antibodies as tumor markers for the diagnosis of gastric cancer in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9). Methods A total of 1031 patients with cT3‐4 gastric cancer were enrolled in the study. NY‐ESO‐1 and p53 antibodies were assessed prior to treatment. The positivity of NY‐ESO‐1 and p53 antibodies, CEA, and CA19‐9 was evaluated before treatment. Results Serum NY‐ESO‐1 and p53 antibodies were positive in 12.6% and 18.1% of the patients, respectively. Positive NY‐ESO‐1 antibody response was correlated with male gender, higher cStage, and upper tumor location. However, a positive p53 antibody response was not associated with tumor factors. The combination of NY‐ESO‐1 or p53 antibody response with CEA and CA19‐9, or the 4‐factors, was positive in 45.1%, 49.6%, and 53.8% of patients, respectively. Moreover, the 4‐factor combination was able to detect >60% of cStage III‐IV diseases, which was 14% higher than that with the combination of CEA and CA19‐9. Conclusion The combination of NY‐ESO‐1 and p53 antibody responses to CEA and CA19‐9 increases the diagnostic accuracy of gastric cancer. Serum NY‐ESO‐1 and p53 antibodies may be useful tumor markers for gastric cancer.

Abstract Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to the D5 receptor. We previously identified apomorphine as a potential therapeutic agent for mitochondrial diseases by screening a chemical library of fibroblasts from patients with mitochondrial diseases. In this study, we showed that apomorphine prevented ferroptosis in fibroblasts from various types of mitochondrial diseases as well as in normal controls. Well-known biomarkers of ferroptosis include protein markers such as prostaglandin endoperoxide synthase 2 (PTGS2), a key gene for ferroptosis-related inflammation PTGS2, lipid peroxidation, and reactive oxygen species. Our findings that apomorphine induced significant downregulation of PTSG2 and suppressed lipid peroxide to the same extent as other inhibitors of ferroptosis also indicate that apomorphine suppresses ferroptosis. To our knowledge, this is the first study to report that the anti-ferroptosis effect of apomorphine is not related to dopamine receptor agonist action and that apomorphine is a potent inhibitor of ferroptotic cell death independent of dopaminergic receptors.

Abstract Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a 7-month-old female patient with severe intellectual disability, epilepsy, and low levels of serum copper and ceruloplasmin. While heterozygous deletion of exons 16 and 17 of the ATP7A gene was detected in the proband, her mother, and her grandmother, only the proband suffered from Menkes disease clinically. Intriguingly, X chromosome inactivation (XCI) analysis demonstrated that the grandmother and the mother showed skewing of XCI toward the allele with the ATP7A deletion and that the proband had extremely skewed XCI toward the normal allele, resulting in exclusive expression of the pathogenic ATP7A mRNA transcripts. Expression bias analysis and recombination mapping of the X chromosome by the combination of whole genome and RNA sequencing demonstrated that meiotic recombination occurred at Xp21-p22 and Xq26-q28. Assuming that a genetic factor on the X chromosome enhanced or suppressed XCI of its allele, the factor must be on either of the two distal regions derived from her grandfather. Although we were unable to fully uncover the molecular mechanism, we concluded that unfavorable switching of skewed XCI caused Menkes disease in the proband.

Abstract Background Bivalent COVID-19 vaccines have been implemented worldwide since the booster vaccination campaigns of autumn of 2022, but little is known about their effectiveness. Thus, this study holistically evaluated the effectiveness of bivalent vaccines against infection in older adults in Japan. Methods We adopted the test-negative design using COVID-19 test data of individuals, aged ≥ 65 years, residing in three municipalities in Japan, who underwent tests in medical institutions between October 1 and December 30, 2022. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. Vaccine effectiveness was defined as (1 − odds ratio) × 100%. Results A total of 3,908 positive and 16,090 negative results were included in the analyses. Receiving a bivalent dose in addition to ≥ 2 monovalent doses was 33.6% (95% confidence interval [CI]: 20.8, 44.3%) more effective than receiving no vaccination, and 18.2% (95% CI: 9.4, 26.0%) more effective than receiving ≥ 2 monovalent doses but not receiving a bivalent vaccination. In addition, the effectiveness peaked at 14–20 days after administration and then gradually declined over time. Furthermore, a bivalent booster dose provided 18.6% (95% CI: 9.9, 26.5%) additional protection among those vaccinated with ≥ 2 monovalent doses, in the absence of a previous infection history. However, we did not find sufficient evidence of effectiveness of bivalent vaccines among previously infected older adults. Conclusions Bivalent vaccines are effective against COVID-19 infections among older adults without a history of infection.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric α-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with α-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of α-actinin and enhanced the α-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to α-actinin via its globular ends. The interaction between α-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with α-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

The role of ferroptosis in steatohepatitis development is largely unknown. We investigated (1) whether hepatocyte ferroptosis occurs in a gene-modified steatohepatitis model without modifying dietary components, (2) whether ferroptosis occurs at an early stage of steatohepatitis, and (3) whether apomorphine, recently reported as a ferroptosis inhibitor, can ameliorate steatohepatitis. Hepatocyte-specific PTEN KO mice were used. Huh 7 and primary cultured hepatocytes isolated from the mice were used in this study. The number of dead cells increased in 10-week-old PTEN KO mice. This cell death was suppressed by the administration of ferroptosis inhibitor ferrostatin-1 for 2 weeks. Apomorphine also ameliorated the severity of steatohepatitis. Treatment with ferroptosis inhibitors, including apomorphine, decreases the level of lipid peroxidase. Apomorphine suppressed cell death induced by RSL-3 (a ferroptosis inducer), which was not suppressed by apoptosis or necroptosis inhibitors. Apomorphine showed a radical trapping capacity with much more potent activity than ferrostatin-1 and Trolox, a soluble form of vitamin E. In addition, apomorphine activated nrf2 and its downstream genes, including HO-1 and xCT. In conclusion, ferroptosis occurs in steatohepatitis from an early stage in PTEN KO mice. In addition, apomorphine ameliorates the severity of steatohepatitis by inhibiting ferroptosis.

Eating out of home (EOH), with its diverse food options, can benefit those with difficulty preparing their meals, especially older adults. Oral health status may be a determinant of EOH, as food accessibility is influenced by oral health, but this association remains unclear. This cross-sectional study used merged data from two national statistical surveys conducted in 2019. Participants were individuals aged ≥ 65 years who responded to both surveys. The frequency of EOH (