Although balanced chromosomal translocations in humans are generally regarded as clinically benign, some male carriers exhibit infertility, such as azoospermia or oligozoospermia. Previous studies using mouse models have suggested that impaired sex chromosome inactivation during meiotic prophase I may contribute to infertility, but the precise mechanisms underlying variable fertility outcomes among male carriers remain unclear. In this study, we investigated male meiosis in the T6/T6 strain, a model carrying a homozygous reciprocal translocation. T6/wt males exhibited variable fertility—ranging from semi-fertile to sterile—depending on the genetic background of their mating partners. Analysis of pachytene spermatocyte spreads revealed defective synapsis of the translocation chromosomes, which frequently co-localized with the XY body. Aberrant RNA polymerase II immunofluorescence signals were observed around both the sex chromosomes and the quadrivalents, indicating failure of meiotic sex chromosome inactivation (MSCI), further supported by elongated sex chromosome morphology suggestive of heterochromatin decondensation. Notably, phase separation of the XY body appeared disrupted, likely due to the close contact with negatively charged transcripts derived from translocation chromosomes. The degree of MSCI impairment and XY body disorganization correlated with the severity of reproductive defects. These findings indicate that variable fertility among male reciprocal translocation carriers may result from differences in the degree of sex chromosome-specific phase separation during spermatogenesis, which can be perturbed by transcriptional activity from translocation chromosomes.
With recent advances in chemotherapy for unresectable pancreatic ductal adenocarcinoma (PDAC) with liver metastasis (LM), attempts have been made to resect the primary tumor in patients showing favorable responses to anti-cancer treatment (so-called “conversion surgery”; CS). This study aimed to clarify the outcomes of CS for PDAC with LM in a nationwide multicenter study. This retrospective, multicenter study was conducted as a project study of the Japan Pancreas Society and included patients with PDAC with LM at initial diagnosis, diagnosed radiologically or intraoperatively (occult LM), who underwent CS after at least 4 months of chemotherapy between 2010 and 2022. Survival outcomes and prognostic factors were analyzed. 90 patients were enrolled from 31 Japanese institutions. Median duration of preoperative chemotherapy was 10.4 (range, 4.2–58.5) months, and gemcitabine plus nab-paclitaxel was the most common first-line regimen, followed by folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin. Liver metastasectomy was performed in 27 patients (30
Postoperative cerebrospinal fluid (CSF) leakage and sphenoid sinusitis remain major concerns after endoscopic endonasal approaches (EEAs) for midline skull base tumors. To our knowledge, this study is among the first to directly compare synthetic polyurethane foam (SPF) with balloon catheters (BCs) for sphenoid sinus packing, assessing efficacy and safety, including in high‑flow CSF leaks. This retrospective, single-center, observational study included 116 patients who underwent EEAs between April 2016 and March 2025. Since May 2021, SPF has replaced BCs for sphenoid sinus packing. Propensity score matching (PSM) generated 43 matched pairs based on age, body mass index, and intraoperative CSF leak grade (Esposito classification). Outcomes were postoperative CSF leakage and magnetic resonance imaging-detected sphenoid mucosal changes. Among 116 patients (median age, 50 years), 57 received SPF and 59 BCs. Postoperative CSF rhinorrhea occurred in 10 patients (8.6
This systematic review and meta-analysis aimed to investigate the efficacy and safety of adding nuclear factor erythroid 2-related factor 2 (Nrf2) activators to antipsychotic treatments for individuals with schizophrenia. The primary outcome was overall symptom improvement. Other efficacy outcomes involve the improvement of positive symptoms, negative and depressive symptoms, Positive and Negative Syndrome Scale general subscale (PANSS-G) scores, and cognitive function composite scores and individual cognitive domain scores (only for sulforaphane). Further, we included all-cause discontinuation, adverse event-related discontinuation, incidence of individual adverse events, and changes in blood inflammatory biomarkers, lipid profiles, and glucose levels. Our review included 16 randomized-controlled trials (n = 953, mean age = 35.27 years; 66.74
Precise navigation of a guidewire tip to a target within the three-dimensional (3D) structure of a coronary artery—controlled from 140 cm away—requires “3D wiring,” a technique involving wire manipulation based on 3D imaging. Hypothesizing that 3D wiring enables the standardization of wiring techniques for chronic total occlusion (CTO) intervention, we have established a 3D wiring method utilizing fluoroscopy and intravascular ultrasound (IVUS). As a first step to visualize guidewire movement within CTO lesions, we collaborated with Terumo Corporation to develop the Navifocus WR in 2012, a CTO-specific IVUS featuring a small diameter and a short tip. Observing guidewire movement during CTO PCI using this IVUS provided the insights necessary to understand how the shaft and tip must be visualized to facilitate effective 3D wiring. We first established angiography-guided 3D wiring using “3D imaging rules” in 2014. Subsequently, to achieve real-time IVUS-guided 3D wiring, we devised the tip detection (TD) method in 2017 and developed the AnteOwl WR IVUS (Terumo Corporation)—a short-tip, pullback-compatible catheter—in 2019, establishing a strategic approach for TD-intra-plaque tracking. Contrary to the traditional view that IVUS guidance is limited to intra-plaque tracking, our 2021 findings show that re-entry is routinely feasible through TD-guided perpendicular puncture (TD-ADR: Antegrade Dissection and Re-entry). This evolution elevated the TD method into a more robust technique for wire crossing. This review aims to systematically organize the theory of 3D wiring and disseminate this knowledge to the global community.
