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In this work we investigate the two-neutron decay of 13Li and of the excited states of 11Li populated via one-proton removal from 14Be and 12Be, respectively. A phenomenological model is used to describe the decay of 11Li and 13Li. While the first one displays important sequential components, the second one appears dominated by the direct two-neutron decay. A microscopic three-body model is used to extract information on the spatial configuration of the emitted neutrons before the decay and shows that the average distance between the neutrons increases going from 11Li to 13Li.

Silicon, traditionally known as an indirect band gap semiconductor, unveils intriguing properties at the nanoscale, stemming from deviations from k-conservation rules within nanostructures. In our study, we scrutinized four hydrogenated Si 0D-nanostructures—Si10H16, Si14H20, Si18H24, and Si22H28—to unravel their dynamic stability under thermal fluctuations and optical characteristics. We initiated our exploration by employing the TD-DFT framework to generate and analyze the optical properties of these geometrically optimized nanostructures. Simultaneously, we conducted ab initio molecular dynamics simulations to examine the structural robustness and thermal stability of the four structures. Leveraging the Car-Parrinello molecular dynamics approach within the Quantum ESPRESSO open software suite, we observed temperature evolution and stability differences among the nanostructures at targeted temperatures 40 and 300 K. Our subsequent investigation delved into the Turbo-Lanczos time-dependent DFT method, unraveling the optical properties and excited-state dynamics of hydrogenated Si nanostructures. The results unveiled shifts towards higher energy absorption edges E0, accompanied by alterations in the permittivity tensor, complex refractive index, oscillator strength, and reflectivity. Notably, the analysis revealed an enlarged HOMO-LUMO gap, distinctive from bulk Si. Furthermore, our models predicted the elimination of phase-dependent E1/E2 optical transition peaks in the imaginary part of the dielectric function, and a gradual decrease in the low-frequency dielectric response with increased hydrogenation of the amorphous structures. These findings underscore the promising applications of hydrogenating Si nanostructures in diverse technological domains such as optoelectronics, memristors, sensors, and quantum computing. Their tunable optical properties, size-dependent behaviors, and compatibility with existing silicon-based devices make them particularly appealing for next-generation technologies.

Detailed γ-ray spectroscopy of the exotic neon isotope 28Ne has been performed for the first time using the one-neutron removal reaction from 29Ne on a liquid hydrogen target at 240 MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for 28Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder p-wave strength providing evidence of the breakdown of the N=20 and N=28 shell gaps. Only a weak, possible f-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large p-wave and small f-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain.

The dineutron correlation is systematically studied in three different Borromean nuclei near the neutron dripline, 11Li, 14Be and 17B, via the (p,pn) knockout reaction measured at the RIBF facility in RIKEN. For the three nuclei, the correlation angle between the valence neutrons is found to be largest in the same range of intrinsic momenta, which can be associated to the nuclear surface. This result reinforces the prediction that the formation of the dineutron is universal in environments with low neutron density, such as the surface of neutron-rich Borromean nuclei.

Polystyrene deuteride shell targets with two holes were imploded by the Gekko XII laser and additionally heated by the LFEX laser in a direct fast ignition experiment. In general, when an ultra-intense laser is injected into a blow-off plasma created by the imploding laser, electrons are generated far from the target core and the energies of electrons increase because the electron acceleration distance has been extended. The blow-off plasma moves not only to the vertical direction but to the lateral direction against the target surface. In a shell target with holes, a lower effective electron temperature can be realized by reducing the inflow of the implosion plasma onto the LFEX path, and high coupling efficiency can be expected. The energies of hot electrons and ions absorbed into the target core were calculated from the energy spectra using three electron energy spectrometers and a neutron time-of-flight measurement system, Mandala. The ions have a large contribution of 74% (electron heating of 4.9 J and ion heating of 14.1 J) to target heating in direct fast ignition.

We report a case of superior trunk brachial plexus injury following a right mini-thoracotomy mitral valve repair. A 45-year-old woman with systemic lupus erythematosus, who was on steroids and immunosuppressive drugs, underwent mitral valve repair via right mini-thoracotomy. The patient was positioned in the left semisagital position with the right upper arm elevated. Postoperatively, she exhibited focal motor and sensory deficits in the right upper extremity, and a superior trunk brachial plexus injury (BPI) on the right side was diagnosed through brachial plexus MRI and electrophysiological examination. The nerve injury was likely due to excessive left lateral flexion of the head during the procedure. Sensation returned to normal 4 weeks postoperatively, and muscle strength fully recovered 3 months postoperatively. Careful attention to positioning during minimally invasive cardiac surgery is crucial to prevent nerve compression in superficial areas and excessive lateral flexion of the head., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Clear cell sarcoma (CCS) and alveolar soft part sarcoma (ASPS) are rare, and standard systemic therapy is not established except for sunitinib in ASPS. It is known that CCS and ASPS have a common biological feature of melanoma and Xp11.2/TFE3 translocation renal cell carcinoma, and immune-checkpoint inhibitors (ICIs) are effective in these tumors. The authors conducted a phase 2 trial to evaluate the efficacy and safety of nivolumab for CCS and ASPS., Methods: The number of patients expected to be enrolled was 15-25 and was determined based on the Bayesian design. The primary end point was the confirmed objective response rate (ORR) according to the central review and the secondary end points included ORR, progression-free survival (PFS), overall survival (OS), and safety., Results: A total of 26 patients (CCS, 12; ASPS, 14) were enrolled. Efficacy and safety were analyzed on 25 and 26 patients, respectively. The minimum number of responses required for a positive conclusion regarding the efficacy was four. However, only one patient (4.0%) with ASPS had a partial response. Complete response, stable disease, progression disease, and not evaluable were 0%, 60%, 32%, and 4.0%, respectively. Adverse events of grade 3 or 4 occurred in 57.7% (15 of 26). The median PFS was 4.9 months (95% confidence interval [CI], 3.7-8.6 months) and the median OS was 15.8 months (95% CI, 8.2-not reached)., Conclusions: The primary end point of the ORR was not met for CCS and ASPS on the central review. Further studies are needed to evaluate ICIs in patients with ASPS., (© 2024 American Cancer Society.)

Background: We report a case of zone II penetrating neck trauma with active bleeding in which endovascular treatment was performed prior to neck exploration to identify and control the bleeding point., Case Presentation: A man in his 50s presented to our emergency department in hemorrhagic shock stemming from a penetrating knife wound injury to the right side of his neck. He was bleeding massively from the right neck wound and oral cavity. Cervical angiography showed bleeding from the right external carotid artery and intimal injury to the right internal carotid artery. Balloon occlusion at the common carotid artery origin and distal to the injured internal carotid artery controlled active bleeding. During vascular balloon occlusion, definitive hemostatic treatment was achieved through ligation of the proximal external carotid artery., Conclusion: Neck exploration combined with endovascular treatment may be one option as a treatment strategy for patients with zone II penetrating neck injury., Competing Interests: Dr. Jun Oda is the Editor‐in‐Chief of the journal and the co‐author of this article. They were excluded from the peer‐review process and all editorial decisions related to the acceptance and publication of this article. Peer review was handled independently by AMS Journal editorial office and Dr. Kuwagata as the Editor to minimize bias., (© 2024 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Functional maturation of the visual cortex is induced by visual experiences during critical periods. Blind animals and humans exhibit improved auditory abilities after losing their vision. Here we investigated the response of the visual cortex to white noise stimuli during the progression of photoreceptor degeneration in a rat model of blindness (Royal College of Surgeons [RCS] (rdy/rdy) rats). Optical coherence tomography of RCS (+/+) rats with normal visual function revealed normal photoreceptor cells, whereas 3-month-old RCS (rdy/rdy) rats demonstrated photoreceptor cell degeneration. Visual cortex responses (VCRs) to a single flash stimulus were negligible in 3-month-old photoreceptor-degenerated rats. However, VCRs with white noise stimuli were significantly increased in blind versus RCS rats (+/+). Slight changes in the intrinsic optical signals of the control rats were observed on the ventral side of the visual cortex. In contrast, responses were markedly increased throughout the visual cortex of RCS (rdy/rdy) rats. These results indicate that the visual cortex rapidly acquires auditory system function over the first 3 months of life and that the entire visual cortex, rather than just the portion close to the auditory cortex, responds to white noise., (© 2024. The Author(s).)

The optimal timing of surgery and the number of courses of perioperative chemotherapy for high-risk soft tissue sarcoma patients are still controversial. Tumour growth during neoadjuvant chemotherapy led to limb amputation in some patients. This study aims to confirm the non-inferiority of surgery and three courses of adjuvant chemotherapy with adriamycin (30 mg/m2, days 1 and 2) plus ifosfamide (2 g/m2, days 1-5) compared with our standard treatment of three courses of neoadjuvant chemotherapy and surgery followed by two courses of adjuvant chemotherapy with adriamycin plus ifosfamide for localized high-risk soft tissue sarcoma patients. This is a multi-center, two-arm, open-label, randomized phase III trial. The primary aim is to confirm the non-inferiority in overall survival (margin: hazard ratio of 1.61). This is the first randomized controlled trial to compare neoadjuvant chemotherapy and immediate surgery for soft tissue sarcoma. This trial was initiated on 16 November 2022 and registered with the Japan Clinical Trials Registry (jRCTs031220446)., (© The Author(s) 2024. Published by Oxford University Press.)

Background/aim: Despite the well-publicized clinical outcomes after unplanned excision (UE) and re-excision (re-excision) in patients with soft-tissue sarcoma (STS), there is little information about the real-life referral patterns for UE, such as patient profile, details of procedures, and subsequent management after UE. We aimed to investigate the characteristics of patients with UE who were referred to sarcoma-specific centers., Patients and Methods: Between May 2022 and June 2023, we registered 97 patients who underwent UE and were referred to sarcoma-specific centers in Japan. We excluded those with well-differentiated liposarcomas and dermatofibrosarcoma protuberances. We investigated the details of UE and additional treatment after UE., Results: There were 49 men and 48 women, with a mean age of 62 years. A broad range of surgeons performed UE; 36 plastic surgeons, 22 orthopedic surgeons, 17 general surgeons, 17 dermatologists, and 5 others. The mean tumor size was 4.1 cm. Local anesthesia was administered to 58 patients. Forty-five patients underwent UE without prior magnetic resonance imaging. Inappropriate transverse skin incisions were performed in 42 patients. Of the 97 patients, 82 underwent re-excision after UE. The mean time between UE and date of initial presentation at the referral hospital was 46 days. The mean interval between UE and re-excision was 96 days. Of the 82 patients, 59 underwent soft-tissue reconstruction after re-excision., Conclusion: A broad range of surgeons performed UE. Continuous education about STS should be considered for all surgeons. UE should be avoided because residual tumors are common, and reconstructive surgery may be necessary., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug-resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell-derived extracellular vesicles identified 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO-1 were identified on extracellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma-derived extracellular vesicles but also Ewing sarcoma cells demonstrated proteomic expression of CD99 and ENO-1 on their surface membranes. ENO-1 + CD63 + extracellular vesicle detection was reduced after tumor resection while both CD99 + CD63 + and ENO-1 + CD63 + extracellular vesicles were detected in serum from Ewing sarcoma-bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO-1 + CD81 + extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P < 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO-1 + CD81 + extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Primary malignant bone tumors, such as osteosarcoma, significantly affect the pediatric and young adult populations, necessitating early diagnosis for effective treatment. This study developed a high-performance artificial intelligence (AI) model to detect osteosarcoma from X-ray images using highly accurate annotated data to improve diagnostic accuracy at initial consultations. Traditional models trained on unannotated data have shown limited success, with sensitivities of approximately 60%-70%. In contrast, our model used a data-centric approach with annotations from an experienced oncologist, achieving a sensitivity of 95.52%, specificity of 96.21%, and an area under the curve of 0.989. The model was trained using 468 X-ray images from 31 osteosarcoma cases and 378 normal knee images with a strategy to maximize diversity in the training and validation sets. It was evaluated using an independent dataset of 268 osteosarcoma and 554 normal knee images to ensure generalizability. By applying the U-net architecture and advanced image processing techniques such as renormalization and affine transformations, our AI model outperforms existing models, reducing missed diagnoses and enhancing patient outcomes by facilitating earlier treatment. This study highlights the importance of high-quality training data and advocates a shift towards data-centric AI development in medical imaging. These insights can be extended to other rare cancers and diseases, underscoring the potential of AI in transforming diagnostic processes in oncology. The integration of this AI model into clinical workflows could support physicians in early osteosarcoma detection, thereby improving diagnostic accuracy and patient care., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The frequency of behavioral and psychological symptoms of dementia (BPSD) is high, and it is a challenge to elucidate its neural substrates underlying their development. In recent years, many findings have been reported on the relationship between BPSD and brain volume in dementia patients. However, the results are not fully conclusive. Furthermore, there have been few population-based studies. Therefore, the relationship between BPSD and brain volume was investigated as an exploratory study. Of the 927 older persons who participated in the fifth Nakayama study, 90 were included in this analysis, consisting of 52 patients with mild cognitive impairment and 38 patients with dementia, with head MRI and the Neuropsychiatric Inventory (NPI) data. Multiple regression analysis was used to examine the association between the total score of each BPSD score on the NPI and brain volume estimated by FreeSurfer. On multivariate adjustment, even after false discovery rate correction, insular cortical volumes decreased significantly as total scores for apathy/indifference increased (p value = 0.002, q-value = 0.01). Similarly, total brain volume decreased significantly as total scores for appetite and eating disturbance increased (p value = 0.03), and parietal, temporal, and hippocampal cortical volumes also decreased significantly as total scores for appetite and eating disturbance increased (all p and q values < 0.05). This study's results suggest that apathy is negatively correlated with insular cortical volume, and that appetite and eating disturbance are also correlated with brain regions, including parietal, temporal, and hippocampal volume in a community-dwelling older population., (© 2024. The Author(s).)

Presented herein is a synthetic biological method using genome mining and heterologous expression systems that provides access to natural products with desirable structural features as building blocks. In this investigation, we synthesized polyketide-peptide hybrid macrocycles with DNA tags, which have the potential to access a DNA-encoded library containing over one million compounds. This study demonstrates that synthetic biology offers a tool for expanding the diversity of building blocks, facilitating the exploration of unexplored chemical space.

Fungal biosynthetic gene clusters often include genes encoding transmembrane proteins, which have been mostly thought to be transporters exporting the products. However, there is little knowledge about subcellular compartmentalization of transmembrane proteins essential for biosynthesis. Fungal mycotoxin cyclochlorotine is synthesized by non-ribosomal peptide synthetase, which is followed by modifications with three transmembrane UstYa-family proteins. Heterologous expression in Aspergillus oryzae revealed that total biosynthesis of cyclochlorotine requires additional two transporter proteins. Here, we investigated subcellular localizations of the five transmembrane proteins under heterologous expression in A. oryzae. Enhanced green fluorescent protein (EGFP) fusions to the transmembrane proteins, which were confirmed to normally function in cyclochlorotine production, were expressed together with organellar markers. All the transmembrane proteins exhibited localizations commonly in line of the trans-Golgi, endosomes, and vacuoles. This study suggests that subcellular compartmentalization of UstYa family proteins and transporters allows corporative functions of delivering intermediates and subsequent modifications, completing cyclochlorotine biosynthesis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Phenazine natural products play various roles such as signal molecules, antibiotics, or electron carriers in their producer strains. Among these products, phenazinomycin and lavanducyanin, which are produced by Streptomyces species, are characterized by an N-alkyl modification. Herein, we established the biosynthetic pathways for these two phenazine natural products. Gene-disruption experiments and in vitro reconstitution of the phenazine-tailoring pathway revealed the late steps of the biosynthetic pathway of the phenazines. The class II terpene cyclase homolog Pzm1 catalyzes the cyclization reaction of farnesyl diphosphate to form monocyclic farnesyl diphosphate. Additionally, the prenyltransferase homolog PzmP functions as the N-prenyltransferase of 5,10-dihydrophenazine-1-carboxylic acid. The flavin monooxygenase homolog PzmS catalyzes the oxidative decarboxylation of prenylated 5,10-dihydrophenazine-1-carboxylic acid to yield phenazinomycin. This study highlights unprecedented modification enzymes for phenazine natural products., (© 2024 The Author(s). ChemBioChem published by Wiley-VCH GmbH.)

Hemophilia B is a quantitative or qualitative factor IX anomaly that manifests as an X-linked recessive inheritance pattern in which females are carriers. Postoperative epidural hematoma emerges as a typical complication in spinal surgery, although its incidence is infrequent. No documentation of postoperative epidural hematoma in carriers of hemophilia B exists. A 64-year-old female patient presented with progressive pain and muscle weakness in both lower limbs. Despite a history of childbirth and prior colorectal cancer surgery, the patient displayed no abnormal bleeding tendencies. Subsequently undergoing decompression surgery for lumbar spinal canal stenosis, the patient experienced paralysis and pain in both legs within 5 hours postoperatively. A magnetic resonance imaging scan revealed severe spinal canal compression attributed to a postoperative epidural hematoma, prompting emergency decompression surgery that ameliorated symptoms. The application of gelatin-thrombin matrix sealants (GTMS) facilitated hematoma removal, resulting in an uneventful recovery. In a postoperative interview, it was revealed that her grandson was undergoing treatment for hemophilia B. Additionally, she exhibited diminished factor IX levels and was diagnosed as a hemophilia B carrier. A definitive preoperative diagnosis of the carrier status is imperative. In instances where surgical intervention is warranted, the implementation of factor IX replacement and intraoperative hemostasis with GTMS is promising for potentially averting the onset of postoperative epidural hematoma., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: Few previous studies evaluated the impact of time from the hospital arrival to the implementation of extracorporeal cardiopulmonary resuscitation (ECPR) (door to ECPR time) on outcomes among out-of-hospital cardiac arrest (OHCA) acute myocardial infarction (MI) patients., Methods: 50 patients with OHCA who received both ECPR and percutaneous coronary intervention (PCI) at Cardiovascular Division, NHO Osaka National Hospital were analyzed. Patients were divided into 2 groups according to the median of door to ECPR time. The primary outcome was all-cause death. Survival analyses were conducted to compare all-cause mortality at 90 days between 2 groups. Neurological outcome at 30 days was also compared between 2 groups using the Cerebral Performance Category (CPC)., Results: The multivariable Cox proportional-hazards model showed that all-cause mortality at 90 days was significantly higher among patients with door to ECPR time ≥ 25 min compared with those with door to ECPR time < 25 min (adjusted hazard ratio [HR]: 3.14; 95 % confidence interval [CI]: 1.21-8.18). The proportion of patients with CPC at 30 days ≤ 2 was significantly higher among patients with shorter door to ECPR time ( P  = 0.048)., Conclusion: Among patients with OHCA due to acute MI who received ECPR and PCI, the shorter door to ECPR time was associated with the lower mortality and favorable neurological outcomes., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yasunori Ueda reports a relationship with 10.13039/100001316Abbott, 10.13039/501100002973Daiichi-Sankyo, Teijin, Japan Lifeline, OrbusNeich, Janssen, Otsuka, Ono, Eli Lilly, Astellas, 10.13039/100002429Amgen, 10.13039/100001003Boehringer Ingelheim, and 10.13039/100004336Novartis that includes: funding grants. Yasunori Ueda reports a relationship with Abbott, Kowa, Bayer, Daiichi-Sankyo, Nipro, Takeda, AstraZeneca, Japan Lifeline, Novartis, Ono, Boehringer Ingelheim, and Amgen that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: This study aimed to classify medullary bridging vein-draining dural arteriovenous fistulas (MBV-DAVFs) located around the foramen magnum (FM) according to their location and characterize their angioarchitecture and treatment outcomes., Methods: Patients with MBV-DAVFs diagnosed between January 2013 and October 2022 were included. MBV-DAVFs were classified into four groups. Jugular vein-bridging vein (JV-BV) DAVF: located in proximity to jugular fossa, Anterior condylar vein (ACV)-BV DAVF: proximity to anterior condylar canal, Marginal sinus (MS)-BV DAVF: lateral surface of FM and Suboccipital cavernous sinus (SCS)-BV DAVF: proximity to dural penetration of vertebral artery., Results: Twenty patients were included, three JV-BV, four ACV-BV, three MS-BV and ten SCS-BV DAVFs, respectively. All groups showed male predominance. There were significant differences in main feeders between JV (jugular branch of ascending pharyngeal artery) and SCS group (C1 dural branch). Pial feeders from anterior spinal artery (ASA) or lateral spinal artery (LSA) were visualized in four SCS and one MS group. Drainage pattern did not differ between groups. Transarterial embolization (TAE) was performed in three, two, one and two cases and complete obliteration was obtained in 100%, 50%, 100% and 0% in JV, ACS, MS and SCS group, respectively. Successful interventions without major complications were finally obtained in 100%, 75%, 100%, and 40% in JV, ACS, MS and SCS group, respectively., Conclusion: JV-BV DAVFs were successfully treated using TAE alone. SCS-BV DAVFs were mainly fed by small C1 dural branches of vertebral artery often with pial feeders from ASA or LSA, and difficultly treated by TAE alone., (© 2024. The Author(s).)

Background: In CAPItello-291, capivasertib-fulvestrant significantly improved progression-free survival (PFS) versus placebo-fulvestrant in the overall and PIK3CA/AKT1/PTEN-altered population with hormone receptor-positive (HR-positive)/human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer. Capivasertib-fulvestrant is approved in Japan for the treatment of patients with one or more tumor biomarker alterations (PIK3CA, AKT1 or PTEN). Here, we report outcomes in the CAPItello-291 subgroup of patients from Japan., Methods: Adults with HR-positive/HER2-negative advanced breast cancer whose disease had relapsed or progressed during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy, were randomly assigned (1:1 ratio) to receive capivasertib or placebo, plus fulvestrant. The dual primary endpoint was investigator-assessed PFS in the overall and PIK3CA/AKT1/PTEN-altered population. Safety was a secondary endpoint., Results: Of 708 patients randomized in CAPItello-291, 78 were from Japan (37 randomized to capivasertib-fulvestrant and 41 to placebo-fulvestrant). In the Japan subgroup, PFS numerically favored the capivasertib-fulvestrant arm (hazard ratio 0.73; 95% CI 0.40-1.28), consistent with the analysis of PFS in the global population. Similarly, in the Japan subgroup of patients with PIK3CA/AKT1/PTEN-altered tumors, PFS favored the capivasertib-fulvestrant arm (hazard ratio 0.65; 95% CI 0.29-1.39), consistent with the global population. The adverse event profile of capivasertib-fulvestrant in the Japan subgroup was broadly similar to that in the global population; no new safety concerns were identified., Conclusion: Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib-fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen., (© 2024. The Author(s).)

Research on postural control in patients with adolescent idiopathic scoliosis (AIS) has focused on static postural control, with few studies assessing dynamic postural control. We aimed to identify factors affecting index of postural stability (IPS), a dynamic postural control parameter, in patients with AIS. The participants comprised 50 female patients with AIS. We measured the IPS using stabilometry to evaluate dynamic postural control ability. We investigated age of the participants, major curve position (thoracic or thoracolumbar/lumbar), Cobb angle, and coronal balance. We then assessed the relationships between stabilometry parameters and other variables. IPS was analyzed with a linear regression model. Coronal balance, major curve position, and age each correlated with dynamic postural control ability. The Cobb angle showed no correlation with any of the parameters. Our results offer new insights into the assessment of postural control in patients with AIS., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Aortic wrapping (AW) has been performed as a less invasive alternative to aortoplasty. However, AW can also cause long-term aortic complications. In this report, we present a rare case of a dissecting aortic aneurysm between the proximal side of the wrap and the sinotubular junction after AW., Case Presentation: A female patient had undergone urgent aortic valve replacement with a 19-mm mechanical valve to treat infective endocarditis and AW to treat an enlarged ascending aorta 26 years prior. At the age of 71 years, the patient was diagnosed with a dissecting aortic aneurysm between the proximal side of the wrap and the sinotubular junction. We performed graft replacement of the ascending aorta, including complete resection of the wrap. The patient was discharged on postoperative day 10, and there have been no cardiovascular events during her ongoing follow up., Conclusions: AW in younger patients can lead to late aortic complications. Careful consideration should be paid when performing AW in young patients, and patients who have previously undergone AW require strict life-long follow-up., (© 2024. The Author(s).)

Benzene is one of the most ubiquitous structural motifs in chemistry. The valence isomers of benzene have also attracted synthetic chemists' attention due to their unique structures, bonding, and reactivity. We have been investigating boron-nitrogen-containing benzene valence isomers via photoisomerization of 1,2-azaborines. In this contribution, we summarize recent developments of these highly strained BN-heterocyclic compounds including their synthesis, characterization, proposed mechanism of formation, and their potential applications., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Iron-based 1111-type superconductors display high critical temperatures and relatively high critical current densities J c . The typical approach to increasing J c is to introduce defects to control dissipative vortex motion. However, when optimized, this approach is theoretically predicted to be limited to achieving a maximum J c of only ∼30% of the depairing current density J d , which depends on the coherence length and the penetration depth. Here we dramatically boost J c in SmFeAsO 1-x H x films using a thermodynamic approach aimed at increasing J d and incorporating vortex pinning centres. Specifically, we reduce the penetration depth, coherence length and critical field anisotropy by increasing the carrier density through high electron doping using H substitution. Remarkably, the quadrupled J d reaches 415 MA cm -2 , a value comparable to cuprates. Finally, by introducing defects using proton irradiation, we obtain high J c values in fields up to 25 T. We apply this method to other iron-based superconductors and achieve a similar enhancement of current densities., (© 2024. The Author(s).)

Objective: To investigate the effect of the use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) on surgical site infection (SSI) and delayed wound healing (DWH) in rheumatoid arthritis (RA) patients undergoing orthopaedic surgery., Patients and Methods: We retrospectively reviewed the records of 965 elective orthopaedic procedures undertaken in RA patients. The incidences of SSI and DWH were compared between the bDMARDs user and non-user groups. Subsequently, univariate and multivariate logistic regression analyses were performed to evaluate risk factors for SSI and DWH after propensity score (PS) matching. The incidence of postoperative flare-up was also examined., Results: In 965 procedures, SSI and DWH were identified in 12 and 28 cases, respectively. SSI and DWH were identified in 3 and 17 of 414 procedures treated with bDMARDs, respectively. Flare-up occurred in 21 cases. PS matching identified 315 cases in both groups, with no significant difference in incidence between the two groups. No risk factors for SSI were identified, whereas age, diabetes mellitus, foot and ankle surgery and a history of musculoskeletal-related infection were identified as risk factors for DWH., Conclusion: The use of bDMARDs was not associated with an increased incidence of SSI or DWH, with the incidence of flare-up being relatively low., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background/objective: The main surgical treatment for medial meniscus posterior root tear (MMPRT) has shifted from meniscectomy to meniscus repair; however, there is no clear consensus regarding the optimal postoperative management strategy after MMPRT repair. This study aimed to perform a comparative analysis of patients who received conventional rehabilitation or fast rehabilitation following MMPRT repair., Methods: The current retrospective cohort study compared clinical, radiological, and arthroscopic outcomes after conventional rehabilitation (group A, January 2020 to April 2020, 24 patients) with those after fast rehabilitation (group B, May 2020 to August 2020, 24 patients) in patients who underwent pullout repair for MMPRT. Partial weight-bearing and range of motion exercises were allowed 2 weeks postoperatively in group A and 1 week postoperatively in group B. In patients with an average weight of approximately 60 kg, full weight bearing was allowed 4 weeks postoperatively in group A and 3 weeks postoperatively in group B., Results: At 12 months postoperatively, the clinical scores, including International Knee Documentation Committee and Japanese Knee Injury and Osteoarthritis Outcome Score, significantly improved in both groups (p < 0.01). Although meniscus healing was achieved in both groups, medial meniscus extrusion significantly progressed by 0.9 mm in group A and 0.8 mm in group B (p < 0.01, compared with preoperative extrusion). There were no significant differences in clinical scores, arthroscopic meniscal healing status, or medial meniscus extrusion progression on magnetic resonance images between the groups., Conclusion: A fast rehabilitation protocol can be safely implemented without compromising patient outcomes after pullout repair for MMPRT., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

The synthesis and crystallographic characterization of BN-benzvalene, the first second-row heteroatom-containing benzvalene, is described. BN-benzvalenes are produced via photoexcitation of C5-aryl-substituted 1,2-azaborines under flow conditions. Mechanistic studies support a boron-specific, two-step photoisomerization pathway involving a BN-Dewar benzene intermediate, which is distinct from the photoisomerization pathway proposed in benzene and phospha- and silabenzenes for the formation of their respective benzvalene analogues.

In aneurysmal subarachnoid hemorrhage, the highest therapeutic priority is to ensure immediate hemostasis without intraprocedural complications. This article outlines the possible intraoperative coil embolization complications for ruptured intracranial aneurysms and discuss strategies for their prevention and treatment.

Objectives: We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis., Methods: Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis., Results: In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59-0.70]; p < 0.001). In multivariable analysis, necrosis 30-50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01-4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04-7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity., Conclusions: The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation., Competing Interests: Declaration of competing interest All authors have no conflicts of interests relevant to this article to disclose., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated. With the deepening of research, circular RNAs (circRNAs) have been found to not only play a significant role in tumor progression and prognosis but also show aberrant expression in various tumor metastases, consequently impacting tumor metastasis through multiple pathways. Therefore, circRNAs are emerging as potential tumor markers and treatment targets. This review summarizes the research progress on elucidating how circRNAs regulate the urological cancer invasion-metastasis cascade response and related processes, as well as their role in immune microenvironment remodeling and circRNA vaccines. This body of work highlights circRNA regulation as an emerging therapeutic target for urological cancers, which should motivate further specific research in this regard., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The second-look arthroscopic score of pullout repair for medial meniscus posterior root tears (MMPRTs) is associated with contemporaneous clinical scores and progression of cartilage damage. However, the relationship among these scores, midterm clinical scores and magnetic resonance imaging (MRI) evaluations is unknown. The relationship between the second-look arthroscopic score at 1 year and the clinical scores or MRI at 3 years was evaluated., Methods: Sixty-three patients were included. Medial meniscus extrusion (MME) was evaluated preoperatively and at 3 years postoperatively. Clinical scores were evaluated preoperatively, and 1 and 3 years postoperatively. Meniscal healing status was assessed using the semiquantitative second-look arthroscopic score at 1 year postoperatively. Correlation coefficients between patient characteristics, postoperative clinical scores or second-look arthroscopic score and the change in MME (ΔMME) were evaluated. Multiple regression analysis was performed on the ΔMME to evaluate the effects of patient characteristics and second-look arthroscopic scores., Results: No significant correlation was observed between patient characteristics and ΔMME. In contrast, a significant correlation was found between the second-look arthroscopic score and ΔMME (p < 0.001) and visual analogue scale pain score (p = 0.016) at 3 years postoperatively. In the subitems of the second-look arthroscopic score, width (p < 0.001) and stability (p = 0.009) scores also showed significant correlations with ΔMME. Multiple regression analysis showed a significant association between the second-look arthroscopic score and ΔMME (p = 0.001)., Conclusions: The second-look arthroscopic score at 1 year postoperatively correlated with the ΔMME and clinical score at 3 years postoperatively. Second-look arthroscopic scores predict midterm meniscal function after pullout repair of MMPRTs., Level of Evidence: Level IV., (© 2024 The Authors. Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Morton neuroma is a common cause of forefoot pain and sensory disturbances, but it is difficult to identify on magnetic resonance imaging (MRI). The aim of this study was to verify the usefulness of a characteristic MRI finding (slug sign) for identifying Morton neuroma and to clarify the relationship between excised neuroma characteristics and preoperative MRI findings., Methods: Twenty-two web spaces were retrospectively assessed from the second and third intermetatarsal spaces of 11 feet of 10 patients (7 women and 3 men, aged average 59.5 years) who underwent surgical excision of Morton neuroma between 2017 and 2022. Asymptomatic web spaces were used as control. Neuromas with 2 branches of the plantar digital nerves on axial T1-weighted MRI (MRI-T1WI) were considered the slug sign. We investigated the preoperative presence of the slug sign in Morton neuroma and asymptomatic control web spaces. We also investigated the relationship between the maximum transverse diameter of the excised specimen and that estimated on coronal MRI-T1WI., Results: A total of 15 Morton neuromas were excised and assessed. The slug signs were present in 10 intermetatarsal spaces in 15 web spaces with Morton neuroma whereas the sign was found in 1 intermetatarsal space in 7 asymptomatic web spaces. The sensitivity and specificity for the slug sign to diagnose Morton neuroma was 66.7% and 85.7%, respectively. The positive and negative predictive values were 90.9% and 54.5%, respectively. The mean maximum transverse diameter of excised neuromas was 4.7 mm. The mean maximum transverse diameter of neuromas on coronal MRI-T1WI was 3.4 mm. A significant positive correlation was found between the maximum transverse diameters of excised specimens and diameters estimated on coronal MRI-T1WI ( r  = 0.799, P  < .001)., Conclusion: The slug sign may be a useful indicator of Morton neuroma on MRI to confirm nerve involvement after bifurcation., Level of Evidence: Level IV, retrospective series., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online., (© The Author(s) 2024.)

The neutron-rich unbound fluorine isotope ^{30}F&#95;{21} has been observed for the first time by measuring its neutron decay at the SAMURAI spectrometer (RIBF, RIKEN) in the quasifree proton knockout reaction of ^{31}Ne nuclei at 235  MeV/nucleon. The mass and thus one-neutron-separation energy of ^{30}F has been determined to be S&#95;{n}=-472±58(stat)±33(sys)  keV from the measurement of its invariant-mass spectrum. The absence of a sharp drop in S&#95;{n}(^{30}F) shows that the "magic" N=20 shell gap is not restored close to ^{28}O, which is in agreement with our shell-model calculations that predict a near degeneracy between the neutron d and fp orbitals, with the 1p&#95;{3/2} and 1p&#95;{1/2} orbitals becoming more bound than the 0f&#95;{7/2} one. This degeneracy and reordering of orbitals has two potential consequences: ^{28}O behaves like a strongly superfluid nucleus with neutron pairs scattering across shells, and both ^{29,31}F appear to be good two-neutron halo-nucleus candidates.

Abnormal α-synuclein (αSyn), including an oligomeric form of αSyn, accumulates and causes neuronal dysfunction in the brains of patients with multiple system atrophy. Neuroprotective drugs that target abnormal αSyn aggregation have not been developed for the treatment of multiple system atrophy. In addition, treating diseases at an early stage is crucial to halting the progress of neuronal damage in neurodegeneration. In this study, using early-stage multiple system atrophy mouse model and in vitro kinetic analysis, we investigated how intranasal and oral administration of trehalose can improve multiple system atrophy pathology and clinical symptoms. The multiple system atrophy model showed memory impairment at least four weeks after αSyn induction. Behavioural and physiological analyses showed that intranasal and oral administration of trehalose reversed memory impairments to near-normal levels. Notably, trehalose treatment reduced the amount of toxic αSyn and increased the aggregated form of αSyn in the multiple system atrophy model brain. In vitro kinetic analysis confirmed that trehalose accelerated the aggregate formation of αSyn. Based on our findings, we propose a novel strategy whereby accelerated αSyn aggregate formation leads to reduced exposure to toxic αSyn oligomers, particularly during the early phase of disease progression., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

There is a lack of data regarding the safety and effectiveness of implanting the Pipeline Embolization Device with Shield technology (PED-Shield) compared with the previous generation of Pipeline (PED-Flex). This retrospective single-center study aimed to compare treatment outcomes between the PED-Shield and PED-Flex for treating unruptured internal carotid artery aneurysms. The PED-Flex was used in 62 procedures (67 aneurysms, 59 patients) and the PED-Shield in 53 procedures (59 aneurysms, 58 patients). The mean aneurysm diameter was significantly lower in the PED-Shield group than in the PED-Flex group (11.9 ± 7.0 mm vs. 15.2 ± 6.9 mm, p < 0.001). At the 12-month follow-up, the complete angiographic occlusion rate was 72.1% and 72.3% in the PED-Flex and PED-Shield groups, respectively (p = 0.9808). Limited to aneurysms larger than 10 mm, 70.6% and 68.0%, respectively (p = 0.8175). The incidence of more than three high signal intensity areas on diffusion-weighted imaging after treatment was significantly lower in the PED-Shield group than in the PED-Flex group (27.7% vs. 67.7%; p < 0.001). Limited to aneurysms larger than 10 mm, 41.1% and 69.6%, respectively (p < 0.0117). Symptomatic ischemic complications occurred within 30 days of four PED-Flex procedures (6.5%) and one PED-Shield procedure (2.0%) (p = 0.2315). Limited to aneurysms larger than 10 mm, 1.8% and 3.2%, respectively (p = 0.6677). The incidence of mRS score worsening at 6 months was 3.2% and 1.9% in the PED-Flex and PED-Shield groups, respectively (p = 0.6534). The PED-Shield can achieve outcomes equivalent to or better than the PED-Flex. Further large-scale studies are warranted to confirm our findings.

Although microglia are macrophages of the central nervous system, their involvement is not limited to immune functions. The roles of microglia during development in humans remain poorly understood due to limited access to fetal tissue. To understand how microglia can impact human neurodevelopment, the methyl-CpG binding protein 2 (MECP2) gene was knocked out in human microglia-like cells (MGLs). Disruption of the MECP2 in MGLs led to transcriptional and functional perturbations, including impaired phagocytosis. The co-culture of healthy MGLs with MECP2-knockout (KO) neurons rescued synaptogenesis defects, suggesting a microglial role in synapse formation. A targeted drug screening identified ADH-503, a CD11b agonist, restored phagocytosis and synapse formation in spheroid-MGL co-cultures, significantly improved disease progression, and increased survival in MeCP2-null mice. These results unveil a MECP2-specific regulation of human microglial phagocytosis and identify a novel therapeutic treatment for MECP2-related conditions., Competing Interests: Declaration of interests A.R.M. is a co-founder and has an equity interest in TISMOO, a company dedicated to genetic analysis and human brain organogenesis focusing on therapeutic applications customized for the disorder autism spectrum and other neurological disorders origin genetics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies. The authors have a patent application in works related to this publication., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We investigated suitable culture conditions for the production of the blue pigment phycocyanin (PC) from the unique filamentous cyanobacteria Pseudanabaena sp. ABRG5-3 and Limnothrix sp. SK1-2-1. White, green, or red LED irradiation at 30 μmol photons/m 2 /s was effective for phycocyanin production when compared with Arthrospira platensis (Spirulina) sp. NIES-39, which is generally grown under high light irradiation. To investigate the safety of the cyanobacteria, ABRG5-3 cells were subjected to Ames (reverse mutation) tests and single oral-dose rat studies, which revealed non-mutagenic and non-toxic properties. When three purified phycocyanins (abPC, skPC, and spPC) were subjected to agarose gel electrophoresis, they showed different mobility, indicating that each phycocyanin has unique properties. abPC exhibited strong antiglycation activities as novel function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Insomnia can coexist with chronic pain and is a major cause of rapidly increasing medical expenses. However, insomnia has not been fully evaluated in patients with chronic pain. This retrospective study aimed to identify the risk factors for insomnia in patients with chronic non-cancer pain. A total of 301 patients with chronic non-cancer pain were enrolled. Patients with the Athens insomnia scale scores ≥ 6 and < 6 were classified into insomnia (+) and insomnia (-) groups, respectively. All patients completed self-report questionnaires as part of their chronic pain treatment approach. Univariate and multivariate analyses were performed to predict insomnia. We found that 219 of 301 (72.8%) patients met the AIS criteria for insomnia. Significant differences were depicted between patients with and without insomnia in terms of body mass index, numeric rating scale, pain catastrophizing scale, hospital anxiety, and depression scale (HADS), pain disability assessment scale, EuroQol 5 dimension (EQ5D), and pain self-efficacy questionnaire. Multiple regression analysis identified the numeric rating scale, HADS, and EQ5D scores as factors related to insomnia in patients with chronic non-cancer pain. Anxiety, depression, and disability were associated with a greater tendency toward insomnia. HADS and EQ5D scores are useful screening tools for preventing insomnia in patients with chronic non-cancer pain., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a widely utilized technique in spine surgery. This study compares the efficacy and safety of MIS-TLIF performed with traditional C-arm fluoroscopy and C-arm-free O-arm navigation. To the best of our knowledge, our study is the first to compare cage positioning between C-arm-free and C-arm techniques for MIS- TLIF., Methods: A retrospective, comparative analysis was conducted on 43 patients undergoing MIS-TLIF. The group was divided based on the utilization of C-arm fluoroscopy or C-arm-free O-arm navigation. Key parameters analyzed included cage orientation, screw insertion accuracy, operative efficiency, and postoperative recovery. Radiographic measurements were used to assess surgical precision and perioperative complications were documented., Results: The study encompassed 43 patients, with no significant differences in demographic characteristics between the two groups. Surgical time and blood loss were comparable between C-arm-free and C-arm groups. O-arm navigation significantly reduced pedicle screw misplacement (p=0.024). Cage positioning differed between groups (p=0.0063): O-arm cages were mostly mid-center, while C-arm cages were more anterior-center. Such differences in the cage location did not cause any impact on clinical outcome. No significant differences were observed in postoperative complications (screw loosenings, dural tears, surgical site infections) between groups. The Oswestry Disability Index scores at the final follow-up showed no significant difference between the O-arm and C-arm groups, indicating similar levels of postoperative disability., Conclusion: Despite the clinically insignificant difference in cage placement between C-arm-free and C-arm dependent, C-arm-free MIS-TLIF significantly improves screw placement accuracy and reduces radiation exposure to operating stuff. This suggests its potential as a valuable tool for safer and more precise spinal fusion surgery., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Uotani et al.)

Purpose: This study aimed to evaluate the association between the progression of medial joint space (MJS) narrowing, medial meniscus extrusion (MME) and clinical scores and the tibial tunnel position in pullout repairs for medial meniscus posterior root tears (MMPRTs)., Methods: This retrospective study examined 54 patients. Changes in MJS (ΔMJS), MME (ΔMME) and clinical scores and their relationship with the tibial tunnel position were evaluated using correlation coefficients. The distance from the anatomical to technical attachment position in the tibial tunnel position was measured in the anterior and medial directions, and the direct distance was measured using the Pythagorean theorem., Results: The mean ΔMJS and ΔMME were 0.6 ± 0.8 and 1.3 ± 1.3 mm, respectively, and the mean anterior, medial and direct distances were 1.4 ± 2.3, 2.2 ± 1.7 and 3.4 ± 1.7 mm, respectively. ΔMJS had a significant positive correlation with the medial (r = 0.580, p < 0.001) and direct (r = 0.559, p < 0.001) distances, while ΔMME had a significant positive correlation with direct distance (r = 0.295, p = 0.030). Several clinical scores were significantly negatively correlated with these distances., Conclusion: In transtibial pullout repair for MMPRTs, accurate tibial tunnel position delayed the progression of MJS narrowing and MME, leading to improved clinical outcomes. The progression of MJS narrowing was associated with the mediolateral direction of the tibial tunnel position, while the clinical scores were associated with the anteroposterior direction of the tibial tunnel position. These findings indicate the need to orient the tip of the guide in a more posterolateral direction when creating the tibial tunnel., Level of Evidence: Level IV., (© 2024 The Authors. Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)