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Akinori Kanzaki,1,2 Kiyoshi Matsui,3 Tadahiko Sukenaga,1,2 Koushi Mase,1 Aya Nishioka,1 Tomoharu Tamori,4 Seiko Kataoka,1 Hiroyuki Konya,1 Shin Mizutani,4 Akira Takeda,1 Masato Koseki,1 Tetsuo Nishiura,1 Hidenori Koyama,2 Hajime Sano3 1Department of Internal Medicine, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan; 2Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; 3Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; 4Department of Surgery, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan Abstract: Polymyalgia rheumatica (PMR) is a disease commonly seen in elderly individuals, however, the etiology has not been reported. Typical clinical features include bilateral shoulder pain and morning stiffness, while serologic autoantibody test findings are negative. Approximately 40%–50% of affected patients present with low-grade fever, fatigue, and appetite loss, which we often experience in the field of general medicine, and thus, the condition should not be given low priority. However, knowledge regarding such constitutional manifestations is also limited. We encountered an elderly woman with a fever of unknown origin that developed following a parathyroidectomy for a single parathyroid adenoma, after which severe shoulder pain and morning stiffness emerged, leading to a diagnosis of PMR. The fever developed several days prior to appearance of severe pain, which is an uncommon presentation in PMR cases. Our patient had low-grade inflammation without pyrexia prior to the surgery, which might have been an important reason for the accelerated immoderate immune activation leading to PMR induced by surgery in this case. Furthermore, she was infected with the influenza A virus 3 weeks before coming to us. Some reports have suggested a relationship between the influenza virus or vaccine and PMR. It is difficult to conclude regarding the definite trigger in our patient, though the details of this case should be helpful for a better understanding of the disease. Keywords: polymyalgia rheumatica, fever of unknown origin, immoderate immune activation, parathyroidectomy, influenza A viral infection, single parathyroid adenoma

Abstract Background The interplay between cardiac and kidney functions is mediated by the autonomic nervous system. Cardiovascular autonomic neuropathy (CAN) is a well-documented dysfunction of this system, with heart rate variability (HRV) serving as the principal diagnostic tool. CAN is recognized as a prognostic marker for adverse kidney outcomes in diabetic kidney disease (DKD). However, the pathogenesis of CAN in patients with nondiabetic chronic kidney disease (CKD) remains underexplored. This study elucidated the prevalence of CAN and its clinicopathologic characteristics in patients with nondiabetic CKD. Methods This cross-sectional analysis evaluated 165 nondiabetic CKD patients who underwent kidney biopsy from 2020 to 2023. HRV was quantified using the coefficient of variation of the RR interval (CVRR). CAN was diagnosed based on the CVRR and defined using the CVRR reference value—derived by defining the age and sex-dependent lower normal limits as the 2.5 percentile point of the distribution of the CVRR values in healthy individuals. Results The median patient age was 47.0 (34.0–57.0) years, and 50.9% were male. The median estimated glomerular filtration rate was 65.0 (42.0–85.0) mL/min/1.73m2, and the CVRR was 3.5 (2.4–4.7)% and 16 patients (9.7%) were diagnosed with CAN. CAN was frequently associated with kidney dysfunction, dyslipidemia, and advanced interstitial fibrosis/tubular atrophy (IF/TA). Multivariable analysis revealed that IF/TA was associated with CVRR, independent of established risk factors for CAN (P = 0.045). Conclusions The prevalence of CAN diagnosed using the CVRR in this nondiabetic CKD cohort was 9.7%, which is four times higher than that in healthy individuals. Nondiabetic CKD patients with CAN was associated with advanced IF/TA.

Based on molecular markers, mating experiments, morphological observations and ecological data, two Pristionchus species (Nematoda: Diplogastridae) new to science are described. Both were collected from different Scarabaeoid beetles in South Korea, have a gonochoristic mode of reproduction and fall into a sub-clade of the pacificus clade. Pristionchus coreanus n. sp. does not show a eurystomatous morph under laboratory conditions and might therefore be suitable for the study of gain and loss of polymorphism. Pristionchus hangukensis n. sp. is phylogenetically close to Chinese and Japanese species and helps to separate an Asian clade from an American clade.

Abstract Odours used by insects for foraging and mating are carried by the air. Insects induce airflows around them by flapping their wings, and the distribution of these airflows may strongly influence odour source localisation. The flightless silkworm moth, Bombyx mori, has been a prominent insect model for olfactory research. However, although there have been numerous studies on antenna morphology and its fluid dynamics, neurophysiology, and localisation algorithms, the airflow manipulation of the B. mori by fanning has not been thoroughly investigated. In this study, we performed computational fluid dynamics (CFD) analyses of flapping B. mori to analyse this mechanism in depth. A three-dimensional simulation using reconstructed wing kinematics was used to investigate the effects of B. mori fanning on locomotion and pheromone capture. The fanning of the B. mori was found to generate an aerodynamic force on the scale of its weight through an aerodynamic mechanism similar to that of flying insects. Our simulations further indicate that the B. mori guides particles from its anterior direction within the ~ 60° horizontally by wing fanning. Hence, if it detects pheromones during fanning, the pheromone can be concluded to originate from the direction the head is pointing. The anisotropy in the sampling volume enables the B. mori to orient to the pheromone plume direction. These results provide new insights into insect behaviour and offer design guidelines for robots for odour source localisation.

Background: There are reports indicating that between 10 and 38.5 % of patients with chronic lateral ankle instability (CLAI) have an os subfibulare. In cases where CLAI accompanied by os subfibulare is resistant to conservative treatment, surgery may be necessary; however, there is no consensus on the most appropriate surgical method. We report outcomes of arthroscopic lateral ligament repair for chronic lateral ankle instability with os subfibulare at our hospital, followed for over 2 years post-operatively. Methods: We reviewed 33 patients (39 ankles) whom underwent arthroscopic lateral ankle ligament repair (ALLR) for CLAI and followed for at least 2 years post-operatively between November 2015 and May 2020. Patients were classified into two groups: a group with os subfibulare (ossicle group) and a group without os subfibulare (non-ossicle group), based on the presence of an os subfibulare on pre-operative plain radiographs. ALLR surgeries were performed without resection of the os subfibulare in ossicle group. Clinical outcomes were assessed using the Japanese Society for Surgery of the Foot (JSSF) scale and the Self-administered Foot Evaluation Questionnaire (SAFE-Q). In addition, the bone-union rate was evaluated by using plain computer tomography in the ossicle group. Results: There were significant improvements in the mean total JSSF scale scores from pre-operative to post-operative measurements in both the ossicle and non-ossicle groups. The mean scores for pain and related symptoms, foot function and activities of daily living, social functioning, shoe-related, and general health and well-being subscales of the SAFE-Q also showed significant improvements in both groups. There were no significant differences between the post-operative ossicle and non-ossicle groups regarding the JSSF scale scores or the SAFE-Q subscale scores. In the ossicle group, the bone-union rate was 14.3 % (2 of 14 ankles), but no symptom recurrence was observed. Conclusion: The 2 years outcomes of arthroscopic lateral ligament repair for chronic lateral ankle instability with os subfibulare revealed good results and no symptom recurrence.

Abstract Ossicular fixation disturbs the mobility of the ossicular chain and causes conductive hearing loss. To diagnose the lesion area, otologists typically assess ossicular mobility through intraoperative palpation. Quantification of ossicular mobility and evidence-based diagnostic criteria are necessary for accurate assessment of each pathology, because diagnosis via palpation can rely on the surgeons’ experiences and skills. In this study, ossicular mobilities were simulated in 92 pathological cases of ossicular fixation as compliances using a finite-element (FE) model of the human middle ear. The validity of the ossicular mobilities obtained from the FE model was verified by comparison with measurements of ossicular mobilities in cadavers using our newly developed intraoperative ossicular mobility measurement system. The fixation-induced changes in hearing were validated by comparison with changes in the stapedial velocities obtained from the FE model with measurements reported in patients and in temporal bones. The 92 cases were classified into four groups by conducting a cluster analysis based on the simulated ossicular compliances. Most importantly, the cases of combined fixation of the malleus and/or the incus with otosclerosis were classified into two different surgical procedure groups by degree of fixation, i.e., malleo-stapedotomy and stapedotomy. These results suggest that pathological characteristics can be detected using quantitatively measured ossicular compliances followed by cluster analysis, and therefore, an effective diagnosis of ossicular fixation is achievable.

Background: The significance of pulmonary artery (PA) diameter in patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) who undergo pulmonary resection has not been elucidated. Methods: Data of 357 patients with NSCLC and COPD who underwent pulmonary resection were retrospectively reviewed. The main PA diameter, determined by preoperative computed tomography, relative to the body surface area (PBR), was used as an index of PA dilatation, and patients were divided into 2 groups using median values. The relationship between the PBR and short- and long-term outcomes was also analyzed. Results: The mean age was 70.8 years, and 82% of the patients were men. The median main PA diameter was 24 mm (range, 17-43 mm), and the median PBR was 14.5 (range, 10.4-28.6). Lobectomy or more was performed in 276 patients (78%) and sublobar resection in 81 patients (22%). The postoperative complication rates did not differ between the low- and high-PBR groups (33% vs 32%, P = .91). The relapse-free survival (RFS) and overall survival (OS) rates of the low-PBR group were significantly better than those of the high-PBR group (5-year RFS: 76% vs 59%, P = .0003; 5-year OS: 88% vs 72%, P = .0010). A multivariable analysis identified high PBR as a poor prognostic factor for both RFS and OS. Conclusions: PA dilatation was associated with poor long-term outcomes and was an independent poor prognostic factor for both RFS and OS in NSCLC patients with COPD who underwent pulmonary resection.

Abstract Background Evidence regarding the association between hyperuricemia and arrhythmia recurrence after catheter ablation for paroxysmal atrial fibrillation (AF) is scarce. We investigated whether hyperuricemia predicts arrhythmia recurrence after catheter ablation for paroxysmal AF and the relationship between hyperuricemia and alcohol consumption in AF recurrence. Methods Patients who underwent catheter ablation for paroxysmal AF were divided into the hyperuricemia (index serum uric acid [UA] >7.0 mg/dL; n = 114) and control (UA ≤7.0 mg/dL; n = 609) groups and were followed for a median of 24 (12–48) months after ablation. Results The hyperuricemia group had more patients with an alcohol intake of ≥20 g/day (33.3% vs. 22.7%, p = .017) and a lower incidence of AF‐free survival (p = .019). Similarly, those with an alcohol intake of ≥20 g/day had a lower incidence of AF‐free survival than other patients. Multivariate Cox regression analysis revealed the following independent predictors of AF recurrence (adjusted hazard ratio, 95% confidence interval): hyperuricemia (1.64, 1.12–2.40), female gender (1.91, 1.36–2.67), brain natriuretic peptide level >100 pg/mL (1.59, 1.14–2.22), and alcohol consumption ≥20 g/day (1.49, 1.03–2.15) (all p

Abstract Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future.

Objective: Imaging is essential for diagnosing large-vessel vasculitis (LVV). During diagnostic imaging, assessing disease activity and vascular damage separately is important. Acute-phase findings represent disease activity, while chronic-phase findings represent vascular damage; however, whether the imaging findings are acute or chronic may be unclear. We investigated how vascular lesions change before and after treatment and whether they were acute- or chronic-phase findings. Methods: Fifty-one patients with LVV who had undergone contrast-enhanced computed tomography (CT) scans from the neck to the pelvis before treatment and 1-4 months after treatment were recruited. Wall thickening, wall contrast enhancement, stenosis, occlusion, dilation, aneurysm, and calcification were semi-quantitatively assessed in 21 vessels from the common carotid to the common iliac artery. Results: Twenty-four patients were diagnosed with Takayasu arteritis (TAK), and 27 with giant cell arteritis (GCA). Wall thickening and wall contrast enhancement improved after the treatment, which was especially significant in the GCA group. No significant differences in stenosis, occlusion, dilation, aneurysm, or calcification were observed before and after treatment. Stenosis and occlusion were more common with TAK, while calcification was more common with GCA. Conclusion: Wall thickening and wall contrast enhancement are acute-phase findings (activity), while stenosis, occlusion, dilation, aneurysm, and calcification are chronic-phase findings (damage). The frequencies of these findings differ between TAK and GCA.

Abstract Background Curved varus osteotomy (CVO) is an effective femoral head-preserving surgical procedure for osteonecrosis of the femoral head (ONFH) classified as type B or C1 according to the Japanese Investigation Committee (JIC) classification; it reportedly provides better postoperative outcomes than transtrochanteric rotational osteotomy (TRO). We have developed a new procedure called spherical varus rotational osteotomy (SVRO) in which osteotomy of the femur into a spherical shape is followed by varus and anterior rotation using navigation to increase indications and improve postoperative outcomes. Methods Nine joints of eight patients who underwent SVRO and could be followed up for > 1 year were included in the study. Disease types determined preoperatively according to the JIC classification were type C1 for four joints and type C2 for five joints. Preoperative disease JIC classification stages were 3a for eight joints and 1 for one joint. SVRO was performed using OrthoMap® 3D Navigation software, and the following variables were measured: surgery time, intraoperative blood loss, difference between preoperative and postoperative angles of anteversion, postoperative lower limb length discrepancy, and postoperative intact area occupancy. The Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) was used for clinical evaluation. Visual Analog Scale and JHEQ scores were evaluated preoperatively and at the final follow-up. Results The measurement results were as follows: surgery time, 130 min; blood loss, 200 ml; angle of varus, 20°; angle of anterior rotation, 30°; preoperative angle of anteversion, 15°; postoperative angle of anteversion, 22°; lower limb shortening, 11 mm; preoperative intact area occupancy, 0%; and postoperative intact area occupancy, 74.2%. There were no cases of progression in the postoperative stages or re-collapse. Conclusion SVRO allows for the repositioning of the exterior and posterior intact areas, providing a broader intact region postoperatively. This technique is particularly beneficial for young patients with ONFH and extensive necrosis and is a less invasive alternative to TRO. This procedure has been shown to be effective in achieving favorable outcomes in patients with extensive necrosis who would have otherwise required rotational osteotomy, depending on the necrosis location. Further longitudinal studies are necessary to validate these findings and establish long-term benefits.