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Isolation by distance and landscape connectivity are fundamental factors underlying speciation and evolution. To understand how landscapes affect gene flow and shape population structures, island species provide intrinsic study objects. We investigated the effects of landscapes on the population structure of the endangered frog species, Odorrana ishikawae and O. splendida, which each inhabit an island in southwest Japan. This was done by examining population structure, gene flow and demographic history of each species by analyzing 12 microsatellite loci and exploring causal environmental factors through ecological niche modeling (ENM) and the cost-distance approach. Our results revealed that the limited gene flow and multiple-population structure in O. splendida and the single-population structure in O. ishikawae were maintained after divergence of the species through ancient vicariance between islands. We found that genetic distance correlated with geographic distance between populations of both species. Our landscape genetic analysis revealed that the connectivity of suitable habitats influences gene flow and leads to the formation of specific population structures. In particular, different degrees of topographical complexity between islands are the major determining factor for shaping contrasting population structures of two species. In conclusion, our results illustrate the diversification mechanism of organisms through the interaction with space and environment. Our results also present an ENM approach for identifying the key factors affecting demographic history and population structures of target species, especially endangered species. [ABSTRACT FROM AUTHOR]

The differentiation of a vegetative cell and a generative cell is a critical event during pollen development. The Lilium GlsA is known to localize in pollen and is considered to be involved in development of the generative cell. Here, we cloned a glsA ortholog from Alstroemeria, a commercially important cut flower. The expression of AaglsA ( Alstroemeria aurea glsA) transcripts increased gradually after pollen mitosis I (PMI) and reached a significant level when the generative cell started to elongate. Analysis of the promoter of AaglsA suggests that AaglsA expression is controlled by several cis-regulatory elements during pollen development. This is the first investigation of reproductive factors regulating male gametogenesis in Alstroemeria. [ABSTRACT FROM AUTHOR]

Background: Immune editing, in which human leukocyte antigens (HLA) have critical roles, has been suggested to shape the landscape of human cancer. This study prospectively investigated whether HLA gene zygosity is associated with the prognosis of primary androgen deprivation therapy in advanced prostate cancer., Methods: KYUCOG-1401-A was conducted in conjunction with a prospective clinical trial (KYUCOG-1401). Among the patients enrolled in KYUCOG-1401 and treated with primary androgen deprivation therapy, only Japanese patients were included. HLA genotypes of HLA-A, B, C, DRB1, DQB1, and DPB1 were determined. The effect of divergence of HLA genotypes on time to progression, prostate cancer-specific survival, and overall survival was evaluated., Results: Among 127 patients, homozygosity for HLA-DRB1 (HR, 95% CI; 4.05, 1.54-10.7, P = 0.0047) and HLA-DQB1 (HR, 95% CI; 3.75, 1.47-9.58, P = 0.0058) was associated with an increased risk of prostate cancer-specific mortality. Patients with higher HLA evolutionary divergence scores at HLA-DQB1 (HR, 95% CI; 0.90, 0.82-0.97, P = 0.0093) had lower risks of prostate cancer-specific mortality. Androgen-responsive gene sets were upregulated in CD4low and CD8low tumors in the prostate cancer cohort, but not in the bladder and kidney cancer cohorts., Conclusions: This study suggested that the diversity of HLA-II loci including HLA-DRB1 and HLA-DQB1 plays an important role in advanced prostate cancer survival, contributing to improved risk stratification in advanced prostate cancer. Moreover, it was shown that CD4 + T cells play an important role in androgen deprivation therapy, suggesting that immunotherapy targeting CD4 + T cells is promising for prostate cancer., Competing Interests: Competing interests: MS received honoraria from Janssen Pharmaceutical, AstraZeneca, Astellas Pharma, Sanofi, and Bayer and research funding support from Daiichi Sankyo. TK received research funding support from Janssen Pharmaceutical, Astellas Pharma, Shin Nippon Biomedical Laboratories, Ono Pharmaceutical, Bayer, Sanofi, and Takeda Pharmaceutical. HM received honoraria from Janssen Pharmaceutical, AstraZeneca, Astellas Pharma, Bayer, Chugai Pharmaceutical, and Merck and research funding support from Janssen Pharmaceutical, Takeda Pharmaceutical, and Kyowa Kirin. HS received honoraria from Takeda Pharmaceutical and Astellas Pharma. TI received honoraria from Janssen Pharmaceutical and Astellas Pharma. TK received honoraria from Takeda Pharmaceutical, AstraZeneca and Merck. AY received honoraria from Janssen Pharmaceutical and Astellas Pharma. ME received honoraria from Takeda Pharmaceutical, Janssen Pharmaceutical, AstraZeneca, and Astellas Pharma and research funding support from Astellas Pharma, Sanofi, and Takeda Pharmaceutical. Ethics approval: The study protocol was approved by the institutional review board of each institute. Consent to participate: All participants provided written informed consent., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background/Objective : Maintaining sufficient ankle joint range of motion (ROM) contributes to efficient movement in sports and daily activities. Static stretching (SS), while effective, demands significant time, highlighting the need for alternative, time-efficient approaches to improve ROM. Therefore, this study aimed to evaluate the effectiveness of combined intervention (CI) using neuromuscular electrical stimulation (NMES) and elastic tape versus SS. Methods : This randomized crossover trial was conducted in healthy university students. They underwent both interventions with a 1-week washout period. The CI entailed the application of elastic tape to the plantar surface of the foot coupled with NMES targeting the posterior lower leg muscles for 1 min. SS was administered for 5 min using a tilt table. Outcome measures included the dorsiflexion angle (DFA), finger-floor distance (FFD), straight leg raise (SLR) angle, plantar flexor strength (PFS), and knee flexor strength (KFS), assessed pre- and post-intervention. DFA was analyzed using equivalence testing with a predefined margin. Results : Both interventions yielded significant improvements in DFA, FFD, and SLR. The combination of NMES and elastic tape demonstrated equivalence to 5 min of SS in enhancing DFA. Neither intervention resulted in a significant reduction in PFS or KFS. Conclusions : The CI of NMES and elastic tape effectively and safely improves flexibility in a short time. Its time efficiency makes it a promising alternative to SS, especially for brief warm-ups or limited rehabilitation time. Further research should explore its long-term effects and broader applicability.

Background: Immuno-oncology (IO) combination therapies, including IO + IO or IO + vascular endothelial growth factor targeted therapies (VEGF-TT), have become the standard first-line treatment for advanced renal cell carcinoma (RCC). However, the optimal regimen for patients without prior nephrectomy remains unclear., Methods: Data from 99 patients with advanced RCC without nephrectomy, treated with VEGF-TT, IO + IO, or IO + VEGF-TT between May 2008 and May 2024, were retrospectively reviewed and analyzed. Patients were divided into VEGE-TT, IO + IO, and IO + VEGF-TT groups based on their first-line treatment, and survival and tumor response were compared., Results: All patients included in this study were categorized as either intermediate or poor risk according to the International Metastatic RCC Database Consortium risk classification. Among the 99 included patients, 41 initiated first-line therapy with VEGF-TT, 36 with IO + IO, and 22 with IO + VEGF-TT. The objective response rates were 17.5% for VEGF-TT, 38.9% for IO + IO, and 61.9% for IO + VEGF-TT. Notably, the IO + VEGF-TT group showed the greatest shrinkage of target kidney lesions (p = 0.0042). In multivariate analyses, bone metastasis (hazard ratio (HR) = 1.812, 95% confidence interval (CI) 1.017-3.228, p = 0.0436) and the first-line regimen (VEGF-TT vs IO + VEGF-TT: HR = 0.129, 95% CI 0.045-0.369, p = 0.0001) were independent prognostic factors for progression-free survival. The first-line regimen (VEGF-TT vs IO + VEGF-TT: HR = 0.303, 95% CI 0.104-0.879, p = 0.0279) independently affected overall survival., Conclusion: IO combination therapy, especially IO + VEGF-TT, has demonstrated a higher anti-tumor response in patients with advanced RCC without nephrectomy and may also be highly effective against primary renal tumors. Therefore, further studies are needed to improve patient survival and validate efficacy of IO combination therapy., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest., (© 2025. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background/aim: The prognostic significance of prostate-specific antigen (PSA) kinetics in metastatic castration-sensitive prostate cancer (mCSPC) patients treated with upfront therapy remains unclear. This study investigated the correlation between early PSA response and clinical outcomes in patients with mCSPC who received upfront therapy., Patients and Methods: We analyzed 106 patients with mCSPC who received upfront therapies [abiraterone acetate (ABI), enzalutamide (ENZ), apalutamide (APA), and docetaxel (DOC)] at Kurume University Hospital and its affiliated hospitals., Results: Thirty-nine, 15, 38, and 14 patients were treated with ABI, DOC, ENZ, and APA, respectively. Among the total number of patients, 67 met the criteria for high-volume disease. Additionally, 83 patients were categorized as high risk. Patients with a PSA decline rate of ≥90% at 4 and 12 weeks post-upfront therapies had a significantly longer time to develop CRPC than those with a PSA decline of <90%. PSA cutoff values >26 ng/ml at 4 weeks post-upfront therapies and a PSA decline rate of ≥90% at 12 weeks post-upfront therapies were independent predictors of poor prognosis. Furthermore, patients were stratified into three groups based on PSA levels at 4 weeks and PSA decline rate at 12 weeks., Conclusion: A larger PSA decline within three months of initiating upfront therapy is significantly associated with a longer time to CRPC in patients with mCSPC treated with upfront therapy. A combination of early PSA kinetics can be used to stratify the risk of CRPC progression in patients with mCSPC treated with upfront therapies., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare aggressive lymphoma. Recently, genetic classification using Next Generation Sequencing (NGS) demonstrated that PSDLBCL largely consists of the MCD genotype, which has a poor prognosis mainly driven by MYD88 L265P and CD79B gene abnormalities. This study investigated the prevalence and clinicopathological significance of MYD88 L265P and CD79B Y196 mutations using droplet digital PCR in 55 patients with PSDLBCL, as well as the translocation of BCL2 / BCL6 / c-Myc with FISH. We found mutations in MYD88 L265P (29/55, 52.7%) and CD79B Y196 (20/55, 36.4%). The MCD-like subtype, defined by the mutation of MYD88 and/or CD79B , was found in 32 out of 55 cases (58.2%). This subtype largely consists of non-GCB type (31/32, 96.9%; P <0.01) and double-expressor cases (20/32, 62.5%; P =0.01) compared with the MYD88 / CD79B co-wild type, with BCL6 translocation in a small subset (2/32, 6.3%) and no translocations of BCL2 (0/32) or c-Myc (0/32). The MCD-like subtype tended to relapse in specific sites such as the central nervous system, testis, and/or skin compared with the co-wild type ( P =0.03), showing poorer outcomes in overall survival ( P =0.02) and progression-free survival ( P =0.01). In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Enhanced expression of transforming growth factor (TGF) β in the kidneys of patients with lupus nephritis (LN) can lead to progressive fibrosis, resulting in end-organ damage. ADAM9 activates TGFβ1 by cleaving the latency-associated peptide (LAP). We hypothesized that ADAM9 in the kidney may accelerate fibrogenesis by activating TGFβ1., Methods: We assessed the expression of ADAM9 in the kidneys of mice and humans who were lupus prone. In vitro experiments were conducted using tubular epithelial cells (TECs) isolated from mice and explored the mechanisms responsible for the up-regulation of ADAM9 and the subsequent activation of TGFβ1. To assess the role of ADAM9 in the development of tubular-intestinal fibrosis in individuals with LN, we generated MRL/lpr mice who were Adam9 deficient., Results: ADAM9 was highly expressed in tubules from MRL/lpr mice. The transcription factor hypoxia-inducible factor-1α was found to promote the transcription of ADAM9 in TECs. TECs from mice who were Adam9 deficient and exposed to the hypoxia mimetic agent dimethyloxalylglycine failed to cleave the LAP to produce bioactive TGFβ1 from latent TGFβ1. Coculture of TECs from mice who were Adam9 deficient with fibroblasts in the presence of dimethyloxalylglycine and latent TGFβ1 produced decreased amounts of type I collagen and α-smooth muscle actin (SMA) by fibroblasts. MRL/lpr mice who were Adam9 deficient showed reduced interstitial fibrosis. At the translational level, ADAM9 expression in tissues and urine of patients with LN was found to increase., Conclusion: Hypoxia promotes the expression of ADAM9 by TECs, which is responsible for the development of interstitial fibrosis in patients with LN by enhancing the TGFβ1 activation, which promotes fibroblasts to produce collagen and α-SMA., (© 2024 American College of Rheumatology.)

The occurrence of diseases characterized by irregular spinal alignment, such as kyphosis, lordosis, scoliosis, and dropped head syndrome (DHS) is increasing, particularly among older adults. DHS is characterized by an excessive forward tilt of the head and neck, causing the head to droop. Although it is believed that muscle activity plays a role in both the onset and treatment of DHS, the underlying mechanisms remain unclear. To elucidate the mechanism, we used a human body finite element model, which included the erector spinae muscle group, and a muscle controller with fixed legs for spinal posture stabilization. The model replicated muscle activation levels during the maintenance of an upright posture under gravity, similar to those obtained from experimental data. Parametric simulations to investigate the effect of each spinal muscle impairment on upright posture with and without compensatory activities of the other muscles suggest that trunk extensors; the multifidus L1-S and longissimus thoracis muscles, and hip flexors; psoas major and iliacus muscles play an integral role in maintaining an upright posture. These findings support the results of a rehabilitation study that reported that exercises targeting the trunk, psoas muscles, and cervical extensors could improve global spinal alignment and clinical outcomes in DHS., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

[Purpose] The Y Balance test is a dynamic balance assessment tool widely used in sports. Although its reliability has been established in professional male athletes, its suitability for female high-school athletes remains unclear. Therefore, this study aimed to evaluate the reliability of the Y Balance test in this population. [Participants and Methods] Thirty-one female high school students underwent five Y Balance test measurements in each direction for both the right and left lower extremities. Intraclass correlation coefficients and one-way analysis of variance were used to assess intra-rater reliability. [Results] The intra-rater reliability for the five assessments ranged from 0.83 to 0.96, indicating high reliability. The first and second measurements were lower than the third and subsequent measurements, and the third to the fifth measurements, excluding that of the posterolateral right leg, showed no significant differences. [Conclusion] Altogether, the Y Balance test is a highly reliable, dynamic balance assessment tool for female high-school athletes. Furthermore, This study further indicates that high reliability is consistently achieved from the third to the fifth measurement, with the exception of the posterolateral direction on the right leg., Competing Interests: The authors declare no conflict of interest., (2025©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Objective: Chronic lung disease (CLD) is a complication of prematurity. Studies examining the effects of long-chain polyunsaturated fatty acids (LC-PUFAs) on CLD are conflicting. This study investigated LC-PUFAs in the red blood cell membrane (RBCM) in preterm infants., Study Design: This prospective observational study included infants with gestational age <32 weeks or birth weight <2 kg and at least one LC-PUFA measurement in the first month of life. Subjects without CLD (CON group) were compared to those with CLD (CLD group) and then by CLD severity., Results: Seventy infants were included (CON n=29; CLD n=41). Twenty six infants had Grade 1 CLD; 12 had Grade 2 CLD; 3 had Grade 3 CLD. When the CLD group was compared to the CON group, the overall mean (95% confidence interval) RBCM% for linoleic acid (LA) was similar (CLD vs. CON 12.5% [11.7% - 13.4%] vs. 11.2% [10.2 - 12.3%] p=0.06) but the overall mean arachidonic acid (ARA) was lower (17.6% [17.1% - 18.0%] vs. 18.6% [18.1% - 19.2%], p<0.01). During weeks 1-4, LA% was similar, while ARA% was lower in weeks 2 and 3 (18.8% ± 2.2% vs. 20.0% ± 1.5%, p=0.05, 16.8% ± 2.0% vs. 18.3% ± 1.6%, p=0.01). A similar trend was noted when groups were compared by CLD severity. The CLD group had a higher overall mean ∝-linolenic acid (ALA) compared to the CON group (0.4% [0.3% - 0.4%] vs. 0.2% [0.2 % - 0.3%], p<0.01) but no difference in docosahexaenoic acid (DHA) (3.8% [3.4% - 4.1%] vs. 3.8% [3.4% - 4.3%], p=0.80). During weeks 1-4, ALA% was higher during week 1 only (0.4% ± 0.3% vs. 0.2% ± 0.1%, p<0.01), and DHA% was similar for weeks 1-4. Results were similar when groups were compared by CLD severity., Conclusions: In this study, low ARA status was associated with CLD., Competing Interests: KLC has served as an advisor for Fresenius Kabi and has received research support from Fresenius Kabi. KLC has served as an advisor for Mead Johnson Nutrition and Baxter. KLC serve as an institutional principal investigator, with no salary funding, for a consortium database sponsored by Mead Johnson Nutrition. Please see ICJME COI forms attached at the time of this submission from each author., (Thieme. All rights reserved.)

Background: Distal radial fractures are common forearm injuries. A key rehabilitation objective is achieving adequate wrist palmar and dorsal flexion range-of-motion (ROM). However, few studies have explored this relationship, with even lesser number of studies investigating the impact of distal radius alignment on wrist ROM limitation due to fractures. We aimed to determine the effect of radial alignment on wrist palmar and dorsal flexion ROM after conservative treatment for distal radial fractures., Patients and Methods: This retrospective, cohort study, included 82 patients with distal radial fractures (11 men, 71 women, mean age: 65.9 ± 16.6 years) who underwent examination at an orthopedic clinic. Wrist ROM limitation was defined as ˂60° of dorsal flexion and ˂55° of palmar flexion. The palmar tilt (PT), radial length (RL), and radial inclination (RI) were radiographically measured. The patient's age, residual symptoms, and rehabilitation period were extracted from medical records. Univariate and multivariate analyses were conducted with the presence/absence of wrist ROM limitation as the objective variable, with the PT, RL, and RI as explanatory variables. A comparison of age, and rehabilitation period between the groups with and without wrist ROM limitation was performed using the Mann-Whitney U test. The presence/absence of residual symptoms were compared between two groups using the chi-squared test., Results: Univariate analysis revealed that PT, RL and RI were associated with palmar flexion ROM limitation. Multivariate analysis showed that PT was the only factor associated with palmar flexion ROM limitation (odds ratio: 0.85, 95% confidence interval: 0.78-0.91, p < 0.001), while dorsal flexion ROM limitation was not associated with any of the three measurements. The group with palmar flexion ROM limitation presented older age (73.1 vs. 59.6 years), higher residual symptom frequency (23 vs. 12 patients), and longer rehabilitation period (159.2 vs. 73.9 days) compared to the group without the limitation ( p < 0.01)., Conclusion: Dorsal displacement of the distal radius induces alterations in the wrist joint motion axis, potentially affecting limitation in palmar flexion ROM. Patients with palmar flexion ROM limitation had more residual symptoms and longer rehabilitation period than those without. These findings may contribute to the development of evidence-based joint ROM exercises, risk management, goal setting, and rehabilitation programs for patients with distal radial fractures.