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Objective In 2022, Wenning et al. proposed the Movement Disorder Society Criteria (MDS criteria) for the Diagnosis of Multiple System Atrophy (MSA). These criteria were expected to provide useful alternatives to the second consensus statement. We examined trends in these diagnostic criteria. Methods We used patient data registered with the Hokkaido Rare Disease Consortium for Multiple System Atrophy, which has been recruiting patients with MSA through medical facilities in Hokkaido since November 2014. Patients were evaluated according to the MDS criteria based on neurological examinations and imaging findings at three separate times: the first evaluation, the time of enrollment (diagnosis), and the most recent evaluation (final evaluation). Results The MDS criteria were examined in 68 of 244 patients enrolled between November 2014 and July 2022. At the initial evaluation, the classifications were as follows: clinically established (n=27; 39.7%); clinically probable (n=13; 19.1%); possible prodromal (n=12; 17.6%); and negative [did not meet criteria (n=16; 23.5%)]. At the time of diagnosis, the classifications were as follows: clinically established (n=45; 66.2%); clinically probable (n=12; 17.6%); possible prodromal (n=4; 5.9%); and negative (n=7; 10.3%). At the final evaluation, the classifications were as follows: clinically established (n=52; 76.5%); clinically probable (n=9; 13.2%); possible prodromal (n=2; 2.9%); and negative (n=5; 7.4%). Conclusion We were able to clarify the changes in the criteria values and transition of patients due to the clarification of imaging and supportive findings in the MDS criteria.

Introduction/aims: The common presentations of statin intolerance are muscle-specific symptoms. Although statins are one type of drug reported to cause myasthenic worsening, myasthenic worsening has not been recognized as statin intolerance. The purpose of the present study is to investigate in a large cohort the safety profiles of statins in patients with myasthenia gravis (MG)., Methods: A total of 1710 consecutive patients with MG who visited sites associated with the Japan MG registry 2021 group between April and October 2021 were reviewed. Statin-associated myasthenic worsening was defined as worsening of any myasthenic symptoms on statin use and improvement of the symptom by stopping the statin or by undertaking additional treatment with patient and doctor confirmation., Results: Among the 400 patients who used statins, 8 (2%) patients experienced statin intolerance and 6 (1.5%) patients experienced myasthenic worsening. No patients developed MG on the statin. Ptosis was a main symptom of myasthenic worsening in 4 (67%) patients. Atorvastatin was used in all patients with statin-associated myasthenic worsening. The symptoms of statin intolerance and statin-associated myasthenic worsening were improved within 2 months and 3 months, respectively, in all patients by cessation of statin use., Discussion: Regarding statin-associated myasthenic worsening, prevalence was low, and severity was mild; with cessation of statin use, symptoms improved within a few months, and outcomes were generally good. Although statins can be used in MG patients with little concern, statin-associated myasthenic worsening should be noted in addition to the classical statin intolerance associated with statin use., Competing Interests: Declaration of competing interest T. Sugimoto declares no potential conflicts of interest related to this article. S. Suzuki received speakers' fees from Alexion Pharmaceuticals, the Japan Blood Products Organization, Asahi Kasei Medical, and Argenx and participated in advisory board meetings of Alexion Pharmaceuticals and Argenx. A. Uzawa has received honoraria from Alexion Pharmaceuticals and Argenx. T. Yamawaki declares no potential conflicts of interest related to this article. M, Masuda declares no potential conflicts of interest related to this article. N. Minami declares no potential conflicts of interest related to this article. N. Kawaguchi declare no financial or other conflicts of interest. T. Kubota reports honoraria for lectures from Alexon Pharmaceuticals. M. P. Takahashi reports unrestricted research grants from Japan Blood Products Organization, Astellas Pharma, Mitsubishi Tanabe Pharma and Pfizer, outside the submitted work, and has served as a paid Consultant for Alexion, Argenx, Sanofi, and UCB Pharma and received honoraria for lectures from Argenx, Alexion Pharmaceuticals and UCB Pharma. Y. Suzuki declares no potential conflicts of interest related to this article. G Watanabe declares no potential conflicts of interest related to this article. S. Konno declares no potential conflicts of interest related to this article. T. Kimura declares no potential conflicts of interest related to this article. M. Samukawa declares no potential conflicts of interest related to this article. K. Ishizuchi declares no potential conflicts of interest related to this article. H. Akamine declares no potential conflicts of interest related to this article. Y. Onishi declares no potential conflicts of interest related to this article. M. Yasuda declares no potential conflicts of interest related to this article. Y. Nagane has received honoraria from Alexion Pharmaceuticals, Argenx, the Japan Blood Products Organization, and UCB Pharma. H. Maruyama declares no potential conflicts of interest related to this article. H. Murai has served as a paid consultant for UCB Pharma, Argenx, Janssen Pharma, Viela Bio, Chugai Pharma, Hanall BioPharma, and Mitsubishi Tanabe Pharma, and has received speaker honoraria from Argenx, Alexion Pharmaceuticals, and the Japan Blood Products Organization. K. Utsugisawa has served as a paid consultant for UCB Pharma, Argenx, Janssen Pharma, Viela Bio, Chugai Pharma, Hanall BioPharma, Merck and Mitsubishi Tanabe Pharma, and has received speaker honoraria from Argenx, Alexion Pharmaceuticals, UCB Pharma and the Japan Blood Products Organization., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Disability in ambulation has a critical impact on activities of daily living in patients with multiple sclerosis (MS). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a self-reported instrument developed to assess the impact of MS on walking. The scale's 12 items assess various aspects of walking-related tasks during the past 2 weeks. MSWS-12 has been used in multiple clinical studies and translated into several languages. In the present study, we translated the MSWS-12 into Japanese and evaluated its psychometric properties in a cross-sectional study., Methods: The original English MSWS-12 version 2 (v2) was translated into Japanese through a standard procedure. Sixty consecutive Japanese MS patients completed the newly prepared Japanese MSWS-12v2 questionnaire and repeated the test 14 days later. Physical disability was assessed by the Expanded Disability Status Scale (EDSS), Timed 25-foot Walk (T25FW), and 9-hole Peg Test (9HPT). Cognitive performance was evaluated using the Processing Speed Test (PST). Fatigue and health-related quality of life were assessed using the Japanese versions of the Fatigue Severity Scale (FSS) and the Functional Assessment of MS (FAMS)., Results: The mean age of the patients was 42.5 years, with median disease duration of 10 years, and median EDSS of 2.0 (range 0, 6.5). Forty-seven patients (78.3 %) had relapsing-remitting, 9 (15.0 %) had secondary-progressive, and 4 (6.7 %) had primary-progressive phenotypes. The median score of the MSWS-12v2 was 5.95 (interquartile range 0, 50.6). Twenty-seven patients (45 %) scored the lowest possible score (0 points), while one (1.7 %) scored the highest possible score (100 points). Cronbach's alpha was 0.98 (95 % confidence interval [CI] 0.97, 0.98), and the test-retest intraclass correlation was 0.95 (95%CI 0.94, 0.96). MSWS-12v2 score was strongly correlated with EDSS (Spearman's ρ = 0.73 [95%CI 0.58, 0.83]), T25FW (ρ = 0.70 [95%CI 0.55, 0.81]), and total FAMS score (ρ = -0.80 [95%CI -0.88, -0.69]), and moderately correlated with 9HPT (ρ = 0.65 [95%CI 0.47, 0.77] for the dominant hand; ρ = 0.62 [95%CI 0.43, 0.75] for the non-dominant hand), PST (ρ = -0.65 [95%CI -0.78, -0.47]), and FSS (ρ = 0.68 [95%CI 0.52, 0.80]). Among the subcomponents of FAMS, the mobility subcomponent showed the most robust correlation with MSWS-12v2 score (ρ = -0.91 [95%CI -0.94, -0.81]). In patients with minimal or no objective disability (EDSS < 3.0, n = 40), only the mobility subcomponent of FAMS was strongly correlated with MSWS-12v2 score (ρ = -0.76 [95% CI -0.87, -0.58]). In contrast, correlations of MSWS-12v2 score with EDSS and T25FW were weak in this subgroup (ρ = 0.28 [95%CI -0.03, 0.55] for EDSS; ρ = 0.25 [95%CI -0.06, 0.52] for T25FW). Response patterns for the single items showed that 32.5 % of the patients with EDSS below 3.0 reported having problems with balance, followed by climbing stairs and standing while doing things (both 25 %)., Conclusion: The Japanese version of the MSWS-12v2 developed in this study is reliable, valid, and helpful for screening walking disability in Japanese MS patients, including those with minimal objective disability., Competing Interests: Declaration of competing interest Yusei Miyazaki has received travel and speaker honoraria from Alexion Pharma, Biogen Japan, Chugai Pharmaceutical Company, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, and Teijin Pharma. Masaaki Niino has received travel and speaker honoraria from Alexion Pharma, Biogen Japan, Chugai Pharmaceutical Company, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, and Takeda Pharmaceutical Company. Naoya Minami has received travel and speaker honoraria from Argenx Japan. The other authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Macrophage activation syndrome (MAS) involves an excessive amount of acute inflammatory responses to inflammatory cytokines, particularly interleukin-6 (IL-6). IL-6 is also strongly associated with the pathophysiology of certain neuroimmunological diseases. However, there have so far been few reports of MAS being accompanied by neuroimmunological diseases. We herein report two cases of MAS comorbid with myasthenia gravis or neuromyelitis optica spectrum disorders, IL-6 related neuroimmunological diseases. Standard immunosuppressive therapies could not stabilize the symptoms in our cases until antibodies against the IL-6 receptor were administered. This finding suggests that it is important to consider the underlying pathophysiology of MAS in relation to these neuroimmunological diseases when treating affected patients.

Case: We report a case of intraneural nodular fasciitis in the forearm initially suspected as a schwannoma, emphasizing the importance of accurate diagnosis. A 40-year-old woman presented with mass on the lateral aspect of her right forearm and radial neuropathy symptoms for 2 months. An excisional biopsy and histopathological examination confirmed nodular fasciitis. Postoperative evaluation at 4.5 years found no pain, paralysis, or recurrence., Conclusion: Awareness of nodular fasciitis is crucial to prevent misdiagnosis and unnecessary treatment. Despite its rapid growth, nodular fasciitis generally has an excellent prognosis without long-term consequences., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C419)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background and Objectives: Efgartigimod, which has been well tolerated and efficacious in individuals with generalized myasthenia gravis (MG), is available in Japan not only for the treatment of anti-acetylcholine receptor-positive (AChR+) but also anti-muscle-specific receptor tyrosine kinase (MuSK+) and seronegative generalized MG. We report details of the use of efgartigimod for generalized MG in clinical practice in Japan., Methods: We included patients with generalized MG in the 2021 survey of Japan Myasthenia Gravis Registry (JAMG-R) study group who received an initial cycle of efgartigimod between May and September 2022. We defined "responders" as patients who achieved a score ≥2 points for MG activities of daily living (MG-ADL) in the first treatment cycle. The MG composite and the Revised scale of the 15-item Myasthenia Gravis-Quality of Life scale (MG-QOL15-r) were also evaluated., Results: Of 1,343 JAMG-R patients, 36 (2.7%) started efgartigimod (female 68%, age 53 years). Their serologic profiles were as follows: AChR+, n = 19 (53%); MuSK+, n = 6 (17%); and seronegative, n = 11 (31%). Twenty-six patients (72%) had refractory MG. There were 81 cycles of efgartigimod during the 26-week observation in 34 patients (average, 2.4 cycles). The mean interval between cycles was 5.9 weeks. A continuous 4-weekly infusion of efgartigimod was performed in 65 (80%) of 81 cycles. In the first cycle, the MG-ADL score of the 34 patients decreased significantly from 10.5 ± 4.3 to 6.9 ± 5.1 ( p = 0.003). Similarly, the mean MG composite and MG-QOL15-r decreased from 18.4 ± 13.6 to 11.8 ± 9.6 ( p = 0.004) and from 19.2 ± 6.3 to 14.2 ± 8.3 ( p = 0.007), respectively. Twenty-one (62%) patients were responders. Therapeutic responses were observed in the subsequent cycles. The duration of effectiveness of efgartigimod was varied among the responders; 4 responders had only a single effective cycle. Significant improvement was observed in the MuSK+ patients. Prednisolone dose of 7 patients was reduced. Our examination of the patients' postintervention status revealed that 6 patients achieved minimal manifestations. COVID-19 occurred in 5 patients. We failed to detect clinical or laboratory findings associated with responders., Discussion: Efgartigimod can be considered for the treatment of patients with generalized MG who do not achieve minimal manifestations, with a broad flexibility of patient selection and treatment schedules., Competing Interests: S. Suzuki has received personal fees from Alexion Pharmaceuticals, Argenx, UCB Pharma, the Japan Blood Products Organization, and Asahi Kasei Medical. A. Uzawa has received honoraria from Alexion Pharmaceuticals and Argenx. Y. Nagane has received speaker honoraria from Argenx, Alexion Pharmaceuticals, and the Japan Blood Products Organization. M. Masuda and S. Konno declare no potential conflicts of interest related to this article. T. Kubota has received honoraria for lectures from Alexon Pharmaceuticals, Argenx, and UCB Pharma. M. Samukawa, K. Ishizuchi, D. Tokuyasu, H. Handa, M. Yasuda, N. Kawaguchi, T. Kimura, Y. Suzuki, T. Sugimoto, and N. Minami declare no potential conflicts of interest related to this article. M.P. Takahashi reports unrestricted research grants from Japan Blood Products Organization, Astellas Pharma, Mitsubishi Tanabe Pharma, and Pfizer outside the submitted work and honoraria for lectures from Argenx, Alexion Pharmaceuticals, and UCB Pharma. H. Murai has served as a paid consultant for Alexion, AstraZeneca Rare Disease, Argenx, and UCB and has received speaker honoraria from the Japan Blood Products Organization and Chugai Pharmaceutical and research support from the Ministry of Health, Labour and Welfare, Japan. K. Utsugisawa has served as a paid consultant for UCB Pharma, Argenx, Janssen Pharma, Viela Bio, Chugai Pharma, Hanall BioPharma, and Mitsubishi Tanabe Pharma and has received speaker honoraria from Argenx, Alexion Pharmaceuticals, and the Japan Blood Products Organization. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

In Brief: Proper early embryonic development in mammals relies on precise cellular signaling pathways. This study reveals that NSUN5 is crucial for the regulation of the Hippo pathway, ensuring normal proliferation and differentiation in mouse preimplantation embryos., Abstract: NOL1/NOP2/Sun domain family, member 5 (NSUN5) is an enzyme belonging to the 5-methylcytosine (m5C) writer family that modifies rRNA and mRNA. Our data revealed an upregulation of Nsun5 at the two-cell stage of mouse preimplantation development, suggesting its significance in early embryonic development. Given m5C's important role in stabilizing rRNA and mRNA and the Hippo signaling pathway's critical function in lineage segregation during embryogenesis, we hypothesized that NSUN5 controls cell differentiation by regulating the expression of components of the Hippo signaling pathway in mouse early embryos. To examine this hypothesis, we employed Nsun5-specific small interfering RNAs for targeted gene silencing in mouse preimplantation embryos. Nsun5 knockdown resulted in significant developmental impairments including reduced blastocyst formation, smaller size of blastocysts, and impaired hatching from the zona pellucida. Nsun5 knockdown also led to decreased cell numbers and increased apoptosis in embryos. We also observed diminished nuclear translocation of yes-associated protein 1 (YAP1) in Nsun5 knockdown embryos at the morula stage, indicating disrupted cell differentiation. This disruption was further evidenced by an altered ratio of CDX2-positive to OCT4-positive cells. Furthermore, Nsun5 depletion was found to upregulate the Hippo signaling-related key genes, Lats1 and Lats2 at the morula stage. Our findings underscore the essential role of Nsun5 in early embryonic development by affecting cell proliferation, YAP1 nuclear translocation, and the Hippo pathway.

Objective: Eculizumab and ravulizumab are complement protein C5 inhibitors, showing efficacy and tolerability for patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG) in phase 3 clinical trials and subsequent analyses. The purpose of the present study was to evaluate the clinical significance of eculizumab and switching to ravulizumab for refractory AChR+ gMG patients in the real-world experience., Methods: Among the database of Japan MG registry survey 2021, we studied AChR+ gMG patients who received eculizumab. We also evaluated these patients who switched from eculizumab to ravulizumab. Responder was defined as an improvement of at least 3 points in MG-ADL. We performed a questionnaire of preference between eculizumab and ravulizumab., Results: Among 1,106 patients with AChR+ gMG, 36 patients (3%) received eculizumab (female 78%, mean age 56.0 years). Eculizumab was preferentially used in severe and refractory MG patients. The duration of eculizumab treatment was 35 months on average. MG-ADL improved from 9.4 ± 4.9 to 5.9 ± 5.1, and 25 (70%) of the 36 gMG patients were responders. Postintervention status was markedly improved after the eculizumab treatment. Of 13 patients who did not continue eculizumab, 6 showed insufficiencies. Early onset MG was most effective. However, 15 patients switching from eculizumab to ravulizumab kept favorable response and tolerability. Questionnaire surveys showed preference for ravulizumab over eculizumab., Interpretation: Eculizumab and switching to ravulizumab showed to be effective for refractory AChR+ gMG patients in clinical settings., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

We retrospectively reviewed the medical histories, examination results, treatments, and prognoses of nine patients with cryptococcal meningitis who were diagnosed and treated at Hokkaido University Hospital and its affiliated hospitals over the past 10 years. Cryptococcal meningitis can develop even in immunocompetent hosts, and its prognosis is poor owing to diagnostic difficulties and delayed treatment. Although liposomal amphotericin B and oral 5-fluorocytosine are standard therapies, voriconazole or intraventricular administration of amphotericin B may also be considered treatment options for refractory patients. Some patients develop delayed exacerbations owing to immunological mechanisms that require steroid therapy.

Background: Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed., Methods: We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021., Results: Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG., Conclusion: Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG., (© 2024. The Author(s).)

Murine endogenous retrovirus with leucine tRNA primer, also known as MERVL, is expressed during zygotic genome activation in mammalian embryos. Here we show that protein arginine N-methyltransferase 6 (Prmt6) forms a chimeric transcript with MT2B2, one of the long terminal repeat sequences of murine endogenous retrovirus with leucine tRNA primer, and is translated into an elongated chimeric protein (PRMT6MT2B2) whose function differs from that of the canonical PRMT6 protein (PRMT6CAN) in mouse preimplantation embryos. Overexpression of PRMT6CAN in fibroblast cells increased asymmetric dimethylation of the third arginine residue of both histone H2A (H2AR3me2a) and histone H4 (H4R3me2a), while overexpression of PRMT6MT2B2 increased only H2AR3me2a. In addition, overexpression of PRMT6MT2B2 in one blastomere of mouse two-cell embryos promoted cell proliferation and differentiation of the blastomere into epiblast cells at the blastocyst stage, while overexpression of PRMT6CAN repressed cell proliferation. This is the first report of the translation of a chimeric protein (PRMT6MT2B2) in mouse preimplantation embryos. Our results suggest that analyzing chimeric transcripts with murine endogenous retrovirus with leucine tRNA primer will provide insight into the relationship between zygotic genome activation and subsequent intra- and extra-cellular lineage determination., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Microorganisms, including native yeasts, are abundant in vineyard fields. Herein, we studied the possibility of using vineyard-derived wild yeast as a microbial pesticide against Botrytis cinerea, a pathogen that causes grape gray mold disease, to boost the initial alcohol production of spontaneously fermented wine. We identified the Saccharomyces cerevisiae strain KONDO170908, which showed the most effective antifungal activity in an ex vivo yeast dripping experiment on grape berries. This strain was utilized in an in vivo spray test on grape bunches in vineyard fields and was proven to significantly suppress gray mold disease on the grape berries in test plot #16 when the yeast was sprayed during both the flowering and ripening periods (morbidity 11.2% against 15.3% of the control plot, χ 2 test, p < 0.0001). However, in test plot #17, spraying the yeast during only the ripening period had no effect (morbidity 16.3%). The grapes from each test plot were also submitted for spontaneous wine fermentation. Alcoholic fermentation of the grapes from test plot #16 provided the most active bubbling of CO 2 gas and the highest ethanol production and colony counts over seven days of fermentation. Unique changes in the different strains of S. cerevisiae among the plots were observed throughout the early fermentation stage. Thus, yeast spraying during the flowering period might trigger modification of the entire microbiota and could ultimately contribute to promoting alcohol production in the spontaneously fermented wine, although it decreased the grape yield by 20%., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: We previously reported a modification of the CUT&Tag method (NTU-CAT) that allows genome-wide histone modification analysis in individual preimplantation embryos. In the present study, NTU-CAT was further simplified by taking advantage of the Well-of-the-Well (WOW) system, which enables the processing of multiple embryos in a shorter time with less reagent and cell loss during the procedure (WOW-CUT&Tag, WOW-CAT)., Results: WOW-CAT allowed histone modification profiling from not only a single blastocyst but also from a portion of it. WOW-CAT generated similar H3K4me3 profiles as NTU-CAT, but they were closer to the profiles produced by chromatin immunoprecipitation-sequencing, such as a valley-like trend and relatively lower false positive rates, indicating that WOW-CAT may attenuate the bias of Tn5 transposase to cut open chromatin regions. Simultaneous WOW-CAT of two halves of single blastocysts was conducted to analyze two different histone modifications (H3K4me3 and H3K27ac) within the same embryo. Furthermore, trophectoderm cells were biopsied and subjected to WOW-CAT in anticipation of preimplantation diagnosis of histone modifications. WOW-CAT allowed the monitoring of epigenetic modifications in the main body of the embryo. For example, analysis of H3K4me3 modifications of XIST and DDX3Y in trophectoderm biopsies could be used to sex embryos in combination with quantitative PCR, but without the need for deep sequencing., Conclusions: These results suggest the applicability of WOW-CAT for flexible epigenetic analysis of individual embryos in preimplantation epigenetic diagnosis., (© 2024. The Author(s).)

In ruminants, the overgrowth of offspring produced by in vitro fertilization (IVF) is a common problem. Abnormal epigenetic modifications caused by environmental factors during the early embryonic period are suspected as an aetiology of overgrowth. In this study, we investigated the genome-wide histone H3K4me3 profiles of bovine placentae that play a pivotal role in foetal development and compared their characteristics between artificial insemination (AI)- and IVF-derived samples. Cotyledons were harvested from the placentae obtained at parturition of 5 AI- and 13 IVF-derived calves, and chromatin immunoprecipitation sequencing was performed for H3K4me3. We confirmed no significant maternal tissue contamination in the samples we used. The revealed H3K4me3 profiles reflected the general characteristics of the H3K4me3 modification, which is abundantly distributed in the promoter region of active genes. By extracting common modifications from multiple samples, the genes involved in placenta-specific biological processes could be enriched. Comparison with the H3K4me3 modifications of blastocyst samples was also effective for enriching the placenta-specific features. Principal component analysis suggested the presence of differential H3K4me3 modifications in AI- and IVF-derived samples. The genes contributing to the difference were related to the developmental biological processes. Imprinted genes such as BEGAIN, ZNF215 and DLX5 were among the extracted genes. Principal component and discriminant analyses using only male samples categorized the samples into three groups based on foetal weight and calf-production methods. To our knowledge, this is the first study to profile the genome-wide histone modifications of bovine foetal placentae and reveal their differential characteristics between different calf-production methods., (© 2024 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Introduction: To prevent infection after limb-sparing surgery for primary malignant bone tumors, it is important to cover the megaprosthesis with muscle tissue that has sufficient blood flow. Coverage with a lateral gastrocnemius flap has been reported in cases of distal femoral replacement in which the vastus lateralis and vastus intermedius muscles have been resected; however, the risk of peroneal nerve palsy is reportedly high because the muscle flap passes near the peroneal head. This study was performed to examine the postoperative outcomes of patients with primary malignant bone tumors of the distal femur who underwent wide resection (including the vastus lateralis and vastus intermedius muscles) followed by reconstruction with a megaprosthesis and coverage of the lateral side of the prosthesis with a sartorius muscle flap., Methods: We retrospectively analyzed three patients who underwent reconstruction with a megaprosthesis after wide resection of a primary malignant bone tumor of the distal femur involving the vastus lateralis and vastus intermedius muscles and reconstruction of the soft tissue defect on the lateral side of the prosthesis with a sartorius muscle flap., Results: The average defect size was 6 × 13 cm, the average time required for a sartorius muscle flap was 100 min, and the average implant coverage was 93%. The average postoperative follow-up period was 35 months, during which no postoperative complications such as infection, skin necrosis, or nerve palsy occurred., Discussion: The distally based sartorius muscle flap is easy to elevate in the supine position, has minimal functional loss after harvesting, and has minimal risk of nerve palsy. It can be advocated as the first option for coverage of soft tissue defects lateral to distal femoral replacement., (© The Authors, published by EDP Sciences, 2024.)