Search

Angular Leaf Spot (ALS) caused by Pseudocercospora griseola is responsible for 54% yield loss in Uganda's common beans. Host plant resistance is a safe and cost-effective management strategy for this disease. Identification of resistant common bean genotypes to prevailing races is vital to utilize the crop. Therefore, the objective of this study was to identify genotypes that are resistant to the commonly occurring and virulent P. griseola races in Uganda for breeding purposes. Twenty-seven common bean genotypes and three control varieties (Mexico54, MCM5001, and CAL96) were screened at field conditions for ALS resistance at testing site (National Agricultural Research Laboratories--Kawanda) under natural disease infection. The genotypes were also evaluated in the screen house using frequently occurring P. griseola races: 61:63, 1:6 and 21:39. Variability in the severity of ALS on both leaves and pods was significant whereas the difference between seasons and the interaction between the seasons and genotypes was only significant for yield. The disease severity scores were higher (mean of 3.2) on leaves than on pods (mean of 2.9). Ninety-three percent, 33.3% and 15% of the genotypes were resistant to P. griseola races 21:39, 1:6 and 61:63, respectively. A large-seeded genotype AFR703 was resistant to all the three P. griseola races. A medium seed size genotype AFR702 and three small seed genotypes (G148, G18842 and G6727) were resistant to both 21:39 and 1:6 but moderate resistance to 61:63 whereas a large-seeded genotype AND279 was resistant to both 61:63 and 21:39 but moderate to 1:6. All of these six genotypes (AFR703, AFR702, G148, G18842, G6727 and AND279) expressed moderate resistance to P. griseola races on leaves under field conditions. Thus, these common bean genotypes could be used as sources of ALS resistance for breeding programs to address the ALS constraint; and genes responsible for resistance have to be characterized. Key words: Pathology, Disease, Resistance, Infection, BALSIT, Pathotypes, Prevalent, Races, INTRODUCTION The common bean (Phaseolus vulgaris L.) is an important source of protein (45%), carbohydrate (25%), fiber, vitamins including B complex and minerals such as iron, zinc and sulfur [1-3]. [...]

We report a rare case of an 80-year-old male patient with acute transformation of myelodysplastic syndrome (MDS) in the pericardial cavity, leading to cardiac tamponade.

Common bean (Phaseolus vulgaris L.) is a staple and nutritious leguminous food crop for all income categories in Africa. Efforts to improve its yield performance and nutritional components, especially iron and zinc have resulted in release of several varieties in the sub-Sahara African region. The objective of this study was to assess genetic progress in varieties released in 12 African countries through the Pan African Bean Research Alliance (PABRA) from 1973 to 2017, to inform current breeding decisions. A total of 214 released varieties, land races and breeding lines, of bush and climbing beans were evaluated for yield, micronutrient (Fe and Zn) concentration, and phenology in three locations (Kawanda and Kachwekano in Uganda, and Kitengule in Tanzania) in 2017/2018. There were significant differences (P<0.01) among genotypes for all traits, except days to maturity (DPM). Genotype x environment interaction was also significant (P<0.05) for all assessed traits, except for iron in climbing beans. Across environments, repeatability (H²) was greater than 0.50 for all traits, except for DPM in climbing beans. Annual rates of genetic yield gains were 4.41 and 4.57 kg ha-1 for large and small seed bush beans, and -2.74 and 21.6 kg ha-1 for large and small seeded climbers. Similarly, gains in seed iron (FESEED) were 0.40 and 0.17 ppm for bush and climbing beans, respectively. These represented an annual relative gain over the oldest varieties of 0.6 and 0.7% kg ha-1 for yield of large and small seeded bush beans, -0.3 and 1.6% kg ha-1 for yield of large and small seeded climbers, 0.6 and 0.2% ppm for FESEED of bush and climbers. Overall, genetic progress was slow for both yield and FESEED. [ABSTRACT FROM AUTHOR]

This article discusses a case of a 64-year-old man who was found to have a pancreatic head mass during a follow-up for colon cancer. The mass was confirmed to be a solid pseudopapillary neoplasm (SPN) through a biopsy. The tumor had invaded the main pancreatic duct and showed high-grade malignant transformation. Metastases developed in the para-aortic lymph nodes and liver one year after surgery. The article highlights the importance of careful treatment for patients with SPN suspected of having high-grade malignant transformation. [Extracted from the article]

Background: Undertaking child-focused evaluations using a participatory approach has received recognition in recent years. Such an approach is critical not only to build capacity amongst children and youth but also to increase the rigour, validity and usefulness of evaluation findings. Objectives: The current paper builds on the methods used in a longitudinal evaluation of a parenting programme on reintegration outcomes of children, ages 1–13 years, living in residential care facilities in Uganda. The procedures used to select and modify measures to enable 8–13-year-old children to self-report on their own outcomes are described. Method: Using a grounded theory of child development, the authors describe the data collection protocols and child-friendly measures used as well as the piloting work that was done by engaging children in the feedback process. Results: The study underscored the importance of adapting hybrid methods to the local context of a child-focused evaluation, especially in collecting data from young children on sensitive topics across a variety of situations. Conclusion: The process described in this article can be replicated for designing and conducting evaluations that are child centric and have children as informants of their own well-being. Contribution: The article contributes to a growing body of knowledge on child-focused evaluations by building on a study conducted in Uganda that focused on developing child-centric measures and data collection procedures. This study shows how to involve children as respondents and assists evaluators to design studies that are ethical, safe, and sensitive to the needs of the children.

Contrast-enhanced ultrasound (CEUS) plays a pivotal role in the diagnosis of primary breast cancer and in axillary lymph node (ALN) metastasis. However, the imaging features that are clinically crucial for lymph node metastasis have not been fully elucidated. Hence, we developed a bimodal model to predict ALN metastasis in patients with early breast cancer by integrating CEUS images with the annotated imaging features. The model adopted a light-gradient boosting machine to produce feature importance, enabling the extraction of clinically crucial imaging features. In this retrospective study, the diagnostic performance of the model was investigated using 788 CEUS images of ALNs obtained from 788 patients who underwent breast surgery between 2013 and 2021, with the ground truth defined by the pathological diagnosis. The results indicated that the test cohort had an area under the receiver operating characteristic curve (AUC) value of 0.93 (95% confidence interval: 0.88, 0.98). The model had an accuracy of 0.93, which was higher than the radiologist's diagnosis (accuracy of 0.85). The most important imaging features were heterogeneous enhancement, diffuse cortical thickening, and eccentric cortical thickening. Our model has an excellent diagnostic performance, and the extracted imaging features could be crucial for confirming ALN metastasis in clinical settings., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This retrospective study was approved by the ethics committee of our institution (020–0392), and the requirement for written informed consent was waived. All studies were performed in accordance with the relevant guidelines and regulations., (© 2025. The Author(s).)

Functional MRI (fMRI) is an important tool for investigating functional networks. However, the widely used fMRI with T2*-weighted imaging in rodents has the problem of signal lack in the lateral ventral area of forebrain including the amygdala, which is essential for not only emotion but also noxious pain. Here, we scouted the zero-echo time (ZTE) sequence, which is robust to magnetic susceptibility and motion-derived artifacts, to image activation in the whole brain including the amygdala following the noxious stimulation to the hind paw. ZTE exhibited higher temporal signal-to-noise ratios than conventional fMRI sequences. Electrical sensory stimulation of the hind paw evoked ZTE signal increase in the primary somatosensory cortex. Formalin injection into the hind paw evoked early and latent change of ZTE signals throughout the whole brain including the subregions of amygdala. Furthermore, resting-state fMRI using ZTE demonstrated the functional connectivity, including that of the amygdala. These results indicate the feasibility of ZTE for whole brain fMRI including the amygdala and we first show acute and latent activity in different subnuclei of the amygdala complex after nociceptive stimulation., Competing Interests: Declaration of competing interest I have nothing to declare., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study aimed to evaluate the efficacy of the single-energy metal artifact reduction (SEMAR) algorithm in reducing metal artifacts and enhancing image quality in contrast-enhanced computed tomography (CT) for patients undergoing endovascular aneurysm repair (EVAR) with coil embolization. Thirty-eight patients (mean age 81.0 ± 6 years; 31 men, 7 women) who underwent contrast-enhanced CT following EVAR and internal iliac artery coil embolization between September 2022 and May 2023 were retrospectively analyzed. The Artifact Index (AI) quantified metallic artifacts from internal iliac artery aneurysm coils in CT images, calculated from the standard deviation of the artifact-containing region relative to a reference region. CT values of the external iliac artery at the same slice were also evaluated and compared. Two radiologists independently performed qualitative assessments of SEMAR and non-SEMAR images. SEMAR significantly reduced metal artifacts, decreasing the AI from 171.9 ± 74.5 HU to 35.8 ± 16.9 HU (p < 0.001). The mean CT values of the external iliac artery were similar for SEMAR (259.4 ± 63.7 HU) and non-SEMAR (257.1 ± 63.6 HU, indicating no significant difference. Qualitative assessment scores improved significantly with SEMAR (from 1.0 ± 0.0 to 2.5 ± 0.5; p < 0.001), enhancing visualization of internal iliac artery aneurysms. Interobserver agreement was high (κ = 0.83). The SEMAR algorithm effectively reduces metal artifacts in contrast-enhanced CT, significantly enhancing image quality without altering adjacent artery CT values. These improvements enhance the image quality of post-operative assessments in patients undergoing EVAR with coil embolization., Competing Interests: Declarations. Ethical approval: This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of Jichi Medical University Saitama Medical Center (S23-080). Consent to publish: An opt-out policy has been implemented. The opt-out document is available on the Department of Radiology’s website at the Saitama Medical Center, Jichi Medical University, and at the laboratory reception. All participants have been provided the opportunity to decline inclusion in this research. Competing interests: Financial interests: Junji Mochizuki, Osamu Manabe and Noriko Oyama-Manabe have received research funding from Canon Medical Systems. The other authors have no financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Viral RNA synthesis of mononegaviruses occurs in cytoplasmic membraneless organelles called inclusion bodies (IBs). Here, we report that IBs of mumps virus (MuV), which is the causative agent of mumps and belongs to the family Paramyxoviridae , displayed liquid organelle properties formed by liquid-liquid phase separation. Super-resolution microscopic analysis of MuV IBs demonstrated that nucleocapsid and phospho (P)-proteins formed a cage-like structure and that the viral polymerase adopted a reticular pattern and colocalized with viral RNAs. In addition, we characterized host RNAs localized in MuV IBs by a spatial transcriptome analysis, and found that RNAs containing G-quadruplex motif sequences (G4-RNAs) were concentrated. An in vitro phase separation assay showed that the G4-RNAs interacted with the P protein and enhanced condensation in P droplets. Together, our data show that MuV generates IBs with a characteristic cage-like structure and host G4-RNAs play an important role in forming MuV IBs.

Breathing behaviour is subject to emotional regulation, but the underlying mechanisms remain unclear. Here, we demonstrate a direct relationship between the central amygdala, a major output hub of the limbic system associated with emotional brain function, and the brainstem pre-Bötzinger complex, which generates the fundamental rhythm and pattern for breathing. The connection between these two sites is monosynaptic and inhibitory, involving GABAergic central amygdala neurons whose axonal projections act predominantly via ionotropic GABA A receptors to produce inhibitory postsynaptic currents in pre-Bötzinger neurons. This pathway may provide a mechanism to inhibit breathing in the context of freezing to assess threats and plan defensive action. The existence of this pathway may further explain how epileptic seizures invading the amygdala cause long-lasting apnea, which can be fatal. Although their ultimate importance awaits further behavioural tests, these results elucidate a link between emotional brain function and breathing, which underlies survival-related behaviour in mammals and pertains to human anxiety disorders., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype‒phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Bacterial toxin-antitoxin (TA) systems consist of a toxin that inhibits essential cellular processes, such as DNA replication, transcription, translation, or ATP synthesis, and an antitoxin neutralizing their cognate toxin. These systems have roles in programmed cell death, defense against phage, and the formation of persister cells. Here, we characterized the previously identified Staphylococcus aureus TA system, tsaAT, which consists of two putative membrane proteins: TsaT and TsaA. Expression of the TsaT toxin caused cell death and disrupted membrane integrity, whereas TsaA did not show any toxicity and neutralized the toxicity of TsaT. Furthermore, subcellular fractionation analysis demonstrated that both TsaA and TsaT localized to the cytoplasmic membrane of S. aureus expressing either or both 3xFLAG-tagged TsaA and 3xFLAG-tagged TsaT. Taken together, these results demonstrate that the TsaAT TA system consists of two membrane proteins, TsaA and TsaT, where TsaT disrupts membrane integrity, ultimately leading to cell death. Although sequence analyses showed that the tsaA and tsaT genes were conserved among Staphylococcus species, amino acid substitutions between TsaT orthologs highlighted the critical role of the 6th residue for its toxicity. Further amino acid substitutions indicated that the glutamic acid residue at position 63 in the TsaA antitoxin and the cluster of five lysine residues in the TsaT toxin are involved in TsaA's neutralization reaction. This study is the first to describe a bacterial TA system wherein both toxin and antitoxin are membrane proteins. These findings contribute to our understanding of S. aureus TA systems and, more generally, give new insight into highly diverse bacterial TA systems., (© 2024 The Author(s). The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Anderson-Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a pathological variant of the α-galactosidase A (GLA) gene that results in deficient GLA activity. GLA deficiency leads to the accumulation of globotriaosylceramide (Gb3) and lyso-Gb3 in many tissues. A certain number of FD patients have burning pain or acroparesthesia in the feet and hands since childhood. Enzyme replacement therapy (ERT) is available for FD patients. However, ERT does not dramatically improve these FD-related peripheral neuropathic pain. We generated an adeno-associated virus serotype PHP.eB (AAV-PHP.eB) vector encoding mouse GLA cDNA, which was administered to FD mice intrathecally (it) or intravenously (iv). In the it-administered AAV (it-AAV) FD mice, the GLA enzyme activity in the lumbar dorsal root ganglion (DRG) was significantly greater than that in the untreated (NT) FD mice, and the level of activity was similar to that in wild-type (WT) B6 mice. However, in iv-administered AAV (iv-AAV) FD mice, GLA activity in the DRG did not increase compared to that in NT FD mice. Gb3 storage in the DRG of it-AAV FD mice was reduced compared to that in the DRG of NT FD mice. However, compared with NT FD mice, iv-AAV FD mice did not exhibit a significant reduction in the expression of the Gb3 substrate. Compared with WT mice, FD mice were thermally hyposensitive at 52 °C according to the hot plate test. The it-AAV FD mice showed significant recovery from thermal hyposensitivity. However, the iv-AAV FD mice did not exhibit significant improvement in thermal hyposensitivity. These results suggest that the intrathecal delivery of AAV-PHP.eB-mGLA may be a valuable tool for the treatment of FD-related peripheral neuropathic pain., Competing Interests: Declaration of competing interest H Kobayashi has received research grants from Amicus Therapeutics Icn. (Japan), Sumitomo Pharma Co., Ltd. (Japan), and JCR Pharmaceuticals Co., Ltd. (Japan). T Ohashi is a research advisor for JCR Pharmaceuticals Co., Ltd. (Japan). The other authors declare no conflicting interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: There is limited evidence between lumbar disk degeneration and normal lumbar segmental range of motions (SRMs), because previous studies were skewed by age and lacked large cohort of asymptomatic data. We aimed to characterize the normal lumbar SRMs according to age and gender and determine its association with disk degeneration., Methods: A total of 639 healthy Japanese volunteers (≥50 individuals of each decade of age from 20 to 79) without any symptom or morphological spinal abnormalities, who underwent lumbar radiograph and magnetic resonance image (MRI), were selected retrospectively. SRMs were evaluated by the flexion-extension radiographs taken in the recumbent position. Disk degenerations were assessed according to the Pfirrmann grade using MRI T2 imaging., Results: The mean SRMs became larger in the lower lumbar level. The range of the mean SRMs was smallest at L1-2 and largest at L4-5: 6 to 9 degrees at L1/2, to peaking at 11-14 degrees at L4/5 in male, and 6-8 degrees at L1/2, to peaking at 11-17 degrees at L4/5 in female. Lumbar disk degeneration progressed faster with age in the lower lumbar spine than in the upper lumbar level. SRM did not change depending on the severity of disk degeneration in upper lumbar spine, but significantly decreased with progressive disk degeneration in the lower lumbar spine., Conclusions: These findings could help to identify the normal lumbar SRMs that might be useful to evaluate the instability or inflexibility in the clinical situation. Furthermore, our results demonstrated the transition of the normative lumbar SRMs based on age, gender, and lumbar level., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2025 The Japanese Society for Spine Surgery and Related Research.)

Common beans (CB), a vital source for high protein content, plays a crucial role in ensuring both nutrition and economic stability in diverse communities, particularly in Africa and Latin America. However, CB cultivation poses a significant threat to diseases that can drastically reduce yield and quality. Detecting these diseases solely based on visual symptoms is challenging, due to the variability across different pathogens and similar symptoms caused by distinct pathogens, further complicating the detection process. Traditional methods relying solely on farmers' ability to detect diseases is inadequate, and while engaging expert pathologists and advanced laboratories is necessary, it can also be resource intensive. To address this challenge, we present a AI-driven system for rapid and cost-effective CB disease detection, leveraging state-of-the-art deep learning and object detection technologies. We utilized an extensive image dataset collected from disease hotspots in Africa and Colombia, focusing on five major diseases: Angular Leaf Spot (ALS), Common Bacterial Blight (CBB), Common Bean Mosaic Virus (CBMV), Bean Rust, and Anthracnose, covering both leaf and pod samples in real-field settings. However, pod images are only available for Angular Leaf Spot disease. The study employed data augmentation techniques and annotation at both whole and micro levels for comprehensive analysis. To train the model, we utilized three advanced YOLO architectures: YOLOv7, YOLOv8, and YOLO-NAS. Particularly for whole leaf annotations, the YOLO-NAS model achieves the highest mAP value of up to 97.9% and a recall of 98.8%, indicating superior detection accuracy. In contrast, for whole pod disease detection, YOLOv7 and YOLOv8 outperformed YOLO-NAS, with mAP values exceeding 95% and 93% recall. However, micro annotation consistently yields lower performance than whole annotation across all disease classes and plant parts, as examined by all YOLO models, highlighting an unexpected discrepancy in detection accuracy. Furthermore, we successfully deployed YOLO-NAS annotation models into an Android app, validating their effectiveness on unseen data from disease hotspots with high classification accuracy (90%). This accomplishment showcases the integration of deep learning into our production pipeline, a process known as DLOps. This innovative approach significantly reduces diagnosis time, enabling farmers to take prompt management interventions. The potential benefits extend beyond rapid diagnosis serving as an early warning system to enhance common bean productivity and quality., (© 2024. The Author(s).)

Purpose: To evaluate the utility of model-based deep learning reconstruction in prostate diffusion-weighted imaging (DWI)., Methods: This retrospective study evaluated two prostate diffusion-weighted imaging (DWI) methods: deep learning reconstruction (DL-DWI) and traditional parallel imaging (PI-DWI). We examined 32 patients with radiologically diagnosed and histologically confirmed prostate cancer (PCa) lesions ≥10 mm. Image quality was evaluated both qualitatively (for overall quality, prostate conspicuity, and lesion conspicuity) and quantitatively, using the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) for prostate tissue., Results: In the qualitative evaluation, DL-DWI scored significantly higher than PI-DWI for all three parameters (p<0.0001). In the quantitative analysis, DL-DWI showed significantly higher SNR and CNR values compared to PI-DWI (p<0.0001). Both the prostate tissue and the lesions exhibited significantly higher ADC values in DL-DWI compared to PI-DWI (p<0.0001, p=0.0014, respectively)., Conclusion: Model-based DL reconstruction enhanced both qualitative and quantitative aspects of image quality in prostate DWI. However, this study did not include comparisons with other DL-based methods, which is a limitation that warrants future research., Competing Interests: The authors of this manuscript declare relationships with the following companies: Masami Yoneyama and Jihun Kwon are currently employed by Philips Japan. The other authors declare that they have no conflicts of interest., (© 2024 The Authors.)

Differentially Private Federated Learning (DP-FL) has garnered attention as a collaborative machine learning approach that ensures formal privacy. Most DP-FL approaches ensure DP at the record-level within each silo for cross-silo FL. However, a single user's data may extend across multiple silos, and the desired user-level DP guarantee for such a setting remains unknown. In this study, we present Uldp-FL, a novel FL framework designed to guarantee user-level DP in cross-silo FL where a single user's data may belong to multiple silos. Our proposed algorithm directly ensures user-level DP through per-user weighted clipping, departing from group-privacy approaches. We provide a theoretical analysis of the algorithm's privacy and utility. Additionally, we improve the utility of the proposed algorithm with an enhanced weighting strategy based on user record distribution and design a novel private protocol that ensures no additional information is revealed to the silos and the server. Experiments on real-world datasets show substantial improvements in our methods in privacy-utility trade-offs under user-level DP compared to baseline methods. To the best of our knowledge, our work is the first FL framework that effectively provides user-level DP in the general cross-silo FL setting.

Itch is a protective/defensive function with divalent motivational drives. Itch itself elicits an unpleasant experience, which triggers the urge to scratch, relieving the itchiness. Still, it can also result in dissatisfaction when the scratch is too intense and painful or unsatisfactory due to insufficient scratch effect. Therefore, it is likely that the balance between the unpleasantness/pleasure and satisfaction/unsatisfaction associated with itch sensation and scratching behavior is determined by complex brain mechanisms. The physiological/pathological mechanisms underlying this balance remain largely elusive. To address this issue, we targeted the "reward center" of the brain, the nucleus accumbens (NAc), in which itch-responsive neurons have been found in rodents. We examined how neurons in the NAc are activated or suppressed during histamine-induced scratching behaviors in mice. The mice received an intradermal injection of histamine or saline at the neck, and the scratching number was analyzed by recording the movement of the bilateral hind limbs for about 45 min after injection. To experimentally manipulate the scratch efficacy in these histamine models, we compared histamine's behavioral and neuronal effects between mice with intact and clipped nails on the hind paws. As expected, the clipping of the hind limb nail increased the number of scratches after the histamine injection. In the brains of mice exhibiting scratching behaviors, we analyzed the expression of the c-fos gene (Fos) as a readout of an immediate activation of neurons during itch/scratch and dopamine receptors (Drd1 and Drd2) using multiplex single-molecule fluorescence in situ hybridization (RNAscope) in the NAc and surrounding structures. We performed a model-free analysis of gene expression in geometrically divided NAc subregions without assuming the conventional core-shell divisions. The results indicated that even within the NAc, multiple subregions responded differentially to various itch/scratch conditions. We also found different clusters with neurons showing similar or opposite changes in Fos expression and the correlation between scratch number and Fos expression in different itch/scratch conditions. These regional differences and clusters would provide a basis for the complex role of the NAc and surrounding structures in encoding the outcomes of scratching behavior and itchy sensations., (© 2024. The Author(s).)

Paramyxo- and filovirus genomes are equipped with bipartite promoters at their 3 ' ends to initiate RNA synthesis. The two elements, the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2), are separated by a spacer region that must be precisely a multiple of 6 nucleotides (nts), indicating these viruses adhere to the "rule of six." However, our knowledge of PE2 has been limited to a narrow spectrum of virus species. In this study, a comparative analysis of 1,647 paramyxoviral genomes from a public database revealed that the paramyxovirus PE2 can be clearly categorized into two distinct subcategories: one marked by C repeats at every six bases (exclusive to the subfamily Orthoparamyxovirinae ) and another characterized by CG repeats every 6 nts (observed in the subfamilies Avulavirinae and Rubulavirinae ). This unique pattern collectively mirrors the evolutionary lineage of these subfamilies. Furthermore, we showed that PE2 of the Rubulavirinae , with the exception of mumps virus, serves as part of the gene-coding region. This may be due to the fact that the Rubulavirinae are the only paramyxoviruses that cannot propagate without RNA editing. Filoviruses have three to eight consecutive uracil repeats every six bases (UN 5 ) in PE2, which is located in the 3 ' end region of the genome. We obtained PE2 sequences from 2,195 filoviruses in a public database and analyzed the sequence conservation among virus species. Our results indicate that the continuity of UN 5 hexamers is consistently maintained with a high degree of conservation across virus species., Importance: The genomic intricacies of paramyxo- and filoviruses are highlighted by the bipartite promoters-promoter element 1 (PE1) and promoter element 2 (PE2)-at their 3 ' termini. The spacer region between these elements follows the "rule of six," crucial for genome replication. By a comprehensive analysis of paramyxoviral genome sequences, we identified distinct subcategories of PE2 based on C and CG repeats that were specific to Orthoparamyxovirinae and Avulavirinae / Rubulavirinae , respectively, mirroring their evolutionary lineages. Notably, the PE2 of Rubulavirinae is integrated into the gene-coding region, a unique trait potentially linked to its strict dependence on RNA editing for virus growth. This study also focused on the PE2 sequences in filovirus genomes. The strict conservation of the continuity of UN 5 among virus species emphasizes its crucial role in viral genome replication., Competing Interests: The authors declare no conflict of interest.

Background: Young-onset dementia (YOD) community care requires personalised approaches. Yet, the specific details of YOD consultations are unclear. This study explored how initial consultations correlate with client profiles., Methods: Data from regional YOD helplines were used to analyze the main characteristics of people living with YOD or who had concerns about the possibility of YOD (n = 132). Among several categorical variables, the following were used for analysis: age group, sex, type of living arrangement, employment status, presence of dementia, and content of the consultation. To identify groups of items that frequently occur together, strongly connected rules were identified using association rule analysis with the a priori algorithm. To focus on the characteristics of clients, rules related to client characteristics were extracted based on the type of consultation., Results: A total of 51 rules were identified for the consultations. These rules fell into two categories: (1) consultations for medical matters, which mainly involved employed individuals with undiagnosed dementia, and (2) other consultations on daily life or work, which mainly involved individuals diagnosed with dementia and were characterised by the influence of sex. These rules indicate the importance of medical involvement in confirming the diagnosis and specific individualised care following diagnosis for people living with YOD., Conclusion: Clients with or without a dementia diagnosis were consulted differently in the YOD helplines. Before receiving a diagnosis, medical matters were the main theme of consultations, whereas after receiving a diagnosis, adjustments to daily life or work were the main themes. The results of this study suggest that the needs of people living with YOD and the services they require may vary depending on their backgrounds., (© 2024 Japanese Psychogeriatric Society.)

The monosynaptic connection from the lateral parabrachial nucleus (LPB) to the central amygdala (CeA) serves as a fundamental pathway for transmitting nociceptive signals to the brain. The LPB receives nociceptive information from the dorsal horn and spinal trigeminal nucleus and sends it to the "nociceptive" CeA, which modulates pain-associated emotions and nociceptive sensitivity. To elucidate the role of densely expressed mu-opioid receptors (MORs) within this pathway, we investigated the effects of exogenously applied opioids on LPB-CeA synaptic transmission, employing optogenetics in mice expressing channelrhodopsin-2 in LPB neurons with calcitonin gene-related peptide (CGRP). A MOR agonist ([D-Ala 2 ,N-Me-Phe 4 ,Glycinol 5 ]-enkephalin, DAMGO) significantly reduced the amplitude of light-evoked excitatory postsynaptic currents (leEPSCs), in a manner negatively correlated with an increase in the paired-pulse ratio. An antagonist of MORs significantly attenuated these effects. Notably, this antagonist significantly increased leEPSC amplitude when applied alone, an effect further amplified in mice subjected to lipopolysaccharide injection 2 h before brain isolation, yet not observed at the 24-h mark. We conclude that opioids could shut off the ascending nociceptive signal at the LPB-CeA synapse through presynaptic mechanisms. Moreover, this gating process might be modulated by endogenous opioids, and the innate immune system influences this modulation., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Functional somatic syndromes (FSSs) represent a clinically important group of disorders that are often stress-related. Their autonomic pathophysiology, including reduced heart rate variability (HRV), has been reported. However, the response pattern to mental stress and recovery in FSSs remains unclear. Thus, we aimed to clarify the pattern of autonomic stress response and recovery to mental arithmetic stress in patients with FSS compared to that in healthy controls. This cross-sectional study included 79 patients with FSS who visited the Department of Psychosomatic Medicine at a university hospital in Japan and 39 healthy controls. Following a mood questionnaire and obtaining epidemiologic information, HRV was measured during three periods (5 min each): relaxation baseline resting, stress (mental arithmetic task), and post-stress recovery period. The HRV analysis included inter-beat interval, low frequency power, and high frequency power. Compared to healthy controls, patients with FSS exhibited significantly higher scores on the mood questionnaire, prolonged duration of illness, and decreased functionality in daily activities. While the healthy control group showed a pronounced stress response pattern with a significant decrease in vagal HRV and recovery, the FSS group showed a "flat" vagal stress response pattern, and the HRV in the FSS group was lower at relaxation baseline, remained low during the stress, and did not change post stress. Patients with severe FSS exhibit an altered stress response pattern. Our results could provide significant clues for the diagnosis and treatment of such patients, as well as useful insights into the relationship between stress and illness., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Skeletal muscle development is a highly ordered process orchestrated transcriptionally by the myogenic regulatory factors. However, the downstream molecular mechanisms of myogenic regulatory factor functions in myogenesis are not fully understood. Here, we identified the RNA-binding protein Musashi2 (Msi2) as a myogenin target gene and a post-transcriptional regulator of myoblast differentiation. Msi2 knockdown in murine myoblasts blocked differentiation without affecting the expression of MyoD or myogenin. Msi2 overexpression was also sufficient to promote myoblast differentiation and myocyte fusion. Msi2 loss attenuated autophagosome formation via down-regulation of the autophagic protein MAPL1LC3/ATG8 (LC3) at the early phase of myoblast differentiation. Moreover, forced activation of autophagy effectively suppressed the differentiation defects incurred by Msi2 loss. Consistent with its functions in myoblasts in vitro, mice deficient for Msi2 exhibited smaller limb skeletal muscles, poorer exercise performance, and muscle fiber-type switching in vivo. Collectively, our study demonstrates that Msi2 is a novel regulator of mammalian myogenesis and establishes a new functional link between muscular development and autophagy regulation., (© 2024 Wang et al.)

Dengue virus (DENV) causes dengue fever and dengue hemorrhagic fever, and DENV infection kills 20,000 people annually worldwide. Therefore, the development of anti-DENV drugs is urgently needed. Sofosbuvir (SOF) is an effective drug for HCV-related diseases, and its triphosphorylated metabolite inhibits viral RNA synthesis by the RNA-dependent RNA polymerase (RdRp) of HCV. (2'R)-2'-Deoxy-2'-fluoro-2'-methyluridine (FMeU) is the dephosphorylated metabolite produced from SOF. The effects of SOF and FMeU on DENV1 replication were analyzed using two DENV1 replicon-based methods that we previously established. First, a replicon-harboring cell assay showed that DENV1 replicon replication in human hepatic Huh7 cells was decreased by SOF but not by FMeU. Second, a transient replicon assay showed that DENV1 replicon replication in Huh7 cells was decreased by SOF; however, in hamster kidney BHK-21 cells, it was not suppressed by SOF. Additionally, the replicon replication in Huh7 and BHK-21 cells was not affected by FMeU. Moreover, we assessed the effects of SOF on infectious DENV1 production. SOF suppressed infectious DENV1 production in Huh7 cells but not in monkey kidney Vero cells. To examine the substrate recognition of the HCV and DENV1 RdRps, the complex conformation of SOF-containing DENV1 RdRp or HCV RdRp was predicted using AlphaFold 2. These results indicate that SOF may be used as a treatment for DENV1 infection.

Japanese spotted fever (JSF) is a tick-transmitted infection caused by  Rickettsia japonica  ( R. japonica ), which is indigenous to Japan. Patients with JSF typically present with fever and spotted erythema on the palms and/or soles, and most of them have site(s) of tick bites. The prognosis is good, but some cases have a fatal course. Kawasaki disease (KD) is a systemic vasculitis with an unknown cause that is characterized by symptoms such as fever, conjunctival injection, oral findings, amorphous rash, rigid edema, and nonsuppurative cervical lymphadenopathy. Although the symptoms of JSF are partially similar to those of KD, case reports of JSF overlapping KD have never been internationally published. Herein, we report a boy with JSF and KD symptoms. A five-year-old boy presented with fever and rash after he had been on a mountain inhabited by  R. japonica . On the fifth day, erythema was spotted mainly on his bilateral palms, bilateral cervical lymphadenopathy, rigid edema of his lower feet, and mild conjunctival injection appeared. Intravenous immunoglobulin (IVIG) therapy was performed because these symptoms satisfied five out of the six diagnostic criteria for KD. However, on the sixth day, the fever persisted, and then we readministered IVIG in addition to tosufloxacin and azithromycin since we found a tick-bite eschar, which suggested a complication of JSF. His symptoms resolved soon after this treatment. Coronary artery lesions were never observed. This case indicates that the R. japonica  infection overlaps clinically with KD. Tosufloxacin and azithromycin should be considered to avoid the use of minocycline in younger patients with JSF., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sasaki et al.)

We numerically study the anisotropic Turing patterns (TPs) of an activator-inhibitor system described by the reaction-diffusion (RD) equation of Turing, focusing on anisotropic diffusion using the Finsler geometry (FG) modeling technique. In FG modeling, the diffusion coefficients are dynamically generated to be direction dependent owing to an internal degree of freedom (IDOF) and its interaction with the activator and inhibitor. Because of this dynamical diffusion coefficient, FG modeling of the RD equation sharply contrasts with the standard numerical technique in which direction-dependent coefficients are manually assumed. To find the solution of the RD equations in FG modeling, we use a hybrid numerical technique combining the Metropolis Monte Carlo method for IDOF updates and discrete RD equations for steady-state configurations of the activator-inhibitor variables. We find that the newly introduced IDOF and its interaction are a possible origin of spontaneously emergent anisotropic patterns of living organisms, such as zebra and fishes. Moreover, the IDOF makes TPs controllable by external conditions if the IDOF is identified with the direction of cell diffusion accompanied by thermal fluctuations.

Introduction: Pembrolizumab (Pemb) therapy in conjunction with carboplatin and paclitaxel (PTX)/nab-PTX has been efficacious in treating non-small cell lung cancer (NSCLC). However, the response predictors of this combination therapy (Pemb-combination) remain undetermined. We aimed to evaluate whether Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are potential factors in prognosticating the response to Pemb-combination therapy in advanced NSCLC patients., Methods: We retrospectively recruited 144 NSCLC patients receiving first-line treatment with Pemb-combination therapy from 13 institutions between December 1, 2018, and December 31, 2020. GPS, NLR, BMI, PLR, and PNI were assessed for their efficacy as prognostic indicators. Cox proportional hazard models and the Kaplan-Meier method were used to compare the progression-free survival (PFS) and overall survival (OS) of the patients., Results: The treatment exhibited a response rate of 63.1% (95% confidence interval [CI]: 55.0-70.6%). Following Pemb-combination administration, the median PFS and OS were 7.3 (95% CI: 5.3-9.4) and 16.5 (95% CI: 13.9-22.1) months, respectively. Contrary to PNI, NLR, GPS, BMI, and PLR did not display substantially different PFS in univariate analysis. However, multivariate analysis did not identify PNI as an independent prognostic factor for PFS. Furthermore, univariate analysis revealed that GPS, BMI, and PLR exhibited similar values for OS but not NLR and PNI. Patients with PNI ≥45 were predicted to have better OS than those with PNI &lt;45 (OS: 23.4 and 13.9 months, respectively, p = 0.0028). Multivariate analysis did not establish NLR as an independent prognostic factor for OS., Conclusion: The PNI evidently predicted OS in NSCLC patients treated with Pemb-combination as first-line therapy, thereby validating its efficiency as a prognostic indicator of NSCLC., (© 2023 S. Karger AG, Basel.)

Congenital tracheal stenosis is a rare life-threatening disorder caused by narrow O-shaped tracheal ring without smooth muscle. Its underlying genetic cause has not been elucidated. We performed whole exome sequencing in a patient with congenital tracheal stenosis and congenital heart defect, and identified a de novo pathogenic TBX5 variant (NM&#95;181486.4:c.680T>C, p.(Ile227Thr)). The Ile227Thr-TBX5 protein was predicted to have a decreased stability by in silico protein structural analyses, and was shown to have a significantly reduced activity for the NPPA promoter by luciferase assay. The results, together with the expression of mouse Tbx5 in the lung and trachea and the development of tracheal cartilage dysplasia in the lung-specific Tbx5 null mice, imply the relevance of TBX5 pathogenic variants to congenital tracheal stenosis., (© 2023 Japanese Teratology Society.)

With the rapid expansion of genomic medicine, more citizens are compelled to think about genetics in their daily lives. This study aims to explore appropriate types of educational media and methods to enlighten activities for genetics and hereditary cancer. We presented an 18-min YouTube video on genetics and hereditary cancer to participants at a scientific event, Science Agora 2020, and administered a web questionnaire to investigate their opinions about when and how citizens should start learning about genetics and hereditary cancer. We recruited 133 participants who watched the video, and 26.3% (35/133) responded to the questionnaire. Most of them were evaluated to understand and appreciate the contents of the video. They identified websites, or videos as suitable learning media, irrespective of their sex, age, or profession. They highlighted upper elementary school or junior high school as appropriate educational stages to start learning about genetics and hereditary cancer to facilitate collecting their own genetic information by themselves. Our findings show that educational institutions should provide opportunities to learn about genetics and hereditary cancers, especially for upper elementary school and junior high school students, using learning media, such as videos, depending on their level or demand., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The patient was a 33-year-old female. She was referred to our hospital from a previous clinic with abdominal pain and vomiting. Contrast-enhanced abdominal CT revealed intussusception, leading to a diagnosis of intussusception with a small intestinal tumor as an advanced part. Intestinal obstruction symptoms were observed, and emergency surgery was performed on the same day. As a technique, single port surgery was selected, and laparoscopic reduction was attempted. However, it was ineffective. The site of intussusception was induced outside the body through a small laparotomy wound, and reduction was performed using Hutchinson's procedure. As an adjacent lymph node was markedly swollen, the mesentery involving this lymph node was dissected in a fan shape, and the tumor was extirpated. The tumor measured 40 mm in long diameter, being a hemicircular, protruding lesion. Histologically, disarray of short spindle tumor cells was observed. Immunostaining showed Kit- and DOG1-negtive reactions and partially α-SMA and desmin-positive reactions, suggesting leiomyosarcoma. With the establishment of an immunostaining-test-based classification, leiomyosarcoma is currently rare. In this study, we report a patient in whom single port surgery for intussusception related to small intestinal leiomyosarcoma was successful.

Background: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity., Case Presentation: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated., Conclusions: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions., (© 2023. The Author(s).)

Neonates infected with enterovirus in utero would be fulminant at birth or develop symptoms within a few days. Echovirus 11 causes life-threatening hepatic necrosis with coagulopathy and adrenal hemorrhagic necrosis. The prognosis depends on the enterovirus serotype and the absence of serotype-specific maternal antibodies at the time of delivery. We describe a fatal neonatal case of congenital echovirus 11 infection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Context: We have previously reported that a specific "AGATC" haplotype in a >34 kb tight linkage disequilibrium (LD) block within ESR1 is strongly associated with cryptorchidism and hypospadias in Japanese boys., Objective: We aimed to determine the true susceptibility factor for cryptorchidism and hypospadias linked to the "AGATC" haplotype., Methods: We performed various molecular studies in hitherto unreported 230 Italian boys (80 with cryptorchidism and 150 with normal genitalia) and previously reported and newly recruited 415 Japanese boys (149 with cryptorchidism, 141 with hypospadias, and 125 with normal genitalia). We also performed ESR1 expression analyses using breast cancer-derived MCF-7 cells., Results: Haplotype analysis revealed the LD block and positive association of the "AGATC" haplotype with cryptorchidism in Italian boys. Whole genome sequencing identified an identical 2249-bp microdeletion (ΔESR1) generated by a microhomology-mediated replication error in both Japanese and Italian boys with the specific haplotype. ΔESR1 was found to be strongly associated with cryptorchidism and hypospadias by Cochran-Armitage trend test and was revealed to show nearly absolute LD with the "AGATC" haplotype. ESR1 expression was upregulated in MCF-7 cells with a homozygous deletion encompassing ΔESR1 and those with a homozygous deletion involving a CTCF-binding site within ΔESR1., Conclusion: The results reveal that ΔESR1, which has been registered as "DEL&#95;6&#95;75504" in gnomAD SVs v2.1, is the true susceptibility factor for cryptorchidism and hypospadias. It appears that ΔESR1 was produced in a single ancestral founder of modern humans and has been maintained within the genome of multiple ethnic groups by selection., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory multisystem condition associated with coronavirus disease (COVID-19). Critically ill COVID-19 patients may develop multiorgan damage and elevated inflammatory responses, thus making it difficult to differentiate between progression to organ damage due to COVID-19 itself or MIS-A. This study aimed to explore the characteristics and complications of MIS-A in critical COVID-19 patients., Methods: The Japan Extracorporeal Membrane Oxygenation (ECMO) Network and ICU Collaboration Network developed a web-based database system called the CRoss Intensive Care Unit Searchable Information System (CRISIS) to monitor critical COVID-19 patients throughout Japan. We retrospectively identified patients with MIS-A among critical COVID-19 patients enrolled from March 2020 to December 2021, using CRISIS. Our MIS-A definition required patients to be at least 18 years of age, have laboratory evidence of inflammation, severe dysfunction of at least two extrapulmonary organ systems, and no plausible alternative diagnoses., Results: Of the 1052 patients, 26 (2.5%) were diagnosed with MIS-A. The MIS-A patients had a higher likelihood of using ECMO (13% vs. 46%, p  < 0.001) and lower overall survival (77% vs. 42%, p  < 0.001) than non-MIS-A patients. More than 80% of the MIS-A cases occurred 3 weeks after the COVID-19 onset., Conclusion: Multisystem inflammatory syndrome in adults can occur in 2.5% of critically ill COVID-19 patients, and the mortality rate is high. Multisystem inflammatory syndrome in adults may be considered when there is a re-elevation of the unexplained inflammatory response and severe dysfunction of at least two extrapulmonary organ systems several weeks after the onset of COVID-19., Competing Interests: Authors declare no conflict of interest for this article. Dr. Shigeki Kushimoto is an Editorial Board member of Acute Medicine and Surgery and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication., (© 2023 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Introduction: Ileorectal fistulas following sigmoid colon vaginoplasty are rare. Reports on the management of the surgical complications of sex reassignment operations among transgender patients are few., Presentation of Case: A 40-year-old patient with a male-to-female sex identity disorder underwent sigmoid vaginoplasty for sex reassignment 4 months prior to presentation. The patient was referred for persistent diarrhea and postoperative lower abdominal pain. Proctoscopy, gastrografin enema, and small bowel enterography revealed rectal anastomotic stenosis and an ileorectal fistula. The prior anastomotic site and ileal rectal fistula were resected, and ileal interposition reconstruction was performed to avoid damaging the blood supply to the artificial vagina. Routine follow-up after the closure of the diverting ileostomy showed no new pathologies., Discussion: This case highlighted the management of surgical complications after sex reassignment surgery., Conclusion: Ileal interposition was a useful reconstruction method after resecting the colonic anastomotic site to preserve the artificial vagina., Competing Interests: Declaration of competing interest None of the authors had conflicts of interests associated with this case report., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives : This study aimed to elucidate the role of laser photocoagulation therapy in the treatment of diabetic macular edema (DME) as an alternative to, or in conjunction with, the first-line treatment, anti-vascular endothelial growth factor (VEGF). Materials and Methods : A comprehensive literature search to identify studies that evaluated the efficacy of laser photocoagulation therapy in the management of DME was performed. The relevant findings of the efficacy of focal/grid laser therapy from data in randomized, controlled trials were synthesized, and the potential of new laser technologies, such as navigated laser systems, pattern scan lasers, and subthreshold lasers, was explored. The usefulness of multimodal imaging-guided laser therapy was also evaluated, with a focus on the potential contribution to anti-VEGF therapy. Results : Focal laser photocoagulation targeting microaneurysms remains an effective therapeutic approach to chronic refractory edema, despite the widespread use of anti-VEGF therapy. To achieve the best possible treatment outcomes, precise identification of microaneurysms is essential. This requires the use of multimodal imaging-guided, highly accurate, minimally invasive coagulation techniques. Subthreshold laser therapy can also reduce the frequency of anti-VEGF injections and minimize treatment burden. Conclusions : Further studies are needed to determine the optimal timing and settings for laser photocoagulation therapy and the potential of new laser technologies in the management of DME. Nevertheless, laser photocoagulation therapy plays an important role in the management of DME, in conjunction with anti-VEGF therapy.

Aims: This study aimed to determine whether pathological changes in the bone marrow cause Osteoarthritis (OA) pain based on magnetic resonance imaging (MRI), immunohistochemistry, and electrophysiology., Main Methods: Adjuvant-induced arthritis (AIA) was achieved by injecting 150 μL of complete Freund's adjuvant into the right knee joints of male Sprague-Dawley rats. AIA rats were compared with saline-injected rats., Key Findings: AIA significantly induced mechanical hyperalgesia and spontaneous pain in the right hind paw 1-14 days after induction. Intratibial injection of 50 μL of 1 % lidocaine significantly suppressed AIA-induced mechanical hyperalgesia (p = 0.0001) and spontaneous pain (p = 0.0006) 3 days after induction. In T2-weighted MRI, AIA induced high-signal intensity within the proximal tibial metaphysis, and the mean T2 values in this area significantly increased on days 3 (p = 0.0043) and 14 (p = 0.0012) after induction. AIA induced intraosseous edema and significantly increased the number of intraosseous granulocytes on days 3 (p < 0.0001) and 14 (p < 0.0001) after induction. The electrophysiological study on days 3-7 after induction showed significantly increased spontaneous firing rates (p = 0.0166) and evoked responses to cutaneous stimuli (brush, p < 0.0001; pinching, p = 0.0359) in the right hind paw plantar surface and intratibial stimuli (p = 0.0002) in wide-dynamic-range neurons of the spinal dorsal horn., Significance: Intraosseous changes caused by OA induce hypersensitivity in the sensory afferents innervating bone marrow may be involved in OA pain. Novel bone marrow-targeted therapies could be beneficial for treating OA pain., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

We present a case of breast angiosarcoma. Although B-mode ultrasonography did not indicate a tumor, contrast-enhanced ultrasonography (CEUS) was successfully delineated it. CEUS helped identify the tumor and its extent., (© 2023 Wiley Periodicals LLC.)

Intravitreal injection of triamcinolone acetonide (TA) is essential for clinical treatment in patients who insufficiently respond to vascular endothelial factor inhibitors for diabetic macular edema (DME). The aim of this study was to investigate microvascular changes treated with TA using optical coherence tomography angiography (OCTA). After TA in twelve eyes of eleven patients with central retinal thickness (CRT), there was a 20% or more reduction observed. Visual acuity, the number of microaneurysms, vessel density, and the foveal avascular zone (FAZ) area were compared before and at 2 months after TA. At baseline, the number of microaneurysms was 2.1 ± 1.1 in the superficial capillary plexuses (SCP) and 2.0 ± 1.1 in the deep capillary plexuses (DCP), with a significant decrease post-treatment to 1.0 ± 1.0 for SCP and 0.8 ± 0.8 for DCP (SCP; p = 0.018, DCP; p = 0.008). There was significant enlargement of the FAZ area from 0.28 ± 0.11 mm 2 to 0.32 ± 0.14 mm 2 ( p = 0.041). There was no significant difference in the visual acuity and vessel density of SCP and DCP. Results indicated that OCTA was useful for the evaluation of qualitative and morphological retinal microcirculation and that intravitreal TA may decrease microaneurysms., Competing Interests: The authors have no proprietary interest in the materials used in this study.

Dengue is a febrile illness caused by the dengue virus (DENV) that belongs to the genus Flavivirus in the family Flaviviridae. Cross-reactivity between flaviviruses poses a challenge while interpreting serological test results. In the present study, the cross-reactivity of sera of the patients with dengue, who traveled from Japan to DENV-endemic countries, was analyzed by using an enzyme-linked immunosorbent assay (ELISA) and neutralization test (NT). Sixteen serum samples were collected from patients with dengue and were tested for: i) IgM antibodies against Zika virus (ZIKV), West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) using IgM ELISA, ii) IgG antibody against TBEV using IgG ELISA, and iii) neutralizing antibody against ZIKV, WNV, TBEV, and JEV. Among the 16 samples tested using ELISA, seven samples were IgM-positive for at least one of the other flaviviruses, and nine samples were IgG-positive for TBEV. Neutralizing antibody titers (NATs) against ZIKV, WNV, and TBEV were one-fourth or lower than those against the causative DENV in all samples. The NATs against JEV were one-fourth or lower than those against the causative DENV in six convalescent-phase serum sample among the seven convalescent-phase serum samples. The NAT against DENV of the residual one convalescent-phase serum was similar to that against JEV and that against JEV of its relevant acute-phase serum sample. These results showed that NTs with paired serum samples are important to correctly interpret the serological test results for DENV., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Nociplastic pain, the most recently proposed mechanistic descriptor of chronic pain, is the pain resulting from an altered nociceptive system and network without clear evidence of nociceptor activation, injury or disease in the somatosensory system. As the pain-associated symptoms in many patients suffering from undiagnosed pain would result from the nociplastic mechanisms, it is an urgent issue to develop pharmaceutical therapies that would mitigate the aberrant nociception in nociplastic pain. We have recently reported that a single injection of formalin to the upper lip shows sustained sensitization lasting for more than 12 days at the bilateral hindpaws, where there is no injury or neuropathy in rats. Using the equivalent model in mice, we show that pregabalin (PGB), a drug used for treating neuropathic pain, significantly attenuates this formalin-induced widespread sensitization at the bilateral hindpaws, even on the 6 day after the initial single orofacial injection of formalin. On the 10th day after formalin injection, the hindlimb sensitization before PGB injection was no more significant in mice receiving daily PGB injections, unlike those receiving daily vehicle injections. This result suggests that PGB would act on the central pain mechanisms that undergo nociplastic changes triggered by initial inflammation and mitigate widespread sensitization resulting from the established changes., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fusao Kato is a recipient of a collaborative study on the effects of novel gabapentinoids with Daiichi-Sankyo Co. Ltd., (© 2023 The Author(s).)

We investigated the ability of echo-planar imaging with L1-regularized iterative sensitivity encoding-based diffusion-weighted imaging (DWI) to improve the image quality and reduce the scanning time in prostate magnetic resonance imaging. We retrospectively analyzed 109 cases of prostate magnetic resonance imaging. We compared variables in the quantitative and qualitative assessments among 3 imaging groups: conventional parallel imaging-based DWI (PI-DWI) with an acquisition time of 3 minutes 15 seconds; echo-planar imaging with L1-regularized iterative sensitivity encoding-based DWI (L1-DWI) with a normal acquisition time (L1-DWINEX12) of 3 minutes 15 seconds; and L1-DWI with a half acquisition time (L1-DWINEX6) of 1 minute 45 seconds. As a quantitative assessment, the signal-to-noise ratio (SNR) of DWI (SNR-DWI), the contrast-to-noise ratio (CNR) of DWI (CNR-DWI), and the CNR of apparent diffusion coefficient were measured. As a qualitative assessment, the image quality and visual detectability of prostate carcinoma were evaluated. In the quantitative analysis, L1-DWINEX12 showed significantly higher SNR-DWI than PI-DWI (P = .0058) and L1-DWINEX6 (P < .0001). In the qualitative analysis, the image quality score for L1-DWINEX12 was significantly higher than those of PI-DWI and L1-DWINEX6. A non-inferiority assessment demonstrated that L1-DWINEX6 was non-inferior to PI-DWI in terms of both quantitative CNR-DWI and qualitative grading of image quality with a <20% inferior margin. L1-DWI successfully demonstrated a reduced scanning time while maintaining good image quality., Competing Interests: The authors declare relationships with the following companies: MY is currently employed by Philips Japan. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)