Search

Lacrimal punctal agenesis is an extremely rare condition with an unclear genetic basis. Here, we report a 3‐year‐old male patient harboring a hemizygous variant in glypican 4 (GPC4), which causes Keipert syndrome, who presented with complete lacrimal punctal agenesis, distinctive craniofacial features, mild developmental delay, mild intellectual disability, and autism. The craniofacial features included a prominent forehead, epicanthus, depressed and broad nasal bridge, hypoplastic columella, midface hypoplasia, tented upper lip, and low‐set ears. Proband exome sequencing identified a hemizygous variant in GPC4: NM_001448.3:c.1051C > T (p.Arg351*). The GPC4 variant was inherited from his heterozygous mother; X‐inactivation followed a skewed pattern in his mother. This patient demonstrated clinical features consistent with Keipert syndrome including craniofacial features, brachydactyly, broad distal phalanx, broad first toe, and mild developmental delay; however, agenesis of the lacrimal puncta has not been reported previously in Keipert syndrome. Our findings suggest that GPC4, which encodes a heparan‐sulfate proteoglycan, may play an important role in lacrimal morphogenesis. Our observations also suggest that Keipert syndrome should be considered in patients with lacrimal punctal agenesis. [ABSTRACT FROM AUTHOR]

Cellulose acetate (CA), synthesized by solid–liquid acetylation of low crystalline cellulose (LCCell) obtained by cold shearing in a short time under environmentally benign conditions, effectively enhanced the crystallization of poly(lactic acid) (PLA). The composite of PLA compounded with CA from LCCell exhibited higher crystallinity of PLA and flexural modulus than those from pristine PLA. CAs obtained from crystalline and recrystallized cellulose also improved the mechanical strength of PLA by compounding, but their effects were weaker than that of CA from LCCell. The factor of the effectiveness of CA obtained from LCCell is the higher miscibility with PLA originating from the sufficiently released interchain hydrogen bonds in the cellulose fibrils by cold shearing, which allows the dissolution of macroscopic aggregation of the CA chains in the composite. [ABSTRACT FROM AUTHOR]

Summary: Structural variations involving enhancer hijacking induce aberrant oncogene expression and cause tumorigenesis. A rare translocation, t(3;8)(q26.2;q24), is associated with MECOM and MYC rearrangement, causing myeloid neoplasms with a dismal prognosis. The most recent World Health Organization classification recognises myeloid neoplasms with MECOM rearrangement as acute myeloid leukaemia (AML) with defining genetic abnormalities. Recently, the increasing use of induced pluripotent stem cell (iPSC) technology has helped elucidate the pathogenic processes of haematological malignancies. However, its utility for investigating enhancer hijacking in myeloid neoplasms remains unclear. In this study, we generated iPSC lines from patients with myelodysplastic syndromes (MDS) harbouring t(3;8)(q26.2;q24) and differentiated them into haematopoietic progenitor cells to model the pathophysiology of MDS with t(3;8)(q26.2;q24). Our iPSC model reproduced the primary patient's MECOM expression changes and histone H3 lysine 27 acetylation (H3K27ac) patterns in the MECOM promoter and MYC blood enhancer cluster (BENC). Furthermore, we revealed the apoptotic effects of the bromodomain and extra‐terminal motif (BET) inhibitor on iPSC‐derived MDS cells by suppressing activated MECOM. Our study demonstrates the usefulness of iPSC models for uncovering the precise mechanism of enhancer hijacking due to chromosomal structural changes and discovering potential therapeutic drug candidates for cancer treatment. [ABSTRACT FROM AUTHOR]

Botulism is a deadly neuroparalytic condition caused by the botulinum neurotoxin (BoNT) produced by Clostridium botulinum and related species. Toxin‐neutralizing antibodies are the most effective treatments for BoNT intoxication. We generated human monoclonal antibodies neutralizing type B botulinum neurotoxin (BoNT/B), designated M2 and M4. The combination of these antibodies exhibited a strong neutralizing effect against BoNT/B toxicity. In this study, we analyzed the mechanisms of action of these antibodies in vitro. M4 binds to the C‐terminus of the heavy chain (the receptor‐binding domain) and inhibits BoNT/B binding to neuronal PC12 cells. Although M2 recognized the light (L) chain (the metalloprotease domain), it did not inhibit substrate (VAMP2) cleavage in the cleavage assay. M2 increased the surface localization of BoNT/B in PC12 cells at a later time point, suggesting that M2 inhibits the translocation of the L chain from synaptic vesicles to the cytosol. These results indicate that M2 and M4 inhibit the different processes of BoNT/B individually and that multistep inhibition is important for the synergistic effect of the combination of monoclonal antibodies. Our findings may facilitate the development of effective therapeutic antibodies against BoNTs. [ABSTRACT FROM AUTHOR]

Objectives: The osteological paradox recognizes that the presence of lesions is not always directly related with increased mortality. When combined with the clinical, historical, and epidemiological literature on scurvy, survivorship analysis, a form of statistical analysis to assess the relationship between the presence of diseases in the archeological record and survival, helps determine the overall burden of the disease both in terms of morbidity and mortality. This article explores the relationship between scurvy and survivorship in 26 adults from Man Bac, a Neolithic site from northern Vietnam together with prepublished evidence of scurvy in the nonadult population (n = 44). Methods: Diagnosis of scurvy included differential diagnosis combined with the Snoddy, A. M. E., Buckley, H. R., Elliott, G. E., Standen, V. G., Arriaza, B. T., & Halcrow, S. E. (2018). Macroscopic features of scurvy in human skeletal remains: A literature synthesis and diagnostic guide. American Journal of Physical Anthropology, 167(4), 876–895. https://doi.org/10.1002/ajpa.23699 threshold criteria and the Brickley, M. B., & Morgan, B. (2023). Assessing diagnostic certainty for scurvy and rickets in human skeletal remains. American Journal of Biological Anthropology, 181, 637–645 diagnostic certainty approaches. Kaplan–Meier survival curves were produced to assess the relationship between the presence of probable scurvy and age‐at‐death. Results: The prevalence of probable scurvy in adults (35%) was considerably lower than reported for the nonadults (80%). Almost all lesions observed in the adults were in a mixed stage of healing. Kaplan–Meier analysis demonstrated no difference in survivorship between infants and children (<15 years) with or without probable scurvy, whereas a meaningful difference was observed for the adults and adolescents (15+ years). Conclusions: The findings demonstrate that scurvy considerably decreased survivorship to older age categories. The degree of lesion remodeling, however, indicates that scurvy was not necessarily the direct cause of death but contributed to an overall disease burden that was ultimately fatal. [ABSTRACT FROM AUTHOR]

A gaseous mixture of CO2 and C5F10O has been widely investigated as one of the alternative gases for SF6. Due to the better electron attachment ability of oxygen molecule O2, it is generally expected that adding of O2 gas would improve the dielectric strength of arc quenching and insulating gas for electric power equipment. Therefore, in this paper, the dielectric breakdown properties of hot CO2/O2/C5F10O gas mixture were numerically estimated. The calculation results revealed that the critical electric field strength of the CO2/C5F10O gas mixture is disappointingly decreased by the addition of O2 gas, especially in the temperature range of 3000 K to 1000 K. This is brought about by the increase of ionization reaction of CO2 molecules with an increase in the O2 concentration in the arc‐quenching gas of CO2/O2/C5F10O. © 2024 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Background and Aim: The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance–pH (MII‐pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter‐based 24‐h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII‐pH test. Methods: Of the 366 patients who underwent MII‐pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high‐resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET > 6% identified from a derivation cohort (n = 109). A scoring system predicting AET > 6% was then constructed and externally validated with a separate cohort (n = 146). Results: Three variables were derived from the prediction model: male gender, Hill grades III–IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1–3 points), and high (4 points) risk groups. The probabilities of having an AET > 6% were 6%, 34%, and 100% for these groups, respectively. A score of < 1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort. Conclusions: We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD. [ABSTRACT FROM AUTHOR]

Many animal species have movement abilities. Behavior is important for evolutionary ecology because animal movement leads to dispersal, migration, search for food and mates, and escaping from enemies. However, individual differences in movement activity are found within a population. This phenomenon can be affected by various factors, one of which is suggesting that higher moving activity has fitness cost, whereas lower moving activity has benefits. Animal movement may also affect reproduction (e.g., resource allocation tradeoff between movement and reproduction as well as intra‐ and intersexual selection). Although many previous studies have investigated the relationship between movement and reproduction, less attention has been paid to walking movement. In this study, previous studies that investigated the relationship between movement and reproduction were reviewed using the flour beetle Tribolium castaneum, a model insect in behavioral ecology and genetics. Several previous studies suggest that beetle walking is strongly associated with male and female reproductive traits. In recent years, empirical studies on the correlation between walking and other traits have increased, particularly in T. castaneum. Although this species can fly and walk, the movement is often discussed without discriminating between flight and walk. Differences in modes of movement may affect the correlation between movement and other traits; thus, discussing each mode of movement separately is necessary. [ABSTRACT FROM AUTHOR]

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo‐electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population. [ABSTRACT FROM AUTHOR]

A novel and efficient method for the synthesis of sulfenamides with an S−N bond, which have attracted attention as industrial reagents and biologically active substances, is described herein. The reactions of benzoazole‐2‐thiones with various primary or secondary amines in the presence of triphenylbismuth dichloride at 60 °C in DMSO under aerobic conditions afforded the corresponding sulfenamides in moderate‐to‐excellent yields. This reaction is the first example of an efficient S−N bond formation reaction utilizing a low‐toxicity pentavalent organobismuth reagent under mild reaction conditions. The reaction will likely be applied to develop bioactive compounds with medicinal value or compounds with industrial utility. [ABSTRACT FROM AUTHOR]

Monitoring tactile pressure and recognizing action are important functionalities for artificial electronic skin (e‐skin). Furthermore, in order to create conformable coverings for 3D objects, an e‐skin needs to be stretchable, without sacrificing sensitivity to tactile pressure. However, stretching of sensors normally affects their output stability. In this study, a stretchable e‐skin is developed using laser‐induced graphene and a liquid metal alloy, GaInSn, in an elastic ecoflex polymer to create a stretchable, resistive‐type tactile pressure sensor. Furthermore, a pressure sensor array is fabricated as an e‐skin, and output is signal‐processed using machine learning. With this system, the e‐skin also monitors its stretching state, with the result that tactile pressure can be calculated regardless of the degree of stretching. With machine learning‐assisted e‐skin, actions such as patting, sliding, and grabbing are successfully recognized in the manner of human skin. [ABSTRACT FROM AUTHOR]

Förster resonance energy transfer (FRET) is ubiquitous in optical processes in the natural world. A methodology is proposed that uses an optical force to control its efficiency without contact in an aqueous solution of a thermo‐responsive polymer, polyvinyl methyl ether (PVME). Focusing irradiation of a near infrared laser beam into the solution results in the formation and trapping of a single polymer droplet. The polymer concentration in the droplet is controllable by changing the optical force from the laser light is shown. The polarity inside the droplet decreases with increasing the optical force. When small amounts of dye molecules, D (energy donor) and A (energy accepter), are dissolved in the polymer solution, D and A are absorbed (extracted) into the droplet. The concentrations of D and A are controllable by the optical force. Based on this mechanism, FRET between D and A is induced successfully, and can control the FRET efficiency. Finally, the modulation of fluorescence color of the droplet from blue, green, yellow, to an orange color is demosntrated simply by changing the optical force. The concept and technique are unique and will open a new channel to develop droplet chemistry and photochemistry. [ABSTRACT FROM AUTHOR]

Aims/Introduction: This study aimed to characterize the global cognition and executive functions of older adults with type 1 diabetes mellitus in comparison with type 2 diabetes mellitus. Materials and Methods: This study included 37 patients with type 1 diabetes mellitus aged ≥65 years and 37 age‐ and sex‐matched patients with type 2 diabetes mellitus. Patients with dementia scoring <24 on the Mini‐Mental State Examination were excluded. General cognition, memory, classic, and practical executive function were investigated. Results: Patients with type 1 diabetes mellitus demonstrated lower psychomotor speed scores on Trail Making Tests A and B (P < 0.001, P < 0.013) than those with type 2 diabetes mellitus. The dysexecutive syndrome behavioral assessment revealed similar results in patients with types 1 and 2 diabetes mellitus. The Wechsler Memory Scale‐Revised verbal episodic memory and Montreal Cognitive Assessment Japanese version were similar in terms of general cognition, but worse delayed recall subset on the latter was associated with type 2 diabetes mellitus (P = 0.038). A worse Trail Making Test‐A performance was associated with type 1 diabetes mellitus and age (P < 0.004, P < 0.029). Conclusions: Executive function of psychomotor speed was worse in older outpatient adults without dementia with type 1 diabetes mellitus than in those with type 2 diabetes mellitus but with no significant differences in the comprehensive and practical behavioral assessment of dysexecutive syndrome. Patients with type 1 diabetes had more severely impaired executive function, whereas those with type 2 had greater impaired memory than executive function. [ABSTRACT FROM AUTHOR]

Cultured epidermal autograft, JACE®, was introduced into the Japanese national health insurance system in 2009 and has been used in more than 1000 cases of extensive burns. The aim of this study was to investigate whether the use of JACE® contributes to survival rate in extensive burns. In this study, 119 cases were selected from 3990 cases in Tokyo Burn Unit Association registry data from 2009 to 2023, excluding cases with less than 40% total body surface area, cases of deaths within 4 weeks and cases with unknown length of hospital stay. In total, 25 patients treated with JACE® were selected and matched with another 25 patients who did not receive JACE® using propensity score matching. The results showed that patients treated with JACE® had a significantly higher survival rate than did those who were not treated with JACE® at all time points between 6 and 9 weeks post‐injury. In addition, there was no significant difference in length of hospital stay between the groups. These results suggest that the use of JACE® in patients with extensive burns contributes to patient survival and does not prolong hospital stay. [ABSTRACT FROM AUTHOR]

Aim: Quality of care is important to reduce disease progression, and improve both survival and quality of life. The Japan Society of Gynecologic Oncology has published treatment guidelines to promote standardized high‐quality care for ovarian cancer in Japan. We developed quality indicators based on the guideline recommendations and used them on large datasets of health service use to examine the quality of ovarian cancer care. Methods: A panel of experts developed the indicators using a modified Delphi method. Adherence to each indicator was evaluated using data from a hospital‐based cancer registry of patients diagnosed in 2018. All patients receiving first‐line treatment at participating facilities were included. The adherence rates were returned to participating hospitals, and reasons for nonadherence were collected. A total of 580 hospitals participated, and the study examined the care received by 6611 patients with ovarian cancer and 1879 with borderline tumors using 11 measurable quality indicators. Results: The adherence rate ranged from 22.6% for "Estrogen replacement within 6 months of operation" to 93.5% for "Bleomycin, etoposide, and cisplatin for germ cell tumor more than Stage II." Of 580 hospitals, 184 submitted the reasons for nonadherence. Conclusions: The quality of ovarian cancer care should be continuously assessed to encourage the use of best practices. These indicators may be a useful tool for this purpose. [ABSTRACT FROM AUTHOR]

We present a rare case involving a 54‐year‐old man with a history of pancreatitis who developed a retroperitoneal lumbar vein aneurysm that was initially misidentified as a pancreatic pseudocyst. Subsequent imaging revealed an enlarged mass and retroperitoneal perforation. Despite initial hesitation, the patient eventually underwent radical surgery that enabled the successful removal of the mass, which was near the inferior vena cava. Pathological examination confirmed varicose veins, and the final diagnosis was lumbar vein aneurysm in the retroperitoneum. The patient's postoperative recovery was uneventful, with no symptoms or recurrence observed on 6‐month follow‐up imaging. We investigated a potential link between pancreatitis and recurrent bleeding due to weakened venous walls. The findings from this case underscore the rarity of venous aneurysms and the diagnostic and treatment challenges due to the limited number of cases; furthermore, they emphasize that surgery should be carefully considered based on the lesion location and associated risks. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate whether a plate adapted to the anatomy of the proximal medial porcine's tibia would provide maintenance of the anterior gap (AG), posterior gap (PG) and posterior tibial slope (PTS). Methods: Twenty‐seven porcine tibias were biomechanically evaluated by performing MOWHTO and placing TOMOFIX (n = 9), AC plate (n = 9) and TriS (n = 9) anteromedially. Cyclic testing (800 N, 2000 cycles, 0.5 Hz) was performed to investigate the PTS over time for MOWHTO. The particular displacement calculated from the maximum to the minimum point with the load‐displacement curve along the mechanical axis during cyclic testing, the final AG and PG changes at the osteotomy site, the increased PTS calculated by subtracting AG from PG after 2000 cycles were compared among the three groups. The displacement was evaluated by repeated‐measures analysis of variance (ANOVA), and changes in AG and PG and increased PTS were evaluated by one‐way ANOVA. The sample size for α and β errors were <0.05 and <0.20, and the effect size was 0.64 for one‐way ANOVA and 0.49 for repeated‐measures ANOVA. Results: There were no significant differences in displacement among the groups. A significant difference was observed in the AG (p = 0.044) and PG (p = 0.0085) changes. There were no significant differences in increased PTS among the groups. Conclusion: When anteromedially placed, the AC plate and TriS resulted in significant maintenance of AG and PG compared with that of TOMOFIX in MOWHTO after cyclic loading. Level of Evidence: Level Ⅳ. [ABSTRACT FROM AUTHOR]

Purpose: To compare the postoperative clinical and radiological outcomes in patients aged ≥70 years following neutral alignment medial opening‐wedge high tibial osteotomy (NA‐MOWHTO) for medial compartment knee osteoarthritis (KOA) to those observed in younger patients. Methods: The data of patients who underwent NA‐MOWHTO for medial compartment KOA between September 2018 and June 2022 were retrospectively analysed. The patients were categorised into groups Y (<70 years) and O (≥70 years). Age, sex, Kellgren–Lawrence classification, pre‐ and postoperative mechanical axis, weight‐bearing line ratio, medial proximal tibial angle, preoperative Tegner Activity Score and pre‐ and postoperative Lysholm scores were compared between the groups. Results: Overall, 81 patients (60 and 21 in groups Y and O, respectively) who underwent NA‐MOWHTO were included in this study. No significant differences were found in patient characteristics between the two groups, except for the preoperative Tegner Activity Score, which was significantly higher in group Y than in group O (3 [2–4] vs. 2 [2–2], respectively; p = 0.011). The two groups exhibited no significant differences in pre‐ and postoperative knee alignments. Postoperatively, Lysholm scores improved significantly in both groups without significant differences. Additionally, no correlation was found between age and pre‐ and postoperative Lysholm scores. Conclusions: The postoperative improvement following NA‐MOWHTO for medial compartment KOA is comparable in patients aged ≥70 and younger. Level of Evidence: Level III, Retrospective comparative study. [ABSTRACT FROM AUTHOR]

Many species often show male–male combat for mating opportunities and resources within the species. Sexual selection through this radical combat leads to the evolution of males with exaggerated traits used as weapons, such as horns or mandibles, that often result in victory during combat. However, heterospecific interaction due to errors in species identification has often been observed, which results in decreased mating opportunities within the same species and fewer fertilized eggs. Males with exaggerated weapons may show dominance in resource acquisition over males without weapons and may decrease the reproductive success of the latter due to competition between the two. However, few studies have examined heterospecific interaction focusing on males with or without weapons. In this study, we investigated the effects of the male weapon on reproductive traits in heterospecific interaction in two species: the broad‐horned flour beetle (Gnatocerus cornutus), in which males have exaggerated weapon traits; and the red flour beetle (Tribolium castaneum), in which males have no weapon traits. Both species are closely related and use the same food resources. G. cornutus males interfered with the resource acquisition and reproductive opportunities of T. castaneum by attacking T. castaneum. The reproductive success of T. castaneum decreased when they cohabited with G. cornutus males. These findings show that male weapon traits, which are important for sexual selection within the same species, can also greatly influence reproduction in other species. [ABSTRACT FROM AUTHOR]

We investigate how common ownership affects welfare in a vertically related market. Although common ownership mitigates the double marginalization problem and improves welfare, it restricts competition among downstream firms and harms welfare. We find that whether common ownership is welfare‐improving depends on the degree of competitiveness in the downstream market. Common ownership is more likely to improve welfare when there are fewer downstream firms and a greater degree of product differentiation. In other words, common ownership may improve welfare when competition in the downstream market is weak. [ABSTRACT FROM AUTHOR]

Positive homotropic artificial allosteric systems are important for the regulation of cooperativity, selectivity and nonlinear amplification. Stereodynamic homotropic allosteric receptors can transmit and amplify induced chirality by the first ligand binding to axial chirality between two chromophores. We herein report stereodynamic allosteric urea receptors consisting of a rotational shaft as the axial chirality unit, terphenyl units as structural transmission sites and four urea units as binding sites. NMR titration experiments revealed that the receptor can bind two carboxylate guests in a positive homotropic allosteric manner attributed to the inactivation by intramolecular hydrogen‐bonding between urea units within the receptor. In addition, the VT‐CD spectra observed upon binding of the urea receptor with l‐ or D‐amino acid salts in MeCN showed interesting temperature‐dependent Cotton effects, based on the differences of the receptor shaft unit and the guest structure. The successful discrimination of hydrocarbon‐based side chains of amino acid salts indicated that the input of chiral and steric information for the guest was amplified as outputs of the Cotton effect and the temperature‐dependence of VT‐CD spectra through cooperativity of positive allosteric binding. [ABSTRACT FROM AUTHOR]

Aim: Oral cGVHD is one of the phenotypes of organ involvement of cGVHD and is a complex, frequent, and highly impactful complication of allogeneic hematopoietic cell transplantation (HSCT). Few studies have compared the incidences and risk factors of oral cGVHD, and they have not been discussed. We performed to evaluate the risk factors for oral cGVHD after allogeneic HSCT in a single center. Methods: A retrospective study of clinical hematological data of all consecutive patients who underwent HSCT for malignant hematologic disease and then developed oral chronic graft versus host disease (cGVHD) in a single center from 2012 to the present was performed to evaluate the risk factors for oral cGVHD. Allogeneic HSCT was performed for 179 patients. Assessment of individual risk factors (age, sex, primary diagnosis, stem cell source, human leukocyte antigen [HLA] matching, regimen, donor age, and status after remission induction therapy) was completed to identify the effects of covariates of the independent variables. Results: Seventy‐two (40.2%) patients were considered to have oral cGVHD within 36 months after HSCT. Statistical analysis showed that age, sex, stem cell source, HLA matching, regimen, donor age, and status after remission induction therapy were not significant factors related to oral cGVHD, whereas the primary disease was significant. Conclusion: The primary disease was a significant risk factor for oral cGVHD. The oral cGVHD was more common in myeloid neoplasms (MNs) patients than in lymphoid neoplasms (LNs) patients. [ABSTRACT FROM AUTHOR]

Oncolytic viruses (OVs) can selectively replicate in tumor cells and remodel the microenvironment of immunologically cold tumors, making them a promising strategy to evoke antitumor immunity. Similarly, agonists of the stimulator of interferon genes (STING)‐interferon (IFN) pathway, the main cellular antiviral system, provide antitumor benefits by inducing the activation of dendritic cells (DC). Considering how the activation of the STING‐IFN pathway could potentially inhibit OV replication, the use of STING agonists alongside OV therapy remains largely unexplored. Here, we explored the antitumor efficacy of combining an HSV‐1‐based OV, C‐REV, with a membrane‐impermeable STING agonist, 2′3′‐GAMP. Our results demonstrated that tumor cells harbor a largely defective STING‐IFN pathway, thereby preventing significant antiviral IFN induction regardless of the permeability of the STING agonist. In vivo, the combination therapy induced more proliferative KLRG1‐high PD1‐low CD8+ T‐cells and activated CD103+ DC in the tumor site and increased tumor‐specific CD44+ CD8+ T‐cells in the lymph node. Overall, the combination therapy of C‐REV with 2′3′‐cGAMP elicited antitumor immune memory responses and significantly enhanced systemic antitumor immunity in both treated and non‐treated distal tumors. [ABSTRACT FROM AUTHOR]

Background: A case of retropharyngeal abscess complicated by both artery and nerve injury has rarely been reported. Methods: A 36‐year‐old woman suddenly presented with right eye visual loss, dilated pupil, reduced direct light reflex, ptosis and ocular motility disorder on the side of inflammation progression, and was diagnosed with retropharyngeal abscess due to Fusobacterium necrophorum. The patient was treated only with antibiotics and, no further surgery was necessary but tracheotomy. Four months later, MRA showed right ICA occlusion and left ICA stenosis. MRI revealed continuous spread of inflammation due to the abscess from the retropharyngeal to the intracranial space. Results: These severe complications would be attributed to an endothelial damage to the arterial wall and an ischemic neuropathy caused by inflammation and thrombogenesis due to Fusobacterium necrophorum. Conclusions: This case should provide a better understanding of the mechanism of vascular and cranial nerve injury due to retropharyngeal infections, and highlights the need for early antibiotic therapy and repeated vascular evaluation. [ABSTRACT FROM AUTHOR]

Background: First‐line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab‐containing regimens in many countries. We report longer‐term follow‐up data. Methods: This open‐label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression‐free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD‐L1) expression of ≥1% and then in the overall population. Results: A total of 970 patients were randomly assigned. After 29 months of minimum follow‐up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46–0.76]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65–0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48–0.80]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65–0.92]). In patients with tumor cell PD‐L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51–0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79–1.36]). Among all treated patients (n = 936), Grade 3–4 treatment‐related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. Conclusions: Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow‐up, further supporting use as first‐line standard treatment options for patients with advanced ESCC. [ABSTRACT FROM AUTHOR]

Objectives: People living with HIV (PLWH) have been shown to have lower bone density at the spine, hip, and radius. However, whether a similar bone phenotype is seen in craniofacial bones is not known. The goal of this study was to evaluate the bone microarchitecture of the mandibular condyle in PLWH. Methods: We recruited 212 participants, which included 88 HIV‐negative participants and 124 PLWH on combination antiretroviral therapy with virological suppression from a single academic center. Each participant filled out a validated temporomandibular disorder (TMD) pain screening questionnaire and had cone beam computed tomography (CBCT) of their mandibular condyles. Qualitative radiographic evidence of temporomandibular joint disorders‐osteoarthritis (TMJD‐OA) assessment and quantitative microarchitecture analysis of their mandibular condylar bones were conducted. Results: There was no statistically significant difference in either self‐reported TMD or in radiographic evidence of TMJD‐OA in PLWH compared with HIV‐negative controls. Linear regression analysis revealed that positive HIV status remained significantly associated with increased trabecular thickness, decreased cortical porosity, and increased cortical bone volume fraction after adjusting for race, diabetes, sex, and age. Conclusion: PLWH have increased mandibular condylar trabecular bone thickness and cortical bone volume fraction compared with HIV‐negative controls. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Economics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Catheter ablation (CA) for premature ventricular contractions (PVCs) restores cardiac and renal functions in patients with reduced left ventricular ejection fraction (LVEF); however, its effects on preserved EF remain unelucidated. Methods: The study cohort comprised 246 patients with a PVC burden of >10% on Holter electrocardiography. Using propensity matching, we compared the changes in B-type natriuretic peptide (BNP) levels and estimated glomerular filtration rate (eGFR) in patients who underwent CA or did not. Results: Postoperative BNP levels were decreased significantly in the CA group, regardless of the degree of LVEF, whereas there was no change in those of the non- CA group. Among patients who underwent CA, BNP levels decreased from 44.1 to 33.0 pg/mL in those with LVEF ≥50% (p = .002) and from 141.0 to 87.9 pg/mL in those with LVEF <50% (p < .001). Regarding eGFR, postoperative eGFR was significantly improved in the CA group of patients with LVEF ≥50% (from 71.4 to 74.7 mL/ min/1.73 m², p = .006), whereas it decreased in the non-CA group. A similar trend was observed in the group with a reduced LVEF. Adjusted for propensity score matching, there was a significant decrease in the BNP level and recovery of eGFR after CA in patients with LVEF >50%. Conclusions: This study showed that CA for frequent PVCs decreases BNP levels and increases eGFR even in patients with preserved LVEF. [ABSTRACT FROM AUTHOR]

Plants produce various phytochemicals against herbivory, but phytophagous insects have encountered phytochemicals in the co‐evolutionary history between plants and insects. Selection pressure exerted by phytochemicals triggers a preadaptation to insecticide resistance in insect pests that is due to detoxification systems that are common to phytochemicals and insecticides in the insect's body. We investigated the interaction between the host plant resistance of rice cultivars and the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae). Forty brown planthopper resistance gene loci (BPHs) that are related to phytochemicals in various cultivars of rice inhibit feeding by N. lugens, but this planthopper has developed virulence to resistant rice cultivars possessing some genes. Nilaparvata lugens has also developed resistance to some insecticides as a rapid adaptation to human‐driven selection. We tested the hypothesis that the evolution of insects' resistance to an insecticide is promoted by their encounters with phytochemicals. We compared the virulence of imidacloprid‐resistant and control N. lugens strains toward seven rice cultivars that possess different genes, and we observed that the imidacloprid‐resistant N. lugens had reduced virulence to three rice cultivars, Rathu Heenati (BPH3, BPH17), Babawee (BPH4), and Balamawee (BPH27, three quantitative trait loci), meaning that the development of imidacloprid resistance has a negative impact on the virulence of N. lugens to three cultivars. Our results indicate trade‐offs rather than a co‐relationship between the evolution of insecticide resistance and encounters with host plant defense. [ABSTRACT FROM AUTHOR]

Carcinoma showing thymus‐like elements (CASTLE) is a rare tumor that commonly occurs in the thyroid gland. Extrathyroidal CASTLE is rarer, and only 11 cases of CASTLE of major salivary glands have been reported to date. We report the first case of amyloid deposition in parotid CASTLE. A 63‐year‐old man presented with a slowly growing mass in the left parotid region. Computed tomography revealed an approximately 28 × 23 mm mass lesion in the left parotid gland, and squamous cell carcinoma was suspected on biopsy. The patient underwent a parotidectomy with neck dissection. Morphologically, the tumor cells were squamoid and formed nests with lymphoid infiltration. Immunohistochemically, the tumor cells exhibited immunoreactivity for CD5, CD117/c‐kit and Bcl‐2, p40, and CK5 but not for p16. We diagnosed the tumor as parotid CASTLE. Amyloid deposition was also observed in the primary tumor and metastatic lymph node lesions, which were immunoreactive for cytokeratin 5. Tumor cytokeratin‐derived amyloid deposition may be one of characteristics of parotid CASTLE. [ABSTRACT FROM AUTHOR]

T‐cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α‐Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α‐pinene as an antitumor agent for the treatment of T‐cell tumors. We found that α‐pinene inhibited the proliferation of hematologic malignancies, especially in T‐cell tumor cell lines EL‐4 and Molt‐4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF‐κB p65 translocation into the nucleus, leading to robust apoptosis in EL‐4 cells. Collectively, these findings suggest that α‐pinene has potential as a therapeutic agent for T‐cell malignancies, and further investigation is warranted. [ABSTRACT FROM AUTHOR]

Obesity‐induced adipose tissue inflammation plays a critical role in the development of metabolic diseases. For example, NK1.1+ group 1 innate lymphoid cells (G1‐ILCs) in adipose tissues are activated in the early stages of inflammation in response to a high‐fat diet (HFD). In this study, we examined whether the composition of fatty acids affected adipose inflammatory responses induced by an HFD. Mice were fed a stearic acid (C18:0)‐rich HFD (HFD‐S) or a linoleic acid (C18:2)‐rich HFD (HFD‐L). HFD‐L‐fed mice showed significant obesity compared with HFD‐S‐fed mice. Visceral and subcutaneous fat pads were enlarged and contained more NK1.1+KLRG1+ cells, indicating that G1‐ILCs were activated in HFD‐L‐fed mice. We examined early changes in adipose tissues during the first week of HFD intake, and found that mice fed HFD‐L showed increased levels of NK1.1+CD11b+KLRG1+ cells in adipose tissues. In adipose tissue culture, addition of 4‐hydroxynonenal, the most frequent product of lipid peroxidation derived from unsaturated fatty acids, induced NK1.1+CD11b+CD27− cells. We found that calreticulin, a ligand for the NK activating receptor, was induced on the surface of adipocytes after exposure to 4‐hydroxynonenal or a 1‐week feeding with HFD‐L. Thus, excess fatty acid intake and the activation of G1‐ILCs initiate and/or modify adipose inflammation. [ABSTRACT FROM AUTHOR]

Background: Skin disorders are the most common side effect associated with epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) therapy. It is important to manage skin lesions. Adapalene has been used to treat skin lesions caused by EGFR‐TKIs in some cases. The aim of this study was to investigate the functional mechanism of adapalene in erlotinib‐induced skin disorder. Methods: To analyze the effect of adapalene on skin rash, afatinib and adapalene were administered to mice. The relationship between the concentration of adapalene and skin disorders was also examined by analyzing AQP3 expression. A skin lesion model was experimentally established in human skin keratinocytes (HaCaT) by using erlotinib with TNF‐α and IL‐1β. We used qRT–PCR to analyze chemokine‐induced inflammation and western blotting to analyze the effects of adapalene on the NF‐κB signaling pathway. Antimicrobial peptides and adhesion factors were also examined using qRT–PCR. Results: Mice administered 0.01% adapalene had less skin inflammation than mice treated with afatinib alone. The expression level of AQP3 decreased in an adapalene concentration‐dependent manner. The mRNA levels of proinflammatory cytokines such as CCL2 and CCL27 in HaCaT cells were significantly reduced by adapalene. The expression of an antimicrobial peptide, hBD3, was upregulated after adapalene treatment. Adhesion factors, such as E‐cadherin, were significantly downregulated by EGFR‐TKI and significantly upregulated by adapalene treatment. Western blot analysis suggested that erlotinib‐induced phosphorylation of p65 was decreased by adapalene. Conclusion: We suggest that adapalene may be a possible treatment option for skin disorders induced by EGFR‐TKIs. [ABSTRACT FROM AUTHOR]

This paper presents evidence for hypomineralization disorders (rickets and osteomalacia) in non‐adults at Man Bac, a Neolithic site from northern Vietnam dated to 4000–3500BP, contributing to the well‐described disease burden at the site that includes scurvy, treponemal disease, thalassemia, and malaria. Forty‐four non‐adults (<20 years of age‐at‐death) were assessed for macroscopic and radiographic evidence for hypomineralization disorders. Differential diagnosis was completed using traditional methods and three‐level standardized criteria to combat the challenges of overlapping pathological features between hypomineralization disorder and the other diseases already diagnosed at the site. In addition, a diagnostic certainty approach was applied to investigate the impact of lesion ambiguity on our findings. Kaplan–Meier and Fishers exact tests were applied to assess age‐at‐death‐related epidemiological patterns of hypomineralization disorder and co‐morbid relationships with scurvy, thalassemia, and treponemal disease. Almost 50% of the non‐adult assemblage presented with evidence for hypomineralization disorder, which was associated with decreased survivorship in childhood. Potential epidemiological relationships between scurvy and hypomineralization disorders, and thalassemia and hypomineralization disorders are described. The former relationship may be due to the likelihood of the introduction of rice resulting in multi‐micronutrient deficiency, including vitamin C and calcium deficiency, and cultural attitudes to sunlight. The latter relationship may relate to the pathophysiology of thalassemia that can result in secondary osteomalacia possibly contributing to the development of hypomineralization disorder in the thalassemic non‐adults. The findings are significant as they present possible approaches for diagnosis of disease embedded within complex disease burdens where individuals are likely suffering from co‐morbidities. [ABSTRACT FROM AUTHOR]

Incisional scarring is a factor of cosmetic appearance evaluated after breast reconstruction, along with the shape, position, and size of the breast. This study aimed to examine the effect of the incision scar location on patient satisfaction after breast reconstruction. Using the Japanese version of the SCAR‐Q, we assessed the scar appearance, symptoms and psychosocial effects. Plastic surgeons performed assessments using the Manchester Scar Scale. The patients were divided into two groups: those with scars on the margins of the breast (MB group) and those with scars in the breast area (IB group). The results revealed that patients in the MB group reported significantly higher satisfaction with the scar appearance and psychological impact than those in the IB group. However, assessments using the Manchester Scar Scale did not reveal any significant differences between the two groups. In conclusion, this study underscores the importance of patient‐reported outcomes in the evaluation of scar satisfaction after breast reconstruction. Patients tend to prefer and have higher satisfaction with scars along the breast margin, which offers valuable insights into surgical decisions. Further studies with larger and more diverse sample sizes are required for validation. [ABSTRACT FROM AUTHOR]

The Park‐Bench Position (PBP) is associated with a high incidence rate of intraoperatively acquired pressure injuries (IAPIs). Preventive measures must be established to prevent the development of IAPIs. We investigated the risk factors for PBP by applying a soft silicone multilayered foam dressing (SMD) under core temperature management to prevent IAPIs. We conducted a prospective, single‐centre, open‐label observational study of patients undergoing elective neurosurgery operations using PBP in a university hospital in Japan. The incidence rate of IAPIs in this study was compared with that in our two previous studies, in which a film dressing was applied and core temperature management was not performed. IAPIs developed in 90 patients (6.7%); in the lateral thoracic region in five patients and the iliac crest region in one patient. The operative time (every 1 h: p = 0.0001, OR: odds ratio 3.62, 95% CI: confidence interval 1.73–11.42) was significantly associated with the incidence of IAPIs. In our two previous studies, the incidence rate of IAPIs was 11.0% and 24.1%, respectively, when film dressing was used. SMD may weaken the involvement of risk factors in IAPIs. [ABSTRACT FROM AUTHOR]

Organisms must adapt to environmental stresses to ensure their survival and prosperity. Different types of stresses, including thermal, mechanical, and hypoxic stresses, can alter the cellular state that accompanies changes in gene expression but not the cellular identity determined by a chromatin state that remains stable throughout life. Some tissues, such as adipose tissue, demonstrate remarkable plasticity and adaptability in response to environmental cues, enabling reversible cellular identity changes; however, the mechanisms underlying these changes are not well understood. We hypothesized that positive and/or negative "Integrators" sense environmental cues and coordinate the epigenetic and transcriptional pathways required for changes in cellular identity. Adverse environmental factors such as pollution disrupt the coordinated control contributing to disease development. Further research based on this hypothesis will reveal how organisms adapt to fluctuating environmental conditions, such as temperature, extracellular matrix stiffness, oxygen, cytokines, and hormonal cues by changing their cellular identities. [ABSTRACT FROM AUTHOR]

B‐cell receptor (BCR) signaling is critically activated and stable for mantle cell lymphoma (MCL), but the underlying mechanism of the activated BCR signaling pathway is not clear. The pathogenic basis of miR‐17‐92 cluster remains unclear although the oncogenic microRNA (miRNA) miR‐17‐92 cluster is highly expressed in patients with MCL. We revealed that miR‐17‐92 cluster overexpression is partly dependent on SOX11 expression and chromatin acetylation of MIR17HG enhancer regions. Moreover, miR‐17‐92 cluster regulates not only cell proliferation but BCR signaling activation in MCL cell lines. To comprehensively identify miR‐17‐92 cluster target genes, we performed pulldown‐seq, where target RNA of miRNA was captured using the biotinylated miRNA mimics and magnetic bead‐coated streptavidin, and quantified using next‐generation sequencing. The pulldown‐seq identified novel miRNA target genes, including tumor suppressors such as BTG2 (miR‐19b), CDKN2A (miR‐17), SYNE1 (miR‐20a), TET2 (miR‐18, miR‐19b, and miR‐92a), TNFRSF10A (miR‐92a), and TRAF3 (miR‐17). Notably, the gene expression profile data of patients with MCL revealed that BTG2 expression was negatively associated with that of BCR signature genes, and low BTG2 expression was associated with poor overall survival. Moreover, BTG2 silencing in MCL cell lines significantly induced BCR signaling overactivation and cell proliferation. Our results suggest an oncogenic role of miR‐17‐92 cluster‐activating BCR signaling throughout BTG2 deregulation in MCL. Furthermore, this may contribute to the prediction of the therapeutic efficacy and improved outcomes of MCL. [ABSTRACT FROM AUTHOR]

Aim: The post‐treatment quality of life (QOL) of patients with cancer has become an important issue owing to significant improvements in the outcomes of cancer treatment. The oral cavity has not only life‐sustaining functions but also important social functions, including talking. Thus, many reports have assessed the post‐treatment QOL of patients with oral cancer. However, the sample sizes in most studies were insufficient to control for potential confounding variables. Additionally, previous studies have indicated that racial/ethnic differences may be associated with health‐related QOL. Thus, this study aimed to clarify factors influencing post‐treatment QOL using multiple regression analysis in a large number of Japanese patients with tongue cancer. Methods: In total, 106 patients with tongue cancer were recruited from the oral surgery departments of three university hospitals sharing a common treatment plan for tongue cancer. QOL was evaluated using the University of Washington Quality of Life Questionnaire, and depressive tendencies were assessed using the Self‐rating Depression Scale (SDS). Results: Neck dissection was most widely associated with physical and socio‐emotional QOL. Reconstruction, radiotherapy, and higher T‐stage and SDS scores were the second most widely associated factors with QOL. Interestingly, a higher SDS score was negatively related only to socio‐emotional factors. Furthermore, only SDS scores were associated with the general QOL. Conclusion: This study suggested that the physical and socio‐emotional QOL was widely affected by neck dissection, reconstruction, radiotherapy, T‐stage, and SDS scores, whereas the general QOL was affected only by SDS scores. These findings should be considered when treating patients with oral cancer. [ABSTRACT FROM AUTHOR]

This research conducted investigations of buildings equipped with radiant systems and expert interviews in 2021–2022 with manufacturers and mechanical, electrical, and plumbing (MEP) engineers in Japan who had experience designing radiant heating and cooling systems for non‐residential buildings. In total, interviews were conducted with 56 respondents from 16 companies. Results from the building investigation showed that 69% of the identified buildings had radiant ceilings, and 30% had radiant floors. In terms of working fluid, 56% were water‐based, and 43% were air‐based. For the expert interview, 79% of all respondents answered that the use of radiant systems will continue to increase in the future. In total, 54% of all respondents answered that it has become easier to design radiant systems at present compared to the 2010s. Based on the results, knowledge gaps and challenges in the design of radiant systems were summarized in terms of design method, room temperature control, auxiliary systems, and their relevance to building decarbonization. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Even in a country where vancomycin–resistant enterococcus is rare, multidrug‐resistant organism precautions are necessary when admitting patients with a history of medical exposure in other countries. On admission, screening is necessary and if infection is confirmed, a multidisciplinary approach involving different specialists is required. The patient was a 49‐year‐old Japanese female living in the United States. Total pelvic exenteration for cervical carcinoma, Miami pouch formation, and ileostomy had been performed in the United States. She returned to Japan to undergo postoperative adjuvant chemotherapy. Fever and abdominal pain occurred 42 days after surgery. She consulted the fever outpatient clinic, and a diagnosis of urinary retention‐associated acute renal failure and pyelonephritis was made. We detected vancomycin‐resistant enterococcus on urine/blood culture 5 days after admission. Infection control measures were implemented, and the ward was closed for 3 days. We administered linezolid, which was effective for pyelonephritis and bacteremia. [ABSTRACT FROM AUTHOR]

Long‐term monitoring of wild bee communities at fixed locations using a consistent sampling procedure has been rare, although declines in their diversity and abundance due to anthropogenic impacts are a major concern. At two sites in urban green areas in Sapporo city, northern Japan, where wild bee surveys were conducted in 1959, 1979, 1989, 2018, and 2019, the number of individuals of bee genera was recorded. Patterns of seasonal changes in bee abundance collected at weekly censuses differed between 1979–1989 and 2018–2019. The total bee abundance collected in annual surveys consisting of standardized censuses demonstrated 50% and 41% declines at the two sites from 1959–1989 to 2018–2019. Among the 16 genera found in the surveys, 3 abundant genera, Andrena, Lasioglossum, and Ceratina, always exhibited lower abundance in 2018–2019 than in 1959–1989 at both sites. The remarkable declines in wild bee abundance should be examined in relation to various possible factors of anthropogenic impacts. [ABSTRACT FROM AUTHOR]

The CFA ratio, calculated using pretreatment C‐reactive protein (CRP), fibrinogen, and albumin levels (CRP × fibrinogen/albumin), was previously reported to be a significant prognostic factor for acute myeloid leukemia (AML). This multicenter retrospective study evaluated the prognostic value of the CFA ratio in 328 adult patients with newly diagnosed AML from April 2000 to March 2018. The median age was 49.5 years (range, 15–75 years), and 60.7% of the population were males. According to the European LeukemiaNet (ELN) risk classification, 67 patients (20.4%) were in the favorable‐risk group, 197 patients (60.1%) in the intermediate‐risk group, and 58 patients (17.7%) in the adverse‐risk group. The median CFA ratio was 1.07 (0–67.69). Based on the calculated cutoff CFA ratio of 1.44, the cohort included 176 and 152 patients with low and high CFA ratios, respectively. At a median follow‐up of 91.2 months, the 7‐year overall survival (OS) and disease‐free survival (DFS) rates were 51.2% and 48.6%, respectively, in the overall cohort. The 7‐year OS rates were 61.7% and 39.0% in the low and high CFA ratio groups, respectively (p < 0.001). The 7‐year DFS rates were 58.1% and 37.0% in the low and high CFA ratio groups, respectively (p = 0.004). In univariate analysis, age ≥50 years, male sex, ELN risk class, and comorbidities were associated with poor OS. Age, ELN risk class, comorbidities, and high CFA ratio were associated with poor OS in multivariate analysis. Subgroup analysis revealed that the CFA ratio was significant in the intermediate and adverse ELN risk classes. These findings indicate the prognostic significance of the CFA ratio in AML. [ABSTRACT FROM AUTHOR]

Objective: Becker muscular dystrophy (BMD) is a milder variant of Duchenne muscular dystrophy (DMD), a lethal X‐linked muscular disorder. Here, we aim to investigat the clinical involvement of skeletal, respiratory, cardiac, and central nervous systems in patients with BMD, as well as genotype–phenotype relationships. Methods: This nationwide cohort study investigated the clinical manifestations and genotype–phenotype relationships in 225 patients with BMD having in‐frame deletion from 22 medical centers. The primary outcome was to elucidate the association of genotype with skeletal muscle, respiratory, cardiac, and central nervous system disorders. Descriptive statistics were used to analyze the data. Results: The average age of the subjects was 31.5 (range, 1–81) years. Initial symptoms of BMD were muscular (60%), followed by asymptomatic hypercreatine kinasemia (32.4%) and central nervous system disorders (5.3%). Gait disturbance was observed in 53.8% of patients and the average age at wheelchair introduction was 36.5 years. The ventilator introduction rate was 6.7% at an average age of 36.6 years. More than 30% of patients had an abnormal electrocardiogram and approximately 15% had heart failure symptoms. Cardiac function on echocardiography varied significantly among the patients. The frequencies of seizures and intellectual/developmental disability were 8.0% and 16.9%, respectively. Exon 45–47deletion (del) was the most common (22.6%), followed by exon 45–48del (13.1%). Patients with exon 45–49del patients demonstrated severe skeletal muscle damage. Patients with exon 45–47del and exon 45–55del patients did not require ventilator use. Interpretation: The study provides important prognostic information for patients and clinicians to establish therapy plans and to implement preventative medicine. [ABSTRACT FROM AUTHOR]

Human herpesvirus‐8 (HHV‐8) viremia is associated with refractory conditions in patients infected with HIV‐1. Therefore, we evaluated the factors related to plasma HHV‐8‐DNA. Participants included patients infected with HIV‐1 who visited our hospital. Plasma HHV‐8‐DNA levels were measured using real‐time polymerase chain reaction, and anti‐HHV‐8 antibodies were assessed through enzyme immunoassays using multiple antigens (K8.1, ORF59, ORF65, and LANA). Factors related to plasma HHV‐8‐DNA were examined using Fisher's exact test or Mann–Whitney U test. The study involved 36 patients infected with HIV‐1, of whom 19 were histologically diagnosed with Kaposi's sarcoma (KS), two had multicentric Castleman's disease (MCD), and 15 did not exhibit HHV‐8‐related disease. Before the introduction of antiretroviral therapy (ART), plasma HHV‐8‐DNA was detected in 44% (7/16) of patients with KS and in 9% (1/11) of patients without HHV‐8‐related disease. Among patients with KS, elevated plasma HHV‐8‐DNA levels (≥0.05 copies/µL) correlated with the presence of CDC category C diseases other than KS (p = 0.0337), anti‐HHV‐8 antibody negativity (p = 0.0337), anemia (p = 0.0474), and thrombocytopenia (p = 0.0146). Following ART initiation, the percentage of patients positive for plasma HHV‐8‐DNA decreased from 44% (7/16) to 6% (1/17), and the percentage of patients positive for anti‐HHV‐8 antibodies increased from 44% (7/16) to 88% (15/17). Finally, plasma HHV‐8‐DNA positivity and anti‐HHV‐8 antibody negativity were observed in two patients with MCD. Our findings suggest that insufficient production of anti‐HHV‐8 antibodies was associated with HHV‐8 viremia, and that anti‐HHV‐8 antibody production was recovered with ART; thus, indicating the possibility of involvement of humoral immunity in suppressing HHV‐8 viremia. [ABSTRACT FROM AUTHOR]