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Rapid establishment of herd immunity with vaccination is effective to combat emerging infectious diseases. Although the incorporation of adjuvant and intradermal (ID) injection could augment early responses to the vaccine, the current chemical or biological adjuvants are inappropriate for this purpose with their side effects and high reactogenicity in the skin. Recently, a near-infrared (NIR) laser has been shown to augment the immune response to ID vaccination and could be alternatively used for mass vaccination programs. Here, we determined the effect of NIR laser as well as licensed chemical adjuvants on the immunogenicity 1, 2, and 4 weeks after ID influenza vaccination in mice. The NIR laser adjuvant augmented early antibody responses, while the widely used alum adjuvant induced significantly delayed responses. In addition, the oil-in-water and alum adjuvants, but not the NIR laser, elicited escalated TH2 responses with allergenic immunoglobulin E (IgE) responses. The effect of the NIR laser was significantly suppressed in the basic leucine zipper transcription factor ATF-like 3 (Batf3) knockout mice, suggesting a critical role of the cluster of differentiation 103+ (CD103)+ dendritic cells. The current preliminary study suggests that NIR laser adjuvant is an alternative strategy to chemical and biological agents to timely combat emerging infectious diseases. Moreover, its immunomodulatory property could be used to enhance the efficacy of immunotherapy for allergy and cancer.

Abstract We propose a field theory of closed p-brane C p interacting with a (p + 1)-form gauge field A p+1. This is a generalization of the Ginzburg-Landau theory (Abelian-Higgs model) for superconducting particles to higher-dimensional superconducting branes. A higher-form gauge invariant action is constructed by utilizing the Area derivative, which is a higher-dimensional generalization of the ordinary derivative. We find that the fundamental phenomena of superconductivity, such as the Meisser effect, topological defects, topological order, are naturally extended in the brane-field theory. We explicitly construct a topologically non-trivial static configuration that is characterized by the first homotopy group. Then, we calculate the low-energy effective theory in the presence of the topological defect and find that it is described by a BF-type topological field theory coupled with the world-volume of the topological defect. We also discuss a potential duality between the superconducting brane-field model and a brane-field model with a global U(1) higher-form symmetry as a generalization of the Particle-Vortex duality.

Abstract There have been several reports of skin manifestations in patients with coronavirus disease 2019 (COVID-19). However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected on the skin surface, including the sebum, of these patients. In this study, SARS-CoV-2 RNA was detected using real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of skin surface lipids (SSLs) collected using an oil-blotting film from the faces of hospitalized patients with COVID-19. Human transcriptome analysis was also performed using the same samples. In facial SSLs of patients with COVID-19, the RT-PCR positivity rate was 84.6% (11/13 samples) within 5 days and 30.4% (7/23 samples) by 6–10 days of symptom onset. In the transcriptome analysis, the most characteristic SSL-RNA profile was the upregulation of interferon-stimulated gene (ISG)-related genes, such as ISG15, IFITM1, and MX1. This study presents an alternative technique using SSLs for non-invasive SARS-CoV-2 RNA detection and simultaneous analysis of human molecular pathogenesis in patients with COVID-19.

Abstract We investigate a structure of a 4-dimensional bulk space constructed from the O(N) invariant critical φ 4 model in 3-dimension using the conformal smearing. We calculate a bulk metric corresponding to the information metric and the bulk-to-boundary propagator for a composite scalar field φ 2 in the large N expansion. We show that the bulk metric describes an asymptotic AdS space at both UV (near boundary) and IR (deep in the bulk) limits, which correspond to the asymptotic free UV fixed point and the Wilson-Fisher IR fixed point of the 3-dimensional φ 4 model, respectively. The bulk-to-boundary scalar propagator, on the other hand, encodes ∆ φ 2 $$ {\Delta }_{\varphi^2} $$ (the conformal dimension of φ 2) into its z (a coordinate in the extra direction of the AdS space) dependence. Namely it correctly reproduces not only ∆ φ 2 $$ {\Delta }_{\varphi^2} $$ = 1 at UV fixed point but also ∆ φ 2 $$ {\Delta }_{\varphi^2} $$ = 2 at the IR fixed point for the boundary theory. Moreover, we confirm consistency with the GKP-Witten relation in the interacting theory that the coefficient of the z ∆ φ 2 $$ {z}^{\Delta _{\varphi^2}} $$ term in z → 0 limit agrees exactly with the two-point function of φ 2 including an effect of the φ 4 interaction.

Science, technology, engineering, and mathematics (STEM) fields are incredibly valuable to the world as innovations can help improve infrastructure and save lives. The United States has called for improvements in mentoring to help build a larger STEM workforce. Many studies and reports have focused on the experience of mentees within communities of practice (COP) to determine mentoring best practices. But few studies have investigated how mentors define their role within the COP. In this study, we provide data from interviews with mentors in a Research Experience for Undergraduate program and a Research Experience for Teachers program. We compare the views of mentors who work with undergraduates to those who work with teachers to highlight the differing views of these two groups and how this affects the type of mentoring provided. Our findings show that mentors struggle to see their role in the RET program since there is not a direct link between mentoring teachers and building the STEM workforce. This is problematic as teachers could be crucial allies in this endeavor.

Abstract In-home automated scoring systems are in high demand; however, the current systems are not widely adopted in clinical settings. Problems with electrode contact and restriction on measurable signals often result in unstable and inaccurate scoring for clinical use. To address these issues, we propose a method based on ensemble of small sleep stage scoring models with different input signal sets. By excluding models that employ problematic signals from the voting process, our method can mitigate the effects of electrode contact failure. Comparative experiments demonstrated that our method could reduce the impact of contact problems and improve scoring accuracy for epochs with problematic signals by 8.3 points, while also decreasing the deterioration in scoring accuracy from 7.9 to 0.3 points compared to typical methods. Additionally, we confirmed that assigning different input sets to small models did not diminish the advantages of the ensemble but instead increased its efficacy. The proposed model can improve overall scoring accuracy and minimize the effect of problematic signals simultaneously, making in-home sleep stage scoring systems more suitable for clinical practice.

Abstract Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming. Analysis of public datasets suggested that various fatty acid metabolizing enzymes were expressed at higher levels in CC tissues than in normal tissues. Correspondingly, 11 free fatty acids (FFAs) showed significantly different serum levels in CC patient samples compared with healthy donor samples. Nine of these 11 FFAs also displayed significant alterations in CIN2/3 patients. We then generated diagnostic models using combinations of these FFAs, with the optimal model including stearic and dihomo-γ-linolenic acids. Receiver operating characteristic curve analyses suggested that this diagnostic model could detect CC and CIN2/3 more accurately than using serum squamous cell carcinoma antigen level. In addition, the diagnostic model using FFAs was able to detect patients regardless of clinical stage or histological type. Overall, the serum FFA diagnostic model developed in this study could be a powerful new tool for the non-invasive early detection of CC and CIN2/3.

Abstract Q-balls are non-topological solitons in field theories whose stability is typically guaranteed by the existence of a global conserved charge. A classic realization is the Friedberg-Lee-Sirlin (FLS) Q-ball in a two-scalar system where a real scalar χ triggers symmetry breaking and confines a complex scalar Φ with a global U(1) symmetry. A quartic interaction κχ 2|Φ|2 with κ > 0 is usually considered to produce a nontrivial Q-ball configuration, and this repulsive force contributes to its stability. On the other hand, the attractive cubic interaction Λχ|Φ|2 is generally allowed in a renormalizable theory and could induce an instability. In this paper, we study the behavior of the Q-ball under the influence of this attractive force which has been overlooked. We find approximate Q-ball solutions in the limit of weak and moderate force couplings using the thin-wall and thick-wall approximations respectively. Our analytical results are consistent with numerical simulations and predict the parameter dependencies of the maximum charge. A crucial difference with the ordinary FLS Q-ball is the existence of the maximum charge beyond which the Q-ball solution is classically unstable. Such a limitation of the charge fundamentally affects Q-ball formation in the early Universe and could plausibly lead to the formation of primordial black holes.

Research shows that employers play a key role in work-based learning (WBL) programs such as internships but are seldom involved in conversations around the topic (Greenfield & Stevens, 2018). While the benefits of work-based learning are well documented, employers are often unaware of the benefits they would receive from participating in an effort to strategically link education and workforce preparation (Greenfield & Stevens, 2018). This study qualitatively examined the experiences of employers that provide work-based learning opportunities, primarily internships, for postsecondary students. Findings illuminated the importance of developing and maintaining strong community partnerships and establishing recruitment pipelines. The results also indicated that lack of information impedes growth, virtual experiences are essential, and financial constraints impact participation.

Abstract Background Dynamic navigation for implant placement is becoming popular under the concept of top-down treatment. The purpose of this study is to verify the accuracy of a dynamic navigation system for implant placement. Methods Implant placement was performed on 38 patients using 50 implant fixtures. Patients in group C were treated using a conventional method, in which thermoplastic clips were fixed to the teeth, and patients in group M were treated using thermoplastic clips fixed to a mouthpiece attached to the teeth. The groups were compared to verify whether an accuracy difference existed. A treatment planning support program for dental implants was used to superimpose the postoperative computed tomography data on the preoperative implant design data to measure the entry point, apex point, and angular deviation. Results The accuracy of group C was 1.36 ± 0.51 mm for entry point, 1.30 ± 0.59 mm for apex point, and 3.20 ± 0.74° for angular deviation. The accuracy of group M was 1.06 ± 0.31 mm for the entry point, 1.02 ± 0.30 mm for the apex point, and 2.91 ± 0.97° for angular deviation. Significant differences were observed in the entry and apex points between the two groups. Conclusions The results indicate that group M exhibited better accuracy than group C, indicating that the stability of the thermoplastic clip is important for ensuring the accuracy of the dynamic navigation system. No previous studies have verified the accuracy of this system using the mouthpiece method, and additional data is required to confirm its accuracy for dental implant placement. The mouthpiece method improves the accuracy of implant placement and provides a safer implant treatment than the conventional method. Trial registration University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), Registration Number: UMIN000051949, URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view_his.cgi on August 21, 2023.

Yu Kawasaki,1 Takatoshi Kasai,2– 5 Yuko Sakurama,6 Fusae Kawana,2 Nanako Shiroshita,2 Natsue Koikawa6,7 1Department of Obstetrics and Gynecology, Juntendo University Graduate School of Medicine, Tokyo, Japan; 2Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; 3Department of Cardiovascular Management and Remote Monitoring, Juntendo University Graduate School of Medicine, Tokyo, Japan; 4Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; 5Sleep and Sleep-Disordered Breathing Center, Juntendo University Hospital, Tokyo, Japan; 6Japanese Center for Research on Women in Sport, Juntendo University, Tokyo, Japan; 7Graduate School of Health and Sports Science, Juntendo University, Chiba, JapanCorrespondence: Takatoshi Kasai, Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, Japan, Tel +81-33813-3111, Fax +81-5689-0627, Email kasai-t@mx6.nisiq.netPurpose: Female athletes with menstrual abnormalities have poor sleep quality. However, whether female athletes with poor sleep quality based on subjective assessment have distinctive changes in objective measures of sleep in association with menses remains unclear. This study aimed to compare changes in objective sleep measurements during and following menses between collegiate female athletes with and without poor subjective sleep quality.Patients and Methods: Female collegiate athletes (age range/mean ± standard deviation: 18– 22/ 22.2± 1.1) with regular menstrual cycles were recruited. The participants underwent home electroencephalogram monitoring during the first and second nights after the onset of menses and one night between the seventh and 10th nights after menses onset (mid-follicular phase). The Pittsburgh Sleep Quality Index (PSQI) was used to assess the subjective sleep quality. Interactions between the presence of poor subjective sleep quality (ie, PSQI ≥ 6) and changes in objective measures of sleep in association with menses were analyzed.Results: Data of 45 athletes, including 13 with poor subjective sleep quality, showed that changes in arousal index in athletes with poor subjective sleep quality were distinctive from those in athletes without poor subjective sleep quality (p = 0.036 for interaction). In athletes with poor subjective sleep quality, the arousal index was significantly increased in menses (p for analysis of variance, 0.015), especially on the first night after the onset of menses compared with during the mid-follicular phase (p = 0.016).Conclusion: Collegiate female athletes with regular menstrual cycles are likely to have poor subjective sleep quality in association with more frequent arousal during the first night after the onset of menses than during the mid-follicular phase.Keywords: electroencephalogram, menstruation, Pittsburgh sleep quality index, sports, women

Abstract Relapsing polychondritis (RP) is a rare inflammatory disorder involving immune‐mediated destruction of cartilaginous structures. Herein, we present the first report of a strong association between COVID‐19 vaccination and RP development. Clinicians should be aware that RP is among the autoimmune diseases that can develop after mRNA vaccination.

Mavacamten is a first-in-class cardiac myosin ATPase inhibitor, approved by the United States Food and Drug Administration for the treatment of hypertrophic cardiomyopathy with obstructive physiology (oHCM). Here, we present the real-world use of mavacamten in 50 patients with oHCM at a tertiary care referral center. In both our highlighted case and in our aggregate data, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and New York Heart Association symptom class. Moreover, in our center's experience, neither arrhythmia burden, nor contractility have worsened in the vast majority of patients: we note a clinically insignificant mean decrease in left ventricular ejection fraction (LVEF), with only two patients requiring temporary mavacamten discontinuance for LVEF

Extracellular vesicles (EVs) are crucial for transferring bioactive materials between cells and play vital roles in both health and diseases. Cellular protrusions, including filopodia and microvilli, are generated by the bending of the plasma membrane and are considered to be rigid structures facilitating various cellular functions, such as cell migration, adhesion, and environment sensing. Compelling evidence suggests that these protrusions are dynamic and flexible structures that can serve as sources of a new class of EVs, highlighting the unique role they play in intercellular material transfer. Cytonemes are specialized filopodia protrusions that make direct contact with neighboring cells, mediating the transfer of bioactive materials between cells through their tips. In some cases, these tips fuse with the plasma membrane of neighboring cells, creating tunneling nanotubes that directly connect the cytosols of the adjacent cells. Additionally, virus particles can be released from infected cells through small bud-like of plasma membrane protrusions. These different types of protrusions, which can transfer bioactive materials, share common protein components, including I-BAR domain-containing proteins, actin cytoskeleton, and their regulatory proteins. The dynamic and flexible nature of these protrusions highlights their importance in cellular communication and material transfer within the body, including development, cancer progression, and other diseases.

Summary: Suvorexant is an orexin receptor antagonist that targets the wake-promoting system. Orexin is also known to regulate energy metabolism in rodents, but its role in humans remains largely unknown. Here, we assessed the effect of suvorexant (20 mg) on energy metabolism during sleep and shortly after awakening in a randomized, double-blind, placebo-controlled, crossover study in 14 healthy men. Suvorexant increased rapid eye movement (REM) but decreased nonrapid eye movement (NREM) stage 1. Energy expenditure during wake after sleep onset (WASO) was higher than that during NREM and REM sleep in the placebo but not in the suvorexant trial, suggesting that the increase in energy expenditure during WASO was due to an activation of the orexin system. Fat oxidation during sleep increased, and its effect remained after waking the next morning. Suvorexant decreased protein catabolism but did not affect overall energy expenditure. The orexin system may affect fat oxidation independent of its roles in sleep regulation in humans.

Abstract Efforts to simplify standard polysomnography (PSG) in laboratories, especially for obstructive sleep apnea (OSA), and assess its agreement with portable electroencephalogram (EEG) devices are limited. We aimed to evaluate the agreement between a portable EEG device and type I PSG in patients with OSA and examine the EEG-based arousal index’s ability to estimate apnea severity. We enrolled 77 Japanese patients with OSA who underwent simultaneous type I PSG and portable EEG monitoring. Combining pulse rate, oxygen saturation (SpO2), and EEG improved sleep staging accuracy. Bland–Altman plots, paired t-tests, and receiver operating characteristics curves were used to assess agreement and screening accuracy. Significant small biases were observed for total sleep time, sleep latency, awakening after falling asleep, sleep efficiency, N1, N2, and N3 rates, arousal index, and apnea indexes. All variables showed > 95% agreement in the Bland–Altman analysis, with interclass correlation coefficients of 0.761–0.982, indicating high inter-instrument validity. The EEG-based arousal index demonstrated sufficient power for screening AHI ≥ 15 and ≥ 30 and yielded promising results in predicting apnea severity. Portable EEG device showed strong agreement with type I PSG in patients with OSA. These suggest that patients with OSA may assess their condition at home.

Abstract GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron microscopy structures of human GPR34-Gi complex bound with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. The ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster. The acyl chain of S3E-LysoPS is bent and fits into the L-shaped hydrophobic pocket in TM4-5 gap, and the aromatic fatty acid surrogate of M1 fits more appropriately. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34.

We investigated the association of marine biological indicators (polysaccharides, protein-like gel particles, and chl a) with the formation of fluorescent aerosol particles, cloud condensation nuclei (CCNs), and ice-nucleating particles (INPs) over the North Pacific Ocean, Bering Sea, and Arctic Ocean during September–November 2019. The abundance of bioindicators was high in the North Pacific Ocean and the Bering Sea (e.g., up to 1.3 mg m−3 of chl a), suggesting high biological activity due to a phytoplankton bloom. In the North Pacific Ocean, particles were characterized by high mass fractions of organics and sulfate with a predominance of terrestrial air masses. Conversely, in the Bering Sea and the Arctic Ocean, particles were characterized by high mass fractions of sea salt and sulfate with a predominance of maritime air masses. The averaged range/value of the CCN concentration at 0.4 % supersaturation were 99–151, 43–139, and 36 cm−3 over the North Pacific Ocean with terrestrial influences, over the Bering Sea with marine biogenic influences, and over the Arctic Ocean with marine influences, respectively, and the corresponding range/value of the hygroscopicity parameter κ were 0.17–0.59, 0.42–0.68, and 0.66, respectively. The averaged INP concentration (NINP) measured at temperatures of −18 and −24 ∘C with marine sources in the North Pacific and Bering Sea was 0.01–0.09 and 0.1–2.5 L−1, respectively, and that over the Arctic Ocean was 0.001–0.016 and 0.012–0.27 L−1, respectively. When marine sources were dominant, fluorescent bioaerosols in the fine mode were strongly correlated with all bioindicator types (R: 0.81–0.88) when the effect of wind-induced uplift from the sea surface to the atmosphere was considered. Correlations between NINP measured at −18 and −24 ∘C and all bioindicator types (R: 0.58–0.95 and 0.79–0.93, respectively) were positive, even when the extreme outlier point was omitted, as were those between NINP and fluorescent bioaerosols (R: 0.50 and 0.60, respectively), suggesting that marine bioindicators contributed substantially as sources of bioaerosols and to cloud formation.

Abstract We propose an effective field theory for branes with higher-form symmetry as a generalization of ordinary Landau theory, which is an extension of the previous work by Iqbal and McGreevy for one-dimensional objects to an effective theory for p-dimensional objects. In the case of a p-form symmetry, the fundamental field ψ[C p ] is a functional of p-dimensional closed brane C p embedded in a spacetime. As a natural generalization of ordinary field theory, we call this theory the brane field theory. In order to construct an action that is invariant under higher-form transformation, we generalize the idea of area derivative for one-dimensional objects to higher-dimensional ones. Following this, we discuss various fundamental properties of the brane field based on the higher-form invariant action. It is shown that the classical solution exhibits the area law in the unbroken phase of U(1) p-form symmetry, while it indicates a constant behavior in the broken phase for the large volume limit of C p . In the latter case, the low-energy effective theory is described by the p-form Maxwell theory. We also discuss brane-field theories with a discrete higher-form symmetry and show that the low-energy effective theory becomes a BF-type topological field theory, resulting in topological order. Finally, we present a concrete brane-field model that describes a superconductor from the point of view of higher-form symmetry.

Cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN), are caused by high-risk human papillomavirus (HPV) viral infection and are highly susceptible to host immunity targeting of HPV viral proteins, which include both foreign antigens and cancer antigens expressed by tumors. Immunotherapy that induces Th1 immunoreactivity against viral proteins is expected to take advantage of this immunological regression mechanism. However, although cancer immunotherapies for cervical cancer and CIN have been developed over the past several decades, none have been commercialized. Most of these immunotherapies target the viral cancer proteins E6 and E7, which are generally the same. The reasons for the underdevelopment of HPV-targeted immunotherapy differ depending on whether the target is invasive cancer or CIN. We here summarize the developmental history of cancer immunotherapy for CIN and discuss strategies for solving the problems that led to this underdevelopment. We note that CIN is a mucosal lesion and propose that inducing mucosal immunity may be the key.

Abstract IgG4‐related diseases are adverse events that occur after receiving treatment with immune checkpoint inhibitors (ICI). This study reports the first case of IgG4‐related retroperitoneal fibrosis after the administration of chemotherapy with nivolumab and ipilimumab (NI therapy). An 80‐year‐old man developed lower abdominal pain eight months after NI therapy was initiated. Although the primary lesion maintained its reduced size on computed tomography, there was an increase in the soft tissue shadows intensity around the abdominal aorta, bladder, and seminal vesicles, suggesting retroperitoneal fibrosis. Blood tests showed elevated IgG4 levels. Computed tomography‐guided biopsy of the retroperitoneum showed B cell‐dominant lymphocyte infiltration consistent with IgG4‐related retroperitoneal fibrosis and characteristic CD8‐positive lymphocyte infiltration, suggestive of the involvement of cytotoxic T cells. Based on the clinical, imaging, and pathological findings, the patient was diagnosed with IgG4‐related retroperitoneal fibrosis due to ICI. Immunotherapy discontinuation alone did not result in improvement; therefore, steroid therapy was initiated. In clinical practice, IgG4‐related retroperitoneal fibrosis can occur as an immune‐related adverse event when administering anti‐PD‐1 and anti‐CTLA‐4 antibodies for cancer immunotherapy. Early steroid therapy could be effective in controlling this immune‐related adverse event.

A 35-year-old primigravida with a history of adenomyosis enucleation was diagnosed with abnormal fetal position at 25 weeks of gestation. The patient presented with normal vital signs and no symptoms. A cardiotocogram and transabdominal ultrasound revealed a healthy fetus, normal amniotic fluid volume, and no intra-abdominal bleeding. Pelvic magnetic resonance imaging (MRI) indicated a ruptured muscular layer of the uterine fundus, with the fetus completely prolapsed into the abdominal cavity. An emergency cesarean section was performed, during which the fetus was found wrapped within the amniotic membrane in the abdominal cavity. The uterus exhibited extensive tearing along the line of the previous surgical scar; however, no hemorrhage was observed. In this case, despite uterine rupture, blood flow through the umbilical cord from the placenta in the uterus resulted in the survival of the fetus. In addition, MRI was essential in determining the appropriate timing to save the fetus.