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Introduction: Lung adenocarcinoma with parathyroid hormone (PTH)-related hypercalcemia is uncommon. Case Presentation: A 69-year-old man was admitted to our hospital due to anorexia and fatigue. Serum calcium (15.0 mg/dL) and carcinoembryonic antigen (361.7 ng/mL) were extremely high, and PTH-related protein (PTH-rP) also elevated (16.7 pmol/L). Systemic computed tomography revealed multiple enlarged lymph nodes and disseminated peritoneal nodules, with irregularly shaped nodules in the upper lobe in the left lung. Ultrasound-guided biopsy from the axillary lymph node revealed adenocarcinoma. Immunohistological staining showed the tumor cells to be positive for cytokeratin 7 and PTH-rP and negative for cytokeratin 20 and thyroid transcription factor-1. Although the primary origin remains undetermined despite detailed examinations, possible primary tumor was considered to be lung adenocarcinoma in the present case. The serum calcium level was reduced by denosumab, but the patient died 20 days after admission. Conclusion: The present case demonstrated the importance of considering oncological emergency, such as hypercalcemia and/or PTH-rP-producing hypercalcemia, in patients with adenocarcinoma.

Abstract High myopia can lead to pathologic myopia and visual impairment, whereas its causes are unclear. We retrospectively researched high myopia cases from patient records to investigate the association between axial elongation and myopic maculopathy. Sixty-four eyes were examined in patients who visited the department between July 2017 and June 2018, had an axial length of 26 mm or more, underwent fundus photography, and had their axial length measured twice or more. The average axial length was 28.29 ± 1.69 mm (mean ± standard deviation). The average age was 58.3 ± 14.4 years old. Myopic maculopathy was categorized as mild (grades 0 and 1) and severe (grades 2, 3, and 4). The severe group had longer axial lengths than the mild group (P

Background Several studies have shown that the retrieval of positive memories may play a role in emotional regulation. However, it is unclear whether the effects of neutral and positive autobiographical memories differ. It is necessary to confirm whether genuinely neutral autobiographical memories can be retrieved without bias when prompted to recall neutral memories. Methods In this pilot study, using “home” and “study” as cue words, we investigated whether participants were able to retrieve appropriate autobiographical memories when asked to recall a limited number of neutral or positive memories. Results Although participants were asked to recall neutral autobiographical memories, they tended to recall positive memories. Conclusions Our results support the concept of positive memory bias and suggest that future work should consider combining neutral and positive autobiographical memories by asking participants to recall neutral–positive memories.

Summary: MOTS-c is a mitochondrial microprotein that improves metabolism. Here, we demonstrate CK2 is a direct and functional target of MOTS-c. MOTS-c directly binds to CK2 and activates it in cell-free systems. MOTS-c administration to mice prevented skeletal muscle atrophy and enhanced muscle glucose uptake, which were blunted by suppressing CK2 activity. Interestingly, the effects of MOTS-c are tissue-specific. Systemically administered MOTS-c binds to CK2 in fat and muscle, yet stimulates CK2 activity in muscle while suppressing it in fat by differentially modifying CK2-interacting proteins. Notably, a naturally occurring MOTS-c variant, K14Q MOTS-c, has reduced binding to CK2 and does not activate it or elicit its effects. Male K14Q MOTS-c carriers exhibited a higher risk of sarcopenia and type 2 diabetes (T2D) in an age- and physical-activity-dependent manner, whereas females had an age-specific reduced risk of T2D. Altogether, these findings provide evidence that CK2 is required for MOTS-c effects.

Background/objectives: Dry eye disease (DED) and myopia are common ocular disorders. This systematic review and meta-analysis investigated the association between DED and myopia. Methods: PubMed and EMBASE were searched for articles published between 1984 and 2022. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist, and analysis was conducted using the DerSimonian–Laird random-effects model. Results: Of the 1,313 studies identified, 15 studies on DED and myopia were included. The meta-analysis revealed that the overall prevalence of subjective DED symptoms in the myopia population was 45.1 % (95 % confidence interval: 0.287–0.616). There was a significant association between DED and myopia. The myopia population had higher Ocular Surface Disease Index scores and shorter tear film breakup times than the non-myopia population. Additionally, the meta-regression analysis showed that spherical equivalent was significantly associated with the prevalence of DED symptoms in adults with myopia. Conclusion: Interventions to prevent DED are required in the myopia population. Enhancing patient awareness and self-management for DED, in addition to early screening and detection, is especially critical for younger populations who are at a higher risk of developing myopia.

Summary: Functional refinement of neural circuits is a crucial developmental process in the brain. However, how synaptic maturation and axon wiring proceed cooperatively to establish reliable signal transmission is unclear. Here, we combined nanotopography of release machinery at the active zone (AZ), nanobiophysics of neurotransmitter release, and single-neuron reconstruction of axon arbors of lemniscal fibers (LFs) in the developing mouse somatosensory thalamus. With development, the cluster of Cav2.1 enlarges and translocates closer to vesicle release sites inside the bouton, and LFs drastically shrink their arbors and form larger boutons on the perisomatic region of target neurons. Experimentally constrained simulations show that the nanotopography of mature synapses enables not only rapid vesicular release but also reliable transmission following repetitive firing. Sensory deprivation impairs the developmental shift of molecular nanotopography and axon wiring. Thus, we uncovered the cooperative nanotopographical and morphological mechanisms underlying the developmental establishment of reliable synaptic transmission.

Abstract Background Hay fever (HF) presents with various symptoms, including allergic conjunctivitis and rhinitis, and requires cross‐organ treatment. This study assessed the impact of the coronavirus disease 2019 (COVID‐19) pandemic on HF treatment trends. Methods This retrospective cohort study utilized data from the JMDC database collected between January 2018 and May 2021. Patients with HF were identified based on the relevant International Classification of Diseases 10th Revision diagnosis codes and the prescription of HF‐related medications. The treatment approaches were compared during the cedar and cypress pollen allergy season (January to May in Japan) before and during the COVID‐19 pandemic (2018 and 2019, and 2020 and 2021, respectively). Results This study included 2,598,178 patients with HF. The numbers of prescribed HF‐related claims in 2018, 2019, 2020, and 2021 were 3,332,854, 3,534,198, 2,774,380, and 2,786,681 times, respectively. Oral second‐generation antihistamine prescriptions decreased by >10% from 2019 to 2020, with a 10% from 2019 to 2020 but increased by >10% from 2020 to 2021. Compared with 2018, 2019, and 2020, the number of claims in the rhinitis symptoms dominant group was significantly decreased in 2021 (p

Azusa Sugimoto1, Shinichi Koyama2, Akira Midorikawa3, Akinori Futamura1, Kiichi Ishiwata4, Kenji Ishii4, Michael W Miller5, Mitsuru Kawamura11Department of Neurology, Showa University School of Medicine, Tokyo, 2Design Psychology Unit, Department of Design Science, Graduate School of Engineering, Chiba University, Chiba, 3Department of Psychology, Faculty of Letters, Chuo University, Tokyo, 4Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, 5Medical Sciences Training Programme, Faculty of Medicine, University of Tokyo, Tokyo, JapanAbstract: Prosopagnosia, the inability to recognize faces, has a history going back to Charcot and Hughlings-Jackson, but was first named by Bodamer in 1947. Its anatomical loci are still unclear. However, progressive prosopagnosia is normally linked to right dominant temporal lobe atrophy, and diagnosed as part of frontotemporal lobar degeneration. Here we report a case of prosopagnosia linked to posterior cortical atrophy. Although case reports of posterior cortical atrophy-prosopagnosia do already exist, it is normally described as an accessory symptom. The interest of our own posterior cortical atrophy patient, possibly the first such case, is that he had a rare apperceptive type of prosopagnosia unrelated to the associative, frontotemporal lobar degeneration-type.Keywords: dementia, Alzheimer's disease, frontotemporal lobar degeneration, neuropsychology

Contribution: This article describes one approach to foster technical skills (Digital Electronics) and professional skills (critical thinking, problem solving, communication, and collaboration) for Computer Engineering students in a fully remote way. Background: Engineering competencies development requires practical activities. Besides the technical skills, professional skills such as communication are necessary in the workplace. Intended Outcomes: When compared to face-to-face offering, the fully remote course must have no statistically relevant differences in terms of student performance. The course must also support the enhancement of professional skills (e.g., collaboration). Application Design: This study presents a comparison of the face-to-face (one year) and the fully remote (two years) Digital Electronics lab offerings. A course organization framework is proposed with two blocks: (1) controlled experiments and (2) projects in groups of two students. The study investigates how Project-Based Learning and Peer Assessment are perceived by students in the fully remote offering. A total of 110 students participated in the years 2019 (face-to-face), 2020, and 2021 (fully remote). Findings: Students in the second remote course offering (2021) presented a higher performance in their projects than face-to-face students (2019). Besides the student performance and technical skills development, it was observed that problem solving and collaboration, professional skills could be enhanced according to the students' perceptions. However, the same did not occur for critical thinking or communication professional skills even with the Peer Assessment and project pitches. The main concern is the high workload for students.

Abstract Background The purpose of this study was to evaluate the clinicopathological characteristics of patients who underwent surgical resection for thymic neuroendocrine tumors (TNET) or thymic carcinoma. Methods In this study, we retrospectively evaluated the clinicopathological characteristics of our surgical patients at Fukuoka University Hospital from January 1995 to December 2018. Results There were nine cases of TNET and 16 cases of thymic carcinoma. Regarding the pathological type, the TNET group included three atypical carcinoid cases, two large cell neuroendocrine tumor cases, two small cell carcinoma cases, and two other cases. The thymic carcinoma group included 15 squamous carcinoma cases and one case of adenosquamous carcinoma. Based on the Masaoka-Koga staging system, six TNET cases and 11 thymic carcinoma cases were stage III or IV. The complete resection rate was 77% in the TNET group and 81% in the thymic carcinoma group. Additional chemotherapy and/or radiotherapy was performed in five cases of TNET and 11 cases of thymic carcinoma. The five-year survival rate and five-year disease-free survival rate were 87.5% and 75.0% in the TNET group and 58.9% and 57.1% in the thymic carcinoma group, respectively, with no significant difference between the two groups (P = 0.248 and P = 0.894, respectively). In the univariate analysis, complete resection was a statistically significant prognostic factor (P = 0.017). Conclusion In this study, no difference in prognosis was observed between TNET and thymic carcinomas. To understand the characteristics of these tumors, further case accumulation and multicenter clinical studies are needed. (243words)

Purpose: This study aimed to compare subjective allergic conjunctivitis symptoms and anti-allergic eye drop use patterns between antihistamine-releasing contact lens users and daily disposable soft contact lens users during Japan's hay fever season. Methods: This web-based retrospective cohort study included daily disposable soft contact lens or antihistamine-releasing contact lens users with a history of seasonal allergic conjunctivitis who regularly used daily disposable soft contact lenses since the previous year. The total ocular symptom score (range 0–20) based on 5-item questionnaire scores and time from the start of the hay fever season to the initiation of anti-allergic eye drop treatment were compared between antihistamine-releasing contact lens users and daily disposable soft contact lens users. Results: The study included 24 participants: 17 using daily disposable soft contact lenses and 7 using antihistamine-releasing contact lenses. Antihistamine-releasing contact lens users experienced a greater reduction in total ocular symptom score from 2021 to 2022 compared with daily disposable soft contact lens users (mean total ocular symptom score [standard deviation]: daily disposable soft contact lens: −0.65 [1.4], antihistamine-releasing contact lens: −4.7 [3.6]; n = 24; Mann–Whitney U test, P = 0.010). Fourteen daily disposable soft contact lens users and five antihistamine-releasing contact lens users eventually required anti-allergic eye drops. Kaplan–Meier analysis revealed a significant delay in the initiation of anti-allergic eye drop treatment among those using antihistamine-releasing contact lenses compared with those using daily disposable soft contact lenses (median days, daily disposable soft contact lenses: 19 days, antihistamine-releasing contact lens: 57 days; n = 24; log-rank test, P = 0.045). Conclusions: Antihistamine-releasing contact lenses can potentially mitigate worsening ocular allergic responses during the hay fever season when used appropriately as a preventive measure.

Abstract This retrospective study aimed to determine the optimal cutoff values of the Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire for diagnosing dry eye disease (DED) and classifying DED severities. Participants completed the DEQS questionnaire, the Japanese version of the Ocular Surface Disease Index (J-OSDI) questionnaire, and DED examinations. DED was diagnosed according to the 2016 Asia Dry Eye Society diagnostic criteria based on DED symptoms (J-OSDI ≥ 13 points) and tear film breakup time ≤ 5 s. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the DEQS summary score for detecting DED and grading its severity. Among 427 patients, 296 (69.3%) and 131 (30.7%) were diagnosed with DED and non-DED, respectively. ROC analysis determined an optimal cutoff value of 15.0 points for DED diagnosis, with 83.5% sensitivity, 87.0% specificity, and an area under the curve of 0.915. The positive and negative predictive values for DEQS ≥ 15.0 points were 93.6% and 69.9%, respectively. DEQS cutoff values of 15.0, 20.0, and 26.8 points could be accepted for severity classification of DED subjective symptoms in clinical use and represent mild, moderate, and severe DED, respectively. Conclusively, the optimal cutoff values of DEQS enable DED detection and subjective symptom severity classification.

Background Several studies have shown that the retrieval of positive memories may play a role in emotional regulation. However, it is unclear whether the effects of neutral and positive autobiographical memories differ. There is a need to confirm that genuinely neutral autobiographical memories can be retrieved without bias in response to a prompt to recall neutral memories. Methods In this pilot study, using “home” and “study” as cue words, we investigated whether participants were able to retrieve appropriate autobiographical memories when asked to recall a limited number of neutral or positive memories. Results Although participants were asked to recall neutral autobiographical memories, they tended to recall positive memories. Conclusions Our results support the concept of positive memory bias and suggest that future work should consider combining neutral and positive autobiographical memories, namely by asking participants to recall neutral–positive memories.

Abstract The carrier-envelope phase (CEP) of an ultrashort laser pulse is becoming more crucial to specify the temporal characteristic of the pulse’s electric field when the pulse duration becomes shorter and attains the subcycle regime; here, the pulse duration of the intensity envelope is shorter than one cycle period of the carrier field oscillation. When this subcycle pulse involves a structured wavefront as is contained in an optical vortex (OV) pulse, the CEP has an impact on not only the temporal but also the spatial characteristics owing to the spatiotemporal coupling in the structured optical pulse. However, the direct observation of the spatial effect of the CEP control has not yet been demonstrated. In this study, we report on the measurement and control of the spatial wavefront of a subcycle OV pulse by adjusting the CEP. To generate subcycle OV pulses, an optical parametric amplifier delivering subcycle Gaussian pulses and a Sagnac interferometer as a mode converter were integrated and provided an adequate spectral adaptability. The pulse duration of the generated OV pulse was 4.7 fs at a carrier wavelength of 1.54 µm. To confirm the wavefront control with the alteration of the CEP, we developed a novel $$f$$ f -2 $$f$$ f interferometer that exhibited spiral fringes originating from the spatial interference between the subcycle OV pulse and the second harmonic of the subcycle Gaussian pulse producing a parabolic wavefront as a reference; this resulted in the successful observation of the rotation of spiral interference fringes during CEP manipulation.

Background: This study aimed to delineate the interplay between depression, hopelessness, and episodic future thinking (EFT), focusing on cognitive biases towards negative future thinking that are central to depressive symptomatically. Methods: A Japanese university student was utilized to scrutinize divergences in EFT across groups stratified by varying degrees of depression and hopelessness. The research leveraged a modified future thinking task (FTT), the Beck Hopelessness Scale, and the Beck Depression Inventory-II to gauge participants’ levels of hopelessness and depressive symptoms. Results: Consistent with prior research, the non-depressed group showed a reduction in positive EFT, reinforcing the idea that diminished positive future thinking is a hallmark of depressive conditions, even in the absence of a clinical diagnosis. Moreover, individuals with comorbid depression and elevated hopelessness demonstrated a significant decrease in positive EFT and an increase in negative EFT, substantiating a distinctive cognitive profile for this subgroup. This finding suggests that the presence of hopelessness exacerbates the negative cognitive biases associated with depression. Conclusions: The study emphasizes the importance of considering hopelessness as an independent construct when assessing EFT in clinical contexts. The pronounced impact of hopelessness on future thinking in those with depression suggests that targeted interventions, such as future-directed therapy (FDT), may be particularly effective for individuals with hopelessness depression by focusing on modifying negative future thinking patterns and enhancing life quality.

Abstract Background The transferrin receptor (TfR) encoded by TFRC gene is the main cellular iron importer. TfR is highly expressed in many cancers and is expected to be a promising new target for cancer therapy; however, its role in nasopharyngeal carcinoma (NPC) remains unknown. Methods The TfR levels were investigated in NPC tissues and cell lines using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. Knockdown of TFRC using two siRNA to investigate the effects on intracellular iron level and biological functions, including proliferation by CKK-8 assay, colony formation, cell apoptosis and cell cycle by flow cytometry, migration and invasion, and tumor growth in vivo by nude mouse xenografts. RNA sequencing was performed to find possible mechanism after TFRC knockdown on NPC cells and further verified by western blotting. Results TfR was overexpressed in NPC cell lines and tissues. Knockdown of TFRC inhibited cell proliferation concomitant with increased apoptosis and cell cycle arrest, and it decreased intracellular iron, colony formation, migration, invasion, and epithelial-mesenchymal transition in HK1-EBV cells. Western blotting showed that TFRC knockdown suppressed the levels of the iron storage protein FTH1, anti-apoptotic marker BCL-xL, and epithelial-mesenchymal transition markers. We confirmed in vivo that TFRC knockdown also inhibited NPC tumor growth and decreased Ki67 expression in tumor tissues of nude mouse xenografts. RNA sequencing and western blotting revealed that TFRC silencing inhibited the PI3K/Akt/mTOR signaling pathway. Conclusions These results indicated that TfR was overexpressed in NPC, and TFRC knockdown inhibited NPC progression by suppressing the PI3K/Akt/mTOR signaling pathway. Thus, TfR may serve as a novel biomarker and therapeutic target for NPC.

Background: The coronavirus disease (COVID) 2019 pandemic has been reported to have resulted in psychological disturbances. The Japanese term “hikikomori” refers to a state of preferring to stay at home. The COVID pandemic provided an opportunity to extend our current understanding of hikikomori by examining the psychological states of individuals who were in this state under lockdown, during which, paradoxically, their condition may have been adaptive. Methods: We administered a questionnaire to examine psychological changes among 600 people with hikikomori traits in Japan. The Hospital Anxiety and Depression Scale (HADS), Subjective Stress Scale, and Stigma Questions for hikikomori were administered retrospectively at three time points. We also collected descriptive data regarding the participants’ coping strategies. Results: The participants’ sense of stigma regarding hikikomori was improved during the pandemic, whereas depression and anxiety worsened. The participants with ‘definite’ hikikomori (they met the diagnostic criteria) reported more severe depression and anxiety than those with ‘possible’ hikikomori. Their coping strategies were adaptive to the pandemic situation. Conclusion: Although the sense of stigma against hikikomori was improved and adaptive strategies were employed, the participants with hikikomori experienced a worsening of depression and anxiety during the COVID lockdowns. The improvement of stigma and the participants’ indoor adaptive coping strategies could not ameliorate the mental state of hikikomori. Therapeutic interventions should be considered in the future for definite hikikomori meeting the criteria.

Abstract The coronavirus disease (COVID-19) pandemic has emphasized the paucity of non-contact and non-invasive methods for the objective evaluation of dry eye disease (DED). However, robust evidence to support the implementation of mHealth- and app-based biometrics for clinical use is lacking. This study aimed to evaluate the reliability and validity of app-based maximum blink interval (MBI) measurements using DryEyeRhythm and equivalent traditional techniques in providing an accessible and convenient diagnosis. In this single-center, prospective, cross-sectional, observational study, 83 participants, including 57 with DED, had measurements recorded including slit-lamp-based, app-based, and visually confirmed MBI. Internal consistency and reliability were assessed using Cronbach’s alpha and intraclass correlation coefficients. Discriminant and concurrent validity were assessed by comparing the MBIs from the DED and non-DED groups and Pearson’s tests for each platform pair. Bland–Altman analysis was performed to assess the agreement between platforms. App-based MBI showed good Cronbach’s alpha coefficient, intraclass correlation coefficient, and Pearson correlation coefficient values, compared with visually confirmed MBI. The DED group had significantly shorter app-based MBIs, compared with the non-DED group. Bland–Altman analysis revealed minimal biases between the app-based and visually confirmed MBIs. Our findings indicate that DryEyeRhythm is a reliable and valid tool that can be used for non-invasive and non-contact collection of MBI measurements, which can assist in accessible DED detection and management.

Background: Multidisciplinary efforts to prospectively collect and analyze symptoms of hay fever are limited. We aimed to identify the characteristics of nasal and ocular symptoms of hay fever, using the AllerSearch smartphone application. Methods: This mobile health-based prospective observational study using the AllerSearch smartphone application was conducted between February 1, 2018, and May 1, 2020. Individuals who downloaded AllerSearch from Japan and provided comprehensive self-assessments (including 17 items related to quality of life [QoL]-related items) were included. The characteristics and risk factors for allergic rhinitis (AR) and allergic conjunctivitis (AC) were identified using hierarchical heat maps and multivariate logistic regression. Results: Of the 9041 participants with hay fever, 58.8% had AR and AC, 22.2% had AR, and 5.7% had AC. The AR–AC comorbid cohort showed worse symptoms of hay fever and QoL scores than the other cohorts. Factors (odds ratio, 95% confidence interval) associated with AR–AC included a lower age (0.98, 0.97–0.98), female sex (1.31, 1.19–1.45), liver disease (1.58, 1.26–2.35), dry eye disease (1.45, 1.30–1.63), unknown dry eye disease status (1.46, 1.31–1.62), contact lens use discontinuation during the hay fever season (1.69, 1.28–2.23), and bedroom flooring material other than hardwood, carpet, tatami, or vinyl (1.91, 1.16–3.14). Conclusions: Analysis of medical big data for hay fever performed using a mobile health app helped identify risk factors and characteristics of AC, AR, and AR–AC. Phenotyping of highly variable symptoms of hay fever, such as nasal and ocular symptoms, can facilitate better-quality clinical care.