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Purpose: To comprehensively evaluate baseline characteristics of patients with central serous chorioretinopathy (CSC) and develop predictive risk scores to identify visual prognosis., Methods: This single-institute, retrospective cohort study included 144 eyes of 144 patients with CSC who underwent photodynamic therapy and achieved serous retinal detachment resolution. We developed and assessed the performance of several risk scores for best-corrected visual acuity (BCVA) outcomes six months post-treatment: i) BCVA improvement (≤-1.0 logMAR), and ii) BCVA deterioration (≥+ 1.0 logMAR)., Results: The BCVA improvement models used photoreceptor outer segment thickness, loss of photoreceptor outer segment, and neurosensory retinal thickness (NSRT), while the BCVA deterioration models included outer nuclear layer thickness and NSRT. The BCVA improvement models demonstrated a corrected area under the curve (AUC) of 0.786 (95% confidence interval [CI]: 0.699-0.864), with 80.4% sensitivity, and 71.2% specificity. The BCVA deterioration models achieved a corrected AUC of 0.864 (95% CI: 0.742-0.958), with 85.7% sensitivity, and 83.5% specificity., Conclusion: The predictive models for CSC exhibited favorable performance in predicting individual visual prognoses. A thinner outer nuclear layer may be associated with BCVA deterioration, whereas preservation of the photoreceptor outer segment may be correlated with BCVA improvement., Key Messages: WHAT IS KNOWN : Pre-treatment best-corrected visual acuity, thickness of each sensory retinal layer, time from onset to treatment, and macular atrophy were each found to be associated with visual prognosis for patients with central serous chorioretinopathy (CSC)., What Is New: The current study comprehensively assessed potential prognostic factors and precisely identified individual likelihood of visual prognosis. The study found that different regions of the sensory retina were associated with either worsening or improving visual acuity. Accurately predicting visual outcomes after photodynamic therapy for CSC would help healthcare providers create personalized treatment plans and enable patients to make informed decisions about their treatment based on their expected visual results., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Kagoshima University (no. 170283) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Since this study was a retrospective study, obtaining informed consent was waived in the study. This design is approved by the Ethics Committee of Kagoshima University (no. 170283). Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Taiji Sakamoto- although the co-author is an editor of the journal, there was no involvement with the peer review process for this article., (© 2024. The Author(s).)

This study aimed to characterize the detailed multi-modal imaging findings of red blood cell (RBC)-coated intraocular lenses (IOLs). A 68-year-old patient with polypoidal choroidal vasculopathy underwent vitrectomy for subretinal and vitreous hemorrhage. Subsequently, RBC-coated IOL was diagnosed. The iris and IOL surface exhibited a reddish discoloration, while the fundus was completely obscured by slit-lamp examination and ultra-widefield scanning laser ophthalmoscopy. However, posterior segment optical coherence tomography (OCT) allowed visualization of retinal structures. Anterior segment OCT revealed no opacity in the optic part of the IOL in either eye, with comparable findings between both eyes. Given the high absorption spectrum of blood in the visible light range and its minimum absorption at approximately 1100 nm, RBC-coated IOLs may minimally affect anterior and posterior segment OCT images. Conversely, they significantly impair slit-lamp examination and direct fundus visualization. The discrepancy in imaging outcomes between fundus image and OCT could be a characteristic feature of RBC-coated IOLs. This may serve as a characteristic of RBC-coated IOLs. In cases of suspected IOL opacification or RBC-coated IOL following vitreous hemorrhage, anterior segment OCT can evaluate the IOL optic clarity. Additionally, comparing image quality between fundus photographs and posterior segment OCT may provide valuable diagnostic information., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sawazono et al.)

Objective: This study aimed to investigate the factors influencing the clinical outcomes of regenerative therapy using recombinant human fibroblast growth factor-2 (rhFGF-2)., Background: rhFGF-2 promotes periodontal regeneration, and identifying the factors influencing this regeneration is important for optimizing the effectiveness of rhFGF-2., Methods and Materials: This study used a hospital information-integrated database to identify patients who underwent periodontal regenerative therapy with rhFGF-2. Factors included age, smoking status, diabetes mellitus (DM), periodontal inflamed surface area (PISA) at the initial visit, whether the most posterior tooth was involved or not, and preoperative radiological bone defect angle. Periodontal regenerative therapy outcomes were defined as good if radiographic bone fill ≥35% or periodontal pocket closure at 9-15 months after surgery. Bone fill rate (%) and periodontal pocket depth (mm) were also used as outcome measures. Factors were evaluated by simple regression analysis, and then the association between factors and the outcomes was determined by multivariate analysis., Results: PISA and age at the first visit did not significantly influence the success or failure of bone fill rate byrhFGF-2. However, DM, radiographic bone defect angle, and the most posterior tooth significantly influenced the regenerative effect (success/failure in bone fill) of rhFGF-2. The most posterior tooth was significantly associated with bone fill rate by rhFGF-2. Examination of the association between pocket closure and factors shows that the most posterior tooth significantly influenced. The most posterior tooth and preoperative PPD were significantly associated with pocket reduction depth. For the most posterior tooth, a significantly higher bone regeneration rate (p < .05) was observed with a combination of autologous bone graft and rhFGF-2 than with rhFGF-2 alone, and the effect was significant in multivariate analysis., Conclusions: The radiographic bone defect angle, the involvement of most posterior teeth, and the presence of DM influenced the effectiveness of rhFGF-2 in periodontal regeneration. However, PISA values and age at the initial visit had no significant effect., (© 2024 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

This study aims to develop a method to quantify choroidal vessels in normal eyes using wide-field optical coherence tomography (OCT) en-face images. The study included participants with normal eyes in whom wide-angle OCT images were acquired to generate planarized choroidal en-face and thickness map images. The images were segmented into central, midperipheral, and peripheral areas, and the midperipheral and peripheral areas were further segmented into supratemporal, infratemporal, supranasal, and infranasal sectors. The mean planarized choroidal-vessel density (p-CVD), planarized choroidal-vessel size (p-CVS), and choroidal thickness (CT) were calculated in each sector. Sex differences were analyzed using the Mann-Whitney U test. The study included 162 participants comprising 84 female (mean age, 43.5 years; axial length, 24.0 mm) and 78 male (mean age, 44.4 years; axial length, 24.2 mm) participants with no significant differences in demographics (P ≥ 0.107). Men had a higher mean p-CVD in all regions (P < 0.001). The mean p-CVS was greater in men in all regions except for the supratemporal sector (P < 0.001). No significant differences in sex in the mean CT were observed in all regions (P ≥ 0.106). The p-CVD and p-CVS in normal eyes differ between sexes. This finding may contribute to the understanding of the pathophysiology of choroidal diseases., (© 2024. The Author(s).)

Oral bacteria are known to be associated with perioperative complications during hospitalization. However, no presented reports have clarified the relationship of oral bacterial number with medical costs for inpatients. The Diagnosis Procedure Combination (DPC) database system used in Japan provides clinical information regarding acute hospital patients. The present study was conducted to determine the association of oral bacterial numbers in individual patients treated at a single institution with length of hospital stay and medical costs using DPC data. A total of 2369 patients referred by the medical department to the dental department at Hiroshima University Hospital were divided into the low (n = 2060) and high (n = 309) oral bacterial number groups. Length of hospital stay and medical costs were compared between the groups, as well as the associations of number of oral bacteria with Charlson comorbidity index (CCI)-related diseases in regard to mortality and disease severity. There was no significant difference in hospital stay length between the low (24.3 ± 24.2 days) and high (22.8 ± 20.1 days) oral bacterial number groups. On the other hand, the daily hospital medical cost in the high group was significantly greater (US$1456.2 ± 1505.7 vs. US$1185.7 ± 1128.6, P < 0.001). Additionally, there was no significant difference in CCI score between the groups, whereas the daily hospital medical costs for patients in the high group treated for cardiovascular disease or malignant tumors were greater than in the low number group (P < 0.05). Multivariate regression analysis was also performed, which showed that oral bacterial number, age, gender, BMI, cardiovascular disease, diabetes, malignant tumor, and hospital stay length were independently associated with daily hospitalization costs. Monitoring and oral care treatment to lower the number of oral bacteria in patients affected by cardiovascular disease or cancer may contribute to reduce hospitalization costs., (© 2024. The Author(s).)

The combination of amphiphilic ions and metal complexes may enable the construction of assemblies in which the assembly structure and electronic state of the metal complexes change concertedly. In this work, an alternating layered structure of [Co 2 Fe 2 ] complexes and amphiphilic anions was constructed. In the crystal structure, [Co 2 Fe 2 ] complexes and water molecules formed a hydrogen-bonded supramolecular one-dimensional (1D) chain in the hydrophilic layer. A reversible structural change between the 1D chain and discrete [Co 2 Fe 2 ] complexes was found to occur concertedly with an electron transfer-coupled spin transition (ETCST) of the [Co 2 Fe 2 ] complex and desorption/adsorption of water molecules.

Background: To compare the one-year outcomes between intravitreal brolucizumab (IVBr) monotherapy and photodynamic therapy (PDT) as a second-line treatment in patients with polypoidal choroidal vasculopathy (PCV) who did not respond to first-line therapy., Methods: This case-control study included eyes with PCV that do not respond to aflibercept or ranibizumab. The patients were retrospectively registered. We compared outcomes, including best-corrected visual acuity (BCVA), anatomical results, and the need for additional treatments, between IVBr and a combination therapy using PDT as second-line treatments for refractory PCV, after adjusting for potential confounders. We analyzed E-values to evaluate the robustness of the results against unmeasured confounders., Results: Twenty-two eyes received IVBr, and twenty-four underwent PDT. No apparent differences were observed in BCVA and central macular thickness (CMT) changes from baseline between the groups (IVBr vs. PDT: BCVA, 0.01 ± 0.47 logMAR vs. 0.04 ± 0.18 logMAR, P-value = 0.756; CMT: - 36.3 ± 99.4 μm vs. - 114.7 ± 181.4 μm, P-value = 0.146). Only in the PDT group, five eyes (20.8%) did not require additional treatment after the second-line treatment, the adjusted odds ratio indicating no further treatment needed was 11.98 (95% confidence interval: 1.42-2070.07, P-value = 0.019). The E-value for the adjusted odds ratio was 23.44., Conclusions: Both second-line treatments for PCV exhibited similar visual and anatomical outcomes. Only in the PDT-treated eyes were there some patients who did not require further treatment after second-line therapy., (© 2024. The Author(s).)

Complex socio-technical health information systems (HIS) issues can create new error risks. Therefore, we evaluated the management of HIS-related errors using the proposed human, organization, process, and technology-fit framework to identify the lessons learned. Qualitative case study methodology through observation, interview, and document analysis was conducted at a 1000-bed Japanese specialist teaching hospital. Effective management of HIS-related errors was attributable to many socio-technical factors including continuous improvement, safety culture, strong management and leadership, effective communication, preventive and corrective mechanisms, an incident reporting system, and closed feedback loops. Enablers of medication errors include system sophistication and process factors like workarounds, variance, clinical workload, slips and mistakes, and miscommunication. The case management effectiveness in handling the HIS-related errors can guide other clinical settings. The potential of HIS to minimize errors can be achieved through continual, systematic, and structured evaluation. The case study validated the applicability of the proposed evaluation framework that can be applied flexibly according to study contexts to inform HIS stakeholders in decision-making. The comprehensive and specific measures of the proposed framework and approach can be a useful guide for evaluating complex HIS-related errors. Leaner and fitter socio-technical components of HIS can yield safer system use., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Krüppel-like factor (KLF)5, which is overexpressed in carcinomas such as oral cancer, inhibits epidermal differentiation. KLF5 induces dedifferentiation of carcinoma cells, which effectuates carcinoma progression; nevertheless, the regulatory mechanism affecting the transcription of the KLF5 gene remains ambiguous., Methods: Transcriptional activity of the KLF5 silencer, specifically the 425-bp region (425-region), was examined using reporter assays. An additional analysis was conducted to assess the impact of the minimal essential region (MER) of KLF5 on its basal expression. The affinity of cAMP responsive element binding protein 1 (CREB1) for three potential CREB1-binding sites in the 425-region was analyzed using DNA pull-down and quantitative chromatin immunoprecipitation assays. Reporter assays employing a human oral squamous carcinoma cell line, HSC2, transfected with small interfering RNA or complementary DNA for CREB1, were performed to investigate the effect of CREB1 binding sites on MER activity., Results: The 425-region exhibited no transcriptional activity and suppressed MER transcriptional activity. This region encodes three putative CREB1-binding sites, and CREB1 demonstrated equal binding affinity for all three sites. The deletion of each of these binding sites reduced CREB1 precipitation and enhanced MER activity. Endogenous CREB1 knockdown and overexpression elevated and reduced MER activity, respectively, at the intact sites. Conversely, site deletion hampered and improved MER activity upon CREB1 knockdown and overexpression, respectively., Conclusions: Suppression of KLF5 basal expression via CREB1 binding to the 425-region requires all three CREB1-binding sites to remain intact in oral carcinoma cells. Consequently, deletion of the CREB1-binding site relieves suppression of KLF5 basal expression., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2023 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Seed-mediated growth has been widely used to synthesize noble metal nanoparticles with controlled size and shape. Although it is becoming possible to directly observe the nucleation process of metal atoms at the single atom level by using transmission electron microscopy (TEM), it is challenging to control the formation and growth of seeds with only a few metal atoms in homogeneous solution systems. This work reports site-selective formation and growth of atomic scale seeds of the Au nanoparticle in a nanospace of an organic cage molecule. We synthesized a cage molecule with amines and phenols, which were found to both capture and reduce Au(III) ions to spontaneously form the atomic scale seeds containing Au(0) in the nanospace. The growth reaction of the atomic scale seeds afforded Au nanoparticles with an average diameter of 2.0±0.2 nm, which is in good agreement with the inner diameter of the cage molecule., (© 2023 Wiley-VCH GmbH.)

Objective: Colour scanning laser ophthalmoscope (cSLO) offers several advantages, including improved image quality and better visualisation of the retinal structures compared with colour fundus photograph (CFP). This study aimed to identify whether cSLO could be used to predict systemic arterial stiffness., Methods and Analysis: We retrospectively analysed the data of 54 patients with 103 eyes. In addition to blood pressure and blood data, all patients had cardio-ankle vascular index (CAVI) measurements, as well as images of the fundus acquired using cSLO and CFP. We determined the retinal artery sclerosis (RAS) index from the colour of the retinal artery in cSLO images, the ratio of arterial to venous diameter (A/V ratio), and Scheie's classification in CFP images. The correlation between each parameter and CAVI was examined using Spearman's rank correlation coefficient, and the correlation between Scheie's classification and CAVI was examined using Steel-Dowass tests., Results: CAVI showed a significant positive correlation with the RAS index (r=0.679, p<0.001) but not with the A/V ratio or Scheie's classification. Multiple regression analysis showed that the RAS index was significantly and independently correlated with CAVI., Conclusion: cSLO is a non-invasive imaging modality that has the potential to accurately and instantaneously detect early systemic arterial stiffness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to examine baseline characteristics for identifying factors associated with vision loss (VL) in patients with central serous chorioretinopathy (CSC) who successfully responded to photodynamic therapy (PDT)., Design: A retrospective, clinical case-control study., Methods: This study included 85 eyes with CSC, which underwent PDT, and resolved serous retinal detachment. These eyes were classified into 2 groups: the VL group (best-corrected visual acuity 6 months after PDT was worse than that at baseline) and the vision maintenance or improved group (the others). Baseline factors were analyzed to determine the characteristics of the VL group and assess the diagnostic potential of these factors., Result: Seventeen eyes were included in the VL group. The mean values of the neurosensory retinal (NSR) thickness, the internal limiting membrane-external limiting membrane thickness (IET), and the external limiting membrane-photoreceptor outer segment thickness (EOT) in the VL group were significantly thinner than those in the vision maintenance or improved group (NSR thickness, 123.2 ± 39.7 µm vs 166.3 ± 49.6 µm, P < .001; IET, 63.1 ± 17.0 µm vs 88.0 ± 25.4 µm, P < .001; EOT, 60.1 ± 28.6 µm vs 78.3 ± 33.1, P = .041). The sensitivity, specificity, and positive and negative predictive values for predicting VL were 94.1%, 50.0%, 32.0%, and 97.1% for NSR thickness; 94.1%, 51.5%, 32.7%, and 97.2% for IET; and 94.1%, 30.9%, 25.4%, and 95.5% for EOT, respectively., Conclusions: Pretreatment sensory retinal layer thickness could predict VL after PDT for CSC and may be a helpful reference for PDT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Delirium, a neurocognitive disorder, typically occurs in older patients and those with advanced cancer. Although there have been numerous reports on delirium in patients with cancer in various conditions, there are no reports that specifically focus on patients with musculoskeletal tumours. This prospective study aimed to investigate the incidence, risk factors and prognostic implications of delirium in patients with musculoskeletal tumours., Methods: In this single institutional study, 148 patients with musculoskeletal oncology were enrolled. The estimated risk factors included age, sex, alcohol abuse, performance status (PS), dietary status, admission route, tumour malignancy, oncological stage and blood test results. The significance of delirium in survival was also examined., Results: Only 18 patients with malignant tumours had delirium (12.2%). Based on univariate analysis, older age, poor PS, dietary status, admission from another hospital, malignant tumour, carcinoma rather than sarcoma, anaemia and some laboratory abnormalities were found to be significant risk factors for delirium. Multivariate analysis showed that poor PS was significantly correlated with delirium. Additionally, delirium was significantly correlated with poor survival., Conclusions: The incidence of delirium among patients with musculoskeletal tumours was 12.2% and was observed only in patients with malignant tumours. PS is a significant risk factor for delirium. Delirium is correlated with poor prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to establish a treatment index based on functional outcomes of photodynamic therapy (PDT) for central serous chorioretinopathy (CSC)., Design: A retrospective clinical case-control study., Methods: This was a single-institute study. Eighty (80) eyes with CSC, who were treated by PDT and whose subretinal fluid resolves within 6 months were divided into two groups: those with poor visual outcome (PVO) (best-corrected visual acuity [BCVA] ≤ 0.5 6 months post-PDT), and the remaining eyes (better visual outcome [BVO]). The areas under the curve (AUC) and cutoff values from receiver operating characteristic curves were examined. These was used to predict the groups using pretreatment BCVA and the thickness of each retinochoroidal layer., Result: Twenty-one (21) eyes were in the PVO group and 59 eyes in the BVO group were included. The AUCs were 0.959 for BCVA, 0.959 for the thickness from the internal limiting membrane to the external limiting membrane (IET), 0.820 for the thickness from the external limiting membrane to the photoreceptor outer segment layer, 0.715 for the subfoveal retinal thickness, and 0.515 for the subfoveal choroidal thickness. The BCVA and IET cut-off values were 0.267 logMAR and 71.5 µm, respectively. Using the combination of the cutoff values of BCVA and IET, the highest values for the sensitivity, specificity, positive predictive value, and negative predictive value were 95.2%, 94.9%, 85.0%, and 98.0%, respectively., Conclusion: The combination of pre-PDT BCVA and IET in CSC can accurately predict the post-treatment visual prognosis. These values could be used as a treatment index of PDT for CSC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to describe a case of polypoidal choroidal vasculopathy, showing a newly developed focal choroidal excavation during a 4-year follow-up period with multiple intravitreal antivascular endothelial growth factor injections., Methods: This study was a case report., Results: A 64-year-old man was referred for treatment of age-related macular degeneration in his left eye. His corrected visual acuity at initial presentation was 20/20 in both the right and left eye. Optical coherence tomography of the left eye revealed a steep retinal pigment epithelial detachment and subretinal fluid, and indocyanine green angiography confirmed a polypoidal lesion, leading to the diagnosis of polypoidal choroidal vasculopathy with pachychoroid features. Thereafter, antivascular endothelial growth factor intravitreal injections were continued on a pro re nata basis. Two years after the initial presentation, the sharp pigment epithelial detachment began to shrink, and a novel focal choroidal excavation gradually emerged surrounding the pigment epithelial detachment with an inner choroidal layer attenuation., Conclusion: Multiple antivascular endothelial growth factor injections for polypoidal choroidal vasculopathy resulted in atrophy of the polypoidal lesion and a decrease in the blood flow in the adjacent inner choroidal vasculature, leading to the formation of a novel focal choroidal excavation.

Combining metal complexes with amphiphilic molecules leads to a wide variety of functional self-assembled nanostructures. Metal complexes exhibiting spin transitions can be good candidates as the trigger to cause structural conversion of such assembly because they respond to various external stimuli. In this work, we studied a structural conversion of a supramolecular assembly containing a [Co 2 Fe 2 ] complex through a thermally induced electron transfer-coupled spin transition (ETCST). With an amphiphilic anion, the [Co 2 Fe 2 ] complex formed reverse vesicles in solution and showed thermal ETCST. In contrast, thermal ETCST in the presence of a bridging hydrogen-bond donor caused structural conversion from the reverse vesicle structure to entangled one-dimensional chains through hydrogen bond formation., (© 2023 Wiley-VCH Verlag GmbH.)

Invited for the cover of this issue is the group of Masayuki Nihei at the University of Tsukuba. The image depicts the electron transfer-triggered structural conversion of the supramolecular assembly of a [Co 2 Fe 2 ] complex between reverse vesicles and entangled one-dimensional chains. Read the full text of the article at 10.1002/chem.202300954., (© 2023 Wiley-VCH GmbH.)

Purpose: To analyze the choroidal morphological changes in central serous chorioretinopathy (CSC) using ultra-widefield (UWF)-optical coherence tomography (OCT)., Methods: This single-center, case-control study included 65 CSC eyes (52 males; age, 55.6 ± 13.0 years) and 65 healthy eyes (50 males; age, 57.1 ± 17.9 years). UWF-OCT (viewing angle, 200°) with real-shape correction was used to create an automated choroidal thickness (CT) map. The CT map had three sub-areas: the central (0-30°), middle (30-60°), and peripheral areas (60-100°), and was divided by vertical and horizontal lines. Differences in the CT and the CT change rate (CTCR) from the central to peripheral areas were examined between the CSC and control groups after adjusting for subjects' demographic and clinical factors. Furthermore, we assessed the vortex veins dilation patterns (VVDP) in the macula and examined the CT and the CTCR differences between CSC patients and controls for each VVDP., Results: CSC patients had greater CT than those of the controls in all sectors (CSC vs. controls, the peripheral area: supratemporal 284.4 ± 71.2 μm vs. 220.4 ± 71.2 μm, infratemporal 263.3 ± 69.2 μm vs. 195.3 ± 52.3 μm, supranasal 251.9 ± 70.3 μm vs. 189.5 ± 58.1 μm, infranasal 193.6 ± 71.2 μm vs. 146.3 ± 48.9 μm, P < 0.0001 for all sectors). The CTCR was apparently larger in CSC eyes than controls only for the upper-dominant type of VVDP (CSC patients vs. controls, supratemporal 32.1 ± 9.9% vs. 4.6 ± 23.1%, infratemporal 44.0 ± 11.2% vs. 25.6 ± 16.8%, supranasal 42.6 ± 9.8% vs. 22.2 ± 19.4%, infranasal 57.6 ± 41.2% vs. 41.2 ± 13.9%, P < 0.0001 for all sectors)., Conclusions: CSC has a thicker choroid, even in the peripheral areas, and the macular choroidal thickening was more severe in the upper-dominant type of VVDP. VVDP may affect the location of excessive fluid., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A series of tetranuclear [Cu 3 Ln] complexes, [Cu 3 Gd(L) 3 (NO 3 ) 2 (H 2 O) 3 ](NO 3 )·H 2 O (1), [Cu 3 Tb(L) 3 (NO 3 ) 2 (H 2 O) 3 ](NO 3 ) (2) and [Cu 3 Dy(L) 3 (NO 3 ) 3 (H 2 O) 2 ]·1.5(H 2 O) (3), were synthesized by a one-pot reaction using a simple tetraketone-type ligand (H 2 L = (3 Z ,5 Z )-4,5-dihydroxy-3,5-octadiene-2,7-dione). X-ray structural analyses revealed that each complex has a planar tetranuclear core of [Cu 3 Ln] (Ln = Gd, Tb, and Dy), in which the Ln ion is accommodated in the centre of a Cu 3 O 6 metallocycle. A cryomagnetic study revealed that all complexes show intramolecular ferromagnetic interactions between Cu(II) and Ln(III) ions. The [Cu 3 Gd] complex (1) has an S T = 5 spin ground state and shows a magneto-caloric effect with a maximum magnetic entropy change (-Δ S m ) of 16.4 J kg -1 K -1 (5 T, 2.4 K). On the other hand, the [Cu 3 Tb] complex (2) shows a slow magnetic relaxation behavior under a zero magnetic field. The analysis of an Arrhenius plot reveals that the effective energy barrier of spin reversal is 13.1 K. The [Cu 3 Dy] complex (3) also shows a slow magnetic relaxation under 1300 Oe dc magnetic field with an effective energy barrier of 6.82 K.

Purpose: Choroidal stasis plays an important role in the pathogenesis of many conditions and leads to choroidal thickening. However, the normal peripheral choroidal thickness (PCT) pattern remains unknown. This study investigated PCT and associated factors using ultrawidefield optical coherence tomography in healthy eyes., Methods: This cross-sectional study included 120 healthy eyes (57 males; age, 52.0 ± 20.5 years). We used choroidal thickness maps created by ultrawidefield optical coherence tomography (viewing angle, 200°) with real-shape correction. The peripheral area was defined from 60° to 100° and further separated vertically and horizontally. The PCT and the correlations between PCT and subjects' characteristics were examined., Results: The PCT were 227.1 ± 57.0 µ m, 199.6 ± 53.9 µ m, 196.6 ± 57.1 µ m, and 148.0 ± 38.2 µ m in supratemporal, infratemporal, supranasal, and infranasal areas, respectively. The thickest peripheral sector was most frequently observed in supratemporal (69.2%). The PCT negatively correlated with age in all regions ( P -values < 0.001) and axial length in supratemporal, supranasal, and infranasal areas ( P -values ≤ 0.003). The temporal PCT was thicker on the side contiguous with the posterior pole Haller's vessels ( P -values ≤ 0.020)., Conclusion: The PCT is associated with age, axial length, and the running pattern of Haller's vessels.

Background : When scleral buckling is performed using a #240 encircling band anterior to the equator for rhegmatogenous retinal detachment, buckle migration may occur anteriorly, eroding the rectus muscle. There are few cases of buckle migration occurring simultaneously with buckle infection. Notably, most previous reports included inadequate data on the pathophysiology of buckle migration and did not include the Hess test and perioperative images. Case presentation : A 36-year-old man with a history of atopic dermatitis underwent scleral buckling for rhegmatogenous retinal detachment of the left eye with #287 and #240 encircling bands at Kagoshima University Hospital. Four years later, he developed discharge, redness, and diplopia of the left eye. He was then referred to our hospital because buckle infection was suspected. The buckle was partially visible on the lower nasal side. Optical coherence tomography of the anterior chamber revealed the buckle to be on the nasal side and overlying the medial rectus muscle. Buckle migration and infection in the left eye was diagnosed, and early buckle removal was recommended. Two weeks later, on the day before surgery, conjunctival melting progressed in the nasal and inferior areas, and the buckle was exposed to a greater extent. In the surgical video at the initial surgery, the silicone band was confirmed to pass under the four rectus muscles, specifically the inferior and medial rectus muscles. At the beginning of the second surgery, we confirmed that the buckles were over the inferior and medial rectus muscles. As far as could be observed after buckle removal, the inferior and medial rectus muscles were not present at the normal location. Postoperatively, ocular pain and discharge quickly resolved. The subjective symptoms of diplopia also improved, and the postoperative Hess chart showed an improved ocular movement in the upward and lateral directions. Conclusions : Buckle migration is a rare postoperative complication of scleral buckling; however, patients at risk of buckle migration, such as those with encircling scleral buckle anterior to the eyeball, should be monitored with caution. If a buckle infection develops, buckle migration may occur within a short period, and early buckle removal should be considered.

Purpose: To explore the effect of photodynamic therapy (PDT) on the choroid of medial area from optic disc and factors correlated with treatment outcomes, we evaluated choroidal changes using ultra-widefield optical coherence tomography (UWF-OCT) after PDT for central serous chorioretinopathy (CSC)., Methods: In this retrospective case-series, we included CSC patients who received a standard-dose of full-fluence PDT. UWF-OCT were examined at baseline and 3 months after treatment. We measured choroidal thickness (CT), classified into central, middle, and peripheral sectors. We examined CT changes after PDT by sectors and treatment outcome., Results: Twenty-two eyes of 21 patients (20 males; mean age 58.7 ± 12.3 years) were included. CT reduction after PDT was significant in all sectors, including peripheral areas: supratemporal, 330.5 ± 90.6 μm vs. 237.0 ± 53.2 μm; infratemporal, 240.0 ± 89.4 μm vs. 209.9 ± 55.1 μm; supranasal, 237.7 ± 59.8 vs 209.3 ± 69.3 μm; infranasal, 172.6 ± 47.2 μm vs. 155.1 ± 38.2 μm (P < 0.001, for all). In patients with retinal fluid resolution, despite no apparent difference in baseline CT, there was more significant reduction after PDT in supratemporal and supranasal peripheral sectors, compared with patients without resolution: supratemporal, 41.9 ± 30.3 μm vs. -1.6 ± 22.7 μm; supranasal, 24.7 ± 15.3 μm vs. 8.5 ± 3.6 μm (P < 0.019, for both)., Conclusions: Whole CT decreased after PDT, including in medial areas from optic disc. This may be associated with the treatment response of PDT for CSC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Funatsu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, we aimed to map and characterize the choroidal thickness over a wide area from the posterior pole to the vortex vein in normal eyes. This observational study included 146 healthy eyes (63 male). Three-dimensional volume data were acquired to create a choroidal thickness map using swept-source optical coherence tomography. The map was classified as type A if an area with a choroidal thickness >250 µm in the vertical direction from the optic disc, and the area corresponding to the watershed was not observed, or as type B if such an area was observed. The relationship between the ratio of groups A to B and age was compared by classifying the age for three age groups: <40, 40-60, and >60 years in men and women. In men and women, 69.8% and 49.4% were classified as type A, respectively, with significant sex differences ( p = 0.013). The proportion of type B decreased with increasing age in both the sexes. There was a significant difference between ≤60 and >60 years in men and between ≤40 and >40 years in women ( p < 0.05). To conclude, the wide-area choroidal thickness and the age-dependent changes in healthy eyes differed between the sexes.

Numerous biomimetic molecular catalysts inspired by methane monooxygenases (MMOs) that utilize iron or copper-oxo species as key intermediates have been developed. However, the catalytic methane oxidation activities of biomimetic molecule-based catalysts are still much lower than those of MMOs. Herein, we report that the close stacking of a μ-nitrido-bridged iron phthalocyanine dimer onto a graphite surface is effective in achieving high catalytic methane oxidation activity. The activity is almost 50 times higher than that of other potent molecule-based methane oxidation catalysts and comparable to those of certain MMOs, in an aqueous solution containing H 2 O 2 . It was demonstrated that the graphite-supported μ-nitrido-bridged iron phthalocyanine dimer oxidized methane, even at room temperature. Electrochemical investigation and density functional theory calculations suggested that the stacking of the catalyst onto graphite induced partial charge transfer from the reactive oxo species of the μ-nitrido-bridged iron phthalocyanine dimer and significantly lowered the singly occupied molecular orbital level, thereby facilitating electron transfer from methane to the catalyst in the proton-coupled electron-transfer process. The cofacially stacked structure is advantageous for stable adhesion of the catalyst molecule on the graphite surface in the oxidative reaction condition and for preventing decreases in the oxo-basicity and generation rate of the terminal iron-oxo species. We also demonstrated that the graphite-supported catalyst exhibited appreciably enhanced activity under photoirradiation owing to the photothermal effect., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Krüppel-like factor 5 (KLF5) is a transcription factor regulating the proliferation and differentiation of epithelial cells, and its uncontrolled expression is closely associated with carcinoma progression. Sp3 binding to the minimal essential region (MER) of KLF5 gene is critical for KLF5 basal expression, but the expression control mechanism is unknown., Objective: This study aimed to identify a regulatory region for KLF5 basal expression and the binding protein in carcinoma cells by analyzing the promoter upstream region., Methods: Reporter assays determined the silencer region. The protein binding to the region was identified by database analysis and ChIP assay. The protein mediating the interaction between the region and the MER was confirmed through chromosome conformation capture (3 C) on ChIP assay. The effects of the protein on KLF5 expression were analyzed using qRT-PCR and western blot., Results: Reporter assay localized the 425-region from upstream KLF5 gene as the silencer. Database analysis and ChIP assay found CREB1 binding to the 425-region. CREB1 siRNA or mutation of CREB1-binding site in the 425-region increased luciferase activities and decreased the binding to 425-region. 3 C on ChIP assay showed that CREB1 mediated interaction of the 425-region and the MER. CREB1 overexpression decreased endogenous KLF5 expression and luciferase activity., Conclusions: The 425-region is the silencer of KLF5 basal expression, and CREB1 binding suppresses the expression.

Invited for the cover of this issue are Kentaro Tanaka at Nagoya University and co-workers. The image depicts the importance of the flexibility of bridging alkyl chains in a molecular conjugate to pack the components closely to generate efficient molecular communication. Read the full text of the article at 10.1002/chem.202200819., (© 2022 Wiley-VCH GmbH.)

Purpose: To compare surgical outcomes of filtered air and sulfur hexafluoride (SF6) as an internal tamponade in patients undergoing primary 25-gauge pars plana vitrectomy for uncomplicated rhegmatogenous retinal detachment with inferior breaks., Methods: Patients with uncomplicated rhegmatogenous retinal detachment associated with inferior breaks (between 4 and 8 o'clock positions) who were undergoing primary pars plana vitrectomy were enrolled. All eyes underwent pars plana vitrectomy and complete drainage of subretinal fluid, followed by filtered air or 20% SF6 tamponade. The main outcome measures included single-surgery anatomical success rates and final visual recovery., Results: Overall, 116 eyes of 116 patients (81 men and 35 women with a mean age of 55.2 years) were assessed. Air was used in 52 eyes (air group) and gas in 64 eyes (gas group). Single-surgery anatomical success was achieved in 50 (96.2%) and 60 (93.8%) eyes in the air and gas groups, respectively (P = 0.69), and final anatomical success was achieved in all eyes. The mean final Snellen visual acuity was similar in the air (20/23) and gas groups (20/21; P = 0.13)., Conclusion: No significant differences were observed in single-surgery anatomical success rates and final visual recovery when comparing air with SF6 gas tamponade in pars plana vitrectomy for primary uncomplicated rhegmatogenous retinal detachment with inferior breaks.

Spatial distance is an important factor in controlling the functional interactions between molecular units in a conjugate; therefore, the bridging unit has been closely examined. Here, we examined the effect of the flexibility of bridging alkyl chains on the proximity of stacked porphyrin and phthalocyanine conjugated with a fourfold rotaxane linkage. We found that closely stacking two π systems requires bridging alkyl chains above a certain length, and the shorter bridges hinder stacking because of their lower flexibility. The stacking distance between porphyrin and phthalocyanine in the conjugate with decyl (C 10 ) chains was estimated to be 4.03 Å and showed a unique physical character arising from short-distance interactions. The longer alkyl chains minimized steric restriction inside the fourfold rotaxane and allowed efficient communication between the porphyrin and phthalocyanine units. This is due to the flexibility of the side chains., (© 2022 Wiley-VCH GmbH.)

The collection and use of large-scale medical information for developing artificial intelligence engines are actively ongoing. In Japan, collection systems have been built to collect data for medical image analysis and disease repositories. In the experimental project for the next generation medical infrastructure law, a centrally integrated basic system was developed, and standardized electronic medical record (EMR) storage data distributed to each hospital were transferred into one data center and imported to a database for secondary use. The law requires a mechanism for maintaining a list of notified or opted-out patients. To operate these systems, safe and efficient secondary use of collected information is essential not just for the law but also for large-scale data collection projects, such as multifacility clinical research. This paper considers whole-somely, requirements for providing medical care information to data collection projects and proposes additional requirements for a gateway system under development.

The mutation and deletion of high mobility group AT-hook 2 (Hmga2) gene exhibit skeletal malformation, but almost nothing is known about the mechanism. This study examined morphological anomaly of facial bone in Hmga2 -/- mice and osteoblast differentiation of pre-osteoblast MC3T3-E1 cells with Hmga2 gene knockout (A2KO). Hmga2 -/- mice showed the size reduction of anterior frontal part of facial bones. Hmga2 protein and mRNA were expressed in mesenchymal cells at ossification area of nasal bone. A2KO cells differentiation into osteoblasts after reaching the proliferation plateau was strongly suppressed by alizarin red and alkaline phosphatase staining analyses. Expression of osteoblast-related genes, especially Osterix, was down-regulated in A2KO cells. These results demonstrate a close association of Hmga2 with osteoblast differentiation of mesenchymal cells and bone growth. Although future studies are needed, the present study suggests an involvement of Hmga2 in osteoblast-genesis and bone growth., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial of financial relationship that could be considered as a potential conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A series of trinuclear complexes, [MnII2Y III (L) 2 (HL) 2 (NO 3 ) 3 ][Y III (NO 3 ) 5 ]·7H 2 O (1'), [MnII2Gd III (HL) 4 (NO 3 ) 4 ] 2 [MnII2Gd III (L)(HL) 3 (NO 3 ) 4 ][Gd III (NO 3 ) 5 ] 4 ·2( o -Xy)·12H 2 O (2') and [MnII3(L)(HL) 2 (NO 3 ) 4 ](NO 3 )·1.25( p -Xy) (3'), were synthesized using a β-diketone ligand HL (HL = 1,3-bis(pyridin-2-yl)propane-1,3-dione). X-ray structural analyses revealed that each complex has a trinuclear core with an Mn(II)-M-Mn(II) arrangement (M = Y III (1), Gd III (2), and Mn II (3)). In 1' with a diamagnetic Y(III) ion, negligible antiferromagnetic interactions between terminal Mn(II) ions are operative. On the other hand, 2' shows ferromagnetic interactions between Mn(II) and Gd(III) ions, affording a spin ground state of S T = 17/2. The homometallic Mn(II) 3 complex of 3' has an S T = 5/2 spin ground state resulting from the antiferromagnetic interactions between neighboring Mn(II) ions. The maximum magnetic entropy change (-Δ S m ) of 1'-3' was estimated to be 12.3, 24.8, and 8.0 J kg -1 K -1 , respectively.

Background: Medicines may cause various adverse reactions. An enormous amount of money and effort is spent investigating adverse drug events (ADEs) in clinical trials and postmarketing surveillance. Real-world data from multiple electronic medical records (EMRs) can make it easy to understand the ADEs that occur in actual patients., Objective: In this study, we generated a patient medication history database from physician orders recorded in EMRs, which allowed the period of medication to be clearly identified., Methods: We developed a method for detecting ADEs based on the chronological relationship between the presence of an adverse event and the medication period. To verify our method, we detected ADEs with alanine aminotransferase elevation in patients receiving aspirin, clopidogrel, and ticlopidine. The accuracy of the detection was evaluated with a chart review and by comparison with the Roussel Uclaf Causality Assessment Method (RUCAM), which is a standard method for detecting drug-induced liver injury., Results: The calculated rates of ADE with ALT elevation in patients receiving aspirin, clopidogrel, and ticlopidine were 3.33% (868/26,059 patients), 3.70% (188/5076 patients), and 5.69% (226/3974 patients), respectively, which were in line with the rates of previous reports. We reviewed the medical records of the patients in whom ADEs were detected. Our method accurately predicted ADEs in 90% (27/30patients) treated with aspirin, 100% (9/9 patients) treated with clopidogrel, and 100% (4/4 patients) treated with ticlopidine. Only 3 ADEs that were detected by the RUCAM were not detected by our method., Conclusions: These findings demonstrate that the present method is effective for detecting ADEs based on EMR data., (©Kei Teramoto, Toshihiro Takeda, Naoki Mihara, Yoshie Shimai, Shirou Manabe, Shigeki Kuwata, Hiroshi Kondoh, Yasushi Matsumura. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 01.11.2021.)

Health information systems (HIS) and clinical workflows generate medication errors that affect the quality of patient care. The rigorous evaluation of the medication process's error risk, control, and impact on clinical practice enable the understanding of latent and active factors that contribute to HIS-induced errors. This paper reports the preliminary findings of an evaluation case study of a 1000-bed Japanese secondary care teaching hospital using observation, interview, and document analysis methods. Findings were analysed from a process perspective by adopting a recently introduced framework known as Human, Organisation, Process, and Technology-fit. Process factors influencing risk in medication errors include template- and calendar-based systems, intuitive design, barcode check, ease of use, alert, policy, systematic task organisation, and safety culture Approaches for managing medication errors also exert an important role on error reduction and clinical workflow.

[Purpose] To clarify the cutoff point of the Functional Independence Measure tool for predicting home discharge of patients in convalescent rehabilitation wards. [Participants and Methods] This retrospective observational study analyzed the data of 91 inpatients with cerebrovascular disease who received rehabilitation treatment at a convalescent rehabilitation ward. We categorized the participants into two groups: the home-discharged group and the non-home discharged group. We divided the outcome parameters in the two groups into different categories and compared them using the Mann-Whitney U test. To identify the relevant cutoff points in a clinical setting, we applied the receiver operating characteristic curve. [Results] In patients with cerebrovascular disease, the Functional Independence Measure motor, cognitive, and total scores were significantly higher in the home-discharged group than in the non-home discharged group. We statistically calculated the Functional Independence Measure motor score cutoff point that can predict home discharge, and the predicted Functional Independence Measure motor score at the time of hospitalization was 53.5-60.0 points. [Conclusion] It is important to start rehabilitation at an early stage and increase the amount of training to increase the likelihood of returning home., Competing Interests: The authors declare no potential conflicts of interest with respect to this research., (2020©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Controlled directional transport of molecules is essential to complex natural systems, from cellular transport up to organismal circulatory systems. In contrast to these natural systems, synthetic systems that enable transport of molecules between several spatial locations on the macroscopic scale, when external stimuli are applied, remain to be explored. Now, the transfer of a supramolecular cage is reported with controlled directionality between three phases, based on a cage that responds reversibly in two distinct ways to different anions. Notably, circulatory phase transfer of the cage was demonstrated based on a system where the three layers of solvent are arranged within a circular track. The direction of circulation between solvent phases depended upon the order of addition of anions., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

This study investigated if scores on tests of personal qualities are affected by whether they will determine selection decisions ("high stakes") or not; and whether they are stable for individuals and groups across a four-year medical course. Two tests, one assessing values and one assessing components of personality, were administered either at the same time as a medical university entrance exam (first cohort; N  = 216), or after entry was confirmed (second cohort; N  = 142). Both cohorts took the tests again after four years of medical school. Analysis of variance was used to compare group mean scores and interactions, and correlation coefficients to measure temporal reliability. The high stakes cohort initially presented themselves in a significantly more positive light on the personality test. After four years of medical school scores on both tests changed significantly, towards more communitarian values and less empathic attitudes. Thus, personality scores were affected by both the conditions under which the initial tests were conducted and by the passage of time, but values only by the passage of time. Before and after scores were significantly correlated.

Development of supramolecular methods to further activate a highly reactive intermediate is a fascinating strategy to create novel potent catalysts for activation of inert chemicals. Herein, a supramolecular approach to enhance the oxidizing ability of a high-valent oxo species of a nitrido-bridged iron porphyrinoid dimer that is a known potent molecular catalyst for light alkane oxidation is reported. For this purpose, a nitrido-bridged dinuclear iron complex of porphyrin-phthalocyanine heterodimer 3 5+ , which is connected through a fourfold rotaxane, was prepared. Heterodimer 3 5+ catalyzed ethane oxidation in the presence of H 2 O 2 at a relatively low temperature. The site-selective complexation of 3 5+ with an additional anionic porphyrin (TPPS 4- ) through π-π stacking and electrostatic interactions afforded a stable 1:1 complex. It was demonstrated that the supramolecular post-synthetic modification of 3 5+ enhances its catalytic activity efficiently. Moreover, supramolecular conjugates achieved higher catalytic ethane oxidation activity than nitrido-bridged iron phthalocyanine dimer, which is the most potent iron-oxo-based molecular catalyst for light-alkane oxidation reported so far. Electrochemical measurements proved that the electronic perturbation from TPPS 4- to 3 5+ enhanced the catalytic activity., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Because drug-induced interstitial pneumonia (DIP) is a serious adverse drug reaction, its quantitative risk with individual medications should be taken into due consideration when selecting a medicine. We developed an algorithm to detect DIP using medical record data accumulated in a hospital. Chest computed tomography (CT) is mainly used for the diagnosis of IP, and chest X-ray reports, KL-6, and SP-D values are used to support the diagnosis. The presence of IP in the reports was assessed by a method using natural language-processing, in which IP was estimated according to the product of the likelihood ratio of characteristic keywords in each report. The sensitivity and the specificity of the method for chest CT reports were 0.92 and 0.97, while those for chest X-ray reports were 0.83 and 1, respectively. The occurrence of DIP was estimated by the patterns of presence of IP before, during, and after the administration of the target medicine. The occurrence rate of DIP in cases administered Gefitinib; Methotrexate (MTX); Tegafur, Gimeracil, and Oteracil potassium (TS-1); and Tegafur and Uracil (UTF) was 6.0%, 2.3%, 1.4%, and 0.7%, respectively. The estimated DIP cases were checked by having the medical records independently reviewed by medical doctors. By chart review, the positive predictive values of DIP against Gefitinib, MTX, TS-1, and UFT were 69.2%, 44.4%, 58.6%, and 77.8%, respectively. Although the cases extracted by this method included some that did not have DIP, this method can estimate the relative risk of DIP between medicines.

Cofacial assemblies of metalloporphyrinoids represent a fascinating platform for the fabrication of novel functional molecular assemblies based on π-π, d-d, and d-π interactions between components. In this paper, we present a novel synthetic strategy for the programmable arrangement of different metal ions inside a cofacially stacked trimer of porphyrinoids. A combination of two different assemblies was utilized for our purpose: a tetracationic fourfold rotaxane heterodimer between a porphyrin with four alkylammonium chains and a phthalocyanine bearing four peripheral crown ethers, and a stacked assembly between the fourfold rotaxane heterodimer and an additional tetraanionic porphyrin. Three metal ions, namely Cu(ii), Ag(ii), and Au(iii), were arranged inside the cofacially stacked assembly of three porphyrinoids. Moreover, paramagnetic Cu(ii) ions were arranged inside a cofacially stacked heterotrimer of porphyrinoids and were precisely programmed, affording the desired spin-spin communications as readable information. These results indicated that the developed strategy is effective for arranging various metal ions in cofacially stacked assemblies of porphyrinoids toward the creation of molecular tags or bar codes.

A μ-oxo-dinuclear iron complex of a supramolecular porphyrin-phthalocyanine conjugate was synthesized and its catalytic electrochemical oxygen reduction properties were investigated. In the conjugate, porphyrin and phthalocyanine units were connected to form a cofacial dimeric structure through a flexible fourfold rotaxane linkage, which was advantageous for accommodating small substrates between the iron centers. The conjugate showed efficient catalytic properties, at more positive potentials than those of other reported dinuclear porphyrinoid iron complexes, to selectively afford water through a four-electron reduction process., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Krüppel-like factor 5 (KLF5) transcriptionally controls the proliferation-differentiation balance of epithelium and is overexpressed in carcinomas. Although genomic region modifying KLF5 expression is widespread in different types of cells, the region that commonly regulates basal expression of the genes across cell-types is uncertain. In this study we determined the minimal essential region for the expression and its regulatory transcription factors using oral carcinoma cells. A reporter assay defined a 186bp region downstream of the transcription start site and a cluster of six GC boxes (GC1-GC6) as the minimal essential region. Mutation in the GC1 or GC6 regions but not other GC boxes significantly decreased the reporter expression. The decrease by the GC1 mutation was reproduced in the 2kbp full-length promoter, but not by the GC6 mutation. Additionally, specificity proteins (Sp) that can be expressed in epithelial cells and bind GC box, Sp3 co-localized with KLF5 in oral epithelium and carcinomas and chromatin immunoprecipitation analyses showed Sp3 as the prime GC1-binding protein. Inhibition of Sp-GC box binding by mithramycin A and knockdown of Sp3 by the short interfering RNA decreased expression of the reporter gene and endogenous KLF5. These data demonstrate that a 186bp region is the minimal essential region and that Sp3-GC1 binding is essential to the basal expression of KLF5., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The redox potential of a supramolecular porphyrin-phthalocyanine heterodimer was perturbed by the stacking of an extra metalloporphyrin to the phthalocyanine. This stacking gave rise to π-π and electrostatic interactions between the tetracationic dimer and the tetraanionic metalloporphyrin, with a Au(iii) metalloporphyrin exhibiting a larger effect than Cu(ii) and Pd(ii) complexes among square planar complexes.

To improve the efficiency of clinical research, we developed a system to integrate electronic medical records (EMRs) and the electronic data capture system (EDC). EDC is divided into case report form (CRF) reporter and CDMS with CRF receiver with data communication using the operational data model (ODM). The CRF reporter is incorporated into the EMR to share data witth the EMR. In the data transcription type, doctors enter data using a progress note template, which are transmitted to the reporter template. It then generates the ODM. In the direct record type, reporter templates open from the progress note and generate narrative text to make record in the progress note. The configuration files for a study are delivered from the contents server to minimize the setup. This system has been used for 15 clinical studies including 3 clinical trials. This system can save labor and financial costs in clinical research.

Electronic health record (EHR) systems are necessary for the sharing of medical information between care delivery organizations (CDOs). We developed a document-based EHR system in which all of the PDF documents that are stored in our electronic medical record system can be disclosed to selected target CDOs. An access control list (ACL) file was designed based on the HL7 CDA header to manage the information that is disclosed.

Early diagnosis and treatment of pancreatic cancer is challenging. We attempted to find diagnostic rules for pancreatic cancer from laboratory data in the Osaka University Hospital's data warehouse using Bayesian estimation. We calculated the pretest odds based on the number of laboratory tests and the cutoff value at which the diagnostic accuracy is over 20%. By this method, we identified diagnostic rules of 6 types for one item and 79 types for 2 items. Pancreatic cancer is difficult to detect from only general laboratory tests. However, this method may be promising in early diagnosis.

Issues related to ensuring patient privacy and data ownership in clinical repositories prevent the growth of translational research. Previous studies have used an aggregator agent to obscure clinical repositories from the data user, and to ensure the privacy of output using statistical disclosure control. However, there remain several issues that must be considered. One such issue is that a data breach may occur when multiple nodes conspire. Another is that the agent may eavesdrop on or leak a user's queries and their results. We have implemented a secure computing method so that the data used by each party can be kept confidential even if all of the other parties conspire to crack the data. We deployed our implementation at three geographically distributed nodes connected to a high-speed layer two network. The performance of our method, with respect to processing times, suggests suitability for practical use.

There is a great need to reuse data stored in electronic medical records (EMR) databases for clinical research. We previously reported the development of a system in which progress notes and case report forms (CRFs) were simultaneously recorded using a template in the EMR in order to exclude redundant data entry. To make the data collection process more efficient, we are developing a system in which the data originally stored in the EMR database can be populated within a frame in a template. We developed interface plugin modules that retrieve data from the databases of other EMR applications. A universal keyword written in a template master is converted to a local code using a data conversion table, then the objective data is retrieved from the corresponding database. The template element data, which are entered by a template, are stored in the template element database. To retrieve the data entered by other templates, the objective data is designated by the template element code with the template code, or by the concept code if it is written for the element. When the application systems in the EMR generate documents, they also generate a PDF file and a corresponding document profile XML, which includes important data, and send them to the document archive server and the data sharing saver, respectively. In the data sharing server, the data are represented by an item with an item code with a document class code and its value. By linking a concept code to an item identifier, an objective data can be retrieved by designating a concept code. We employed a flexible strategy in which a unique identifier for a hospital is initially attached to all of the data that the hospital generates. The identifier is secondarily linked with concept codes. The data that are not linked with a concept code can also be retrieved using the unique identifier of the hospital. This strategy makes it possible to reuse any of a hospital's data.

In clinical trials, investigating the ratio of patients with each disease who are treated in a hospital is important for determining the number of patients who are allocated to hospitals. The Japanese health insurance claims data includes standardized disease and medicine data. However, the disease data has some problems in terms of reliability, because the healed diseases are sometimes not deleted or because a disease that a patient does not actually have is registered to claim the cost of the examination. On the other hand, therapeutic medicines are administered to target particular diseases. In this study, we developed a system for estimating the number of patients with each disease using the disease data and the therapeutic medicine data. We converted the ICD-10 code to a 4-grade classification code so that we could predict the diseases in the shallow layer (e.g. gastrointestinal disease) when it was difficult to predict the precise diseases in the deep layer (e.g. gastric ulcers). A table showing the disease code and the corresponding therapeutic medicine code was provided by the Japan Pharmaceutical Information Center (JAPIC). We calculated the disease probability score from the diseases and therapeutic medicines and recorded the predicted disease. For the system evaluation, we used the health insurance claims data from Osaka University Hospital for January 2015. A total of 58,526 diseases were predicted from the health insurance claims data of 18,393 patients. One hundred twenty patients were randomly extracted for use in a chart review that was performed by an expert physician. Two hundred twenty-four of 329 predicted diseases, were correctly predicted; 56 were reasonably predicted, and 49 were incorrectly predicted. The main disease was correctly predicted in 71 patients. In conclusion, we could estimate the number of patients with each disease using the health insurance claims data with a certain degree of accuracy.

Proliferation-differentiation balance of epithelial cells is regulated by Krüppel-like factors (KLF) 4 and 5, and the unbalanced expression relates to carcinoma progression. However, little is known about the expression and role in oral carcinomas. This study examined expression of KLF4 and KLF 5 in the carcinomas by immunohistochemistry (n = 67) and the involvement in proliferation and differentiation of carcinoma cells. KLF4 was detected in keratinizing carcinoma cells and KLF5 in non-keratinizing cells. KLF4 staining declined in the patient with lymph node metastasis (P < 0.05) and in parallel with the histological dedifferentiation (P = 0.09). Exogenous overexpression of KLF4 arranged cells in a cobble-like structure with desmosomes and KLF5 elongated cells like fibroblasts without desmosomes. KLF4 suppressed fibronectin expression, and KLF5 down-regulated and degraded E-cadherin. The proliferation was not affected by KLFs. Thus, down-regulation of KLF4 and up-regulation of KLF5 may stimulate oral carcinoma progression through the dedifferentiation of carcinoma cells.

Adverse events are detected by monitoring the patient's status, including blood test results. However, it is difficult to identify all adverse events based on recognition by individual doctors. We developed a system that can be used to detect hematotoxicity adverse events according to blood test results recorded in an electronic medical record system. The blood test results were graded based on Common Terminology Criteria for Adverse Events (CTCAE) and changes in the blood test results (Up, Down, Flat) were assessed according to the variation in the grade. The changes in the blood test and injection data were stored in a database. By comparing the date of injection and start and end dates of the change in the blood test results, adverse events related to a designated drug were detected. Using this method, we searched for the occurrence of serious adverse events (CTCAE Grades 3 or 4) concerning WBC, ALT and creatinine related to paclitaxel at Osaka University Hospital. The rate of occurrence of a decreased WBC count, increased ALT level and increased creatinine level was 36.0%, 0.6% and 0.4%, respectively. This method is useful for detecting and estimating the rate of occurrence of hematotoxicity adverse drug events.