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Background: Human T-cell leukemia virus type 1 (HTLV-1) is a blood-borne virus, and mandatory testing of donated blood for HTLV-1 antibodies has been adopted by Japanese Red Cross blood centers since 1986. A confirmatory line immunoassay was initiated in 2019 for individuals who were seroreactive in the screening test. This decreased the incidence of indeterminate individuals, however, donors with indeterminate results are not informed of their HTLV-1 seroreactivity and they can continue to donate blood., Objectives: To clarify the characteristics of indeterminate line immunoassay results among Japanese blood donors., Study Design: Of 759,259 blood donors in the Kyushu district of Japan, an area endemic for HTLV-1, 101 cases were classified as indeterminate by line immunoassay testing. We examined these cases using alternative secondary antibodies, anti-human-Ig (IgG/IgM/IgA) and -IgM antibodies, to detect the early phase of HTLV infection., Results: Using anti-human-Ig and -IgM antibodies, HTLV infection status was confirmed in 37 individuals (HTLV-1-positive, 2; HTLV-positive, 27; HTLV-negative, 8). Among the remaining 64 indeterminate individuals, we identified one HTLV-2-infected 18-year-old female. A previous blood donation from this individual showed a negative anti-HTLV screening test result (signal-to-cutoff ratio = 0.1). Therefore, this case was considered to be an HTLV-2 seroconversion case., Conclusions: These results indicate that the procedure for diagnosing HTLV infection should be reconsidered and that an accurate detection system for the early phase of HTLV infection is urgently needed for public health in Japan. Moreover, the issue of HTLV-2 infection needs a higher profile in Japan., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest in this manuscript., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Solar steam generation (SSG) is a promising photothermal technology to solve the global water storage issue. The potential of π-conjugated polymers as photothermal materials is significant, because their absorption range can be customized through molecular design. In this study, naphthalenediimide (NDI) and thiadiazolobenzotriazole (TBZ) were employed as bifunctional monomers to produce conjugated polymers. There are two types of polymers, P1 and P2 . P1 is based on NDI, while P2 is a copolymer of NDI and TBZ in a ratio of 9:1. Both polymers had high molecular weights and sufficient thermal stability. UV-vis-near-infrared (NIR) absorption spectra revealed that both polymers have large extinction coefficients ascribed to the NDI and TBZ chromophores. Notably, the absorption spectrum of P2 exhibited a significant red shift compared to P1 , resulting in a narrow optical bandgap and absorption in the NIR range. This result suggested that P2 has a higher light absorption than P1 . Photoluminescence (PL) spectra were measured to elucidate the conversion of the absorbed light into thermal energy. It was found that P2 has a reduced fluorescence quantum yield as a result of the TBZ unit, signifying a proficient conversion of the photothermal energy. Based on the results, it appears that the P2 film has a greater photothermal property compared to that of the P1 film. The surface temperature of the P2 film reached approximately 50 °C under the investigated conditions. In addition, copolymer P2 exhibited an impressive SSG efficiency of 72.4% under 1 sun (1000 W/m 2 ) irradiation. All the results suggested that narrow bandgap conjugated polymers containing the TBZ unit are highly effective materials for achieving optimal performance in SSGs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Abemaciclib-induced diarrhea (AID) impairs quality of life (QOL) and treatment adherence in patients with breast cancer. Supportive treatment with loperamide is associated with constipation. We hypothesized that probiotics and trimebutine maleate (TM) would decrease the frequency of AID without causing constipation., Methods: Hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer patients were randomized into the probiotic Bifidobacterium (A) or probiotic Bifidobacterium and TM (B) groups. Endocrine therapy, Abemaciclib and probiotic Bifidobacterium three times a day for 28 days, was administered to both arms. Arm B was treated with TM upon the onset of diarrhea. The primary endpoint was the percentage of patients who experienced grade ≥2 diarrhea. The secondary endpoints were safety, frequency, and duration of all-grade diarrhea; frequency of emesis and constipation; usage of loperamide; and health-related QOL/patient-reported outcome during the study. We evaluated whether the primary endpoint of each arm exceeded the predetermined threshold., Results: Fifty-one patients completed treatment. Grade 2 diarrhea occurred in 52% and 50% of patients in Arm A and Arm B, respectively. One patient experienced grade 3 diarrhea in each arm. The median duration of grade2 diarrhea was 2 and 2.5day, and only one patient required dose reduction. Grade ≥2 constipation was observed in 4% of Arm A and 3.6% of Arm B., Conclusions: Probiotic Bifidobacterium or the combination of probiotic Bifidobacterium with TM did not decrease the incidence of grade 2 or greater diarrhea compared with historical control, although the grade 3 or greater diarrhea was reduced., Clinical Trial Registration: jRCT (Japan registry of clinical trials). jRCTs031190154., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Many studies have shown that the prognosis of invasive lobular carcinoma (ILC) is better than that of invasive ductal carcinoma (IDC). However, both disorders exhibit different prognoses according to molecular subtype, and the prognosis of ILC subtypes might depend on their hormone receptor positivity rate. This study clarified the prognosis of ILC and IDC in each subtype and examined the effectiveness of adjuvant chemotherapy (CT) in luminal ILC., Methods: We planned the analysis using data from the Breast Cancer Registry in Japan. Because it was presumed that there are differences in characteristics between ILC and IDC, we created matched cohorts using exact matching to compare their prognoses. We compared the prognosis of ILC and IDC for each subtype. We also compared the prognosis of luminal ILC between the CT and non-CT groups., Results: For all subtypes, the disease-free survival (DFS) and overall survival (OS) of ILC were poorer than those of IDC. In the analysis by each subtype, no statistically significant difference was found in DFS and OS in luminal human epidermal growth factor 2 (HER2), HER2, and triple-negative cohorts; however, luminal ILC had significantly poorer DFS and OS than luminal IDC. The CT effects on the prognosis of luminal ILC were greater in more advanced cases., Conclusion: Luminal ILC had a poorer prognosis than luminal IDC, contributing to the worse prognosis of ILC than that of IDC in the overall cohort. Different therapeutic approaches from luminal IDC are essential for a better prognosis of luminal ILC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The restriction enzyme-based digital methylation-specific polymerase chain reaction (RE-dMSP) assay is useful for diagnosing sentinel lymph node (SN) metastasis in patients with breast cancer, by detecting tumor-derived methylated Ras association domain-containing protein 1 (RASSF1A). In addition, this assay has high concordance (95.0%) with one-step nucleic acid amplification (OSNA). The present study aimed to perform RE-dMSP using OSNA lysate from more patients and to re-evaluate its clinical usage. Overall, 418 SNs from 347 patients were evaluated using both OSNA and RE-dMSP. The concordance rate was 83.3% (348/418). RASSF1A methylation of the primary tumors was negative in 36 patients. When these patients were excluded, the concordance rate improved to 88.2% (330/374). Of the 79 OSNA-negative cases, 19 were RE-dMSP-positive, although all were positive for cytokeratin 19 expression in the primary tumor, suggesting that RE-dMSP can detect tumor-derived DNA with a higher sensitivity. The percent of methylated reference of the breast tumors showed a wide variety in the 16 OSNA-positive/RE-dMSP-negative cases, and such variability of methylation could have affected the results in these patients. In conclusion, although RE-dMSP can diagnose SN metastasis with high sensitivity and accuracy, and can be a supplementary tool to OSNA in breast cancer, RE-dMSP showed certain discordance with OSNA and critically depended on the absence or heterogeneity of DNA methylation in breast tumors. Further research is expected to develop an assay targeting other DNA alterations, such as mutations., Competing Interests: NK received a research grant from AstraZeneca. KS received a research grant from AstraZeneca and ROHTO Pharmaceutical Co., Ltd. KS has received honoraria from Sysmex and AstraZeneca. KA, TY, and TM have received honoraria from AstraZeneca. The other authors declare that they have no competing interests., (Copyright: © Park et al.)

Background: Radiotherapy (RT) following breast-conserving surgery (BCS) is mainly used to decrease the rate of ipsilateral breast tumor recurrence (IBTR) in women with breast ductal carcinoma in situ (DCIS). Recent studies have demonstrated that low-dose tamoxifen significantly reduces IBTR in breast DCIS. Here, we aim to determine whether the administration of low-dose tamoxifen is non-inferior to RT in preventing IBTR in patients with low-risk characteristics of breast DCIS., Methods/design: This is a prospective, international, open-label, randomized, non-inferiority trial. Patients with low-risk clinicopathologic features (> 40 years old, low risk of breast cancer susceptibility gene (BRCA) 1 and BRCA2 mutations, mammographically detected unicentric and non-mass lesions, low- or intermediate-grade without comedo or necrosis, measuring < 2.5 cm with margins ≥ 3 mm, and estrogen receptor-positive status) of DCIS who underwent BCS will be randomized at a 1:1 ratio to either receive tamoxifen (5 mg/day) for 5 years or undergo RT with conventional fractions (50 Gy in 25 fractions) or hypofractionations (40.05 Gy in 15 fractions). Randomization will be stratified by the Taiwan Breast Cancer Consortium. As approximately 5% of patients cannot tolerate the side effects of low-dose tamoxifen and will receive RT, we estimate that 405 patients will be randomized to a low-dose tamoxifen arm and 405 patients to the RT arm, according to a non-inferiority margin within 5% of IBTR difference and 90% β-power noticing non-inferiority. The primary endpoints are breast tumor recurrence, including ipsilateral, regional, contralateral, and distant recurrence of breast DCIS or invasive cancer. The secondary endpoints are overall survival and adverse effects of RT and tamoxifen. Translational studies will also be conducted for this trial., Discussion: This is the first non-inferiority trial on breast DCIS. This study will provide an important recommendation for clinical physicians on whether to use low-dose adjuvant tamoxifen for patients with low-risk breast DCIS who do not want to receive adjuvant RT., Trial Registration: ClinicalTrials.gov, ID: NCT04046159, Registered on April 30, 2019., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Financial toxicity (FT) is a notable concern for patients with breast cancer worldwide. The situation regarding FT in Japan, however, has not been well explored. This study examined FT in patients with breast cancer in Japan and presented an overview of the group study's overall findings., Methods: The survey used the Questant application and primarily targeted patients with breast cancer attending research facilities and physicians who are members of the Japanese Breast Cancer Society. The Japanese version of the Comprehensive Score for FT (COST) was used to quantify patients' FT. Multiple regression analysis was used to identify factors related to FT in patients with breast cancer in Japan and evaluate the sufficiency of information support level (ISL) for medical expenses., Results: We collected 1558 responses from patients and 825 from physicians. In terms of factors affecting FT, recent payments had the highest impact, followed by stage, and related departments positively affecting FT. Conversely, factors such as income, age, and family support were found to negatively affect FT. A significant discrepancy was identified between patients and physicians in perceived information support, with patients frequently feeling unsupported and physicians believing that they have provided adequate support. Furthermore, differences in the frequency of explanations and opportunities to ask questions about medical costs across FT grades were found. The analysis also showed that physicians with a better understanding of information support needs and greater knowledge of medical costs tended to provide more support that is comprehensive., Conclusion: This study emphasizes the importance of addressing FT in patients with breast cancer in Japan and highlights the need for enhanced information support, deeper understanding by physicians, and collaborative efforts among professionals to mitigate financial burden and provide personalized, tailored support for individual needs., (© 2023. The Author(s).)

Background: Triple-negative breast cancer (TNBC) is characterized as highly immunogenic and lacks specific targeted therapies. Interleukin 17A (IL-17A) is a controversial cytokine and is known to have anti-tumor and pro-tumor roles depending on the tumor microenvironment. In addition, IL-17A has been recently implicated in the recruitments of neutrophil into tumor tissues. Although IL-17A is considered tumor-promoting in breast cancer, its significance in the possible regulation of neutrophil infiltration in TNBC is not clearly defined., Materials and Methods: We immunolocalized IL-17A, CD66b (neutrophil marker), and chemokine (C-X-C motif) ligand 1 (CXCL1, neutrophil chemoattractant) in 108 TNBC specimens and assessed their correlation among each other. The correlation between these markers and clinicopathological parameters was also assessed. We subsequently performed in vitro study to address the possible regulation of CXCL1 by IL-17A using TNBC cell lines, MDA-MB-231 and HCC-38., Results: It was revealed that IL-17A correlated significantly with CXCL1 and CD66b, also CD66b with CXCL1. Furthermore, IL-17A was significantly associated with shorter disease-free and overall survival, especially in a high density CD66b group of patients. In vitro results revealed that IL-17A upregulated CXCL1 mRNA expression in a dose and time dependent manner, and this induction was significantly suppressed by an Akt inhibitor., Conclusion: IL-17A was considered to contribute to neutrophil infiltration by inducing CXCL1 in TNBC tissues and educating neutrophils to promote tumor progression. IL-17A might therefore serve as a potent prognostic factor in TNBC., (© 2023. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

The mechanical failure of polymers remains challenging to understand and predict, as it often involves highly localised phenomena that cannot be probed with bulk characterisation techniques. Here, we present a generalisable protocol based on optical microscopy, tensile testing, and image processing that permits the spatially resolved interrogation of mechanical deformation at the molecular level around defects in mechanophore-containing polymers. The approach can be applied to a broad range of polymeric materials, mechanophores, and deformation scenarios.

Purpose: Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive breast malignancy. Glucocorticoid (GC)-glucocorticoid receptor (GR) pathway plays a pivotal role in the cellular responses to various stresses including chemotherapy. Serum- and glucocorticoid-induced kinase-1 (SGK1) is known as an important downstream effector molecule in the GR signaling pathway, we attempted to explore its clinicopathological and functional significance in TNBC in which GR is expressed., Methods: We first immunolocalized GR and SGK1 and correlated the results with clinicopathological variables and clinical outcome in 131 TNBC patients. We also evaluated the effects of SGK1 on the cell proliferation and migration in TNBC cell lines with administration of dexamethasone (DEX) to further clarify the significance of SGK1., Results: The status of SGK1 in carcinoma cells was significantly associated with adverse clinical outcome in TNBC patients examined and was significantly associated with lymph node metastasis, pathological stage, and lymphatic invasion of the patients. In particular, SGK1 immunoreactivity was significantly associated with an increased risk of recurrence in GR-positive TNBC patients. Subsequent in vitro studies also demonstrated that DEX promoted TNBC cell migration and the silencing of gene expression did inhibit the cell proliferation and migration of TNBC cells under DEX treatment., Conclusions: To the best of our knowledge, this is the first study to explore an association between SGK1 and clinicopathological variables and clinical outcome of TNBC patients. SGK1 status was significantly positively correlated with adverse clinical outcome of TNBC patients and promoted carcinoma cell proliferation and migration of carcinoma cells., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: It is crucially important to understand the risk factors for rectal bleeding after volumetric-modulated arc radiotherapy (VMAT) for prostate cancer to prevent subsequent rectal bleeding. We assayed clinical and dosimetric data to investigate the risk factors for rectal bleeding after VMAT of prostate cancer., Materials and Methods: This study included 149 patients with prostate cancer who received VMAT from February, 2012 to June, 2020. Irradiated total doses were 78 Gy/39 fractions in 33 patients (22.1%), 76 Gy/38 fractions in 89 (59.7%), 74 Gy/37 fractions in 4 (2.7%), and 72 Gy/36 fractions in 23 (15.4%). We investigated multiple clinical and dosimetric factors with reference to rectal bleeding., Results: The median observation period was 38 months. Fourteen patients (9.4%) experienced rectal bleeding: five (3.4%) were classified as Grade 2, and nine (6.0%) as Grade 1. There were significant differences between Grade ≥ 1 and Grade 0 patients in the overlap region of the planning target volume (PTV) and the rectum, the rectal V30-75, and the mean rectal dose (p < 0.05). There were significant differences between Grade 2 and Grade 0-1 patients in rectal V30-65 and mean rectal dose (p < 0.05)., Conclusions: Rectal bleeding occurred, but its grades and rate of occurrence were permissible. Higher rectal doses were shown to be related to rectal bleeding, and reduction of low/intermediate and mean rectal doses will be important for preventing rectal bleeding., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest, (© 2023 Greater Poland Cancer Centre.)

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type-I (HTLV-1). This study investigated whether the number of newly diagnosed patients with ATL is decreasing in the background of a declining number of individuals infected by HTLV-1 in Kagoshima, Japan, one of the most endemic areas of HTLV-1 in the world. We retrospectively analyzed the number of newly diagnosed patients with ATL between January 2001 and December 2021 in three major hospitals. The number of newly diagnosed patients with B-cell non-Hodgkin lymphoma (B-NHL) in the same period was examined as an internal control. One thousand eighteen and 2,029 patients with ATL and B-NHL were registered, respectively. The age-adjusted incidence of ATL steadily increased between 2001 and 2012, whereas that between 2013 and 2021 decreased. Despite the limitation of its retrospective nature, this is the first report indicating a decrease in ATL patients in Japan.

An estimated 1.08 million carriers of human T-lymphotropic virus 1 (HTLV-1) were living in Japan in 2006-2007. Since that study, new data on horizontal infection, nationwide antenatal screening for anti-HTLV-1 in pregnant women, and social educational campaigns on HTLV-1 infection have emerged in Japan. To estimate the current number of HTLV-1 carriers in Japan, confirmed HTLV-1 infections among first-time blood donors in 2020-2021 from across Japan were investigated. Age-, sex- and geographic area-specific information associated with HTLV-1 antibody detection was evaluated. Data obtained were compared with predictions based on 2006-2007 data, considering a birth cohort effect that assumed lifelong maintenance of seropositivity. HTLV-1 seroprevalence in women was almost equivalent to that in men. The prevalence in men was similar to that predicted from 2006 to 2007 data. In contrast, the prevalence in women was lower in all age strata than that predicted by each birth cohort. The estimate for the entirety of Japan was 534 000 carriers from measured prevalence, whereas that from the birth cohort effect-adjusted prevalence was 658 000. The number of HTLV-1 carriers in Japan was estimated to have decreased by approximately 40% during the past 14 years., (© 2023 Wiley Periodicals LLC.)

The molecular shuttling function of rotaxanes can be exploited to design mechanoresponsive reporter molecules. Here, we report a new approach to such rotaxane-based mechanophores, in which the fluorescence resonance energy transfer (FRET) between a donor-acceptor pair is mechanically controlled. A cyclic molecule containing a green-light-emitting FRET donor connected to a red-light-emitting FRET acceptor was threaded onto an axle equipped with a quencher at its center and two stoppers in the peripheral positions. In the force-free state, the green emitter is located near the quencher so that charge transfer interactions or photo-induced electron transfer between the two moieties suppress green emission and prevent the FRET from the green to the red emitter. The mechanophore was covalently incorporated into a linear polyurethane-urea (PUU), and stretchable hydrogels were prepared by swelling this polymer with water. Upon deformation of the PUU hydrogels and under an excitation light that selectively excites the donor, the intensity of the red fluorescence increases, as a result of a force-induced separation of the green emitter from the quencher, which enables the FRET. The switching contrast is much more pronounced in the gels than in dry films, which is due to increased molecular mobility and hydrophobic effects in the hydrogel, which both promote the formation of inclusion complexes between the ring containing the green emitter and the quencher.

HER2-targeted anticancer therapies may be associated with cardiovascular adverse events. This study evaluated effects of the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd, DS-8201a) on QT/QTc interval and its pharmacokinetics. Patients with heavily pretreated, metastatic HER2-expressing breast cancer were enrolled at seven study sites in Japan. T-DXd was administered intravenously at 6.4 mg/kg on day 1 of each 21-day cycle. Primary end points were baseline-adjusted QTcF interval and pharmacokinetics parameters. Key secondary end points included safety events, serum concentration of T-DXd and DXd at the time of electrocardiographic measurements, and antitumor activity parameters. Among 51 total patients, 47 (92.2%) had HER2-low breast cancer (immunohistochemistry 1+ or 2+ and in situ hybridization-negative/equivocal/missing). Pharmacokinetic parameters after a single dose of T-DXd were consistent with previous studies. After multiple doses, T-DXd showed moderate accumulation (accumulation ratio (cycle 3/cycle 1), 1.35), but DXd showed minimal accumulation (1.09). The upper bound of the 90% confidence interval for mean ΔQTcF interval was < 10 ms at all timepoints, and at mean maximum serum concentration was also < 10 ms. Based on concentration-QT analysis, ΔQTcF increased with increasing concentrations of T-DXd and DXd. No clinically meaningful QTcF prolongation was observed. T-DXd had a manageable safety profile and showed antitumor activity in HER2-low breast cancer. In this study, a T-DXd dose of 6.4 mg/kg, higher than the 5.4-mg/kg dose currently approved for breast cancer, was not associated with clinically relevant QTcF prolongation in heavily pretreated patients with HER2-expressing metastatic breast cancer. This study adds to our understanding of T-DXd for treatment of HER2-low breast cancer., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of the life-threatening diseases, adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy. Following implementation of antenatal screening in Japan, novel transmission of HTLV-1 in adolescent and adult generations is expected to replace vertical transmission as the main route for transmission., Objectives: To obtain the current status of HTLV-1 horizontal infection and to assess the fluctuation of transmission occurring among adolescents and adults in Japan., Study Design: We followed-up 5,017,916 eligible repeat blood donors for 8 years from 2013 to 2021. We evaluated HTLV-1 transmission rate by age group (16-69 years-old), and calculated the total number of novel transmissions in Japan using demographic statistics published by the government of Japan., Results: We identified 457 seroconverters (men, 203; women, 254) in a total of 19,244,604 person-years during the study period. The number of seroconversions per 100,000 person-years was 1.54 for men and 4.21 for women. An increase in the number of novel infections was observed in both sexes in adolescent and young adult generations despite the health bias of blood donors., Conclusions: We estimate that more than 2,800 new HTLV-1 infections occur annually in Japan. It is a serious concern that without immediate measures against new HTLV-1 infections, such as guideline formulation, an inclusion of HTLV as routine screening in sexual health services, an information campaign, and surveillance of the general population, novel HTLV-1 infection could continue to increase in Japan and be a source of global transmission., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest in this manuscript., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Cerebral palsy (CP) is the most prevalent motor disorder of childhood. It typically results from in utero or perinatal brain injury. Recently, it has been reported that autologous cord blood (ACB) infusion for children with CP improved gross motor function and brain connectivity, but unfortunately, it has never been tried in Japan. We conducted a pilot study of the infusing of ACB, which was delivered from private bank, in the children with CP to assess the safety and feasibility to the procedure as well as any effect in improving neurological function., Methods: After demonstrating the induction of tissue regeneration in animal model studies conducted a single-arm pilot study of intravenous ACB infusion in 6 young Japanese children with CP (ages 1-6 years). Primary outcomes were safety assessed by vital signs, clinical symptoms, and blood and urinary examinations at baseline and 1 weeks, 1, 2 and 3 years after treatment. In addition, motor function evaluations, neurodevelopmental examinations, magnetic resonance imaging, and electroencephalography (EEG) were performed at the same time., Results: Infusion was generally well-tolerated, although one patient experienced microhematuria 1 year after treatment and another one patient experienced febrile convulsion once 9 months after treatment. These events were transient, no relapse was seen during observation study. All patients improved a median of 6.8 points on the 1-year Gross Motor Functional Measure-66 (GMFM-66) scores, greater than predicted by age and severity. Furthermore, the 2-year and 3-year GMFM-66 scores were also greater than expected (median 6.2 points and 5.5 points, respectively). Overall scales and language-social scales of the developmental quotient (DQ) improved in 3 of 6 patients, who had greater changes in their GMFM-66 scores than the other cases after treatment. There were no significant correlations among the GMFM-66 scores, DQ, and infusion cell counts., Conclusion: ACB infusion was safe and feasible for clinical use in patients with CP. However, much more clinical study with larger numbers of patients and in-depth studies of treatment mechanism of CP are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Mechanochromic mechanophores are reporter molecules that indicate mechanical events through changes of their photophysical properties. Supramolecular mechanophores in which the activation is based on the rearrangement of luminophores and/or quenchers without any covalent bond scission, remain less well investigated. Here, we report a cyclophane-based supramolecular mechanophore that contains a 1,6-bis(phenylethynyl)pyrene luminophore and a pyromellitic diimide quencher. In solution, the blue monomer emission of the luminophore is largely quenched and a faint reddish-orange emission originating from a charge-transfer (CT) complex is observed. A polyurethane elastomer containing the mechanophore displays orange emission in the absence of force, which is dominated by the CT-emission. Mechanical deformation causes a decrease of the CT-emission and an increase of blue monomer emission, due to the spatial separation between the luminophore and quencher. The ratio of the two emission intensities correlates with the applied stress., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Purpose: We evaluated the diagnostic performance of the texture features of dynamic contrast-enhanced (DCE) MRI for breast cancer diagnosis in which the discriminator was optimized, so that the specificity was maximized via the restriction of the negative predictive value (NPV) to greater than 98%., Methods: Histologically proven benign and malignant mass lesions of DCE MRI were enrolled retrospectively. Training and testing sets consist of 166 masses (49 benign, 117 malignant) and 50 masses (15 benign, 35 malignant), respectively. Lesions were classified via MRI review by a radiologist into 4 shape types: smooth (S-type, 34 masses in training set and 8 masses in testing set), irregular without rim-enhancement (I-type, 60 in training and 14 in testing), irregular with rim-enhancement (R-type, 56 in training and 22 in testing), and spicula (16 in training and 6 in testing). Spicula were immediately classified as malignant. For the remaining masses, 298 texture features were calculated using a parametric map of DCE MRI in 3D mass regions. Masses were classified into malignant or benign using two thresholds on a feature pair. On the training set, several feature pairs and their thresholds were selected and optimized for each mass shape type to maximize specificity with the restriction of NPV > 98%. NPV and specificity were computed using the testing set by comparison with histopathologic results and averaged on the selected feature pairs., Results: In the training set, 27, 12, and 15 texture feature pairs are selected for S-type, I-type, and R-type masses, respectively, and thresholds are determined. In the testing set, average NPV and specificity using the selected texture features were 99.0% and 45.2%, respectively, compared to the NPV (85.7%) and specificity (40.0%) in visually assessed MRI category-based diagnosis., Conclusion: We, therefore, suggest that the NPV of our texture-based features method described performs similarly to or greater than the NPV of the MRI category-based diagnosis.

Stimuli-responsive polymers are of great interest due to their ability to translate changing environmental conditions into responses in defined materials. One possibility to impart such behavior is the incorporation of optically active molecules into a polymer host. Here, we describe how sensor molecules that consist of a π-extended benzothiadiazole emitter and a naphthalene diimide quencher can be exploited in this context. The two optically active entities were connected via different spacers and, thanks to attractive intramolecular interactions between them, the new sensor molecules assembled into cyclic structures in which the fluorescence was quenched by up to 43% when compared to solutions of the individual dyes. Detailed spectroscopic investigations of the sensor molecules in solution show that the extent of donor/acceptor interactions is influenced by various factors, including solvent polarity and ion concentration. The new sensor molecule was covalently incorporated into a polyurethane; the investigation of the optical characteristics in both the solid and solvent-swollen states indicates that a stimulus-induced formation of associated dye pairs is possible in polymeric materials. Indeed, a solvatochromic quenching effect similar to the behavior in solution was observed for solvent-swollen polymer samples, leading to an effective change of the green emission color of the dye to a yellow color.

Background: Optimal cosmetic results after breast-conserving surgery (BCS) improve patient satisfaction. The suture scaffold technique (SST) is a breast reconstruction technique that all breast surgeons can perform without any extensive training in plastic surgery., Objective: We aimed to investigate patient satisfaction after BCS and compare blood loss and operative duration between the SST, breast glandular flap technique (BGFT), and no oncoplastic technique (NOT)., Methods: This was a prospective, single-center, cross-sectional study. All patients who underwent BCS from August 2017 to September 2019 in our institution were included, with the exception of those with cT3 tumors or those who underwent nipple excision or bilateral breast surgery. The BREAST-Q™ was used to survey the patients, and the raw sum scale scores of the BREAST-Q™ were converted into BREAST-Q scores., Results: Overall, we identified 421 eligible patients. The NOT was used in 47 (11.1%) patients, the BGFT was used in 231 (54.8%) patients, and the SST was used in 143 (33.9%) patients. In the univariable model, the BGFT and the SST had higher BREAST-Q scores than the NOT, while in the multivariable model, the SST had significantly higher BREAST-Q scores than the NOT (ß = +7.7, 95% confidence interval [CI] 0.9-13.7; p = 0.01). Blood loss was significantly less with the SST compared with the BGFT (ß = -4.4, 95% CI -7.3 to -1.4), and there was no difference in operative duration between the methods., Conclusions: Patient satisfaction with the SST was higher than with the NOT and was similar to the BGFT. The SST is an oncoplastic technique that all breast surgeons can perform and which requires comparable blood loss and operative duration in the NOT., (© 2022. Society of Surgical Oncology.)

A Nankai Trough earthquake is highly likely to occur in near future, and perinatal medical resources and care in Kochi Prefecture may be insufficient after such an event. Therefore, we evaluated the medical and public health measures needed to prepare for caring for pregnant women in Kochi Prefecture in the aftermath of such an earthquake and the potential action plans for the prefecture. We estimated that immediately after an earthquake, approximately 30 pregnant women will require urgent medical treatment, most of whom will be in the prefectural capital, Kochi City, and perinatal medical care in Kochi City may be insufficient. Therefore, we used the projected flooding areas to divide Kochi City and its surrounding areas into 3 areas and allocated at least one Disaster Liaison for Pediatrics and Perinatal Medicine (DLPPM) to each disaster base hospital in those 3 areas. In a disaster, the DLPPMs will serve as key individuals in their respective areas and coordinate the allocation of medical care. A DLPPM will be allocated also within the Disaster Medical Response Headquarters of Kochi Prefecture and be responsible for overseeing perinatal care in the whole of Kochi Prefecture. Our study shows that estimating the number of affected pregnant women and requirement for perinatal medical care is an effective way to prepare realistic disaster measures and to enable a specific plan to be formulated for effective allocation and management of DLPPMs. We believe that our system can serve as a model in perinatal disaster medicine.

Japan is one of the world's highly endemic areas for human T cell leukemia virus type 1 (HTLV-1), and it is known that the infection rate of HTLV-1 increases with age. The infection rate among the elderly has been estimated based on data from blood donors under the age of 65, and the actual number and rate of infection among the elderly are unknown. Data of 26,090 preoperative HTLV-1 screening tests conducted at Kagoshima University Hospital from 2001 to 2020, including 2726 HTLV-1-positive patients, were used for calculating the decadal infection rates for the year of birth. Estimated infection rates by birth year and demographic tables were used to estimate the current number of infected people in Kagoshima. The estimated total numbers of people infected with HTLV-1 in Kagoshima prefecture were 139,436 in 2005 and 80,975 in 2019. The infection rate increased with age for both men and women, reaching 17.3% for women born before the 1920s. Next, we tried to clarify whether the increase in infection rates with age was due to post-school age infections. The age of birth with the greatest increase in infection rate after 10 years was women born in the 1970s, and the increase in infection rate was only 0.98%, which is not a statistically significant increase. The number of infected people in Kagoshima was >80,000 in 2019. No data were available in this study to point to the involvement of horizontal transmission after school age in the high infection rate among the elderly. The high infection rate among the elderly is thought to have been high even when they were infants.

Vibrio has a polar flagellum driven by sodium ions for swimming. The force-generating stator unit consists of PomA and PomB. PomA contains four transmembrane regions and a cytoplasmic domain of approximately 100 residues, which interacts with the rotor protein, FliG, to be important for the force generation of rotation. The 3D structure of the stator shows that the cytosolic interface (CI) helix of PomA is located parallel to the inner membrane. In this study, we investigated the function of CI helix and its role as stator. Systematic proline mutagenesis showed that residues K64, F66 and M67 were important for this function. The mutant stators did not assemble around the rotor. Moreover, the growth defect caused by PomB plug deletion was suppressed by these mutations. We speculate that the mutations affect the structure of the helices extending from TM3 and TM4 and reduce the structural stability of the stator complex. This study suggests that the helices parallel to the inner membrane play important roles in various processes, such as the hoop-like function in securing the stability of the stator complex and the ion conduction pathway, which may lead to the elucidation of the ion permeation and assembly mechanism of the stator., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Retinal dystrophies (RDs) lead to irreversible vision impairment with no radical treatment. Although photoreceptor cells (PRCs) differentiated from human induced pluripotent stem cells (iPSCs) are essential for the study of RDs as a scalable source, current differentiation methods for PRCs require multiple steps. To address these issues, we developed a method to generate PRCs from human iPSCs by introducing the transcription factors, CRX and NEUROD1. This approach enabled us to generate induced photoreceptor-like cells (iPRCs) expressing PRC markers. Single-cell RNA sequencing revealed the transcriptome of iPRCs in which the genes associated with phototransduction were expressed. Generated iPRCs exhibited their functional properties in calcium imaging. Furthermore, light-induced damage on iPRCs was inhibited by an antioxidant compound. This simple approach would facilitate the availability of materials for PRC-related research and provide a useful application for disease modeling and drug discovery., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

The current study examined the antimicrobial resistance of Chlamydia trachomatis (CT) genital infection during pregnancy in Japan. We requested 2,146 obstetrical facilities that are members of Japan Association of Obstetricians and Gynecologists to provide information of CT screening tests and antimicrobial resistance in pregnant women between April 2020 and March 2021. The prevalence of CT genital infection in Japan was 2.1%. The antimicrobial resistance was recognized in 2.0 and 2.4% of the cases using azithromycin and clarithromycin, respectively. There were no significant differences in the antimicrobial resistance rate between the 2 analogues ( P = 0.28). In Japan, azithromycin and clarithromycin have effectively treated genital CT infections during pregnancy., Competing Interests: No conflict of interest., (Copyright © 2022 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Purpose: Radiotherapy (RT) and endocrine therapy (ET) are standard treatment options after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We investigated the national patterns of adjuvant therapy use after BCS for DCIS in Japan., Methods: We obtained relevant data of patients diagnosed with DCIS undergoing surgery and treated with BCS between 2014 and 2016 from the Japanese Breast Cancer Registry database. The relationship between the clinicopathologic, institutional, and regional factors, and adjuvant treatment was examined using multivariable analyses., Results: We identified 9516 patients who underwent BCS for DCIS. Overall, 23% received no adjuvant treatment, 71% received RT, 32% received ET, and 26% received combination therapy. The percentages of patients who received ET and combination therapy in 2016 were significantly lower [odds ratio (OR): 0.71, 0.77, respectively] than in 2014. The proportion of RT was low among young or elderly patients (OR: 0.75, 0.44, respectively) and in non-certified facilities (OR: 0.56). The proportion of ET was high in non-certified facilities (OR: 1.58) and among patients with positive margins (OR: 1.62). Combination therapy was higher among patients with positive margins (OR: 1.53)., Conclusions: Our study found a distinct adjuvant treatment pattern after BCS for DCIS depending on clinicopathologic factors, year, age, which indicate that physicians provide individualized treatment according to the background of the patients and the biology of DCIS. The facilities and regions remain significant factors of influencing adjuvant treatment pattern., (© 2021. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background: Omarigliptin is one of several once-weekly dipeptidyl peptidase-4 inhibitors (DPP-4is). Despite the high frequency of switching from various daily DPP-4is to omarigliptin in actual clinical practice, data regarding its efficacy in patients with type 2 diabetes (T2D) after switching are limited., Aim: To analyze the efficacy of omarigliptin in Japanese patients with T2D who had previously received treatment with other glucose-lowering agents., Methods: Forty-nine T2D patients treated for the first time with omarigliptin were recruited retrospectively and divided into four groups defined as either add-on or switched from daily DPP-4is: switched from linagliptin, switched from sitagliptin, and switched from vildagliptin. During a 3-mo follow-up, the clinical parameters among these groups were assessed and compared, with the impact of the switch on glycemic variability as measured by continuous glucose monitoring also being evaluated in the switched groups., Results: Hemoglobin A1c levels saw a significant decrease of -0.32% ± 0.41% in the add-on group ( P = 0.002). However, the other groups' variables depended on the pre-switch daily DPP-4i: switched from linagliptin, -0.05% ± 0.22%; switched from sitagliptin, -0.17% ± 0.33%; and switched from vildagliptin, 0.45% ± 0.42%, which saw significant worsening ( P = 0.0007). Multivariate logistic regression analysis revealed that switching from vildagliptin to omarigliptin was independently associated with worsening glycemic control ( P = 0.0013). The mean and standard deviation of sensor glucose value, the mean amplitude of glycemic excursions, and the mean of daily difference significantly improved when switching the patient from either linagliptin or sitagliptin to omarigliptin. However, in patients switched from vildagliptin, not only did the glucose variability indices see no improvements, the mean of daily difference even underwent significant worsening., Conclusion: Administering omarigliptin as add-on therapy or switching to it from sitagliptin and linagliptin, but not vildagliptin, improves glycemic control and thus should help in decision making when selecting DPP-4is for T2D patients., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Human T-cell leukaemia virus type 1 (HTLV-1) tests have been mandated in Japan since 1986, and notification of HTLV-1-seropositive donors started in 1999. However, donor knowledge and response to notification has not been assessed., Study Design and Methods: A questionnaire survey was conducted among blood donors notified of HTLV-1 seropositivity regarding their knowledge of HTLV-1 and unmet information needs. To reduce anxiety among notified individuals and raise awareness of their infection status, we created a booklet containing information that would be useful for these individuals without causing unnecessary anxiety while also requesting that they refrain from donating blood in the future., Results: A questionnaire survey conducted before the distribution of a new booklet revealed that 15.0% of respondents donated blood again despite receiving an HTLV-1-seropositive notification at the previous donation. While 62.2% of respondents reacted to the notification favourably, 40.2% expressed anxiety and 32.5% requested information on related diseases and medical institutions for consultation. In the secondary survey after distribution of the new booklet, 87.9% of respondents reported that the information was comprehensible, and an increase in consultations of medical institutions by notification recipients was observed. Furthermore, no re-visiting donors were observed among the HTLV-1-seropositive recipients who were notified using the new information booklet., Conclusion: The new information booklet provided enlightenment on HTLV-1 infection and facilitated the consultation of medical institutions by seropositive donors, leading to an improvement in the health-related quality of life of seropositive blood donors and the safety of blood products., (© 2021 The Authors. Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)

The current study was conducted to examine the number of human T-cell leukemia virus type 1 (HTLV-1) carriers and how horizontal transmission affected the prevalence of HTLV-1 carriers among pregnant Japanese women in 2019. We requested 2,214 obstetrical facilities to provide information on HTLV-1 tests for pregnant women who delivered in 2019. The estimated number of HTLV-1 carriers among pregnant Japanese women was 952. At least 10% or more of the carriers acquired HTLV-1 through horizontal transmission.

Background: We have previously demonstrated S-1 is non-inferior to taxane with respect to overall survival as first-line chemotherapy for HER2-negative metastatic breast cancer. We aimed to confirm whether S-1 is also non-inferior to anthracycline-containing regimens in the same setting., Methods: We conducted an open-label, non-inferiority, Phase 3 study. Individuals who had HER2-negative metastatic breast cancer, had received no chemotherapy for advanced disease and had endocrine therapy resistance, were randomly assigned to the anthracycline-containing regimens or S-1. The primary endpoint was overall survival. A pre-planned combined analysis of our two Phase 3 studies was also carried out., Results: We enrolled 230 patients (anthracycline, n = 115; S-1, n = 115). Median overall survival was 30.1 months (95% CI 24.9-35.8) with the S-1 group and 33.7 months (95% CI 25.5-36.9) with the anthracycline group. The HR for the anthracycline group was 1.09 (95% CI 0.80-1.48). The combined analysis constituted 814 patients (395 assigned to standard treatment (anthracycline or taxane); 419 assigned to S-1). Median overall survival was 36.3 months in the standard treatment group and 32.7 months in the S-1 group. S-1 was non-inferior to standard treatment in terms of overall survival (HR 1.06 (95% CI 0.90-1.25); P non-inferiority = 0.0062)., Conclusions: S-1 could be considered a new treatment option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer., Clinical Trial Registration: The University Hospital Medical Information Network, Japan: UMIN000005449. This trial was registered on 15 April, 2011., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Tubal reanastomosis or tubal reversal, a surgical method used to reverse tubal sterilization, may be an option for women who for various reasons wish to reestablish their fertility. A 38-year-old Chinese woman, gravida 2, para 2 (both delivered through cesarean section) presented to our outpatient gynecology clinic requesting bilateral tubal recanalization. After other causes of infertility were excluded, laparoscopic tubal reanastomosis was performed. Here, we present our tips and techniques for laparoscopic tubal reanastomosis that rapidly resulted in an intrauterine pregnancy, which delivered at term. Laparoscopic tubal reanastomosis is a well-established procedure with good prognosis, as reported in the literature. For women who wish to become pregnant after tubal sterilization, it is necessary to present the option of surgery as well as in vitro fertilization.

Schizophrenia (SCZ) is one of the major psychiatric disorders. The genetic factor is certainly influential in the onset of the disease but is not decisive. There is no identified molecular/cellular marker of the disease, and the pathomechanism is still unknown. In this study, we generated human induced pluripotent stem cells (iPSCs) derived from SCZ-discordant fraternal twins, and they could contribute to elucidation of the pathomechanism of SCZ., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

A supramolecular mechanophore that can be integrated into polymers and indicates deformation by a fluorescence color change is reported. Two perylene diimides (PDIs) were connected by a short spacer and equipped with peripheral atom transfer polymerization initiators. In the idle state, the motif folds into a loop and its emission is excimer dominated. Poly(methyl acrylate) (PMA) chains were grown from the motif and the mechanophore-containing polymer was blended with unmodified PMA to afford materials that display a visually discernible fluorescence color change upon deformation, which causes the loops to unfold. The response is instant, and correlates linearly with the applied strain. Experiments with a reference polymer containing only one PDI moiety show that looped mechanophores that display intramolecular excimer formation offer considerable advantages over intermolecular dye aggregates, including a concentration-independent response, direct signaling of mechanical processes, and a more pronounced optical change., (© 2021 Wiley-VCH GmbH.)

Mechanochromic mechanophores permit the design of polymers that indicate mechanical events through optical signals. Here we report rotaxane-based supramolecular mechanophores that display both reversible and irreversible fluorescence changes. These responses are triggered by different forces and are achieved by exploiting the molecular shuttling function and force-induced dethreading of rotaxanes. The new rotaxane mechanophores are composed of a ring featuring a luminophore, which is threaded onto an axle with a matching quencher and two stoppers. In the stress-free state, the luminophore is preferentially located in the proximity of the quencher, and the emission is quenched. The luminophore slides away from the quencher when a force is applied and the fluorescence is switched on. This effect is reversible, unless the force is so high that the luminophore-carrying ring slips past the stopper and dethreading occurs. We show that the combination of judiciously selected ring and stopper moieties is crucial to attain interlocked structures that display such a dual response. PU elastomers that contain such doubly responsive rotaxanes exhibit reversible fluorescence changes over multiple loading-unloading cycles due to the shuttling function, whereas permanent changes are observed upon repeated deformations to high strains due to breakage of the mechanical bond upon dethreading of the ring from the axle. This response allows one, at least conceptually, to monitor the actual deformation of polymer materials and examine mechanical damage that was inflicted in the past on the basis of an optical signal.

Background/aim: Little is known on urine biomarkers that are associated with malignant behavior in patients with bladder cancer (BC). Our aim was to identify BC-related factors in urine samples using our original method "immune complexome analysis", based on detecting the immune complex (IC)., Patients and Methods: Immune complexome analysis was performed using urine samples from 97 BC patients, including 67 with non-muscle invasive BC (NMIBC)., Results: Eight IC-antigens were recognized as candidates for BC-related factors from 20,165 proteins. IC-serum albumin, -fibrinogen γ chain, -hemoglobin subunit α, -hemoglobin subunit β, -ceruloplasmin, and fibrinogen β chain were significantly associated with either pathological features and/or outcome. IC-ceruloplasmin was most widely associated with pathological features in all BC patients and lamina propria invasion and urinary tract recurrence in NMIBC., Conclusion: Based on detection of IC-antigens it was demonstrated that six IC-antigens, especially IC-ceruloplasmin, are potential urine biomarkers in BC., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: To decrease the risk of bleeding or perforation, ischemic polypectomy is performed using a detachable snare or endoclip with double-balloon endoscopy (DBE) for small-bowel polyps in patients with Peutz - Jeghers syndrome. The aim of this study was to determine the effectiveness and feasibility of ischemic polypectomy., Methods: We retrospectively reviewed patients who underwent two or more sessions of ischemic polypectomy using DBE from July 2004 to August 2017., Results: 67 therapeutic DBEs were performed in nine patients during the study period and 352 polyps were treated. The median observation period was 34 months (range 12 - 66). There was a declining trend over time in the median number of polyps > 15 mm treated per patient first DBE session 6, second 2, third 1.5, fourth 0.5, fifth 0.5; P  = 0.11, Friedman test). No patient required laparotomy due to intussusception during the study period. One patient developed mild acute pancreatitis after the procedure., Conclusions: Ischemic polypectomy was feasible for the control of small-bowel polyps in patients with Peutz - Jeghers syndrome., Competing Interests: Dr. Yamamoto is a consultant for Fujifilm Corp. and has received honoraria, grants, and royalties from the company. Drs. Sakamoto, Yano, and Sunada have received honoraria from Fujifilm Corp. Dr. Sakamoto has also received a grant from Fujifilm Medical Corporation. Other authors declare no conflicts of interest regarding this study., (Thieme. All rights reserved.)

Background: We conducted a prospective study with the intention to omit surgery for patients with ductal carcinoma in situ (DCIS) of the breast. We aimed to identify clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with DCIS., Patients and Methods: We retrospectively analyzed patients with DCIS diagnosed through biopsy between April 1, 2010 and December 31, 2014, from 16 institutions. Clinical, radiological, and histological variables were collected from medical records., Results: We identified 2,293 patients diagnosed with DCIS through biopsy, including 1,663 DCIS (72.5%) cases and 630 IDC (27.5%) cases. In multivariate analysis, the presence of a palpable mass (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.2-2.6), mammography findings (≥ category 4; OR 1.8; 95% CI 1.2-2.6), mass formations on ultrasonography (OR 1.8; 95% CI 1.2-2.5), and tumor size on MRI (> 20 mm; OR 1.7; 95% CI 1.2-2.4) were independent predictors of IDC. Among patients with a tumor size on MRI of ≤ 20 mm, the possibility of postoperative upstaging to IDC was 22.1%. Among the 258 patients with non-palpable mass, nuclear grade 1/2, and positive for estrogen receptor, the possibility was 18.1%, even if the upper limit of the tumor size on MRI was raised to ≤ 40 mm., Conclusion: We identified four independent predictive factors of upstaging to IDC after surgery among patients with DCIS diagnosed by biopsy. The combined use of various predictors of IDC reduces the possibility of postoperative upstaging to IDC, even if the tumor size on MRI is larger than 20 mm.

Idiopathic basal ganglia calcification (IBGC) is a rare neurodegenerative disease, characterized by abnormal calcium deposits in basal ganglia of the brain. The affected individuals exhibit movement disorders, and progressive deterioration of cognitive and psychiatric ability. The genetic cause of the disease is mutation in one of several different genes, SLC20A2, PDGFB, PDGFRB, XPR1 or MYORG, which inheritably or sporadically occurs. Here we generated an induced pluripotent stem cell (iPSC) line from an IBGC patient, which is likely be a powerful tool for revealing the pathomechanisms and exploring potential therapeutic candidates of IBGC., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

A new approach to cyclophane-based supramolecular mechanophores is presented. We report a mechanically responsive cyclic motif that contains two fluorescent 1,6-bis(phenylethynyl)pyrene moieties that are capable of forming intramolecular excimers. The emission spectra of dilute solutions of this cyclophane and a polyurethane elastomer into which a small amount of the mechanophore (0.08 wt %) had been covalently integrated are dominated by excimer emission. Films of the cyclophane-containing polyurethane also display a considerable portion of excimer emission, but upon deformation, the fluorescence becomes monomer-dominated and a perceptible change from cyan to blue is observed. The response is instant, reversible, and consistent with a mechanically induced change of the molecular conformation of the mechanophore so that the excimer-promoting interactions between the luminophores are suppressed. In-depth investigations show a correlation between the applied strain and the emission color, which can conveniently be expressed by the ratio of monomer to excimer emission intensity. The current study suggests that cyclophanes can be utilized to develop various supramolecular mechanophores that detect and visualize weak forces occurring in polymeric materials or generated by living tissues.

Background: Advance care planning (ACP) is a process that supports adults in understanding and sharing their personal values, life goals, and preferences regarding future medical care. We examined the current status of ACP and end-of-life (EOL) communication between oncologists and patients with metastatic breast cancer., Materials and Methods: We conducted a survey among 41 institutions that specialize in oncology by using an online tool in October 2019. Participants (118 physicians) from 38 institutions completed a 39-item questionnaire that measured facility type and function; physicians' background and clinical approach, education about EOL communication, and understanding about ACP; and the current situation of ACP and EOL discussions., Results: Ninety-eight responses concerning physicians' engagement in ACP with patients were obtained. Seventy-one (72%) answered that they had engaged in ACP. Among these, 23 (33%) physicians used a structured format to facilitate the conversation in their institutions, and only 6 (8%) settled triggers or sentinel events for the initiation of ACP. In the multivariable analysis, only the opportunity to learn communication skills was associated with physicians' engagement with ACP (odds ratio: 2.8, 95% confidence interval: 1.1-7.0). The frequency and timing of communication about ACP and EOL care with patients substantially varied among the oncologists. Communication about patients' life expectancy was less frequent compared with other topics., Conclusion: The opportunity to improve EOL communication skills promoted physicians' engagement with ACP among patients with metastatic/advanced breast cancer. However, there were still substantial variabilities in the method, frequency, and timing of ACP and EOL communication among the oncologists., Implications for Practice: This study found that the opportunity to improve end-of-life (EOL) communication skills promoted physicians' engagement in advance care planning (ACP) among patients with metastatic/advanced breast cancer. All oncologists who treat said patients are encouraged to participate in effective education programs concerning EOL communication skills. In clinical practice, there are substantial variabilities in the method, frequency, and timing of ACP and EOL communication among oncologists. As recommended in several clinical guidelines, the authors suggest a system that identifies patients who require conversations about their care goals, a structured format to facilitate the conversations, and continuous measurement for improving EOL care and treatment., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Background: Breast tuberculosis, also known as tuberculous mastitis, is an extremely rare form of tuberculosis. It accounts for <0.1% of all breast diseases and <2% of all cases of tuberculosis. It is often misdiagnosed as breast cancer, which can potentially lead to a delayed diagnosis., Case Presentation: A 69-year-old Japanese woman presented with a tumor-mimicking lesion in her right breast, followed by intractable mastitis with a fistula formation. The time until the correct diagnosis of tuberculosis of the breast and sternal bone was 14 months., Conclusions: Although rare, it is important to recognize that tuberculous mastitis can present as refractory abscesses/mastitis or mass lesions that mimic carcinomas in women of reproductive age and elderly people. Breast tuberculosis should always be considered in the differential diagnoses, particularly in patients with a history of tuberculosis and those living in areas where tuberculosis is endemic.

Background: Infection, such as by human immunodeficiency virus (HIV), has been reported to cause atherosclerosis by inducing inflammation. Because human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus, as is HIV, we investigated the possible influence of HTLV-1 on the pathogenesis of atherosclerosis by use of established atherosclerosis parameters., Methods: The study was done on Iki Island, Fukuoka, an area endemic for HTLV-1. The data of 1,424 residents who reported to an annual health check were available for analysis. Anti-HTLV-1 antibody status and factors associated with atherosclerosis were examined, including maximum intima-media thickness (Max-IMT) and brachial-ankle pulse wave velocity (PWV)., Results: HTLV-1 positive participants had significantly higher Max-IMT (1.15 ± 0.55 vs. 1.08 ± 0.61 mm, P = 0.04) and PWV (1,760.6 ± 414.5 vs. 1,657.1 ± 425.5 cm/s, P < 0.01) values than did those negative. Moreover, in multiple regression analysis (odds ratio: 1.39, P < 0.01) of participants with Max-IMT 1.1 mm or over, HTLV-1 was extracted as an independent factor for the development of atherosclerosis., Conclusion: Our results indicate that HTLV-1 infection confers a high risk of atherosclerosis, although its opposite relation is also possible. It is important to carefully follow the health status of HTLV-1 carriers., Competing Interests: None to declare., (Copyright 2021, Takeoka et al.)

Background: Neoadjuvant systemic therapy (NST) induces tumor shrinkage and boosts the chance of breast-conserving thearpy (BCT) in patients with breast cancer. However, only a few trials have evaluated the effect of NST in conversion from BCT ineligibility to BCT eligibility in HER2-positive breast cancer., Methods: We conducted the surgical sub-study of a phase II randomized trial, which compared standard neoadjuvant treatment or an experimental treatment modified according to the interim Ki-67 evaluation in women with stage II or III HER2-positive breast cancer. The treating surgeons assessed eligibility for BCT before and after NST. We evaluated the change in BCT eligibility following NST. We also analyzed the type of surgery performed and the success rate of BCT., Results: Two hundred six patients were included in this study. Of these, 44.0% were considered BCT candidates at baseline, while 69.8% were deemed eligible for BCT after NST (P < 0.001). Among non-BCT candidates at baseline, 46% successfully converted to BCT candidates. Of 139 patients deemed eligible for BCT following NST, 84.2% attempted BCT, and successful BCT, defined as tumor-free at all surgical margins, was achieved in 96.8% of patients. Different treatment arms did not affect the rate of post-NST BCT eligibility (70.0% vs 69.7%)., Conclusions: This study demonstrated that NST resulted in an absolute increase of 25.8% in the rate of BCT eligibility in HER2-positive breast cancer. About a half of non-BCT candidates converted to BCT candidates. BCT was successful in most patients who attempted BCT. There were still patients who chose mastectomy even though they were deemed eligible for BCT. Patients considered BCT-ineligible due to large tumor size most likely converted to BCT-eligible with NST. On the other hand, NST had less impact on the surgical indication of patients with multicentric disease or probable poor cosmetic outcome., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Japan is endemic for human T-cell leukemia virus type 1 (HTLV-1), and the horizontal transmission of HTLV-1 is often reported. However, the window period (WP) for serologic or molecular screening is unclear., Study Design and Methods: Results for anti-HTLV-1 screening and confirmatory tests obtained from 648 591 repeated blood donors in the Kyushu district, one of the most endemic areas of HTLV-1 in the world, were evaluated. A lookback study was conducted for seroconverters., Results: During 2012 to 2019, 436 seroconverters (155 men, 281women) were identified with use of a screening chemiluminescence enzyme-immunoassay (CLEIA) and multiple confirmatory tests. Because the period between the latest seronegative donation and seroconversion was highly variable (2.1-276.7 months), 19 cases that seroconverted within 6 months were subjected to the analysis. The WP of the particle agglutination assay and CLEIA was estimated to be 2.2 ± 0.6 and 2.6 ± 1.7 months, respectively. The WP of the indirect immunofluorescence assay was 4.8 ± 6.5 months. Although the WP of western blotting was estimated to be 6.3 ± 8.7 months, four cases were still indeterminate through the study period. Chemiluminescence and line immunoassays, the current screening and confirmatory tests used in the Japanese blood program, showed the shortest WP of 2.2 ± 0.6 months. The WP of real-time polymerase chain reaction for HTLV-1 was estimated to be 4.1 ± 7.8 months., Conclusions: The WP in commercially available testing systems for HTLV-1/2 was determined for natural infection among repeated blood donors. Considering the HTLV-1 WP will help increase transfusion safety and facilitate the accurate diagnosis of HTLV-1 infection., (© 2020 AABB.)