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BACKGROUND: Adverse Drug Events (ADE) are key information present in unstructured portions of Electronic Health Records. These pose a significant challenge in healthcare, ranging from mild discomfort to severe complications, and can impact patient safety and treatment outcomes. METHODS: We explore the influence of domain shift between a set of dummy clinical notes and a real-world hospital corpus of Japanese clinical notes of breast cancer treatment when extracting ADEs from free text. We annotated a subset of the hospital dataset and used it to fine-tune a Named Entity Recognition (NER) model, initially trained with the set of dummy documents. We used increasing amounts of the annotated data and evaluated the impact on the model's performance. Additionally, we examined the extracted information to identify combinations of drugs that are likely to cause ADEs. RESULTS: We show that domain adaptation can significantly improve model performance in the new domain, as by feeding a small subset of 100 documents for the fine-tuning process we saw a 40% improvement in model performance. However, we also noticed diminishing returns when fine-tuning the model with a larger dataset. For instance, by feeding eight times more data, we only saw further 18% improvement in extraction performance. CONCLUSION: While variations in writing style and vocabulary in clinical corpora can significantly impact the quality of NER results. We show that domain adaptation can be of great aid in mitigating these discrepancies and achieving better performance. Yet, while providing in-domain data to a model helps, there are diminishing returns when fine-tuning with large amounts of data.
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Although the survival rate of patients with childhood cancer has greatly improved, long-term survivors face specific problems such as the late effects of cancer treatment. In this study, we estimated the number of people who had experienced childhood cancer to predict their needs for medical care and social resources. Using data from the population-based Osaka Cancer Registry, we identified children aged 0-14 years who were diagnosed with cancer between 1975 and 2019. We estimated the prevalence on December 31, 2019, and the 5- and 10-year prevalence (i.e., the number of survivors living up to 5 or 10 years after the diagnosis of cancer) over time. The prevalence proportion was age-standardized using a direct standardization method. The prevalence estimates for Osaka were applied to the national population to determine the national prevalence in Japan. Among 8186 patients diagnosed with childhood cancer in Osaka, 5252 (987 per million) survived until December 31, 2019. The 5-year prevalence per million increased from 194 in 1979 to 417 in 2019 (+116%), while the 10-year prevalence increased from 391 in 1984 to 715 in 2019 (+83%). Based on the long-term registry data, an estimated 73,182 childhood cancer survivors were living in Japan by the end of 2019. The increasing 5-year and 10-year prevalence proportions indicate the continued need for cancer survivorship support for children, adolescents, and young adults. These estimates of the prevalence of childhood cancer survivors, including long-term survivors, may be useful for policymakers and clinicians to plan and evaluate survivorship care.
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Sobreviventes de Câncer , Neoplasias , Sistema de Registros , Humanos , Sobreviventes de Câncer/estatística & dados numéricos , Criança , Sistema de Registros/estatística & dados numéricos , Adolescente , Japão/epidemiologia , Pré-Escolar , Lactente , Masculino , Feminino , Prevalência , Neoplasias/epidemiologia , Recém-Nascido , Taxa de SobrevidaRESUMO
Background: The incidence of malignancy and cardiovascular disease (CVD) is increasing worldwide. However, it is not entirely clear how the coexistence of CVD at the time of cancer diagnosis affects the overall survival of patients with cancer. Methods and results: We used the cancer registries and administrative claims data of patients diagnosed with cancer at 36 designated cancer care hospitals in Osaka, Japan, from 2010 to 2015. The Cox proportional hazard model was used to examine how coexisting CVD (heart failure [HF], ischemic heart disease, peripheral arterial disease, cerebrovascular accidents, and atrial fibrillation) affected overall survival and the impact of HF severity, as documented by the New York Heart Association (NYHA) classification. Of the 131,701 patients with cancer, 9704 had coexisting CVD. The 3-year survival rates for patients with and without coexisting CVD were 62.9 % and 77.6 %, respectively. The adjusted hazard ratio (aHR) for all-cause mortality for coexisting CVD was 1.47 (95 % confidence interval, 1.41-1.52). Among the CVD subtype, patients with coexisting HF had the poorest prognosis. The aHRs in patients with HF by NYHA classification, using the patients without HF as a reference, were as follows: Class I: 1.33 (p = 0.217); II: 1.68 (p < 0.001); III: 1.54 (p = 0.011); IV: 2.47 (p < 0.001). Conclusion: Coexisting CVD and HF severity at cancer diagnosis is associated with survival in patients with cancer.
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We investigate the relationship between primary dendrite selection of Purkinje cells and migration of their presynaptic partner granule cells during early cerebellar development. During postnatal development, each Purkinje cell grows more than three dendritic trees, from which a primary tree is selected for development, whereas the others completely retract. Experimental studies suggest that this selection process is coordinated by physical and synaptic interactions with granule cells, which undergo a massive migration at the same time. However, technical limitations hinder continuous experimental observation of multiple cell populations. To explore possible mechanisms underlying this selection process, we constructed a computational model using a new computational framework, NeuroDevSim. The study presents the first computational model that simultaneously simulates Purkinje cell growth and the dynamics of granule cell migrations during the first two postnatal weeks, allowing exploration of the role of physical and synaptic interactions upon dendritic selection. The model suggests that interaction with parallel fibers is important to establish the distinct planar morphology of Purkinje cell dendrites. Specific rules to select which dendritic trees to keep or retract result in larger winner trees with more synaptic contacts than using random selection. A rule based on afferent synaptic activity was less effective than rules based on dendritic size or numbers of synapses.
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Dendritos , Células de Purkinje , Axônios , Sinapses , CerebeloRESUMO
BACKGROUND: In recent years, the survival of patients with breast cancer has improved. However, few published studies have a longer than 10-year follow-up. Conditional relative survival (CRS), which is relative survival (RS) of patients who have survived beyond a certain period after diagnosis, is useful for assessing excess mortality among long-term survivors compared with the general population. METHODS: This was a retrospective observational cohort study. Population-based cancer registry data in Osaka, Japan were used to determine 15-year RS and 5-year CRS of women with breast cancer diagnosed between 2001 and 2002 and followed up for at least 15 years. Fifteen-year RS and age-standardized RS (ASR) were calculated by Ederer II and cohort methods. Five-year CRS according to age group and extent of disease (localized, regional, and distant) was estimated for every year from diagnosis to 10 years. RESULTS: In the cohort of 4006 patients, the ASR declined progressively, the 5-year ASR being 85.8%, 10-year ASR 77.3%, and 15-year ASR 71.6%. The overall 5-year CRS exceeded 90% at 5 years after diagnosis, reflecting a small excess mortality compared with the general population. The 5-year CRS of patients with regional and distant disease did not reach 90% within 10 years of follow-up (89.4% for regional and 72.9% for distant disease 10 years after diagnosis), indicating that these patients had substantial excess mortality. CONCLUSION: Long-term survival data can help cancer survivors plan their lives and receive better medical care and support.
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Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Estudos de Coortes , Japão/epidemiologia , Sobreviventes , Sistema de Registros , Taxa de SobrevidaRESUMO
TAFRO syndrome is a systemic inflammatory disease of unknown aetiology. It is characterised by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly. Herein, we report the case of a 60-year-old male with TAFRO syndrome. A few weeks after the patient developed an intermittent fever, he presented to our hospital with diarrhoea, abdominal distension, and whole-body oedema (face, extremities, and abdomen). Autoantibody and lip biopsy findings supported the diagnosis of primary Sjögren's syndrome. High-dose steroids and tocilizumab were used to treat his refractory thrombocytopenia and ascites. However, systemic inflammation and renal dysfunction did not improve, resulting in temporary haemodialysis. Eventually, combined B-cell immunomodulation therapy with rituximab and belimumab ameliorated the patient's symptoms. About 16 weeks after discharge, the overall condition of the patient had improved. The TAFRO syndrome may be a severe manifestation of primary Sjögren's syndrome. Considering the immunological context, combined B-cell immunomodulation therapy provides new insights into improving this life-threatening disease and enables rapid steroid tapering.
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Nefropatias , Síndrome de Sjogren , Trombocitopenia , Masculino , Humanos , Pessoa de Meia-Idade , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Rituximab/uso terapêutico , Edema/tratamento farmacológico , Trombocitopenia/diagnóstico , Nefropatias/tratamento farmacológicoRESUMO
Bitterness is an important physiological function in the defense responses to avoid toxic foods. The taste receptor 2 family is well known to mediate bitter taste perception in Type II taste cells. Here, we report that the polycystic kidney disease 2-like 1 (PKD2L1) channel is a novel sensor for the bitter aftertaste in Type III taste cells. The PKD2L1 channel showed rebound activation after the washout of quinine, a bitter tastant, in electrophysiological whole-cell recordings of the PKD2L1-expressing HEK293T cells and Ca2+-imaging analysis of Type III taste cells isolated from wild-type PKD2L1 mice. In the short-term two-bottle preference and lick tests in vivo, the wild-type mice avoided normal water while the PKD2L1-knockout mice preferred normal water after they ingested the quinine-containing water. These results may explain the new mechanism of the quinine-triggered bitter aftertaste perception in Type III taste cells.
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Canais de Cálcio , Receptores de Superfície Celular , Paladar , Animais , Humanos , Camundongos , Canais de Cálcio/genética , Células HEK293 , Camundongos Knockout , Quinina/farmacologia , Receptores de Superfície Celular/genética , Paladar/fisiologia , Percepção GustatóriaRESUMO
In the era of universal varicella vaccination, diagnosis of varicella is challenging, especially for breakthrough cases. We sought to clarify the reliability of direct varicella-zoster virus (VZV) loop-mediated isothermal amplification (LAMP) and DermaQuick® VZV using the immunochromatography technique as rapid diagnostic tests for varicella. In addition, the usefulness of saliva as a sample type for direct LAMP was investigated. Among the 46 enrolled patients with suspected VZV infection, 31 patients (67.3%) were positive for the nucleic acid test based on real-time PCR from skin swab samples. Direct LAMP of skin swabs was positive in 29 (63.0%) of 46 patients. DermaQuick® VZV was positive in 25 (54.3%) of 46 patients. VZV DNA was detected in only 48.4% of oral swabs with the direct LAMP method. With real-time polymerase chain reaction (PCR) as the standard for diagnosing varicella, the sensitivity and specificity of DermaQuick® VZV were 80.7% and 100%, respectively. The sensitivity and specificity of direct LAMP from skin swabs were 93.6% and 100%, respectively. The sensitivity and specificity of real-time PCR for DNA extracted from oral swabs were 74.2% and 93.3%, respectively. Thus, oral swab samples are not suitable for breakthrough varicella diagnosis. Although DermaQuick® VZV is considered the most convenient point-of-care test for varicella, its sensitivity and specificity were lower than those of direct VZV LAMP.
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Varicela , Herpes Zoster , Humanos , Herpesvirus Humano 3/genética , Testes de Diagnóstico Rápido , Reprodutibilidade dos Testes , DNA Viral/genéticaRESUMO
BACKGROUND: Little is known about dementia's impact on patterns of diagnosis, treatment, and outcomes in cancer patients. This study aimed to elucidate the differences in cancer staging, treatment, and mortality in older cancer patients with and without preexisting dementia. METHODS: Using cancer registry data and administrative data from 30 hospitals in Japan, this multicentre retrospective cohort study examined patients aged 65-99 years who were newly diagnosed with gastric, colorectal, or lung cancer in 2014-2015. Dementia status (none, mild, and moderate-to-severe) at the time of cancer diagnosis was extracted from clinical summaries in administrative data, and set as the exposure of interest. We constructed multivariable logistic regression models to analyse cancer staging and treatment, and multivariable Cox regression models to analyse three-year survival. RESULTS: Among gastric (n = 6016), colorectal (n = 7257), and lung (n = 4502) cancer patients, 5.1%, 5.8%, and 6.4% had dementia, respectively. Patients with dementia were more likely to receive unstaged and advanced-stage cancer diagnoses; less likely to undergo tumour resection for stage I, II, and III gastric cancer and for stage I and II lung cancer; less likely to receive pharmacotherapy for stage III and IV lung cancer; more likely to undergo tumour resection for all-stage colorectal cancer; and more likely to die within three years of cancer diagnosis. The effects of moderate-to-severe dementia were greater than those of mild dementia, with the exception of tumour resection for colorectal cancer. CONCLUSION: Older cancer patients with preexisting dementia are less likely to receive standard cancer treatment and more likely to experience poorer outcomes. Clinicians should be aware of these risks, and would benefit from standardised guidelines to aid their decision-making in diagnosing and treating these patients.
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Neoplasias Colorretais , Demência , Neoplasias Pulmonares , Idoso , Humanos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Demência/complicações , Demência/diagnóstico , Demência/epidemiologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Estadiamento de Neoplasias , Estudos Retrospectivos , JapãoRESUMO
AIMS/INTRODUCTION: We investigated the association between coexisting diabetes at the time of cancer diagnosis, and the overall survival and incidence of second primary cancer in patients with cancer and receiving drug therapy for diabetes. MATERIALS AND METHODS: We used cancer registry and administrative data of patients diagnosed with cancer at designated cancer care hospitals in Osaka Prefecture between 2010 and 2015. The presence of diabetes was identified from the prescription records of antidiabetic drugs in Diagnosis Procedure Combination System data. After adjusting for patient characteristics, we compared overall survival between patients with cancer with coexisting diabetes and those without coexisting diabetes using the Cox proportional hazards model. In addition, the impact of coexisting diabetes on the risk of developing second primary cancer was evaluated using a competing risk analysis. RESULTS: Of the 131,701 patients with cancer included in the analysis, 6,135 (4.7%) had coexisting diabetes. The 5-year survival rates for patients with and without coexisting diabetes were 56.2% (95% confidence interval 54.8-57.6) and 72.7% (95% confidence interval 72.4-73.0), respectively. Coexisting diabetes was associated with a higher risk of developing second primary cancer (subdistribution hazard ratio 1.23; 95% confidence interval 1.08-1.41). In site-specific analysis, coexisting diabetes was associated with an increased risk for the development of second primary cancer of multiple myeloma, and cancer of the uterus, pancreas and liver. CONCLUSIONS: Coexisting diabetes was associated with a higher mortality and risk of developing second primary cancer in Japanese patients with cancer and on drug therapy for diabetes.
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Diabetes Mellitus , Segunda Neoplasia Primária , Neoplasias , Feminino , Humanos , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Estudos Retrospectivos , Japão/epidemiologia , Neoplasias/complicações , Neoplasias/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
Second primary cancer (SPC) is one of the most life-threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population-based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0-14 years during 1975-2014 and survived 2 months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person-years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan-Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR = 28.0) followed by digestive system (EAR = 15.1), thyroid (EAR = 8.3), and bones and joints (EAR = 7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58-fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5-year and 10-year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk-based long-term follow-up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.
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Sobreviventes de Câncer , Segunda Neoplasia Primária , Neoplasias Cutâneas , Humanos , Criança , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Incidência , Japão , Sistema de Registros , Fatores de RiscoRESUMO
STUDY QUESTION: Does mono- (1PN) and tri-pronuclear (3PN) fertilization recapitulate the morphokinetic changes of normal bi-pronuclear (2PN) fertilization? SUMMARY ANSWER: Abnormal fertilization retraces the overall choreography of normal fertilization but reveals novel morphokinetic phenomena and raises scientifically and clinically relevant questions. WHAT IS KNOWN ALREADY: ART has allowed the extracorporeal observation of early human development. Time-lapse technology (TLT) has revealed the complexity of the morphokinetic changes underpinning fertilization and the importance of this process for the genetic and cellular integrity of the embryo. Abnormal fertilization has remained neglected, despite its relevance to the physiology and pathology of early human development. STUDY DESIGN, SIZE, DURATION: This retrospective study involved TLT observation of normally (2PN, N = 2517) and abnormally (1PN, N = 41; 3PN, N = 27) fertilized oocytes generated in ICSI cycles performed between October 2019 and December 2020. Oocyte retrieval was carried out after clomiphene citrate-based minimal ovarian stimulation. Oocytes of patients with different diagnoses of infertility were included in the analysis, while cases involving cryopreserved gametes or surgically retrieved sperm were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included 1231 couples treated for diverse infertility causes. The fraction of male factor cases was substantial (36.1%). Microinjected oocytes were assessed by a combined TLT-culture system. Oocytes not suitable for TLT assessment, owing to an excess of residual corona cells or inadequate orientation for correct observation, were not analysed. Phenomena relevant to meiotic resumption, pronuclear dynamics, cytoplasmic/cortical modifications, cleavage patterns and embryo quality were annotated and compared between groups. MAIN RESULTS AND THE ROLE OF CHANCE: Extrusion of the second polar body (PBII) was observed in almost all 2PN/1PN (99.9% and 100.0%, respectively) and in a vast majority of 3PN zygotes (92.1%). Rates of PBII fusion with the ooplasm were much higher in 1PN and 3PN zygotes (P < 0.0001 versus 2PN). The cytoplasmic wave was observed not only in 2PN and 3PN but also in 1PN zygotes (positivity rates of 99.8% and 100% and 82.9%, respectively; P < 0.0001). More rarely, 2PN and 1PN zygotes emitted a third polar body (PBIII). The average times of this event were comparable. The presence and position of the cytoplasmic halo were comparable among the three classes of zygotes. In the 1PN group, the single PN was maternally or paternally derived in 17 and 24 zygotes, respectively, while in the vast majority of 3PN zygotes (121/127) the supernumerary PN was of maternal origin. Average times of maternal PN appearance were comparable, while average times of paternal PN appearance were delayed in 3PN zygotes (P = 0.0127). Compared with the control group, the area of the maternal PN was larger in 1PN zygotes, but smaller in 3PN zygotes (P < 0.0001). The paternal PNs displayed the same trend (P < 0.0001), although such values were consistently smaller than maternal PNs. The area of the third PN in the 3PN group was on average more than 50% smaller than those of maternal and paternal PNs. In maternal PNs of 3PN zygotes, nucleolus precursor bodies (NPBs) aligned along the area of PN juxtaposition at a lower rate compared with the 2PN group. The rate of NPB alignment was â¼50% smaller in 1PN zygotes (P = 0.0001). In paternal PNs, the rates of NPB alignment were not statistically different among the three groups. Asynchronous PN breakdown was increased in 3PN compared with 2PN zygotes (P = 0.0026). In 1PN zygotes, a developmental delay was observed starting from the disappearance of the cytoplasmic halo, reaching 9 h at the time of the first cleavage (P < 0.0001). Higher rates of abnormal cleavage patterns and blastomere fragmentation (P < 0.0001) were observed in 1PN compared to 2N and 3PN zygotes. Cleavage progression was increasingly affected after abnormal fertilization, especially 1PN, finally resulting in blastocyst formation rates of 70.2%, 12.2% and 53.5% in 2PN, 1PN and 3PN embryos, respectively (P < 0.0001). Both maternal and paternal ages were higher in cases involving 3PN fertilization. LIMITATIONS, REASONS FOR CAUTION: The study data were obtained from ICSI, but not standard IVF, treatments carried out in a single centre. The study findings therefore require independent verification. WIDER IMPLICATIONS OF THE FINDINGS: This study reports the first detailed morphokinetic map of human abnormal fertilization. Collectively, this evidence prompts new scientific hypotheses and raises clinical questions relevant to the aetiology and the treatment of abnormal fertilization. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the participating institutions. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
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Infertilidade , Zigoto , Clomifeno , Fertilização/fisiologia , Fertilização in vitro/métodos , Humanos , Infertilidade/terapia , Masculino , Nitrobenzenos , Estudos Retrospectivos , SêmenRESUMO
INTRODUCTION: The burden of stomach cancer remains high, particularly among Asian countries. Although Japan is known to achieve high survival from stomach cancer, little is known regarding the survival trends for recent years and survival by subsite and stage. We report age-standardised 1-, 3-, 5- and 10-year net survival for patients diagnosed with stomach cancer in Osaka, Japan. METHODS: We analysed patients diagnosed with primary stomach cancer and registered in the population-based cancer registry in Osaka Prefecture between 2001 and 2014. We used the non-parametric Pohar Perme method to derive net survival for each year. Both cohort and period approaches were used. Age was standardised using weights of the external population of the International Cancer Survival Standard. Multiple imputation was applied to handle missing information on subsite and stage before estimating age-standardised net survival by subsite (cardia and non-cardia) and stage (localised, regional and distant metastasis). We then examined general trends in the cohort-based survival estimates, as well as by subsite and stage, using linear regression. RESULTS: A total of 97,276 patients were included in the analysis. Age-standardised net survival improved steadily (mean annual absolute change ≥1.2%). Net survival for both subsites improved, but cardia cancer showed 7-23% lower survival than non-cardia cancer throughout the study period. Five-year net survival remained high (≥80%) in the localised stage from the beginning of this study. Net survival increased steeply (≥1.4% per year) in the regional stage. Although 1-year net survival increased by 14% in the distant stage, 5-year and 10-year net survival remained below 10%. CONCLUSION: Age-standardised net survival for stomach cancer in Japan improved during the study period owing to an increase in the number of patients with localised stage at diagnosis and improved treatment. Monitoring both short- and long-term survival should be continued as management of stomach cancer progresses.
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Neoplasias Gástricas , Ásia , Estudos de Coortes , Gerenciamento de Dados , Humanos , Japão/epidemiologia , Sistema de Registros , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: An increasing number of cancer survivors have developed multiple primaries. This study aims to describe the incidence and risk patterns of metachronous second primary cancers (SPCs) in Osaka, Japan. METHODS: Data were obtained from the Osaka Cancer Registry, a population-based database of all cancers diagnosed in Osaka. The study subjects were individuals who were first diagnosed with invasive cancers in 16 major cancer sites during 2000-2014, aged 15-79 years, survived at least 3 months, and were followed up for 10 years. We measured incidence rates, cumulative risks, and standardized incidence ratios (SIRs: with the Osaka general population as the referent) of developing SPCs during 3 months to 10 years after the first diagnosis. RESULTS: During 2000-2015, among 418,791 cancer survivors, 24,368 (5.8%) developed SPCs within 10 years of first diagnosis. Males had higher incidence rates than females except among young-onset survivors (aged 15-39 years). 10-year cumulative risks among survivors aged 70-79 years (the most dominant age group) were 24.0% (male) and 11.8% (female). 10-year SIRs were 1.38 (95% CI, 1.36-1.40; male) and 1.44 (95% CI, 1.41-1.48; female) with higher estimates among younger survivors in both sexes. Strong bidirectional associations were observed between oral/pharyngeal, esophageal, and laryngeal cancers. Survivors of any smoking-related cancers had elevated SIRs of developing smoking-related SPCs. Similar results were observed for alcohol-related cancers. CONCLUSIONS: Cancer survivors are at excess risk of developing SPCs compared to the general population. Continued surveillance is warranted to inform survivorship care through risk-based long-term care planning and lifestyle-changing efforts to prevent new cancers.
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Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/mortalidade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Adulto JovemRESUMO
The expression and function of some xenobiotic transporters varies according to the time of day, causing the dosing time-dependent changes in drug disposition and toxicity. Multidrug resistance-associated protein-4 (MRP4), an ATP-binding cassette (ABC) efflux transporter encoded by the Abcc4 gene, is highly expressed in bone marrow cells (BMCs) and protects them against xenobiotics, including chemotherapeutic drugs. In this study, we demonstrated that MRP4 was responsible for the extrusion of oxaliplatin (L-OHP), a platinum (Pt)-based chemotherapeutic drug, from BMCs of mice, and that the efflux transporter expression exhibited significant diurnal variation. Therefore, we investigated the relevance of the diurnal expression of MRP4 in BMCs for L-OHP-induced myelotoxicity in mice maintained under standardized light/dark cycle conditions. After intravenous injection of L-OHP, the Pt content in BMCs varied according to the injection time. Lower Pt accumulation in BMCs was detected in mice after injection of L-OHP at the mid-dark phase, during which the expression levels of MRP4 increased. Consistent with these observations, the myelotoxic effects of L-OHP were attenuated when mice were injected with L-OHP during the dark phase. This dosing schedule also alleviated the L-OHP-induced reduction of the peripheral white blood cell count. The present results suggest that the myelotoxicity of L-OHP is attenuated by optimizing the dosing schedule. Diurnal expression of MRP4 in BMCs is associated with the dosing time-dependent changes in L-OHP-induced myelotoxicity.
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Ritmo Circadiano/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos/farmacologia , Células da Medula Óssea/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Compostos Organoplatínicos/farmacologia , Oxaliplatina/farmacologiaRESUMO
PURPOSE: Phrenic nerve injury (PNI) is one of the important complications during cryoballoon (CB) ablation. Recording diaphragmatic compound motor action potentials (CMAPs) during CB ablation can predict PNI. CMAP monitoring may be inaccurate when CMAP amplitudes are low. We examined the effect of positioning an electrocardiography (ECG) electrode at the dorsal side. METHODS: We retrospectively analyzed the cases of 197 consecutive patients who underwent CB ablation for pulmonary vein isolation (PVI) (April 2016 to December 2018) at our institution. CMAP amplitudes were monitored using two recording methods just before cryoapplication. (a) Conventional method: right-arm ECG electrode positioned 5 cm above the xiphoid on the ventral side; left-arm ECG electrode positioned along the costal margin. (b) Our original method: right-arm electrode positioned 5 cm above the xiphoid on the dorsal side; left-arm electrode positioned along the costal margin. RESULTS: The CMAP amplitude during right phrenic nerve pacing was significantly higher at the dorsal side than the ventral side (0.80 ± 0.31 mV vs 0.66 ± 0.29 mV, P < .01). Similarly, the CMAP amplitude during left phrenic nerve pacing was significantly higher at the dorsal side than the ventral side (0.92 ± 0.39 mV, 0.73 ± 0.37 mV, P < .01). PNI occurred in six patients (3.0%); three patients experienced transient PNI, another three patients experienced persistent PNI, and none developed permanent PNI. CONCLUSIONS: CMAP amplitudes were significantly high at the dorsal side compared to the ventral side. Monitoring phrenic nerve function using an ECG electrode at the dorsal side is a simple and easy procedure.
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An ankle-foot orthosis is often prescribed in the rehabilitation of patients with neurological motor disorders such as hemiparesis. However, walking with a unilateral ankle-foot orthosis may not be effectively achieved just by trying to reproduce normal intact walking with a symmetrical gait pattern. Understanding skills to facilitate walking gait with a unilateral ankle-foot orthosis has implications for better rehabilitative interventions to help restore walking ability in patients with stroke. We, therefore, analyzed the kinematics and ground reaction forces of walking with and without an ankle-foot orthosis in healthy subjects to infer the possible skills to facilitate walking gait with a unilateral ankle-foot orthosis. Adult male participants were asked to walk with and without an ankle-foot orthosis across two force platforms set in a wooden walkway, and body kinematics and ground reaction force profiles in the sagittal plane were simultaneously recorded. We found that the forward tilting angle of the trunk at the time of toe-off of the leg with the ankle-foot orthosis was significantly larger than that of the leg without the ankle-foot orthosis, to adaptively compensate for the loss of ankle joint mobility due to the unilateral ankle-foot orthosis. Furthermore, the peak vertical ground reaction force at heel-contact was significantly larger in the leg without the ankle-foot orthosis than in the leg with the ankle-foot orthosis owing to the fact that the stance phase duration of the leg with the ankle-foot orthosis was relatively shorter. Such information may potentially be applied to facilitate walking training in stroke patients wearing a unilateral ankle-foot orthosis.
Assuntos
Tornozelo , Órtoses do Pé , Voluntários Saudáveis , Fenômenos Mecânicos , Caminhada , Adulto , Fenômenos Biomecânicos , Humanos , MasculinoRESUMO
Amylose content is an important determinant of rice quality. Accurate non-destructive determination of amylose content remains a primary challenge for the rice industry. Here, we analysed the accuracy of three models for the non-destructive determination of amylose content. The models were developed by combining near-infrared spectra, colour, and physicochemical information relative to 832 brown rice samples from ten varieties produced between 2009 and 2017 in various regions of Hokkaido, Japan. Models describing low and ordinary amylose varieties were developed individually, merged, and validated using production year samples (2016-2017) different from the calibration set (2009-2015). The resulting accuracy was suitable for industrial application. With standard error of predictionâ¯=â¯0.70% and ratio of performance deviationâ¯=â¯3.56, the combination of near-infrared spectra and physicochemical information produced the most robust model, enabling more precise rice quality screening at grain elevators.
Assuntos
Amilose/análise , Oryza/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Amilose/normas , Calibragem , Cor , Qualidade dos Alimentos , Espectroscopia de Luz Próxima ao Infravermelho/normasRESUMO
A domino synthesis of 2,3-dialkylidenetetrahydrofurans based on Prins-type cyclization of 3,5-diynols and aldehydes is described. In the present reaction, skeletal reorganization of the Prins-cyclized intermediates proceeds via a ring-opening reaction followed by intramolecular (hemi)acetalization of the resulting 4-en-1-yn-3-ones. Furthermore, a representative product undergoes a Diels-Alder reaction with dimethyl acetylenedicarboxylate (DMAD) to afford a highly substituted 2,3-dihydrobenzofuran.
RESUMO
A number of diverse cell-surface proteins are anchored to the cytoskeleton via scaffold proteins. Na+/H+ exchanger regulatory factor-1 (NHERF1), encoded by the Slc9a3r1 gene, functions as a scaffold protein, which is implicated in the regulation of membrane expression of various cell-surface proteins. Here, we demonstrate that the circadian clock component PERIOD2 (PER2) modulates transcription of the mouse Slc9a3r1 gene, generating diurnal accumulation of NHERF1 in the mouse liver. Basal expression of Slc9a3r1 was dependent on transcriptional activation by p65/p50. PER2 bound to p65 protein and prevented p65/p50-mediated transactivation of Slc9a3r1. The time-dependent interaction between PER2 and p65 underlay diurnal oscillation in the hepatic expression of Slc9a3r1/NHERF1. The results of immunoprecipitation experiments and liquid chromatography-mass spectrometry analysis of mouse liver revealed that NHERF1 time-dependently interacted with fatty acid transport protein-5 (FATP5). Temporary accumulation of NHERF1 protein stabilized plasmalemmal localization of FATP5, thereby enhancing hepatic uptake of fatty acids at certain times of the day. Our results suggest an unacknowledged role for PER2 in regulating the diurnal expression of NHERF1 in mouse liver. This machinery also contributed to diurnal changes in the ability of hepatic cells to uptake fatty acids.