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Taku Yamada,1 Taketomo Kikuchi,1 Sachiko Nagasu,2,3 Kayoko Hashimoto,4 Eri Furukawa,4 Hirokazu Matsumoto,1 Kazuki Tsutsumi,1 Toshimitsu Tanaka,2,5 Miho Kugishima,3 Takumi Kawaguchi,5 Fumihiko Fujita,3 Kyouko Higuchi,1 Keisuke Miwa2 1Department of Pharmacy, Kurume University Hospital, Kurume, Fukuoka, Japan; 2Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kurume, Fukuoka, Japan; 3Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan; 4Department of Nursing, Kurume University Hospital, Kurume, Fukuoka, Japan; 5Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, JapanCorrespondence: Keisuke Miwa, Multidisciplinary Treatment Cancer Center, Kurume University Hospital, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan, Tel +81-942-31-7566, Fax +81-942-34-0709, Email miwa_keisuke@kurume-u.ac.jpPurpose: Elastomeric infusion pumps are widely used in colorectal cancer chemotherapy. However, no studies to date have investigated patient preferences regarding different infusion pump types.Patients and Methods: Twenty patients with unresectable colorectal cancer undergoing chemotherapy were initially treated with a portable hard-shelled continuous infusion pump, followed by a soft-shelled continuous infusion pump. The respondents used a numerical rating scale (0– 10) to rate their comfort when using each pump, their ease of carrying it, the pump size and shape, its weight, their ease of reading its memory, and their overall satisfaction with it. They were then asked to determine which pump they would ultimately prefer.Results: In terms of comfort, significantly higher user satisfaction was reported for the soft-shelled pump during the daytime and when going out (P < 0.001, P < 0.001, respectively). For pump portability, size, shape, and weight, the soft-shelled type also outperformed the hard-shelled one (P < 0.001, P=0.0011, P < 0.001, respectively). However, the hard-shelled pump scored significantly better in terms of ease of viewing memory (P < 0.001). Overall satisfaction was significantly higher for the soft-shelled pump than the hard-shelled type (P=0.0095). Finally, 13 patients (65%) indicated that they would prefer a soft-shelled pump for their next treatment, while only one patient (5%) preferred a hard-shelled alternative. A preference for soft-shelled pump was observed, particularly in female patients and those with a body mass index of < 22 kg/m2.Conclusion: The selection of portable elastomeric infusion pumps should consider the preferences of patients with colorectal cancer, as these devices have the potential to enhance their quality of life.Keywords: colorectal cancer, chemotherapy, infusion pump, elastomeric infusion pump, portable infusion pump, patient preference

BACKGROUND: Burkholderia cepacia, a gram-negative pathogen, has been a known cause of hospital outbreaks because of a contaminated common source such as multidose medications. We describe an outbreak with Burkholderia cepacia infection in 2 major hospitals affiliated to the National Guard, related to an intrinsic contamination of a locally manufactured, multidose Albuterol nebulization solution (Tabouk Pharmaceutical Company, Tabouk, Saudi Arabia) and we report the interventions taken to interrupt this outbreak. METHODS: During the outbreak period between May 2003 and March 2004, a combined prospective surveillance and a retrospective chart and microbiologic data review were conducted in 4 major hospitals affiliated to the National Guard. Microbiologic cultures were also performed on environmental objects of concern, as well as certain medications. In addition, a questionnaire was distributed to the respiratory therapy staff to evaluate the process of administering respiratory medications and their adherence to sound infection control practices. RESULTS: An intrinsic contamination of a locally manufactured brand of multidose Albuterol nebulization with B cepacia was identified. Two of the 4 hospitals were found to be involved: hospital A a 700-bed tertiary care center and Hospital B a 150-bed hospital. A total of 2121 patients were exposed to Albuterol nebulization as inpatients at hospital A and 318 as outpatients. For hospital B, a total of 283 inpatients and 34 outpatients were exposed to the Albuterol nebulization. Forty and 12 patients, from hospital A and hospital B, respectively, were found to have at least 1 positive culture for B cepacia. From hospital A, most samples were respiratory, and, from hospital B, most were from blood. Molecular typing of 34 available isolates showed that 23 cases were of a single strain of B cepacia that matched the strain isolated from the 3 different batches of multidose Albuterol nebulization. Three culture-positive patients never received Albuterol nebulization of that brand but were in the same room of a patient who had been receiving the medication. CONCLUSIONS: We identified a large outbreak of B cepacia in 2 major hospitals affiliated with the National Guard, linked to an intrinsic contamination of a multidose Albuterol nebulization solution. During the period of prospective surveillance, only a few cases were identified as a result of nosocomial transmission. Immediate notification of the Ministry of Health and withdrawal of the medication and revisiting the respiratory therapy practices were necessary to halt this outbreak. [ABSTRACT FROM AUTHOR]

Introduction: The neurobiology of reinforcement has been subject to intense scientific study in recent years. In contrast, relatively little attention has been paid to environmental and cultural influences. Objective: To compare the sensitivity of normally developing Japanese and New Zealand school children to changes in reward frequency. Method: We are currently collecting data from Japanese elementary school children using a signal detection task in which correct identification of one of two possible stimuli is reinforced more frequently (4:1). The response alternative associated with the higher rate of reinforcement changes twice during the task, each time after the delivery of 20 reinforcers. Results: Existing data from NZ children demonstrates response bias (preference for the better alternative) tracks the changes in response alternative offering the higher rate of reinforcement. We hypothesize the performance of Japanese children on the same task will demonstrate similar sensitivity to changing reinforcement contingencies. Discussion and conclusions: Sensitivity to reinforcement contingencies is assumed to be largely free of cultural influences. Findings from the current study will indicate if this assumption holds true for Japanese children. [ABSTRACT FROM AUTHOR]

Introduction and objective: Attention deficit hyperactivity disorder (ADHD) affects children and adults across cultures. If ADHD is biological in origin the disorder should be largely free of environmental variances. However, cultural traditions and practices influence how the disorder is perceived, assessed, expressed and treated. There may also be cultural differences in the expectations of reward and punishment influencing behavior and ADHD symptoms. Few studies have been conducted using the same experimental paradigms across multiple countries. Method: We are currently examining sensitivity to reinforcement in children with ADHD in Japan, Brazil and New Zealand. Results: Technical and theoretical training in psychology and psychiatry varies widely across the participating countries. Availability of equivalent appropriate assessment tools is limited in Japan and Brazil. Limited professional expertise/understanding contributes to increased stigma. We have observed differences in use and perception of positive reinforcement in Japan. Discussion and conclusions: We believe that cross-cultural research can contribute significantly to the advancement of knowledge in the assessment and treatment of ADHD. It may also provide important insight into the neurobiological and environmental contributors to ADHD. [ABSTRACT FROM AUTHOR]

Stent implantation in the rabbit aorta has been shown to increase vessel wall compliance at the inflow to the stent, but it is uncertain whether similar effects might be seen in the coronary arteries of humans and whether this would have any significant clinical consequences. First, we measured vessel compliance (systolic lumen area--diastolic lumen area/pulse pressure) before, immediately after, and at the 6-month follow-up visit at a site 5 mm upstream of the proximal edge of an implanted coronary stent in patients undergoing coronary intervention using motorized pull-back intravascular ultrasound recordings. Compliance in the upstream segment increased significantly immediately after stenting (before 7.13 +/- 1.49 vs after 10.73 +/- 1.36 mm2/mm Hg, p = 0.03), an effect that was unchanged at 6 months of follow-up (11.84 +/- 2.11 mm2/mm Hg, p = 0.08 vs before stenting). Second, we examined the site of plaque rupture in all patients presenting with an acute coronary syndrome in whom the culprit lesion was in a vessel that had had a stent implanted >12 months previously (n = 31). Plaque rupture was statistically more likely at the inflow to the stent (n = 22) than at other sites within the culprit vessel (n = 9, p <0.01). We conclude that stenting causes an increase in vessel compliance immediately proximal to the stent, and that when a vessel has been previously stented, plaque rupture is most likely to occur at the stent inflow site. [ABSTRACT FROM AUTHOR]

Study aims and objectives. This study aims to evaluate the accuracy of medical knowledge in the most advanced LLMs (GPT-4o, GPT-4, Gemini 1.5 Pro, and Claude 3 Opus) as of 2024. It is the first to evaluate these LLMs using a non-English medical licensing exam. The insights from this study will guide educators, policymakers, and technical experts in the effective use of AI in medical education and clinical diagnosis., Method: Authors inputted 790 questions from Japanese National Medical Examination into the chat windows of the LLMs to obtain responses. Two authors independently assessed the correctness. Authors analyzed the overall accuracy rates of the LLMs and compared their performance on image and non-image questions, questions of varying difficulty levels, general and clinical questions, and questions from different medical specialties. Additionally, authors examined the correlation between the number of publications and LLMs' performance in different medical specialties., Results: GPT-4o achieved highest accuracy rate of 89.2% and outperformed the other LLMs in overall performance and each specific category. All four LLMs performed better on non-image questions than image questions, with a 10% accuracy gap. They also performed better on easy questions compared to normal and difficult ones. GPT-4o achieved a 95.0% accuracy rate on easy questions, marking it as an effective knowledge source for medical education. Four LLMs performed worst on "Gastroenterology and Hepatology" specialty. There was a positive correlation between the number of publications and LLM performance in different specialties., Conclusions: GPT-4o achieved an overall accuracy rate close to 90%, with 95.0% on easy questions, significantly outperforming the other LLMs. This indicates GPT-4o's potential as a knowledge source for easy questions. Image-based questions and question difficulty significantly impact LLM accuracy. "Gastroenterology and Hepatology" is the specialty with the lowest performance. The LLMs' performance across medical specialties correlates positively with the number of related publications., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: This study quantitatively evaluated the understandability and actionability of webpages for patients undergoing hemodialysis (HD)., Methods: In June 2022, we searched on Google and Yahoo Japan using the top five keywords associated with end-stage kidney disease and HD to identify relevant materials. Subsequently, we used the Japanese version of the Patient Education Materials Assessment Tool to assess the understandability and actionability of these materials, rating them on a scale from 0% to 100%. The threshold was set at 70%., Results: Among the included 194 materials, the overall understandability was 66.7%, and the actionability was 33.3%. Only 38.7% and 16.5% of the materials were deemed understandable and actionable, respectively. Challenges included the need for plain language and concise summaries to improve understandability, along with the use of effective visual aids for actionability., Conclusion: This study suggests that existing webpages on HD are not presented in a manner that patients can utilize., (© 2024 The Author(s). Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Accurate estimation of tumor mutational burden (TMB) as a predictor of responsiveness to immune checkpoint inhibitors in gene panel assays requires an adequate panel size. The current calculations of TMB only consider coding regions, while most of gene panel assays interrogate non-coding regions. Leveraging the non-coding regions is a potential solution to address this panel size limitation. However, the impact of including non-coding regions on the accuracy of TMB estimates remains unclear. This study investigated the validity of leveraging non-coding regions to supplement panel size using the OncoGuide NCC Oncopanel System (NOP). The aim of this study was to evaluate test performance against orthogonal assays and the association with responsiveness to immune checkpoint inhibitors was not included in the evaluation. We compared TMB status and values between TMB calculated only from coding regions (NOP-coding) and from both coding and non-coding regions (NOP-overall) using whole exome sequencing (WES) and FoundationOne®CDx (F1CDx) assay. Our findings revealed that NOP-overall significantly improved the overall percent agreement (OPA) with TMB status compared with NOP-coding for both WES (OPA: 96.7% vs. 73.3%, n = 30) and F1CDx (OPA: 90.0% vs. 73.3%). Additionally, the mean difference in TMB values compared with WES was lower for NOP-overall (3.55 [95% CI: 0.98-6.13]) than for NOP-coding (6.22 [95% CI: 3.73-8.70]). These results exemplify the utility of incorporating non-coding regions to maintain accurate TMB estimates in small-sized panels., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: Chronic obstructive pulmonary disease (COPD) is a risk factor for pneumonia following esophagectomy. This study aimed to investigate the efficacy of perioperative inhaled tiotropium in patients with COPD undergoing esophagectomy., Methods: This open-label, randomized controlled trial randomly assigned 32 patients with COPD undergoing esophagectomy to conventional management or addition of tiotropium inhalation. The intervention group received tiotropium from two weeks before esophagectomy until the final evaluation one month after esophagectomy. The primary outcome was the incidence of pneumonia within 30 postoperative days. We also assessed the changes and the percentages from baseline in pulmonary function and walking distance of the incremental shuttle walking test to just before esophagectomy and final evaluation., Results: Enrolled patients were randomly assigned to the control group (n = 18) and the intervention group (n = 14). Pneumonia was recorded in 4 (28.6%) and 5 (27.8%) patients in the intervention and control groups, respectively (risk difference: 0.8%, 95% confidence interval: - 30.6 to 32.2). The intervention group demonstrated a significant improvement in pulmonary function and walking distance preoperatively. Further, the pulmonary function test was significantly better preoperatively in the intervention group than in the control group. Postoperatively, pulmonary function deterioration was more significant in the control group than in the intervention group., Conclusions: Preoperative tiotropium inhalation significantly improved pulmonary function and exercise tolerance in patients with COPD undergoing esophagectomy. The perioperative tiotropium did not reduce pneumonia after esophagectomy, but it may contribute to patient recovery by reducing postoperative pulmonary function deterioration., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background: A stronger preference for immediate rewards has been reported in individuals with ADHD and other disorders. However, the consistency of the associations between this preference and psychiatric conditions as well as functional outcomes have been questioned. Research on its association with longitudinal outcomes is scarce., Methods: The current study used data on a choice delay task (CDT) from a school-based cohort of Brazilian children with those at higher risk for psychiatric disorders over-sampled ( n  = 1917). The sample included typically developing children ( n  = 1379), those with ADHD ( n  = 213), and other disorders. The frequency of the trials where children chose a larger later reward versus a smaller sooner reward was compared for those with ADHD and typically developing children. Cross-sectionally and longitudinally, the study also evaluated whether children's preference for larger delayed rewards at baseline predicted the presence of psychiatric disorders and functional life outcomes (academic performance, alcohol use, early pregnancy, criminal conviction, BMI)., Results: Children with ADHD and their typically developing peers performed similarly on the CDT. Their baseline task performance was not related to psychiatric conditions or life outcomes., Conclusions: The current results raise questions regarding the use of the CDT with diverse populations and whether a preference for larger delayed rewards is predictive of positive long-term outcomes as widely assumed., Competing Interests: The authors have declared they have no competing or potential conflicts of interest., (© 2024 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

This study aimed to determine the applicability of a tail-attached device in monitoring animal-based indicators (ABI) associated with changes in environmental conditions in calves through investigating the relationship between sensor-derived ABI and the temperature-humidity index (THI). Furthermore, to identify effective ABI indicative of heat stress status, sensor-derived ABI of calves under differing heat stress levels based on rectal temperature (RT) were compared. The tail-attached device, which is capable of measuring skin temperature (ST), activity intensity, and roll angle along the longitudinal axis of the tail at 3-min intervals, was attached to 99 preweaning female Holstein calves for an average of 4 wk (26.4 ± 6.8 d). After selecting data from mild to hot days (daily average THI of ≥55), physiological (daily maximum tail ST) and behavioral (daily average activity intensity, daily total lying time, and daily total body position change) ABI were computed, and their relationship with the daily average THI was determined using piecewise regression analysis. Additionally, during the hot season, RT of 20 randomly selected tested calves were measured thrice a week (every 2.4 ± 0.5 d), and a comparison was conducted between the ABI of calves with normal RT (<39.5°C) and those with high RT (≥39.5°C), utilizing data from days characterized by potential heat stress (daily average THI of ≥75). During the study, ambient temperature (°C) and relative humidity (%) were recorded every 10 min using an automatic digital data logger, from which the daily average THI was calculated. Piecewise regression analysis identified THI breakpoints of 73.6 for tail ST, 79.1 for average activity intensity, 72.3 for lying time, and 79.1 for position change. All the tested ABI tended to increase as THI increased, and this trend was pronounced in tail ST, activity intensity, and position change after the breakpoint. These 3 ABI were higher in calves with high RT compared with those with normal RT, whereas lying time shared similar values between the RT groups. Overall, these findings suggest that the tail-attached device can simultaneously monitor both physiological and behavioral ABI in calves, and among the ABI, tail ST, activity intensity, and position change are the effective ABI indicative of heat stress status., (© 2024.)

Introduction: One of the purported underlying causal mechanisms of attention deficit hyperactivity disorder (ADHD) is altered motivational processes. Questionnaires have been used to identify the characteristics of reward and punishment sensitivity in individuals with ADHD. However, these questionnaires were initially developed to measure individual traits related to anxiety (inhibitory) and impulsivity (approach) tendencies or differences in pleasure-seeking. These reward and punishment sensitivity questionnaires are useful but might not capture all relevant aspects of altered motivational processes in ADHD. The proposed scoping review aims to: (1) examine which aspects of hypothesised altered reward and punishment sensitivity correspond to constructs measured by existing questionnaires, (2) characterise the relationships between ADHD symptomatology and reward and punishment sensitivity as measured by existing questionnaires and (3) evaluate the consistency between the altered reward and punishment sensitivity as measured by existing questionnaires and experimental task performance., Methods and Analysis: Reporting of the scoping review results will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and the Joanna Briggs Methodology for Scoping Reviews. Published English-language literature was searched in three electronic databases (PubMed, Web of Science, APA PsycINFO) on 16 November 2023, with no restriction on the year of publication. Two researchers independently screened all identified titles/abstracts before proceeding to full-text review and additional handsearching of relevant studies. A narrative review and conclusions will be presented together with tables summarising the articles reviewed and the results organised by the three aims., Ethics and Dissemination: This study reviews existing publications with ethical approval in place. Therefore, ethical approval is not required. Review results will be disseminated through academic conferences and peer-reviewed manuscripts. Scoping review results will also inform future research to measure and identify altered motivational processes in ADHD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previous studies have not fully determined whether online education materials on chronic kidney disease (CKD) for Japanese patients are easy to understand and help change their behavior. Therefore, this study quantitatively assessed the understandability and actionability of online CKD education materials., Methods: In September 2021, we searched Google and Yahoo Japan using the keywords "kidney," "kidney disease," "CKD," "chronic kidney disease," and "renal failure" to identify 538 webpages. We used the Japanese version of the Patient Education Materials Assessment Tool (PEMAT), ranging from 0 to 100%, to evaluate the understandability and actionability of webpages. We set the cutoff point to 70%., Results: Of the 186 materials included, the overall understandability and actionability were 61.5% (± 16.3%) and 38.7% (± 30.6%), respectively. The materials were highly technical in their terminology and lacked clear and concise charts and illustrations to encourage action. Compared to lifestyle modification materials on CKD overview, symptoms/signs, examination, and treatment scored significantly lower on the PEMAT. In addition, the materials produced by medical institutions and academic organizations scored significantly lower than those produced by for-profit companies., Conclusion: Medical institutions and academic organizations are encouraged to use plain language and to attach explanations of medical terms when preparing materials for patients. They are also expected to improve visual aids to promote healthy behaviors., (© 2023. The Author(s).)

Aim: It remains undetermined whether online education videos for Japanese patients with chronic kidney disease (CKD) are easy to understand and allow adoption of behavioural changes. This study quantitatively assessed the understandability and applicability of online education videos for patients with CKD., Methods: In September 2021, we identified 200 videos on YouTube using the Japanese translations of the keywords 'kidney,' 'kidney disease,' 'CKD,' and 'chronic kidney disease.' We used the Japanese version of the Patient Education Materials Assessment Tool to evaluate the understandability and usability of webpages on a scale of 0% to 100%. The cut-off was set at 70%., Results: A total of 54 videos were evaluated. The overall understandability and actionability of the materials were 57.6 (SD = 22.6) and 53.7 (SD = 33.4), respectively. Approximately 70% and 60% of the materials were considered insufficiently understandable and actionable, respectively. Most videos lacked a summary and had difficulty in using only everyday language. Most videos included at least one action for the audience to take. However, many failed to break down the action into sequential steps. They also lack visual aids to encourage the audience to take action., Conclusion: Our results suggest that current information on pre-dialysis chronic kidney disease was not presented in a manner that can be applied by laypeople., (© 2023 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Objective: In Japan, educational materials on the home care of coronavirus disease 2019 (COVID-19) were developed owing to limited access to medical care during the pandemic. This study quantitatively evaluated the understandability, actionability, natural flow, and readability of 87 materials published by local governments in Japan for patients with COVID-19. Their understandability and actionability were rated using the Japanese version of the Patient Education Material Evaluation Tool for Printed Materials (PEMAT-P). Natural flow and readability were rated using Global Quality Score (GQS) and jReadability, respectively., Results: Of the 87 materials, 55 (62.1%) were understandable and 33 (37.9%) were actionable according to the PEMAT-P. Regarding understandability, the materials used medical terms without providing definitions and lacked summaries. Regarding actionability, the materials did not demonstrate explicit steps or utilize visual aids to help the readers take action. The mean (SD) of GQS was 3.44 (0.98), indicating a moderate level of naturalness and comprehensiveness of the materials. The mean (SD) score for readability was 2.4 (0.6), indicating a "lower advanced" level. However, challenges regarding the materials' plain language remained, such as defining medical terms, summarizing the content for understandability, and using charts and tables that encourage patients to act., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) is a debilitating condition affecting children and their families worldwide. Behavioral parent training is a recommended form of empirically supported non-pharmacological intervention for young children with mild to moderate ADHD. However, access to such treatment is limited in many countries. Here we identify the treatment needs of Brazilian families with children demonstrating symptoms of ADHD, and the barriers families face in accessing behavioral treatment., Methods: A qualitative needs assessment was undertaken with parents ( n = 23), educators ( n = 15), and healthcare providers ( n = 16). Semi-structured telephone interviews were conducted, and common themes were identified through inductive coding of participants' responses., Results: Participants reported a lack of accessible behavioral treatment, and delays in accessing treatment when available. The majority of parents had not received behavioral parent training, despite it being a recommended form of treatment. Parents, educators and healthcare providers strongly endorsed a need for practical tools to manage the behavior of children with ADHD., Conclusion: Existing services might not meet the needs of children with ADHD and their families in Brazil. Easily accessed behavioral parent training programs are recommended to address the identified treatment gap for Brazilian children with ADHD and their families., Competing Interests: PM has received research grant and speaker honoraria from Takeda in the last 3 years. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bado, da Costa, Bernardes, Tripp, Mattos and Furukawa.)

Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) is generally considered to be a high-risk subtype. We retrospectively analyzed the clinical outcomes of adult patients diagnosed with ETP-ALL or other T-cell ALL (non-ETP T-ALL). The subjects were 82 patients (ETP-ALL: n = 18, non-ETP T-ALL: n = 64) for whom relevant immunophenotype data needed for classification were available. ETP-ALL patients were older (median age, 50.5 vs. 33.5 years, P = 0.042) and had less mediastinal involvement (27.8 vs. 73.4%, P < 0.001). The rate of complete remission (CR) with the first induction therapy was significantly lower in the ETP group (33.3 vs. 64.0%, P = 0.03), but the CR rate within 2 cycles of chemotherapy did not differ significantly (61.1 vs. 76.6%, P = 0.232). The 3-year overall survival (OS) rate was also similar in both groups (43.2 vs. 45.8%, P = 0.992). The ETP phenotype had no impact on survival in the transplant group or the non-transplant group. A multivariate analysis identified the male sex as a poor prognostic factor (HR: 4.43, P < 0.01), but not the immunophenotype of ETP. The prognosis for adult patients with ETP-ALL was comparable to that of non-ETP T-ALL patients. However, further studies aimed at improving the remission rate for ETP-ALL are needed., (© 2023. Japanese Society of Hematology.)

The present study investigated the applicability of a calving prediction model based on supervised machine learning of ruminal temperature (RT) data in dairy cows. The existence of cow subgroups for prepartum RT changes was also examined, and the predictive performance of the model was compared among these subgroups. RT data were collected from 24 Holstein cows at 10 min intervals using an RT sensor system. The average hourly RT was calculated and data were expressed as residual RTs (rRT = actual RT - mean RT for the same time on the previous three days). The mean rRT decreased beginning at approximately 48 h before calving to a low of -0.5°C at 5 h before calving. However, two cow subgroups were identified: cows with a late and small rRT decrease (Cluster 1, n = 9) and those with an early and large rRT decrease (Cluster 2, n = 15). A calving prediction model was developed using five features extracted from the sensor data (indicative of prepartum rRT changes) through a support vector machine. Cross-validation showed that calving within 24 h was predicted with a sensitivity of 87.5% (21/24) and precision of 77.8% (21/27). A significant difference in sensitivity was observed between Clusters 1 and 2 (66.7 vs. 100%, respectively), while none was observed for precision. Therefore, the model based on RT data with supervised machine learning has the potential to efficiently predict calving, although improvements for specific cow subgroups are required.

Although establishment and maintenance of mitochondria are essential for the production of massive amounts of heme in erythroblasts, mitochondria must be degraded upon terminal differentiation to red blood cells (RBCs), thus creating a biphasic regulatory process. Previously, we reported that iron deficiency in mice promotes mitochondrial retention in RBCs, suggesting that a proper amount of iron and/or heme is necessary for the degradation of mitochondria during erythroblast maturation. Because the transcription factor GATA1 regulates autophagy in erythroid cells, which involves mitochondrial clearance (mitophagy), we investigated the relationship between iron or heme and mitophagy by analyzing the expression of genes related to GATA1 and autophagy and the impact of iron or heme restriction on the amount of mitochondria. We found that heme promotes the expression of GATA1-regulated mitophagy-related genes and the induction of mitophagy. GATA1 might induce the expression of the autophagy-related genes Atg4d and Stk11 for mitophagy through a heme-dependent mechanism in murine erythroleukemia (MEL) cells and a genetic rescue system with G1E-ER-GATA1 erythroblast cells derived from Gata1-null murine embryonic stem cells. These results provide evidence for a biphasic mechanism in which mitochondria are essential for heme generation, and the heme generated during differentiation promotes mitophagy and mitochondrial disposal. This mechanism provides a molecular framework for understanding this fundamentally important cell biological process., (Copyright © 2022 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Altered motivational processing is purported to contribute to ADHD symptoms. A stronger preference for immediate over delayed reward is well documented in ADHD. However, little attention has been paid to children's capacity to withhold responding until a "better" reward becomes available, and their actions while waiting. Using a novel computer task, we examine the ability of children with and without ADHD to wait to collect a large reward in the presence of a small available reward. The effects of a reward-predicting cue on response times and response choices are also explored. Data from 136 children (6-12 years), 90 with ADHD and 46 typically developing (TD) children, are included. The children could collect a small immediately available reward or wait to access a larger reward after a variable delay, its imminent availability sometimes signaled by a cue. Subsequent probe trials explored the effects of longer waiting times and disruption of the cue-reward association. As expected, children with ADHD collected the small immediately available reward more often than TD children. Importantly, they were more likely to terminate waiting once commenced, collecting the small reward or attempting to collect the large reward early. The cue decreased their response time but disrupted their waiting when it no longer consistently predicted reward. Children with ADHD were more likely to abandon efforts to wait, especially when wait times were extended and when expected rewards failed to appear. Behavioral interventions for ADHD should take into account reduced waiting capacity that extends beyond children's preference for immediate reward.

Altered reward sensitivity has been proposed to underlie symptoms of attention deficit hyperactivity disorder (ADHD). Functional magnetic resonance imaging (fMRI) studies have reported hypoactivation to reward-predicting cues in the ventral striatum among individuals with ADHD, using experimental designs with and without behavioral response requirements. These studies have typically used monetary incentives as rewards; however, it is unclear if these findings extend to other reward types. The current study examined striatal responses to anticipation and delivery of both affiliative and food reward images using a classical conditioning paradigm. Data from 20 typically developing young adults, and 20 individuals diagnosed with ADHD were included in a region-of-interest analysis for a priori striatal regions. Consistent with findings from studies using monetary rewards, individuals with ADHD showed decreased activation to cues predicting affiliative rewards in the bilateral ventral and dorsal striatum and increased activation to the delivery of affiliative rewards in the ventral striatum. No group differences were found in striatal responses to food reward cues or images. These results suggest hyposensitivity to reward-predicting cues in ADHD extends to affiliative rewards, with important implications for understanding and managing the learning and social functioning of those with ADHD., Competing Interests: Declaration of Competing Interest PM received research grant and speaker honoraria from Takeda in the last three years., (Copyright © 2022. Published by Elsevier B.V.)

Background: The Patient Education Materials Assessment Tool (PEMAT) systematically evaluates the understandability and actionability of patient education materials. This study aimed to develop a Japanese version of PEMAT and verify its reliability and validity., Methods: After assessing content validation, experts scored healthcare-related leaflets and videos according to PEMAT to verify inter-rater reliability. In validation testing with laypeople, the high-scoring material group ( n = 800) was presented with materials that received high ratings on PEMAT, and the low-scoring material group ( n = 799) with materials that received low ratings. Both groups responded to the understandability and actionability of the materials and perceived self-efficacy for the recommended actions., Results: The Japanese version of PEMAT showed strong inter-rater reliability (PEMAT-P: % agreement = 87.3, Gwet's AC1 = 0.83. PEMAT-A/V: % agreement = 85.7, Gwet's AC1 = 0.80). The high-scoring material group had significantly higher scores for understandability and actionability than the low-scoring material group (PEMAT-P: understandability 6.53 vs. 5.96, p < 0.001; actionability 6.04 vs. 5.49, p < 0.001; PEMAT-A/V: understandability 7.65 vs. 6.76, p < 0.001; actionability 7.40 vs. 6.36, p < 0.001). Perceived self-efficacy increased more in the high-scoring material group than in the low-scoring material group., Conclusions: Our study showed that materials rated highly on Japanese version of PEMAT were also easy for laypeople to understand and action.

A severe negative energy balance and high circulating free fatty acids (FFA) in postpartum cows impair fertility. The lipotoxicity of FFA has been shown to decrease the quality of bovine oocytes in vitro. Therefore, excess FFA in cells is converted to triacylglycerol (TAG), a non-toxic form, to avoid lipotoxicity. We recently reported that the TAG content in oocytes was higher in postpartum lactating cows subjected to grazing management than in heifers (Theriogenology 176: 174-182, 2021). The present study investigated the compositions of the energy metabolism-related lipids, FFA and TAG, in the plasma and oocytes of cows at different lactation stages under indoor intensive feeding management in order to obtain insights into lipotoxicity in oocytes, particularly those in early postpartum cows. Blood and oocytes were collected from 20 lactating cows categorized into the following lactation groups: 20-30 days in milk (DIM) (n = 5), 40-50 DIM (n = 5), 60-80 DIM (n = 5), and 130-160 DIM (n = 5). Daily energy balance data were obtained for 3 weeks prior to oocyte collection using the ovum pick up (OPU) method. The contents and compositions of FFA and TAG in plasma and oocytes were analyzed using liquid chromatography-mass spectrometry. As expected, plasma FFA was high at 20-30 DIM, decreased by 50 DIM, and was maintained at a low level for the remainder of the experimental period. Similar changes were observed in oocyte FFA and TAG with DIM as plasma FFA. Oocyte FFA positively correlated with plasma FFA (P < 0.05), but negatively correlated with the mean energy balance 1 and 21 days before OPU (P < 0.05). Relationships were noted between the composition and content of FFA in plasma and oocytes, with the FFA 16:1/16:0 and 18:1/18:0 ratios positively correlating with the total amount of FFA (P < 0.05). Elevated oocyte FFA in cows in the early postpartum period under intensive feeding management suggested that oocytes were at a high risk of FFA lipotoxicity. Furthermore, the present results implied that the severe negative energy balance in the previous few weeks was closely related to increases in oocyte FFA, which supports the importance of long-term cow feeding management for preserving the quality of oocytes in the early postpartum period. The present results provide insights into the effects of high circulating FFA on the fertility of postpartum cows., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Along with the comparator model, the perception of action-outcome regularity is involved in the generation of sense of agency. In addition, the perception of action-outcome regularity is related to motor performance. However, no studies have examined the developmental changes in the perception of action-outcome regularity. The current study measured perceptual sensitivity to action-outcome regularity and manual dexterity in 200 children aged between 5 and 16 years. The results showed that perceptual sensitivity to action-outcome regularity was significantly lower in 5-6-year-old children than in 9-16-year-old children, and that it was significantly lower in children with low manual dexterity than in children with medium to high manual dexterity. Correlation analyses revealed significant correlations of age and perceptual sensitivity to action-outcome regularity, but no significant correlation of manual dexterity and perceptual sensitivity to action-outcome regularity, either overall or in any age band. The present study suggests that perceptual sensitivity to action-outcome regularity is immature at 5-6 years of age and that it may be impaired in 5-16-year-old children with poor manual dexterity., (© 2022. The Author(s).)

Conventional culture systems for bovine embryos are unable to support sustained embryonic development until the developmentally mature blastocyst stage. Although we have previously developed an on-gel culture system that enables bovine blastocysts to complete cell segregation events at day (D) 10 following in vitro culture, the development of D10 blastocysts to term has yet to be achieved. In this study, we attained full-term development of D10 mature blastocysts produced using an on-gel culture system. Two calves derived from on-gel-cultured embryos were vaginally born, showing normal birth and placental weights and no obvious morphological abnormalities. Moreover, we detected no abnormalities in blood metabolic profile analyses. Our findings indicate that on-gel culturing can be used to facilitate the development of developmentally mature blastocysts to term, and produce healthy viable calves. This culture system could make a valuable contribution to cattle production and would enable a range of analyses for characterizing bovine-specific pre-implantation development.

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) has a favorable prognosis in general; however, some cases are resistant to chemotherapy, which leads to a poor clinical outcome. We herein report the case of a 32-year-old male with aggressive ALK+ ALCL who presented with hemorrhage from a large tumor in the duodenum and multiple tumors in the lungs, mediastinum, and peritoneal cavity. Although induction chemotherapy resulted in a marked reduction of the tumor lesions, premature progression with massive pulmonary infiltration and central nervous system invasion occurred immediately after the completion of chemotherapy. The patient was then promptly treated with brentuximab vedotin (BV) and high-dose methotrexate, which resulted in complete remission. Subsequently, he successfully underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor and has been healthy and did not relapse for more than 3 years after transplantation without any additional therapy. Allo-HSCT may be a promising treatment option for ALK+ ALCL due to its graft-versus-lymphoma effect. In addition, molecular targeting agents, such as BV, may be promising as a bridging therapy before allo-HSCT to achieve disease remission.

The transcription factor Nrf2 plays a crucial role in the anti-oxidative stress response, protection of DNA from injury and DNA repair mechanisms. Nrf2 activity reduces cancer initiation, but how Nrf2 affects whole-genome alterations upon carcinogenic stimulus remains unexplored. Although recent genome-wide analysis using next-generation sequencing revealed landscapes of nucleotide mutations and copy number alterations in various human cancers, genomic changes in murine cancer models have not been thoroughly examined. We elucidated the relationship between Nrf2 expression levels and whole exon mutation patterns using an ethyl-carbamate (urethane)-induced lung carcinogenesis model employing Nrf2-deficient and Keap1-kd mice, the latter of which express high levels of Nrf2. Exome analysis demonstrated that single nucleotide and trinucleotide mutation patterns and the Kras mutational signature differed significantly and were dependent on the expression level of Nrf2. The Nrf2-deficient tumors exhibited fewer copy number alterations relative to the Nrf2-wt and Keap1-kd tumors. The observed trend in genomic alterations likely prevented the Nrf2-deficient tumors from progressing into malignancy. For the first time, we present whole-exome sequencing results for chemically-induced lung tumors in the Nrf2 gain or loss of function mouse models. Our results demonstrate that different Nrf2 expression levels lead to distinct gene mutation patterns that underly different oncogenic mechanisms in each tumor genotype., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We investigated the optimal timing of artificial insemination (AI) for achieving pregnancy according to the onset/end of estrus detected by an accelerometer system in Holstein cattle. The conception rates of conventional semen were used as a reference. The conception rate from AI of sex-sorted semen was higher at -4 to 4 h (57.1%) from the end of estrus than those at -12 to -4 h (37.7%) and 12-20 h (30.3%), whereas AI at 4-12 h showed an intermediate conception rate (47.4%). Conversely, conception rates were similar in AI performed between 0 and 32 h from the onset of estrus. Regarding conventional semen, the interval from the onset and end of estrus did not affect conception rates. The present results suggest that the time of the end of estrus is the better indicator of optimal AI timing for sex-sorted semen than the onset of estrus.