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The Four-circle Off-centered Neutron DiffractometER (FONDER), which is a four-circle neutron diffractometer used to study structures under various sample environments with single crystals, has been revealed to be an efficient instrument not only for the measurement of crystal and magnetic structural analyses, but also for the quantitative measurements of superlattice reflections and diffuse scattering. Here, the performance of FONDER and the comparison of its use with the curved two-dimensional position sensitive detector (C-2DPSD) are described, and studies using FONDER for the structural analyses of trehalose dihydrate, the multiferroic compound RMn2O5, and short-range magnetic ordering in Pt–Mn alloys are reviewed. The prospects for combining the technique with X-ray or time-of-flight (TOF) Laue diffraction techniques are discussed. [ABSTRACT FROM AUTHOR]

Abstract Background The relationships between developmental strategies for additional indications and drug price revisions have not been thoroughly studied. Here, we investigated the price revisions for anticancer drugs approved in Japan. Methods The study was based on published information on anticancer drugs approved between January 2009 and March 2020 in Japan. We investigated the relationships between the pharmacological and regulatory characteristics of anticancer drugs and occurrence/non-occurrence of the Japanese National Health Insurance (NHI) price revisions. Results Eighty-one new anticancer drugs were given NHI price listings during the survey. On April 1, 2020, the prices of 23 anticancer drugs had been revised from the initial pricing, the prices were reduced for 21 drugs (91.3%). Several parameters showed the relationships between drug characteristics and NHI price revisions. The achievement of additional indications and compound type were identified as explanatory factors for these relationships. Additional indication profiles were defined to assess the relationships between the methods for additional indication achievement and price revisions. When the type of additional indication was “Expansion”, the percentage of drugs received NHI price revisions was the highest (P

Abstract In percutaneous coronary intervention (PCI) to the culprit lesion of acute myocardial infarction (AMI), unsuccessful guidewire crossing causes immediate poor outcomes. It is important to determine the factors associated with unsuccessful guidewire crossing in AMI lesions. The purpose of this study was to find factors associated with difficulty in crossing the culprit lesion of AMI. We defined the difficult group when the guidewire used to cross the culprit lesion was a polymer jacket type guidewire or a stiff guidewire. We included 937 patients, and divided those into the non-difficult group (n = 876) and the difficult group (n = 61). Proximal reference diameter was significantly smaller in the difficult group than in the non-difficult group (p

Abstract Aims White blood cell (WBC) count in healthy people is associated with the risk of coronary artery disease (CAD) and mortality. This study aimed to determine whether WBC count predicts heart failure (HF) requiring hospitalization as well as all‐cause death, acute myocardial infarction (AMI) and stroke in patients with Type 2 diabetes mellitus and established CAD. Methods We conducted this retrospective registry study that enrolled consecutive patients with Type 2 diabetes mellitus and CAD based on coronary arteriography records and medical charts at 70 teaching hospitals in Japan from 2005 to 2015. A total of 7608 participants (28.2% women, mean age 68 ± 10 years) were eligible. In the cohort, the median (interquartile range) and mean follow‐up durations were 39 (16.5–66.1 months) and 44.3 ± 32.7 months, respectively. The primary outcome was HF requiring hospitalization. The secondary outcomes were AMI, stroke, all‐cause death, 3‐point major adverse cardiovascular events (MACE) (AMI/stroke/death) and 4‐point MACE (AMI/stroke/death/HF requiring hospitalization). Outcomes were reported as cumulative incidences (proportion of patients experiencing an event) and incidence rates (events/100 person‐years). The primary and secondary outcomes were assessed using the Kaplan–Meier method and were compared using the log‐rank test stratified by the baseline WBC count. The association between the WBC count at baseline and each MACE was assessed using the Cox proportional hazard model and expressed as the hazard ratio (HR) and 95% confidence interval (CI) after adjusting for other well‐known risk factors for MACE. Results During the follow‐up, 880 patients were hospitalized owing to HF. The WBC Quartile 4 (≥7700 cells/μL) had significantly lower HF event‐free survival rate (log‐rank test, P

Chylothorax is a potentially fatal postoperative complication of neck, thoracic, and abdominal surgery in children. We report the case of a 3-month-old infant who developed persistent chylothorax with respiratory insufficiency successfully managed using a microsurgical technique and intraoperative embolotherapy. This was achieved using a combination of intermittent digital X rays and live near-infrared fluorescence imaging we have termed “dual imaging lymphangiography” to guide therapy in real time. The chylothorax resolved and the patient returned to normal diet without recurrence. This microsurgical approach with dual imaging lymphangiography provides a useful tool for intraoperative visualization and treatment of complicated chylothoraces.

In this study, we analyzed prognostic radiological tools and surgical outcomes for radiologically pure solid adenocarcinomas (AD) and squamous cell carcinoma (SQ) in clinical stage IA. We retrospectively investigated 130 patients who underwent surgical resections. We assessed the predictive risk factors for recurrence and pathological lymph node metastasis (LNM). There was no statistical difference in recurrence free survival (RFS) or cancer-specific survival (CSS) between AD and SQ groups (p = 0.642 and p = 0.403, respectively). In the whole cohort, tumor size on lung window and mediastinal settings, and tumor disappearance ratio using high-resolution computed tomography (HRCT) were not prognostic parameters (p = 0.127, 0.066, and 0.082, respectively). The maximal standardized uptake value (SUVmax) using positron emission tomography-CT was associated with recurrence (p = 0.016). According to the receiver operating characteristic curve, the cut-off value of SUVmax for recurrence was 4.6 (p = 0.016). The quantitative continuous variables using any radiological tools were not associated with LNM. However, tumor diameter on mediastinal setting ≥8 mm with SUVmax ≥2.4 could be a risk factor for LNM. Pure solid AD and SQ were equivalent for the RFS and CSS. SUVmax was useful to predict recurrence. The tumor diameter on a mediastinal setting and SUVmax were useful in predicting pathological LNM.

Background: The anti- Mycobacterium avium complex (MAC) antibody test measures levels of IgA antibody against the glycopeptidolipid (GPL) core in the bacterial cell walls and is a useful clinical indicator of nontuberculous mycobacterium pulmonary disease (NTM-PD). However, it is not currently possible to diagnose the disease using anti-MAC antibodies alone. Objectives: The study aim was to assess the efficacy of the combination of anti-MAC antibodies and clinical findings for diagnosing potential NTM-PD. Methods: This cross-sectional study included 938 patients tested using the anti-MAC antibody. NTM-PD was diagnosed by multiple positive cultures of the same species in sputum samples. Multivariate logistic regression models were used to identify the clinical factors related to NTM-PD. Results: Overall, 19.6% (184/938) of participants were diagnosed with NTM-PD. In multivariate analysis, positive anti-MAC antibodies, low body mass index, absence of malignancy, and cavity-forming lung lesions were significantly associated with NTM-PD at diagnosis. The positive rates of the anti-MAC antibody test were 79.4% (135/170) for MAC and 55.6% (5/9) for Mycobacterium abscessus complex, respectively. Conclusions: Bronchoscopic examinations should be performed especially in certain types of individuals from whom sputum samples cannot be obtained. Anti-MAC antibodies are also positive in patients other than those harboring MAC, but the rate may be low because of the different components in GPLs.

Abstract Graves' disease is a recurrent syndrome often accompanied by depression. I report a rare case in which dysphagia and bulbar myopathy indicated a relapse of Graves' disease, accompanied by recurrent depression.

Purpose: : A prominent view of language acquisition involves learning to ignore irrelevant auditory signals through functional reorganization, enabling more efficient processing of relevant information. Yet, few studies have characterized the neural spatiotemporal dynamics supporting rapid detection and subsequent disregard of irrelevant auditory information, in the developing brain. To address this unknown, the present study modeled the developmental acquisition of cost-efficient neural dynamics for auditory processing, using intracranial electrocorticographic responses measured in individuals receiving standard-of-care treatment for drug-resistant, focal epilepsy. We also provided evidence demonstrating the maturation of an anterior-to-posterior functional division within the superior-temporal gyrus (STG), which is known to exist in the adult STG. Methods: : We studied 32 patients undergoing extraoperative electrocorticography (age range: eight months to 28 years) and analyzed 2,039 intracranial electrode sites outside the seizure onset zone, interictal spike-generating areas, and MRI lesions. Patients were given forward (normal) speech sounds, backward-played speech sounds, and signal-correlated noises during a task-free condition. We then quantified sound processing-related neural costs at given time windows using high-gamma amplitude at 70–110 Hz and animated the group-level high-gamma dynamics on a spatially normalized three-dimensional brain surface. Finally, we determined if age independently contributed to high-gamma dynamics across brain regions and time windows. Results: : Group-level analysis of noise-related neural costs in the STG revealed developmental enhancement of early high-gamma augmentation and diminution of delayed augmentation. Analysis of speech-related high-gamma activity demonstrated an anterior-to-posterior functional parcellation in the STG. The left anterior STG showed sustained augmentation throughout stimulus presentation, whereas the left posterior STG showed transient augmentation after stimulus onset. We found a double dissociation between the locations and developmental changes in speech sound-related high-gamma dynamics. Early left anterior STG high-gamma augmentation (i.e., within 200 ms post-stimulus onset) showed developmental enhancement, whereas delayed left posterior STG high-gamma augmentation declined with development. Conclusions: : Our observations support the model that, with age, the human STG refines neural dynamics to rapidly detect and subsequently disregard uninformative acoustic noises. Our study also supports the notion that the anterior-to-posterior functional division within the left STG is gradually strengthened for efficient speech-sound perception after birth.

Abstract Background and Aim We aimed to identify clinical features that suggest that coronavirus disease 2019 (COVID‐19) should be a differential diagnosis in patients presenting with a chief complaint of fever and abnormal liver function. Methods We retrospectively studied the presence or absence of abnormal liver function in 216 patients diagnosed with mild–moderate severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection between February and September 2020. Results Abnormal liver function was observed in 51 patients with mild–moderate COVID‐19. The median peak aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were 57.5, 75.5, and 332.5 U/L, respectively. The median number of days from symptom onset to peak AST, ALT, and LDH were 8.5, 9, and 8.5, respectively. The median peak LDH/AST ratio was 9.0. Low lymphocyte‐to‐white blood cell ratio and elevated LDH were found to be independent contributing factors for intensive care unit (ICU) admission on a multivariate analysis. Conclusions AST‐predominant AST/ALT/LDH elevation peaking 8–9 days after symptom onset and not accompanied by elevated alkaline phosphatase or gamma‐glutamyl transferase may be a useful clinical feature for differentiating COVID‐19 from other diseases. Since the median LDH/AST ratio was 9.0, it seems that the abnormal liver function caused by SARS‐CoV‐2 is an indirect damage to liver cells due to elevated cytokine levels caused by liver‐infiltrating lymphocytes. SARS‐CoV‐2 infection should be considered in patients presenting with a chief complaint of fever and liver injury; those with a high lymphocyte‐to‐white blood cell ratio or and a high LDH/AST ratio may be admitted to the ICU.

Abstract Background This study was performed to evaluate the clinical outcomes of hybrid treatment involving surgical resection and percutaneous radiofrequency ablation for patients with multiple lung metastases. Methods Seventeen patients (6 men, 11 women; median age, 52 years; range, 16–78 years) underwent hybrid treatment involving surgery and radiofrequency ablation to treat multiple lung metastases (median number, 4; range, 2–26) between May 2014 and February 2020. The primary lesions were colorectal carcinoma (n = 9), uterine endometrial carcinoma (n = 3), osteosarcoma (n = 2), renal cell carcinoma (n = 1), glottic carcinoma (n = 1), and fibrolamellar hepatocellular carcinoma (n = 1). Twenty‐four sessions each of surgery and radiofrequency ablation were performed. Safety, disease‐free survival, and overall survival were evaluated. Safety was assessed according to the Clavien‐Dindo Classification. Results A grade IVa adverse event of empyema developed in one patient (4%, 1/24) after surgery. A grade IIIa adverse event of pneumothorax and a grade II adverse event of lung abscess occurred in four (17%, 4/24) and one session (4%, 1/24) after radiofrequency ablation, respectively. During the median follow up of 34 months (range, 8–67 months), 10 patients (59%, 10/17) developed new metastases. The 5‐year disease‐free survival rate was 32%. Four or fewer lung metastases (p = 0.008) and metastases from colorectal carcinoma (p = 0.02) were factors significantly associated with longer disease‐free survival. One patient (6%, 1/17) died of tumor progression 29 months after initial treatment. The 5‐year overall survival rate was 88%. Conclusions The strategy of hybrid treatment involving surgery and radiofrequency ablation may offer good outcomes for patients with multiple lung metastases.

Background There is significant regional or institutional variation in the use of thrombus aspiration (TA) in patients undergoing percutaneous coronary intervention (PCI). We investigated the temporal trend in TA use and its association with clinical outcomes in acute coronary syndrome using the nationwide J‐PCI (Japanese PCI) registry. Methods and Results Between 2016 and 2018, patients with acute coronary syndrome undergoing PCI (n=282 606; median age, 71.0 years; interquartile range, 62.0–79.0 years; women, 24.7%) at 1124 hospitals were stratified on the basis of whether TA was performed (TA and non‐TA). The patients were subdivided according to clinical presentation (ST‐segment–elevation myocardial infarction, non–ST‐segment–elevation myocardial infarction, and unstable angina). Successful PCI, defined as the achievement of TIMI (Thrombolysis in Myocardial Infarction) 3 flow, and in‐hospital mortality were assessed. During the study period, 83 422 patients (29.5%) underwent TA (52.9%, 23.5%, and 5.2% for ST‐segment–elevation myocardial infarction, non–ST‐segment–elevation myocardial infarction, and unstable angina, respectively), and the TA implementation rate remained relatively stable throughout. Patients treated with TA had higher rate of successful PCI than non‐TA (98.7% versus 97.8%; P

Objective: Our daily activities require frequent switches among competing responses at the millisecond time scale. We determined the spatiotemporal characteristics and functional significance of rapid, large-scale brain network dynamics during task switching. Methods: This cross-sectional study investigated patients with drug-resistant focal epilepsy who played a Lumosity cognitive flexibility training game during intracranial electroencephalography (iEEG) recording. According to a given task rule, unpredictably switching across trials, participants had to swipe the screen in the direction the stimulus was pointing or moving. Using this data, we described the spatiotemporal characteristics of iEEG high-gamma augmentation occurring more intensely during switch than repeat trials, unattributable to the effect of task rule (pointing or moving), within-stimulus congruence (the direction of stimulus pointing and moving was same or different in a given trial), or accuracy of an immediately preceding response. Diffusion-weighted imaging (DWI) tractography determined whether distant cortical regions showing enhanced activation during task switch trials were directly connected by white matter tracts. Trial-by-trial iEEG analysis deduced whether the intensity of task switch-related high-gamma augmentation was altered through practice and whether high-gamma amplitude predicted the accuracy of an upcoming response among switch trials. Results: The average number of completed trials during five-minute gameplay was 221.4 per patient (range: 171–285). Task switch trials increased the response times, whereas later trials reduced them. Analysis of iEEG signals sampled from 860 brain sites effectively elucidated the distinct spatiotemporal characteristics of task switch, task rule, and post-error-specific high-gamma modulations. Post-cue, task switch-related high-gamma augmentation was initiated in the right calcarine cortex after 260 ms, right precuneus after 330 ms, right entorhinal after 420 ms, and bilateral anterior middle-frontal gyri after 450 ms. DWI tractography successfully showed the presence of direct white matter tracts connecting the right visual areas to the precuneus and anterior middle-frontal regions but not between the right precuneus and anterior middle-frontal regions. Task-related high-gamma amplitudes in later trials were reduced in the calcarine, entorhinal and anterior middle-frontal regions, but increased in the precuneus. Functionally, enhanced post-cue precuneus high-gamma augmentation improved the accuracy of subsequent responses among switch trials. Conclusions: Our multimodal analysis uncovered two temporally and functionally distinct network dynamics supporting task switching. High-gamma augmentation in the visual-precuneus pathway may reflect the neural process facilitating an attentional shift to a given updated task rule. High-gamma activity in the visual-dorsolateral prefrontal pathway, rapidly reduced through practice, may reflect the cost of executing appropriate stimulus-response translation.

Abstract Complications such as slow flow are frequently observed in percutaneous coronary intervention (PCI) with rotational atherectomy (RA). However, it remains unclear whether the high incidence of slow flow results in the high incidence of periprocedural myocardial infarction (PMI), reflecting real myocardial damage. The aim of this study was to compare the incidence of PMI between PCI with versus without RA using propensity score-matching. We included 1350 elective PCI cases, which were divided into the RA group (n = 203) and the non-RA group (n = 1147). After propensity score matching, the matched RA group (n = 190) and the matched non-RA group (n = 190) were generated. The primary interest was to compare the incidence of PMI between the matched RA and non-RA groups. Before propensity score matching, the incidence of slow flow and PMI was greater in the RA group than in the non-RA group. After matching, the incidence of slow flow was still greater in the matched RA group than in the matched non-RA group (16.8% vs. 9.5%, p = 0.048). However, the incidence of PMI was similar between the matched RA and matched non-RA group (7.4% vs. 5.3%, p = 0.528, standardized difference: 0.086). In conclusion, although use of RA was associated with greater risk of slow flow, use of RA was not associated with PMI after a propensity score-matched analysis. The fact that RA did not increase the risk of myocardial damage in complex lesions would have an impact on revascularization strategy for severely calcified coronary lesions.

Abstract Background T790M mutation causes resistance to tyrosine kinase inhibitors (TKIs) in approximately 49% of patients with epidermal growth receptor‐mutant non‐small cell lung cancer (NSCLC). The cause of resistance in the remaining half of the cases is a minor mutation or unknown. Here, we conducted a retrospective study of epidermal growth receptor‐mutant NSCLC patients with T790M‐negative or an unidentified mutation to appraise the therapeutic response to first‐ or second‐generation tyrosine kinase inhibitors as a second‐line treatment. Methods The study included 39 patients treated in our institution from April 2012 through March 2020 with second‐line tyrosine kinase inhibitors or chemotherapy after completing a first‐line therapy with tyrosine kinase inhibitors. Results The patients were allocated to two groups: chemotherapy (n = 28) and a tyrosine kinase inhibitor (n = 11) groups. The median progression‐free survival (PFS) was 5.4 months in the chemotherapy group and 3.4 months in the tyrosine kinase inhibitor group (p‐value = 0.36), while the median overall survival (OS) was 16.1 months in the chemotherapy group and 12.8 months in the tyrosine kinase inhibitor group (p‐ value = 0.20). This study showed no significant difference in PFS and OS between the chemotherapy and tyrosine kinase inhibitor groups. Conclusions These observations suggest that first‐ and second‐generation tyrosine kinase inhibitors are not recommended for second‐line treatment in epidermal growth factor receptor‐mutated NSCLC patients with T790M‐negative mutation who have received tyrosine kinase inhibitors as first‐line treatment.

Abstract Background The aim of this study was to evaluate regional postoperative preserved pulmonary function (PPPF) and three‐dimensional (3D) volumetric changes according to the number of resected subsegments and investigate the factors that most affected pre‐/post PPPF. Methods Patients who underwent thoracoscopic lobectomy (n = 73), and segmentectomy (n = 87) were eligible for inclusion in the study. They were classified according to the number of resected subsegments which ranged from 1 to 10. The percentage of pre‐/postoperative forced expiratory volume in 1 s (FEV1) was used for comparison. Furthermore, lung volumetric changes were calculated using 3D computed tomography (CT) volumetry. Results The percentage of pre‐/postoperative EFV1 between 4 and 5–7 and between 5–7 and 10 were significant (p = 0.03 and p

Mental nerve paresthesia is a serious postoperative complication of mandibular third molar extraction. It appears that no study has examined the relationship between the surface morphology of the mandibular third molar roots and the possibility of mental nerve paresthesia following tooth extraction. Therefore, the root morphology of the mandibular third molars was examined according to age using dental cone beam computed tomography (CBCT), and the possibility of mental nerve paresthesia following tooth extraction was evaluated. The study included 1216 patients who had undergone mandibular third molar extractions. The root morphology of 1534 teeth in 791 patients who had CBCT performed before surgery was studied. Factors evaluated were age, complete or incomplete formation of the mandibular third molar roots, periodontal ligament atrophy of the mandibular third molar roots, hypercementosis, and mandibular canal deformation. Mandibular third molar root formation was completed between the ages of 19 and 30 years. Complete formation of the mandibular third molar roots (P = 0.002) and deformation of the mandibular canal (P < 0.001) were identified as risk factors for mental nerve paresthesia. These findings suggest that the risk of mental nerve paresthesia could be reduced if the extraction of third molars is performed prior to complete root formation. [ABSTRACT FROM AUTHOR]

Abstract Percutaneous coronary intervention (PCI) is sometimes considered as an alternative therapeutic strategy to surgical revascularization in patients with coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF). However, the types or conditions of patients that receive the clinical benefit of left ventricular reverse remodelling (LVRR) remain unknown. The purpose of this study was to investigate the determinants of LVRR following PCI in CAD patients with reduced LVEF. From 4394 consecutive patients who underwent PCI, a total of 286 patients with reduced LV systolic function (LVEF