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Abstract We developed a surgical support system that visualises important microanatomies using artificial intelligence (AI). This study evaluated its accuracy in recognising the thoracic nerves during lung cancer surgery. Recognition models were created with deep learning using images precisely annotated for nerves. Computational evaluation was performed using the Dice index and the Jaccard index. Four general thoracic surgeons evaluated the accuracy of nerve recognition. Further, the differences in time lag, image quality and smoothness of movement between the AI system and surgical monitor were assessed. Ratings were made using a five-point scale. The computational evaluation was relatively favourable, with a Dice index of 0.56 and a Jaccard index of 0.39. The AI system was used for 10 thoracoscopic surgeries for lung cancer. The accuracy of thoracic nerve recognition was satisfactory, with a recall score of 4.5 ± 0.4 and a precision score of 4.0 ± 0.9. Though smoothness of motion (3.2 ± 0.4) differed slightly, nearly no difference in time lag (4.9 ± 0.3) and image quality (4.6 ± 0.5) between the AI system and the surgical monitor were observed. In conclusion, the AI surgical support system has a satisfactory accuracy in recognising the thoracic nerves.

Purpose: Muscle quality is explained by the ratio between muscle size and strength. Conventionally, muscle size is evaluated without considering the composition of contractile and non-contractile tissues in muscle, hence the influence of non-contractile tissues on muscle quality is not fully understood, especially within aging muscle. This study investigated the differences in intramuscular non-contractile tissues between different age and sex groups, and investigated their influence on muscle quality. Methods: Eighty-two older and 64 young females and males participated. Muscle cross-sectional area (quadriceps and hamstrings), separating contractile and non-contractile areas, was calculated from the magnetic resonance image of the right mid-thigh. Maximal voluntary isometric knee extension and flexion torque was measured. Torque/muscle area and torque/contractile area were calculated for each age and sex group. Results: Non-contractile/muscle area was higher in older than in young individuals in both muscle groups (p females) (p

Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically defined cells in the Drosophila brain, we here revealed substantial post-transcriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias toward the 5′ leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open-reading frames in the 5’ leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.

Abstract More specific screening systems for cervical cancer may become necessary as the human papillomavirus (HPV) vaccine becomes more widespread. Although p16/Ki-67 dual-staining cytology has several advantages, it requires advanced diagnostic skills. Here, we developed an automated on-chip immunostaining method using a microfluidic device. An electroactive microwell array (EMA) microfluidic device with patterned thin-film electrodes at the bottom of each microwell was used for single-cell capture by dielectrophoresis. Immunostaining and dual staining for p16/Ki-67 were performed on diagnosed liquid cytology samples using the EMA device. The numbers of p16/Ki-67 dual-stained cells captured by the EMA device were determined and compared among the cervical intraepithelial neoplasia (CIN) lesion samples. Seven normal, fifteen CIN grade 3, and seven CIN grade 2 samples were examined. The percentage of dual-positive cells was 18.6% in the CIN grade 2 samples and 23.6% in the CIN grade 3 samples. The percentages of dual-positive staining increased significantly as the severity of the cervical lesions increased. p16/Ki67 dual immunostaining using the EMA device is as sensitive as the conventional method of confirming the histopathological diagnosis of cervical samples. This system enables a quantified parallel analysis at the individual cell level.

Abstract The impact of deep space cosmic rays on food resources is as important as the risks of cosmic rays to the human body. This study demonstrates the potential for neutrons as secondary radiation in deep space spacecraft to cause meat activation and oxidative modification of proteins and lipids. We conducted a series of experiments such as the neutron irradiation experiment, the radioactivation analysis and the biochemical analysis. Neutrons with energies from 1 to 5 MeV with doses from 0.01 Gy to 4 Gy were irradiated by the RIKEN accelerated-driven neutron source (RANS). Radioactive nuclei, 24Na, 42K, and 38Cl, were detected in the neutron-irradiated meat. The modification products of the proteins by oxidative nitration, 6-nitrotryptophan (6NO2Trp), and by a lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE), were detected in several proteins with neutron dose dependent. The proteome analysis showed that many oxidative modifications were detected in actin and myosin which are major proteins of myofibrils. This study is of crucial importance not only as risk factors for human space exploration, but also as fundamental effects of radiation on the components of the human body.

Worldwide, lung cancer is the leading cause of cancer-related deaths. To manage lung nodules, radiologists observe computed tomography images, review various imaging findings, and record these in radiology reports. The report contents should be of high quality and uniform regardless of the radiologist. Here, we propose an artificial intelligence system that automatically generates descriptions related to lung nodules in computed tomography images. Our system consists of an image recognition method for extracting contents-namely, bronchopulmonary segments and nodule characteristics from images-and a natural language processing method to generate fluent descriptions. To verify our system's clinical usefulness, we conducted an experiment in which two radiologists created nodule descriptions of findings using our system. Through our system, the similarity of the described contents between the two radiologists (p = 0.001) and the comprehensiveness of the contents (p = 0.025) improved, while the accuracy did not significantly deteriorate (p = 0.484).

Abstract Metal homeostasis is tightly regulated in cells and organisms, and its disturbance is frequently observed in some diseases such as neurodegenerative diseases and metabolic disorders. Previous studies suggest that zinc and iron are necessary for the normal functions of pancreatic β cells. However, the distribution of elements in normal conditions and the pathophysiological significance of dysregulated elements in the islet in diabetic conditions have remained unclear. In this study, to investigate the dynamics of elements in the pancreatic islets of a diabetic mouse model expressing human islet amyloid polypeptide (hIAPP): hIAPP transgenic (hIAPP-Tg) mice, we performed imaging analysis of elements using synchrotron scanning X-ray fluorescence microscopy and quantitative analysis of elements using inductively coupled plasma mass spectrometry. We found that in the islets, zinc significantly decreased in the early stage of diabetes, while iron gradually decreased concurrently with the increase in blood glucose levels of hIAPP-Tg mice. Notably, when zinc and/or iron were decreased in the islets of hIAPP-Tg mice, dysregulation of glucose-stimulated mitochondrial respiration was observed. Our findings may contribute to clarifying the roles of zinc and iron in islet functions under pathophysiological diabetic conditions.

The retina is comprised of diverse neural networks, signaling from photoreceptors to ganglion cells to encode images. The synaptic connections between these retinal neurons are crucial points for information transfer; however, the input-output relations of many synapses are understudied. Starburst amacrine cells in the retina are known to contribute to retinal motion detection circuits, providing a unique window for understanding neural computations. We examined the dual transmitter release of GABA and acetylcholine from starburst amacrine cells by optogenetic activation of these cells, and conducted patch clamp recordings from postsynaptic ganglion cells to record excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs). As starburst amacrine cells exhibit distinct kinetics in response to objects moving in a preferred or null direction, we mimicked their depolarization kinetics using optogenetic stimuli by varying slopes of the rising phase. The amplitudes of EPSCs and IPSCs in postsynaptic ganglion cells were reduced as the stimulus rising speed was prolonged. However, the sensitivity of postsynaptic currents to the stimulus slope differed. EPSC amplitudes were consistently reduced as the steepness of the rising phase fell. By contrast, IPSCs were less sensitive to the slope of the stimulus rise phase and maintained their amplitudes until the slope became shallow. These results indicate that distinct synaptic release mechanisms contribute to acetylcholine and GABA release from starburst amacrine cells, which could contribute to the ganglion cells’ direction selectivity.

Abstract Tyrosine kinase inhibitors (TKIs) improve the prognosis of patients with gastrointestinal stromal tumors (GISTs). We conducted a retrospective cohort study using cancer registries linked with health utilization data in Japan and Taiwan to assess TKI usage in older and non-older patients. Patients diagnosed with GIST (2012–2014) were categorized into the following: adjuvant and advanced/metastatic settings. The duration and patterns of imatinib therapy were compared between the older (aged ≥ 75 years) and non-older (

Abstract Glenohumeral internal rotation deficit (GIRD) and weakness in prone external rotation are risk factors for shoulder and elbow injuries in high school baseball pitchers. While a shoulder-stretching prevention program to improve GIRD decreases the injury rate, the effects of external rotation strength remain unclear. This non-inferiority (NI) study investigates the hypothesis that external rotation strength training is not inferior to sleeper stretching for shoulder and elbow injury prevention in high school baseball pitchers. Participants were randomly allocated to the stretching (n = 62; active control group) and muscle-training (n = 51) groups. Specific exercises were performed each night. Elbow and shoulder injuries were monitored for 150 days. Kaplan–Meier survival curves were generated, and the hazard ratios (HRs) for injury occurrence were calculated using multivariate Cox regression. The log-rank test was used to compare the injury-free time. A one-sided NI test using a fixed NI margin was performed (significance level, P = 0.025). The injury rates were 22.6% (n = 14) in the stretching group and 9.8% (n = 5) in the muscle-training group. The muscle-training group had a lower injury rate (P

Abstract The emergence of antimicrobial resistance (AMR) caused by the excess use of antimicrobials has come to be recognized as a global threat to public health. There is a ‘tragedy of the commons’ type social dilemma behind this excess use of antimicrobials, which should be recognized by all stakeholders. To address this global threat, we thus surveyed eight countries/areas to determine whether people recognize this dilemma and showed that although more than half of the population pays little, if any, attention to it, almost 20% recognize this social dilemma, and 15–30% of those have a positive attitude toward solving that dilemma. We suspect that increasing individual awareness of this social dilemma contributes to decreasing the frequency of AMR emergencies.

Abstract Trichoderma reesei is a widely used host for producing cellulase and hemicellulase cocktails for lignocellulosic biomass degradation. Here, we report a genetic modification strategy for industrial T. reesei that enables enzyme production using simple glucose without inducers, such as cellulose, lactose and sophorose. Previously, the mutated XYR1V821F or XYR1A824V was known to induce xylanase and cellulase using only glucose as a carbon source, but its enzyme composition was biased toward xylanases, and its performance was insufficient to degrade lignocellulose efficiently. Therefore, we examined combinations of mutated XYR1V821F and constitutively expressed CRT1, BGLR, VIB1, ACE2, or ACE3, known as cellulase regulators and essential factors for cellulase expression to the T. reesei E1AB1 strain that has been highly mutagenized for improving enzyme productivity and expressing a ß-glucosidase for high enzyme performance. The results showed that expression of ACE3 to the mutated XYR1V821F expressing strain promoted cellulase expression. Furthermore, co-expression of these two transcription factors also resulted in increased productivity, with enzyme productivity 1.5-fold higher than with the conventional single expression of mutated XYR1V821F. Additionally, that productivity was 5.5-fold higher compared to productivity with an enhanced single expression of ACE3. Moreover, although the DNA-binding domain of ACE3 had been considered essential for inducer-free cellulase production, we found that ACE3 with a partially truncated DNA-binding domain was more effective in cellulase production when co-expressed with a mutated XYR1V821F. This study demonstrates that co-expression of the two transcription factors, the mutated XYR1V821F or XYR1A824V and ACE3, resulted in optimized enzyme composition and increased productivity.

Daytime napping offers benefits for motor memory learning and is used as a habitual countermeasure to improve daytime functioning. A single nap has been shown to ameliorate motor memory learning, although the effect of consecutive napping on motor memory consolidation remains unclear. This study aimed to explore the effect of daytime napping over multiple days on motor memory learning. Twenty university students were divided into a napping group and no-nap (awake) group. The napping group performed motor adaption tasks before and after napping for three consecutive days, whereas the no-nap group performed the task on a similar time schedule as the napping group. A subsequent retest was conducted one week after the end of the intervention. Significant differences were observed only for speed at 30 degrees to complete the retention task, which was significantly faster in the napping group than in the awake group. No significant consolidation effects over the three consecutive nap intervention periods were confirmed. Due to the limitations of the different experimental environments of the napping and the control group, the current results warrant further investigation to assess whether consecutive napping may benefit motor memory learning, which is specific to speed.

Neurons form dense neural circuits by connecting to each other via synapses and exchange information through synaptic receptors to sustain brain activities. Excitatory postsynapses form and mature on spines composed predominantly of actin, while inhibitory synapses are formed directly on the shafts of dendrites where both actin and microtubules (MTs) are present. Thus, it is the accumulation of specific proteins that characterizes inhibitory synapses. In this study, we explored the mechanisms that enable efficient protein accumulation at inhibitory postsynapse. We found that some inhibitory synapses function to recruit the plus end of MTs. One of the synaptic organizers, Teneurin-2 (TEN2), tends to localize to such MT-rich synapses and recruits MTs to inhibitory postsynapses via interaction with MT plus-end tracking proteins EBs. This recruitment mechanism provides a platform for the exocytosis of GABAA receptors. These regulatory mechanisms could lead to a better understanding of the pathogenesis of disorders such as schizophrenia and autism, which are caused by excitatory/inhibitory (E/I) imbalances during synaptogenesis.

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Abstract Since the clinical outcome of patients with sarcoidosis is still unpredictable, a good prognostic biomarker is necessary. Autotaxin (ATX) and phosphatidylserine-specific phospholipase A1 (PS-PLA1) function as main enzymes to produce lysophospholipids (LPLs), and these enzymes are attracting attention as useful biomarkers for several chronic inflammatory diseases. Here, we investigated the relationships between LPLs-producing enzymes and the disease activity of sarcoidosis. In total, 157 patients with sarcoidosis (active state, 51%) were consecutively enrolled. Using plasma or urine specimens, we measured the values of LPLs-producing enzymes. Urine ATX (U-ATX) levels were significantly lower in the active state compared to those in the inactive state, while the plasma ATX (P-ATX) and PS-PLA1 levels showed no significant difference between these two states. Concerning the comparison with existing clinical biomarkers for sarcoidosis, U-ATX showed a weak negative correlation to ACE, P-ATX a weak positive correlation to both ACE and sIL-2R, and PS-PLA1 a weak positive one to sIL-2R. Notably, only the U-ATX levels inversely fluctuated depending on the status of disease activity whether OCS had been used or not. These findings suggest that U-ATX is likely to be a novel and useful molecule for assessing the disease activity of sarcoidosis.

Abstract The presence of hopping carriers and grain boundaries can sometimes lead to anomalous carrier types and density overestimation in Hall-effect measurements. Previous Hall-effect studies on carbon nanotube films reported unreasonably large carrier densities without independent assessments of the carrier types and densities. Here, we have systematically investigated the validity of Hall-effect results for a series of metallic, semiconducting, and metal–semiconductor-mixed single-wall carbon nanotube films. With carrier densities controlled through applied gate voltages, we were able to observe the Hall effect both in the n- and p-type regions, detecting opposite signs in the Hall coefficient. By comparing the obtained carrier types and densities against values derived from simultaneous field-effect-transistor measurements, we found that, while the Hall carrier types were always correct, the Hall carrier densities were overestimated by up to four orders of magnitude. This significant overestimation indicates that thin films of one-dimensional SWCNTs are quite different from conventional hopping transport systems.

Abstract Brain endothelial cells (BECs) are involved in the pathogenesis of ischemic stroke. Recently, several microRNAs (miRNAs) in BECs were reported to regulate the endothelial function in ischemic brain. Therefore, modulation of miRNAs in BECs by a therapeutic oligonucleotide to inhibit miRNA (antimiR) could be a useful strategy for treating ischemic stroke. However, few attempts have been made to achieve this strategy via systemic route due to lack of efficient delivery-method toward BECs. Here, we have developed a new technology for delivering an antimiR into BECs and silencing miRNAs in BECs, using a mouse ischemic stroke model. We designed a heteroduplex oligonucleotide, comprising an antimiR against miRNA-126 (miR-126) known as the endothelial-specific miRNA and its complementary RNA, conjugated to α-tocopherol as a delivery ligand (Toc-HDO targeting miR-126). Intravenous administration of Toc-HDO targeting miR-126 remarkably suppressed miR-126 expression in ischemic brain of the model mice. In addition, we showed that Toc-HDO targeting miR-126 was delivered into BECs more efficiently than the parent antimiR in ischemic brain, and that it was delivered more effectively in ischemic brain than non-ischemic brain of this model mice. Our study highlights the potential of this technology as a new clinical therapeutic option for ischemic stroke.

Abstract Background In the field of oncofertility, patients with breast cancer are often administered letrozole as an adjuvant drug before and after oocyte retrieval to prevent an increase in circulating estradiol. Case presentation We report a case of abdominal hemorrhage due to an ovarian rupture in a 29-year-old Japanese patient who restarted letrozole 2 days after an oocyte retrieval procedure in which 14 mature oocytes were retrieved. The patient had sought embryo cryopreservation as a fertility preservation option before undergoing treatment for recurrent breast cancer. A day after restarting letrozole treatment, the patient unexpectedly developed severe abdominal pain. Laparoscopic hemostasis was performed to manage the ovarian swelling and hemorrhage. Conclusions The ovaries can be restimulated by restart letrozole after an oocyte retrieval procedure. Therefore, reproductive-medicine practitioners should understand the potential complications of letrozole administration in such cases and take steps to ensure that they are minimized.

Abstract Asymptomatic elbow abnormalities are relatively common in young baseball players, but the factors responsible are unclear. To prospectively identify risk factors related to symptom manifestation in asymptomatic elbow abnormalities, we recruited 573 baseball players (age: 7–14 years) at a pre-participation medical/physical examination in the preseason who were right-handed and had asymptomatic medial elbow abnormalities on ultrasound (US). Baseline preseason and postseason participant characteristics were assessed. A “symptomatic” elbow was defined as an elbow with medial elbow joint problems that prevented ball throwing for ≥ 8 days. After exclusions, 82 players were enrolled, of whom 22 (26.8%) developed a symptomatic elbow. In univariate analyses, the external and internal rotation strengths of the dominant shoulder were significantly greater in the symptomatic group than in the asymptomatic group (P = 0.021). Multivariate logistic regression analysis showed that the internal rotation strength of the dominant shoulder was a significant independent risk factor (odds ratio = 1.091, P = 0.027) for developing a symptomatic elbow. In young asymptomatic baseball players with abnormalities in the medial elbow region of the dominant arm on US, stronger preseason internal rotation strength of the dominant shoulder was a significant independent risk factor for the development of a “symptomatic” elbow.

Abstract Pitching motion requires whole-body coordination; therefore, poor control of the lower extremities, pelvis and trunk may cause shoulder and elbow injuries. However, few studies have described the relationship between the shoulder joint function and low back injury in high-school baseball pitchers. A total of 128 healthy high school pitchers underwent pre-season medical checkups, where their shoulder range of motion and shoulder strength were measured. The participants completed a self-recorded daily questionnaire regarding the presence of low back pain. Pitchers were divided into injured and non-injured groups. Low back injury was observed in 13 participants (13.4%). In the injured group, horizontal adduction on the dominant shoulder was significantly less than in the non-injured group. A logistic regression analysis showed that horizontal adduction on the dominant side was a significant independent risk factor for low back injury during the season. It is important to recognize that restriction of the shoulder function not only causes shoulder and elbow injuries but can also risk low back injury.

Background Although ample evidence has demonstrated that daytime napping is beneficial for health and cognitive performance, bedding for napping has not yet been scientifically investigated. Objectives To explore the effect of a bean bag chair on daytime napping and physiological parameters related to sleep. Methods Fourteen healthy participants were enrolled within the context of a randomized, single-blind, crossover study to evaluate the effects of a bean bag chair in comparison with those of a urethane chair manufactured to have a similar shape. Electroencephalogram, electromyogram, and heart rate variability were recorded and compared between wakefulness and napping. Results Electroencephalogram analyses revealed no significant differences in sleep architecture or frequency components; however, a significant decrease was found in electromyogram recordings in the trapezius muscle, which represents the neck region (p = 0.019). Additionally, a significant main effect of bedding in the low-frequency/high-frequency ratio (F[1,20] = 4.314, p = 0.037) was revealed. Conclusions These results suggest that napping in a bean bag chair may provide a comfortable napping environment involving muscle relaxation and proper regulation of the autonomic nervous function.

Abstract The intestinal stroma provides an important microenvironment for immune cell activation. The perturbation of this tightly regulated process can lead to excessive inflammation. We know that upregulated Toll-like receptor 4 (TLR4) in the intestinal epithelium plays a key role in the inflammatory condition of preterm infants, such as necrotizing enterocolitis (NEC). However, the surrounding stromal contribution to excessive inflammation in the pre-term setting awaits careful dissection. Ex vivo co-culture of embryonic day 14.5 (E14.5) or adult murine intestinal stromal cells with exogenous monocytes was undertaken. We also performed mRNAseq analysis of embryonic and adult stromal cells treated with vehicle control or lipopolysaccharide (LPS), followed by pathway and network analyses of differentially regulated transcripts. Cell characteristics were compared using flow cytometry and pHrodo red phagocytic stain, candidate gene analysis was performed via siRNA knockdown and gene expression measured by qPCR and ELISA. Embryonic stromal cells promote the differentiation of co-cultured monocytes to CD11bhighCD11chigh mononuclear phagocytes, that in turn express decreased levels of CD103. Global mRNAseq analysis of stromal cells following LPS stimulation identified TLR signaling components as the most differentially expressed transcripts in the immature compared to adult setting. We show that CD14 expressed by CD11b+CD45+ embryonic stromal cells is a key inducer of TLR mediated inflammatory cytokine production and phagocytic activity of monocyte derived cells. We utilise transcriptomic analyses and functional ex vivo modelling to improve our understanding of unique molecular cues provided by the immature intestinal stroma.

Abstract The relationship between ankle joint function and throwing-related injuries has not been demonstrated. We hypothesized that limited ankle joint range of motion (ROM) was related to risk factors for shoulder and elbow injuries in young baseball players. This 12-month prospective cohort study evaluated the age, height, weight, playing position, shoulder, elbow, and ankle function of 228 enrolled baseball players. Shoulder and elbow injuries were tracked during the season. Univariate and multivariate analyses were performed to identify risk factors for shoulder and elbow injuries among participants divided into non-injured and injured groups. Univariate analysis showed that age, height, weight, ROM of elbow flexion in the dominant arm, muscle strength ratio of shoulder abduction, and the likelihood of being a pitcher or a catcher were significantly greater in the injured group than in the non-injured group. ROM of shoulder abduction-external/internal rotation, shoulder total arc on the dominant arm, ankle joint dorsiflexion, and plantar flexion on the back (non-lead) and front (lead) legs were significantly less in the injured group than in the non-injured group. In conclusion, ROM dorsiflexion deficits in the back leg, shoulder abduction-external rotation in the dominant arm, ROM increase in elbow flexion on the dominant side, older age, and being a pitcher were significant independent risk factors for injury.

Abstract Dysregulated motivation to consume psychoactive substances leads to addictive behaviors that often result in serious health consequences. Understanding the neuronal mechanisms that drive drug consumption is crucial for developing new therapeutic strategies. The fruit fly Drosophila melanogaster offers a unique opportunity to approach this problem with a battery of sophisticated neurogenetic tools available, but how they consume these drugs remains largely unknown. Here, we examined drug self-administration behavior of Drosophila and the underlying neuronal mechanisms. We measured the preference of flies for five different psychoactive substances using a two-choice feeding assay and monitored its long-term changes. We found that flies show acute preference for ethanol and methamphetamine, but not for cocaine, caffeine or morphine. Repeated intake of ethanol, but not methamphetamine, increased over time. Preference for methamphetamine and the long-term escalation of ethanol preference required the dopamine receptor Dop1R1 in the mushroom body. The protein level of Dop1R1 increased after repeated intake of ethanol, but not methamphetamine, which correlates with the acquired preference. Genetic overexpression of Dop1R1 enhanced ethanol preference. These results reveal a striking diversity of response to individual drugs in the fly and the role of dopamine signaling and its plastic changes in controlling voluntary intake of drugs.

Abstract Moyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries. Although RNF213 was identified as a susceptibility gene for MMD, the exact pathogenesis remains unknown. Immunohistochemical analysis of autopsy specimens from a patient with MMD revealed marked accumulation of hyaluronan and chondroitin sulfate (CS) in the thickened intima of occlusive lesions of MMD. Hyaluronan synthase 2 was strongly expressed in endothelial progenitor cells in the thickened intima. Furthermore, MMD lesions showed minimal staining for CS and hyaluronan in the endothelium, in contrast to control endothelium showing positive staining for both. Glycosaminoglycans of endothelial cells derived from MMD and control induced pluripotent stem cells demonstrated a decreased amount of CS, especially sulfated CS, in MMD. A computational fluid dynamics model showed highest wall shear stress values in the terminal portion of the internal carotid artery, which is the predisposing region in MMD. Because the peri-endothelial extracellular matrix plays an important role in protection, cell adhesion and migration, an altered peri-endothelial matrix in MMD may contribute to endothelial vulnerability to wall shear stress. Invading endothelial progenitor cells repairing endothelial injury would produce excessive hyaluronan and CS in the intima, and cause vascular stenosis.

Abstract Studies on the relationship between baseball loads (practice, training, and competition hours) and shoulder and elbow injuries among high school pitchers are limited. Therefore, this study included 92 male high school baseball pitchers and evaluated their preseason shoulder and elbow conditions. All participants completed a self-recorded questionnaire regarding baseball load, presence of shoulder pain or elbow pain, or both, and pitching limitations due to shoulder and/or elbow pain experienced daily to determine the occurrence of injuries and record the baseball load. The optimal load cutoff value was determined using a receiver operating characteristic curve analysis. Participants were categorized into high-load and low-load groups according to the aforementioned cutoff value. The Kaplan–Meier method was used to obtain time-to-event curves, and cox proportional hazards models were used to calculate the hazard ratios for injury rates. The cutoff value of the average baseball load was 324.4 min per day. A high load (> 5.5 h/day) led to a 2.6-times greater risk of injuries and 3.3-times earlier occurrence of injuries than a low load (

Abstract While previous studies have revealed factors affecting the progression of rotator cuff tear (RCT), none have yet described factors affecting its onset. The purpose of this longitudinal observational study was to analyze factors affecting the RCT onset and progression in the general population. The present study included 185 shoulders from 93 participants who completed all the examinations in both 2012 and 2017. Participants received a questionnaire with age, gender, arm dominance, and presence of pain at rest, in motion, and at night. The range of motion (ROM), simple shoulder test (SST) were also examined. Anteroposterior radiograph of the shoulder joint was performed to evaluate the degree of osteoarthritic changes by the Samilson-Prieto (S-P) classification. The degree of RCT was examined by ultrasonography. There were 132 shoulders without RCT and 53 with RCT in 2012. RCT occurred in 21 of 132 shoulders, and the factor affecting the RCT onset was S-P grade 2 osteoarthritic change in 2012 (odds ratio [OR] 10.10). RCT progressed in 22 of 53 shoulders, and the factor affecting RCT progression was the presence of motion pain in 2012 (OR 13.76). These results added new knowledge regarding the natural course of RCT onset and progression.

Abstract Baseball players frequently injure their shoulders and elbows. Preseason risk factors for such injuries have been relatively well studied, but in-season risk factors are less known, and the relationship between the number of pitches and the incidence of such injuries in baseball pitchers of any level is unclear. Identifying the risk factors related to the number of daily pitches is particularly important to prevent baseball-related arm injuries among young pitchers. Thus, we prospectively investigated the relationship between the number of daily full-power pitches in high school baseball pitchers and the incidence of shoulder and elbow injuries. We observed that a small number of daily full-power pitches,

Abstract Background Ovarian hyperstimulation syndrome is normally induced by ovarian stimulation drugs. Severe cases of ovarian hyperstimulation syndrome involve complications such as renal failure and thrombosis. Evidence has recently been developed for a method to prevent ovarian hyperstimulation syndrome. Most cases of ovarian hyperstimulation syndrome are of an early-onset type, which occurs shortly after injection of human chorionic gonadotropin. However, late-onset ovarian hyperstimulation syndrome, which occurs in a pregnancy cycle, also requires caution. We report our experience in treating a woman who was transported to our hospital with a severe case of ovarian hyperstimulation syndrome occurring during ovarian stimulation and who was determined to have an ectopic pregnancy. Case presentation Assisted reproductive technology was planned for a 29-year-old nulligravida Japanese woman diagnosed with bilateral fallopian tube obstruction and right-sided hydrosalpinx. On day 1 of controlled ovarian stimulation, the result of her human chorionic gonadotropin urine test was negative, and her serum levels of luteinizing hormone, estradiol, and progesterone were normal. On day 11 of controlled ovarian stimulation, the levels of estradiol and progesterone had risen to 9679 pg/ml and 16 ng/ml, respectively, prompting suspension of controlled ovarian stimulation. Eleven days after controlled ovarian stimulation was suspended, the patient demonstrated ascites that did not improve despite administration of cabergoline, and she was transported to our hospital 2 days after. Late-onset ovarian hyperstimulation syndrome suggested that she was pregnant, and her serum human chorionic gonadotropin level was 27,778 IU/ml. She underwent laparoscopic bilateral salpingectomy and was diagnosed with right tubal pregnancy. Conclusion In an ectopic pregnancy, human chorionic gonadotropin sometimes increases later than in an intrauterine pregnancy. In our patient’s case, endogenous human chorionic gonadotropin following the start of controlled ovarian stimulation may have caused late-onset ovarian hyperstimulation syndrome. The key to early detection of similar cases may be to suspect pregnancy in the event of unexpectedly high progesterone levels during ovarian stimulation.

BackgroundAlthough vitamin D concentration is reportedly associated with the pathogenesis and pathology of systemic lupus erythematosus (SLE), benefits of vitamin D supplementation in SLE patients have not been elucidated, to our knowledge. We investigated the clinical impacts of vitamin D supplementation in SLE.MethodsA cross-sectional analysis was performed using data from a lupus registry of nationwide institutions. We evaluated vitamin D supplementation status associated with disease-related Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) as a parameter of long-term disease activity control.ResultsOf the enrolled 870 patients (mean age: 45 years, mean disease duration: 153 months), 426 (49%) received vitamin D supplementation. Patients with vitamin D supplementation were younger (43.2 vs 47.5 years, P < 0.0001), received higher doses of prednisolone (7.6 vs 6.8 mg/day, P = 0.002), and showed higher estimated glomerular filtration rates (79.3 vs 75.3 mL/min/1.73m2, P = 0.02) than those without supplementation. Disease-related SDI (0.73 ± 1.12 vs 0.73 ± 1.10, P = 0.75), total SDI, and SLE Disease Activity Index (SLEDAI) did not significantly differ between patients receiving and not receiving vitamin D supplementation. Even after excluding 136 patients who were highly recommended vitamin D supplementation (with age ≥ 75 years, history of bone fracture or avascular necrosis, denosumab use, and end-stage renal failure), disease-related SDI, total SDI, and SLEDAI did not significantly differ between the two groups.ConclusionsEven with a possible Vitamin D deficiency and a high risk of bone fractures in SLE patients, only half of our cohort received its supplementation. The effect of vitamin D supplementation for disease activity control was not observed.

Chlamydia trachomatis infections may occur in multiple organs, including the lungs, lymph nodes, peritoneal cavity, and genitourinary systems. This disease results in significant ascites, the swelling of lymph nodes, and elevated tumor markers (CA125), sometimes mimicking an ovarian malignancy. At our hospital, we often perform examination laparoscopic surgery in cases of suspected gynecologic cancers before initial treatment. In this paper, we report the case of a 19-year-old woman who came to our hospital because of an ovarian tumor and ascites. There was no history of sexual intercourse (self-reported). We suspected ovarian cancer from image inspections, so we performed laparoscopic surgery for diagnosis. The final pathological diagnosis was acute-to-chronic inflammation of the bilateral fallopian tubes, and a cytologic examination of the ascites was negative for malignant cells. The C. trachomatis antigen was positive on vaginal examination after the operation. Based on this result, we diagnosed this patient with C. trachomatis infection. Chlamydia peritonitis should be a differential diagnosis for cancer peritonitis in juvenile patients with abnormal ascites. Exploratory laparoscopy should help confirm the pathological diagnosis.

Abstract Plastic bronchitis is a rare and fatal disease that is characterized by the presence of long dendritic bronchial casts in the airway. It is encountered most frequently in children with congenital heart disease after correction surgery. We reported a case of plastic bronchitis after mitral valve surgery in a 70‐year‐old woman.

Autoimmune coagulation factor XIII deficiency is a bleeding disorder caused by the formation of autoantibodies against the coagulation factor XIII (FXIII); however, the molecular mechanism underlying this process is unknown. Therefore, in the present study, we aimed to elucidate this mechanism by performing whole-exome sequencing analysis of 20 cases of autoimmune FXIII deficiency. We identified approximately 21,788-23,916 variants in each case. In addition to their ability to activate T cells, present antigens, and immune tolerance, the candidate alleles were further narrowed down according to their allelic frequencies and the magnitude of damage caused by the substitution of amino acids. After selecting 44 candidate alleles, we investigated whether they were associated with the FXIII inhibitory titers and/or the anti-FXIII autoantibodies. We found that two polymorphisms whose variant allele frequencies were significantly lower in the patients tended to decrease FXIII inhibitory titers as the number of variant alleles increased. We also found that five polymorphisms whose variant allele frequencies were significantly higher in the patients tended to increase the levels of the anti-FXIII autoantibodies as the number of variant alleles increased. All of these polymorphisms were found in the human leukocyte antigen (HLA) class I and II molecules and their associated genes. In particular, the HLA class II molecule and its associated genes were found to be involved in the presentation of foreign antigens as well as the negative regulation of the proliferation of T-cells and the release of cytokines. Polymorphisms in the HLA class II molecules and the cytotoxic T lymphocyte antigen 4 have been reported to be associated with the development of autoantibodies in acquired hemophilia A. Therefore, we hypothesized that these polymorphisms may be associated with the development of autoantibodies in autoimmune FXIII deficiency.

The prevalence of symptomatic insomnia and the prevalence of restless legs syndrome (RLS) are known to be higher among patients with rheumatic diseases compared to the general population. The prevalences of insomnia and RLS reported in a questionnaire by Japanese patients with rheumatic diseases at an outpatient clinic were analyzed herein. The association between the patients' disease activity and their sleep quality was analyzed. Of 121 rheumatic disease patients, 70 were enrolled. The median (interquartile range) age at enrollment was 62.0 (47.8-68.0) years. There were 58 women (82.9%) and 12 men (17.1%), and 43 patients (61.4%) with rheumatoid arthritis (RA), nine (12.9%) with systemic lupus erythematosus (SLE), and 18 (25.7%) with other rheumatic diseases. Twenty patients (28.6%) had one or more moderate-to-severe insomnia symptoms, and 10 (14.3%) were diagnosed with RLS. Among the patients with RA, the swollen joint count based on a 28-joint assessment (SJC28) was significantly higher in the insomnia group (n = 13) compared to the non-insomnia group (n = 30) (p = 0.006). A classification and regression tree (CART) analysis showed that the cut-off points of ≥3 mg/day prednisolone (PSL) treatment and

Pentatricopeptide repeat (PPR) proteins, composed of PPR motifs repeated in tandem, are sequence-specific RNA binding proteins. Recent bioinformatic studies have shown that the combination of polar amino acids at positions 5 and last in each PPR motif recognizes RNA bases, and an RNA recognition code for PPR proteins has been proposed. Subsequent studies confirmed that the P (canonical length) and S (short) motifs bind to specific nucleotides according to this code. However, the contribution of L (long) motifs to RNA recognition is mostly controversial, owing to the presence of a nonpolar amino acid at position 5. The PLS-class PPR protein PpPPR_56 is a mitochondrial RNA editing factor in the moss Physcomitrella patens. Here, we performed in vitro RNA binding and in vivo complementation assays with PpPPR_56 and its variants containing mutated L motifs to investigate their contributions to RNA recognition. In vitro RNA binding assay showed that the original combination of amino acids at positions 5 and last in the L motifs of PpPPR_56 is not required for RNA recognition. In addition, an in vivo complementation assay with RNA editing factors PpPPR_56 and PpPPR_78 revealed the importance of nonpolar amino acids at position 5 of C-terminal L motifs for efficient RNA editing. Our findings suggest that L motifs function as non-binding spacers, not as RNA-binding motifs, to facilitate the formation of a complex between PLS-class PPR protein and RNA. As a result, the DYW domain, a putative catalytic deaminase responsible for C-to-U RNA editing, is correctly placed in proximity to C, which is to be edited.

The physiological actions of orally ingested peptides on the brain remain poorly understood. This study examined the effects of 39 orally administered synthetic Tyr-containing dipeptides on the enhancement of brain norepinephrine metabolism in mice by comparing the concentration of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). Although Tyr-Tyr administration increased blood and cerebral cortex (Cx) Tyr concentrations the most, Tyr-Trp increased Cx MHPG concentration the most. The oral administration of Tyr-Trp ameliorated a short-term memory deficit of a mouse model of cognitive dysfunction induced by amyloid beta peptide 25-35. Gene expression profiling of mouse brain using a microarray indicated that Tyr-Trp administration led to a wide variety of changes in mRNA levels, including the upregulation of genes encoding molecules involved in catecholamine metabolism. A comparative metabolome analysis of the Cx of mice given Tyr-Trp or Tyr-Tyr demonstrated that Tyr-Trp administration yielded higher concentrations of Trp and kynurenine pathway metabolites than Tyr-Tyr administration, as well as higher L-dopa levels, which is the initial product of catecholamine metabolism. Catecholamines were not significantly increased in the Cx of the Tyr-Tyr group compared with the Tyr-Trp group, despite a marked increase in Tyr. Presumably, Tyr-Trp administration enhances catecholamine synthesis and metabolism via the upregulation of genes involved in Tyr and Trp metabolism as well as metabolites of Tyr and Trp. These findings strongly suggest that orally ingested Tyr-Trp modulates the brain metabolome involved in catecholamine metabolism and contributes to higher brain function.

In some athletic races, such as cycling and types of speed skating races, athletes have to complete a relatively long distance at a high speed in the presence of direct opponents. To win such a race, athletes are motivated to hide behind others to suppress energy consumption before a final moment of the race. This situation seems to produce a social dilemma: players want to hide behind others, whereas if a group of players attempts to do so, they may all lose to other players that overtake them. To support that speed skaters are involved in such a social dilemma, we analyzed video footage data for 14 mass start skating races to find that skaters that hid behind others to avoid air resistance for a long time before the final lap tended to win. Furthermore, the finish rank of the skaters in mass start races was independent of the record of the same skaters in time-trial races measured in the absence of direct opponents. The results suggest that how to strategically cope with a skater's dilemma may be a key determinant for winning long-distance and high-speed races with direct opponents.

The effectiveness of a simulated microgravity environment as a novel method for preserving the freshness of vegetables was investigated. Three types of vegetables were selected: vegetable soybean, mung bean sprouts, and white radish sprouts. These selected vegetables were fixed on a three-dimensional rotary gravity controller, rotated slowly. The selected vegetables were stored at 25°C and 66% of relative humidity for 9, 6, or 5 d while undergoing this process. The simulated microgravity was controlled utilizing a gravity controller around 0 m s-2. The mung bean sprouts stored for 6 d under simulated microgravity conditions maintained higher thickness levels than the vegetable samples stored under normal gravity conditions (9.8 m s-2) for the same duration. The mass of all three items decreased with time without regard to the gravity environment, though the samples stored within the simulated microgravity environment displayed significant mass retention on and after 3 d for mung bean sprout samples and 1 d for white radish sprout samples. In contrast, the mass retention effect was not observed in the vegetable soybean samples. Hence, it was confirmed that the mass retention effect of microgravity was limited to sprout vegetables. As a result of analysis harnessing a mathematical model, assuming that the majority of the mass loss is due to moisture loss, a significant difference in mass reduction coefficient occurs among mung bean sprouts and white radish sprouts due to the microgravity environment, and the mass retention effect of simulated microgravity is quantitatively evaluated utilizing mathematical models. Simulated microgravity, which varies significantly from conventional refrigeration, ethylene control, and modified atmosphere, was demonstrated effective as a novel method for preserving and maintaining the freshness of sprout vegetables. This founding will support long-term space flight missions by prolonging shelf life of sprout vegetables.

Abstract The Dirac fermion is an important fundamental particle appearing in high-energy physics and topological insulator physics. In particular, a Dirac fermion in a one-dimensional lattice system exhibits the essential properties of topological physics. However, the system has not been quantum simulated in experiments yet. Herein, we propose a one-dimensional generalized lattice Wilson-Dirac fermion model and study its topological phase structure. We show the experimental setups of an atomic quantum simulator for the model, in which two parallel optical lattices with the same tilt for trapping cold fermion atoms and a laser-assisted hopping scheme are used. Interestingly, we find that the model exhibits nontrivial topological phases characterized by gapless edge modes and a finite winding number in the broad regime of the parameter space. Some of the phase diagrams closely resemble those of the Haldane model. We also discuss topological charge pumping and a lattice Gross-Neveu model in the system of generalized Wilson-Dirac fermions.

Abstract Predator-prey systems have been studied intensively for over a hundred years. These studies have demonstrated that the dynamics of Lotka-Volterra (LV) systems are not stable, that is, exhibiting either cyclic oscillation or divergent extinction of one species. Stochastic versions of the deterministic cyclic oscillations also exhibit divergent extinction. Thus, we have no solution for asymptotic stability in predator-prey systems, unlike most natural predator-prey interactions that sometimes exhibit stable and persistent coexistence. Here, we demonstrate that adding a small immigration into the prey or predator population can stabilize the LV system. Although LV systems have been studied intensively, there is no study on the non-linear modifications that we have tested. We also checked the effect of the inclusion of non-linear interaction term to the stability of the LV system. Our results show that small immigrations invoke stable convergence in the LV system with three types of functional responses. This means that natural predator-prey populations can be stabilized by a small number of sporadic immigrants.

Abstract Understanding mechanisms of biodiversity has been a central question in ecology. The coexistence of three species in rock-paper-scissors (RPS) systems are discussed by many authors; however, the relation between coexistence and network structure is rarely discussed. Here we present a metapopulation model for RPS game. The total population is assumed to consist of three subpopulations (nodes). Each individual migrates by random walk; the destination of migration is randomly determined. From reaction-migration equations, we obtain the population dynamics. It is found that the dynamic highly depends on network structures. When a network is homogeneous, the dynamics are neutrally stable: each node has a periodic solution, and the oscillations synchronize in all nodes. However, when a network is heterogeneous, the dynamics approach stable focus and all nodes reach equilibriums with different densities. Hence, the heterogeneity of the network promotes biodiversity.

Abstract Immune responses to parasitic pathogens are affected by the host physiological condition. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) are transporters of lipids between the liver and peripheral tissues, and modulate pro-inflammatory immune responses. Pathogenic mycobacteria are parasitic intracellular bacteria that can survive within macrophages for a long period. Macrophage function is thus key for host defense against mycobacteria. These basic facts suggest possible effects of HDL and LDL on mycobacterial diseases, which have not been elucidated so far. In this study, we found that HDL and not LDL enhanced mycobacterial infections in human macrophages. Nevertheless, we observed that HDL remarkably suppressed production of tumor necrosis factor alpha (TNF-α) upon mycobacterial infections. TNF-α is a critical host-protective cytokine against mycobacterial diseases. We proved that toll-like receptor (TLR)-2 is responsible for TNF-α production by human macrophages infected with mycobacteria. Subsequent analysis showed that HDL downregulates TLR2 expression and suppresses its intracellular signaling pathways. This report demonstrates for the first time the substantial action of HDL in mycobacterial infections to human macrophages.

Abstract Comprehensive crystal structural study is performed for BiFeO3 (BFO) film grown on KTaO3 (KTO) substrate using transmission electron microscopy (TEM) and x-ray diffraction (XRD). Nano-beam electron diffraction (NBED) combined with structure factor calculation and high resolution TEM images clearly reveal that the crystal structure within BFO thin film is rhombohedral BFO, i.e., bulk BFO phase. Epitaxial relationship found by NBED indicates the BFO film grows in a manner that minimizes lattice mismatch with KTO. It further suggests BFO film is under slight biaxial tensile stress (~0.35%) along in-plane direction. XRD reveals BFO lattice is under compressive stress (~1.6%), along out-of-plane direction as a result of the biaxial tensile strain applied along in-plane direction. This leads to Poisson’s ratio of ~0.68. In addition, we demonstrate (1) why hexagonal notation rather than pseudocubic one is required for accurate BFO phase evaluation and (2) a new XRD method that shows how rhombohedral BFO can readily be identified among other phases by measuring a rhombohedral specific Bragg’s reflection.

Abstract Ayu fish form feeding territories during a non-breeding (growing) season. When the density of the fish increases, phases gradually change. In the early growing season, all fish can hold territories at low density. Once all territory sites are occupied, newcomers become floaters. As the density further increases, territory holders have to spend much more time in defending their own territory and lose the time to feed on algae. Eventually, all fish give up their own territories and then form a school. In contrast, when the density decreases, territories are directly reformed from the school. In short, ayu fish exhibit a different transition, called hysteresis, where the two transitions occur widely-apart from each other. The dynamics of this intrinsic phenomena has not been demonstrated in previous studies. We develop a rate equation to describe the population dynamics within territorial competition. Our model successfully reproduces territorial hysteresis and indicates that territory holders and floaters can coexist only in the process of population growth. Moreover, we also find that the two critical densities of territorial hysteresis are conspicuously different from each other when the increase of the density of floaters sharply influences (step-function-like) the territories.

Epidermal growth factor receptor (EGFR) mutations have been used as the strongest predictor of effectiveness of treatment with EGFR tyrosine kinase inhibitors (TKIs). Three most common EGFR mutations (L858R, exon 19 deletion, and T790M) are known to be major selection markers for EGFR-TKIs therapy. Here, we developed a multiplex picodroplet digital PCR (ddPCR) assay to detect 3 common EGFR mutations in 1 reaction. Serial-dilution experiments with genomic DNA harboring EGFR mutations revealed linear performance, with analytical sensitivity ~0.01% for each mutation. All 33 EGFR-activating mutations detected in formalin-fixed paraffin-embedded (FFPE) tissue samples by the conventional method were also detected by this multiplex assay. Owing to the higher sensitivity, an additional mutation (T790M; including an ultra-low-level mutation,

Cerebral white matter lesions are ischemic symptoms caused mainly by microangiopathy; they are diagnosed by MRI because they show up as abnormalities in MRI images. Because patients with white matter lesions do not have any symptoms, MRI often detects the lesions for the first time. Generally, head MRI for the diagnosis and grading of cerebral white matter lesions is performed as an option during medical checkups in Japan. In this study, we develop a mathematical model for the prediction of white matter lesions using data from routine medical evaluations that do not include a head MRI. Linear discriminant analysis, logistic discrimination, Naive Bayes classifier, support vector machine, and random forest were investigated and evaluated by ten-fold cross-validation, using clinical data for 1,904 examinees (988 males and 916 females) from medical checkups that did include the head MRI. The logistic regression model was selected based on a comparison of accuracy and interpretability. The model variables consisted of age, gender, plaque score (PS), LDL, systolic blood pressure (SBP), and administration of antihypertensive medication (odds ratios: 2.99, 1.57, 1.18, 1.06, 1.12, and 1.52, respectively) and showed Areas Under the ROC Curve (AUC) 0.805, the model displayed sensitivity of 72.0%, and specificity 75.1% when the most appropriate cutoff value was used, 0.579 as given by the Youden Index. This model has shown to be useful to identify patients with a high-risk of cerebral white matter lesions, who can then be diagnosed with a head MRI examination in order to prevent dementia, cerebral infarction, and stroke.

Accurate evaluation of disease activity is essential for choosing an appropriate treatment and follow-up plan for patients with inflammatory bowel disease (IBD). Endoscopy is required for accurately evaluating disease activity, but the procedures are sometimes invasive and burdensome to patients. Therefore, alternative non-invasive methods for evaluating or predicting disease activity including mucosal status are desirable. Fecal calprotectin (Fcal) is the most widely used fecal marker for IBD, and many articles have described the performance of the marker in predicting disease activity, mucosal healing (MH), treatment efficacy, and risk of relapse. Fecal immunochemical test (FIT) can quantify the concentration of hemoglobin in stool and was originally used for the screening of colorectal cancer. We recently reported that FIT is also a useful biomarker for IBD. A direct comparison between the use of Fcal and FIT showed that both methods predicted MH in ulcerative colitis equally well. However, in the case of Crohn's disease, FIT was less sensitive to lesions in the small intestine, compared to Fcal. FIT holds several advantages over Fcal in regards to user-friendliness, including a lower cost, easy and clean handling, and the ability to make rapid measurements by using an automated measurement system. However, there is insufficient data to support the application of FIT in IBD. Further studies into the use of FIT for evaluating the inflammatory status of IBD are warranted.