Impact of computer-aided characterization for diagnosis of colorectal lesions, including sessile serrated lesions: Multireader, multicase study.

OBJECTIVES: Computer-aided characterization (CADx) may be used to implement optical biopsy strategies into colonoscopy practice; however, its impact on endoscopic diagnosis remains unknown. We aimed to evaluate the additional diagnostic value of CADx when used by endoscopists for assessing colorectal polyps. METHODS: This was a single-center, multicase, multireader, image-reading study using randomly extracted images of pathologically confirmed polyps resected between July 2021 and January 2022. Approved CADx that could predict two-tier classification (neoplastic or nonneoplastic) by analyzing narrow-band images of the polyps was used to obtain a CADx diagnosis. Participating endoscopists determined if the polyps were neoplastic or not and noted their confidence level using a computer-based, image-reading test. The test was conducted twice with a 4-week interval: the first test was conducted without CADx prediction and the second test with CADx prediction. Diagnostic performances for neoplasms were calculated using the pathological diagnosis as reference and performances with and without CADx prediction were compared. RESULTS: Five hundred polyps were randomly extracted from 385 patients and diagnosed by 14 endoscopists (including seven experts). The sensitivity for neoplasia was significantly improved by referring to CADx (89.4% vs. 95.6%). CADx also had incremental effects on the negative predictive value (69.3% vs. 84.3%), overall accuracy (87.2% vs. 91.8%), and high-confidence diagnosis rate (77.4% vs. 85.8%). However, there was no significant difference in specificity (80.1% vs. 78.9%). CONCLUSIONS: Computer-aided characterization has added diagnostic value for differentiating colorectal neoplasms and may improve the high-confidence diagnosis rate.

Isoform-Selective Fluorescent Labeling of 14-3-3σ by Acrylamide-Containing Fusicoccins.

The 14-3-3 family of proteins is central to the regulation of signaling pathways driven by serine/threonine kinases. In humans, 14-3-3 consists of seven highly conserved isoforms, yet the function of each isoform remains to be fully elucidated. Synthetic agents capable of isoform-specific fluorescent labeling of 14-3-3 would provide a useful tool for studying in depth the biological roles of isoforms. In this study, the 14-3-3σ isoform was evaluated, which possesses a unique Cys38, and a natural product-based fluorescent labeling agent was designed by introducing an acrylamide group and a fluorescent dye to fusicoccin (FC). In vitro evaluation demonstrated that 12-hydroxy 1 and 2 exhibit 14-3-3σ selective labeling activity over 14-3-3ζ in the presence of a mode-3 phospholigand. Furthermore, 2 was shown to label 14-3-3σ in cell lysate in the presence of a C-terminal mode-3 phosphopeptide derived from ERα, with no apparent nonspecific labeling. These results indicate that 2 is capable of selective fluorescent detection of 14-3-3σ upon binding to mode-3 phospholigand under biologically relevant conditions.

Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on Emergency Patients Hospitalized With Cardiocerebrovascular Diseases in Osaka Prefecture, Japan　- A Population-Based Study.

BACKGROUND: Little is known about the transport and outcomes of emergency patients with cardiocerebrovascular diseases in Japan before and during the COVID-19 pandemic.Methods and Results: Data were extracted from a population-based registry in Osaka, Japan, from 2019 to 2021. There were almost no differences in the numbers of emergency patients hospitalized with myocardial infarction, stroke, or heart failure or their deaths. However, the number of cases of difficulty obtaining patient acceptance by hospitals increased in 2020 and 2021 compared with 2019. CONCLUSIONS: The numbers of emergency patients hospitalized with cardiocerebrovascular diseases and their deaths in Osaka were not affected by the COVID-19 epidemic.

People with high empathy show increased cortical activity around the left medial parieto-occipital sulcus after watching social interaction of on-screen characters.

People with high empathy interpret others' mental states in daily social interactions. To investigate their characteristics of social cognitive processing, we compared neuromagnetic activities between 20 males with high empathy and 23 males with low empathy while watching social interactions between two characters. Twenty stories of four-panel comic strips were presented; the first three panels described social interactions, and the last panel described empathic/nonempathic behaviors. People with high empathy exhibited increased cortical activity in the right occipital region, medial part of the bilateral superior frontal gyri, and right posterior insula while watching social interaction scenes, which suggests that they paid attention to others' faces and bodies, and inferred others' mental states. They also exhibited increased cortical activity in the left superior frontal gyrus while watching empathic behaviors. Moreover, they exhibited increased cortical activity in the region around the left medial parieto-occipital sulcus, which is related to self-projection, while passively watching both empathic and nonempathic endings. Taken together, these results suggest that people with high empathy pay attention to others and actively infer others' mental states while watching social interactions and that they reconstruct others' mental states and intentions through self-projection after watching a sequence of others' behaviors.

Effectiveness of Screening Using Fecal Occult Blood Testing and Colonoscopy on the Risk of Colorectal Cancer: The Japan Public Health Center-based Prospective Study.

BACKGROUND: Few cohort studies have used multiple surveys of screening attendance to simultaneously evaluate the effectiveness of fecal occult blood test (FOBT) and colonoscopy. METHODS: We analyzed data of 30,381 middle-aged Japanese adults from a population-based prospective cohort study. Information on FOBT and colonoscopy was obtained from three questionnaire surveys (every 5 years). We classified the subjects into three groups: the FOBT (15,649 subjects), screening colonoscopy (2,407 subjects), and unscreened (12,325 subjects) groups. We used the unscreened group as the reference group to compare the mortality and incidence of colorectal cancer (CRC). RESULTS: During the 14-year follow-up, 64, 12, and 104 CRC deaths were identified in the FOBT, screening colonoscopy, and unscreened groups, respectively. The risk of CRC death reduced with increasing the number of FOBTs (P for trend = 0.02) and was reduced by 44% in the subjects screened twice or thrice using FOBT (hazard ratio [HR] 0.56; 95% confidence interval [CI], 0.33-0.94). Significant decreases were seen for the incidence of CRC but not seen for the incidence of non-advanced CRC in the FOBT group. Concerning the screening colonoscopy, subjects screened at the start of follow-up showed a 69% reduced risk of CRC death (HR 0.31; 95% CI, 0.10-0.9996). Significant decreases were also seen for the incidence of CRC and non-advanced CRC in the subjects screened at the start of follow-up. CONCLUSION: FOBT, depending on the number of FOBTs, and colonoscopy, depending on recency, reduced the risk of death due to CRC and the incidence of CRC.

Effect of cyborg-type robot Hybrid Assistive Limb on patients with severe walking disability in acute stroke: A randomized controlled study.

OBJECTIVES: To investigate whether early gait training using Hybrid Assistive Limb (HAL) is feasible and improves walking and independency compared with conventional physical therapy (CPT) in patients with severe walking disability after stroke. METHODS: We conducted a single-center, randomized controlled study. Patients with first-ever stroke who had severe walking disability were included. All patients started gait training within 10 days post-stroke onset. Twenty-four patients were randomly assigned into HAL or CPT groups. Outcome measures were collected at three time points, at baseline, completion of 20 sessions of gait training (second assessment), and 3 months after the initiation of gait training. The primary outcomes were changes in motor sub-scores of the Functional Independence Measure or Functional Ambulation Category at the completion of the second assessment from baseline. RESULTS: Twenty-two patients (median age, 68 years; 12 patients in the HAL group and 10 patients in the CPT group) completed the study. There were no significant differences in primary outcomes. Apathy scale, one of the secondary outcomes, showed a decreasing trend in the HAL group (mean change of -3.8, 95% CI -8.14 to 0.475), and a slight increasing trend in the CPT group (mean change of 1.2, 95% CI -2.66 to 5.06) at the second assessment. Patients in the HAL group experienced no adverse events. CONCLUSIONS: Early gait training in patients with severe walking disability after stroke using HAL was feasible. Walking ability and independency were not improved at the completion of 20 sessions of gait training.

Moderately Oxidizing Thioxanthylium Organophotoredox Catalysts for Radical-Cation Diels-Alder Reactions.

Moderately oxidizing thioxanthylium photoredox catalysts that operate under irradiation with green light have been developed. These catalysts exhibit relatively moderate excited-state reduction potentials [E1/2(C*/C•-) = 1.75-1.94 V vs saturated calomel electrode (SCE)] and can efficiently promote radical-cation Diels-Alder reactions under irradiation with green light. Interestingly, ß-halogenostyrenes (Ep/2 = 1.57-1.61 V vs SCE) are well tolerated, affording synthetically useful halocyclohexenes.

Study of the Structure-Activity Relationship of an Anti-Dormant Mycobacterial Substance 3-(Phenethylamino)Demethyl(oxy)aaptamine to Create a Probe Molecule for Detecting Its Target Protein.

The current tuberculosis treatment regimen is long and complex, and its failure leads to relapse and emergence of drug resistance. One of the major reasons underlying the extended chemotherapeutic regimen is the ability of Mycobacterium tuberculosis to attain a dormant state. Therefore, the identification of new lead compounds with chemical structures different from those of conventional anti-tuberculosis drugs is essential. The compound 3-(phenethylamino)demethyl(oxy)aaptamine (PDOA, 1), isolated from marine sponge of Aaptos sp., is known as an anti-dormant mycobacterial substance, and has been reported to be effective against the drug resistant strains of M. tuberculosis. However, its target protein still remains unclear. This study aims to clarify the structure-activity relationship of 1 using 15 synthetic analogues, in order to prepare a probe molecule for detecting the target protein of 1. We succeeded in creating the compound 15 with a photoaffinity group that retained antimicrobial activity, which proved to be a suitable probe molecule for identifying the target protein of 1.

Beyond complete endoscopic healing: Goblet appearance using an endocytoscope to predict future sustained clinical remission in ulcerative colitis.

OBJECTIVES: Complete endoscopic healing, defined as Mayo endoscopic score (MES) = 0, is an optimal target in the treatment of ulcerative colitis (UC). However, some patients with MES = 0 show clinical relapse within 12 months. Histologic goblet mucin depletion has emerged as a predictor of clinical relapse in patients with MES = 0. We observed goblet depletion in vivo using an endocytoscope, and analyzed the association between goblet appearance and future prognosis in UC patients. METHODS: In this retrospective cohort study, all enrolled UC patients had MES = 0 and confirmed clinical remission between October 2016 and March 2020. We classified the patients into two groups according to the goblet appearance status: preserved-goblet and depleted-goblet groups. We followed the patients until March 2021 and evaluated the difference in cumulative clinical relapse rates between the two groups. RESULTS: We identified 125 patients with MES = 0 as the study subjects. Five patients were subsequently excluded. Thus, we analyzed the data for 120 patients, of whom 39 were classified as the preserved-goblet group and 81 as the depleted-goblet group. The patients were followed-up for a median of 549 days. During follow-up, the depleted-goblet group had a significantly higher cumulative clinical relapse rate than the preserved-goblet group (19% [15/81] vs. 5% [2/39], respectively; P = 0.02). CONCLUSIONS: Observing goblet appearance in vivo allowed us to better predict the future prognosis of UC patients with MES = 0. This approach may assist clinicians with onsite decision-making regarding treatment interventions without a biopsy.

Influence of commuting methods on low back pain and musculoskeletal function of the lower limbs in elementary school children: A cross-sectional study.

BACKGROUND: Lower limb flexibility is known to be decreased in those living in mountainous areas, and musculoskeletal growth is often influenced by lifestyle factors. The purpose of this study was to determine the relationship between the means of transportation to school and lower limb musculoskeletal function and low back pain. METHODS: During routine medical examinations conducted in two cities in a prefecture in 2016, a questionnaire was administered. The parents of 15,259 students who attended elementary school answered questions evaluating the following parameters: (1) anteflexion limit in the standing posture, (2) crouching failure, (3) one leg standing failure, (4) low back pain during lumbar extension, (5) lower limb alignment abnormalities, and (6) flat foot. Students were divided into a walking commuting group (13,569 students) and a vehicle commuting group (1690 students), and findings were compared between the two groups using chi-square tests. RESULTS: In the walking and vehicle commuting groups, anteflexion limit in the standing posture was present in 23.3% and 26.1% of students, respectively (p = 0.013). Crouching failure was present in 4.6% and 7.3% of students (p < 0.001); one leg standing failure in 5.3% and 8.5% of students (p < 0.001); low back pain in 5.0% and 7.1% of students (p < 0.001); positive leg alignment abnormalities in 7.3% and 8.0% of students (p = 0.260); and flat foot in 7.4% and 8.7% of students (p = 0.067), respectively. Significant differences were observed in all four of the failure measures. No significant differences were observed in the two methods evaluating morphological abnormalities. CONCLUSIONS: The decreased walking duration and increased sitting duration associated with vehicle commuting had little effect on lower limb morphology but could induce lower limb dysfunction and low-back pain in children. Thus, supplemental walking should be instated for children who commute by car.

Smoking and colorectal cancer: A pooled analysis of 10 population-based cohort studies in Japan.

Smoking has been consistently associated with the risk of colorectal cancer (CRC) in Western populations; however, evidence is limited and inconsistent in Asian people. To assess the association of smoking status, smoking intensity and smoking cessation with colorectal risk in the Japanese population, we performed a pooled analysis of 10 population-based cohort studies. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox's proportional hazards model and then pooled using a random-effects model. Among 363 409 participants followed up for 2 666 004 person-years, 9232 incident CRCs were identified. In men, compared with never smokers, ever smokers showed higher risk of CRC. The HRs (95% CI) were 1.19 (1.10-1.29) for CRC, 1.19 (1.09-1.30) for colon cancer, 1.28 (1.13-1.46) for distal colon cancer and 1.21 (1.07-1.36) for rectal cancer. Smoking was associated with risk of CRC in a dose-response manner. In women, compared with never smokers, ever smokers showed increased risk of distal colon cancer (1.47 [1.19-1.82]). There was no evidence of a significant gender difference in the association of smoking and CRC risk. Our results confirm that smoking is associated with an increased risk of CRC, both overall and subsites, in Japanese men and distal colon cancer in Japanese women.

Integrated Flow Synthesis of α-Amino Acids by In Situ Generation of Aldimines and Subsequent Electrochemical Carboxylation.

The synthesis of α-amino acids was carried out in a continuous flow system. In this system, aldimines were efficiently generated in situ via the dehydration-condensation of aldehydes with anilines in a desiccant bed column filled with 4 Å molecular sieves desiccant, followed by reaction with CO2 in an electrochemical flow microreactor to afford the α-amino acids in high to moderate yields. The present system can provide α-amino acids without using stoichiometric amounts of metal reagents or highly toxic cyanide reagents.

Visible-light-induced [4 + 2] cycloaddition of pentafulvenes by organic photoredox catalysis.

We have developed thioxanthylium photoredox catalyzed [4 + 2] cycloaddition of pentafulvenes at room temperature under green light irradiation, which affords tetrahydrocyclopenta[b]chromenes with high regioselectivities. The present reaction provides a sustainable approach to carry out the cycloaddition of pentafulvenes without the use of transition metal catalysts or high-temperature conditions. This procedure enables a mild and straightforward access to 1,3a,9,9a-tetrahydrocyclopenta[b]chromenes. The quantum yield of the reaction (Φ = 0.15) indicates that the reaction would mainly proceed via photocatalytic pathways.

Organophotoredox-Catalyzed Intermolecular Oxa-[4+2] Cycloaddition Reactions.

An intermolecular oxa-[4+2] cycloaddition reaction promoted by a thioxanthylium photoredox catalyst under irradiation with green light has been developed. The reaction of ortho-quinone methides with styrenes smoothly affords the desired cycloadducts. Especially styrenes bearing electron-donating groups are efficiently transformed in this reaction. This method represents a sustainable way to carry out oxa-[4+2] cycloaddition reactions using only a catalytic amount of a photocatalyst and visible light.

Access to Electron-Deficient 2,2-Disubstituted Chromanes: A Highly Regioselective One-Pot Synthesis via an Inverse-Electron-Demand [4 + 2] Cycloaddition of ortho-Quinone Methides.

We report the one-pot synthesis of 2,2-disubstituted chromanes with electron-withdrawing substituents. This reaction provides a simple yet efficient route to a wide range of electron-deficient chromanes in high yield and excellent regioselectivity. The reaction of salicylaldehyde with 1,1-disubstituted ethylenes smoothly furnishes these electron-deficient chromanes, which can be further transformed into functionalized chromanes or chromene. For example, BW683C was effectively synthesized from 5-chlorosalicylaldehyde with 4-chlorostyrene in two steps in excellent yield. The present reaction thus provides versatile access to functionalized electron-deficient chromanes and chromenes and therefore constitutes a promising tool for the synthesis of biologically and photochemically active molecules.

Change in MRI findings of medial collateral ligament injury in adolescent baseball players with no clinical symptoms over time.

OBJECTIVE: Elbow screening of adolescent baseball players began in 2014 using ultrasound, palpation, and dedicated magnetic resonance imaging (MRI). We frequently encountered subjects showing MCL injury on MRI but no clinical symptoms. We assessed variations in asymptomatic MCL injury findings at follow-up MRI, and clarified the pathogenesis of these findings. MATERIALS AND METHODS: Using a 0.2-T-dedicated MRI, 30 subjects with asymptomatic MCL injury at initial MRI who agreed to follow-up MRI were included. We classified the findings at repeat MRI as follows: (a) disappeared, (b) better, and (c) worse. RESULTS: There were 6, 16, and 8 subjects in groups a, b, and c, respectively. The average age at follow-up was 14.0, 12.1, and 12.4 years in groups a, b, and c, respectively. There were significant differences between groups a and b and between groups a and c. Average height at follow-up of groups a, b, and c was 1.64, 1.52, and 1.57 cm, respectively, with a statistically significant difference between groups a and b. The average size of the short axis of the MCL of subjects in group a was 2.0 cm on the dominant side and 1.5 cm on the contradominant side (P < 0.04). CONCLUSION: Players with asymptomatic MCL injury can continue to play baseball with no limitations, as these findings usually disappear around the age of 14.0 years, when the growth spurt occurs. This finding may be a precursor of 'adaptation', which is generally observed in high school baseball players, suggesting that the MCL adapts as growth occurs.

Screening for musculoskeletal problems in children using a questionnaire.

BACKGROUND: On April 1, 2016, the Ministerial ordinance was enforced, and musculoskeletal examination of the extremities was made mandatory. From 2008, the University of us started musculoskeletal direct examination. To expand the examination, from 2016, we started to use the marksheet-type questionnaire. This study aimed to report the results of a musculoskeletal examination and investigate the association between musculoskeletal examination and age/gender and reports the reliability of the collected questionnaire data. METHODS: Direct musculoskeletal examination was performed in K school by 7 orthopedic surgeons. A marksheet-type screening questionnaire was distributed to all the elementary and junior high school students in Tsukuba and Hitachiomiya cities. The rates of abnormal findings for scoliosis, standing flexion, full squatting with the heels on the floor, general joint laxity, and standing on one leg, torticollis, and flat feet were calculated. We compared the results of the questionnaire and direct examination and calculated sensitivity, specificity, and odds ratio. RESULTS: A total of 1844 students in K school had direct examination, and 22,494 questionnaires were able to correct in Tsukuba and Hitachiomiya cities. The rates of abnormal findings in direct examination/questionnaire in scoliosis, standing flexion, full squat, general joint laxity, standing on one leg, torticollis and flat foot were 18.7% (344/1842)/5.1% (1094/21441), 20.2% (372/1841)/26.6% (5817/22078), 6.2% (114/1832)/6.9% (1516/22101), 7.5% (1648/22252), 4.9% (1100/22077), 2.2% (31/1844)/1.2% (272/21687), and 12.5% (231/1842)/8.7% (1785/20871), respectively. Sensitivities of the questionnaire for scoliosis, stand flexion, full squatting, torticollis, and flat feet were 16.8% (53/316), 67.9% (250/368), 48.2% (55/114), 18.9% (7/37), and 32.2% (65/202), respectively. CONCLUSION: We reported the result of musculoskeletal examination. Accuracy and reliability of this questionnaire were not satisfactory. To perform high quality musculoskeletal examinations, we will aim to increase the quality of screening methods.

Friedel-Crafts approach to the one-pot synthesis of methoxy-substituted thioxanthylium salts.

An efficient synthesis of methoxy-substituted thioxanthylium salts has been developed. The reaction of diaryl sulfides with benzoyl chlorides in the presence of TfOH smoothly proceeded to give the desired thioxanthylium salts in good yields. In their UV-vis spectra, the maximum absorption wavelengths of methoxy-functionalized thioxanthylium salts were observed at around 460 nm, which show a drastic red shift compared to the parent thioxanthylium salts. The present reaction provides a versatile access to functionalized thioxanthylium salts, and therefore it constitutes a promising tool for the synthesis of biologically and photochemically active molecules.

Normal imaging laterality on magnetic resonance imaging of the medial epicondyle of the elbow on the dominant side of adolescent male baseball players.

OBJECTIVE: Multimodality elbow screening of adolescent baseball players shows apparent laterality in morphology and signal intensity of the medial epicondyle on dedicated magnetic resonance imaging. We aimed to elucidate actual imaging laterality in the medial epicondyle by comparing magnetic resonance images of the dominant and contradominant elbows and to clarify the clinical meaning and mechanism of this phenomenon. MATERIALS AND METHODS: We used a 0.2-T dedicated magnetic resonance imaging scanner. Eighty adolescent baseball players were enrolled and divided into four age groups: 9-10 years (13 patients); 11 years (28 patients); 12 years (24 patients) and 13-14 years (15 patients). The long and short axes of the ossification center and distance of the epiphyseal plate and the cartilage of the lower pole of the medial epicondyle were measured. Signal intensity of the ossification center was visually evaluated. RESULTS: Owing to their age, ossification and cartilage size on the dominant side were significantly larger in all boys (P < 0.01). All age groups had larger ossification and cartilage in the dominant elbow (P < 0.01). Ossification showed an apparent lower signal intensity on the dominant side (P < 0.01). CONCLUSIONS: Larger ossification and cartilage size of the medial epicondyle in the dominant elbow suggested that the medial collateral ligament to the medial epicondyle induces excessive repetitive tensile stress, but without clinical symptoms. Functional or microanatomical damage of the medial epicondyle may induce a lower ossification signal in the dominant elbow, thereby decreasing fatty bone marrow and inducing sclerotic changes.

Three-dimensional MRI Analysis of Femoral Head Remodeling After Reduction in Patients With Developmental Dysplasia of the Hip.

BACKGROUND: Previous reports on patients with developmental dysplasia of the hip (DDH) showed that the prereduced femoral head was notably smaller and more nonspherical than the intact head, with growth failure observed at the proximal posteromedial area. We evaluated the shape of the femoral head cartilage in patients with DDH before and after reduction, with size and sphericity assessed using 3-dimensional (3D) magnetic resonance imaging (MRI). METHODS: We studied 10 patients with unilateral DDH (all female) who underwent closed reduction. Patients with avascular necrosis of the femoral head on the plain radiograph 1 year after reduction were excluded. 3D MRI was performed before reduction and after reduction, at 2 years of age. 3D-image analysis software was used to reconstruct the multiplanes. After setting the axial, coronal, and sagittal planes in the software (based on the femoral shaft and neck axes), the smallest sphere that included the femoral head cartilage was drawn, the diameter was measured, and the center of the sphere was defined as the femoral head center. We measured the distance between the center and cartilage surface every 30 degrees on the 3 reconstructed planes. Sphericity of the femoral head was calculated using a ratio (the distance divided by each radius) and compared between prereduction and postreduction. RESULTS: The mean patient age was 7±3 and 26±3 months at the first and second MRI, respectively. The mean duration between the reduction and second MRI was 18±3 months. The femoral head diameter was 26.7±1.5 and 26.0±1.6 mm on the diseased and intact sides, respectively (P=0.069). The ratios of the posteromedial area on the axial plane and the proximoposterior area on the sagittal plane after reduction were significantly larger than before reduction (P<0.01). CONCLUSIONS: We demonstrated that the size of the reduced femoral head was nearly equal to that of the intact femoral head and that the growth failure area of the head before reduction, in the proximal posteromedial area, was remodeled after reduction. LEVEL OF EVIDENCE: Level IV-case series.