A mutually communicable external system resource in remote monitoring for cardiovascular implantable electronic devices.

BACKGROUND: Using third-party resources to manage remote monitoring (RM) data from implantable cardiac electronic devices (CIEDs) can assist in device clinic workflows. However, each hospital-acquired data is not used for further analysis as big data. METHODS AND RESULTS: We developed a real-time and automatically centralized system of CIED information from multiple hospitals. If the extensive data-based analysis suggests individual problems, it can be returned to each hospital. To show its feasibility, we prospectively analyzed data from six hospitals. For example, unexpected abnormal battery levels were easily illustrated without recall information. CONCLUSIONS: The centralized RM system could be a new platform that promotes the utilization of device data as big data, and that information could be used for each patient's practice.

Survey on the implementation status and reproductive outcomes of oocyte and ovarian tissue cryopreservation in Japan: Historical comparison with nationwide surveys.

PURPOSE: To clarify the reproductive outcomes of fertility preservation (FP) treatment. METHODS: We conducted a mailed-in questionnaire survey at institutions certified by the Japan Society of Obstetrics and Gynecology to investigate the number of oocyte cryopreservations (OC) and ovarian tissue cryopreservations (OTC) performed from December 2016 to the end of 2020. And, we conducted a detailed investigation of cases in which frozen specimens were used during the investigation period, and made historical comparisons with previous nationwide studies. RESULTS: Responses were received from 114 out of 150 facilities (response rate: 76.0%) for OC and 43 out of 51 for OTC (response rate: 84.3%). Breast cancer was the most common disease among patients whose FP specimens were used. During the study period, 1237 OCs and 198 OTCs were performed. In addition, 57 cycles of embryo transfer (ET) using cryopreserved oocytes and 12 cases of ovarian tissue transplantation (OTT) were performed. The mean age of patients who underwent ET using cryopreserved oocytes was 34.8 (±5.8) years, with a median age of 36 years. The pregnancy rate per ET using cryopreserved oocytes was 26.3% and the live birth rate (LBR) was 17.5%. Further, the LBR per patient was 43.3%, and the pregnancy rate following OTTs was 33.3%. Also, controlled ovarian stimulation using the random start method or the combination of aromatase inhibitors had no effect on pregnancy outcome. CONCLUSION: Implementation of both OCs and OTCs have markedly increased over time in Japan, with comparable reproductive outcomes as other reports.

Reproductive outcomes of embryo cryopreservation and transfer at the start-up phase of fertility preservation in Japan.

Purpose: To verify the effectiveness of embryo transfer (ET) using cryopreserved embryo as fertility preservation (FP). Methods: This study was a questionnaire survey. The total number of embryo cryopreservation (EC) was investigated between 2014 and 2020. And for patients who underwent ET among study period, details of EC, outcome of ET, number of live births, and mortality were investigated. Results: Of the 150 facilities, 114 responded (76.0%). A total of 1420 EC were performed during the study period; and ET was performed for 417 patients. Breast cancer was the most common primary disease. A total of 199 live births (including prospective) were obtained by ET; 1.7 EC and 2.2 ET were performed per patient, and live birth rate was 21.4% per ET (28.1% on 35-37-year-old patients). The number of EC and ET increased with age. The final birth rate, including pregnancies other than FP, was 51.8%. Ovarian stimulation with aromatase inhibitors was commonly used, although with no effect on live birth rates. Random start stimulation was also common, experienced by 36.3% of breast cancer patients. Conclusion: Reproductive outcomes of ETs following EC as FP are acceptable. This research project was registered in the University Hospital Medical Information Network (UMIN000043664).

Headache education by leaflet distribution during COVID-19 vaccination and school-based on-demand e-learning: Itoigawa Geopark Headache Awareness Campaign.

OBJECTIVE: We prospectively performed the Itoigawa Headache Awareness Campaign from August 2021 to June 2022, with two main interventions, and evaluated its effectiveness. BACKGROUND: Headache is a common public health problem, but its burden could be reduced by raising awareness about headache and the appropriate use of acute and prophylactic medication. However, few studies on raising headache awareness in the general public have been reported. METHODS: The target group was the general public aged 15-64. We performed two main interventions synergistically supported by other small interventions. Intervention 1 included leaflet distribution and a paper-based questionnaire about headache during COVID-19 vaccination, and intervention 2 included on-demand e-learning and online survey through schools. In these interventions, we emphasize the six important topics for the general public that were described in the Clinical Practice Guideline for Headache Disorders 2021. Each response among the two interventions' cohorts was collected on pre and post occasions. The awareness of the six topics before and after the campaign was evaluated. RESULTS: We obtained 4016 valid responses from 6382 individuals who underwent vaccination in intervention 1 and 2577 from 594 students and 1983 parents in intervention 2; thus, 6593 of 20,458 (32.2%) of the overall working-age population in Itoigawa city experienced these interventions. The percentage of individuals' aware of the six topics significantly increased after the two main interventions ranging from 6.6% (39/594)-40.0% (1606/4016) to 64.1% (381/594)-92.6% (1836/1983) (p < 0.001, all). CONCLUSIONS: We conducted this campaign through two main interventions with an improved percentage of individuals who know about headache. The two methods of community-based interventions could raise headache awareness effectively. Furthermore, we can achieve outstanding results by doing something to raise disease awareness during mass vaccination, when almost all residents gather in a certain place, and school-based e-learning without face-to-face instruction due to the COVID-19 pandemic.

IMPACT OF GAS/AIR TAMPONADE ON REFRACTIVE OUTCOMES AFTER FLANGED INTRASCLERAL INTRAOCULAR LENS FIXATION.

PURPOSE: This study aims to investigate the postoperative refractive outcomes in eyes that underwent the flanged intrascleral intraocular lens (IOL) fixation combined with vitrectomy with or without gas/air tamponade. METHODS: The eyes were divided into two groups (Group A; eyes that underwent flanged intrascleral IOL fixation with gas/air tamponade, and Group B; eyes that underwent flanged intrascleral IOL fixation without gas/air tamponade). The predicted spherical equivalent (SE) refraction values were calculated using the Sander-Retzlaff-Kraff Theoretical formula. Then, the prediction error was calculated by subtracting the predicted SE refraction from the postoperative objective SE refraction and the absolute prediction error was calculated as the absolute value of the prediction error for each eye. RESULTS: A total of 68 eyes were included in the current study. There was a significant correlation between the predicted and postoperative SE refraction in both groups (Group A, r = 0.968, P < 0.0001, Group B, r = 0.943, P < 0.0001, linear regression analysis). The prediction error demonstrated a mild myopic shift after the flanged intrascleral IOL fixation in both groups (Group A, -0.40 ± 0.96 diopter, Group B, -0.59 ± 0.95 diopter). There was no significant difference in prediction error and absolute prediction error between the two groups ( P = 0.44, P = 0.70, Wilcoxon rank sum test). CONCLUSION: The postoperative SE refraction after flanged intrascleral IOL fixation was not influenced by gas/air tamponade.

Seismic detection with distributed acoustic sensors using a convolutional neural network in the frequency wavenumber spectrum.

With the development of optical fiber distributed acoustic sensors (DAS), their application to seismic observation has become popular. We conducted DAS measurements from November 19 to December 2, 2019, using dark fiber of an ocean bottom cable seismic and tsunami observation system off the Sanriku coast in northeastern Japan and investigated seismic detection methods from the obtained strain rate data. We examined a new seismic detection method using a convolutional neural network, to the best of our knowledge, treating a frequency wavenumber spectrum of strain rate as an image. This method effectively captured a characteristic wave described as the T-phase in a sound fixing and ranging channel even with low signal-to-noise ratio data.

The effect of aromatase inhibitor on controlled ovarian stimulation for oocyte cryopreservation in adolescent and young cancer patients.

AIM: To determine the impact of aromatase inhibitor (AI) use in oocyte cryopreservation among Japanese adolescent and young adult (AYA) cancer patients for fertility preservation, we evaluated the oocyte cryopreservation outcomes following AI therapy in combination with the follicular phase start (FPS) and random start (RS) protocols. METHODS: This retrospective study included 81 cycles of controlled ovarian stimulation (COS) among 73 AYA patients with cancer who underwent oocyte cryopreservation to maintain fertility. The outcome measures were the total number of matured oocytes that were retrieved and cryopreserved, as well as their maturation rates. The AI (+) and AI (-) groups were compared using the RS and FPS protocols. RESULTS: Our results showed that the combined use of AI and COS decreases serum E2 levels and maintains the number of retrieved and cryopreserved mature oocytes. We also confirmed the efficacy of the RS protocol, which was found to have comparable outcomes to that of the FPS protocol in both AI (+) and AI (-) groups. CONCLUSION: The combined use of AI and COS is beneficial for oocyte cryopreservation in patients with estrogen-sensitive cancer, regardless of the menstrual cycle phase of COS initiation.

The study of the efficiency of in vitro maturation of ovarian tissue oocytes in pediatric patients.

PURPOSE: Although recent in vitro maturation (IVM) studies in pediatric patients have demonstrated successful retrieval and maturation of oocytes, the studies included only a small number of premenarchal patients. In the present study, we examined the potential use of oocyte retrieval and maturation for pediatric patients who undergo ovarian tissue cryopreservation (OTC). METHODS: We retrospectively examined the clinical records of pediatric patients who underwent OTC at our institution between October 2015 and December 2022. Data on the age, primary disease, menstrual history, pre-procedure chemotherapy, anti-Müllerian hormone (AMH) level, number of oocytes collected ex vivo from ovarian tissue, and number of mature oocytes from IVM were examined. RESULTS: Data of 60 pediatric patients (aged 1 to 17 years) were included for analysis. Oocytes were retrieved from 36 patients; the oocytes of 18 of these patients could be cryopreserved. The IVM rate was significantly lower in the premenarchal patients than in the postmenarchal patients. The number of mature oocytes retrieved from IVM was higher in the no-chemotherapy group than in the chemotherapy group. A significant positive correlation was observed between the AMH level and the IVM outcomes. CONCLUSION: Oocyte retrieval and maturation in pediatric patients undergoing OTC is particularly useful in those not receiving chemotherapy. In patients receiving chemotherapy, the AMH level may be useful for predicting the IVM outcome. Activation of the oocyte maturation process in vivo in pediatric patients and better understanding of the major regulators of oocyte maturation are necessary to improve the utility of the IVM procedure.

Evaluation of Lower-Limb Kinematics during Timed Up and Go (TUG) Test in Subjects with Locomotive Syndrome (LS) Using Wearable Gait Sensors (H-Gait System).

Few studies have dealt with lower-limb kinematics during the timed up and go (TUG) test in subjects with locomotive syndrome (LS). This study aimed to evaluate the characteristics of lower-limb kinematics during the TUG test in subjects with LS using the wearable sensor-based H-Gait system. A total of 140 participants were divided into the non-LS (n = 28), the LS-stage 1 (n = 78), and LS-stage 2 (n = 34) groups based on the LS risk test. Compared with the non-LS group, the LS-stage 1 and LS-stage 2 groups showed significantly smaller angular velocity of hip and knee extension during the sit-to-stand phase. The LS-stage 2 group showed significantly smaller peak angles of hip extension and flexion during the walking-out phase compared to the non-LS group. These findings indicate that the evaluation of the lower-limb kinematics during the TUG test using the H-Gait system is highly sensitive to detect LS, compared with the evaluation of the lower-limb kinematics when simply walking.

Ambulatory electrocardiographic markers predict serious cardiac events in patients with chronic kidney disease: The Japanese Noninvasive Electrocardiographic Risk Stratification of Sudden Cardiac Death in Chronic Kidney Disease (JANIES-CKD) study.

BACKGROUND: Noninvasive electrocardiographic markers (NIEMs) are promising arrhythmic risk stratification tools for assessing the risk of sudden cardiac death. However, little is known about their utility in patients with chronic kidney disease (CKD) and organic heart disease. This study aimed to determine whether NIEMs can predict cardiac events in patients with CKD and structural heart disease (CKD-SHD). METHODS: We prospectively analyzed 183 CKD-SHD patients (median age, 69 years [interquartile range, 61-77 years]) who underwent 24-h ambulatory electrocardiographic monitoring and assessed the worst values for ambulatory-based late potentials (w-LPs), heart rate turbulence, and nonsustained ventricular tachycardia (NSVT). The primary endpoint was the occurrence of documented lethal ventricular tachyarrhythmias (ventricular fibrillation or sustained ventricular tachycardia) or cardiac death. The secondary endpoint was admission for cardiovascular causes. RESULTS: Thirteen patients reached the primary endpoint during a follow-up period of 24 ± 11 months. Cox univariate regression analysis showed that existence of w-LPs (hazard ratio [HR] = 6.04, 95% confidence interval [CI]: 1.4-22.3, p = .007) and NSVT [HR = 8.72, 95% CI: 2.8-26.5: p < .001] was significantly associated with the primary endpoint. Kaplan-Meier analysis demonstrated that the combination of w-LPs and NSVT resulted in a lower event-free survival rate than did other NIEMs (p < .0001). No NIEM was useful in predicting the secondary endpoint, although the left ventricular mass index was correlated with the secondary endpoint. CONCLUSION: The combination of w-LPs and NSVT was a significant risk factor for lethal ventricular tachyarrhythmias and cardiac death in CKD-SHD patients.

Evaluation of gait characteristics in subjects with locomotive syndrome using wearable gait sensors.

BACKGROUND: Individuals with locomotive syndrome (LS) require nursing care services owing to problems with locomotion and the musculoskeletal system. Individuals with LS generally have a reduced walking speed compared with those without LS. However, differences in lower-limb kinematics and gait between individuals with and without LS are not fully understood. This study aimed to clarify the characteristics of the gait kinematics of individuals with LS using wearable sensors. METHODS: We assessed 125 participants (mean age 73.0 ± 6.7 years) who used a public health promotion facility. Based on the 25-question Geriatric Locomotive Function Scale (GLFS-25), these participants were grouped into the non-LS (GLFS-25 < 7), LS-stage 1 (GLFS-25 7-16), and LS-stage 2 (GLFS-25 ≥ 16) groups (larger GLFS-25 scores indicate worse locomotive ability). Spatiotemporal parameters and lower-limb kinematics during the 10-m walk test were analyzed by the "H-Gait system", which is a motion analysis system that was developed by the authors and is based on seven inertial sensors. The peak joint angles during the stance and swing phases, as well as the gait speed, cadence, and step length were compared among all groups. RESULTS: There were 69 participants in the non-LS group, 33 in the LS-stage 1 group, and 23 in the LS-stage 2 group. Compared with the non-LS group, the LS-stage 2 group showed significantly smaller peak angles of hip extension (9.5 ± 5.3° vs 4.2 ± 8.2°, P = 0.002), hip flexion (34.2 ± 8.8° vs 28.5 ± 9.5°, P = 0.026), and knee flexion (65.2 ± 18.7° vs 50.6 ± 18.5°, P = 0.005). The LS-stage 1 and LS-stage 2 groups had a significantly slower mean gait speed than the non-LS group (non-LS: 1.3 ± 0.2 m/s, LS-stage 1: 1.2 ± 0.2 m/s, LS-stage 2: 1.1 ± 0.2 m/s, P < 0.001). CONCLUSIONS: The LS-stage 2 group showed significantly different lower-limb kinematics compared with the non-LS group, including smaller peak angles of hip extension, hip flexion, and knee flexion. It would be useful to assess and improve these small peak joint angles during gait for individuals classified as LS-stage 2.

Detecting the presence of supernumerary teeth during the early mixed dentition stage using deep learning algorithms: A pilot study.

BACKGROUND: Supernumerary teeth are a common anomaly and are frequently observed in paediatric patients. To prevent or minimize complications, early diagnosis and treatment is ideal in children with supernumerary teeth. AIM: This study aimed to apply convolutional neural network (CNN)-based deep learning to detect the presence of supernumerary teeth in children during the early mixed dentition stage. DESIGN: Three CNN models, AlexNet, VGG16-TL, and InceptionV3-TL, were employed in this study. A total of 220 panoramic radiographs (from children aged 6 years 0 months to 9 years 6 months) including supernumerary teeth (cases, n = 120) or no anomalies (controls, n = 100) were retrospectively analyzed. The CNN performances were assessed according to accuracy, sensitivity, specificity, receiver operating characteristic (ROC) curves, and area under the ROC curves for a cross-validation test dataset. RESULTS: The VGG16-TL model had the highest performance according to accuracy, sensitivity, specificity, and area under the ROC curve, but the other models had similar performance. CONCLUSION: CNN-based deep learning is a promising approach for detecting the presence of supernumerary teeth during the early mixed dentition stage.

Anterograde trafficking of ciliary MAP kinase-like ICK/CILK1 by the intraflagellar transport machinery is required for intraciliary retrograde protein trafficking.

ICK (also known as CILK1) is a mitogen-activated protein kinase-like kinase localized at the ciliary tip. Its deficiency is known to result in the elongation of cilia and causes ciliopathies in humans. However, little is known about how ICK is transported to the ciliary tip. We here show that the C-terminal noncatalytic region of ICK interacts with the intraflagellar transport (IFT)-B complex of the IFT machinery and participates in its transport to the ciliary tip. Furthermore, total internal reflection fluorescence microscopy demonstrated that ICK undergoes bidirectional movement within cilia, similarly to IFT particles. Analysis of ICK knockout cells demonstrated that ICK deficiency severely impairs the retrograde trafficking of IFT particles and ciliary G protein-coupled receptors. In addition, we found that in ICK knockout cells, ciliary proteins are accumulated at the bulged ciliary tip, which appeared to be torn off and released into the environment as an extracellular vesicle. The exogenous expression of various ICK constructs in ICK knockout cells indicated that the IFT-dependent transport of ICK, as well as its kinase activity and phosphorylation at the canonical TDY motif, is essential for ICK function. Thus, we unequivocally show that ICK transported to the ciliary tip is required for retrograde ciliary protein trafficking and consequently for normal ciliary function.

Brillouin optical correlation-domain reflectometry based on arbitrary waveform modulation: a theoretical study.

We put forward a new theory on Brillouin optical correlation-domain reflectometry (BOCDR) based on arbitrary waveform modulation. We derive a universal representation for the spatial resolution using the foot convexity of the beat spectrum. This result well explains the previous results based on sinusoidal modulation, and thus our theory is the consistent extension of the conventional theory on BOCDR. This representation is also applicable to the spatial resolution evaluation of more complicated modulation schemes, such as the combined use of intensity and frequency modulations even with some phase delay. We also discuss what kinds of modulation waveforms should not be employed for distributed measurement to ensure high spatial resolution.

Pulmonary tumor thrombotic microangiopathy in occult early gastric cancer that was undetectable on upper endoscopy: a case report and review of similar cases.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM), a rare manifestation of metastatic cancer with poor prognosis, is characterized by subacute/acute fatal pulmonary hypertension. The main cause of PTTM is gastric cancer, and cases of early gastric cancer confirmed using autopsy have been reported. Moreover, several cases of early gastric cancer that are undetectable on endoscopy or macroscopic postmortem examination have been reported. CASE PRESENTATION: A previously healthy 50-year-old man presented with progressive dyspnea and cough for 1 month. Echocardiography suggested pulmonary hypertension. Computed tomography revealed diffuse lymphadenopathy, whereas blood work revealed an elevation in several serum tumor marker levels. Despite normal upper endoscopic findings, a presumptive diagnosis of PTTM due to gastric cancer was made based on pathological findings of cervical lymph node biopsy, which indicated signet ring cell carcinoma. Imatinib and tegafur/gimeracil/oteracil plus oxaliplatin therapy were started on day 7. The patient's condition was initially stable. However, his symptoms suddenly progressed, and the patient died on day 8. Macroscopic postmortem examination revealed no abnormal gastric wall findings. Microscopically, PTTM was confirmed, and multiple serial sections of the stomach revealed early gastric cancer. CONCLUSIONS: Despite normal endoscopic findings, micro-occult gastric cancer can lead to PTTM. Physicians should be aware of this disease presentation. Taking prompt action is needed when PTTM is suspected, even if the patient appears stable.

Relocation of dehydroquinate dehydratase to the periplasmic space improves dehydroshikimate production with Gluconobacter oxydans strain NBRC3244.

3-Dehydroshikimate (3-DHS) is a key intermediate for the synthesis of various compounds, including the antiviral drug oseltamivir. The Gluconobacter oxydans strain NBRC3244 intrinsically oxidizes quinate to produce 3-dehydroquinate (3-DHQ) in the periplasmic space. Even though a considerable activity is detected in the recombinant G. oxydans homologously overexpressing type II dehydroquinate dehydratase (DHQase) encoded in the aroQ gene at a pH where it grows, an alkaline shift of the culture medium is required for 3-DHS production in the middle of cultivation. Here, we attempted to adopt type I DHQase encoded in the aroD gene of Gluconacetobacter diazotrophicus strain PAL5 because the type I DHQase works optimally at weak acid, which is preferable for growth conditions of G. oxydans. In addition, we anticipated that subcellular localization of DHQase is the cytoplasm, and therefore, transports of 3-DHQ and 3-DHS across the cytoplasmic membrane are rate-limiting steps in the biotransformation. The Sec- and TAT-dependent signal sequences for secretion were attached to the N terminus of AroD to change the subcellular localization. G. oxydans that expresses the TAT-AroD derivative achieved 3-DHS production at a tenfold higher rate than the reference strain that expresses wild-type AroD even devoid of alkaline shift. Enzyme activity with the intact cell suspension and signal sequence cleavage supported the relocation of AroD to the periplasmic space. The present study suggests that the relocation of DHQase improves 3-DHS production in G. oxydans and represents a proof of concept for the potential of enzyme relocation in metabolic engineering. KEY POINTS: • Type-I dehydroquinate dehydratase (DHQase) was expressed in Gluconobacter oxydans. • Cytoplasmic DHQase was relocated to the periplasmic space in G. oxydans. • Relocation of DHQase in G. oxydans improved 3-dehydroshikimate production.

High early phase hemoglobin level is associated with favorable neurological outcome in patients with severe traumatic brain injury.

BACKGROUND: The appropriate hemoglobin (Hb) level threshold for the early phase (i.e. from Emergency Department to ICU admission) in patients with severe traumatic brain injury (TBI) is still unknown. Therefore, we aimed to examine the association between Hb levels during the early phase and neurological outcomes in patients with severe TBI using data from the Brain Hypothermia (B-HYPO) Study Group. METHODS: We performed a post-hoc analysis of the B-HYPO study (a prospective, multicenter, randomized controlled trial on patients with severe TBI who received either mild therapeutic hypothermia [MTH; 32.0 °C-34.0 °C] or fever control [35.5 °C-37.0 °C]). We calculated Hb levels during early phase by the formula: (admission Hb + Hb on day 1) / 2. The primary outcome was the association between during early phase Hb levels and 6-month neurological outcome after the TBI based on the Glasgow Outcome Scale scores (a measure of functional recovery defined as moderate disability or good recovery). RESULTS: We reviewed data from 130 patients and found favorable neurological outcomes in 48.5% of them. We found significant differences between the favorable and unfavorable neurological outcome groups in terms of their Hb levels on admission and on day 1. But, we found no Hb level differences after day 3 (including 1 day after rewarming). Our multivariable analysis showed that Hb levels during early phase were significantly associated with favorable neurological outcomes (odds ratio, 1.387; 95% confidence interval, 1.057-1.858; P = 0.018). CONCLUSIONS: High early phase Hb levels are associated with favorable neurological outcomes after severe TBI.

Influence of Constant Torque Stretching at Different Stretching Intensities on Flexibility and Mechanical Properties of Plantar Flexors.

ABSTRACT: Oba, K, Samukawa, M, Nakamura, K, Mikami, K, Suzumori, Y, Ishida, Y, Keeler, N, Saitoh, H, Yamanaka, M, and Tohyama, H. Influence of constant torque stretching at different stretching intensities on flexibility and mechanical properties of plantar flexors. J Strength Cond Res 35(3): 709-714, 2021-The purpose of this study was to examine the effects of constant torque stretching (CTS) at different stretching intensities on the maximal range of motion (ROM) and muscle-tendon unit (MTU) stiffness of plantar flexors. Fourteen healthy men performed 4 trials of differing stretch intensities: no stretching (control), 50, 75, and 100%. Stretch intensity was defined as maximum passive resistive torque predetermined at a familiarization trial. Each stretch trial consisted of 5 sets of 60-second CTS at the designated stretch intensity. Both maximal ROM and passive resistive torque were assessed during passive dorsiflexion, and MTU stiffness was calculated using the torque-angle curves measured before and after CTS. There were no significant differences in maximal ROM or MTU stiffness at the baseline condition. After the intervention, significantly greater maximal ROM and significantly lower MTU stiffness were observed in the 100% CTS condition than the control condition, whereas there were no significant differences between the submaximal intensity condition (i.e., 50 or 75% intensity) and the control condition. Therefore, our findings suggest that maximal intensity stretching is the most effective approach for improving both flexibility and MTU stiffness with CTS.

Ciliopathy-associated mutations of IFT122 impair ciliary protein trafficking but not ciliogenesis.

The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. Mutations in the genes encoding the six subunits of the IFT-A complex (IFT43, IFT121, IFT122, IFT139, IFT140, and IFT144) are known to cause skeletal ciliopathies, including cranioectodermal dysplasia (CED). As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. Indeed, we here showed that knockout (KO) of the IFT122 gene in hTERT-RPE1 cells using the CRISPR/Cas9 system led to a severe ciliogenesis defect, whereas KO of other IFT-A genes had minor effects on ciliogenesis but impaired ciliary protein trafficking. Exogenous expression of not only wild-type IFT122 but also its CED-associated missense mutants, which fail to interact with other IFT-A subunits, rescued the ciliogenesis defect of IFT122-KO cells. However, IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation. The trafficking defects partially resembled those observed in IFT144-KO cells, which demonstrate failed assembly of the functional IFT-A complex at the base of cilia. These observations make it likely that, although IFT122 is essential for ciliogenesis, CED-type missense mutations underlie a skeletal ciliopathy phenotype by perturbing ciliary protein trafficking with minor effects on ciliogenesis per se.

Noise suppression technique for distributed Brillouin sensing with polymer optical fibers.

We develop a new noise suppression technique to perform distributed strain and temperature sensing based on a higher-speed configuration of Brillouin optical correlation-domain reflectometry even when a polymer optical fiber (POF) is used as a sensing fiber. We acquire the spectral difference between with and without reference light, leading to selective observation of the beat signal of Brillouin-scattered light and reference light, which is effective for distributed sensing. After experimentally showing the usefulness of this technique, we demonstrate POF-based distributed temperature sensing and dynamic strain sensing.