Risk factors for nonresponse to 2 years of denosumab administration in patients with osteoporosis: A retrospective single-center cohorts study.

Background and Aims: To investigate the factors associated with changes in bone mineral density (BMD) and the incidence of fractures in osteoporotic patients treated with denosumab. Methods: This retrospective study included 162 osteoporotic patients treated with denosumab for 24 months between 2013 and 2019. Patients were divided according to the changes in BMD as nonresponders (NL group: <3% increase in lumbar spine BMD [LBMD], NH group: <0% increase in femoral neck BMD [FNBMD]) or responders (RL group: ≥3% increase in LBMD, RH group: ≥0% increase in FNBMD). Results: The respective changes in the LBMD and FNBMD after 24 months of denosumab treatment were 9.3% (95% confidence interval [CI]: 8.1-10.6) and 3.3% (95% CI: 2.1-4.5). Twenty-eight (17.3%) patients were in the NL group, and 134 (82.7%) were in the RL group. A history of bisphosphonate treatment was a risk factor for being in the NL group (odds ratio [OR]: 3.84, 95% CI: 1.38-10.71, p = 0.007; adjusted OR: 3.21, 95% CI: 1.01-10.19, p = 0.048). Although the NH (n = 48; 30.8%) and RH (n = 108; 69.2%) groups had similar baseline characteristics, the NH group had a significantly higher baseline FNBMD than the RH group (p = 0.003). The change in FNBMD was negatively associated with the FNBMD at baseline (r = -0.34, p < 0.001). No new osteoporotic fractures occurred in either group during follow-up. Conclusion: In osteoporotic patients receiving denosumab treatment, a history of bisphosphonate treatment was a risk factor for a lack of increase in LBMD, and a higher FNBMD at baseline was negatively associated with the change in FNBMD.

Prevalence of amyloid deposition and cardiac amyloidosis in shoulder disease compared to carpal tunnel syndrome.

Background: Cardiac amyloidosis is a fatal disease of severe heart failure caused by the accumulation of amyloid in the myocardium. This disease is often advanced by the time cardiac symptoms appear; therefore, early detection and treatment are critical for a good prognosis. Recently, it has been suggested that cardiac amyloidosis is implicated in several orthopedic diseases, including carpal tunnel syndrome (CTS), which is often reported to precede cardiac dysfunction. Shoulder disease has also been suggested to be associated with cardiac amyloidosis; however, there have been no reports investigating the rate of amyloid deposition in shoulder specimens and the simultaneous prevalence of cardiac amyloidosis. Herein, we investigated the prevalence of intraoperative specimen amyloid deposition and cardiac amyloidosis in shoulder disease and CTS to determine the usefulness of shoulder specimen screening as a predictor of cardiac amyloidosis development. Methods: A total of 41 patients undergoing arthroscopic shoulder surgery and 33 patients undergoing CTS surgery were enrolled in this study. The shoulder group included rotator cuff tears, contracture of the shoulder, synovitis, and calcific tendonitis. In the shoulder group, a small sample of synovium and the long head of the biceps brachii tendon were harvested, while the transverse carpal ligament was harvested from the CTS group. The intraoperative specimens were pathologically examined for amyloid deposition, and patients with amyloid deposition were examined for the presence of cardiac amyloidosis by cardiac evaluation. Results: In the shoulder group, three cases (7.3%) of transthyretin amyloid deposition were found, all of which involved rotator cuff tears. None of these three cases with amyloid deposition were associated with cardiac amyloidosis. When examining the specimens, the amyloid deposition rate in the long head of the biceps brachii tendon was higher than that in the synovium. In the CTS group, 12 cases (36.4%) of transthyretin amyloid deposition were observed. Of these cases, seven underwent cardiac evaluation and two were identified with cardiac amyloidosis. Conclusion: While the prevalence of amyloid deposition and cardiac amyloidosis in the CTS group was consistent with previous reports, the shoulder group showed a lower deposition rate and no concomitant cardiac amyloidosis. Therefore, it remains debatable whether investigating amyloid deposition in samples obtained from shoulder surgery is beneficial for the early detection of cardiac amyloidosis.

Using In-Shoe Inertial Measurement Unit Sensors to Understand Daily-Life Gait Characteristics in Patients With Distal Radius Fractures During 6 Months of Recovery: Cross-Sectional Study.

BACKGROUND: A distal radius fracture (DRF) is a common initial fragility fracture among women in their early postmenopausal period, which is associated with an increased risk of subsequent fractures. Gait assessments are valuable for evaluating fracture risk; inertial measurement units (IMUs) have been widely used to assess gait under free-living conditions. However, little is known about long-term changes in patients with DRF, especially concerning daily-life gait. We hypothesized that, in the long term, the daily-life gait parameters in patients with DRF could enable us to reveal future risk factors for falls and fractures. OBJECTIVE: This study assessed the spatiotemporal characteristics of patients with DRF at 4 weeks and 6 months of recovery. METHODS: We recruited 16 women in their postmenopausal period with DRF as their first fragility fracture (mean age 62.3, SD 7.0 years) and 28 matched healthy controls (mean age 65.6, SD 8.0 years). Daily-life gait assessments and physical assessments, such as hand grip strength (HGS), were performed using an in-shoe IMU sensor. Participants' results were compared with those of the control group, and their recovery was assessed for 6 months after the fracture. RESULTS: In the fracture group, at 4 weeks after DRF, lower foot height in the swing phase (P=.049) and higher variability of stride length (P=.03) were observed, which improved gradually. However, the dorsiflexion angle in the fracture group tended to be lower consistently during 6 months (at 4 weeks: P=.06; during 6 months: P=.07). As for the physical assessments, the fracture group showed lower HGS at all time points (at 4 weeks: P<.001; during 6 months: P=.04), despite significant improvement at 6 months (P<.001). CONCLUSIONS: With an in-shoe IMU sensor, we discovered the recovery of spatiotemporal gait characteristics 6 months after DRF surgery without the participants' awareness. The consistently unchanged dorsiflexion angle in the swing phase and lower HGS could be associated with fracture risk, implying the high clinical importance of appropriate interventions for patients with DRF to prevent future fractures. These results could be applied to a screening tool for evaluating the risk of falls and fractures, which may contribute to constructing a new health care system using wearable devices in the near future.

In vitroanalysis of insoluble salt formation mechanism associated with Mg corrosion-variations depending on the diffusion environment in model tissue.

Magnesium (Mg) alloys have attracted attention as biodegradable metals, but the details of their corrosion behavior under biological environment have not been elucidated. Previous studies have suggested that diffusion through blood flow may influence Mg corrosion. Therefore, to understand the degradation behaviors of Mg, we analyzed insoluble salt precipitation associated with Mg corrosion in model tissue with different diffusion rates. A pure Mg specimen was immersed into a model tissue prepared with cell culture medium supplemented by a thickener at a different concentration (0.2%-0.5%) to form the gel. Micro-focus x-ray computed tomography of the gel was performed to observe gas cavity formation around the specimen. The insoluble salt layer formed on the specimen surface were analyzed by scanning electron microscopy with energy-dispersive x-ray spectroscopy, and Raman spectroscopy. As results, gas cavity formation was observed for all specimens. At day 7, the gas cavity volume was the highest at 0.5% thickener gel followed by 0.3% thickener gel. The insoluble salts were classified into three types based on their morphology; plate-like, granular-like, and crater-like salts. The crater-like salts were observed to cover 16.8 ± 3.9% of the specimen surface immersed in the 0.5% thickener gel, at the specimen area contacted to the gas cavity. The crater-like salts were composed by Mg hydroxide and carbonate from the deepest to the top layer. In plate-like or granular-like salts, Mg carbonate was formed in the deepest layer, but phosphates and carbonates, mainly containing calcium not Mg, were formed on the surface layer. In conclusion, the increase in the thickener concentration increased the gas cavity volume contacting to the specimen surface, resulting in the increase in precipitation of Mg hydroxide and carbonate, composing crater-like salts. Mg hydroxide and carbonate precipitation suggests the local increase in OH-concentration, which may be attributed to the decrease in diffusion rate.

Retrospective comparative study of robot-assisted surgery, laparoscopic surgery, and laparotomy for endometrial cancer in patients with a low risk of recurrence.

AIM: Minimally invasive surgeries for endometrial cancer are increasing worldwide. In Japan, some articles have examined surgical outcomes, but only a few have addressed oncological outcomes. This study aims to compare robot surgery, laparoscopic surgery, and laparotomy in terms of surgical and oncological outcomes within a low-risk group for endometrial cancer recurrence. METHODS: This study included patients with endometrial cancer deemed to be at low risk of recurrence and who underwent surgery between January 2011 and December 2020. We studied 99 patients who underwent robot surgery, 85 patients who underwent laparotomy, and 77 patients who underwent laparoscopic surgery. Surgical and oncological outcomes were compared retrospectively for these groups of patients. RESULTS: The median follow-up period was 47, 61, and 60 months in the laparotomy, laparoscopy, and robotic groups, respectively. The three groups had similar perioperative and pathological data. No significant differences in overall survival and disease-free survival were observed among the groups. Univariate and multivariate analyses conducted on the overall study population for disease-free survival and overall survival showed that the surgical approach did not have any influence. Minimally invasive surgery groups had longer operating times compared to the laparotomy group, but they had significantly less blood loss. The number of resected pelvic lymph nodes was similar, and the complication rate was not significant. CONCLUSIONS: Robot-assisted surgery and laparoscopic surgery were found to be less invasive and showed similar oncologic outcomes compared to laparotomy surgery for endometrial cancer in patients with a low risk of recurrence.

Six-month outcomes of switching from aflibercept to faricimab in refractory cases of neovascular age-related macular degeneration.

PURPOSE: To assess 6-month outcomes of switching from aflibercept to faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) previously requiring monthly injections. METHODS: This multicenter retrospective study examined nAMD eyes receiving monthly aflibercept injections switched to faricimab administered monthly up to 4 injections followed by injections at a minimum of 2-month intervals as per drug labeling. Data regarding age, sex, number of previous injections, treatment intervals, and best-corrected visual acuity (BCVA) were collected. Central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximal pigment epithelial detachment (PED) height were measured by optical coherence tomography. RESULTS: The study included 130 eyes of 124 patients. At 6 months, 53 eyes (40.8%) continued on faricimab treatment (Group 1), while 77 eyes (59.2%) discontinued faricimab for various reasons (Group 2) the most common being worse exudation. There were no significant differences between the two groups at baseline. In Group 1, CRT and SFCT significantly decreased at 1 month (P = 0.013 and 0.008), although statistical significance was lost at 6 months (P = 0.689 and 0.052). BCVA and maximal PED height showed no significant changes; however, mean treatment intervals were extended from 4.4 ± 0.5 weeks at baseline to 8.7 ± 1.7 weeks at 6 months (P < 0.001) in Group 1. No clear predictors of response were identified. CONCLUSION: Switching from aflibercept to faricimab allowed for extension of treatment intervals from monthly to bimonthly in roughly 40% of eyes, suggesting that faricimab may be considered in refractory nAMD cases.

Gait characteristics in patients with distal radius fracture using an in-shoe inertial measurement system at various gait speeds.

BACKGROUND: Distal radius fractures (DRF) commonly occur in early postmenopausal females as the first fragility fracture. Although the incidence of DRF in this set of patients may be related to a lower ability to control their balance and gait, the detailed gait characteristics of DRF patients have not been examined. RESEARCH QUESTION: Is it possible to identify the physical and gait features of DRF patients using in-shoe inertial measurement unit (IMU) sensors at various gait speeds and to develop a machine learning (ML) algorithm to estimate patients with DRF using gait? METHODS: In this cross-sectional case control study, we recruited 28 postmenopausal females with DRF as their first fragility fracture and 32 age-matched females without a history of fragility fractures. The participants underwent several physical and gait tests. In the gait performance test, the participants walked 16 m with the in-shoe IMU sensor at slower, preferred, and faster speeds. The gait parameters were calculated by the IMU, and we applied the ML technique using the extreme gradient boosting (XGBoost) algorithm to predict the presence of DRF. RESULTS: The fracture group showed lower hand grip strength and lower ability to change gait speed. The difference in gait parameters was mainly observed at faster speeds. The amplitude of the change in the parameters was small in the fracture group. The XGBoost model demonstrated reasonable accuracy in predicting DRFs (area under the curve: 0.740), and the most relevant variable was the stance time at a faster speed. SIGNIFICANCE: Gait analysis using in-shoe IMU sensors at different speeds is useful for evaluating the characteristics of DRFs. The obtained gait parameters allow the prediction of fractures using the XGBoost algorithm.

Ovarian Mesonephric-like Adenocarcinoma Recurring With a Rhabdomyosarcoma Component: A Case Report.

Mesonephric-like adenocarcinoma (MLA) has recently been described as a tumor of the endometrium or ovaries, which, morphologically and immunohistochemically, resembles mesonephric adenocarcinoma arising mostly in the uterine cervix. Herein, we report, to our knowledge, the first case of ovarian MLA that developed into an extremely rapidly growing recurrent mesonephric-like carcinosarcoma, as confirmed by a genomic profiling test. A 51-year-old woman underwent chemotherapy with complete debulking surgery for ovarian carcinoma. Pathologically, the patient was diagnosed with stage IVB ovarian MLA. Subsequent to 15 months of complete remission, an enhanced computed tomography scan revealed a solid tumor of 10 cm diameter in the abdominal cavity. Secondary surgery was terminated with a 2 cm2 tumor biopsy specimen collection considering perioperative complications. Histologically, the tumor consisted of short spindle cells, and immunohistochemical staining revealed a rhabdomyosarcomatous profile without an epithelial component. Despite treatment for the sarcoma, she died 3 months after the detection of the tumor. The genomic profiling of the primary ovarian carcinoma and secondary resected tumor biopsy specimens revealed an identical KRAS mutation in both. Therefore, we concluded that the ovarian MLA recurred with a rhabdomyosarcoma component.

Foot characteristics of the daily-life gait in postmenopausal females with distal radius fractures: a cross-sectional study.

BACKGROUND: Gait decline in older adults is related to falling risk, some of which contribute to injurious falls requiring medical attention or restriction of activity of daily living. Among injurious falls, distal radius fracture (DRF) is a common initial fragility fracture associated with the subsequent fracture risk in postmenopausal females. The recent invention of an inertial measurement unit (IMU) facilitates the assessment of free-living gait; however, little is known about the daily gait characteristics related to the risk of subsequent fractures. We hypothesized that females with DRF might have early changes in foot kinematics in daily gait. The aim of this study was to evaluate the daily-life gait characteristics related to the risk of falls and fracture. METHODS: In this cross-sectional study, we recruited 27 postmenopausal females with DRF as their first fragility fracture and 28 age-matched females without a history of fragility fractures. The participants underwent daily gait assessments for several weeks using in-shoe IMU sensors. Eight gait parameters and each coefficient of variance were calculated. Some physical tests, such as hand grip strength and Timed Up and Go tests, were performed to check the baseline functional ability. RESULTS: The fracture group showed lower foot angles of dorsiflexion and plantarflexion in the swing phase. The receiver operating characteristic curve analyses revealed that a total foot movement angle (TFMA) < 99.0 degrees was the risk of subsequent fracture. CONCLUSIONS: We extracted the daily-life gait characteristics of patients with DRF using in-shoe IMU sensors. A lower foot angle in the swing phase, TFMA, may be associated with the risk of subsequent fractures, which may be effective in evaluating future fracture risk. Further studies to predict and prevent subsequent fractures from daily-life gait are warranted.

The Potential of ChatGPT as a Self-Diagnostic Tool in Common Orthopedic Diseases: Exploratory Study.

BACKGROUND: Artificial intelligence (AI) has gained tremendous popularity recently, especially the use of natural language processing (NLP). ChatGPT is a state-of-the-art chatbot capable of creating natural conversations using NLP. The use of AI in medicine can have a tremendous impact on health care delivery. Although some studies have evaluated ChatGPT's accuracy in self-diagnosis, there is no research regarding its precision and the degree to which it recommends medical consultations. OBJECTIVE: The aim of this study was to evaluate ChatGPT's ability to accurately and precisely self-diagnose common orthopedic diseases, as well as the degree of recommendation it provides for medical consultations. METHODS: Over a 5-day course, each of the study authors submitted the same questions to ChatGPT. The conditions evaluated were carpal tunnel syndrome (CTS), cervical myelopathy (CM), lumbar spinal stenosis (LSS), knee osteoarthritis (KOA), and hip osteoarthritis (HOA). Answers were categorized as either correct, partially correct, incorrect, or a differential diagnosis. The percentage of correct answers and reproducibility were calculated. The reproducibility between days and raters were calculated using the Fleiss κ coefficient. Answers that recommended that the patient seek medical attention were recategorized according to the strength of the recommendation as defined by the study. RESULTS: The ratios of correct answers were 25/25, 1/25, 24/25, 16/25, and 17/25 for CTS, CM, LSS, KOA, and HOA, respectively. The ratios of incorrect answers were 23/25 for CM and 0/25 for all other conditions. The reproducibility between days was 1.0, 0.15, 0.7, 0.6, and 0.6 for CTS, CM, LSS, KOA, and HOA, respectively. The reproducibility between raters was 1.0, 0.1, 0.64, -0.12, and 0.04 for CTS, CM, LSS, KOA, and HOA, respectively. Among the answers recommending medical attention, the phrases "essential," "recommended," "best," and "important" were used. Specifically, "essential" occurred in 4 out of 125, "recommended" in 12 out of 125, "best" in 6 out of 125, and "important" in 94 out of 125 answers. Additionally, 7 out of the 125 answers did not include a recommendation to seek medical attention. CONCLUSIONS: The accuracy and reproducibility of ChatGPT to self-diagnose five common orthopedic conditions were inconsistent. The accuracy could potentially be improved by adding symptoms that could easily identify a specific location. Only a few answers were accompanied by a strong recommendation to seek medical attention according to our study standards. Although ChatGPT could serve as a potential first step in accessing care, we found variability in accurate self-diagnosis. Given the risk of harm with self-diagnosis without medical follow-up, it would be prudent for an NLP to include clear language alerting patients to seek expert medical opinions. We hope to shed further light on the use of AI in a future clinical study.

Screening for degenerative cervical myelopathy with the 10-second grip-and-release test using a smartphone and machine learning: A pilot study.

Objective: Early detection and intervention are essential for the mitigation of degenerative cervical myelopathy (DCM). However, although several screening methods exist, they are difficult to understand for community-dwelling people, and the equipment required to set up the test environment is expensive. This study investigated the viability of a DCM-screening method based on the 10-second grip-and-release test using a machine learning algorithm and a smartphone equipped with a camera to facilitate a simple screening system. Methods: Twenty-two participants comprising a group of DCM patients and 17 comprising a control group participated in this study. A spine surgeon diagnosed the presence of DCM. Patients performing the 10-second grip-and-release test were filmed, and the videos were analyzed. The probability of the presence of DCM was estimated using a support vector machine algorithm, and sensitivity, specificity, and area under the curve (AUC) were calculated. Two assessments of the correlation between estimated scores were conducted. The first used a random forest regression model and the Japanese Orthopaedic Association scores for cervical myelopathy (C-JOA). The second assessment used a different model, random forest regression, and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Results: The final classification model had a sensitivity of 90.9%, specificity of 88.2%, and AUC of 0.93. The correlations between each estimated score and the C-JOA and DASH scores were 0.79 and 0.67, respectively. Conclusions: The proposed model could be a helpful screening tool for DCM as it showed excellent performance and high usability for community-dwelling people and non-spine surgeons.

A screening method for cervical myelopathy using machine learning to analyze a drawing behavior.

Early detection of cervical myelopathy (CM) is important for a favorable outcome, as its prognosis is poor when left untreated. We developed a screening method for CM using machine learning-based analysis of the drawing behavior of 38 patients with CM and 66 healthy volunteers. Using a stylus pen, the participants traced three different shapes displayed on a tablet device. During the tasks, writing behaviors, such as the coordinates, velocity, and pressure of the stylus tip, along with the drawing time, were recorded. From these data, features related to the drawing pressure, and time to trace each shape and combination of shapes were used as training data for the support vector machine, a machine learning algorithm. To evaluate the accuracy, a receiver operating characteristic curve was generated, and the area under the curve (AUC) was calculated. Models with triangular waveforms tended to be the most accurate. The best triangular wave model identified patients with and without CM with 76% sensitivity and 76% specificity, yielding an AUC of 0.80. Our model was able to classify CM with high accuracy and could be applied to the development of disease screening systems useful outside the hospital setting.

Three-month outcomes of faricimab loading therapy for wet age-related macular degeneration in Japan.

This multicenter study aimed to assess the short-term effectiveness and safety of faricimab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in Japan. We retrospectively reviewed 63 eyes of 61 patients with wAMD, including types 1, 2, and 3 macular neovascularization as well as polypoidal choroidal vasculopathy (PCV). Patients received three consecutive monthly intravitreal injections of faricimab as loading therapy. Over these 3 months, visual acuity improved gradually compared to baseline. Moreover, the central foveal thickness decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). At 3 months after initiation of faricimab therapy, a dry macula (defined as absence of intraretinal or subretinal fluid) was achieved in 82% of the eyes. Complete regression of polypoidal lesions was observed in 52% of eyes with PCV. Subfoveal choroidal thickness also decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). Although retinal pigment epithelium tears developed in two eyes, there were no other ocular or systemic complications observed during the 3 months of loading therapy. In conclusion, loading therapy using faricimab resulted in improved visual acuity and retinal morphology in Japanese patients with wAMD without particular safety issues.

Clinical and genetic features of cystic fibrosis in Japan.

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in CF transmembrane conductance regulator (CFTR). While CF is the most common hereditary disease in Caucasians, it is rare in East Asia. In the present study, we have examined clinical features and the spectrum of CFTR variants of CF patients in Japan. Clinical data of 132 CF patients were obtained from the national epidemiological survey since 1994 and CF registry. From 2007 to 2022, 46 patients with definite CF were analyzed for CFTR variants. All exons, their boundaries, and part of promoter region of CFTR were sequenced and the presence of large deletion and duplications were examined by multiplex ligation-dependent probe amplification. CF patients in Japan were found to have chronic sinopulmonary disease (85.6%), exocrine pancreatic insufficiency (66.7%), meconium ileus (35.6%), electrolyte imbalance (21.2%), CF-associated liver disease (14.4%), and CF-related diabetes (6.1%). The median survival age was 25.0 years. The mean BMI percentile was 30.3%ile in definite CF patients aged < 18 years whose CFTR genotypes were known. In 70 CF alleles of East Asia/Japan origin, CFTR-dele16-17a-17b was detected in 24 alleles, the other variants were novel or very rare, and no pathogenic variants were detected in 8 alleles. In 22 CF alleles of Europe origin, F508del was detected in 11 alleles. In summary, clinical phenotype of Japanese CF patients is similar to European patients, but the prognosis is worse. The spectrum of CFTR variants in Japanese CF alleles is entirely different from that in European CF alleles.

Identification of characteristics of foot position and angle during swing phase in fallers using principal component analysis.

Identifying the characteristics of fallers is important for preventing falls because such events may reduce quality of life. It has been reported that several variables related to foot positions and angles during gait (e.g., sagittal foot angle and minimum toe clearance) differ between fallers and non-fallers. However, examining such representative discrete variables may not be sufficient to detect crucial information, which may be contained in the large portions of unanalyzed data. Therefore, we aimed to identify the comprehensive characteristics of foot position and angle during the swing phase of gait in non-fallers and fallers using principal component analysis (PCA). Thirty non-fallers and 30 fallers were recruited for this study. We performed PCA to reduce the dimensions of foot positions and angles during the swing phase and obtained principal component scores (PCSs) for each principal component vector (PCV), which were then compared between groups. The results revealed that the PCS of PCV3 in fallers was significantly larger than that in non-fallers (p = 0.003, Cohen's d = 0.80). We reconstructed waveforms of foot positions and angles during the swing phase using PCV3 and our main findings can be summarized as follows. Compared to non-fallers, fallers have a 1) low average foot position in the z-axis (i.e., height) during the initial swing phase 2) small average foot angle in the x-axis (i.e., rotation in the sagittal plane), during the initial swing phase, and 3) large variability in foot position in the y-axis (i.e., anterior/posterior position) during the initial swing phase. We can conclude that these are characteristics of gait related to fallers. Therefore, our findings may be beneficial for evaluating fall risk during gait using a device such as a shoe- or insole-embedded inertial measurement unit.

Efficient Identification of the MYC Regulator with the Use of the CRISPR Library and Context-Matched Database Screenings.

MYC is a major oncogene that plays an important role in cell proliferation in human cancers. Therefore, the mechanism behind MYC regulation is a viable therapeutic target for the treatment of cancer. Comprehensive and efficient screening of MYC regulators is needed, and we had previously established a promoter screening system using fluorescent proteins and the CRISPR library. For the efficient identification of candidate genes, a database was used, for which mRNA expression was correlated with MYC using datasets featuring "Similar" and "Not exactly similar" contexts. INTS14 and ERI2 were identified using datasets featuring the "Similar" context group, and INTS14 and ERI2 were capable of enhancing MYC promoter activity. In further database analysis of human cancers, a higher expression of MYC mRNA was observed in the INTS14 mRNA high-expressing prostate and liver cancers. The knockdown of INTS14 in prostate cell lines resulted in decreased MYC mRNA and protein expression and also induced G0/1 arrest. This study confirmed that CRISPR screening combined with context-matched database screening is effective in identifying genes that regulate the MYC promoter. This method can be applied to other genes and is expected to be useful in identifying the regulators of other proto-oncogenes.

A case of recurrent endometrial cancer with long-term complete remission following pembrolizumab-induced severe immune-related adverse event colitis.

Endometrial cancer is generally diagnosed at an early stage and has a good prognosis, although once it recurs, the prognosis is poor because of few therapeutic options. Since endometrial cancer has a high frequency of microsatellite instability-high/mismatch repair deficiency, the anti-PD-1 antibody pembrolizumab is expected to be one of the key therapeutic agents for recurrent endometrial cancer. Immune-related adverse events (irAEs) are autoimmune-like unique and occasionally life-threatening side effects of immune checkpoint inhibitors. Here, we report a rare case of recurrent endometrial cancer that showed long-term complete remission after developing relapsing severe irAE colitis following the introduction of pembrolizumab.

Development of a Model System for Gas Cavity Formation Behavior of Magnesium Alloy Implantation.

Clinical applications of magnesium (Mg)-based screws have reported gas cavity formation in the surrounding tissue, which sometimes delays the fixation of the bone fracture. The gas cavity formation is considered to depend on the balance between hydrogen generation by Mg corrosion reacting with water in the body fluid and its diffusion into the surrounding tissue by capillary flow. In order to understand the gas cavity formation behavior by Mg-based material implantation, we developed a new in vitro model system to recreate this cavity formation phenomenon: the hydrogen generation by corrosion and its diffusion into the medium. A model tissue is prepared by gelation of the cell culture medium in a sterile condition. The immersion of Mg alloy samples was performed under 5% CO2 atmosphere with periodic observation by X-ray computed tomography, which enabled us to observe gas cavity growth up to 28 d. For demonstrating the usefulness of our model system, Mg alloy samples with different corrosion rates were prepared by a biodegradable polymer coating. AZ31 screws were spin-coated by poly-l-lactide (PLLA) and classified into three groups by their coating thickness as 1.0 ± 0.0, 1.6 ± 0.2, and 2.0 ± 0.1 µm (ave. ± s.d.). Upon their immersion into the model tissue, the gas cavity volumes formed were 1.57 ± 0.23, 1.06 ± 0.22, and 0.38 ± 0.09 mm3/mm2 for 1.0, 1.6, and 2.0 µm coating samples, having the weight loss of 20.2 ± 2.93, 18.5 ± 2.84, and 11.3 ± 3.54 µg/mm2, respectively (ave. ± s.d.). This result clearly indicates the dependence of gas cavity formation on the corrosion rate of the sample. The gas cavity volume was only 3.3∼7.5% of the total hydrogen gas volume estimated based on the weight loss of the samples at 28 d, which is in the range of those calculated from the clinical report (3.2∼9.4% at 4w). This system can be an effective tool to investigate the gas cavity formation behavior and contribute to understand the mechanisms and controlling factors of this phenomenon.