Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition.

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Blood flow restriction attenuates surface mechanomyography lateral and longitudinal, but not transverse oscillations during fatiguing exercise.

Objective. Surface mechanomyography (sMMG) can measure oscillations of the activated muscle fibers in three axes (i.e.X,Y, andZ-axes) and has been used to describe motor unit activation patterns (X-axis). The application of blood flow restriction (BFR) is common in exercise studies, but the cuff may restrict muscle fiber oscillations. Therefore, the purpose of this investigation was to examine the acute effects of submaximal, fatiguing exercise with and without BFR on sMMG amplitude in theX,Y, andZ-axes among female participants.Approach. Sixteen females (21 ± 1 years) performed two separate exercise bouts to volitional exhaustion that consisted of unilateral, submaximal (50% maximal voluntary isometric contraction [MVIC]) intermittent, isometric, leg extensions with and without BFR. sMMG was recorded and examined across percent time to exhaustion (%TTE) in 20% increments. Separate 2-way repeated measures ANOVA models were constructed: (condition [BFR, non-BFR]) × (time [20, 40, 60, 80, and 100% TTE]) to examine absolute (m·s-2) and normalized (% of pretest MVIC) sMMG amplitude in theX-(sMMG-X),Y-(sMMG-Y), andZ-(sMMG-Z) axes.Main results. The absolute sMMG-X amplitude responses were attenuated with the application of BFR (mean ± SD = 0.236 ± 0.138 m·s-2) relative to non-BFR (0.366 ± 0.199 m·s-2, collapsed across time) and for sMMG-Y amplitude at 60%-100% of TTE (BFR range = 0.213-0.232 m·s-2versus non-BFR = 0.313-0.445 m·s-2). Normalizing sMMG to pretest MVIC removed most, but not all the attenuation which was still evident for sMMG-Y amplitude at 100% of TTE between BFR (72.9 ± 47.2%) and non-BFR (98.9 ± 53.1%). Interestingly, sMMG-Z amplitude was not affected by the application of BFR and progressively decreased across %TTE (0.332 ± 0.167 m·s-2to 0.219 ± 0.104 m·s-2, collapsed across condition.)Significance. The application of BFR attenuated sMMG-X and sMMG-Y amplitude, although normalizing sMMG removed most of this attenuation. Unlike theXandY-axes, sMMG-Z amplitude was not affected by BFR and progressively decreased across each exercise bout potentially tracking the development of muscle fatigue.

Tongue-in-Groove: A Novel Implant Design for a Blow-Out Fracture.

Background: During blow-out fracture surgery, restoration of the orbital volume and rigid implant fixation are essential. The migration of an implant is a concern of most surgeons. The purpose of this study was to introduce a simple idea of molding and fixing an orbital implant. Methods: In the tongue-in-groove method, an incision of about 2 mm was made on the edge of the implant and it was bent to form a slot. A hole was made in the center of the implant for fitting a bone hook, and the implant was firmly fit into the remaining intact bone. Before and after surgery, computed tomography (CT) was used to evaluate changes in the orbital volume and the location of the implant. Statistically significant restoration of the orbital volume was confirmed on postoperative CT. Results: Compared with the unaffected orbital volume, the affected orbital volume was increased from 87.06 ± 7.92% before surgery to 96.14 ± 6.11% after surgery (p < 0.001). There was one case of implant migration during follow-up. However, the degree of movement was not severe, and there were no events during the follow-up period. Conclusions: The tongue-in-groove technique offers advantages, such as easy fixation of the implant, with minimal trauma to the surrounding tissues. In addition, the method offers advantages, such as being easy to learn, requiring little time for trimming the implant, and being relatively low cost. Therefore, it can be one of the options for implant fixation.

A complex case of posterior reversible encephalopathy syndrome after combined spinal epidural of preeclampsia parturient: A case report.

Posterior reversible encephalopathy syndrome (PRES) is a disorder characterized by vasogenic edema affecting the posterior brain region. We report a case of PRES in a 36-year-old woman with preeclampsia who underwent an emergency cesarean section with spinal anesthesia. After surgery, she developed right leg weakness, headache, and seizures. Imaging showed white matter edema consistent with PRES. The exact cause of PRES is unclear, but elevated blood pressure and endothelial dysfunction are implicated. Tight blood pressure control in PRES is crucial for management, and prompt recognition and treatment are essential for favorable outcomes.

Design and characterization of a variable-stiffness ankle-foot orthosis.

BACKGROUND: Ankle-foot orthoses (AFOs) are a type of assistive device that can improve the walking ability of individuals with neurological disorders. Adjusting stiffness is a common way to customize settings according to individuals' impairment. OBJECTIVE: This study aims to design a variable-stiffness AFO by stiffness module and characterize the AFO stiffness range to provide subject-specific settings for the users. METHODS: We modeled AFO using bending beams with varying fulcrum positions to adjust the stiffness. To characterize the stiffness range and profile, we used the superposition method to generate the theoretical model to analyze the AFO numerically. The intrinsic deformation of the bending beam in the AFO is considered a combination of 2 bending deformations to replicate actual bending conditions. The corresponding experiments in different fulcrum positions were performed to compare with and optimize the theoretical model. The curve fitting method was applied to tune the theoretical model by adding a fulcrum position-related coefficient. RESULTS: The AFO stiffness increased as the fulcrum moved to the proximal position. The maximum stiffness obtained was 1.77 Nm/° at a 6-cm fulcrum position, and the minimum stiffness was 0.82 Nm/° at a 0.5-cm fulcrum position with a 0.43-cm thick fiberglass beam. The corresponding theoretical model had maximum and minimum stiffness of 1.71 and 0.80 Nm/°, respectively. The theoretical model had a 4.08% difference compared with experimental values. CONCLUSIONS: The stiffness module can provide adjustable stiffness with the fulcrum position and different kinds of fiberglass bars, especially the thickness and material of the beam. The theoretical model with different fulcrum positions can be used to profile the real-time stiffness of the AFO in a dynamic motion and to determine the appropriate dimensions of the bending beam.

Does the advantage of transcutaneous oximetry measurements in diabetic foot ulcer apply equally to free flap reconstruction?

BACKGROUND: Transcutaneous oxygen pressure (TcpO2) is a precise method for determining oxygen perfusion in wounded tissues. The device uses either electrochemical or optical sensors. AIM: To evaluate the usefulness of TcpO2 measurements on free flaps (FFs) in diabetic foot ulcers (DFUs). METHODS: TcpO2 was measured in 17 patients with DFUs who underwent anterolateral thigh (ALT)-FF surgery and compared with 30 patients with DFU without FF surgery. RESULTS: Significant differences were observed in the ankle-brachial index; duration of diabetes; and haemoglobin, creatinine, and C-reactive protein levels between the two groups. TcpO2 values were similar between two groups except on postoperative days 30 and 60 when the values in the ALT-FF group remained < 30 mmHg and did not increase > 50 mmHg. CONCLUSION: Even if the flap is clinically stable, sympathectomy due to adventitia stripping during anastomosis and arteriovenous shunt progression due to diabetic polyneuropathy could lead to low TcpO2 values in the ALT-FF owing to its thick fat tissues, which is supported by the slow recovery of the sympathetic tone following FF. Therefore, TcpO2 measurements in patients with DFU who underwent FF reconstruction may be less accurate than in those who did not.

Successful reconstruction using a buccal fat pad flap in misdiagnosed buccinators intramuscular synovial sarcoma: A case report.

INTRODUCTION: Synovial sarcoma (SS) is a subtype of soft tissue sarcoma that primarily usually occurs in the lower extremities but rarely arises in the head and neck areas, including the oral cavity. Due to its variable presentation and similarity to benign masses in terms of age at onset, growth rate, and favorable outcomes, SS is often misdiagnosed as a benign tumor. However, it is a malignant tumor. PATIENT CONCERNS: We report the case of intramuscular SS in the oral cavity. Initially, the lesion was clinically suspected as a benign mass but was ultimately confirmed as malignant SS. DIAGNOSIS: Although histopathological examination is the first step in diagnosing SS, molecular testing to confirm the presence of SYT-SSX fusion can provide a definitive diagnosis when the histopathology is inconclusive. In this patient as well, the postoperative pathological report confirmed the diagnosis of biphasic SS, and molecular testing revealed positive SYT/SSX fusion. THERAPEUTICS INTERVENTIONS: Following the recommendation of multidisciplinary care system, a wide excision was performed including the buccinators muscle, and reconstruction was performed using a buccal fat pad flap to prevent cheek depression. OUTCOMES: On the final pathologic report, SS was removed margin-free, and there were no metastatic lymph nodes. No evidence of cheek dimpling was observed, and follow-up neck CT showed no significant changes in the lymph nodes. As a result of observation up to several months after surgery, there were no functional and aesthetic complications. CONCLUSIONS: We report a successful case of intramuscular SS resection, initially misdiagnosed as a benign mass, using a buccal fat pad flap. We also highlight the importance of correctly diagnosing SS, especially in the craniofacial region where it can be mistaken for benign masses.

Severe pulmonary edema occurred during endobronchial ultrasound under monitored anesthesia care - A case report.

BACKGROUND: Endobronchial ultrasound (EBUS) is widely used to diagnose lung cancer. Monitored anesthesia care (MAC) can enhance patient comfort and procedural conditions during EBUS. EBUS under MAC is usually safe but can lead to various complications. CASE: A 34-year-old male who had increased sputum for two months showed an enlarged paratracheal lymph node and planned for lymph node biopsy by EBUS. During EBUS under MAC, an unexpected oxygen saturation decline required intervention. After intubation, copious frothy fluid was suctioned from the bronchi, and oxygenation was recovered. A narrowed trachea and the EBUS bronchoscope might have resulted in upper airway obstruction, and suction performed under these conditions might have caused pulmonary edema. The patient received non-invasive ventilation and high-flow nasal cannula and recovered without complications. CONCLUSIONS: When there is an expected risk of upper airway obstruction during EBUS, careful preoperative evaluation and preparation are essential to prevent negative pressure pulmonary edema.

A CARE-compliant article: A case report of unusual eschar and extensive soft tissue necrosis in Tsutsugamushi disease.

RATIONALE: Tsutsugamushi disease is a common infectious disease in the Northern Hemisphere. A patient infected with tsutsugamushi disease will show a characteristic clinical course with eschar formation, which is mostly small and self-limited in nature without causing major problems. We report a rare case of unusually extensive necrosis started from a small eschar. PATIENT CONCERNS: In this report, a 65-year-old female patient with a history of diabetes mellitus present an 8 × 6 cm-sized huge eschar and extensive soft tissue necrosis aggravated from a small eschar. Also, there were 3 other small eschars in the scalp and left flank area. In early July, she was farming in a field in Hongseong-gun, South Korea. She had been treated at another hospital for 2 weeks. However, the eschar became bigger and worse. DIAGNOSES: After admission, escharectomy was performed and extensive soft tissue necrosis was identified. Orientia tsutsugamushi antibody tests were positive from blood test. Providencia rettgeri and Enterococcus faecalis were detected in a tissue bacterial culture test. INTERVENTION: While using oral azithromycin and intravenous imipenem/cilastatin, the necrosis of the thigh was excised and covered by lateral femoral circumflex artery based myocutaneous Keystone flap. OUTCOMES: The remaining small eschars recovered spontaneously, the large eschars that had caused necrosis were successfully treated, and all other clinical symptoms improved without complications. LESSONS: For unusual eschar of an unknown cause, especially in patients with uncontrolled diabetes or immunocompromised, the possibility of Tsutsugamushi should be considered. Careful physical examination and proper management should be performed as soon as possible.

Effectiveness of out-fracture of the inferior turbinate with reduction nasal bone fracture.

BACKGROUND: The nasal bone, being the most protruding bone in the center of the facial bones, is particularly susceptible to damage. Nasal bone fractures can often result in secondary deformation and dysfunction of the nose, including septal fractures. Studies on functional or intra-nasal complications have been rarely reported after nasal bone fracture reduction. AIM: To evaluate the severity of nasal obstruction and its improvement following nasal bone fracture reduction using inferior turbinoplasty. METHODS: We conducted a retrospective review of data from 50 patients with symptomatic nasal obstruction between January to December 2010. All patients underwent preoperative Computed tomography evaluation, and symptom changes and nasal cavity volume were analyzed using a visual analog scale and acoustic rhinometry before and after surgery. Closed reduction and out-fracture of both inferior turbinates performed by the same surgeon. Treatment outcomes were assessed by comparing changes in the nasal airway volume measured using acoustic rhinometry before and after surgery. The minimal cross-sectional area (MCA) was also analyzed based on the Stranc classification. RESULTS: Before reduction, the mean MCA for all cases was 0.59 ± 0.06 cm2, which represented an 11% decrease compared to the average size of a Korean adult (0.65 ± 0.03 cm2). The MCA for frontal impact was 0.60 ± 0.02 cm2 and for lateral impact, it was 0.58 ± 0.03 cm2. After reduction via inferior turbinoplasty, the MCA improved to 0.64 ± 0.04 cm2. CONCLUSION: This study suggests that turbinoplasty is helpful in addressing nasal obstruction. Out-fracture of the inferior turbinate is an effective and durable technique that can be easily performed to enlarge the nasal airway with minimal morbidity.

The correlation between transcutaneous oxygen pressure (TcPO2 ) and forward-looking infrared (FLIR) thermography in the evaluation of lower extremity perfusion according to angiosome.

The increased peripheral arterial disease (PAD) incidence associated with aging and increased incidence of cardiovascular conditions underscores the significance of assessing lower limb perfusion. This study aims to report on the correlation and utility of two novel non-invasive instruments: transcutaneous oxygen pressure (TcPO2 ) and forward-looking infrared (FLIR) thermography. A total of 68 patients diagnosed with diabetic foot ulcer and PAD who underwent vascular studies at a single institution between March 2022 and March 2023 were included. Cases with revascularization indications were treated by a cardiologist. Following the procedure, ambient TcPO2 and FLIR thermography were recorded on postoperative days 1, 7, 14, 21 and 28. In impaired limbs, TcPO2 was 12.3 ± 2 mmHg and FLIR thermography was 28.7 ± 0.9°C. TcPO2 (p = 0.002), FLIR thermography (p = 0.015) and ankle-brachial index (p = 0.047) values significantly reduced with greater vascular obstruction severity. Revascularization (n = 39) significantly improved TcPO2 (12.5 ± 1.7 to 19.1 ± 2.2 mmHg, p = 0.011) and FLIR (28.8 ± 1.8 to 32.6 ± 1.6°C; p = 0.018), especially in severe impaired angiosomes. TcPO2 significantly increased immediately post-procedure, then gradually, whereas the FLIR thermography values plateaued from day 1 to 28 post-procedure. In conclusion, FLIR thermography is a viable non-invasive tool for evaluating lower limb perfusion based on angiosomes, comparable with TcPO2 .

Wearable Motion Capture: Reconstructing and Predicting 3D Human Poses From Wearable Sensors.

Reconstructing and predicting 3D human walking poses in unconstrained measurement environments have the potential to use for health monitoring systems for people with movement disabilities by assessing progression after treatments and providing information for assistive device controls. The latest pose estimation algorithms utilize motion capture systems, which capture data from IMU sensors and third-person view cameras. However, third-person views are not always possible for outpatients alone. Thus, we propose the wearable motion capture problem of reconstructing and predicting 3D human poses from the wearable IMU sensors and wearable cameras, which aids clinicians' diagnoses on patients out of clinics. To solve this problem, we introduce a novel Attention-Oriented Recurrent Neural Network (AttRNet) that contains a sensor-wise attention-oriented recurrent encoder, a reconstruction module, and a dynamic temporal attention-oriented recurrent decoder, to reconstruct the 3D human pose over time and predict the 3D human poses at the following time steps. To evaluate our approach, we collected a new WearableMotionCapture dataset using wearable IMUs and wearable video cameras, along with the musculoskeletal joint angle ground truth. The proposed AttRNet shows high accuracy on the new lower-limb WearableMotionCapture dataset, and it also outperforms the state-of-the-art methods on two public full-body pose datasets: DIP-IMU and TotalCaputre.

In Vitro and In Vivo Evaluation of Epidermal Growth Factor (EGF) Loaded Alginate-Hyaluronic Acid (AlgHA) Microbeads System for Wound Healing.

The management of skin injuries is one of the most common concerns in medical facilities. Different types of biomaterials with effective wound-healing characteristics have been studied previously. In this study, we used alginate (Alg) and hyaluronic acid (HA) composite (80:20) beads for the sustained release of epidermal growth factor (EGF) delivery. Heparin crosslinked AlgHA beads showed significant loading and entrapment of EGF. Encapsulated beads demonstrated biocompatibility with rat L929 cells and significant migration at the concentration of AlgHAEGF100 and AlgHAEGF150 within 24 h. Both groups significantly improved the expression of Fetal Liver Kinase 1 (FLK-1) along with the Intercellular Adhesion Molecule-1 (ICAM-1) protein in rat bone Mesenchymal stem cells (rbMSCs). In vivo assessment exhibited significant epithelialization and wound closure gaps within 2 weeks. Immunohistochemistry shows markedly significant levels of ICAM-1, FLK-1, and fibronectin (FN) in the AlgHAEGF100 and AlgHAEGF150 groups. Hence, we conclude that the EGF-loaded alginate-hyaluronic acid (AlgHA) bead system can be used to promote wound healing.

Removal of unexpected schwannoma with superficial parotidectomy using modified-Blair incision and superficial musculoaponeurotic system folding: A case report.

BACKGROUND: When a firm facial mass in the cheek region is associated with a high index of clinical suspicion of its being of parotid gland origin, preventive parotidectomy is invariably performed. We report a rare case of a schwannoma that was suspected to be of parotid gland origin in a patient, who underwent successful surgical management using a modified-Blair incision and superficial musculoaponeurotic system (SMAS) layer folding method. CASE SUMMARY: A 27-year-old woman presented to the hospital for evaluation of a firm, fixed, non-tender mass (2.5 cm × 3.5 cm), located anterior to the right ear, of 1 year's duration. Contrast-enhanced facial computed tomography revealed a well-encapsulated, low-density mass adherent to the superficial lobe of the right parotid gland, with a high index of clinical suspicion of an accessory parotid gland mass. The patient was scheduled to undergo resection of the mass and superficial parotidectomy. She underwent surgery using a modified-Blair incision, and the SMAS layer was folded posteriorly to reconstruct the defect. Histopathological examination confirmed the diagnosis of a schwannoma., and we observed no postoperative complications such as hematoma, infection, or abnormal facial expressions. The incision scar was unnoticeable 2 mo postoperatively, and the facial contour was maintained without any differences between the affected and unaffected sides. CONCLUSION: We used a modified-Blair incision and SMAS layer folding method to achieve aesthetically good results following resection of a rare schwannoma with superficial parotidectomy in the cheek region.

Anesthetic management of an elderly COVID-19 patient with pulmonary thromboembolism for hip surgery - A case report.

BACKGROUND: COVID-19 and delayed hip surgery are well-known risk factors for thromboembolism in elderly patients. CASE: We report the case of an 88-year-old female patient with COVID-19 and pulmonary thromboembolism (PTE) who underwent delayed hip surgery 21 days after the injury. Heparinization and inferior vena cava filters were used to treat and prevent PTE. Transesophageal echocardiography and extracorporeal membrane oxygenation (ECMO) sheaths were inserted as a precaution in case of emergencies during surgery; the procedure was performed without any specific event. CONCLUSIONS: COVID-19-infected patients suffering from a hip fracture have a high risk of thromboembolism, and therefore, require utmost attention for appropriate evaluation and prevention.

Breast filler granuloma mistaken for implant rupture: A case report.

RATIONALE: Breast augmentation is usually performed by inserting implants into the breasts. However, injectable fillers are sometimes used for the convenience of both patients and surgeons. If foreign substances, such as biomaterials, are injected into the body, complications such as inflammation, granuloma, and tissue necrosis can occur owing to foreign body reactions. PATIENT CONCERNS: A 39-year-old female patient visited our hospital complaining of tenderness, redness, and swelling in both breasts. The patient had undergone bilateral breast augmentation using implants 4 years prior to current consult. DIAGNOSES: On magnetic resonance imaging (MRI), cystic lesions and fluid collections were observed, with findings suggesting implant rupture; hence, surgery was planned to remove both implants. INTERVENTIONS: Intraoperatively, the implant was malpositioned in the upper lateral portion without rupture. Capsular contracture findings were also not prominent. A large amount of inflammatory granuloma was observed and removed in the prepectoral plane, and the implants were immediately inserted into a new subpectoral plane. OUTCOMES: The volume of the new implant was 175 mL, which was smaller than the previous one, as per the patient preference. Cytology of the fluid from the previous implant pocket showed no evidence of malignancy, and the granuloma was identified as inflammatory tissue caused by a foreign body reaction on biopsy. The excessive protrusion of both breasts was corrected after surgery, and the patient was satisfied with the aesthetic outcomes without any complications up to 3 months after surgery. LESSONS: The use of injectable fillers for breast augmentation carries the risk of misdiagnosis, and, therefore, surgeons should always exercise caution.

Simultaneous determination of 11 nootropic substances potentially adulterated in dietary supplements for improving brain function using ultra-performance liquid chromatography and liquid chromatography-quadrupole-time-of-flight mass spectrometry.

Recently, the demand for improved brain function and concentration has increased in the dietary supplement market. However, to artificially enhance their pharmacological efficacy, dietary supplements may be illegally adulterated with unauthorised substances. Therefore, we developed a rapid and accurate method to simultaneously determine 11 nootropic substances using an ultra-high-performance liquid chromatography (UPLC) system equipped with a photodiode array (PDA) detector. In addition, sample preparation procedures were semi-optimised for various types of matrices, including solid (hard capsule, tablet, powder, and pill) and liquid (oil and extract) samples. The method was validated to determine the limit of detection (LOD), limit of quantification (LOQ), method detection limit (MDL), method quantitation limit (MQL), specificity, linearity, precision, accuracy, recovery, stability, and matrix effects. The validation results satisfied international validation guideline requirements. To test the applicability of the method, 55 real samples advertised as effective brain health, memory, and cognition supplements were analysed. Among the real samples, vinpocetine (2.483 and 7.296 µg/g), and kavain (69-44.056 µg/g) were detected. In addition, the detected compounds were confirmed by comparing their fragmentation patterns with those of the reference standards using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF/MS). In conclusion, the UPLC-PDA method not only rapidly and accurately quantifies illegal nootropics but also enables the pre-emptive investigation and identification of 11 nootropic substances in illegal dietary supplements to protect public health.

New scaffolds for type II JAK2 inhibitors overcome the acquired G993A resistance mutation.

Recurrent JAK2 alterations are observed in myeloproliferative neoplasms, B-cell acute lymphoblastic leukemia, and other hematologic malignancies. Currently available type I JAK2 inhibitors have limited activity in these diseases. Preclinical data support the improved efficacy of type II JAK2 inhibitors, which lock the kinase in the inactive conformation. By screening small molecule libraries, we identified a lead compound with JAK2 selectivity. We highlight analogs with on-target biochemical and cellular activity and demonstrate in vivo activity using a mouse model of polycythemia vera. We present a co-crystal structure that confirms the type II binding mode of our compounds with the "DFG-out" conformation of the JAK2 activation loop. Finally, we identify a JAK2 G993A mutation that confers resistance to the type II JAK2 inhibitor CHZ868 but not to our analogs. These data provide a template for identifying novel type II kinase inhibitors and inform further development of agents targeting JAK2 that overcome resistance.

Estimation of Lower Extremity Joint Moments and 3D Ground Reaction Forces Using IMU Sensors in Multiple Walking Conditions: A Deep Learning Approach.

Human kinetics, specifically joint moments and ground reaction forces (GRFs) can provide important clinical information and can be used to control assistive devices. Traditionally, collection of kinetics is mostly limited to the lab environment because it relies on data that are measured from a motion capture system and floor-embedded force plates to calculate the dynamics via musculoskeletal models. This spatially limited method makes it extremely challenging to measure kinetics outside the laboratory in a variety of walking conditions due to the expensive device setup and large space required. Recently, employing machine learning with IMU sensors are suggested as an alternative method for biomechanical analyses. Although these methods enable estimating human kinetic data outside the laboratory by linking IMU sensor data with kinetics dataset, they are limited to show inaccurate kinetic estimates even in highly repeatable single walking conditions due to the employment of generic deep learning algorithms. Thus, this paper proposes a novel deep learning model, Kinetics-FM-DLR-Ensemble-Net for single limb prediction of hip, knee, and ankle joint moments and 3-dimensional GRFs using three IMU sensors on the thigh, shank, and foot under several representatives walking conditions in daily living, such as treadmill, level-ground, stair, and ramp. This is the first study that implements both joint moments and GRFs in multiple walking conditions using IMU sensors via deep learning. Our deep learning model is versatile and accurate for identifying human kinetics across diverse subjects and walking conditions and outperforms state-of-the-art deep learning model for kinetics estimation by a large margin.

Recurrent intramuscular lipoma at extensor pollicis brevis: A case report.

BACKGROUND: This report describes and discusses recurrent intramuscular lipoma (IML) of the extensor pollicis brevis (EPB). An IML usually occurs in a large muscle of the limb or torso. Recurrence of IML is rare. Recurrent IMLs, especially those with unclear boundaries, necessitate complete excision. Several cases of IML in the hand have been reported. However, recurrent IML appearing along the muscle and tendon of EPB on wrist and forearm has not been reported yet. CASE SUMMARY: In this report, the authors describe clinical and histopathological features of recurrent IML at EPB. A 42-year-old Asian woman presented with a slow-growing lump in her right forearm and wrist area six months ago. The patient had a history of surgery for a lipoma of the right forearm one year ago with a scar of 6 cm on the right forearm. magnetic resonance imaging confirmed that the lipomatous mass, which had attenuation similar to subcutaneous fat, had invaded the muscle layer of EPB. Excision and biopsy were performed under general anesthesia. On histological examination, it was identified as an IML showing mature adipocytes and skeletal muscle fibers. Therefore, surgery was terminated without further resection. No recurrence occurred during a follow-up of five years after surgery. CONCLUSION: Recurrent IML in the wrist must be examined to differentiate it from sarcoma. Damage to surrounding tissues should be minimized during excision.