Fragment excision and triceps V-Y advanced reattachment using suture anchor for olecranon nonunion: A case report.

RATIONALE: The nonunion of olecranon fractures is uncommon in simple fractures, and it is challenging to treat surgically due to the disruption of the anatomy of the elbow joint. There is limited literature on surgical options, and several factors to determine the treatment, including the amount and quality of bone stock, age, and degree of articular damage. PATIENT CONCERNS: A 58-year-old man presented at the clinic with neglected olecranon fracture for 1 year (case 1). A 74-year-old man (case 2) presented with consistent pain and limited of motion after surgery for olecranon fracture. DIAGNOSIS: Both patients were diagnosed with olecranon nonunion. INTERVENTION: Both patients received the excision of nonunited fragment and reattaching with V-Y advancement of triceps. OUTCOMES: Range of motion and Mayo elbow performance score were improved after surgery. LESSONS: This technique is useful in patients who cannot undergo other surgical options due to insufficient bone quality and elbow function, and it can lead to satisfactory outcomes with an acceptable range of motion and pain relief.

Overcoming BRAF and CDK4/6 inhibitor resistance by inhibiting MAP3K3-dependent protection against YAP lysosomal degradation.

Transcriptional programs governed by YAP play key roles in conferring resistance to various molecular-targeted anticancer agents. Strategies aimed at inhibiting YAP activity have garnered substantial interest as a means to overcome drug resistance. However, despite extensive research into the canonical Hippo-YAP pathway, few clinical agents are currently available to counteract YAP-associated drug resistance. Here, we present a novel mechanism of YAP stability regulation by MAP3K3 that is independent of Hippo kinases. Furthermore, we identified MAP3K3 as a target for overcoming anticancer drug resistance. Depletion of MAP3K3 led to a substantial reduction in the YAP protein level in melanoma and breast cancer cells. Mass spectrometry analysis revealed that MAP3K3 phosphorylates YAP at serine 405. This MAP3K3-mediated phosphorylation event hindered the binding of the E3 ubiquitin ligase FBXW7 to YAP, thereby preventing its p62-mediated lysosomal degradation. Robust YAP activation was observed in CDK4/6 inhibitor-resistant luminal breast cancer cells. Knockdown or pharmacological inhibition of MAP3K3 effectively suppressed YAP activity and restored CDK4/6 inhibitor sensitivity. Similarly, elevated MAP3K3 expression supported the prosurvival activity of YAP in BRAF inhibitor-resistant melanoma cells. Inhibition of MAP3K3 decreased YAP-dependent cell proliferation and successfully restored BRAF inhibitor sensitivity. In conclusion, our study reveals a previously unrecognized mechanism for the regulation of YAP stability, suggesting MAP3K3 inhibition as a promising strategy for overcoming resistance to CDK4/6 and BRAF inhibitors in cancer treatment.

Volumetric changes in temporomandibular joint space following trans-oral vertical ramus osteotomy in patients with mandibular prognathism: a one-year follow-up study.

This study measured and analyzed chronological changes in temporomandibular joint space volume by compartment following transoral vertical ramus osteotomy (TOVRO) using reconstructed 3-dimensional (3D) images of patients with mandibular prognathism. It included 70 joints of 35 patients who underwent TOVRO between January 2018 and December 2021. Computed tomography (CT) or cone-beam CT (CBCT) was performed before surgery (T0) and at 3 days (T1), 6 months (T2), and 12 months postoperatively (T3). These scans were then analyzed using 3D software. The volumes of the overall (Vjs), anterior (Vajs), posterior (Vpjs), medial (Vmjs), and lateral (Vljs) joint spaces were calculated at each time point. A linear mixed model and repeated-measures covariance pattern with unstructured covariance were used to evaluate significant changes in joint space volume over time. Vjs significantly increased to 134.54 ± 34.28 mm3 at T3 compared to T0 (p < 0.001). Vpjas and Vljs increased by 130.72 ± 10.07 mm3 and 109.98 ± 7.52 mm3 at T3 compared to T0, respectively (p < 0.001). However, no significant difference was observed between T0 and T2 in Vajs and Vmjs (p = 0.9999). The observed volume increases in Vpjs and Vljs appeared to contribute to the overall Vjs increase.

Colloidal Synthesis of Ultrathin and Se-Rich V2Se9 Nanobelts as High-Performance Anode Materials for Li-Ion Batteries.

In this study, the one-dimensional (1D) material V2Se9 was successfully synthesized using a colloidal method with VO(acac)2 and Se powder as precursors in a 1-octadecene solvent. The obtained colloidally synthesized V2Se9 (C-V2Se9) has an ultrathin nanobelt shape and a 4.5 times higher surface area compared with the bulk V2Se9, which is synthesized in a solid-state reaction as previously reported. In addition, all surfaces of C-V2Se9 are exposed to Se atoms, which is advantageous for storing Li through the conversion reaction into the Li2Se phase. Herein, the electrochemical performance of the C-V2Se9 anode material is evaluated; thus, the novelty of C-V2Se9 as a Se-rich 1D anode material is verified. The C-V2Se9 electrode exhibits a reversible capacity of 893.21 mA h g-1 and a Coulombic efficiency of 97.82% at the 100th cycle and excellent structural stability. Compared with the bulk V2Se9 electrode, the outstanding electrochemical performance of C-V2Se9 is attributed to its ultrathin nanobelt shape, high surface area, shorter Li diffusion length, and more electrochemically active sites. This work indicates the great potential of the Se-rich 1D material, C-V2Se9, as a post-transition metal dichalcogenide material for high-performance LIBs.

Glenohumeral versus subacromial steroid injections for impingement syndrome with mild stiffness: a randomized controlled trial.

BACKGROUND: The subacromial (SA) space is a commonly used injection site for treatment of impingement syndrome. For shoulder stiffness, glenohumeral (GH) injections are commonly performed. However, in cases of impingement syndrome with mild shoulder stiffness, the optimal site of steroid injection has yet to be identified. METHODS: This prospective, randomized study compared the short-term outcomes of ultrasound-guided GH and SA steroid injections in patients who were diagnosed with impingement syndrome and mild stiffness. Each group comprised 24 patients who received either a GH or SA injection of 40 mg of triamcinolone. Range of motion and clinical scores were assessed before and 3, 7, and 13 weeks after the injection. RESULTS: GH and SA injections significantly improved the range of motion and clinical scores after 13 weeks of follow-up. Notably, targeting the GH joint resulted in an earlier gain of forward elevation, external rotation, and internal rotation in 3 weeks (P<0.001, P=0.012, and P=0.002, respectively) and of internal rotation and a Constant-Murley score in 7 weeks (P<0.001 and P=0.046). Subsequent measurements were similar between the groups and showed a steady improvement in all ranges of motion and clinical scores. CONCLUSIONS: GH injections may be more favorable than SA injections for treatment of impingement syndrome with mild stiffness, especially in improving the range of motion in the early period. However, the procedures showed similar outcomes after 3 months. Level of evidence: I.

Copy number aberrations in circulating tumor DNA enables prognosis prediction and molecular characterization of breast cancer.

BACKGROUND: Low-pass whole-genome sequencing (LP-WGS)-based circulating tumor DNA (ctDNA) analysis is a versatile tool for somatic copy number aberration (CNA) detection, and this study aims to explore its clinical implication in breast cancer. METHODS: We analyzed LP-WGS ctDNA data from 207 metastatic breast cancer (MBC) patients to explore prognostic value of ctDNA CNA burden and validated it in 465 stage II-III triple-negative breast cancer (TNBC) patients who received neoadjuvant chemotherapy in phase III PEARLY trial (NCT02441933). The clinical implication of locus level LP-WGS ctDNA profiling was further evaluated. RESULTS: We found that a high baseline ctDNA CNA burden predicts poor overall survival and progression-free survival of MBC patients. The post hoc analysis of the PEARLY trial showed that a high baseline ctDNA CNA burden predicted poor disease-free survival independent from pathologic complete response (pCR), validating its robust prognostic significance. The 24-month disease-free survival rate was 96.9% and 55.9% in [pCR(+) and low I-score] and [non-pCR and high I-score] patients, respectively. The locus-level ctDNA CNA profile classified MBC patients into 5 molecular clusters and revealed targetable oncogenic CNAs. LP-WGS ctDNA and in vitro analysis identified the BCL6 amplification as a resistance factor for CDK4/6 inhibitors. We estimated ctDNA-based homologous recombination deficiency status of patients by shallowHRD algorithm, which was highest in the TNBC and correlated with platinum-based chemotherapy response. CONCLUSIONS: These results demonstrate LP-WGS ctDNA CNA analysis as an essential tool for prognosis prediction and molecular profiling. Particularly, ctDNA CNA burden can serve as a useful determinant for escalating or de-escalating (neo)adjuvant strategy in TNBC patients.

On-treatment derived neutrophil-to-lymphocyte ratio and survival with palbociclib and endocrine treatment: analysis of a multicenter retrospective cohort and the PALOMA-2/3 study with immune correlates.

BACKGROUND: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated. METHODS: Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics. RESULTS: In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P < 0.001). In the PALOMA-2 validation cohort, higher on-treatment dNLRs were associated with inferior PFS in patients treated with palbociclib and letrozole (hazard ratio = 1.498, P = 0.009), and reduction in the dNLR after treatment was predictive of a survival benefit (hazard ratio = 1.555, P = 0.026). On-treatment dNLRs were also predictive of PFS following palbociclib and fulvestrant treatment in the PALOMA-3 validation cohort. Using flow cytometry analysis, we found that the CDK4/6 inhibitor prevented T cell exhaustion and diminished myeloid-derived suppressor cell frequency. CONCLUSIONS: On-treatment dNLR significantly predicted PFS in patients with HR-positive, HER2-negative ABC receiving palbociclib and endocrine treatment. Additionally, we observed putative systemic immune responses elicited by palbociclib, suggesting immunologic changes upon CDK4/6 inhibitor treatment.

MRI-Based Personalized Transcranial Direct Current Stimulation to Enhance the Upper Limb Function in Patients with Stroke: Study Protocol for a Double-Blind Randomized Controlled Trial.

Transcranial direct current stimulation (tDCS) has been shown to have the potential to improve the motor recovery of the affected upper limbs in patients with stroke, and recently, several optimized tDCS methods have been proposed to magnify its effectiveness. This study aims to determine the effectiveness of personalized tDCS using brain MRI-based electrical field simulation and optimization, to enhance motor recovery of the upper limbs in the patients. This trial is a double-blind, randomized controlled trial in the subacute to chronic rehabilitation phase. Forty-two adult stroke patients with unilateral upper limb involvement will be randomly allocated to three groups: (1) personalized tDCS with MRI-based electrical field simulation and optimized stimulation, (2) conventional tDCS with bihemispheric stimulation of the primary motor cortex, and (3) sham tDCS. All three groups will undergo 10 intervention sessions with 30 min of 2-mA intensity stimulation, during a regular upper limb rehabilitation program over two weeks. The primary outcome measure for the motor recovery of the upper limb impairment is the Fugl-Meyer assessment for the upper extremity score at the end of the intervention, and the secondary measures include changes in the motor evoked potentials, the frequency power and coherence of the electroencephalography, performance in activities of daily living, and adverse events with a 1-month follow-up assessment. The primary outcome will be analyzed on the intention-to-treat principle. There is a paucity of studies regarding the effectiveness of personalized and optimized tDCS that considers individual brain lesions and electrical field characteristics in the real world. No feasibility or pivotal studies have been performed in stroke patients using brain MRI, to determine a lesion-specific tDCS simulation and optimization that considers obstacles in the segmentation and analysis of the affected brain tissue, such as ischemic and hemorrhagic lesions. This trial will contribute to addressing the effectiveness and safety of personalized tDCS, using brain MRI-based electrical field simulation and optimization, to enhance the motor recovery of the upper limbs in patients with stroke.

Regional nerve blocks for relieving postoperative pain in arthroscopic rotator cuff repair.

Rotator cuff tear is the most common cause of shoulder pain in middle-age and older people. Arthroscopic rotator cuff repair (ARCR) is the most common treatment method for rotator cuff tear. Early postoperative pain after ARCR is the primary concern for surgeons and patients and can affect postoperative rehabilitation, satisfaction, recovery, and hospital day. There are numerous methods for controlling postoperative pain including patient-controlled analgesia, opioid, interscalene block, and local anesthesia. Regional blocks including interscalene nerve block, suprascapular nerve block, and axillary nerve block have been successfully and commonly used. There is no difference between interscalene brachial plexus block (ISB) and suprascapular nerve block (SSNB) in pain control and opioid consumption. However, SSNB has fewer complications and can be more easily applied than ISB. Combination of axillary nerve block with SSNB has a stronger analgesic effect than SSNB alone. These regional blocks can be helpful for postoperative pain control within 48 hours after ARCR surgery.

Colloidal synthesis of 1-D van der Waals material Nb2Se9: study of synergism of coordinating agent in a co-solvent system.

Low-dimensional Nb2Se9 nanocrystals were synthesised through a simple one-pot colloidal synthesis with C18 organic solvents (octadecane, oleylalcohol, octadecanethiol, octadecene (ODE), and oleylamine (OLA)) of varied terminal functional groups. The solvent with high reducing power facilitated the nucleation of the nanoparticle, lowering threshold concentration and broadening the concentration spectrum. As a solvent, reducing agent, and capping agent, ODE functions as a primary factor in the synthesis of high-quality Nb2Se9 nanorods. We further discuss the unique adhesion role of ODE under the co-solvent system and demonstrate morphology control through synergism between ODE and OLA, verified by the electrochemical measurements.

Molecular Characterization of BRCA1 c.5339T>C Missense Mutation in DNA Damage Response of Triple-Negative Breast Cancer

BRCA1 L1780P BRCT domain mutation has been recognized as a pathogenic mutation in patients with breast cancer. However, the molecular significance of this mutation has not yet been studied in triple-negative breast cancer (TNBC) cells in vitro. We established MDA-MB 231, HCC1937, and HCC1395 TNBC cell lines expressing BRCA1 L1780P mutant. BRCA1 L1780P mutant TNBC cells showed increased migration and invasion capacity, as well as increased sensitivity to olaparib and carboplatin compared to BRCA1 wild-type cells. BRCA1 L1780P mutant TNBC cells showed decreased RAD51 expression and reduced nuclear RAD51 foci formation following carboplatin and olaparib treatment. The molecular interaction between p-ATM and BRCA1 was abrogated following introduction of BRCA1 L1780P mutant plasmid in TNBC cells, suggesting that the BRCA1 L1780P mutation disrupts the p-ATM-BRCA1 protein-protein interaction. We established an olaparib-resistant BRCA1 L1780P mutant TNBC cell line by chronic drug treatment. Olaparib-resistant cell lines showed upregulation of RAD51 expression upon olaparib treatment, and reduction in RAD51 expression in olaparib-resistant cells restored olaparib sensitivity. Collectively, these results suggest that the BRCA1 L1780P mutation impairs RAD51 recruitment by disrupting p-ATM-BRCA1 interaction, which is a crucial molecular factor in homologous recombination and olaparib sensitivity. Further therapeutic targeting of RAD51 in BRCA1 L1780P mutant breast cancer is warranted.

Organic Dispersion of Mo3Se3- Single-Chain Atomic Crystals Using Surface Modification Methods.

In this study, single-chain atomic crystals (SCACs), Mo3Se3-, which can be uniformly dispersed, with an atomically thin diameter of ∼0.6 nm were modified to disperse in an organic solvent. Various surfactants were chosen to provide steric hindrance to aqueous-dispersed Mo3Se3- by modifying the surface of Mo3Se3-. The organic dispersions of surface-modified Mo3Se3- SCACs in nonpolar solvent (toluene, benzene, and chloroform) were stable with a uniform diameter of 2 nm, and they have enhanced stability from oxidation (>10 days). With the surfactants that have a polystyrene tail group (PS-NH2), the surface-modified Mo3Se3- SCAC showed high compatibility with a polystyrene polymer matrix. Using the surface-modified Mo3Se3- SCAC, a homogeneous Mo3Se3-/polystyrene/toluene organogel was prepared. More importantly, the Mo3Se3-/polystyrene organogel exhibits significantly enhanced mechanical properties, with the improvement of 202.27% and 279.52% for tensile strength and elongation, respectively, compared with that of the pure organogel. The surface-modified Mo3Se3- had a similar structure with a polymer matrix, and the properties of the polymer can be improved even with a small addition of Mo3Se3-.

One-dimensional van der Waals stacked p-type crystal Ta2Pt3Se8 for nanoscale electronics.

Recently, ternary transition metal chalcogenides Ta2X3Se8 (X = Pd or Pt) have attracted great interest as a class of emerging one-dimensional (1D) van der Waals (vdW) materials. In particular, Ta2Pd3Se8 has been actively studied owing to its excellent charge transport properties as an n-type semiconductor and ultralong ballistic phonon transport properties. Compared to subsequent studies on the Pd-containing material, Ta2Pt3Se8, another member of this class of materials has been considerably less explored despite its promising electrical properties as a p-type semiconductor. Herein, we demonstrate the electrical properties of Ta2Pt3Se8 as a promising channel material for nanoelectronic applications. High-quality bulk Ta2Pt3Se8 single crystals were successfully synthesized by a one-step vapor transport reaction. Scanning Kelvin probe microscopy measurements were used to investigate the surface potential difference and work function of the Ta2Pt3Se8 nanoribbons of various thicknesses. Field-effect transistors fabricated on exfoliated Ta2Pt3Se8 nanoribbons exhibited moderate p-type transport properties with a maximum hole mobility of 5 cm2 V-1 s-1 and an Ion/Ioff ratio of >104. Furthermore, the charge transport mechanism of Ta2Pt3Se8 was analyzed by temperature-dependent transport measurements in the temperature range from 90 to 320 K. To include Ta2Pt3Se8 in a building block for modern 1D electronics, we demonstrate p-n junction characteristics using the electron beam doping method.

High Breakdown Current Density in Quasi-1D van der Waals Layered Material Ta2NiSe7.

We synthesized ternary composition chalcogenide Ta2NiSe7, a quasi-one-dimensional (Q1D) material with excellent crystallinity. To utilize the excellent electrical conductivity property of Ta2NiSe7, the breakdown current density (JBD) according to thickness change through mechanical exfoliation was measured. It was confirmed that as the thickness decreased, the maximum breakdown voltage (VBD) increased, and at 18 nm thickness, 35 MA cm-2 of JBD was measured, which was 35 times higher than that of copper, which is commonly used as an interconnect material. By optimization of the exfoliation process, it is expected that through a theoretical model fitting, the JBD can be increased to about 356 MA cm-2. It is expected that the low-dimensional materials with ternary compositions proposed through this experiment can be used as candidates for current-carrying materials that are required for the miniaturization of various electronic devices.

Ta2 Ni3 Se8 : 1D van der Waals Material with Ambipolar Behavior.

In this study, high-purity and centimeter-scale bulk Ta2 Ni3 Se8 crystals are obtained by controlling the growth temperature and stoichiometric ratio between tantalum, nickel, and selenium. It is demonstrated that the bulk Ta2 Ni3 Se8 crystals could be effectively exfoliated into a few chain-scale nanowires through simple mechanical exfoliation and liquid-phase exfoliation. Also, the calculation of electronic band structures confirms that Ta2 Ni3 Se8 is a semiconducting material with a small bandgap. A field-effect transistor is successfully fabricated on the mechanically exfoliated Ta2 Ni3 Se8 nanowires. Transport measurements at room temperature reveal that Ta2 Ni3 Se8 nanowires exhibit ambipolar semiconducting behavior with maximum mobilities of 20.3 and 3.52 cm2 V-1 s-1 for electrons and holes, respectively. The temperature-dependent transport measurement (from 90 to 295 K) confirms the carrier transport mechanism of Ta2 Ni3 Se8 nanowires. Based on these characteristics, the obtained 1D vdW material is expected to be a potential candidate for additional 1D materials as channel materials.

Impact of Transcranial Direct Current Stimulation on Cognitive Function, Brain Functional Segregation, and Integration in Patients with Mild Cognitive Impairment According to Amyloid-Beta Deposition and APOE ε4-Allele: A Pilot Study.

Anodal transcranial direct current stimulation (anodal-tDCS) is known to improve cognition and normalize abnormal network configuration during resting-state functional magnetic resonance imaging (fMRI) in patients with mild cognitive impairment (MCI). We aimed to evaluate the impact of sequential anodal-tDCS on cognitive functions, functional segregation, and integration parameters in patients with MCI, according to high-risk factors for Alzheimer's disease (AD): amyloid-beta (Aß) deposition and APOE ε4-allele status. In 32 patients with MCI ([18 F] flutemetamol-: n = 10, [18 F] flutemetamol+: n = 22; APOE ε4-: n = 13, APOE ε4+: n = 19), we delivered anodal-tDCS (2 mA/day, five times/week, for 2 weeks) over the left dorsolateral prefrontal cortex and assessed the neuropsychological test battery and resting-state fMRI measurements before and after 2 weeks stimulation. We observed a non-significant impact of an anodal-tDCS on changes in neuropsychological battery scores between MCI patients with and without high-risk factors of AD, Aß retention and APOE ε4-allele. However, there was a significant difference in brain functional segregation and integration parameters between MCI patients with and without AD high-risk factors. We also found a significant effect of tDCS-by-APOE ε4-allele interaction on changes in the functional segregation parameter of the temporal pole. In addition, baseline Aß deposition significantly associated negatively with change in global functional integrity of hippocampal formation. Anodal-tDCS might help to enhance restorative and compensatory intrinsic functional changes in MCI patients, modulated by the presence of Aß retention and the APOE ε4-allele.

Quadruple ultrasound, photoacoustic, optical coherence, and fluorescence fusion imaging with a transparent ultrasound transducer.

Ultrasound and optical imagers are used widely in a variety of biological and medical applications. In particular, multimodal implementations combining light and sound have been actively investigated to improve imaging quality. However, the integration of optical sensors with opaque ultrasound transducers suffers from low signal-to-noise ratios, high complexity, and bulky form factors, significantly limiting its applications. Here, we demonstrate a quadruple fusion imaging system using a spherically focused transparent ultrasound transducer that enables seamless integration of ultrasound imaging with photoacoustic imaging, optical coherence tomography, and fluorescence imaging. As a first application, we comprehensively monitored multiparametric responses to chemical and suture injuries in rats' eyes in vivo, such as corneal neovascularization, structural changes, cataracts, and inflammation. As a second application, we successfully performed multimodal imaging of tumors in vivo, visualizing melanomas without using labels and visualizing 4T1 mammary carcinomas using PEGylated gold nanorods. We strongly believe that the seamlessly integrated multimodal system can be used not only in ophthalmology and oncology but also in other healthcare applications with broad impact and interest.