Learning Curve of Microsurgical Anastomosis: Training for Resident Education.

Background: Acquiring microsurgical anastomosis skills requires considerable time and effort. Moreover, appropriate and systematic training for acquiring microsurgical anastomosis skills is lacking. Therefore, this study investigated the learning curve for acquiring microsurgical anastomosis techniques among orthopaedic surgery residents.

Transferrin-binding domain inserted-adenovirus hexon engineering enables systemic immune evasion and intratumoral T-cell activation.

Adenovirus-based therapies have encountered significant challenges due to host immunity, particularly from pre-existing antibodies. Many trials have struggled to evade antibody response; however, the efficiency of these efforts was limited by the diversity of antibody Fv-region recognizing multiple amino acid sequences. In this study, we developed an antibody-evading adenovirus vector by encoding a plasma-rich protein transferrin-binding domain.

Targeted Circulating Lipid Mediators and Immune Cell Gene Transcripts After ST-Elevation Myocardial Infarction.

Residual inflammation drives atherogenesis to atherosclerosis and myocardial infarction, which triggers acute inflammation. In preclinical studies, polyunsaturated fatty acids-derived specialized pro-resolving mediators (SPMs) have been shown to promote recovery after MI, in contrast to pro-inflammatory lipid mediators (PIMs). However, the dynamic changes of lipid mediators after ST-elevation myocardial infarction (STEMI), particularly after percutaneous coronary intervention (PCI) and respective gene transcripts, are poorly understood.

Efficacy of cold and cryo-preserved nerve allografts with low-dose FK506 for motor nerve regeneration: a preclinical study.

Background: Despite their ability to regenerate as well as autografts, the use of nerve allografts is limited by the need for immunosuppression and the risk of disease transmission. Further, decellularized allografts lacking Schwann cells limit axonal regeneration in long nerve defects. This study evaluated sciatic nerve regeneration in rats implanted with cold- or cryopreserved allografts, and examined the effects of FK506, an immunosuppressant that targets calcineurin function, on motor recovery.

Hydrogen and Solid Carbon Production via Methane Pyrolysis in a Rotating Gliding Arc Plasma Reactor.

Plasma-induced methane pyrolysis is a promising hydrogen production method. However, few studies have focused the decomposition of pure methane as a discharge gas. Herein, a rotating gliding arc reactor was used for the conversion of methane (discharge gas and feedstock) into hydrogen and solid carbon.

GR113808, a serotonin receptor 4 antagonist, prevents high-fat-diet-induced obesity, fatty liver formation, and insulin resistance in C57BL/6J mice.

Background: The burden of nonalcoholic fatty liver disease is increasing, and limited therapeutic drugs are available for its treatment. Serotonin binds to approximately 14 serotonin receptors (HTR) and plays diverse roles in obesity and metabolic complications. In this study, we focused on the function of HTR4 on nonalcoholic fatty liver disease using GR113808, a selective HTR4 antagonist.

The Effects and Risk Factors of Femoral Neck Shortening after Internal Fixation of Femoral Neck Fractures.

Backgroud: Internal fixation has been established as a treatment of choice in relatively young patients with femoral neck fractures. Due to the characteristics of femoral neck anatomy and blood supply, complications such as malunion, nonunion, avascular necrosis, and femoral neck shortening can occur after internal fixation of femoral neck fractures. Unlike other complications such as avascular necrosis or nonunion, femoral neck shortening has not been relatively well studied.

Functional pathogenicity of ESRRB variant of uncertain significance contributes to hearing loss (DFNB35).

Advances in next-generation sequencing technologies have led to elucidation of sensorineural hearing loss genetics and associated clinical impacts. However, studies on the functional pathogenicity of variants of uncertain significance (VUS), despite their close association with clinical phenotypes, are lacking. Here we identified compound heterozygous variants in ESRRB transcription factor gene linked to DFNB35, specifically a novel splicing variant (NM_004452.

Phase III KEYNOTE-789 Study of Pemetrexed and Platinum With or Without Pembrolizumab for Tyrosine Kinase Inhibitor‒Resistant, -Mutant, Metastatic Nonsquamous Non-Small Cell Lung Cancer.

Purpose: Epidermal growth factor receptor () tyrosine kinase inhibitors (TKIs) are standard first-line therapy for -mutant, metastatic non-small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum-based chemotherapy with or without pembrolizumab for TKI-resistant, -mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837).

Discovery of novel disease-causing mutation in and its correction using adenine base editor to improve mitochondrial function.

Mutations in nuclear genes regulating mitochondrial DNA (mtDNA) replication are associated with mtDNA depletion syndromes. Using whole-genome sequencing, we identified a heterozygous mutation (c.272G>A:p.

Outcomes of Osteochondral Autologous Transplantation with Ipsilateral Lateral Talar Autograft for Medial Osteochondral Lesions of the Talus.

Background: Osteochondral autologous transplantation (OAT) has been widely used in the treatment of osteochondral lesion of the talus (OLT). Previous studies have reported successful outcomes following the use of osteochondral autogenous grafts from the intercondylar notch of the knee or a non-weight-bearing region of the femoral condyle. However, donor-site morbidity of the knee joint has been observed in several cases.

Comparison of tissue response and lifting effect induced by non-absorbable elastic thread and commercialized threads in rat model.

As we age, our skin loses elasticity and wrinkles form. To prevent this, most people try to improve skin wrinkles by performing procedures such as fillers, and absorbable lifting threads. Another way to solve this structural problem is to use an elastic thread.

Capmatinib plus nazartinib in patients with EGFR-mutated non-small cell lung cancer.

Purpose: This phase 1b/2 trial evaluated the efficacy and safety of capmatinib plus nazartinib in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC).

Methods: In phase 1b, patients with progression on first-/second-generation EGFR-TKIs received escalating doses of capmatinib 200-400 mg bid plus nazartinib 50-150 mg qd. Once the MTD/RP2D was declared, phase 2 commenced with patient enrollment into groups according to mutation status and prior lines of treatment: group 1 (fasted; EGFR-TKI resistant; 1-3 prior lines; EGFR; any T790M/MET); group 2 (fasted; EGFR-TKI naïve; 0-2 prior lines; de novo T790M+; any MET); group 3 (fasted; treatment-naïve; EGFR; T790M-; any MET); group 4 (with food; 0-2 prior lines; EGFR; any T790M/MET).

Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Backgruound: Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD.

Methods: We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.

Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma.

Purpose: Coblockade of lymphocyte activation gene-3 (LAG-3) and PD-1 receptors could provide significant clinical benefit for patients with advanced melanoma. Fianlimab and cemiplimab are high-affinity, human, hinge-stabilized IgG4 monoclonal antibodies, targeting LAG-3 and PD-1, respectively. We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma.

Intravesical instillation-based mTOR-STAT3 dual targeting for bladder cancer treatment.

Background: Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed.

Methods: An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3.

Rugged Island-Bridge Inorganic Electronics Mounted on Locally Strain-Isolated Substrates.

Various strain isolation strategies that combine rigid and stretchable regions for stretchable electronics were recently proposed, but the vulnerability of inorganic materials to mechanical stress has emerged as a major impediment to their performance. We report a strain-isolation system that combines heteropolymers with different elastic moduli (i.e.

Alectinib in Resected -Positive Non-Small-Cell Lung Cancer.

Background: Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, -positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected -positive NSCLC are lacking.

Methods: We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, -positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles.

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis.

Background & Aims: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions.

Methods: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4.

Transcriptome-based deep learning analysis identifies drug candidates targeting protein synthesis and autophagy for the treatment of muscle wasting disorder.

Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss.

Fluorine-Containing Poly(Fluorene)-Based Anion Exchange Membrane with High Hydroxide Conductivity and Physicochemical Stability for Water Electrolysis.

Improving the hydroxide conductivity and dimensional stability of anion exchange membranes (AEMs) while retaining their high alkaline stability is necessary to realize the commercialization of AEM water electrolysis (AEMWE). A strategy for improving the hydroxide conductivity and dimensional stability of AEMs by inserting fluorine atoms in the core structure of the backbone is reported, which not only reduces the glass transition temperature of the polymer due to steric strain, but also induces distinct phase separation by inducing polarity discrimination to facilitate the formation of ion transport channels. The resulting PFPFTP-QA AEM with fluorine into the core structure shows high hydroxide conductivity (>159 mS cm at 80 °C), favorable dimensional stability (>25% at 80 °C), and excellent alkaline stability for 1000 h in 2 m KOH solution at 80 °C.