BayeshERG: a robust, reliable and interpretable deep learning model for predicting hERG channel blockers.

Unintended inhibition of the human ether-à-go-go-related gene (hERG) ion channel by small molecules leads to severe cardiotoxicity. Thus, hERG channel blockage is a significant concern in the development of new drugs. Several computational models have been developed to predict hERG channel blockage, including deep learning models; however, they lack robustness, reliability and interpretability. Here, we developed a graph-based Bayesian deep learning model for hERG channel blocker prediction, named BayeshERG, which has robust predictive power, high reliability and high resolution of interpretability. First, we applied transfer learning with 300 000 large data in initial pre-training to increase the predictive performance. Second, we implemented a Bayesian neural network with Monte Carlo dropout to calibrate the uncertainty of the prediction. Third, we utilized global multihead attentive pooling to augment the high resolution of structural interpretability for the hERG channel blockers and nonblockers. We conducted both internal and external validations for stringent evaluation; in particular, we benchmarked most of the publicly available hERG channel blocker prediction models. We showed that our proposed model outperformed predictive performance and uncertainty calibration performance. Furthermore, we found that our model learned to focus on the essential substructures of hERG channel blockers via an attention mechanism. Finally, we validated the prediction results of our model by conducting in vitro experiments and confirmed its high validity. In summary, BayeshERG could serve as a versatile tool for discovering hERG channel blockers and helping maximize the possibility of successful drug discovery. The data and source code are available at our GitHub repository (https://github.com/GIST-CSBL/BayeshERG).

Longitudinal investigation of optic chiasm in patients with traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) often precipitates a cascade of neurophysiological alterations, impacting structures such as the optic nerve and ocular motor system. However, the literature lacks expansive investigations into the longitudinal changes in the optic chiasm and its relationship with the clinical recovery of visual processing. This study aimed to scrutinize longitudinal changes in optic chiasm volume (OCV) and establish the relationship of OCV with process speed index at 12 months post-injury. Process speed index is derived from Wechsler Adult Intelligence Scale IV. METHODS: Thorough cross-sectional and longitudinal analyses were executed, involving 42 patients with moderate to severe TBI and 35 healthy controls. OCV was acquired at 3, 6, and 12 months post-injury using T1-weighted images. OCV of healthy controls and that of patients with TBI at 3, 6, and 12 months post-injury were compared using a Mann-Whitney U test. A multiple linear regression model was constructed to assess the association between OCV and PSI and to predict PSI at 12 months post-injury using OCV at 3 months post-injury. RESULTS: OCV of patients with TBI was significantly larger compared to healthy controls, persisting from 3 to 12 months post-injury (p < 0.05). This increased OCV negatively correlated with PSI at 12 months post-injury, indicating that larger OCV sizes were associated with decreased PSI (p = 0.031). Furthermore, the multiple linear regression model was significant in predicting PSI at 12 months post-injury utilizing OCV at 3 months post-injury (p = 0.024). CONCLUSION: For the first time, this study elucidates the increased OCV and the significant association between OCV in sub-chronic stage and PSI at 12 months post-injury, potentially providing clinicians with a tool for anticipatory cognitive rehabilitation strategies following TBI.

Can DNA Methylation Profiling Classify Histologic Subtypes and Grades in Soft Tissue Sarcoma?

BACKGROUND: A clear classification of the subtype and grade of soft tissue sarcoma is important for predicting prognosis and establishing treatment strategies. However, the rarity and heterogeneity of these tumors often make diagnosis difficult. In addition, it remains challenging to predict the response to chemotherapy and prognosis. Thus, we need a new method to help diagnose soft tissue sarcomas and determine treatment strategies in conjunction with traditional methods. Genetic alterations can be found in some subtypes of soft tissue sarcoma, but many other types show dysregulated gene expression attributed to epigenetic changes, such as DNA methylation status. However, research on DNA methylation profiles in soft tissue sarcoma is still insufficient to provide information to assist in diagnosis and therapeutic decisions. QUESTIONS/PURPOSES: (1) Do DNA methylation profiles differ between normal tissue and soft tissue sarcoma? (2) Do DNA methylation profiles vary between different histologic subtypes of soft tissue sarcoma? (3) Do DNA methylation profiles differ based on tumor grade? METHODS: Between January 2019 and December 2022, we treated 85 patients for soft tissue sarcomas. We considered patients whose specimens were approved for pilot research by the Human Biobank of St. Vincent's Hospital, The Catholic University of Korea, as potentially eligible. Based on this, 41% (35 patients) were eligible; 1% (one patient) was excluded because of gender mismatch between clinical and genetic data after controlling for data quality. Finally, 39 specimens (34 soft tissue sarcomas and five normal samples) were included from 34 patients who had clinical data. All tissue samples were collected intraoperatively. The five normal tissue samples were from muscle tissues. There were 20 female patients and 14 male patients, with a median age of 58 years (range 19 to 82 years). Genomic DNA was extracted from frozen tissue, and DNA methylation profiles were obtained. Genomic annotation of DNA methylation sites and hierarchical cluster analysis were performed to interpret results from DNA methylation profiling. A t-test was used to analyze different methylation probes. Benjamini-Hochberg-adjusted p value calculations were used to account for bias resulting from evaluating thousands of methylation sites. RESULTS: The most common histologic subtypes were liposarcoma (n = 10) and leiomyosarcoma (n = 9). The tumor grade was Fédération Nationale des Centres de Lutte Contre Le Cancer Grades 1, 2, and 3 in 3, 15, and 16 patients, respectively. DNA methylation profiling demonstrated differences between soft tissue sarcoma and normal tissue as 21,188 cytosine-phosphate-guanine sites. Despite the small number of samples, 72 of these sites showed an adjusted p value of < 0.000001, suggesting a low probability of statistical errors. Among the 72 sites, 70 exhibited a hypermethylation pattern in soft tissue sarcoma, with only two sites showing a hypomethylation pattern. Thirty of 34 soft tissue sarcomas were distinguished from normal samples using hierarchical cluster analysis. There was a different methylation pattern between leiomyosarcoma and liposarcoma at 7445 sites. Using the data, hierarchical clustering analysis showed that liposarcoma was distinguished from leiomyosarcoma. When we used the same approach and included other subtypes with three or more samples, only leiomyosarcoma and myxofibrosarcoma were separated from the other subtypes, while liposarcoma and alveolar soft-part sarcoma were mixed with the others. When comparing DNA methylation profiles between low-grade (Grade 1) and high-grade (Grades 2 and 3) soft tissue sarcomas, a difference in methylation pattern was observed at 144 cytosine-phosphate-guanine sites. Among these, 132 cytosine-phosphate-guanine sites exhibited hypermethylation in the high-grade group compared with the low-grade group. Hierarchical clustering analysis showed a division into two groups, with most high-grade sarcomas (28 of 31) separated from the low-grade group and few (3 out of 31) clustered together with the low-grade group. However, three high-grade soft tissue sarcomas were grouped with the Grade 1 cluster, and all of these sarcomas were Grade 2. When comparing Grades 1 and 2 to Grade 3, Grade 3 tumors were separated from Grades 1 and 2. CONCLUSION: We observed a different DNA methylation pattern between soft tissue sarcomas and normal tissues. Liposarcoma was distinguished from leiomyosarcoma using methylation profiling. High-grade soft tissue sarcoma samples showed a hypermethylation pattern compared with low-grade ones. Our findings indicate the need for research using methylation profiling to better understand the diverse biological characteristics of soft tissue sarcoma. Such research should include studies with sufficient samples and a variety of subtypes, as well as analyses of the expression and function of related genes. Additionally, efforts to link this research with clinical data related to treatment and prognosis are necessary. LEVEL OF EVIDENCE: Level III, diagnostic study.

Quinone Catalysis Modulates Proton Transfer Reactions in the Membrane Domain of Respiratory Complex I.

Complex I is a redox-driven proton pump that drives electron transport chains and powers oxidative phosphorylation across all domains of life. Yet, despite recently resolved structures from multiple organisms, it still remains unclear how the redox reactions in Complex I trigger proton pumping up to 200 Å away from the active site. Here, we show that the proton-coupled electron transfer reactions during quinone reduction drive long-range conformational changes of conserved loops and trans-membrane (TM) helices in the membrane domain of Complex I from Yarrowia lipolytica. We find that the conformational switching triggers a π → α transition in a TM helix (TM3ND6) and establishes a proton pathway between the quinone chamber and the antiporter-like subunits, responsible for proton pumping. Our large-scale (>20 µs) atomistic molecular dynamics (MD) simulations in combination with quantum/classical (QM/MM) free energy calculations show that the helix transition controls the barrier for proton transfer reactions by wetting transitions and electrostatic effects. The conformational switching is enabled by re-arrangements of ion pairs that propagate from the quinone binding site to the membrane domain via an extended network of conserved residues. We find that these redox-driven changes create a conserved coupling network within the Complex I superfamily, with point mutations leading to drastic activity changes and mitochondrial disorders. On a general level, our findings illustrate how catalysis controls large-scale protein conformational changes and enables ion transport across biological membranes.

KLC3 Regulates Ciliary Trafficking and Cyst Progression in CILK1 Deficiency-Related Polycystic Kidney Disease.

BACKGROUND: Ciliogenesis-associated kinase 1 (CILK1) is a ciliary gene that localizes in primary cilia and regulates ciliary transport. Mutations in CILK1 cause various ciliopathies. However, the pathogenesis of CILK1-deficient kidney disease is unknown. METHODS: To examine whether CILK1 deficiency causes PKD accompanied by abnormal cilia, we generated mice with deletion of Cilk1 in cells of the renal collecting duct. A yeast two-hybrid system and coimmunoprecipitation (co-IP) were used to identify a novel regulator, kinesin light chain-3 (KLC3), of ciliary trafficking and cyst progression in the Cilk1-deficient model. Immunocytochemistry and co-IP were used to examine the effect of KLC3 on ciliary trafficking of the IFT-B complex and EGFR. We evaluated the effects of these genes on ciliary trafficking and cyst progression by modulating CILK1 and KLC3 expression levels. RESULTS: CILK1 deficiency leads to PKD accompanied by abnormal ciliary trafficking. KLC3 interacts with CILK1 at cilia bases and is increased in cyst-lining cells of CILK1-deficient mice. KLC3 overexpression promotes ciliary recruitment of IFT-B and EGFR in the CILK1 deficiency condition, which contributes to the ciliary defect in cystogenesis. Reduction in KLC3 rescued the ciliary defects and inhibited cyst progression caused by CILK1 deficiency. CONCLUSIONS: Our findings suggest that CILK1 deficiency in renal collecting ducts leads to PKD and promotes ciliary trafficking via increased KLC3.

Barium titanate-enhanced hexagonal boron nitride inks for printable high-performance dielectrics.

Printed electronics have been attracting significant interest for their potential to enable flexible and wearable electronic applications. Together with printable semiconductors, solution-processed dielectric inks are key in enabling low-power and high-performance printed electronics. In the quest for suitable dielectrics inks, two-dimensional materials such as hexagonal boron nitride (h-BN) have emerged in the form of printable dielectrics. In this work, we report barium titanate (BaTiO3) nanoparticles as an effective additive for inkjet-printable h-BN inks. The resulting inkjet printed BaTiO3/h-BN thin films reach a dielectric constant (εr) of âˆ¼16 by adding 10% of BaTiO3nanoparticles (in their volume fraction to the exfoliated h-BN flakes) in water-based inks. This result enabled all-inkjet printed flexible capacitors withC âˆ¼ 10.39 nF cm-2, paving the way to future low power, printed and flexible electronics.

A Bayesian Approach to Predict Football Matches with Changed Home Advantage in Spectator-Free Matches after the COVID-19 Break.

Since the coronavirus disease 2019 (COVID-19) pandemic, most professional sports events have been held without spectators. It is generally believed that home teams deprived of enthusiastic support from their home fans experience reduced benefits of playing on their home fields, thus becoming less likely to win. This study attempts to confirm if this belief is true in four major European football leagues through statistical analysis. This study proposes a Bayesian hierarchical Poisson model to estimate parameters reflecting the home advantage and the change in such advantage. These parameters are used to improve the performance of machine-learning-based prediction models for football matches played after the COVID-19 break. The study describes the statistical analysis on the impact of the COVID-19 pandemic on football match results in terms of the expected score and goal difference. It also shows that estimated parameters from the proposed model reflect the changed home advantage. Finally, the study verifies that these parameters, when included as additional features, enhance the performance of various football match prediction models. The home advantage in European football matches has changed because of the behind-closed-doors policy implemented due to the COVID-19 pandemic. Using parameters reflecting the pandemic's impact, it is possible to predict more precise results of spectator-free matches after the COVID-19 break.

Indol-2-ylidene (IdY): Ambiphilic N-Heterocyclic Carbene Derived from Indole*.

The synthesis of ambiphilic N-heterocyclic carbene ligand, indol-2-ylidene (IdY, A), is described. A series of indolenium precursors (2 a-f) were prepared on a gram scale in good yields. Trapping experiments with elemental selenium, [RhCl(cod)]2 and CuCl provided the expected carbene adducts. Further computational and spectroscopic studies supported the ambiphilicity of IdY, which lies between cyclic (alkyl)(amino)carbenes (CAAC-5) and cyclic (amino)(aryl)carbene (CAArC). The copper complexes (6) show high percent buried volume (% Vbur = 58.1) and allow for carboboration of terminal alkynes within 30 minutes in a demonstration of synthetic utility with good yields and high regioselectivity.

Nanoliposomal irinotecan plus fluorouracil and folinic acid as a second-line treatment option in patients with metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: According to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to haematological toxicity. There has been limited information on the clinical benefits and toxicity of this regimen in real-world settings. In this study, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure. METHODS: We conducted a single institution, retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80 mg/m2) with 5-FU/LV every 2 weeks. Kaplan-Meier analysis was performed to obtain median progression free survival and median overall survival. The hazard ratio and 95% confidence interval (CI) were estimated using a stratified Cox regression model. A multivariate Cox proportional hazards regression model was used to identify the effects of clinical factors. RESULTS: Fifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% CI 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced grade 3 or 4 adverse events, most commonly neutropenia (58.8%). Most non-haematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4). CONCLUSIONS: Nal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, following gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Nal-IRI plus 5-FU/LV following gemcitabine with nab-paclitaxel is a feasible sequential treatment option in patients with metastatic pancreatic cancer. TRIAL REGISTRATION: Retrospectively registered.

Nano-Interstice Driven Powerless Blood Plasma Extraction in a Membrane Filter Integrated Microfluidic Device.

Blood plasma is a source of biomarkers in blood and a simple, fast, and easy extraction method is highly required for point-of-care testing (POCT) applications. This paper proposes a membrane filter integrated microfluidic device to extract blood plasma from whole blood, without any external instrumentation. A commercially available membrane filter was integrated with a newly designed dual-cover microfluidic device to avoid leakage of the extracted plasma and remaining blood cells. Nano-interstices installed on both sides of the microfluidic channels actively draw the extracted plasma from the membrane. The developed device successfully supplied 20 µL of extracted plasma with a high extraction yield (~45%) in 16 min.

Loss of Von Hippel-Lindau (VHL) Tumor Suppressor Gene Function: VHL-HIF Pathway and Advances in Treatments for Metastatic Renal Cell Carcinoma (RCC).

Renal cell carcinoma (RCC) is a malignancy of the kidney originating from the tubular epithelium. Inactivation of the von Hippel-Lindau tumor-suppressor gene (VHL) is found in most clear cell renal cell carcinomas (ccRCCs). The VHL-HIF-VEGF/VEGFR pathway, which involves the von Hippel-Lindau tumor suppressor protein (VHL), hypoxia-inducible factor (HIF), vascular endothelial growth factor (VEGF), and its receptor (VEGFR), is a well-studied therapeutic target for metastatic ccRCC. Therefore, over the past decade, anti-angiogenic agents targeting VEGFR have served as the standard treatment for metastatic RCC. Recently, based on the immunomodulatory effect of anti-VEGFR therapy, anti-angiogenic agents and immune checkpoint inhibitor combination strategies have also emerged as therapeutic strategies. These advances were made possible by the improved understanding of the VHL-HIF pathway. In this review, we summarize the historical evolution of ccRCC treatments, with a focus on the involvement of the VHL-HIF pathway.

Adsorption-Based Atmospheric Water Harvesting: Impact of Material and Component Properties on System-Level Performance.

Atmospheric water harvesting (AWH) is the capture and collection of water that is present in the air either as vapor or small water droplets. AWH has been recognized as a method for decentralized water production, especially in areas where liquid water is physically scarce, or the infrastructure required to bring water from other locations is unreliable or infeasible. The main methods of AWH are fog harvesting, dewing, and utilizing sorbent materials to collect vapor from the air. In this paper, we first distinguish between the geographic/climatic operating regimes of fog harvesting, dewing, and sorbent-based approaches based on temperature and relative humidity (RH). Because utilizing sorbents has the potential to be more widely applicable to areas which are also facing water scarcity, we focus our discussion on this approach. We discuss sorbent materials which have been developed for AWH and the material properties which affect system-level performance. Much of the recent materials development has focused on a single material metric, equilibrium vapor uptake in the material (kg of water uptake per kg of dry adsorbent), as found from the adsorption isotherm. This equilibrium property alone, however, is not a good indicator of the actual performance of the AWH system. Understanding material properties which affect heat and mass transport are equally important in the development of materials and components for AWH, because resistances associated with heat and mass transport in the bulk material dramatically change the system performance. We focus our discussion on modeling a solar thermal-driven system. Performance of a solar-driven AWH system can be characterized by different metrics, including L of water per m2 device per day or L of water per kg adsorbent per day. The former metric is especially important for systems driven by low-grade heat sources because the low power density of these sources makes this technology land area intensive. In either case, it is important to include rates in the performance metric to capture the effects of heat and mass transport in the system. We discuss our previously developed modeling framework which can predict the performance of a sorbent material packed into a porous matrix. This model connects mass transport across length scales, considering diffusion both inside a single crystal as well as macroscale geometric parameters, such as the thickness of a composite adsorbent layer. For a simple solar thermal-driven adsorption-based AWH system, we show how this model can be used to optimize the system. Finally, we discuss strategies which have been used to improve heat and mass transport in the design of adsorption systems and the potential for adsorption-based AWH systems for decentralized water supplies.

Artificial Intelligence in Drug Discovery: A Comprehensive Review of Data-driven and Machine Learning Approaches.

As expenditure on drug development increases exponentially, the overall drug discovery process requires a sustainable revolution. Since artificial intelligence (AI) is leading the fourth industrial revolution, AI can be considered as a viable solution for unstable drug research and development. Generally, AI is applied to fields with sufficient data such as computer vision and natural language processing, but there are many efforts to revolutionize the existing drug discovery process by applying AI. This review provides a comprehensive, organized summary of the recent research trends in AI-guided drug discovery process including target identification, hit identification, ADMET prediction, lead optimization, and drug repositioning. The main data sources in each field are also summarized in this review. In addition, an in-depth analysis of the remaining challenges and limitations will be provided, and proposals for promising future directions in each of the aforementioned areas.

The effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing immune checkpoint inhibitor treatment: a retrospective study.

BACKGROUND: This study aimed to assess the effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing treatment with immune checkpoint inhibitors (ICIs). METHODS: The medical records of 234 patients treated with ICIs for any type of solid cancer between February 2012 and May 2018 at the Seoul St. Mary's Hospital were retrospectively reviewed. The data of patients who received antibiotics within 60 days before the initiation of ICI treatment were analyzed. The patients' responses to ICI treatment and their survival were evaluated. RESULTS: Non-small-cell lung carcinoma was the most common type of cancer. About half of the patients were treated with nivolumab (51.9%), and cephalosporin (35.2%) was the most commonly used class of antibiotics. The total objective response rate was 21%. Antibiotics use was associated with a decreased objective response (odds ratio 0.466, 95% confidence interval [CI] 0.225-0.968, p = 0.040). The antibiotics group exhibited shorter progression-free survival (PFS) and overall survival (OS) than the no antibiotics group (median PFS: 2 months vs. 4 months, p < 0.001; median OS: 5 months vs. 17 months, p < 0.001). In the multivariate analysis, antibiotics use was a significant predictor of patient survival (PFS: hazard ratio [HR] 1.715, 95% CI 1.264-2.326, p = 0.001; OS: HR 1.785, 95% CI 1.265-2.519, p = 0.001). CONCLUSIONS: The use of antibiotics may affect the clinical outcomes of patients with solid cancers treated with ICIs. Careful prescription of antibiotics is warranted in candidates who are scheduled for ICI treatment. TRIAL REGISTRATION: Not applicable (retrospective study).

Discordancy and changes in the pattern of programmed death ligand 1 expression before and after platinum-based chemotherapy in metastatic gastric cancer.

BACKGROUND: Our goal was to evaluate changes in PD-L1 expression in primary tumours of metastatic gastric cancer before and after chemotherapy. METHODS: We evaluated the PD-L1 expression of 72 patients with primary gastric cancer, before and after palliative first-line platinum-based chemotherapy, between January 2015 and March 2017. The PD-L1 ratio was defined as pre-chemotherapy PD-L1 expression divided by the post-chemotherapy PD-L1 expression. RESULTS: In 30 patients with PD-L1 negative pre-chemotherapy, 12 (40%) were positive post-chemotherapy; among the 42 patients with PD-L1 positive pre-chemotherapy, 24 (57.1%) were negative post-chemotherapy. The degree of PD-L1 expression decreased from 58.3% before chemotherapy to 41.7% after chemotherapy (P = 0.046). Among patients with complete response/partial response (CR/PR), the degree of PD-L1 expression decreased (P = 0.002), as well as PD-L1 positivity with statistical significance (P = 0.013) after chemotherapy, but not among patients with stable disease/progressive disease (SD/PD). Higher disease control rates (CR/PR/SD) were observed in patients with an elevated PD-L1 ratio (P = 0.043). Patients with a high PD-L1 ratio (> 1) were found to be associated with a better progression-free survival (HR 0.34, 95% CI 0.17-0.67, P = 0.002). CONCLUSIONS: PD-L1 expression can change during chemotherapy. Moreover, changes in patterns of PD-L1 expression might be associated with patient prognosis and response to chemotherapy.

Tunable Metal-Organic Frameworks Enable High-Efficiency Cascaded Adsorption Heat Pumps.

Rising global standards of living coupled to the recent agreement to eliminate hydrofluorocarbon refrigerants are creating intense pressure to develop more sustainable climate control systems. In this vein, the use of water as the refrigerant in adsorption heat pumps is highly attractive, but such adsorption systems are constrained to large size and poor efficiency by the characteristics of currently employed water sorbents. Here we demonstrate control of the relative humidity of water uptake by modulating the pore size in a family of isoreticular triazolate metal-organic frameworks. Using this method, we identify a pair of materials with stepped, nonoverlapping water isotherms that can function in tandem to provide continuous cooling with a record ideal coefficient of performance of 1.63. Additionally, when used in a single-stage heat pump, the microporous Ni2Cl2BBTA has the largest working capacity of any material capable of generating a 25 °C difference between ambient and chiller output.

Osteosarcopenia in Patients with Hip Fracture Is Related with High Mortality.

BACKGROUND: This study evaluated the prevalence of osteosarcopenia, as well as the relationship between one-year mortality and osteosarcopenia, as defined by criteria of the Asian Working Group on Sarcopenia in patients age 60 or older with hip fracture. METHODS: A total of 324 patients age 60 years or older with hip fracture were enrolled in this retrospective observational study. The main outcome measure was the prevalence of osteosarcopenia, as well as the relationship between osteosarcopenia and 1-year mortality. The diagnosis of sarcopenia was carried out according to the Asian Working Group on Sarcopenia. Whole body densitometry analysis was used for skeletal muscle mass measurement and muscle strength were evaluated by handgrip testing. Mortality was assessed at the end of 1-year. Cox regression analysis was utilized to analyze the risk factor of osteosarcopenia. RESULTS: Of 324 patients with hip fracture, 93 (28.7%) were diagnosed with osteosarcopenia. In total, 9.0% died during the one-year follow-up. A one-year mortality of osteosarcopenia (15.1%) was higher than that of other groups (normal: 7.8%, osteoporosis only: 5.1%, sarcopenia only: 10.3%). Osteosarcopenia had a 1.8 times higher mortality rate than non-osteosarcopenia. CONCLUSION: The present study demonstrates that the prevalence of osteosarcopenia is not rare, and has a higher mortality rate than the non-osteosarcopenia group at the 1-year follow-up period. This is the first study evaluating the relationship between mortality and osteosarcopenia in patients with hip fracture.

Mid-Term Survivals After Cementless Bipolar Hemiarthroplasty for Unstable Intertrochanteric Fractures in Elderly Patients.

BACKGROUND: Treatment of unstable intertrochanteric fracture in elderly patients remains challenging. The purpose of this prospective study is to determine clinical and radiological results of cementless bipolar hemiarthroplasty using a fully porous-coated stem in osteoporotic elderly patients with unstable intertrochanteric fractures with follow-up over 5 years. METHODS: From January 2010 to December 2011, we performed 123 cementless bipolar hemiarthroplasties using fully porous-coated stem to treat unstable intertrochanteric fractures in elderly patients with osteoporosis. Clinical and radiographic evaluations were performed. RESULTS: Fifty-three patients died and 14 patients were lost during the follow-up period. Mean follow-up period was 61.8 months postoperatively. Their mean Harris hip score was 77 points (range 36-100). None of these hips had loosening of the stem or osteolysis. Postoperative complications included nonunion of greater trochanter in 2 hips and dislocation in 2 hips. Two patients were reoperated due to periprosthetic fracture. One patient underwent implant revision due to periprosthetic infection. Thirty-one patients maintained walking activities similar to those before fracture. With follow-up period of 83 months, cumulative survival rates were 97.3% and 99.1% with reoperation for any reason and femoral stem revision as endpoint, respectively. CONCLUSION: Cementless bipolar hemiarthroplasty using a fully porous-coated stem is a useful surgical treatment option for unstable intertrochanteric fracture in elderly patients with osteoporosis.

Coumaraz-2-on-4-ylidene: Ambiphilic N-Heterocyclic Carbenes with a Tunable Electronic Structure.

Herein, a coumaraz-2-on-4-ylidene (1) as a new example of an ambiphilic N-heterocyclic carbene, having electronic properties that can be fine-tuned, is reported. The N-carbamic and aryl groups on the carbene carbon center provide exceptionally high electrophilicity and nucleophilicity simultaneously to the carbene center, as evidenced by the 77 Se NMR chemical shifts of their selenoketone derivatives and the CO stretching strengths of their rhodium carbonyl complexes. Since the precursors of 1 could be synthesized from various functionalized Schiff bases in a practical and scalable manner, the electronic properties of 1 can be fine-tuned in a quantitative and predictable way by using the Hammett σ constant of the functional groups on aryl ring. The facile electronic tuning capability of 1 may be applicable to eliciting novel properties in main-group and transition-metal chemistry.

Early Rehabilitation in Elderly after Arthroplasty versus Internal Fixation for Unstable Intertrochanteric Fractures of Femur: Systematic Review and Meta-Analysis.

The purpose of this study was to compare the outcomes focusing on the functional outcome and clinical results of replacement arthroplasty (AP) vs. internal fixation (IF) for the treatment of unstable intertrochanteric femoral fracture in elderly. Systematic review and meta-analysis were performed on 10 available clinical studies (2 randomized controlled trials and 8 comparative studies). Subgroup analysis was performed by type of methodological quality. Partial weight bearing time in AP group was earlier than that in IF group (SMD = -0.86; 95% CI = -0.42, 1.29; P = 0.050). The overall outcomes such as mortality, reoperation rate, and complication showed no significant diffrence between the 2 groups (AP vs. IF). Therefore, this systematic review demonstrates that AP provides superior functional outcomes especially earlier mobilization, as compared to IF in elderly patients with an unstable intertrochanteric femoral fracture.