Nonlinear optical diode effect in a magnetic Weyl semimetal.

Diode effects are of great interest for both fundamental physics and modern technologies. Electrical diode effects (nonreciprocal transport) have been observed in Weyl systems. Optical diode effects arising from the Weyl fermions have been theoretically considered but not probed experimentally. Here, we report the observation of a nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetization introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). We demonstrate a six-fold change of the measured SHG intensity between opposite propagation directions over a bandwidth exceeding 250 meV. Supported by density-functional theory, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of this broadband effect. We further demonstrate current-induced magnetization switching and thus electrical control of the NODE. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials and further opens new pathways for the unidirectional manipulation of light.

Engineering Anomalously Large Electron Transport in Topological Semimetals.

Anomalous transport of topological semimetals has generated significant interest for applications in optoelectronics, nanoscale devices, and interconnects. Understanding the origin of novel transport is crucial to engineering the desired material properties, yet their orders of magnitude higher transport than single-particle mobilities remain unexplained. This work demonstrates the dramatic mobility enhancements result from phonons primarily returning momentum to electrons due to phonon-electron dominating over phonon-phonon scattering. Proving this idea, proposed by Peierls in 1932, requires tuning electron and phonon dispersions without changing symmetry, topology, or disorder. This is achieved by combining de Haas - van Alphen (dHvA), electron transport, Raman scattering, and first-principles calculations in the topological semimetals MX2 (M = Nb, Ta and X = Ge, Si). Replacing Ge with Si brings the transport mobilities from an order magnitude larger than single particle ones to nearly balanced. This occurs without changing the crystal structure or topology and with small differences in disorder or Fermi surface. Simultaneously, Raman scattering and first-principles calculations establish phonon-electron dominated scattering only in the MGe2 compounds. Thus, this study proves that phonon-drag is crucial to the transport properties of topological semimetals and provides insight to engineer these materials further.

Manipulating Topological Phases in Magnetic Topological Insulators.

Magnetic topological insulators (MTIs) are a group of materials that feature topological band structures with concurrent magnetism, which can offer new opportunities for technological advancements in various applications, such as spintronics and quantum computing. The combination of topology and magnetism introduces a rich spectrum of topological phases in MTIs, which can be controllably manipulated by tuning material parameters such as doping profiles, interfacial proximity effect, or external conditions such as pressure and electric field. In this paper, we first review the mainstream MTI material platforms where the quantum anomalous Hall effect can be achieved, along with other exotic topological phases in MTIs. We then focus on highlighting recent developments in modulating topological properties in MTI with finite-size limit, pressure, electric field, and magnetic proximity effect. The manipulation of topological phases in MTIs provides an exciting avenue for advancing both fundamental research and practical applications. As this field continues to develop, further investigations into the interplay between topology and magnetism in MTIs will undoubtedly pave the way for innovative breakthroughs in the fundamental understanding of topological physics as well as practical applications.

Emergent ferromagnetism with superconductivity in Fe(Te,Se) van der Waals Josephson junctions.

Ferromagnetism and superconductivity are two key ingredients for topological superconductors, which can serve as building blocks of fault-tolerant quantum computers. Adversely, ferromagnetism and superconductivity are typically also two hostile orderings competing to align spins in different configurations, and thus making the material design and experimental implementation extremely challenging. A single material platform with concurrent ferromagnetism and superconductivity is actively pursued. In this paper, we fabricate van der Waals Josephson junctions made with iron-based superconductor Fe(Te,Se), and report the global device-level transport signatures of interfacial ferromagnetism emerging with superconducting states for the first time. Magnetic hysteresis in the junction resistance is observed only below the superconducting critical temperature, suggesting an inherent correlation between ferromagnetic and superconducting order parameters. The 0-π phase mixing in the Fraunhofer patterns pinpoints the ferromagnetism on the junction interface. More importantly, a stochastic field-free superconducting diode effect was observed in Josephson junction devices, with a significant diode efficiency up to 10%, which unambiguously confirms the spontaneous time-reversal symmetry breaking. Our work demonstrates a new way to search for topological superconductivity in iron-based superconductors for future high Tc fault-tolerant qubit implementations from a device perspective.

Analysis on key parameters in subretinal injection facilitating a predictable and automated robot-assisted treatment in gene therapy.

BACKGROUND: Subretinal injection (SRI) has become an important surgical method for treating vitreoretinal diseases. Nevertheless, the optimisation of bleb formation in SRI, for the attainment of desired therapeutic outcomes, still requires further investigation. METHODS: This study analysed the influence of surgical parameters on SRI using a robotic setup. The surgical procedure was automated using visual guidance. A predictive model for bleb formation was established through regression analysis. To validate the model, we compared the clinical data's target area with the simulated SRI's actual area using parameters determined by the predictive model. RESULTS: The insertion angle dominated the eccentricity and area of the bleb. The injection speed dominated the axial angle. Automated SRI increased success rate and produced predictable outcomes. CONCLUSIONS: We could provide accurate SRI on phantom models by adjusting surgical parameters based on the patient's clinical information. Automatic robot-assisted SRI is a promising surgical technique with highly predictable results.

Evidence of a coupled electron-phonon liquid in NbGe2.

Whereas electron-phonon scattering relaxes the electron's momentum in metals, a perpetual exchange of momentum between phonons and electrons may conserve total momentum and lead to a coupled electron-phonon liquid. Such a phase of matter could be a platform for observing electron hydrodynamics. Here we present evidence of an electron-phonon liquid in the transition metal ditetrelide, NbGe2, from three different experiments. First, quantum oscillations reveal an enhanced quasiparticle mass, which is unexpected in NbGe2 with weak electron-electron correlations, hence pointing at electron-phonon interactions. Second, resistivity measurements exhibit a discrepancy between the experimental data and standard Fermi liquid calculations. Third, Raman scattering shows anomalous temperature dependences of the phonon linewidths that fit an empirical model based on phonon-electron coupling. We discuss structural factors, such as chiral symmetry, short metallic bonds, and a low-symmetry coordination environment as potential design principles for materials with coupled electron-phonon liquid.

Weyl-mediated helical magnetism in NdAlSi.

Emergent relativistic quasiparticles in Weyl semimetals are the source of exotic electronic properties such as surface Fermi arcs, the anomalous Hall effect and negative magnetoresistance, all observed in real materials. Whereas these phenomena highlight the effect of Weyl fermions on the electronic transport properties, less is known about what collective phenomena they may support. Here, we report a Weyl semimetal, NdAlSi, that offers an example. Using neutron diffraction, we found a long-wavelength helical magnetic order in NdAlSi, the periodicity of which is linked to the nesting vector between two topologically non-trivial Fermi pockets, which we characterize using density functional theory and quantum oscillation measurements. We further show the chiral transverse component of the spin structure is promoted by bond-oriented Dzyaloshinskii-Moriya interactions associated with Weyl exchange processes. Our work provides a rare example of Weyl fermions driving collective magnetism.

Combination Biomarker of Immune Checkpoints Predict Prognosis of Urothelial Carcinoma.

In contrast to Western counties, the incidence of urothelial carcinoma (UC) remains mar-edly elevated in Taiwan. Regulatory T cells (Tregs) play a crucial role in limiting immune responses within the tumor microenvironment. To elucidate the relationship between immune checkpoints in the tumor immune microenvironment and UC progression, we utilize the Gene Expression Omnibus (GEO) to analyze a microarray obtained from 308 patients with UC. We observed that the expression level of CD276 or TIM-3 was positively correlated with late-stage UC and poor prognosis. Patients with simultaneously high CD276 and TIM-3 expression in tumors have significantly reduced both univariate and multivariate survival, indicating that mRNA levels of these immune checkpoints could be independent prognostic biomarkers for UC overall survival and recurrence. Our cohort study showed rare CD8+ cytotoxic T-cells and Tregs infiltration during early-stage UC-known as cold tumors. Approximately 30% of late-stage tumors exhibited highly infiltrated cytotoxic T cells with high PD-1 and FOXP3 expression, which implied that cytotoxic T cells were inhibited in the advanced UC microenvironment. Collectively, our findings provide a better prognosis prediction by combined immune checkpoint biomarkers and a basis for early-stage UC standard treatment to convert cold tumors into hot tumors, followed by immune checkpoint therapy.

Thermodynamic Evidence of Proximity to a Kitaev Spin Liquid in Ag_{3}LiIr_{2}O_{6}.

Kitaev magnets are materials with bond-dependent Ising interactions between localized spins on a honeycomb lattice. Such interactions could lead to a quantum spin-liquid (QSL) ground state at zero temperature. Recent theoretical studies suggest two potential signatures of a QSL at finite temperatures, namely, a scaling behavior of thermodynamic quantities in the presence of quenched disorder, and a two-step release of the magnetic entropy. Here, we present both signatures in Ag_{3}LiIr_{2}O_{6} which is synthesized from α-Li_{2}IrO_{3} by replacing the interlayer Li atoms with Ag atoms. In addition, the dc susceptibility data confirm the absence of a long-range order, and the ac susceptibility data rule out a spin-glass transition. These observations suggest a closer proximity to the QSL in Ag_{3}LiIr_{2}O_{6} compared to its parent compound α-Li_{2}IrO_{3} that orders at 15 K. We discuss an enhanced spin-orbit coupling due to a mixing between silver d and oxygen p orbitals as a potential underlying mechanism.

WMJ-S-001, a Novel Aliphatic Hydroxamate-Based Compound, Suppresses Lymphangiogenesis Through p38mapk-p53-survivin Signaling Cascade.

Background and purpose: Angiogenesis and lymphangiogenesis are major routes for metastatic spread of tumor cells. It thus represent the rational targets for therapeutic intervention of cancer. Recently, we showed that a novel aliphatic hydroxamate-based compound, WMJ-S-001, exhibits anti-angiogenic, anti-inflammatory and anti-tumor properties. However, whether WMJ-S-001 is capable of suppressing lymphangiogenesis remains unclear. We are thus interested in exploring WMJ-S-001's anti-lymphangiogenic mechanisms in lymphatic endothelial cell (LECs). Experimental approach: WMJ-S-001's effects on LEC proliferation, migration and invasion, as well as signaling molecules activation were analyzed by immunoblotting, flow-cytometry, MTT, BrdU, migration and invasion assays. We performed tube formation assay to examine WMJ-S-001's ex vivo anti-lymphangiogenic effects. Key results: WMJ-S-001 inhibited serum-induced cell proliferation, migration, invasion in murine LECs (SV-LECs). WMJ-S-001 reduced the mRNA and protein levels of survivin. Survivin siRNA significantly suppressed serum-induced SV-LEC invasion. WMJ-S-001 induced p53 phosphorylation and increased its reporter activities. In addition, WMJ-S-001 increased p53 binding to the promoter region of survivin, while Sp1 binding to the region was decreased. WMJ-S-001 induced p38 mitogen-activated protein kinase (p38MAPK) activation. p38MPAK signaling blockade significantly inhibited p53 phosphorylation and restored survivin reduction in WMJ-S-001-stimulated SV-LCEs. Furthermore, WMJ-S-001 induced survivin reduction and inhibited cell proliferation, invasion and tube formation of primary human LECs. Conclusions and Implications: These observations indicate that WMJ-S-001 may suppress lymphatic endothelial remodeling and reduce lymphangiogenesis through p38MAPK-p53-survivin signaling. It also suggests that WMJ-S-001 is a potential lead compound in developing novel agents for the treatment of lymphangiogenesis-associated diseases and cancer.

Vitamin D and bisphosphonates therapies for osteoporosis are associated with different risks of atrial fibrillation in women: A nationwide population-based analysis.

Osteoporosis and atrial fibrillation (AF) are common in post-menopausal women. Vitamin D and bisphosphonates are widely used to treat osteoporosis, and these may have different effects on the risk of AF.The goal of this study was to evaluate whether different agents for treating osteoporosis modulate the risk of AF in a population-based database.We identified 20,788 female patients suffering from osteoporosis who were or were not treated with vitamin D or bisphosphonates using the Taiwan National Health Insurance nationwide database from 2000 to 2008 and followed them up for 5 consecutive years to determine if they had a new diagnosis of AF after the diagnosis of osteoporosis.There were 14 (2.67%) new AF diagnoses in osteoporosis patients treated with bisphosphonates, one (0.28%) new AF diagnosis in patients treated with vitamin D, and 279 (1.40%) new AF diagnoses in patients who were not treated with vitamin D or bisphosphonates (neither group). Osteoporosis patients who received bisphosphonates showed a higher incidence of AF occurrence than those that were not treated with bisphosphonates (P = .015). In contrast, 1 patient who received vitamin D had a new diagnosis of AF during the study period; thus, the incidence was significantly lower than that in the patients treated with bisphosphonates (P = .007). In addition, the patients who were treated with vitamin D had a lower incidence of AF than did those who were not treated with either vitamin D or bisphosphonates (P = .074). Kaplan-Meier analysis also showed a significant difference in AF occurrence in different groups during the 5-year follow-up (P = .010).Different treatment for osteoporosis may carry diverse risks of AF occurrence. Vitamin D may have potential beneficial effects of reducing AF occurrence in osteoporosis patients.

Interleukin-6 Induces Vascular Endothelial Growth Factor-C Expression via Src-FAK-STAT3 Signaling in Lymphatic Endothelial Cells.

Elevated serum interleukin-6 (IL-6) levels correlates with tumor grade and poor prognosis in cancer patients. IL-6 has been shown to promote tumor lymphangiogenesis through vascular endothelial growth factor-C (VEGF-C) induction in tumor cells. We recently showed that IL-6 also induced VEGF-C expression in lymphatic endothelial cells (LECs). However, the signaling mechanisms involved in IL-6-induces VEGF-C induction in LECs remain incompletely understood. In this study, we explored the causal role of focal adhesion kinase (FAK) in inducing VEGF-C expression in IL-6-stimulated murine LECs (SV-LECs). FAK signaling blockade by NSC 667249 (a FAK inhibitor) attenuated IL-6-induced VEGF-C expression and VEGF-C promoter-luciferase activities. IL-6's enhancing effects of increasing FAK, ERK1/2, p38MAPK, C/EBPß, p65 and STAT3 phosphorylation as well as C/EBPß-, κB- and STAT3-luciferase activities were reduced in the presence of NSC 667249. STAT3 knockdown by STAT3 siRNA abrogated IL-6's actions in elevating VEGF-C mRNA and protein levels. Moreover, Src-FAK signaling blockade reduced IL-6's enhancing effects of increasing STAT3 binding to the VEGF-C promoter region, cell migration and endothelial tube formation of SV-LECs. Together these results suggest that IL-6 increases VEGF-C induction and lymphangiogenesis may involve, at least in part, Src-FAK-STAT3 cascade in LECs.

Predictors of coronary artery disease in middle-aged Taiwanese women at premenopause, postmenopause and after undergoing hysterectomy.

AIMS AND OBJECTIVES: To examine the predictors of coronary artery disease among middle-aged women at various menopausal statuses. BACKGROUND: Few studies have explored coronary artery disease predictors among middle-aged women at various menopausal statuses, particularly with the inclusion of women who underwent a hysterectomy. DESIGN: A cross-sectional design was adopted. METHODS: Two hundred and twenty-five middle-aged women who were waiting for catheterisation examinations because of possible coronary artery disease were selected. These patients were divided into premenopausal (n = 41), postmenopausal (n = 143) and women who had undergone a hysterectomy groups (n = 41). The differences in the risk factors for coronary artery disease between patients with coronary artery disease (catheterisation results showing stenosis of >50% in at least one major coronary artery) and those without coronary artery disease in the three groups were compared. RESULTS: The participants were aged 56·8 ± 5·9 years. In the premenopausal group, the odds of coronary artery disease among ever or current smokers was 8·46 times the odds of coronary artery disease for the never smokers. In the postmenopausal group, the odds of coronary artery disease among diabetes patients was 2·89 times the odds of coronary artery disease for those without diabetes. Each additional point on the Chinese Beck Depression Inventory-II increased the risk of coronary artery disease by 5%. In the hysterectomy group, each additional increase in 1 mmHg in systolic blood pressure increased the risk of coronary artery disease by 4%. CONCLUSIONS: Smoking, diabetes, depression and systolic blood pressure are predictors of coronary artery disease in middle-aged women at premenopause, postmenopause and after undergoing hysterectomy respectively. RELEVANCE TO CLINICAL PRACTICE: These results are beneficial for middle-aged women at various menopausal stages to effectively implement prevention of coronary artery disease. These findings were among women being evaluated for possible coronary artery disease, we suggest the need for further study in lager, longitudinal studies.

Cloud-based BP system integrated with CPOE improves self-management of the hypertensive patients: A randomized controlled trial.

BACKGROUND: Less than 50% of patients with hypertensive disease manage to maintain their blood pressure (BP) within normal levels. OBJECTIVE: The aim of this study is to evaluate whether cloud BP system integrated with computerized physician order entry (CPOE) can improve BP management as compared with traditional care. METHODS: A randomized controlled trial done on a random sample of 382 adults recruited from 786 patients who had been diagnosed with hypertension and receiving treatment for hypertension in two district hospitals in the north of Taiwan. Physicians had access to cloud BP data from CPOE. Neither patients nor physicians were blinded to group assignment. The study was conducted over a period of seven months. RESULTS: At baseline, the enrollees were 50% male with a mean (SD) age of 58.18 (10.83) years. The mean sitting BP of both arms was no different. The proportion of patients with BP control at two, four and six months was significantly greater in the intervention group than in the control group. The average capture rates of blood pressure in the intervention group were also significantly higher than the control group in all three check-points. CONCLUSIONS: Cloud-based BP system integrated with CPOE at the point of care achieved better BP control compared to traditional care. This system does not require any technical skills and is therefore suitable for every age group. The praise and assurance to the patients from the physicians after reviewing the Cloud BP records positively reinforced both BP measuring and medication adherence behaviors.

Valproic acid suppresses lipopolysaccharide-induced cyclooxygenase-2 expression via MKP-1 in murine brain microvascular endothelial cells.

Inflammation and vascular perturbations are increasingly implicated in the pathogenesis of neurodegenerative diseases. Prevailing evidence suggests that valproic acid (VPA), an antiepileptic and mood stabilizer, exhibits not only neuro-protective effects, but also anti-inflammatory effects in neurodegenerative diseases. However, the underlying mechanism contributing to VPA's suppression of inflammatory responses remains unclear. In this study, we explored the inhibitory action of VPA on cyclooxygenase (COX)-2 expression in bEnd.3 mouse brain microvascular endothelial cells exposed to lipopolysaccharide (LPS), a pro-inflammatory stimulus. The LPS-induced increases in COX-2 protein level and COX-2 promoter-luciferase activity were significantly suppressed by VPA. VPA inhibited p38MAPK and JNK phosphorylation in LPS-stimulated bEnd.3 cells. Treatment of cells with a p38MAPK inhibitor (p38MAPK inhibitor III) or a JNK signaling inhibitor (JNK inhibitor II) significantly inhibited LPS-induced COX-2 expression. VPA inhibited LPS-induced NF-κB subunit p65 phosphorylation and κB-luciferase activity. LPS-increased p65 and C/EBPß binding to the COX-2 promoter region was attenuated in the presence of VPA. In addition, VPA suppression of p38MAPK, JNK and p65 phosphorylation, and subsequent COX-2 expression was restored in cells transfected with mitogen-activated protein kinase phosphatase-1 (MKP-1) dominant negative (DN) mutant. VPA also caused increases in MKP-1 acetylation and MKP-1 phosphatase activity in bEnd.3 cells. In conclusion, VPA may cause MKP-1 activation to dephosphorylate p38MAPK and JNK, leading to decrease in p65 and C/EBPß binding to the COX-2 promoter region and COX-2 down-regulation in LPS-stimulated bEnd.3 cells. The present study therefore supports the therapeutic value of VPA in alleviating brain inflammatory processes.

Bipolar Disorder and Schizophrenia Present Different Risks of Atrial fibrillation: A Nationwide Population-Based Analysis.

BACKGROUND: Atrial fibrillation (AF) is increasingly prevalent in society, and can elevate cardiac morbidity and mortality. Psychosis and gender are known to play important roles in the genesis of AF. However, it is not clear whether gender modulates the impact of different psychoses on the occurrences of AF. METHODS: We identified patients suffering from bipolar disorder and schizophrenia, with and without AF, using the Taiwan National Health Insurance nationwide database. The identified patient population consisted of 927,915 subjects (463,050 males and 464,865 females) from 2001 to 2008, which included 2,963 (3.2 ‰) schizophrenia patients (1,650 males and 1,313 females) and 5,112 (5.5 ‰) bipolar-disorder patients (1,934 males and 3,178 females). RESULTS: The male and female bipolar-disorder patients had higher prevalences of AF than did male (16.5 ‰ vs. 2.4 ‰, p < 0.001) and female (12.9 ‰ vs. 2.3 ‰, p < 0.001) schizophrenia patients. Furthermore, male and female bipolar-disorder patients had higher AF prevalences than did males (8.5 ‰, p < 0.001) and females (7.2 ‰, p < 0.001) in the general population. Schizophrenia patients had lower AF prevalence than the general population in male, but not in female gender. Males had a higher AF prevalence than females. However, male and female bipolar disorder and schizophrenia patients had similar AF prevalences. Those patients with schizophrenia and bipolar-disorder patients with AF were older than those without AF. CONCLUSIONS: Differing risk factors for AF were identified in bipolar-disorder and schizophrenia patients. Compared to the general population, gender may have different impacts on the occurrence of AF in psychosis patients. KEY WORDS: Atrial fibrillation; Bipolar disorder; Population-based study; Schizophrenia.

Src contributes to IL6-induced vascular endothelial growth factor-C expression in lymphatic endothelial cells.

Formation of lymphatic capillaries by lymphatic endothelial cells (LECs) occurs both in normal tissues as well as in pathological processes including tumor metastasis. Interleukin-6 (IL-6), a potent pro-inflammatory cytokine, has been shown to be highly elevated in various cancers. IL-6 has also been shown to increase tumor lymphangiogenesis through vascular endothelial growth factor-C (VEGF-C) induction in tumor cells. Although lymphangiogenesis is associated with lymph node metastasis and also resistance to conventional therapy in various cancers, the precise mechanisms of lymphangiogenesis in LECs remain unclear. This study aimed to investigate the signaling cascade involved in IL-6-induced VEGF-C expression in murine LECs (SV-LEC). The VEGF-C mRNA and protein levels were increased in SV-LECs exposed to IL-6. IL-6 time-dependently induced Src phosphorylation and downstream phosphorylation of ERK1/2 and p38MAPK. In contrast, PP2, an inhibitor of Src signaling, abrogated IL-6's effects on ERK1/2 and p38MAPK phosphorylation. IL-6 exposure also led to increase in VEGF-C promoter-luciferase activity as well as C/EBPß- and κB-luciferase activities. VEGF-C promoter-, C/EBPß- and κB-luciferase activities were all suppressed by Src, ERK1/2 or p38MAPK signaling blockades despite presence of IL-6. Finally, C/EBPß and p65 binding to the VEGF-C promoter region were increased after IL-6 exposure in SV-LECs. Taken together, we report a Src-mediated ERK1/2 and p38MAPK activation resulting in C/EBPß and p65 binding to the promoter region of VEGF-C, leading to VEGF-C expression in IL-6-exposed SV-LECs.

Anti-cancer activity of an osthole derivative, NBM-T-BMX-OS01: targeting vascular endothelial growth factor receptor signaling and angiogenesis.

Angiogenesis occurs during tissue growth, development and wound healing. It is also required for tumor progression and represents a rational target for therapeutic intervention. NBM-T-BMX-OS01 (BMX), derived from the semisynthesis of osthole, an active ingredient isolated from Chinese herb Cnidium monnieri (L.) Cuss., was recently shown to enhance learning and memory in rats. In this study, we characterized the anti-angiogenic activities of NBM-T-BMX-OS01 (BMX) in an effort to develop novel inhibitors to suppress angiogenesis and tumor growth. BMX inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration and endothelial tube formation in human umbilical endothelial cells (HUVECs). BMX also attenuated VEGF-induced microvessel sprouting from aortic rings ex vivo and reduced HCT116 colorectal cancer cells-induced angiogenesis in vivo. Moreover, BMX inhibited the phosphorylation of VEGFR2, FAK, Akt and ERK in HUVECs exposed to VEGF. BMX was also shown to inhibit HCT116 cell proliferation and to suppress the growth of subcutaneous xenografts of HCT116 cells in vivo. Taken together, this study provides evidence that BMX modulates vascular endothelial cell remodeling and leads to the inhibition of tumor angiogenesis. These results also support the role of BMX as a potential drug candidate and warrant the clinical development in the treatment of cancer.

Analysis of 10-year nationwide population-based data on sex differences in hospitalization for heart failure.

Sex-related factors play an important role in the pathophysiology of heart failure (HF). However, trends in sex-related differences in hospital management for HF are not clear. We identified patients hospitalized for HF through a nationwide database (National Health Insurance in Taiwan), containing 722,272 subjects from 1999 to 2008. Higher incidences of diabetes mellitus (37 vs. 25 %, p < 0.001), thyroid dysfunction (2 vs. 0 %, p < 0.001), and transient cerebral ischemia (2 vs. 1 %, p < 0.05), as well as a lower incidence of chronic lung disease (14 vs. 22 %, p < 0.001) differentiated female HF patients from male HF patients. During this 10-year period, both percentage of HF hospitalization and age-adjusted HF rates significantly increased for total HF sample (1.92 vs. 2.49  ‰, p < 0.05, and 20.44 vs. 27.38/100,000, p < 0.05) and for female (1.76 vs. 2.86  ‰, p < 0.05, and 20.94 vs. 32.12/100,000, p < 0.05), but such changes did not occur among male patients (2.12 vs. 2.09  ‰, p > 0.05, and 19.93 vs. 22.51/100,000, p > 0.05). The age at the time of hospitalization and the length of the hospital stay increased significantly for all HF patients during the 10-year study period. However, the daily cost of hospitalization increased in males, but not in females. Compared to the survivors, patients who died were older and had a longer hospitalization and higher daily cost both in males and females. Through our analysis of the NHI database, we observed trends in factors related to hospitalization of HF patients in Taiwan that may be attributable to sex-related differences in the pathophysiology and treatment strategies for HF.