Scalable energy-efficient magnetoelectric spin-orbit logic.

Since the early 1980s, most electronics have relied on the use of complementary metal-oxide-semiconductor (CMOS) transistors. However, the principles of CMOS operation, involving a switchable semiconductor conductance controlled by an insulating gate, have remained largely unchanged, even as transistors are miniaturized to sizes of 10 nanometres. We investigated what dimensionally scalable logic technology beyond CMOS could provide improvements in efficiency and performance for von Neumann architectures and enable growth in emerging computing such as artifical intelligence. Such a computing technology needs to allow progressive miniaturization, reduce switching energy, improve device interconnection and provide a complete logic and memory family. Here we propose a scalable spintronic logic device that operates via spin-orbit transduction (the coupling of an electron's angular momentum with its linear momentum) combined with magnetoelectric switching. The device uses advanced quantum materials, especially correlated oxides and topological states of matter, for collective switching and detection. We describe progress in magnetoelectric switching and spin-orbit detection of state, and show that in comparison with CMOS technology our device has superior switching energy (by a factor of 10 to 30), lower switching voltage (by a factor of 5) and enhanced logic density (by a factor of 5). In addition, its non-volatility enables ultralow standby power, which is critical to modern computing. The properties of our device indicate that the proposed technology could enable the development of multi-generational computing.

Guard Cell-Inspired Ion Channels: Harnessing the Photomechanical Effect via Supramolecular Assembly of Cross-Linked Azobenzene/Polymers.

Stimuli-responsive ion nanochannels have attracted considerable attention in various fields because of their remote controllability of ionic transportation. For photoresponsive ion nanochannels, however, achieving precise regulation of ion conductivity is still challenging, primarily due to the difficulty of programmable structural changes in confined environments. Moreover, the relationship between noncontact photo-stimulation in nanoscale and light-induced ion conductivity has not been well understood. In this work, a versatile design for fabricating guard cell-inspired photoswitchable ion channels is presented by infiltrating azobenzene-cross-linked polymer (AAZO-PDAC) into nanoporous anodic aluminum oxide (AAO) membranes. The azobenzene-cross-linked polymer is formed by azobenzene chromophore (AAZO)-cross-linked poly(diallyldimethylammonium chloride) (PDAC) with electrostatic interactions. Under UV irradiation, the trans-AAZO isomerizes to the cis-AAZO, causing the volume compression of the polymer network, whereas, in darkness, the cis-AAZO reverts to the trans-AAZO, leading to the recovery of the structure. Consequently, the resultant nanopore sizes can be manipulated by the photomechanical effect of the AAZO-PDAC polymers. By adding ionic liquids, the ion conductivity of the light-driven ion nanochannels can be controlled with good repeatability and fast responses (within seconds) in multiple cycles. The ion channels have promising potential in the applications of biomimetic materials, sensors, and biomedical sciences.

Observation of anti-damping spin-orbit torques generated by in-plane and out-of-plane spin polarizations in MnPd3.

Large spin-orbit torques (SOTs) generated by topological materials and heavy metals interfaced with ferromagnets are promising for next-generation magnetic memory and logic devices. SOTs generated from y spin originating from spin Hall and Edelstein effects can realize field-free magnetization switching only when the magnetization and spin are collinear. Here we circumvent the above limitation by utilizing unconventional spins generated in a MnPd3 thin film grown on an oxidized silicon substrate. We observe conventional SOT due to y spin, and out-of-plane and in-plane anti-damping-like torques originated from z spin and x spin, respectively, in MnPd3/CoFeB heterostructures. Notably, we have demonstrated complete field-free switching of perpendicular cobalt via out-of-plane anti-damping-like SOT. Density functional theory calculations show that the observed unconventional torques are due to the low symmetry of the (114)-oriented MnPd3 films. Altogether our results provide a path toward realization of a practical spin channel in ultrafast magnetic memory and logic devices.

Clinical practice consensus for the diagnosis and management of melanoma in Taiwan.

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

Identification of potential classes of glycoligands mediating dynamic endothelial adhesion of human tumor cells.

One critical step of metastasis formation is the extravasation of circulating tumor cells from the bloodstream. This process requires the dynamic interaction of cell adhesion molecules like E-selectin on endothelial cells with carbohydrate ligands on tumor cells. To characterize these glycans in a comprehensible approach, the rolling, tethering, and firm adhesion of nine human tumor cell lines on human umbilical vein endothelial cells was analyzed using laminar flow adhesion assays. The tumor cell lines were grouped into three subsets by their canonical E-selectin ligand status (sialyl-Lewis A and X +/+, -/+, -/-) and their adhesiveness was compared after enzymatic, pharmacologic, chemical treatment or antibody blockade of the tumor cells or endothelial cells, respectively. Tumor cells were also screened regarding their glycosyltransferase expression profile. We found that although E-selectin and terminal α2,3-sialic acid largely determined firm adhesion, adhesive events did not exclusively depend on the presence of sialyl-Lewis A and/or sialyl-Lewis X. Nevertheless, two of the three sialyl-Lewis A/X-/- tumor cells additionally or fully depended on vascular cell adhesion molecule-1 for firm adhesion. The significance of O-GalNAc- and N-glycans for adhesion varied remarkably among the tumor cells. The sialyl-Lewis A/X+/+ subset showed glycoprotein-independent adhesion, suggesting a role of glycolipids as well. All sialyl-Lewis A/X-/- tumor cells lacked FUT3 and FUT7 expression as opposed to sialyl-Lewis A/X+/+ or -/+ cell lines. In summary, the glycans on tumor cells mediating endothelial adhesion are not as much restricted to sialyl-Lewis A /X as previously assumed. The present study specifically suggests α2,3-linked sialic acid, O-GalNAc glycans, glycosphingolipids, and FUT3/FUT7 products as promising targets for future studies.

Impact of the uniaxial strain on terahertz modulation characteristics in flexible epitaxial VO2 film across the phase transition.

Exploring flexible electronics is on the verge of innovative breakthroughs in terahertz (THz) communication technology. Vanadium dioxide (VO2) with insulator-metal transition (IMT) has excellent application potential in various THz smart devices, but the associated THz modulation properties in the flexible state have rarely been reported. Herein, we deposited an epitaxial VO2 film on a flexible mica substrate via pulsed-laser deposition and investigated its THz modulation properties under different uniaxial strains across the phase transition. It was observed that the THz modulation depth increases under compressive strain and decreases under tensile strain. Moreover, the phase-transition threshold depends on the uniaxial strain. Particularly, the rate of the phase transition temperature depends on the uniaxial strain and reaches approximately 6 °C/% in the temperature-induced phase transition. The optical trigger threshold in laser-induced phase transition decreased by 38.9% under compressive strain but increased by 36.7% under tensile strain, compared to the initial state without uniaxial strain. These findings demonstrate the uniaxial strain-induced low-power triggered THz modulation and provide new insights for applying phase transition oxide films in THz flexible electronics.

MFI2 upregulation promotes malignant progression through EGF/FAK signaling in oral cavity squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the predominant histological type of the head and neck squamous cell carcinoma (HNSCC). By comparing the differentially expressed genes (DEGs) in OSCC-TCGA patients with copy number variations (CNVs) that we identify in OSCC-OncoScan dataset, we herein identified 37 dysregulated candidate genes. Among these potential candidate genes, 26 have been previously reported as dysregulated proteins or genes in HNSCC. Among 11 novel candidates, the overall survival analysis revealed that melanotransferrin (MFI2) is the most significant prognostic molecular in OSCC-TCGA patients. Another independent Taiwanese cohort confirmed that higher MFI2 transcript levels were significantly associated with poor prognosis. Mechanistically, we found that knockdown of MFI2 reduced cell viability, migration and invasion via modulating EGF/FAK signaling in OSCC cells. Collectively, our results support a mechanistic understanding of a novel role for MFI2 in promoting cell invasiveness in OSCC.

The interplay between IGF-1R signaling and Hippo-YAP in breast cancer stem cells.

BACKGROUND: Both IGF-1R/PI3K/AKT/mTOR and Hippo pathways are crucial for breast cancer stem cells (BCSCs). However, their interplay remains unclear. METHODS: Four triple negative breast cancer cell lines derived from CSC of two patient-derived xenografts (PDXs), AS-B145, AS-B145-1R, AS-B244, and AS-B244-1R, were used to elucidate the role of YAP in BCSCs. YAP silenced BCSCs were analyzed by cell proliferation, aldehyde dehydrogenase (ALDH) activity, mammosphere formation, and tumorigenesis. The effects of modulating IGF-1R and IGF-1 on YAP expression and localization were evaluated. The clinical correlation of YAP and IGF-1R signaling with the overall survival (OS) of 7830 breast cancer patients was analyzed by KM plotter. RESULTS: Knockdown of YAP abates the viability and stemness of BCSCs in vitro and tumorigenicity in vivo. Depletion of IGF-1R by shRNA or specific inhibitor decreases YAP expression. In contrast, IGF-1 addition upregulates YAP and enhances its nuclear localization. YAP overexpression increased the mRNA level of IGF-1, but not IGF-1R. Data mining of clinical breast cancer specimens revealed that basal-like breast cancer patients with higher level of IGF-1 and YAP exhibit significantly shorter OS. CONCLUSIONS: YAP contributes to stemness features of breast cancer in vitro and in vivo. The expression and localization of YAP was regulated by IGF-1R and YAP expression in turns upregulates IGF-1, but not IGF-1R. Clinically, higher level of YAP and IGF-1 significantly correlated with shorter OS in basal-like breast cancer. Taken together, these findings suggest the clinical relevance of interplay between YAP and IGF-1/IGF-1R pathway in sustaining the properties of BCSCs. Video Abstract.

Acute graft-versus-host disease presenting as Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective cohort study.

BACKGROUND: Cutaneous manifestations resembling Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients with acute graft-versus-host disease (aGVHD); however, the clinicopathological characteristics of SJS/TEN-like aGVHD remain unexplored. OBJECTIVE: To investigate the clinicopathology, complications, and outcomes of patients with SJS/TEN-like aGVHD. METHODS: We analyzed a multicenter cohort of patients with aGVHD between 2000 and 2021. RESULTS: We analyzed 31 patients with aGVHD, including SJS/TEN-like (n = 15) and non-SJS/TEN-like (n = 16). Patients with SJS/TEN-like aGVHD had significantly more extensive erythema and skin detachment/mucositis. SJS/TEN-like aGVHD was significantly associated with higher aGVHD grading and systemic complications, including pancytopenia, leukopenia, anemia, severe thrombocytopenia, coagulation abnormality, hepatitis, diarrhea, renal dysfunction, and bacteremia. A significantly lower hemoglobin/red cell distribution width ratio was identified in SJS/TEN-like aGVHD. Histopathology showed significant severe dyskeratosis and interface change. Patients with SJS/TEN-like aGVHD had lower 2-month survival rates and 5.35-fold higher 5-year mortality rates than those with non-SJS/TEN-like aGVHD. Total mortality rates of patients with SJS/TEN-like aGVHD reached 80% during follow-up; sepsis predominated the causes of death. LIMITATIONS: Retrospective, nonrandomized study with a small sample size. CONCLUSION: SJS/TEN-like aGVHD is associated with multiple systemic complications and high mortality. Early recognition, differential diagnosis from drug-induced-SJS/TEN, and appropriate treatment are critical.

High B3GALT5 expression confers poor clinical outcome and contributes to tumor progression and metastasis in breast cancer.

BACKGROUND: Existence of breast cancer stem cells (BCSCs) is implicated in disease relapse, metastasis, and resistance of treatment. ß1,3-Galactosyltransferase 5 (B3GALT5) has been shown to be a pro-survival marker for BCSCs. However, little is known about the prognostic significance of B3GALT5 in breast cancer. METHODS: Paired tissues (tumor part and adjacent non-tumor part) from a cohort of 202 women with breast cancer were used to determine the expression levels of B3GALT5 mRNA by qRT-PCR. Kaplan-Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of relapse-free survival (RFS) and overall survival (OS). Both breast cancer cells and cancer stem cells (BCSCs) were used to see the in vitro effects of knockdown or overexpression of B3GALT5 on cell migration, invasion, and epithelial-to-mesenchymal transition (EMT). A patient-derived xenograft (PDX) model was used to see the in vivo effects of knockdown of B3GALT5 in BCSCs on tumor growth and metastasis. RESULTS: Higher expression of B3GALT5 in 202 breast cancer tissues, especially in adjacent non-tumor tissue, correlated with poor clinical outcomes including shorter OS and RFS in all patients, especially those with early stage breast cancer. In vitro studies showed B3GALT5 could enhance cell migration, invasion, mammosphere formation, and EMT. Of note, B3GALT5 upregulated the expression of ß-catenin and EMT activator zinc finger E-box binding homeobox 1 (ZEB1) pathway in BCSCs. In vivo studies showed B3GALT5 expression in BCSCs is critical for not only tumor growth but also lymph node and lung metastasis in PDX mice. CONCLUSION: Our results demonstrated the value of B3GALT5 as a prognostic marker of breast cancer, especially among the early stage patients, and its crucial roles in regulating EMT, cell migration, and stemness thereby promoting breast cancer progression.

Proteomic Profiling of Paired Interstitial Fluids Reveals Dysregulated Pathways and Salivary NID1 as a Biomarker of Oral Cavity Squamous Cell Carcinoma.

Patients with oral cavity squamous cell carcinoma (OSCC) are frequently first diagnosed at an advanced stage, leading to poor prognosis and high mortality rates. Early detection of OSCC using body fluid-accessible biomarkers may improve the prognosis and survival rate of OSCC patients. As tumor interstitial fluid is a proximal fluid enriched with cancer-related proteins, it is a useful reservoir suitable for the discovery of cancer biomarkers and dysregulated biological pathways in tumor microenvironments. Thus, paired interstitial fluids of tumor (TIF) and adjacent noncancerous (NIF) tissues from 10 OSCC patients were harvested and analyzed using one-dimensional gel electrophoresis coupled with liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). Using label-free spectral counting-based quantification, 113 proteins were found to be up-regulated in the TIFs compared with the NIFs. The gene set enrichment analysis (GSEA) revealed that the differentially expressed TIF proteins were highly associated with aminoacyl tRNA biosynthesis pathway. The elevated levels of 4 proteins (IARS, KARS, WARS, and YARS) involved in the aminoacyl tRNA biosynthesis were verified in the OSCC tissues with immunohistochemistry (IHC). In addition, nidogen-1 (NID1) was selected for verification as an OSCC biomarker. Salivary level of NID1 in OSCC patients (n = 48) was significantly higher than that in the healthy individuals (n = 51) and subjects with oral potentially malignant disorder (OPMD; n = 53). IHC analysis showed that NID1 level in OSCC tissues was increased compared with adjacent noncancerous epithelium (n = 222). Importantly, the elevated NID1 level was correlated with the advanced stages of OSCC, as well as the poor survival of OSCC patients. Collectively, the results suggested that TIF analysis facilitates understanding of the OSCC microenvironment and that salivary NID1 may be a useful biomarker for OSCC.

The role of postoperative radiotherapy in pN1 oral cavity cancer without extranodal extension.

BACKGROUND: The administration of postoperative radiotherapy remains controversial in pN1 oral cavity cancer patients without extranodal extension. The aim is to determine whether postoperative radiotherapy reduces the neck recurrence rate and improves the survival outcomes of pN1 patients. METHODS: This study consecutively enrolled 1056 patients with newly diagnosed oral squamous cell carcinoma who underwent tumor wide excision and neck dissection from September 2002 to November 2019. One hundred two pN1 patients without extranodal extension were eligible for analysis. Then, a subgroup analysis of 40 patients was performed after patients with other adverse risk factors (positive margins, close margins, lymphovascular invasion, perineural invasion, tumor depth ≥ 10 mm, and poor histological differentiation) were excluded. RESULTS: Of the 102 eligible pN1 patients, 26 patients received surgery alone, and 76 received postoperative radiotherapy. No significant differences were observed in the neck recurrence rate (7.7% vs. 15.8%, p = 0.30). Similarly, in patients without other adverse risk factors, no significant differences were observed in the neck recurrence rate (5% vs. 20%, p = 0.15) between surgery alone group and postoperative radiotherapy group. Moreover, no significant difference was found in the neck recurrence-free survival rate, overall survival, and disease-specific survival (77.1% vs. 52.5%, p = 0.42, 83.5% vs. 64.5%, p = 0.81, and 88.2% vs. 67.9%, p = 0.34, respectively). CONCLUSION: Postoperative radiotherapy did not significantly decrease the probability of neck recurrence and survival outcomes in pN1 patients without extranodal extension. Radical surgery alone may be considered sufficient treatment for pN1 patients without other adverse risk factors.

Interferometric imaging of nonlocal electromechanical power transduction in ferroelectric domains.

The electrical generation and detection of elastic waves are the foundation for acoustoelectronic and acoustooptic systems. For surface acoustic wave devices, microelectromechanical/nanoelectromechanical systems, and phononic crystals, tailoring the spatial variation of material properties such as piezoelectric and elastic tensors may bring significant improvements to the system performance. Due to the much slower speed of sound than speed of light in solids, it is desirable to study various electroacoustic behaviors at the mesoscopic length scale. In this work, we demonstrate the interferometric imaging of electromechanical power transduction in ferroelectric lithium niobate domain structures by microwave impedance microscopy. In sharp contrast to the traditional standing-wave patterns caused by the superposition of counterpropagating waves, the constructive and destructive fringes in microwave dissipation images exhibit an intriguing one-wavelength periodicity. We show that such unusual interference patterns, which are fundamentally different from the acoustic displacement fields, stem from the nonlocal interaction between electric fields and elastic waves. The results are corroborated by numerical simulations taking into account the sign reversal of piezoelectric tensor in oppositely polarized domains. Our work paves ways to probe nanoscale electroacoustic phenomena in complex structures by near-field electromagnetic imaging.

Sirolimus Suppresses Phosphorylation of Cofilin and Reduces Interstitial Septal Thickness in Sporadic Lymphangioleiomyomatosis.

Sporadic lymphangioleiomyomatosis (S-LAM) is a rare lung disease characterized by the proliferation of smooth muscle-like LAM cells and progressive cystic destruction. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has a proven efficacy in patients with LAM. However, the therapeutic mechanisms of sirolimus in LAM remain unclear. We aimed to evaluate sirolimus-related lung parenchymal changes and the potential effect in LAM cells and modulating pathological cystic destruction. Lung specimens were examined for histopathological changes by HMB45 staining and compared the LAM patients treated with and without sirolimus. We detected the overexpression of mTOR, HMB45, and phosphorylation of cofilin (p-cofilin) in LAM patients. Sirolimus showed efficacy in patients with LAM, who exhibited a reduced expression of mTOR and p-cofilin as well as reduced interstitial septal thickness. In addition, sirolimus suppresses mTOR and p-cofilin, thus suppressing the migration and proliferation of LAM cells isolated from the patient's lung tissue. This study demonstrates that interstitial septal thickness, as determined by histological structural analysis. Sirolimus effectively reduced the expression of p-cofilin and interstitial septal thickness, which may be a novel mechanism by sirolimus. Moreover, we develop a new method to isolate and culture the LAM cell, which can test the possibility of medication in vitro and impact this current study has on the LAM field. The development of approaches to interfere with mTOR-cofilin1-actin signaling may result in an option for S-LAM therapy.

Deterministic optical control of room temperature multiferroicity in BiFeO3 thin films.

Controlling ferroic orders (ferroelectricity, ferromagnetism and ferroelasticity) by optical methods is a significant challenge due to the large mismatch in energy scales between the order parameter coupling strengths and the incident photons. Here, we demonstrate an approach to manipulate multiple ferroic orders in an epitaxial mixed-phase BiFeO3 thin film at ambient temperature via laser illumination. Phase-field simulations indicate that a light-driven flexoelectric effect allows the targeted formation of ordered domains. We also achieved precise sequential laser writing and erasure of different domain patterns, which demonstrates a deterministic optical control of multiferroicity at room temperature. As ferroic orders directly influence susceptibility and conductivity in complex materials, our results not only shed light on the optical control of multiple functionalities, but also suggest possible developments for optoelectronics and related applications.

Toward Intrinsic Ferroelectric Switching in Multiferroic BiFeO_{3}.

Using pulsed ferroelectric measurements, we probe switching dynamics in multiferroic BiFeO_{3}, revealing low-ns switching times and a clear pathway to sub-ns switching. Our data is well described by a nucleation and growth model, which accounts for the various timescales in the switching process, namely (1) the ferroelectric polarization switching (bound-charge) dynamics and (2) the RC-limited movement of free charge in the circuit. Our model shows good agreement with observed data and begins to bridge the gap between experiment and theory, indicating pathways to study ferroelectric switching on intrinsic timescales.

The impact of preoperative glycated hemoglobin levels on outcomes in oral squamous cell carcinoma.

OBJECTIVES: This study aimed to investigate the association between preoperative glycated hemoglobin (HbA1c) levels and the treatment outcomes of oral cavity squamous cell carcinoma (OSCC). METHODS: Three hundred and fifty-eight OSCC patients were consecutively enrolled between July 2004 and July 2016. Clinicopathological parameters and survival outcomes were analyzed following HbA1c stratification of 6.5% (HbA1c ≥ 6.5%: n = 74, 20.6%) and 7.0% (HbA1c ≥ 7.0%: n = 53, 14.8%). RESULTS: Higher HbA1c levels were associated with elevated body mass index, lower albumin levels, wider surgical margins, and prolonged hospital stays (HbA1c 6.5%: p = .001, .048, .030, .009, respectively; HbA1c 7.0%: p = .092, .032, .009, .015, respectively). Survival rates stratified by HbA1c 6.5% were as follows: locoregional recurrence-free survival, p = .014; distant metastasis-free survival, p = .013; second primary cancer-free survival, p = .015; overall survival, p = .014; disease-specific survival, p = .002 and HbA1c 7.0%: locoregional recurrence-free survival, p = .013; distant metastasis-free survival, p = .013; second primary cancer-free survival, p = .014; overall survival, p = .015; disease-specific survival, p = .004. Multivariate analyses identified HbA1c as an independent prognostic factor for overall and disease-specific survival (HbA1c 6.5%: p = .014 and .002, respectively; HbA1c 7.0%: p = .036 and .013, respectively). CONCLUSIONS: Oral squamous cell carcinoma patients with higher preoperative HbA1c levels had longer hospitalization and worse survival outcomes.

Influence of Hyperglycemia on Treatment Outcomes of Oral Cavity Squamous Cell Carcinoma.

PURPOSE: The present study investigated the association between perioperative hyperglycemia and the treatment and survival outcomes of patients with oral cavity squamous cell carcinoma (OSCC). PATIENTS AND METHODS: From 2004 to 2016, 385 patients with OSCC were enrolled and stratified into normoglycemic (<180 mg/dL) and hyperglycemic (≥180 mg/dL) groups. The clinicopathologic characteristics and treatment outcomes of OSCC were subsequently analyzed. RESULTS: Of the 385 patients, 61 (15.8%) were in the hyperglycemic group. Hyperglycemia was significantly associated with pT stage, pN stage, overall pathologic stage, extranodal extension, albumin level, and tumor depth (P = .004, P = .042, P = .008, P = .001, P = .004, and P = .011, respectively). Patients with hyperglycemia also required a longer hospital stay (P = .003). The 5-year overall survival and disease-specific survival were poorer in the hyperglycemic group than in the normoglycemic group (P = .001 and P = .002, respectively). Multivariate analysis revealed that hyperglycemia is a significant adverse prognostic indicator for OSCC (hazard ratio, 1.709; 95% confidence interval, 1.003 to 2.912; P = .049). CONCLUSIONS: Hyperglycemia is associated with more advanced disease and poorer survival rates in patients with OSCC. It correlates with adverse clinicopathologic characteristics and longer hospital stay. Screening for hyperglycemia and maintenance of normal glycemic status during the treatment course is imperative in the treatment of OSCC.

Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertension.

BACKGROUND/PURPOSE: Pulmonary veno-occlusive disease (PVOD) is a rare but fatal cause of pulmonary hypertension reported to be linked to mutations of eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4), also known as general control nonderepressible 2 kinase (GCN2). PVOD is difficult to diagnose and often initially misdiagnosed as other types of idiopathic pulmonary arterial hypertension (IPAH). To rapidly and correctly identify PVOD patients and explore the possible pathogenesis, we thoroughly investigated histopathological features and GCN2 protein levels in non-PAH, PVOD and PAH patients. METHODS: Lung specimens were examined for histopathological changes, including those of pulmonary arteries and veins, by Masson's trichrome, modified Verhoeff's and α-SMA staining in the PVOD, IPAH, and non-PAH groups. GCN2 and α-SMA expression in lung tissue was examined by immunohistochemistry and western blotting. RESULTS: PVOD and IPAH patients showed significant intimal and medial thickening of muscular pulmonary arteries compared with non-PAH patients. PVOD patients had more prominent intimal and medial thickening of muscular pulmonary veins than the other two groups. Interestingly, specialized muscle bundles surrounding the tunica adventitia of the pulmonary artery and vein were observed in PVOD patients. A significant decrease in GCN2 expression in the PVOD group was confirmed by immunohistochemistry and western blotting. CONCLUSION: Our study is the first to show remarkable histological structures, including the wreath-like arrangement of a hyperplastic muscle bundle in the adventitia of pulmonary arteries, in PVOD patients as a diagnostic clue and to disclose the biological difference between PAH and PVOD in a Taiwanese population.

Effect of Degree of Arterial Inflow on a Functioning Free Muscle Transplantation in a Rat Gracilis Model.

BACKGROUND: Various surgical effects have previously been studied in an attempt to improve the functional outcome of the functioning free muscle transplantation (FFMT). However, the effect of the recipient arterial inflow on the FFMT has remained uninvestigated. This study was to investigate whether or not high flow versus low flow will affect the functional outcome of FFMT. METHODS: Rat's left gracilis FFMT model was devised and the nutrient arterial inflow was modified. Twenty-four Lewis rats were divided evenly into relatively high (0.071 mL/min) and relatively low (0.031 mL/min) blood flow groups (p < 0.001). The unoperated right sides served as the controls. Cases resulting in poor function were additionally grouped as functional failure group for comparison. Regular swimming exercise was implemented at 1 month postoperatively for 3 months. Gracilis muscle functions were then evaluated. RESULTS: Compared groups were: control (n = 13), low blood flow (n = 10), high blood flow (n = 8), and functional failure (n = 5). The control group showed superior functional results over the experimental groups (p < 0.0001). In the experimental group, successful group showed superior over the poor function group (p < 0.01). However, there was no significant difference between the high- and low-flow groups. CONCLUSION: This is the first study to evaluate the effect of arterial inflow on the FFMT. The rate of blood flow (relatively high vs. low) has little effect on the functional outcome of transferred muscle. Survival of FFMT is the major concern while performing FFMT surgery. Arterial inflow while choosing the recipient artery is not the factor for consideration.