A one-dimensional convolutional neural network based deep learning for high accuracy classification of transformation stages in esophageal squamous cell carcinoma tissue using micro-FTIR.

Among the most frequently diagnosed cancers in developing countries, esophageal squamous cell carcinoma (ESCC) ranks among the top six causes of death. It would be beneficial if a rapid, accurate, and automatic ESCC diagnostic method could be developed to reduce the workload of pathologists and improve the effectiveness of cancer treatments. Using micro-FTIR spectroscopy, this study classified the transformation stages of ESCC tissues. Based on 6,352 raw micro-FTIR spectra, a one-dimensional convolutional neural network (1D-CNN) model was constructed to classify-five stages. Based on the established model, more than 93% accuracy was achieved at each stage, and the accuracy of identifying proliferation, low grade neoplasia, and ESCC cancer groups was achieved 99% for the test dataset. In this proof-of-concept study, the developed method can be applied to other diseases in order to promote the use of FTIR spectroscopy in cancer pathology.

Rapid and sensitive detection of esophageal cancer by FTIR spectroscopy of serum and plasma.

Fourier transform infrared (FTIR) spectroscopy, as a platform technology for cancer detection, must be up to the challenge of clinical transformation. To this end, detection of esophageal squamous cell carcinoma (ESCC) was hereby explored using serum and plasma scrape-coated on barium fluoride (BaF2) disk by transmission FTIR method, and the classification model was built using six multivariate statistical analyses, including support vector machine (SVM), principal component linear discriminant analysis (PC-LDA), decision tree (DT), k-nearest neighbor (KNN) classification, ensemble algorithms (EA) and partial least squares for discriminant analysis (PLS-DA). All statistical analyses methods demonstrated that late-stage cancer could be well classified from healthy people employing either serum or plasma with different anticoagulants. Resulting PC-LDA model differentiated late-stage cancer from normal group with an accuracy of 99.26%, a sensitivity of 98.53%, and a specificity of 100%. The accuracy and sensitivity reached 97.08% and 91.43%, respectively for early-stage cancer discrimination from normal group. This pilot exploration demonstrated that transmission FTIR provided a rapid, cost effective and sensitive method for ESCC diagnosis using either serum or plasma.

Ischaemia-free liver transplantation in humans: a first-in-human trial.

Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences. Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT). Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach. Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers. Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology. Panel: Research in context.

Simple and fast colorimetric and electrochemical methods for the ultrasensitive detection of glucose.

Developing ultrasensitive and user-friendly methods for the detection glucose has attracted more and more attention. By virtue of high selectivity and sensitivity, enzyme-based glucose sensor plays a key role in point-of-care sensing technology for detecting glucose concentration. In this study, Amplex Red (AR), as both indicator and mediator, was investigated to detect glucose in presence of glucose oxidase (GOx) enzymes using colorimetric and electrochemical methods. Without using any advanced techniques and sophisticated nanomaterials, 1 µM glucose can be easily detected through simply detecting the solution color with a visual colorimetric method. On the other hand, the electrochemical method can provide much higher sensitivity for the detection of glucose, which achieves a linear range spanning from 20 nM to 3.56 µM with a limit of 7.3 nM (signal-to-noise ratio SNR = 3). It is also found that the presence of other sugars such as fructose, lactose, and maltose have very limited interference effects on the detection of glucose. More importantly, a bare GC electrode was used in all these electrochemical measurements without any electrode surface modification, guaranteeing a simple and fast operation. The analytical platforms for the detection of glucose presented here not only provide simple, fast, and ultrasensitive methods, but also have the potential to advance the sensing technology in the application of other health diagnostic research areas. Amplex Red (AR) was reported as both an indicator and mediator for the sensitive and specific determination of glucose using the colorimetric and electrochemical methods. The detection limit was 1 µM glucose by the visual colorimetric methods. A bare glassy carbon electrode without any functional modification was employed for the detection as low as 20 nM glucose with LOD of 7.3 nm (SNR = 3) in the electrochemical method.

Blood plasma resonance Raman spectroscopy combined with multivariate analysis for esophageal cancer detection.

We herein report a novel, reliable and inexpensive method for detecting esophageal cancer using blood plasma resonance Raman spectroscopy combined with multivariate analysis methods. The blood plasma samples were divided into late stage cancer group (n = 164), early stage cancer group (n = 35) and normal group (n = 135) based on clinical pathological diagnosis. Using a specially designed quartz capillary tube as sample holder, we obtained higher quality resonance Raman spectra of blood plasma than existing method. The study demonstrated that the carotenoids levels in blood plasma were reduced in esophageal cancer patients. The area under the receiver operating characteristic curve (and 95% confidence interval) calculated by wavenumber selection and principal component analysis combined with linear discriminant analysis (PC-LDA) algorithm were 0.894 (0.858-0.929), 0.901 (0.841-0.960) and 0.871 (0.799-0.942) for differentiating late cancer from normal, late cancer from early cancer, and early cancer from normal respectively. The contribution from the two carotenoids wavenumber regions of 1155 and 1515 cm-1 were more than 84.2%. The results show that the plasma carotenoids could be a potential biomarker for screening esophageal cancer using resonance Raman spectroscopy combined with wavenumber selection and PC-LDA algorithms.

Micro-FTIR combined with curve fitting method to study cellulose crystallinity of developing cotton fibers.

This study aimed to use micro-FTIR with transmission mode to investigate cellulose crystallinity of developing cotton fibers. Compared with ATR-FTIR method, we found that micro-FTIR can obtain more information of cellulose inside of the developing cotton fibers, especially in high wavenumber of 2800-3000 cm-1 region. Combined with curve fitting method, a new IR crystallinity index (CI) method named wax crystallinity index (WCI) was introduced to evaluate the cellulose crystallinity in the development of cotton fibers based on the peak and area ratios of 2900 cm-1/2850 cm-1 and 2900 cm-1/2920 cm-1. The obtained WCI values demonstrated an excellent coefficient of determination with X-ray diffraction (XRD) CI method with the value up to 0.99. This study suggested that micro-FTIR was an effective technique to qualitatively analyze the crystallinity in developing cotton fibers combined with curve fitting method.

Effects of Transition Metal Substituents on Interfacial and Electronic Structure of CH3NH3PbI3/TiO2 Interface: A First-Principles Comparative Study.

To evaluate the influence of transition metal substituents on the characteristics of CH3NH3PbI3/TiO2, we investigated the geometrical and electronic properties of transition metal-substituted CH3NH3PbI3/TiO2 by first-principles calculations. The results suggested that the substitution of Ti4+ at the five-fold coordinated (Ti5c) sites by transition metals is energetically favored. The substituted interface has enhanced visible light sensitivity and photoelectrocatalytic activity by reducing the transition energies. The transition metal substitution can effectively tune the band gap of the interface, which significantly improves the photo-reactivity. The substituted systems are expected to be more efficient in separating the photo-generated electrons-holes and active in the visible spectrum.

The First Case of Ischemia-Free Kidney Transplantation in Humans.

Background: Ischemia-reperfusion injury (IRI) has been considered an inevitable event in organ transplantation since the first successful kidney transplant was performed in 1954. To avoid IRI, we have established a novel procedure called ischemia-free organ transplantation. Here, we describe the first case of ischemia-free kidney transplantation (IFKT). Materials and Methods: The kidney graft was donated by a 19-year-old brain-dead donor. The recipient was a 47-year-old man with end-stage diabetic nephropathy. The graft was procured, preserved, and implanted without cessation of blood supply using normothermic machine perfusion. Results: The graft appearance, perfusion flow, and urine production suggested that the kidney was functioning well-during the whole procedure. The creatinine dropped rapidly to normal range within 3 days post-transplantation. The levels of serum renal injury markers were low post-transplantation. No rejection or vascular or infectious complications occurred. The patient had an uneventful recovery. Conclusion: This paper marks the first case of IFKT in humans. This innovation may offer a unique solution to optimizing transplant outcomes in kidney transplantation.

Reduced combustion mechanism for C1-C4 hydrocarbons and its application in computational fluid dynamics flare modeling.

Emissions from flares constitute unburned hydrocarbons, carbon monoxide (CO), soot, and other partially burned and altered hydrocarbons along with carbon dioxide (CO2) and water. Soot or visible smoke is of particular concern for flare operators/regulatory agencies. The goal of the study is to develop a computational fluid dynamics (CFD) model capable of predicting flare combustion efficiency (CE) and soot emission. Since detailed combustion mechanisms are too complicated for (CFD) application, a 50-species reduced mechanism, LU 3.0.1, was developed. LU 3.0.1 is capable of handling C4 hydrocarbons and soot precursor species (C2H2, C2H4, C6H6). The new reduced mechanism LU 3.0.1 was first validated against experimental performance indicators: laminar flame speed, adiabatic flame temperature, and ignition delay. Further, CFD simulations using LU 3.0.1 were run to predict soot emission and CE of air-assisted flare tests conducted in 2010 in Tulsa, Oklahoma, using ANSYS Fluent software. Results of non-premixed probability density function (PDF) model and eddy dissipation concept (EDC) model are discussed. It is also noteworthy that when used in conjunction with the EDC turbulence-chemistry model, LU 3.0.1 can reasonably predict volatile organic compound (VOC) emissions as well. IMPLICATIONS: A reduced combustion mechanism containing 50 C1-C4 species and soot precursors has been developed and validated against experimental data. The combustion mechanism is then employed in the computational fluid dynamics (CFD) of modeling of soot emission and combustion efficiency (CE) of controlled flares for which experimental soot and CE data are available. The validated CFD modeling tools are useful for oil, gas, and chemical industries to comply with U.S. Environmental Protection Agency's (EPA) mandate to achieve smokeless flaring with a high CE.

Computational fluid dynamics modeling of laboratory flames and an industrial flare.

A computational fluid dynamics (CFD) methodology for simulating the combustion process has been validated with experimental results. Three different types of experimental setups were used to validate the CFD model. These setups include an industrial-scale flare setups and two lab-scale flames. The CFD study also involved three different fuels: C3H6/CH/Air/N2, C2H4/O2/Ar and CH4/Air. In the first setup, flare efficiency data from the Texas Commission on Environmental Quality (TCEQ) 2010 field tests were used to validate the CFD model. In the second setup, a McKenna burner with flat flames was simulated. Temperature and mass fractions of important species were compared with the experimental data. Finally, results of an experimental study done at Sandia National Laboratories to generate a lifted jet flame were used for the purpose of validation. The reduced 50 species mechanism, LU 1.1, the realizable k-epsilon turbulence model, and the EDC turbulence-chemistry interaction model were usedfor this work. Flare efficiency, axial profiles of temperature, and mass fractions of various intermediate species obtained in the simulation were compared with experimental data and a good agreement between the profiles was clearly observed. In particular the simulation match with the TCEQ 2010 flare tests has been significantly improved (within 5% of the data) compared to the results reported by Singh et al. in 2012. Validation of the speciated flat flame data supports the view that flares can be a primary source offormaldehyde emission.

Spectroscopic and quantum mechanical study of three novel azo-materials containing indole and sulfonyl based chromophores.

In this essay, three novel nonlinear optical (NLO) azo-materials containing indole and sulfonyl based chromophores were studied in-depth by using Fourier transform (FT) IR, FT-Raman spectra and density functional theory (DFT). The scaled theoretical results were shown to be in good agreement with the experimental data. In addition, the computed (1)H nuclear magnetic resonance (NMR) and UV-vis absorption wavelengths were also discussed compared with experimental data. The large ß values calculated by the DFT methods showed that the studied molecules were good NLO materials, and the molecule which owned a larger substituent group on the indole chromophore moieties had a larger value. Furthermore, simultaneous infrared and Raman activity suggested that intramolecular charges might transfer through the conjugated framework from the electronic donor group to electronic acceptor group. The HOMO-LUMO gap analysis and molecular electrostatic potential (MEP) maps also supported this viewpoint.

Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface.

Natural killer (NK) cells accumulate at the maternal-fetal interface in large numbers, but their exact roles in successful pregnancy remain poorly defined. Here, we provide evidence that T(H)17 cells and local inflammation can occur at the maternal-fetal interface during natural allogenic pregnancies. We found that decidual NK cells promote immune tolerance and successful pregnancy by dampening inflammatory T(H)17 cells via IFN-γ secreted by the CD56(bright)CD27(+) NK subset. This NK-cell-mediated regulatory response is lost in patients who experience recurrent spontaneous abortions, which results in a prominent T(H)17 response and extensive local inflammation. This local inflammatory response further affects the regulatory function of NK cells, leading to the eventual loss of maternal-fetal tolerance. Thus, our data identify NK cells as key regulatory cells at the maternal-fetal interface by suppressing T(H)17-mediated local inflammation.

Activated mouse CD4(+)Foxp3(-) T cells facilitate melanoma metastasis via Qa-1-dependent suppression of NK-cell cytotoxicity.

The regulatory activities of mouse CD4(+)Foxp3(+) T cells on various immune cells, including NK cells, have been well documented. Under some conditions, conventional CD4(+)Foxp3(-) T cells in the periphery are able to acquire inhibitory function on other T cells, but their roles in controlling innate immune cells are poorly defined. As a potential cellular therapy for cancer, ex vivo activated CD4(+)Foxp3(-) effector T cells are often infused back in vivo to suppress tumor growth and metastasis. Whether such activated T cells could affect NK-cell control of tumorigenesis is unclear. In the present study, we found that mitogen-activated CD4(+)Foxp3(-) T cells exhibited potent suppressor function on NK-cell proliferation and cytotoxicity in vitro, and notably facilitated B16 melanoma metastasis in vivo. Suppression of NK cells by activated CD4(+)Foxp3(-) T cells is cell-cell contact dependent and is mediated by Qa-1:NKG2A interaction, as administration of antibodies blocking either Qa-1 or NKG2A could completely reverse this suppression, and significantly inhibited otherwise facilitated melanoma metastasis. Moreover, activated CD4(+)Foxp3(-) cells from Qa-1 knockout mice completely lost the suppressor activity on NK cells, and failed to facilitate melanoma metastasis when transferred in vivo. Taken together, our findings indicate that innate anti-tumor response is counter regulated by the activation of adaptive immunity, a phenomenon we term as "activation-induced inhibition". Thus, the regulatory role of activated CD4(+)Foxp3(-) T cells in NK-cell activity must be taken into consideration in the future design of cancer therapies.

Novel dynamic flux chamber for measuring air-surface exchange of Hg(o) from soils.

Quantifying the air-surface exchange of Hg(o) from soils is critical to understanding the cycling of mercury in different environmental compartments. Dynamic flux chambers (DFCs) have been widely employed for Hg(o) flux measurement over soils. However, DFCs of different sizes, shapes, and sampling flow rates yield distinct measured fluxes for a soil substrate under identical environmental conditions. In this study, we performed an integrated modeling, laboratory and field study to design a DFC capable of producing a steady and uniform air flow over a flat surface. The new DFC was fabricated using polycarbonate sheets. The internal velocity field was experimentally verified against model predictions using both theoretical and computational fluid dynamics techniques, suggesting fully developed flow with velocity profiles in excellent agreement with model results. Laboratory flux measurements demonstrated that the new design improves data reproducibility as compared to a conventional DFC, and reproduces the model-predicted flux trend with increasing sampling flow. A mathematical relationship between the sampling flow rate and surface friction velocity, a variable commonly parametrized in atmospheric models, was developed for field application. For the first time, the internal shear property of a DFC can be precisely controlled using the sampling flow rate, and the flux under atmospheric condition can be inferred from the measured flux and surface shear property. The demonstrated methodology potentially bridges the gap in measured fluxes obtained by the DFC method and the micrometeorological methods.

Vibrational spectral investigation of four second order nonlinear optical azobenzene-containing materials: a combination of experimental and density functional theoretical (DFT) study.

In this work, four-second order nonlinear optical (NLO) azobenzene-containing materials are studied in-depth by using vibrational spectra and density functional theory (DFT). The Fourier transform infrared (FT-IR) spectra and FT-Raman spectra are recorded in the range of 50-4000 and 100-3600cm(-1), respectively. Meanwhile, the DFT computations are performed at B3LYP/6-31G (d, p) level to derive equilibrium geometry, vibrational wavenumbers and intensities, and first hyperpolarizability, and the scaled theoretical wavenumbers are also shown to be in good agreement with experimental data. The calculated results show that these four azobenzene-containing compounds are good materials and the compound with nitro substituent groups possesses a larger first molecular hyperpolarizability (ß) value. Moreover, the simultaneous infrared and Raman activation of R1 group and CC stretching suggest that the charge transfer interaction might occur between the R1 group and phenyl ring, and the HOMO-LUMO gap analysis also supports this viewpoint.

Blood loss during extensive escharectomy and auto-microskin grafting in adult male major burn patients.

PURPOSE: To improve the accuracy of blood loss estimation during extensive escharectomy and auto-microskin grafting on extremities in adult male major burn patients. METHOD: All adult male major burn patients admitted to our center who underwent extensive escharectomy and auto-microskin graft on extremities for more than 10% TBSA during the period 1 January 2008 to 31 December 2009 were involved in this study. The blood loss during the operation was estimated by the surgeons or calculated according to the changes in hemoglobin levels. RESULTS: The average burn and escharectomy areas for the 64 burn patients included in the study were 74.16 ± 16.96% and 30.27 ± 15.63% TBSA respectively. The auto-microskin donor area was 3.81% TBSA. The volumes of intra-operative calculated and estimated blood losses and transfused blood during the operation were 0.47 ml/cm2, 0.13 ml/cm2 and 0.20 ml/cm2 surgical area 77.29 ml, 20.51 ml and 32.83 ml per 1% TBSA), respectively. Within two weeks after injury surgical blood loss appeared to be greater the later the operation was carried out. Within the first week after injury the mean proportional blood loss was increased with area excised. CONCLUSION: In this study the average calculated blood loss for the operation of extensive escharectomy and microskin graft in adult male major burn patient was 0.47 ml/cm2 (77.29 ml per 1% TBSA). This result will help us to predict expected blood loss more accurately.

Promotion of cutaneous wound healing by local application of mesenchymal stem cells derived from human umbilical cord blood.

This study aimed to determine whether mesenchymal stem cells (MSCs) derived from umbilical cord blood (UCB) would promote cutaneous wound healing. MSCs from human UCB were isolated and identified. The characteristics of the isolated MSCs' growth and proliferation were assayed in vitro. The MSCs labeled with 5-bromodeoxyuridine (BrdU) were applied on fresh cutaneous mice wounds. The healing rates were surveyed. The distribution and the differentiation into keratinocytes of the labeled MSCs in the wound tissue were checked by immunohistochemistry staining. The isolated MSCs could grow and proliferate well in vitro. The isolated MSCs from UCB could be labeled by 5-bromodeoxyuridine successfully. The MSCs derived from UCB could enhance the healing of mice skin defect wounds, and it was found that the implanted MSCs could differentiate into keratinocyte in the wound tissue. It was demonstrated that MSCs from UCB can be isolated and proliferated successfully. The local administration of MSCs derived from UCB improves skin defect wound healing in mice.

Cross-immune tolerance: conception and its potential significance on transplantation tolerance.

The diversity of alloreactive T cells in graft rejection and the presence of extensive crossreactivity among alloreactive T cells indicate that the induction of transplantation tolerance may fundamentally alter the size of host T-cell repertoire involved in protective immunity and immune surveillance, especially those that are crossreactive to conventional antigens. We herein highlight the crossreactive nature of alloreactive T cells and the potential risks of altered T-cell repertoire associated with the induction of transplantation tolerance. The possibility that T-cell tolerance to one set of antigens results in their tolerance to other unrelated antigens due to T-cell crossreactivity and/or heterogeneity is defined as 'cross-immune tolerance'. The definition and significance of this concept were discussed in details.

Inhalation injury in southwest China--the evolution of care.

AIM: This study aims to review the changes in management of inhalation injury and the associated reduction in mortality over the past 2 decades. METHODS: The records of burn patients with inhalation injury hospitalised in our institute from 1986 to 2005 were retrospectively analysed. The incidence of inhalation injury and the associated mortality were analysed. Meanwhile, the relationship of inhalation injury with age, total burn area, tracheostomy intubation and mechanical ventilation were studied. RESULTS: The incidence of inhalation injury was 8.01% in the total 10 608 hospitalised burn patients during the 20 years surveyed. Inhalation injury was always associated with large-sized burn and was more common in adults. The incidence of tracheostomy and mechanical ventilation increased from 39.46 and 30.28% in the period from 1986 to 1995 to 70.12 and 39.74% from 1996 to 2005, respectively. The overall mortality of inhalation-injured burn patients was 15.88% compared with 0.82% of the non-inhalation group. The mortality of the burn patients with inhalation injury dropped from 25.29% during the first 10 years to 11.71% during the second decade (p<0.01). Mortality secondary to inhalation injury as the lead cause decreased from 14.56 to 6.29% (p<0.01). CONCLUSION: The care of inhalation injury has made significant progress over the past 2 decades. The early diagnosis of inhalation injury, early airway control and pulmonary function assistance with mechanical ventilation contribute to the reduction of mortality.

Rapamycin prevents concanavalin A-induced liver injury by inhibiting lymphocyte activation.

BACKGROUND AND AIMS: Liver injury induced by concanavalin A (Con A) is often used as a model to study the pathophysiology of immune mediated liver injury. Rapamycin (Rapa) is an effective immunosuppressant widely used for preventing immune activation and transplant rejection. However, the effect of Rapa on liver injury caused by Con A has not been carefully examined. In the present study, we examined the effect of Rapa on liver injury caused by Con A. METHODS: Mice received intraperitoneal Rapa injection before Con A intravenous administration. The liver injury was examined by measuring serum transaminase and pathology, and the level of cytokines was detected by enzyme linked immunosorbent assay (ELISA). RESULTS: In the present study, we examined the effect of Rapa on liver injury after Con A injection in mice. We found that the treatment of mice with Rapa protected the liver from Con A-induced injury. Pretreatment with Rapa dramatically ameliorated Con A-induced mortality. This protection was associated with reduced transaminase levels in the blood and further confirmed by liver histology. ELISA showed that Rapa suppressed pro-inflammatory cytokines IFN-gamma and TNF-alpha production as compared with the untreated controls. Furthermore, intrahepatic lymphocyte proliferation was significantly inhibited. CONCLUSION: These findings suggested that Rapa has the therapeutic potential for treatment of immune-mediated liver injury in the clinic.