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Purpose This study aimed to explore the impact of ABL1-tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosomepositive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients' prognosis from TKIs intake practices. Materials and Methods Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. Results Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged = 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. Conclusion TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age = 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age = 10 years, which may result in an inferior achievement of relevant treatment milestones. [ABSTRACT FROM AUTHOR]

IL-22 induces IL-18 expression by intestinal epithelial cells. Authors show here that IL-18 is a key barrier maintenance factor during adherent-invasive E. coli invasion, inducing expression of anti-microbial genes in Paneth cells via Stat3, prompting IFNγ expression in T cells and triggering intestinal Lgr5+ stem cell expansion via Tcf4.

This study presents a deep learning-based speech signal-processing mobile application known as CITISEN. The CITISEN can perform three functions: speech enhancement (SE), model adaptation (MA), and background noise conversion (BNC), which allow CITISEN to be used as a platform for utilizing and evaluating SE models and flexibly extend the models to address various noise environments and users. For SE, CITISEN downloads pretrained SE models on the cloud server and then uses these models to effectively reduce noise components from prerecordings or instant recordings provided by users. When it encounters noisy speech signals with unknown speakers or noise types, the MA function allows CITISEN to improve the SE performance effectively. A few audio files of unseen speakers or noise types are recorded and uploaded to the cloud server and then used to adapt the pretrained SE model. Finally, for BNC, CITISEN removes the original background noise using an SE model and then mixes the processed speech signal with new background noise. The novel BNC function can evaluate SE performance under specific conditions, cover people’s tracks, and provide entertainment. The experimental results confirmed the effectiveness of SE, MA, and BNC functions. Compared with the noisy speech signals, the enhanced speech signals by SE achieved about 6% and 33% of improvements, respectively, in terms of short-time objective intelligibility (STOI) and perceptual evaluation of speech quality (PESQ). With MA, the STOI and PESQ could be further improved by approximately 6% and 11%, respectively. Note that the SE model and MA method are not limited to the ones described in this study and can be replaced with any SE model and MA method. Finally, the BNC experiment results indicated that the speech signals of original and converted backgrounds have a close scene identification accuracy and similar embeddings in an acoustic scene classification model. Therefore, the proposed BNC can effectively convert the background noise of a speech signal and be a data augmentation method when clean speech signals are unavailable.

Abstract Parahydrogen-induced polarization of 13C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-13C]acetate and [1-13C]pyruvate esters with application of PH-INEPT-type pulse sequences for 1H to 13C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). The pulse-sequence transfer approach may have its merits in some applications because the entire hyperpolarization procedure is implemented directly in an NMR or MRI instrument, whereas MFC requires a controlled field variation at low magnetic fields. Optimization of the PH-INEPT-type transfer sequences resulted in 13C polarization values of 0.66 ± 0.04% and 0.19 ± 0.02% for allyl [1-13C]pyruvate and ethyl [1-13C]acetate, respectively, which is lower than the corresponding polarization levels obtained with MFC for 1H to 13C polarization transfer (3.95 ± 0.05% and 0.65 ± 0.05% for allyl [1-13C]pyruvate and ethyl [1-13C]acetate, respectively). Nevertheless, a significant 13C NMR signal enhancement with respect to thermal polarization allowed us to perform 13C MR imaging of both biologically relevant hyperpolarized molecules which can be used to produce useful contrast agents for the in vivo imaging applications.

Abstract Oligodendrocytes (OLs), myelin-producing glia in the central nervous system (CNS), produce a myelin extension that enwraps axons to facilitate action potential propagation. An effective approach to induce oligodendrogenesis and myelination is important to foster CNS development and promote myelin repair in neurological diseases. Hericium (H.) erinaceus, an edible and culinary-medicinal mushroom, has been characterized as having neuroprotective activities. However, its effect on OL differentiation has not yet been uncovered. In this study using oligodendrocyte precursor cell (OPC) cultures and an ex vivo cerebellar slice system, we found that the extract from H. erinaceus mycelium (HEM) not only promoted the differentiation of OPCs to OLs in the differentiation medium, but also increased the level of myelin basic protein (MBP) on neuronal fibers. Moreover, daily oral administration of HEM into neonatal rat pups for 7 days enhanced MBP expression and OLs in the corpus callosum of the postnatal rat brain. The effect of HEM-derived bioactive compounds, the diterpenoid xylosides erinacine A (HeA) and HeC and a sesterterpene with 5 isoprene units called HeS, were further evaluated. The results showed that HeA and HeS more potently stimulated MBP expression in OLs and increased the number of OLs. Moreover, overlap between MBP immunoreactivity and neuronal fibers in cultured cerebellar tissue slices was significantly increased in the presence of HeA and HeS. In summary, our findings indicate that HEM extract and its ingredients HeA and HeS display promising functional effects and promote OL maturation, providing insights into their potential for myelination in neurodevelopmental disorders.

Background/purpose: Treatment of chronic hepatitis C (CHC) has entered a new era since the introduction of direct-acting antiviral agents (DAAs). Numerous clinical trials have shown that treatment response as well as tolerability of DAAs are superior to those of conventional therapy with pegylated interferon and ribavirin. However, the results of clinical trials may not be directly applied to real-world practice. Therefore our study tried to investigate the effectiveness of various DAA regimens in Taiwanese patients with chronic hepatitis C. Methods: We performed a retrospective study on 400 CHC patients. The primary endpoint was undetectable HCV RNA (an HCV RNA level of

Abstract Background Pneumococcus is one of the most common human airway pathogens that causes life-threatening infections. Ambient fine particulate matter (PM) with aerodynamic diameter ≤ 2.5 μm (PM2.5) is known to significantly contribute to respiratory diseases. PM2.5-induced airway inflammation may decrease innate immune defenses against bacterial infection. However, there is currently limited information available regarding the effect of PM2.5 exposure on molecular interactions between pneumococcus and macrophages. Results PM2.5 exposure hampered macrophage functions, including phagocytosis and proinflammatory cytokine production, in response to pneumococcal infection. In a PM2.5-exposed pneumococcus-infected mouse model, PM2.5 subverted the pulmonary immune response and caused leukocyte infiltration. Further, PM2.5 exposure suppressed the levels of CXCL10 and its receptor, CXCR3, by inhibiting the PI3K/Akt and MAPK pathways. Conclusions The effect of PM2.5 exposure on macrophage activity enhances pneumococcal infectivity and aggravates pulmonary pathogenesis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Objectives: This study investigated how different concentrations of doxorubicin (DOX) can affect the function of cardiac cells. This study also examined whether activation of prokineticin receptor (PKR)-1 by a nonpeptide agonist, IS20, prevents DOX-induced cardiovascular toxicity in mouse models. Background: High prevalence of heart failure during and following cancer treatments remains a subject of intense research and therapeutic interest. Methods: This study used cultured cardiomyocytes, endothelial cells (ECs), and epicardium-derived progenitor cells (EDPCs) for in vitro assays, tumor-bearing models, and acute and chronic toxicity mouse models for in vivo assays. Results: Brief exposure to cardiomyocytes with high-dose DOX increased the accumulation of reactive oxygen species (ROS) by inhibiting a detoxification mechanism via stabilization of cytoplasmic nuclear factor, erythroid 2. Prolonged exposure to medium-dose DOX induced apoptosis in cardiomyocytes, ECs, and EDPCs. However, low-dose DOX promoted functional defects without inducing apoptosis in EDPCs and ECs. IS20 alleviated detrimental effects of DOX in cardiac cells by activating the serin threonin protein kinase B (Akt) or mitogen-activated protein kinase pathways. Genetic or pharmacological inactivation of PKR1 subdues these effects of IS20. In a chronic mouse model of DOX cardiotoxicity, IS20 normalized an elevated serum marker of cardiotoxicity and vascular and EDPC deficits, attenuated apoptosis and fibrosis, and improved the survival rate and cardiac function. IS20 did not interfere with the cytotoxicity or antitumor effects of DOX in breast cancer lines or in a mouse model of breast cancer, but it did attenuate the decreases in left ventricular diastolic volume induced by acute DOX treatment. Conclusions: This study identified the molecular and cellular signature of dose-dependent, DOX-mediated cardiotoxicity and provided evidence that PKR-1 is a promising target to combat cardiotoxicity of cancer treatments.

Air pollution in cities is a severe and worrying problem because it causes threats to economic development and health. Furthermore, with the development of industry and technology, rapid population growth, and the massive expansion of cities, the total amount of pollution emissions continue to increase. Hence, observing and predicting the air quality index (AQI), which measures fatal pollutants to humans, has become more and more critical in recent years. However, there are insufficient air quality monitoring stations for AQI observation because the construction and maintenance costs are too high. In addition, finding an available and suitable place for monitoring stations in cities with high population density is difficult. This study proposes a spatial-temporal model to predict the long-term AQI in a city without monitoring stations. Our model calculates the spatial-temporal correlation between station and region using an attention mechanism and leverages the distance information between all existing monitoring stations and target regions to enhance the effectiveness of the attention structure. Furthermore, we design a hybrid predictor that can effectively combine the time-dependent and time-independent predictors using the dynamic weighted sum. Finally, the experimental results show that the proposed model outperforms all the baseline models. In addition, the ablation study confirms the effectiveness of the proposed structures.

Objectives The purpose of this study was to estimate the ability of antimalarial medications to induce local infiltration analgesia. Methods Using a rat model of skin infiltration anaesthesia, the effects of antimalarial medications (primaquine, chloroquine, hydroxychloroquine and amodiaquine) were compared with the application of lidocaine. Key findings At a dose of 3 μmol, primaquine and chloroquine displayed better potency (all P < 0.05) and greater duration (all P < 0.01) of cutaneous analgesia than lidocaine, whereas the other antimalarial medications showed a similar potency and duration of cutaneous analgesia when compared with lidocaine. When a dose of 3 μmol antimalarial medication was used, primaquine was the most potent and had the longest duration of action among four antimalarial medications. The relative potency ranking (ED50, 50% effective dose) has been found to be primaquine [2.10 (1.87 - 2.37) μmol] > lidocaine [6.27 (5.32 -7.39) μmol] (P < 0.01). Infiltration analgesia of skin with primaquine had a greater duration of action than did lidocaine on the equipotent (ED25, ED50, ED75) basis (P < 0.01). Conclusions Primaquine and chloroquine have greater potency and longer lasting skin analgesia when compared with lidocaine, while the other antimalarials display a similar potency in comparison with lidocaine. [ABSTRACT FROM AUTHOR]

To alleviate the impact of fake news on our society, predicting the popularity of fake news posts on social media is a crucial problem worthy of study. However, most related studies on fake news emphasize detection only. In this paper, we focus on the issue of fake news influence prediction, i.e., inferring how popular a fake news post might become on social platforms. To achieve our goal, we propose a comprehensive framework, MUFFLE, which captures multi-modal dynamics by encoding the representation of news-related social networks, user characteristics, and content in text. The attention mechanism developed in the model can provide explainability for social or psychological analysis. To examine the effectiveness of MUFFLE, we conducted extensive experiments on real-world datasets. The experimental results show that our proposed method outperforms both state-of-the-art methods of popularity prediction and machine-based baselines in top-k NDCG and hit rate. Through the experiments, we also analyze the feature importance for predicting fake news influence via the explainability provided by MUFFLE.

Metabolite identification, in the early stage, for compound discovery is necessary to assess the knowledge for the pharmaceutical improvement of drug safety and efficacy. Even if the drug has been released into the market, identification and continuous evaluation of the metabolites are required to avoid the risk of post-marketing withdrawal. Hericium erinaceus (HE), a medicinal mushroom, has broadly documented nutraceutical benefits, including anti-oxidant, anti-tumor, anti-aging, hypolipidemic, and gastric mucosal protection effects. Recently, erinacine A has been reported as the main natural bioactive compound in the mycelium of HE for functional food development. In neurological studies, the consumption of enrinacine A enriched HE mycelium demonstrates its significant nutraceutical effects in Alzheimer’s disease, Parkinson’s disease, and ischemic stroke. For the first time, we explored the metabolic process of erinacine A molecule and identified its metabolites from the rat and human liver S9 fraction. Using a liquid chromatography/triple quadrupole mass spectrometer for quantitative analysis, we observed that 75.44% of erinacine A was metabolized within 60 min in rat, and 32.34% of erinacine A was metabolized within 120 min in human S9. Using an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) to identify the metabolites of erinacine A, five common metabolites were identified, and their possible structures were evaluated. Understanding the metabolic process of erinacine A and establishing its metabolite profile database will help promote the nutraceutical application and discovery of related biomarkers in the future.

A series of PtRu/carbon black catalysts were prepared by means of deposition-precipitation and reduced by various reducing agents. NaBH4, HCHO and NaH2PO2, respectively, were used as the reduction agents. Some of the samples were reduced by various amounts of NaH2PO2 to investigate the effects of P/Pt ratios on the characteristics and activity of the catalyst. These catalysts were characterized by X-ray diffraction and transmission electron microscopy. The components of these catalysts were detected by X-ray fluorescence, X-ray photoelectron microscopy, and extended X-ray absorption of fine structures (EXAFS). The methanol oxidation ability of the catalysts was tested by cyclic voltammetry measurement. The results show that NaH2PO2 could effectively reduce the particle size of PtRu metal. It can suppress the growth of metal particles. In addition, the P/Pt ratio is crucial. The catalyst reduced by NaH2PO2 with a P/Pt ratio of 1.2 had the highest activity among all catalysts. It had the higher Pt and Ru metal contents and smaller metal particle size than the other catalysts. Its activity was 253.12 A/g, which is higher that than the commercial catalyst (Johnson Matthey H10100, 251.32 A/g).

Recurrent primary spontaneous pneumothorax (PSP) is a troublesome problem and a major concern for the patients. This study examined whether nuclear factor erythroid 2-related factor 2 (Nrf2) expression in alveolar type I pneumocytes was associated with the clinical manifestations of PSP patients including disease recurrence. Eighty-eight PSP patients who were managed with needlescopic video-assisted thoracoscopic surgery (NVATS) were included in this study. Immunohistochemistry (IHC) was assessed to determine Nrf2 expression in resected lung tissues and the results were correlated with clinicopathological characteristics by the chi-square or the Fisher's exact test. The prognostic value of Nrf2 for overall recurrence was evaluated by univariate and multivariable Cox regression model. The expression of Nrf2 was observed in type I pneumocytes of lung tissues from PSP patients by IHC. We found that low Nrf2 expression in PSP patients, especially in young (age ≤ 20, p = 0.033) and body mass index (BMI) ≥18 kg/m2 (p = 0.019) groups, was significantly correlated with PSP recurrence. In the univariate and multivariate analyses, high Nrf2 expression was a significant protective factor for overall recurrence in PSP patients (univariate: p = 0.026; multivariate: p = 0.004). The expression level of Nrf2 in alveolar type I pneumocytes was a potential factor involved in PSP recurrence. Our findings suggest that elevated Nrf2 expression in PSP patients may be a promising way for reducing PSP recurrence.

Nano-gold catalyst has been reported to have high activity and selectivity for liquid phase hydrogenation reaction. In this study, gold-containing bimetals were loaded on TiO2. For bimetallic catalysts, gold and different metals were prepared by the deposition-precipitation method, and then used NaBH4 to reduce metal cations. The catalysts were characterized by X-ray diffraction, transmission electron microscopy, high resolution transmission electron microscopy, and X-ray photoelectron spectroscopy. The catalytic properties of these catalysts were tested by hydrogenation of p-chloronitrobenzene (p-CNB) in a batch reactor at 1.1 MPa H2 pressure, 373 K and 500 rpm. Cu, Ag, Ru, and Pd formed nano-alloy with Au. In addition, Cu–Au, Ag–Au, and Ru–Au alloy had Cu-, Ag-, and Ru-enriched surface, respectively. Instead, Pd–Au alloy had Pd-enriched surface. There are two kinds of alloy effects: (1) geometric effects, i.e., the surface-enriched metal would change the distance of Au–Au atoms that is required for facilitating the hydrogenation of chloronitrobenzene; and (2) electronic effects, which involve charge transfer between the metals. The activity decreased in the following order: PdAu/TiO2 > Au/TiO2 > NiAu/TiO2 > AgAu/TiO2 > RuAu/TiO2 > CuAu/TiO2. Comparing with other metals, adding Pd in Au showed a higher activity. Adding palladium could reduce gold-valence state, and increased active sites for reaction.

Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is still a troublesome complication for most patients. This study intended to determine the role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in type II pneumocytes of patients with PSP and its relation with recurrence. Ninety-one patients who had undergone needlescopic video-assisted thoracoscopic surgery wedge resection of lung with identifiable blebs for PSP were included in this study. Immunohistochemical (IHC) staining was used to measure the expression of MMP-2 and MMP-9 in lung tissues of PSP patients. The results were further correlated with clinicopathological parameters and recurrence rates using chi-square or Fisher's exact test. The value of MMP-2 and MMP-9 for overall recurrence was analyzed by univariate and multivariable Cox regression model. IHC data revealed that MMP-2 and MMP-9 staining was predominantly observed in type II pneumocytes of patients with PSP. We found that MMP-2 and MMP-9 expression in PSP, especially male PSP patients, was significantly correlated with recurrence. In the univariate and multivariate analyses, MMP-2 and MMP-9 were statistically significant risk factors for overall recurrence in PSP patients. Therefore, high expression levels of MMP-2 and MMP-9 in type II pneumocytes show a positive correlation with PSP recurrence risk. Further studies are needed to validate whether reduction of MMP-2 and MMP-9 expression may be a promising way for decreasing the risk of PSP recurrence in the future.

We conducted a time-lapse monitoring study during a well-pumping test at the Pengtsuo site in Pingtung, Taiwan. Water-level gauges were installed in four wells (P1, W1, O1, and O2) at the Pengtsuo site with different screen depths for the observation. We designed the pumping test to be executed in three phases: the background, the stepwise-pumping, and the continuous-pumping phases. The survey line crossed the four wells so that a comparison would be possible between the resistivity measurements and the water-level records. The resistivity differences relative to the pre-pumping background show that electrical resistivity imaging (ERI) can resolve changes due to dewatering from pumping activity. The time-lapse resistivity images reveal that the maximum resistivity increase took place at the locations in the vadose zone instead of at the groundwater surface. The variation in the resistivity differences in the vadose zone correlated to the change in groundwater level in the stepwise phase. On the other hand, the resistivity-difference change was not fully consistent with the groundwater-level change in the continuous-pumping phase. We attribute the abnormal ERI signals to the dynamic non-equilibrium of the water movement in the vadose zone. The findings suggest that pumping designs can affect the changing resistivity differences and water-content distribution patterns. We show the potential of the ER method to reveal both the water flow and water-content changes in the vadose zone with different transient boundary conditions.

Tc-99m phytate hepatic scintigraphy remains the standard method for evaluating the functional features of Kupffer cells. In this study, we demonstrate the variable uptake feature of focal nodular hyperplasia (FNH) in Tc-99m phytate scintigraphy. We reviewed all patients who underwent Tc-99m phytate hepatic scintigraphy between 2008 and 2012 in Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Cases with FNH were diagnosed on the basis of pathology or at least one or more prior imaging with a periodic clinical follow-up. All patients received a standard protocol of dynamic flow study and planar and Tc-99m phytate single-photon emission computed tomography (E. CAM; Siemens). The correlation of variable nodular radioactivity with parameters such as tumor size and localization was analyzed. In total, 15 lesions of 14 patients in the clinic were diagnosed as FNH. The tumor size was approximately 2.9–7.4 cm (mean size 4.6 cm). Four lesions were larger than 5 cm. The major anatomic distribution was in the right hepatic lobe (10 lesions), particularly in the superior segments (7 lesions). Tc-99m phytate single-photon emission computed tomography imaging for determining the functional features of Kupffer cells included cool/cold (8 lesions), isoradioactive/warm (6 lesions), and hot (1 lesion) patterns of uptake. We did not observe any statistically significant correlation between variable nodular radioactivity and tumor size (p=0.68) or localization (p=0.04). Herein, we demonstrate the variable uptake feature of FNH in Tc-99m phytate scintigraphy. In small FNH tumors (< 5 cm), increased or equal uptake still provided specificity for the differential diagnosis of hepatic solid tumors.

Super scan pattern on technetium-99m methyldiphosphonate (Tc-99m MDP) bone scintigraphy is a special condition of extremely high bone uptake relative to soft tissue with absent or faint renal radioactivity visualization, which is usually seen in diffuse bone metastases or discrete endocrine entities. Here, two cases with super bone scan are presented. One was a young man diagnosed with gastric cancer. The other was a middle-aged woman with a history of breast cancer with recent recurrence. Both cases had 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) diagnosis simultaneously. Based on imaging of 18F-FDG PET/CT, diffusely incremental 18F-FDG avidity in spine/pelvis on PET and subtle erosion of cortical bone on CT were seen. The cytological results of bone marrow biopsy showed evidence of malignant metastasis. However, there were several focal discrepant findings between the 18F-FDG PET/CT and Tc-99m MDP bone scan. According to integration of both imaging findings and the result of bone marrow biopsy, we believe that the disseminated malignant spread in bone marrow is a primitive alternation in the super bone scan and that it is also as a result of neoplasm-related endocrine factors.

We have reported the propensity of a DNA sequence containing CCG repeats to form a stable i-motif tetraplex structure in the absence of ligands. Here we show that an i-motif DNA sequence may transition to a base-extruded duplex structure with a GGCC tetranucleotide tract when bound to the (CoII)-mediated dimer of chromomycin A3, CoII(Chro)2. Biophysical experiments reveal that CCG trinucleotide repeats provide favorable binding sites for CoII(Chro)2. In addition, water hydration and divalent metal ion (CoII) interactions also play a crucial role in the stabilization of CCG trinucleotide repeats (TNRs). Our data furnish useful structural information for the design of novel therapeutic strategies to treat neurological diseases caused by repeat expansions.

Intrathoracic tumor is a rare entity in the pediatric population and neurogenic tumors account for 40-50% of childhood intrathoracic tumors. They can cause severe symptoms, such as respiratory distress, neurological dysfunction and metabolic disturbances. Posterior mediastinal ganglioneuroma (GN) usually occurs in children and can be found accidentally. Precise preoperative diagnosis is very difficult and has a great influence on surgical intervention. Here, we report a 6-year-old girl with a posterior mediastinal GN that was found incidentally on chest radiography. Computed tomography and magnetic resonance imaging demonstrated a right paraspinal tumor with punctuate calcification and intraspinal extension. 18F-fluorodeoxyglucose positron emission tomography revealed low-grade fluorodeoxyglucose avidity of this tumor. Computed tomography and magnetic resonance imaging can characterize GN and positron emission tomography is helpful for differentiating benign or malignant lesions.

This article is available on the website of the old publisher Franco Angeli ( http://www.francoangeli.it/riviste/sommario.asp?IDRivista=152 )

Sentinel lymph node (SLN) biopsy is an alternative to axillary node dissection for staging breast cancer treatment. In this article, we investigated nodal drainage patterns and tumor location using lymphoscintigraphy to predict the axillary sentinel lymph node status. We enrolled 88 patients with clinically suspicious or biopsy-proven breast cancer from March 2001 to October 2002. The average age of subjects was 48 ± 4 years and the clinical stage was T1-2N0Mx. Tc-99m sulfur colloid was used in a hybrid combination of subdermal and perilesional injections around the selected corners of the tumor or biopsy site. Sentinel lymphoscintigraphy was performed 16-20 hours before surgery. Sentinel nodes were marked on the skin. An intraoperative gamma probe was used to confirm the sentinel lymph node location before biopsy. Most primary tumors were in the outer upper quadrant (52.3%), followed by the inner upper quadrant (17.0%), outer inferior quadrant (12.5%), central areolar area (11.4%), and inner inferior quadrant (6.8%). The nodal drainage patterns on 2-hour lymphoscintigraphy were as follows: axillary alone (76.1%), internal mammary nodes alone (1.1%), both axillary and internal mammary nodes (11.4%), and no drainage (11.4%). Internal mammary lymphatic drainage is related to tumor location in the inner quadrants of the breast. About 11.4% of all patients had poorly identified SLNs on lymphoscintigraphy within a 2-hour period, but there was improvement in the overall detection rate up to 95% by intraoperative gamma probe the next day. Preoperative lymphoscintigraphic mapping has value in providing individual lymphatic drainage patterns and tumor location that are important in the interpretation of the results of SLN biopsy during surgery.

The graded shield technique was developed to increase the sentinel node detection rate by improving lymphoscintigraphic image contrast. In a 6-month period, 50 women with clinical suspicion of early stage breast cancer (T1 and T2 tumors) were enrolled in this study. The patients had a mean age of 47.2 ± 10.3 years. A composite graded shield was constructed using three concentric layers of leaded plastic measuring 3 cm, 5 cm, and 7 cm each in diameter. The graded shield was designed with a movable Velcro backing for accurate positioning over the injection site. Images were acquired with a vertical angle dual-head gamma camera using an established injection procedure developed at our institution. The rate of detection of sentinel lymph nodes using lymphoscintigraphic mapping improved from 74% (37/50 patients) to 96% (48/50) using the graded shield (p < 0.05). In addition to the increased detection rate, our technique also increased the number of nodes detected and improved visualization of the adjacent lymphatic basin. By enhancing nodal contrast, we have demonstrated that the graded shield technique is an effective method for improving the rate of sentinel node detection.

Stroke is one of the disorders for which clinically effective therapeutic modalities are most needed, and numerous ways have been explored to attempt to investigate their feasibilities. However, ischemic- or hemorrhagicinduced inflammatory neuron death causes irreversible injuries and infarction regions, and there are currently no truly effective drugs available as therapy. It is therefore urgent to be able to provide a fundamental treatment method to regenerate neuronal brain cells, and therefore, the use of stem cells for curing chronic stroke could be a major breakthrough development. In this review, we describe the features and classification of stroke and focus on the benefits of adipose tissue-derived stem cells and their applications in stroke animal models. The results show that cell-based therapies have resulted in significant improvements in neuronal behaviors and functions through different molecular mechanisms, and no safety problems have so far arisen after transplantation. Further, we propose a clinical possibility to create a homing niche by reducing the degree of invasive intracerebroventricular transplantation and combining it with continuous intravenous administration to achieve a complete cure.

Rheumatoid arthritis (RA) is characterized by chronic inflammatory infiltration of the synovium and elevation of proinflammatory cytokines. Cytosolic phospholipase A2 (cPLA2) is involved in the development of inflammatory diseases. Heme oxygenase-1 (HO-1) has been shown to possess anti-inflammatory properties. The objective of the study was to investigate the detailed mechanisms of TNF-α-induced cPLA2 expression and to determine whether carbon monoxide releasing molecule-2 (CO-RM2) suppresses TNF-α-induced expression of NF-κB-related proinflammatory genes, including cPLA2, via HO-1 induction in RA synovial fibroblasts (RASFs). Here, we reported that TNF-α-induced cPLA2 expression was mediated through TNFR1/PKCα-dependent signaling pathways, including NADPH oxidase (NOX) activation/ROS production and NF-κB activation. CO-RM2 significantly suppressed TNF-α-induced cPLA2 expression by inhibiting the ROS generation and the phosphorylation of NF-κB p65 and IKKα/β, but not the phosphorylation of p38 MAPK and JNK1/2. These results were further confirmed by a ChIP assay to detect the NF-κB DNA-binding activity. Our results demonstrated that induction of HO-1 by CO-RM2 exerted anti-inflammatory and antioxidant effects which were required in concert to prevent the activation of NF-κB leading to induction of various inflammatory genes implicated in the pathogenesis of RA.

Using dictator games in experimental analysis, this lesson report demonstrates the process and results of a postgraduate class project in which university students were instructed to scientifically investigate and explore one of German society’s most hotly-contested issues: the level of discriminatory tendencies of non-Muslims towards Muslims. The results of this class project show little or no discriminatory tendencies toward Muslims. Instead, the university students under our investigation tended to act favorably, or at the very least, fairly toward Muslims. We expect that this lesson report can demonstrate how a postgraduate course can be conducted in an innovative way, empowering students to collect primary data and finishing a small scientific project during the span of a semester. Dieser Bericht stellt die Prozesse und Ergebnisse einer experimentellen Studie eines Postgraduierten-Kurses der Universität Greifswald dar. Wir zeigen, wie Studierende das Thema Migration innovativ untersuchen können, indem sie neben theoretischen Lerninhalten an experimentelle Methoden sowie die Primärforschung herangeführt werden. Anhand eines Diktatorspiels wurden die teilnehmenden Studenten angeleitet, ein in der Öffentlichkeit kontrovers debattiertes Thema wissenschaftlich zu untersuchen: Diskriminierende Tendenzen von Nicht-Muslimen gegenüber Muslimen. Die Ergebnisse dieser Studie lassen jedoch nicht auf diskriminierende Tendenzen der Studenten schließen. Stattdessen deuten sie darauf hin, dass sich die Studierenden zumindest fair gegenüber Muslimen verhalten.

Pain and itch are closely related sensations, yet qualitatively quite distinct. Despite recent advances in brain imaging techniques, identifying the differences between pain and itch signals in the brain cortex is difficult due to continuous temporal and spatial changes in the signals. The high spatial resolution of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) has substantially advanced research of pain and itch, but these are uncomfortable because of expensiveness, importability and the limited operation in the shielded room. Here, we used near infrared spectroscopy (NIRS), which has more conventional usability. NIRS can be used to visualize dynamic changes in oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary networks near activated neural circuits in real-time as well as fMRI. We observed distinct activation patterns in the frontal cortex for acute pain and histamine-induced itch. The prefrontal cortex exhibited a pain-related and itch-related activation pattern of blood flow in each subject. Although it looked as though that activation pattern for pain and itching was different in each subject, further cross correlation analysis of NIRS signals between each channels showed an overall agreement with regard to prefrontal area involvement. As a result, pain-related and itch-related blood flow responses (delayed responses in prefrontal area) were found to be clearly different between pain (τ = +18.7 sec) and itch (τ = +0.63 sec) stimulation. This is the first pilot study to demonstrate the temporal and spatial separation of a pain-induced blood flow and an itch-induced blood flow in human cortex during information processing.