Atmospheric Environment

An integrated sampler for shipboard underway measurement of dimethyl sulfide in surface seawater and air Publication date: 15 July 2019 Source: Atmospheric Environment, Volume 209 Author(s): Miming Zhang, Wei Gao, Jinpei Yan, Yanfang Wu, Christa A. Marandino, Keyhong Park, Liqi Chen, Qi Lin, Guobin Tan, Meijiao Pan Abstract Dimethyl sulfide (DMS), a marine-derived trace gas, can influence atmospheric compositions and has an impact on the global climate. To date, obtaining continuous and coupled shipboard underway measurements of DMS in seawater and air has been challenging. To address this issue, we report a custom-made sampling device based on the purge-and-trap technique. This sampler, in combination with a time-of-flight mass spectrometer (TOF-MS), was successfully utilized to perform coupled shipboard underway measurements of DMS in surface seawater and air around western Antarctica during the 34th Chinese Antarctic Research Expedition from February 2018 to April 2018. The seawater and air streams were continuously introduced into the sampler unit and subsampled every 10 min. The limits of detection (LODs) of DMS in seawater and air were found to be 0.07 nM and 32 pptv, respectively. The variability in the DMS levels in the surface seawater and air can be distinguished and evaluated based on the variations in the DMS peaks. These results demonstrated that the sampling device was effective for consistent, sensitive underway measurements of DMS. Graphical abstract

Impact of dust-polluted convective clouds over the Tibetan Plateau on downstream precipitation Publication date: 15 July 2019 Source: Atmospheric Environment, Volume 209 Author(s): Yuzhi Liu, Qingzhe Zhu, Jianping Huang, Shan Hua, Rui Jia Abstract Based on satellite observations and reanalysis datasets, this study focuses on the effect of aerosols on clouds over the Tibetan Plateau (TP) and the impact of dust-polluted convective clouds on precipitation over downstream regions. A heavy dust event is detected by Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) over the northern slope of the TP on 16 July and 17 July 2016. The high aerosol optical depth (AOD) values are mainly distributed over the northern slope of the TP. Simultaneously, the CloudSat satellite observes deep convective clouds over the northern slope area of the TP, in which convective clouds and dust mix at the same height. With the AOD increasing from 16 July to its peak on 17 July, the ice particle size decreases to a minimum, and convective clouds develop at higher heights because of the prolonged cloud life. Accordingly, a larger ice water path (IWP) is induced by the development of convective clouds that move eastwardly from 16 to 17 July. In the following days, under favorable meteorological conditions, some of the developed convective clouds continuously move eastward and merge with the convective cloud clusters along the motion path, which induces significant precipitation over the Yangtze River basin on 17 July. Furthermore, driven by the northward wind, some developed convective cloud clusters move northward and induce strong precipitation over North China on 19 July. The indirect effect of dust aerosols over the TP could enhance the plateau's cloud development and potentially contribute to downstream precipitation, which is a meaningful factor for weather forecasting.

Computational fluid dynamics simulation of reactive fine particulate matter in a street canyon Publication date: 15 July 2019 Source: Atmospheric Environment, Volume 209 Author(s): Minjoong J. Kim, Rokjin J. Park, Jea-Jin Kim, Sung Hoon Park, Lim-Seok Chang, Dae-Gyun Lee, Jin-Young Choi Abstract We developed a coupled computational fluid dynamics–chemistry model to examine the transport and chemical transformation of reactive aerosols on an urban street. The model was evaluated by comparing the results of simulations with those of observational campaigns in a street canyon in Elche, Spain. The model generally captured the composition of fine particulate matter (PM1) in the street canyon in summer and winter. However, compared with the observed concentration of PM1 in summer, the simulated concentration of PM1 was overestimated by 40%, indicating that the model predicted a weaker canyon vortex. Although the model has some bias, it reasonably reproduced the observed aerosol concentration. We also investigated the diurnal variations and spatial distribution of PM1 and its composition in the street canyon. The simulated sulfate concentrations were mostly affected by boundary transport, showing weak diurnal variations. The nitrate aerosol concentrations exhibited clear sinusoidal diurnal variations following the precursor gas, HNO3, which is mainly formed by photochemical reactions. We also found that nitrate aerosol formation was suppressed by low O3 concentrations under extreme volatile organic compound-limited conditions. The concentrations of PM1, organic carbon, and black carbon followed traffic volume curves, indicating the dominant effect of vehicular emissions on aerosols. Our sensitivity model simulation showed that considering chemical reactions significantly affects the diurnal variations of secondarily produced aerosol concentrations. These results clearly demonstrate that considering chemical production and loss is essential to investigate the diurnal variations of PM1 in street canyons, especially in winter.

Wintertime distribution and atmospheric interactions of reactive nitrogen species along the urban transect of Delhi – NCR Publication date: 15 July 2019 Source: Atmospheric Environment, Volume 209 Author(s): Reema Tiwari, Umesh Kulshrestha Abstract This study reports simultaneous measurements of inorganic Nr trace gases (NH3, NOx, HNO3) and the corresponding particulates (NH4+, NO3−) for elucidating photochemical interactions that are involved in their spatial and diurnal evolution along the north west – south transect of an urban NCR. Three sites were chosen with different land use characteristics where the spatial gradient in Nr precursor gases were observed as Faridabad (92.33 μg m−3) > Delhi (56.01 μg m−3) > Rohtak (24.84 μg m−3). Their percentage fractions in the total Nr composition were estimated as 25.45% of NOx, 28.91% of HNO3, 40.05% of NH3 at industrial Faridabad site respectively; 27.59% of NOx, 8.36% of HNO3, 61.61% of NH3 respectively at urban representative Delhi site and 22.37% of NOx, 15.36% of HNO3, 53.53% of NH3 respectively at background Rohtak site. Particulate Nrconcentrations, on the other hand, exhibited insignificant inter site variability where its percentage contribution to the total Nr had the sequential order as Rohtak (3.56%) > Delhi (1.69%) > Faridabad (0.22%) for NH4+fractions whereas NO3− fractions has the order as Faridabad (5.37%) > Rohtak (5.18%) > Delhi (0.75%). Ionic composition of these particulates was characterized by the dominance of Ca2+ as the major base cation in which the role of photochemical reactions becomes limited. Hence, such Nr distribution patterns were further evaluated for their diurnal behaviour at each site where D/N > 1 ratios were observed for NOx (1.52), HNO3(1.02), NH3 (1.72), NO3− (1.01) at Rohtak as well as for NH4+ (3.02) and NO3− (2.60) at Delhi and Faridabad site respectively. However, their transformation extents in the photochemical reactions were observed to be independent of diurnal phases where the incomplete phase conversions were characterized by the molar ratios of NOx/NOy > 0.8 at Delhi and NH3/NHx > 0.5 at all the sites. The correlation matrix of these parameters confirmed their gas phase oxidation occurring independent of their meteorological condition of temperature and relative humidity. Such observations were thermodynamically evaluated by the calculation of their Km and Kpvalues that were further plotted for their ambient temperature and below deliquesce relative humidity levels for ascertaining the favourable conditions that are existing for the NH4NO3 aerosol formation over the study region.

Analysis of intense dust storms over the eastern Mediterranean in March 2018: Impact on radiative forcing and Athens air quality Publication date: 15 July 2019 Source: Atmospheric Environment, Volume 209 Author(s): D.G. Kaskaoutis, U.C. Dumka, A. Rashki, B.E. Psiloglou, A. Gavriil, A. Mofidi, K. Petrinoli, D. Karagiannis, H.D. Kambezidis Abstract This study examines the multiple dust storms that hit the eastern Mediterranean and Greece during March 2018, emphasizing on the atmospheric dynamics for their generation, the source regions, the dust-induced radiative forcing and the impacts on PM concentrations in Athens. In March 2018, several dust storms facilitated by increased cyclonicity in the western Europe/Mediterranean and by the Sharav cyclogenesis along the north African coast resulted in abnormal-high columnar aerosol loading and PM concentrations over Greece. The dusty days were associated with intense winds (>15 - 20 ms−1) from southwestern directions, triggered by cyclonic circulations over the central/eastern Mediterranean and troughs over Italy and the north African coast. Statistical analysis of the backward air-mass trajectories shows that the highest PM10 concentrations are related to dust sources in Libya, while Ceilometer profiles indicate thick dust plumes with highest intensity between the surface and 3 km over Athens. The monthly-averaged hourly PM10 concentrations at several stations in the Athens basin ranged from 37 μgm−3 to 53 μgm−3, while nine days exhibited PM10 daily-means above 50 μgm−3, characterized as dusty days. The PM10 concentrations in Athens maximized on 25–26 March (∼500 μgm−3 at hourly basis), while the PM2.5 constitutes 38%–59% of PM10, indicating a dominance of coarse particles. Aerosol radiative forcing (ARF) estimates via the synergy of OPAC and SBDART models at three AERONET stations in Greece revealed significant impact of dust on radiation budget, with large (∼−40 W m−2 to −50 W m−2) decrease in surface solar radiation and an overall cooling effect at the top of atmosphere (∼−5 to −30 W m−2). The atmospheric heating via the dust-aerosol absorption results in heating rates of ∼0.5 K day−1. Graphical abstract

MODIS AOD sampling rate and its effect on PM2.5 estimation in North China Publication date: 15 July 2019 Source: Atmospheric Environment, Volume 209 Author(s): Zijue Song, Disong Fu, Xiaoling Zhang, Xinlei Han, Jingjing Song, Jinqiang Zhang, Jun Wang, Xiangao Xia Abstract Much attention has been paid to develop methods to estimate particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) from satellite aerosol optical depth (AOD). One of fundamental limitation of these methods is lack of AOD and thereby PM2.5 cannot be derived from satellites when clouds are present or when surface conditions are not favorable. This would probably result in an inherent clear-sky biased estimate of PM2.5 for air quality assessment that requires continuous 24-h measurements at all-sky conditions. Using the Moderate Resolution Imaging Spectroradiometer (MODIS) AOD and PM2.5 data in North China, a highly polluted area with large spatiotemporal variabilities of AOD and PM2.5 values, missing MODIS AOD retrievals and its potential effect on PM2.5 estimation are studied. The MODIS dark target (DT) algorithm produces very few AODs in winter, with a regional observation rate of 4%, which limits its statistical significance for PM2.5 air quality monitoring. This limitation applies to MODIS DT AOD products at 10-km and 3-km resolutions since they are derived from the same retrieval core (Remer et al., 2013). In contrast, The MODIS deep blue (DB) AOD product complements the MODIS DT AOD coverage, which is remarkable in winter. The MODIS DT and DB merged product has comparable accuracy to that of the DT and DB products but shows a larger sampling rate, therefore, it is more suitable for estimating surface PM2.5. While the regional mean PM2.5 values in the presence and absence of AOD retrievals in spring and summer are comparable, but the former is substantially lower than the latter in autumn by 11.2 μgm−3 and winter by 8.5 μgm−3 on average. The difference in some stations even exceeds 20 μg m−3. Methods to fill missing AOD values in North China are crucial to provide an unbiased sampling and estimate of PM2.5 concentration in all-sky conditions, likely by integrating satellite, surface and modeling data.

Parameterization schemes on dust deposition in northwest China: Model validation and implications for the global dust cycle Publication date: 15 July 2019 Source: Atmospheric Environment, Volume 209 Author(s): Xiao-Xiao Zhang, Brenton Sharratt, Jia-Qiang Lei, Cheng-Lai Wu, Jie Zhang, Chun Zhao, Zi-Fa Wang, Shi-Xin Wu, Sheng-Yu Li, Lian-You Liu, Shuang-Yan Huang, Yu-Hong Guo, Rui Mao, Jie Li, Xiao Tang, Jian-Qi Hao Abstract Accurate estimation of dust deposition is of significance for modelling global radiation and the biochemical carbon cycle in the earth system. However, the paucity of dust deposition data precludes our ability to adequately verify estimations of dust deposition. Based on the environmental monitoring records in Xinjiang Province, northwest China, we conducted a numerical simulation of dust deposition using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) and compared observed and modelled deposition during the spring dust season (March–May). The performance of WRF-Chem on modelling dust deposition was tested and evaluated with adoption of Georgia Tech/Goddard Global Ozone Chemistry Aerosol Radiation and Transport (GOCART) and Shao et al. (2011a) dust emission schemes. Our results indicate that the dry deposition schemes have the capability to predict size-resolved dust deposition. However, modelled and measured dust deposition differed by more than one order of magnitude. The modelled dust dry deposition does not satisfactorily agree well with field measurements. This study suggests significant distinctions exist among these two dust emission schemes when simulating mineral dust dry deposition in northwest China. Uncertainties in estimating the dry dust deposition are in a range of 77–96%. These uncertainties imply that parameterization in the current dust deposition schemes need to be further improved. We found that the estimation of dust deposition is highly underestimated by the Global Climate Model and Regional Climate Model (GCM/RCM). Thus global dust cycles and dust deposition may exceed our current estimates. Graphical abstract Schematic diagram of interactions between desert dust and climate in arid and semi-arid region.

Hourly associations between exposure to ambient particulate matter and emergency department visits in an urban population of Shenzhen, China Publication date: 15 July 2019 Source: Atmospheric Environment, Volume 209 Author(s): Dieyi Chen, Faxue Zhang, Chuanhua Yu, Anqi Jiao, Qianqian Xiang, Yong Yu, Fatemeh Mayvaneh, Kejia Hu, Zan Ding, Yunquan Zhang Abstract Background Ambient particulate matter (PM) has been linked to adverse health outcomes, but evidence is still relatively limited for emergency department visits (EDVs). Most prior studies used daily mean PM as exposure assessment regardless of within-day variations, which might underestimate the potential acute health effects. In this study, we evaluated the hourly associations between PM and EDVs, so as to further understand the very short-term impacts of PM on EDVs. Methods Hourly data for all-cause EDVs, air pollutants and meteorological factors were collected from Shenzhen, China, between March 1, 2015 and February 28, 2018. A time-stratified case-crossover design with conditional logistic regression analysis was performed to assess the hourly associations between PM and EDVs, adjusting for hourly mean temperature and relative humidity. Subgroup analyses stratified by gender, age and clinic department were conducted to identify vulnerable populations. We further classified the whole year into warm (April to September) and cold (October to March of the next year) months to evaluate seasonal effect modification. Results Hourly mean all-cause EDVs peaked at 9 a.m. and 7 p.m., while PM2.5 and PM10 peaked at 8 a.m. and 8 p.m. The hourly associations between PM and EDVs appeared immediately and persisted for about 10 hours. All-cause EDVs increased 0.72% (95% confidence interval (CI): 0.33, 1.12) and 0.72% (95% CI: 0.45, 0.99) associated with per 10 μg/m3 rise in PM2.5 and PM10 at lag 0–10 h, respectively. Stronger effects of PM2.5 and PM10on EDVs were observed among younger groups (age <35 years). Significant PM-EDVs associations were only identified in cold season. A 10 μg/m3 rise in PM2.5 along 0–10 h, for instance, was associated with increased all-cause EDVs risks of 1.13% (95% CI: 0.67, 1.60) in cold season and −0.23% (95% CI: −1.00, 0.53) in warm season, respectively. Conclusions Our study provided hourly perspective for the short-term associations between PM exposure and increased EDVs. The adverse impacts of PM on EDVs were only identified in cold season, and young people suffered more from both PM2.5 and PM10 exposures. These findings may have valuable implications for public policy promotion on air cleaning, as well as hospital management in optimizing allocation of resources on PM-sensitive conditions.

Moss as an indicator of transboundary atmospheric nitrogen pollution in an alpine ecosystem Publication date: 1 July 2019 Source: Atmospheric Environment, Volume 208 Author(s): Yoshitaka Oishi Abstract Increased atmospheric nitrogen (N) pollution affects N deposition in alpine ecosystems. Moss often dominates these ecosystems and their N content (%N) and stable isotope ratio (δ15N) are used as indicators of atmospheric N deposition. Here, we used a single moss species (Hylocomium splendens) as a bioindicator of atmospheric N deposition in the mountainous areas of Japan. The moss was collected from 38 sites on all slope aspects (east, west, south, and north) ranging from 1800 to 2800 m in altitude. The correlation between moss N variables (%N and δ15N) and environmental conditions (altitude and slope aspects) was analyzed using linear models based on a hierarchical Bayesian framework. In the constructed models, %N showed a significant or weak negative correlation with altitude on all slope aspects. In contrast, δ15N was significantly and positively correlated with altitude, with high values on the western alpine slopes. When using δ15N as a marker of N sources, N in alpine moss on the west slope seemed to be influenced by transboundary N pollutants through particulate matter (PM), which is brought to Japan from mainland Asia by prevailing westerly winds and northwest monsoons. However, as moss N is also affected by other factors, such as different N chemical forms, fixed N from cyanobacteria, and seasonal differences in atmospheric N, further research should directly compare moss N with atmospheric N deposition to elucidate the influence of transboundary N pollutants on moss N. Graphical abstract

Spatial characteristics of the nighttime oxidation capacity in the Yangtze River Delta, China Publication date: 1 July 2019 Source: Atmospheric Environment, Volume 208 Author(s): Xiaorui Chen, Haichao Wang, Yuhan Liu, Rong Su, Hongli Wang, Shengrong Lou, Keding Lu Abstract Nighttime chemistry plays an important role in NOx and volatile organic compounds (VOCs) removal. A box model was used to study nighttime nitrate radical (NO3), O3 oxidation and nitrate products in Yangtze River Delta (YRD), China. The model input data were collected from five representative monitoring sites in YRD regions from 20 August to 11 September 2016. The production rate of NO3 was found very fast with the nocturnal average of 1–3 ppbv h−1 in different sites. Large directly NO3 loss frequency was determined from VOCs measurements, with the average of 0.01–0.03 s−1, which represented a lower limit due to the lack of monoterpene measurement. The model results show NO3 governs nocturnal oxidation of hydrocarbons (HCs) in YRD region (80%) and O3 contributes to 20% in average. The oxidation percentage attributable to NO3 increased against the NOx concentration, with 3.5–7.7 ppbv HCs removal by NO3 per night in average, suggesting that the production of organic nitrate by NO3 oxidation may be significant. As to products, the integrated inorganic nitrate production in the nighttime was considerable around 62% ± 20% of the whole day in urban sites, but the percentage was small in rural sites. More inorganic nitrate was produced with the increase of NOx, since the HCs oxidation by NO3 has already been saturated at night. This study highlights nocturnal fast oxidation by NO3 in YRD region, and the variability of oxidation is large in different NOx regime.

Cell and Tissue Research

Expression of OPA1 and Mic60 genes and their association with mitochondrial cristae morphology in Tibetan sheep Abstract In order to investigate the relationship between the expression of OPA1 and Mic60 genes and the shape of mitochondrial cristae and to explore the mechanism of Tibetan sheep adapting to a high altitude hypoxia environment, we investigate respiratory rate, mitochondrial cristae and the expression of OPA1 and Mic60 in four different tissues (myocardial, skeletal muscle, spleen and kidney) in Tibetan sheep and Small Tail Han sheep. Tibetan sheep had a higher respiratory rate than Small Tail Han sheep (p < 0.01). In the same tissue, the expression of OPA1 and Mic60 was higher (p < 0.05) in Tibetan sheep than Small Tail Han sheep. Between tissues, the expression of OPA1 and Mic60 was found to be lower (p < 0.05) in spleen than the other three tissues in both breeds. Mitochondrial cristae was dense and clear in myocardial and skeletal muscle but was relatively sparse and slightly swollen in kidney. In spleen, cristae was least and swollen and the gap between the cristae was large. The width of the mitochondrial cristae in the spleen was significantly larger than the width between the inner and outer membranes; however, it had little difference in the other three tissues. The width of mitochondrial cristae was significantly larger in the spleen than that in other tissues (p < 0.05). The numbers of mitochondrial cristae in the four tissues of Tibetan sheep were larger than those in Small Tail Han sheep (p < 0.05). The unique characters of the mitochondrial cristae in Tibetan sheep may be related to its adaption to a high altitude hypoxia environment.

Identification of calretinin-expressing retinal ganglion cells projecting to the mouse superior colliculus Abstract In mice, retinal ganglion cells (RGCs), which consist of around 30 subtypes, exclusively transmit retinal information to the relevant brain systems through parallel visual pathways. The superior colliculus (SC) receives the vast majority of this information from several RGC subtypes. The objective of the current study is to identify the types of calretinin (CR)-expressing RGCs that project to the SC in mice. To label RGCs, we performed CR immunoreactivity in the mouse retina after injections of fluorescent dye, dextran into mouse SC. Subsequently, the neurons double-labeled for dextran and CR were iontophoretically injected with the lipophilic dye, DiI, to characterize the detailed morphological properties of these cells. The analysis of various morphological parameters, including dendritic arborization, dendritic field size and stratification, indicated that, of the ten different types of CR-expressing RGCs in the retina, the double-labeled cells consisted of at least eight types of RGCs that projected to the SC. These cells tended to have small-medium field sizes. However, except for dendritic field size, the cells did not exhibit consistent characteristics for the other morphometric parameters examined. The combination of a tracer and single-cell injections after immunohistochemistry for a particular molecule provided valuable data that confirmed the presence of distinct subtypes of RGCs within multiple-labeled RGCs that projected to specific brain regions.

Oxidative stress modulates the expression of apoptosis-associated microRNAs in bovine granulosa cells in vitro Abstract Despite its essential role in ovulation, oxidative stress (OS) has been found to be cytotoxic to cells, while microRNAs (miRNAs) are known as a major regulator of genes involved in cellular defense against cytotoxicity. However, a functional link between OS and miRNA expression changes in granulosa cells (GCs) remains to be investigated. Here, we investigate the OS modulation of apoptosis-associated miRNAs and their biological relevance in bovine GCs. Following the evaluation of cell viability, accumulation of reactive oxygen species (ROS), cytotoxicity and mitochondrial activity, we used a ready-to-use miRNA PCR array to identify differentially regulated miRNAs. The results showed that exposure to 150 μM H2O2 for 4 h creates remarkable signs of OS in GCs characterized by more than 50% loss of cell viability, higher nuclear factor erythroid 2–related factor 2 (NRF2) nuclear translocation, significantly (p < 0.05) higher abundance of antioxidant genes, significantly (p < 0.001) higher accumulation of ROS, lower mitochondrial activity and a higher (p < 0.001) number of apoptotic nuclei compared to that of the control group. miRNA expression analysis revealed that a total of 69 miRNAs were differentially regulated in which 47 and 22 miRNAs were up- and downregulated, respectively, in stressed GCs. By applying the 2-fold and p < 0.05 criteria, we found 16 miRNAs were upregulated and 10 miRNAs were downregulated. Target prediction revealed that up- and downregulated miRNAs potentially targeted a total of 6210 and 3575 genes, respectively. Pathway analysis showed that upregulated miRNAs are targeting the genes involved mostly in cell survival, intracellular communication and homeostasis, cellular migration and growth control and disease pathways. Our results showed that OS modulates the expression of apoptosis-associated miRNAs that might have effects on cellular or molecular damages.

Dental pulp stem cell transplantation ameliorates motor function and prevents cerebellar atrophy in rat model of cerebellar ataxia Abstract Cerebellar ataxias (CA) include a range of neurodegenerative disorders hallmarked by deterioration of the cerebellum. Cell replacement therapy (CRT) offers a potential remedy for the diseases associated with the central nervous system (CNS). This study was designed to assess the neurorestorative/protective effects of dental pulp stem cell (DPSC) implantation on a rat model of CA induced by 3-acetylpyridine (3-AP) as a neurotoxin. To begin, human DPSCs were extracted, cultured and phenotypically characterized. Then, experimental ataxia was induced in 20 male adult rats by a single injection of 3-AP and bilateral DPSC transplantation was performed 3 days after 3-AP administration, followed by stereological analysis of cerebellar layers along with assessment of motor skills and inflammatory response. The findings showed that transplantation of DPSCs in a 3-AP model of ataxia ameliorated motor coordination and muscle activity, increased cerebellar volumes of molecular and granular layers plus white matter, reduced the levels of inflammatory cytokines and thwarted the degeneration of Purkinje cells against 3-AP toxicity. Taken together, human DPSCs could be considered as a suitable candidate for CRT-based therapies with a specific focus on CA.

Human umbilical cord blood mesenchymal stem cells expansion via human fibroblast-derived matrix and their potentials toward regenerative application Abstract Large expansion of human mesenchymal stem cells (MSCs) is of great interest for clinical applications. In this study, we examine the feasibility of human fibroblast-derived extracellular matrix (hFDM) as an alternative cell expansion setting. hFDM is obtained from decellularized extracellular matrix (ECM) derived from in vitro cultured human lung fibroblasts. Our study directly compares conventional platforms (tissue culture plastic (TCP), fibronectin (FN)-coated TCP) with hFDM using umbilical cord blood-derived MSCs (UCB-MSCs). Early cell morphology shows a rather rounded shape on TCP but highly elongated morphology on hFDM. Cell proliferation demonstrates that MSCs on hFDM were significantly better compared to the others in both 10 and 2% serum condition. Cell migration assay suggests that cell motility was improved and a cell migration marker CXCR4 was notably up-regulated on hFDM. MSCs differentiation into osteogenic lineage on hFDM was also very effective as examined via gene expression, von Kossa staining and alkaline phosphatase activity. In addition, as the MSCs were expanded on each substrate, transferred to 3D polymer mesh scaffolds and then cultivated for a while, the data found better cell proliferation and more CXCR4 expression with MSCs pre-conditioned on hFDM. Moreover, higher gene expression of stemness and engraftment-related markers was noticed with the hFDM group. Furthermore when UCB-MSCs expanded on TCP or hFDM were injected into emphysema (a lung disease) animal model, the results indicate that MSCs pre-conditioned on hFDM (with 2% serum) retain more advanced therapeutic efficacy on the improvement of emphysema than those on TCP. Current works demonstrate that compared to the conventional platforms, hFDM can be a promising source of cell expansion with a naturally derived biomimetic ECM microenvironment and may find some practical applications in regenerative medicine.

A novel serotonin-containing tuft cell subpopulation in mouse intestine Abstract In this study, a novel subset of doublecortin-like kinase 1 (DCLK1)-immunoreactive (IR) tuft cells that also contain serotonin (5-hydroxytryptamine, 5HT) is described, in terms of their number, regional distribution, possible synthesis or reuptake of 5HT and proximity to 5-HT-containing enterochromaffin (EC) cells. The small intestine from C57BL/6J mice was divided into five segments while the large intestine was kept undivided. Double immunostaining was used to estimate numbers and topographic distribution of 5HT-IR (DCLK1/5HT) tuft cells and their possible expression of tryptophan hydroxylase (TPH) and serotonin transporter (SERT). Also, possible contacts between tuft cells and 5HT-IR EC cells were studied. In the small intestine, up to 80% of all tuft cells were identified as DCLK1/5HT-IR; in the large intestine, such cells were rare. The highest number of DCLK1/5HT-IR cells was found in the upper small intestine. The numbers of DCLK1/5HT-IR cells gradually decreased distally. DCLK1-IR tuft cells were not found to contain TPH, the rate-limiting enzyme in 5HT synthesis. SERT, the selective transporter for 5HT reuptake, could not convincingly be demonstrated in tuft cells. In villi and crypts, 3% and 10%, respectively, of all DCLK1-IR cells were in close proximity to EC cells. EC cells in close proximity to DCLK1-IR cells were, in villi and crypts, 3 and 8%, respectively. We conclude that DCLK1/5HT-IR cells constitute a novel subset of tuft cells that may have unique roles in the GI tract.

Vascularized composite allograft rejection is delayed by infusion of IFN-γ-conditioned BMSCs through upregulating PD-L1 Abstract Mesenchymal stromal cells (MSCs) have been applied in prevention from allograft rejection based on their immunomodulatory effects. However, conflicting results have been presented among recent studies, for which one possibility being acknowledged is that the exact effect is determined by the microenvironment when MSCs are applied in vivo. Using a hind limb composite tissue allograft model, we investigate the influence of IFN-γ-preconditioning on the immunomodulatory effects of MSCs and the subsequent allograft survival. Firstly, different doses of IFN-γ were respectively used to incubate with bone marrow–derived MSCs (BMSCs). We found that IFN-γ altered the expression of PD-L1, a major suppressor gene in the immune system during allograft rejection, in a strictly dose-dependent manner in BMSCs. Ten nanograms per milliliter IFN-γ-incubated BMSCs significantly stimulated PD-L1 expression and suppressed T cell proliferation and differentiation, while 50 ng/mL IFN-γ-incubated BMSCs sharply reduced PD-L1 expression. Moreover, we observed that, in contrast to the naive BMSC transplantation group, BMSCs pre-conditioned with 10 ng/mL IFN-γ (BMSCs-IFN-γ) significantly delayed the allograft rejection in vivo. In vitro mixed lymphocyte reaction (MLR) indicated that BMSCs-IFN-γ inhibited T lymphocyte proliferation and activation via PD-L1. Moreover, BMSCs-IFN-γ did not influence the proliferation and activation of T lymphocytes when PD-L1 protein was neutralized by the PD-L1 antibody. These data collectively reveal a role of recipient ongoing immune microenviroment in BMSC-based immunesuppressive therapy. Graphical abstract ᅟ

Sox11-modified mesenchymal stem cells accelerate cartilage defect repair in SD rats Abstract Cartilage has a limited capacity to heal. Previously, we have shown that overexpression of Sox11 in rMSCs (Rat Mesenchymal Stem Cells) by lentivirus-mediated gene transfer leads to enhanced tri-lineage differentiation and accelerated bone formation in fracture model of rats. We observed that the fracture repair in the rats that received Sox11-modified rMSCs injection proceeded through an endochondral ossification process much faster than those in the control groups. However, the detailed role of Sox11 in rMSCs chondrogenic differentiation, as well as cartilage defect, is still not clearly clarified. Therefore, this study tests the hypothesis that Sox11 promotes chondrogenesis and cartilage defect repair by regulating β-catenin. Sox11 was transduced into rMSCs using lentiviruses. The expression levels of β-catenin and its downstream genes were evaluated by quantitative RT-PCR. The transcriptional activation of β-catenin was proved by dual-luciferase reporter assay and co-immunoprecipitation was performed to evaluate Sox11-β-catenin interaction. In addition, a cartilage defect model in SD rats was used to evaluate the cartilage regeneration ability of Sox11-modified rMSCs in vivo. We found that Sox11 transcriptionally activated β-catenin expression and discovered the core promoter region (from − 242 to − 1414) of β-catenin gene for Sox11 binding. In addition, Sox11 might regulate β-catenin at the post-transcriptional level by protein-protein interaction. Finally, using a cartilage defect model in rats, we found Sox11-modified rMSCs could improve cartilage regeneration. Taken together, our study shows that Sox11 is an important regulator of chondrogenesis and Sox11-modified rMSCs may have clinical implication for accelerating cartilage defect healing.

Salutary effect of fenofibrate on type 1 diabetic retinopathy via inhibiting oxidative stress–mediated Wnt/β-catenin pathway activation Abstract Fenofibrate has been shown to have therapeutic effects on diabetic retinopathy (DR). Our previous studies demonstrated that the oxidative stress–activated Wnt/β-catenin pathway plays a pathogenic role in diabetic complications. In the present study, we evaluate the effect and mechanism of fenofibrate on regulating the oxidative stress–activated Wnt/β-catenin pathway by using the genetic type 1 diabetes model of C57BL/6J-Ins2Akitamice and high glucose (HG)–treated ARPE-19. Our results demonstrated that retinal phosphorylation of LRP6 and nuclear β-catenin were increased in C57BL/6J-Ins2Akita mice suggesting activation of Wnt/β-catenin signaling. Meanwhile, C57BL/6J-Ins2Akita showed upregulation of oxidant enzyme Nox4 and Nox2 and downregulation of antioxidant enzyme SOD1 and SOD2. All these alterations were reversed in C57BL/6J-Ins2Akitamice with fenofibrate treatment. Moreover, fenofibrate significantly ameliorated diabetes-induced retinal vascular leakage in C57BL/6J-Ins2Akita mice. In cultured ARPE-19, fenofibrate decreased HG-induced Nox2 and Nox4 upregulation, attenuated SOD1 and SOD2 downregulation and inhibited LRP6 phosphorylation. Moreover, activation of Wnt/β-catenin by Wnt3a conditional medium (WCM) reduced SOD1 and SOD2 and did not affect Nox2 and Nox4. Fenofibrate suppressed WCM-induced LRP6 phosphorylation and reversed SOD downregulation. Importantly, Nox4 overexpression directly phosphorylated LPR6 in ARPE19; conversely, Nox4 knockdown suppressed HG-induced LPR6 phosphorylation. Taken together, Nox-mediated oxidative stress contributes to Wnt/β-catenin activation in DR. Fenofibrate ameliorated DR through coordinate attenuation of oxidative stress and blockade of Wnt/β-catenin signaling.

Early injection of human adipose tissue-derived mesenchymal stem cell after inflammation ameliorates dextran sulfate sodium-induced colitis in mice through the induction of M2 macrophages and regulatory T cells Abstract Inflammatory bowel diseases (IBDs) are sometimes refractory to current therapy or associated with severe adverse events during immunosuppressive therapy; thus, new therapies are urgently needed. Recently, mesenchymal stem cells (MSCs) have attracted attention based on their multitude of functions including anti-inflammatory effects. However, proper timing of MSC therapy and the mechanisms underlying the therapeutic effects of MSCs on colitis are not fully elucidated. Human adipose tissue-derived mesenchymal stem cells (hAdMSCs; 1 × 106) were administrated via the tail vein on day 3 (early) or 11 (delayed) using a 7-day dextran sulfate sodium (DSS)-induced mouse model of colitis. The effects were evaluated based on colon length, disease activity index (DAI) and histological score. Cytokine-encoding mRNA levels T cells and macrophages were evaluated by real-time PCR and flow cytometry. Regarding the timing of administration, early (day 3) injection significantly ameliorated DSS-induced colitis in terms of both DAI and histological score, compared to those parameters with delayed (day 11) injection. With early cell injection, the tissue mRNA levels of anti-inflammatory cytokine genes (Il10, Tgfb) increased, whereas those of inflammatory cytokine genes (Il6, Tnfa and Il17a) decreased significantly. Regarding the associated mechanism, hAdMSCs suppressed T cell proliferation and activation in vitro, increased the number of regulatory T cells in vivo and changed the polarity of macrophages (into the anti-inflammatory M2 phenotype) in vitro. Timing of injection is critical for the effective therapeutic effects of hAdMSCs. Furthermore, part of the associated mechanism includes T cell activation and expansion and altered macrophage polarization.

Oncology

Interaction of H. pylori with toll-like receptor 2-196 to -174 ins/del polymorphism is associated with gastric cancer susceptibility in southern China Abstract Background Genetic polymorphisms of Toll-like receptors play important roles in gastric carcinogenesis. The aim of this study was to determine the role of TLR2-196 to -174 ins/del polymorphism in gastric cancer susceptibility and prognosis. Methods This study included 520 people from southern China. Samples were genotyped by the allele-specific polymerase chain reaction, among which 10% were randomly selected for sequencing. The serological method was used to determine Helicobacter pylori. Results The TLR2 genotype was not associated with the risk of H. pylori infection. The del/del genotype exhibited significantly higher gastric cancer risk (adjusted OR 2.59, 95% CI 1.33‒5.07) than that of the ins/ins genotype. Further stratification analyses demonstrated that the del/del genotype was associated with a risk of intestinal gastric cancer (adjusted OR 2.62, 95% CI 1.34–5.14). In addition, the presence of the del/del genotype and the H. pylori infection conferred a synergistic effect (OR 3.04, 95% CI 1.33‒6.98) for the development of gastric cancer. The del/del genotype was not associated with a poor prognosis in gastric cancer patients. Conclusion The del/del genotype is associated with an increased gastric cancer risk in the southern Chinese population. However, TLR2 polymorphism is neither associated with H. pylori infection, nor with a poor prognosis.

A multi-institutional observational study on the effects of three-dimensional radiotherapy and weekly 40-mg/m 2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors Abstract Background The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. Methods We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. Results The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. Conclusions The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.

Clinical factors associated with the therapeutic outcome of chemotherapy in very elderly cancer patients Abstract Background The purpose of this study was to detect background factors that might be associated with the therapeutic and curative outcome of chemotherapy in elderly cancer patients aged over 75 years. Methods A retrospective study was conducted for elderly cancer patients aged over 75 years who had received more than 2 courses of chemotherapy at our hospital. We analyzed the relationships between RECIST outcome and background factors, such as age, sex, clinical TNM stage, pre-treatment history, ECOG performance status, serum albumin, and Charlson comorbidity index using logistic regression analysis. Results A total of 103 cancer patients aged over 75 years were analyzed in this study, including 28 with hematological neoplasia, 36 with gastrointestinal tract cancers, 25 with breast cancers, and 14 with other malignancies originating in various tissues. Seventy-one patients (69.1%) had a positive clinical outcome including RECIST CR (complete response), PR (partial response) and SD (stable disease). Multivariate analysis showed that a high serum albumin level of more than 3.5 g/dl and a Charlson comorbidity index score of less than 2 points were positively correlated with a favorable therapeutic outcome. Conclusions The results of the current study suggested that serum albumin level and comorbidity index are the principal clinical factors affecting therapeutic outcomes in elderly cancer patients receiving chemotherapy. In the future, these factors may make chemotherapy adaptations, continuity, and effectiveness easier to predict than GA screening.

Safety and efficacy of concurrent carboplatin or cetuximab plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin Abstract Background Locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is usually treated with cisplatin (CDDP)-based chemoradiotherapy, except when patients are elderly or have renal, cardiac, or neurogenic dysfunction. This study compared the safety and efficacy of concurrent carboplatin (CBDCA) to cetuximab (Cmab) plus radiotherapy (RT) in patients ineligible for CDDP treatment. Methods We retrospectively analyzed LASCCHN patients who received CBDCA plus RT (n = 29) or Cmab plus RT (n = 18) due to ineligibility for CDDP treatment at two Japanese institutions between August 2006 and December 2015. Results Patients characteristics for CBDCA plus RT and Cmab plus RT were: median age, 74 and 75 years; 0–1 performance status, 90% and 100%; main primary tumor site, hypopharynx 52% (n = 15) and oropharynx 39% (n = 7); and stage IV, 90% (n = 26) and 50% (n = 9), respectively. With a median follow-up time of 60.0 months for CBDCA plus RT and 53.6 months for Cmab plus RT, 3-year locoregional control rates were 56% versus 58%, and median progression-free survival was 42.7 versus 11.6 months. CBDCA plus RT was associated with more grade 3/4 hematologic toxicities, including neutropenia and thrombocytopenia, whereas Cmab plus RT was associated with more grade 3/4 oral mucositis and radiation dermatitis. Conclusions CBDCA or Cmab as a concurrent systemic therapy with RT is a possible treatment option for LASCCHN patients ineligible for CDDP treatment, although attention to hematological toxicity should be paid.

Optimal maximum duration for delaying salvage operation when recurrence of retroperitoneal liposarcoma is suspected: a single-center study Abstract Background This study was designed to identify the optimal maximum duration for delaying salvage operation when recurrence of retroperitoneal liposarcoma (LPS) is suspected. Methods Patients who underwent salvage operation at Samsung Medical Center for recurrent retroperitoneal LPS from January 2000 to December 2015 were reviewed. The time interval between recurrence and operation for recurrence was divided by 1, 2 or 3 months. A Cox proportional-hazards model was used to analyze factors related to disease-free survival along with recurrence-to-operation interval divided by 1, 2 or 3 months. Results The 1-, 3-, and 5-year disease-free survival rates were 43.2%, 15.6% and 13.4%, respectively. FNCLCC grade (p = 0.023) and recurrence-to-operation interval divided by 3 months (p = 0.003) were significant factors associated with recurrence. FNCLCC grade 2 (HR 1.940, CI 0.935–4.026, p = 0.238) and grade 3 (HR 4.049, CI 1.767–9.281, p = 0.007) showed increased risk compared to grade 1. Patients who underwent salvage operation more than 3 months after recurrence showed significantly increased risk of recurrence compared to patients within 3 months (HR 2.724, CI 1.391–5.337, p = 0.003). Conclusions Based on our analysis of recurrence-free survival, salvage operation can be delayed for less than 3 months when recurrence is suspected. A short-term follow-up imaging study should be performed within this period.

Castration-resistant prostate cancer patients who had poor response on first androgen deprivation therapy would obtain certain clinical benefit from early docetaxel administration Abstract Background Our specific aim was to investigate the prognostic value of effective duration of first androgen deprivation therapy (ADT) and to evaluate the clinical impact on early docetaxel administration with oncological outcomes in castration-resistant prostate cancer (CRPC) patients treated with docetaxel. Methods We identified 148 mCRPC patients who were treated with 75 mg/m2 docetaxel. We defined 16 months as the threshold for the effective duration of ADT, and defined 12 months as the cut-off time for starting docetaxel from the onset of CRPC. Univariate and multivariate analyses were conducted to investigate the prognostic indicators that influenced the survival outcomes. Results Overall, 81 (54.7%) patients died. The median 1st ADT response was 22.2 months and the median time interval from CRPC onset to docetaxel treatment was 11.7 months. Multivariate analysis indicated that visceral metastasis, bone metastasis extent of disease (EOD) ≥ 2, and effective duration of ADT < 16 months were the independent prognostic indicators for progression-free survival (PFS). Referring to cancer-specific survival (CSS), besides visceral metastasis and effective duration of ADT < 16 months, late docetaxel treatment ≥ 12 months became as the predictors for poor prognosis. Among the ADT poor-responder group (ADT < 16 months), Kaplan–Meier method showed that 1-year and 2-year CSS rates were 96.0% and 80.0% in the patients who introduced docetaxel in early setting (< 12 months), which were significantly higher than those who introduced in late settings (93.6% and 30.8%, respectively, p < 0.001). Conclusion CRPC patients who had poor response during 1st ADT would obtain survival benefit by introducing docetaxel treatment in early stage.

External validation of the systemic immune-inflammation index as a prognostic factor in metastatic renal cell carcinoma and its implementation within the international metastatic renal cell carcinoma database consortium model Abstract Background We conducted a study to validate the influence of the systemic immune-inflammation index (SII) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to verify whether the implementation of the SII in place of neutrophil and platelet counts within the International Metastatic Renal Cell Carcinoma Consortium (IMDC) model might increase its prognostic accuracy. Patients and methods We retrospectively analyzed consecutive patients with mRCC, who were treated with first-line tyrosine kinase inhibitors from 2008 to 2016 in two major oncology centres in Poland. We stratified patients into low SII (< 730) and high SII (≥ 730) groups according to a recent literature report. We used multivariable Cox proportional hazards regressions (CPHRs) to assess the impact of the SII on OS and concordance, global 'goodness-of-fit', calibration and reclassification measures to quantify a potential prognostic benefit from the modification of the IMDC model. Results Overall, 502 patients (294 with low and 208 with high SII) were included. Median OS was 36.7 months [95% confidence interval (CI) 30.4–41.5 months] and 17.0 months (95% CI 12.5–19.6 months) in the low and high SII groups, respectively. The SII status was significant in CPHRs with the hazard ratio ranging from 1.38 to 1.68. All prognostic accuracy measures favored the SII-modified-IMDC model over the original IMDC model. Conclusions Using an external dataset, we showed that high SII was an independent factor for poor OS. The addition of the SII to the IMDC model in place of neutrophil and platelet counts increased the model's prognostic performance.

Recent treatment strategy for advanced squamous cell carcinoma of the lung in Japan Abstract Squamous cell carcinoma of the lung is associated with smoking in its development and comprises about 20–30% of all lung cancers. Its treatment strategy had been limited for the past decades, inevitably resulting in the poor outcome. However in the 2010s, it has dramatically changed mainly with the recent clinical introduction of immune checkpoint inhibitors. In this review, we will introduce various clinical studies involving squamous cell carcinoma of the lung.

Preoperative predictive factors focused on inflammation-, nutrition-, and muscle-status in patients with upper urinary tract urothelial carcinoma undergoing nephroureterectomy Abstract Objective The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with upper urinary tract urothelial carcinoma (UTUC) undergoing curative nephroureterectomy (NUx). Methods The study enrolled 125 patients and the preoperative variables assessed included age, body mass index, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), serum fibrinogen level (Fib), C-reactive protein (CRP), modified Glasgow prognostic score, serum albumin level (Alb), prognostic nutritional index (PNI), skeletal muscle index (SMI), psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables and their prognostic values after NUx were evaluated. Results Five inflammation markers (NLR, MLR, PLR, Fib and CRP) were positively correlated. Fib was positively correlated with NLR, PLR and CRP, but inversely correlated with SMI. PNI was inversely correlated with age and the four inflammation markers (p < 0.001). Age was not significantly correlated with the inflammation markers, but older age was associated with lower Alb, PNI, SMI, PMI, and PEF. Disease-specific survival was independently predicted by preoperative ipsilateral hydronephrosis and low PNI. Overall survival was independently associated with high Fib and low PNI. Conclusion The preoperative inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for UTUC.

Hematology

Coexistence of t(5;17)/NPM1-RARA and t(9;22)/BCR-ABL1 in chronic myeloid leukemia at initial diagnosis

Juvenile myelomonocytic leukemia: a surprising cause of peri-orbital tumor and squint

Oral ulceration: an unusual manifestation of lymphomatoid granulomatosis

Neutrophil faggot cells and inv(16): not such a fortuitous association?

Successful treatment of monomorphic epitheliotropic intestinal T cell lymphoma with pralatrexate

Extracavitary primary effusion lymphoma (PEL) presenting as bilateral adrenal gland involvement in an HIV-positive patient

Atypical bortezomib-induced neutrophilic dermatosis

RNA-binding protein ( RBFOX1 ) inherited polymorphism rs8051518 is not associated with splice factor mutations in myelodysplastic syndromes and myeloproliferative neoplasms

Lymphomatoid granulomatosis mimicking cancer and sarcoidosis Abstract Two cases of misdiagnoses of lymphomatoid granulomatosis are discussed here. Lymphomatoid granulomatosis is an Epstein-Barr virus-associated lymphoproliferative disorder with aggressive behavior. Due to its rarity and many presentations, delay in diagnosis and treatment is common. Its histological features including large atypical B-cells, T cell predominance, angiocentricity, necrosis, and evidence of EBV-positive cells should elicit the diagnosis of lymphomatoid granulomatosis. The settings that are described here have not yet been described in the literature.

Thromboembolic events in polycythemia vera Abstract Thromboembolic events and cardiovascular disease are the most prevalent complications in patients with polycythemia vera (PV) compared with other myeloproliferative disorders and are the major cause of morbidity and mortality in this population. Moreover, a vascular complication such as arterial or venous thrombosis often leads to the diagnosis of PV. The highest rates of thrombosis typically occur shortly before or at diagnosis and decrease over time, probably due to the effects of treatment. Important risk factors include age (≥ 60 years old) and a history of thrombosis; elevated hematocrit and leukocytosis are also associated with an increased risk of thrombosis. The goal of therapy is to reduce the risk of thrombosis by controlling hematocrit to < 45%, a target associated with reduced rates of cardiovascular death and major thrombosis. Low-risk patients (< 60 years old with no history of thrombosis) are managed with phlebotomy and low-dose aspirin, whereas high-risk patients (≥ 60 years old and/or with a history of thrombosis) should be treated with cytoreductive agents. Interferon and ruxolitinib are considered second-line therapies for patients who are intolerant of or have an inadequate response to hydroxyurea, which is typically used as first-line therapy. In this review, we discuss factors associated with thrombosis and recent data on current treatments, including anticoagulation, highlighting the need for more controlled studies to determine the most effective cytoreductive therapies for reducing the risk of thrombosis in patients with PV.

Mycological Progress

Two new taxa of the Auriscalpium vulgare species complex with substrate preferences Abstract Basidiomes of the cone-inhabiting Auriscalpium species, usually regarded as A. vulgare Gray, are widely distributed across the Northern Hemisphere and easily recognized because of their unique macro-morphology. However, phylogenetic diversity patterns among different geographic populations and different substrates are completely unknown. In this study, samples of A. vulgare s.l. in different areas of China were studied phylogenetically, morphologically, and ecologically. For comparison, European collections of A. vulgare were included. Our phylogenetic analyses, inferred from partial nucleotide sequences including the internal transcribed spacers (ITS) 1 and 2 with the 5.8S nrDNA, the large subunit of nuclear ribosomal RNA (nrLSU), and the region between the conserved domain 6 and 7 of the gene for the second largest subunit of RNA polymerase II (RPB2), indicated that three phylogenetic species can be recognized, which correspond well with morphological and ecological evidence. Therefore, three species, having distinct substrate preferences, are documented here, namely the well-known A. vulgare, and the newly described species A. orientale and A. microsporum. Auriscalpium vulgare is widely distributed throughout the northern temperate Eurasia and North America, while the new species have been known mainly from subtropical East Asia and northeastern India to date.

Muyocopron heveae sp. nov. and M. dipterocarpi appears to have host-jumped to rubber Abstract Muyocopron species were collected from dried branches of Hevea brasiliensis in Thailand. These were studied and compared with related taxa, based on the evidence from morphology and phylogenetic analyses of a combined LSU and SSU DNA sequence data. A new host record, Muyocopron dipterocarpi, and a new species, Muyocopron heveae, are described and illustrated. Phylogenetic analyses of combined LSU and SSU sequence data indicated that our strains cluster in Muyocopron and the new taxon forms a distinct clade as a new species in the genus. The germinating ascospores produced appressoria which suggests that it has an endophytic lifestyle. Muyocopron dipterocarpi appears to have host-jumped to rubber, which had been introduced to Thailand.

A new species of Alpestrisphaeria (Dothideomycetes) with monodictys-like anamorph and revision of three Monodictys species Abstract Endophytic fungal strains isolated from the coastal plant Vitex rotundifolia in Taiwan were accommodated in Alpestrisphaeria according to an analysis of internal transcribed spacer (ITS) and large subunit ribosomal RNA gene sequences. Based on this analysis and on a unique monodictys-like anamorph, the species, A. monodictyoides, is proposed as new. Type specimens of three species of Monodictys were investigated. A new name is proposed for the invalid M. indica S.M. Singh & Barde (non M. indica K. Chowdhery & Rehill); the invalid M. saudii is considered sclerotium-like structures of a sterile mycelium and excluded from any taxonomic naming; M. torulosa is synonymized with M. fluctuata. Early stages of conidium ontogeny are suggested as potential phylogenetically significant markers for a future revision of the polyphyletic genus Monodictys.

The genus Inonotus in Africa Abstract A survey of the genus Inonotus in Africa is provided with a key and descriptions of nine species.

On Craterocolla and Ditangium (Sebacinales, Basidiomycota) Abstract In the present paper, we select a neotype for Tremella cerasi and prove that it is conspecific with Ditangium insigne (the genus type of Ditangium). We argue that Ditangium should be restored as a correct genus for T. cerasi, while the currently used generic name Craterocolla is to be treated as its younger synonym. Morphological, ecological and genetic variability of Ditangium cerasi is discussed, and two other Ditangium species are described—D. altaicum, sp. nov. and D. incarnatum, comb. nov. In addition, Exidia fulva is combined in Globulisebacina.

Kevinhydea brevistipitata gen. et sp. nov. and Helicoma hydei sp. nov., (Tubeufiaceae) from decaying wood habitats Abstract Kevinhydea brevistipitata gen. et sp. nov., and Helicoma hydei sp. nov., collected on decaying wood in terrestrial and freshwater habitats, respectively, are described and illustrated. Kevinhydea brevistipitata, the type species for a novel monotypic genus (Kevinhydea), is characterized by its macronematous, short conidiophores, and dictyosporous conidia. Helicoma hydei morphologically resembles H. guttulatum, but they are phylogenetically distinct species. Phylogenetic analyses of combined LSU, ITS, and TEF1α sequence data of 63 taxa were carried out to infer the phylogenetic affinity of new taxa within the family Tubeufiaceae. Additionally, phylogenetic analyses for the genus Helicoma, comprising 33 taxa, were performed separately to justify the new species H. hydei. Kevinhydea brevistipitata and Helicoma hydei are phylogenetically distinct from other species in Tubeufiaceae. A morphological comparison of dictyosporous hyphomycete genera in Tubeufiaceae is provided.

An updated phylogeny and diversity of Phylloporia (Hymenochaetales): eight new species and keys to species of the genus Abstract Phylloporia is shown to be monophyletic according to molecular sequence data. Morphologically, Phylloporia is characterized by annual or perennial basidiomata, a monomitic to dimitic hyphal system, generally presenting a duplex context, absence of setae, and abundant tiny, thick-walled and colored basidiospores. In this study, specimens from China and Brazil a priori identified to Phylloporia species were revised. Phylogenetic analysis based on the nuc 28S rDNA showed that they nested within the Phylloporia clade, in which they formed eight new terminal lineages. According to this result and additional morphological and ecological data (host relationships), these eight lineages are described as eight new species: Phylloporia atlantica, P. cystidiolophora, P. montana, P. perangusta, P. rattanicola, P. solicola, P. splendida, and P. subpulla. Detailed descriptions with illustrations are provided for these new species, and their relationships with similar or allied species are discussed. An identification key for all accepted 56 species with a synoptic description is provided, and two keys to neotropical and Asian Phylloporia species are also provided.

Progress on the phylogeny of the Omphalotaceae: Gymnopus s. str., Marasmiellus s. str., Paragymnopus gen. nov. and Pusillomyces gen. nov. Abstract Omphalotaceae is the family of widely distributed and morphologically diverse marasmioid and gymnopoid agaric genera. Phylogenetic studies have included the family in Agaricales, grouping many traditionally and recently described genera of saprotrophic or parasitic mushroom-producing fungi. However, some genera in Omphalotaceae have not reached a stable concept that reflects monophyletic groups with identifiable morphological circumscription. This is the case of Gymnopus and Marasmiellus, which have been the target of two opposing views: (1) a more inclusive Gymnopus encompassing Marasmiellus, or (2) a more restricted Gymnopus (s. str.) while Marasmiellus remains a distict genus; both genera still await a more conclusive phylogenetic hypothesis coupled with morphological recognition. Furthermore, some new genera or undefined clades need more study. In the present paper, a phylogenetic study was conducted based on nrITS and nrLSU in single and multilocus analyses including members of the Omphalotaceae, more specifically of the genera belonging to the /letinuloid clade. The resulting trees support the view of a more restricted Gymnopus and a distinct Marasmiellus based on monophyletic and strongly supported clades on which their morphological circumscriptions and taxonomic treatments are proposed herein. The results also provide evidence for the description of two new genera: Paragymnopus and Pusillomyces. Pusillomyces manuripioides sp. nov. (type species of the genus) is described with morphological description, taxonomic and ecological remarks, and illustrations.

Anupama : a new genus of Biannulariaceae (Agaricales) from tropical India Abstract Anupama gen. nov. is described from the Kerala State of India with a single species, Anupama indica sp. nov. In the field, Anupama can be characterized by its small to medium-sized, tricholomatoid basidiocarps lacking veils of any kind and growing on the soil, a brownish pileus with a glabrous, somewhat waxy surface, crowded, sinuate lamellae, and a solid, orange-gray stipe tapering towards the base. The diagnostic microscopic features include hyaline, smooth, inamyloid basidiospores, abundant cheilocystidia and scarce pleurocystidia, subregular lamellar trama, a cutis-type pileipellis, and clamped hyphae. The multigene phylogenetic analyses based on two independent data matrices revealed the taxonomic position of Anupama within the Biannulariaceae, in which it formed a lineage distinct from other genera. A taxonomic description, photographs of the basidiocarps in their natural habitat and the microscopic structures, comparisons with phenetically and phylogenetically related genera of the family, phylograms showing the placement of the new genus, and a key to the genera of the family are provided.

Oral Oncology

CorrespondenceAbstract only

Sanctuary site central nervous system relapse-refractory DLBCL responding to nivolumab and lenalidomide

Irappa V. Madabhavi, Swaroop Revannasiddaiah, Malay S. Sarkar, Mitul G. Modi

In Press, Corrected Proof, Available online 19 April 2019

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Abstract

Abstract

Despite improvement in survival in diffuse large B-cell lymphoma (DLBCL) with the introduction of rituximab, central nervous system (CNS) relapse continues to represent a clinical challenge. In diffuse large B-cell lymphoma (DLBCL), the incidence of CNS relapse is only ∼5% in unselected cohorts. Immunotherapy is the treatment that either boosts the patient's own immune system or uses man-made versions of the normal parts of the immune system to kill lymphoma cells or slow their growth. We are presenting a thirty-eight year old man who, presented with neck nodes, axillary nodes, altered sensorium, abnormal body movements, unconsciousness, weight loss and, fever, with a past history of DLBCL in May 2008, treated with 6 cycles of CHOP and completed in November 2008. After 9 years in April 2018, the patient developed similar symptoms and treated with salvage chemotherapy with R-DHAP which was completed in September 2018. Post-treatment PET-CT showed partial metabolic response and we started external beam radiotherapy to initial bulky disease. After completion of radiotherapy, the patient was very reluctant for any type of therapy and went home. After one month he presented to us with persistent vomiting, abnormal body movements and, altered sensorium. On examination, his Glasgow Coma Scale (GCS) was E2V3M2 and he was admitted in Intensive Care Unit. The patient was managed with mannitol, dexamethasone, antiepileptics, antibiotics and other supportive care medicines. His brain magnetic resonance imaging (MRI) was showing multiple heterogeneously enhancing lesions with surrounding vasogenic oedema and his cerebrospinal fluid analysis was positive for malignant cells. He was managed with triple intrathecal chemotherapy with methotrexate 12 mg, Cytarabine 50 mg, and Hydrocortisone 50 mg along with other supportive care medicines, and after 4–5 days he regained consciousness and he was able to talk and understand verbal commands. In view of improvement in general condition and performance status, we started biweekly triple intra-thecal therapy, and Inj. Nivolumab 3 mg per kg q 2 weekly. From the second cycle, we started Lenalidomide 10 mg once a day for 21 days with 7 days gap along with 2 weekly nivolumab and biweekly triple IT chemotherapy. After one month his CSF analysis was negative for malignant cells. Now he is on regular treatment with weekly IT chemotherapy, 2 weekly nivolumab and 3 weeks on and one week off lenalidomide. After 2 months of treatment, his MRI Brain was showing. At the time of submission of this article, he has completed the fifth cycle of immunotherapy and two cycles of lenalidomide. He was able to manage his daily ADL and able to walk with a stick. The patient tolerated immunotherapy, triple IT therapy and lenalidomide very well without much intolerable side effects. Therefore, we concluded that nivolumab and lenalidomide was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory sanctuary site CNS B- cell lymphomas. Additional studies of Nivolumab and lenalidomide in these diseases are ongoing.

select article Human papillomavirus (HPV) vaccine and HPV-related head and neck cancer: What's next?

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Human papillomavirus (HPV) vaccine and HPV-related head and neck cancer: What's next?

F. De Felice, A. Polimeni, V. Tombolini

In Press, Corrected Proof, Available online 5 April 2019

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select article Oral tongue cancer in a patient with hereditary nonpolyposis colorectal cancer: A case report and review of the literature

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Oral tongue cancer in a patient with hereditary nonpolyposis colorectal cancer: A case report and review of the literature

Andrea Ziegler, Eric Thorpe

In Press, Corrected Proof, Available online 15 March 2019

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Abstract

Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by mutations of mismatch repair genes leading to the early development of multiple malignancies. The most common malignancy is colorectal cancer but there is a strong association with malignancies of the ovary, endometrium, small intestine, stomach, skin, brain, and pancreas. We report a case of a 35-year-old female with a history of known HNPCC who presented with adenocarcinoma of the small intestine as well as a synchronous oral tongue squamous cell carcinoma. The patient underwent a combined oncologic surgery involving a hemiglossectomy, selective neck dissection, and partial small bowel resection. Despite the wide range of malignancies seen in patients with HNPCC, no cases of oral cavity cancer have previously been reported. This represents the first case in the literature of oral cavity cancer in a patient with HNPCC.

select article Prognostic implications of pathologic lymph nodes in HPV-positive oropharyngeal cancers: Clinical validity and strategies for routine clinical practice

CorrespondenceNo access

Prognostic implications of pathologic lymph nodes in HPV-positive oropharyngeal cancers: Clinical validity and strategies for routine clinical practice

Rama Jayaraj, Chellan Kumarasamy, Madhav Madurantakam Royam, Shanthi Sabarimurugan, Siddhartha Baxi

In Press, Corrected Proof, Available online 9 March 2019

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select article Revisiting and revising the definition of oral submucous fibrosis

CorrespondenceNo access

Revisiting and revising the definition of oral submucous fibrosis

Mohit Sharma, Raghu Radhakrishnan

In Press, Corrected Proof, Available online 8 March 2019

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select article Ossified Carcinoma Ex Pleomorphic Adenoma in accessory lobe of parotid gland: Complexity in clinical, imaging and histologic diagnosis and minimally invasive surgery

CorrespondenceAbstract only

Ossified Carcinoma Ex Pleomorphic Adenoma in accessory lobe of parotid gland: Complexity in clinical, imaging and histologic diagnosis and minimally invasive surgery

Raffaele Rauso, Giuseppe Colella, Renato Franco, Andrea Ronchi, Fabrizio Chirico

In Press, Corrected Proof, Available online 7 March 2019

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Abstract

Abstract

Carcinoma ex pleomorphic adenoma is not common among malignant salivary tumors and an accessory lobe of parotid gland tumor with a carcinoma ex pleomorphic adenoma histology is even rarer. Management of these tumors include a high index of suspicion, good understanding of the anatomy and a meticulous surgical access. The exceptional localization of an ossified Carcinoma ex Pleomorphic Adenoma in the accessory lobe of the parotid gland, never reported to date in the literature, has prompted us to report this case to stress the challenging difficulties related to clinical and histologic diagnosis and to analyze a minimally invasive intraoral approach.