bluuebunny/crossref_metadata_2025 huggingface dataset:
Production and Chemical Characterization of Exopolysaccharides by Antarctic Yeasts Vishniacozyma victoriae and Tremellomycetes sp.
Authors: Rusinova-Videva Snezhana , Ognyanov Manol , Georgiev Yordan , Kambourova Margarita , Adamov Aleksandar , Krasteva Vasilena
Published: February 2022

The study aimed to investigate exopolysaccharides (EPSs) produced by two Antarctic yeasts isolated from Livingston Island. The species were identified as Vishniacozyma victoriae (V) and Tremellomycetes sp. (T) based on a molecular genetic analysis of ITS1-5.8S-ITS4 regions of the 18S rRNA gene. The EPS production was investigated under stress conditions in culture flasks and a bioreactor. Different chromatographic (HPLC-RID, HPSEC-RID) and spectral (FT-IR) analyses were employed to characterize EPSs. Tremellomycetes sp. accumulated 7 g/L biomass and 4.5 g/L EPS after 120 h of cultivation. The total carbohydrate content of V-EPS and T-EPS was 75.4% and 79.0%, respectively. The EPSs mainly consisted of mannose (30–32%), which was followed by glucose, xylose, galactose, and small amounts of uronic acids (6.3–7.0%). EPSs had appreciable amounts of proteins (11–12%). The FT-IR spectra contained absorption bands typical for hetero-mannans and β-glucans (797–1033 cm−1). EPSs were heterogeneous with a broad molecular weight distribution range (47 × 104–68 × 104 g/mol). In conclusion, both yeasts synthesized high-molecular-weight heteromannans, and Tremellomycetes sp. stood out as being a better producer than V. victoriae. The current study also formed a basis for a better assessment of the potential for practical application of EPSs and yeasts in biochemical engineering and biotechnology.
Spatiotemporal Variation of Air Quality (PM and NO2) in Southern Paris during COVID-19 Lockdown Periods
Authors: Dahech Salem , Abdmouleh Mohamed Ali , Lagmiri Souad
Published: February 2022

In urban areas, road transportation is the main source of pollutants, and weather impacts spatiotemporal variation of air quality. In this paper, we demonstrate the spatiotemporal variabilities of particulate matter (PM10 and PM2.5) and NO2 in the south of Paris, with an emphasis on the comparison of air pollutant levels between COVID-19 lockdown and non-lockdown days according to meteorological conditions. The influence of COVID-19 lockdowns could be region-specific. Thus, it is worthwhile to conduct investigations across different regions and via different methodologies. This manuscript contains data that could be relied upon to evaluate available options for mitigation of urban air pollution. Using Airparif data and mobile survey data collected by Aeroqual 500 sensors, this study confirms that road traffic seems to be the determining factor of air quality in the southern part of Paris. The daily average concentrations of NO2, PM2.5 and PM10 calculated in 2020 show a strong spatiotemporal variability explained by the type of weather on the one hand and by the proximity of emission sources on the other hand. Mobile surveys show that during lockdowns in 2020, when the weather was stable, in 13th arrondissement of Paris, NO2 values exceeded 250 µg/m3 with PM10 values over 70 µg/m3, mainly in three locations: the area between Rue Tolbiac and Rue Nationale, along Rue de Chevaleret, and on Boulevard Périphérique.
Experimental and Theoretical Studies of Trans-2-Pentenal Atmospheric Ozonolysis
Authors: Kalalian Carmen , Grira Asma , Illmann Jan Niklas , Patroescu-Klotz Iulia , El Dib Gisèle , Coddeville Patrice , Canosa André , Wiesen Peter , Aazaad Basheer , Senthilkumar Lakshmipathi , Roth Estelle , Tomas Alexandre , Chakir Abdelkhaleq
Published: February 2022

We investigated the kinetics, mechanism and secondary organic aerosols formation of the ozonolysis of trans-2-pentenal (T2P) using four different reactors with Fourier Transform InfraRed (FTIR) spectroscopy and Gas Chromatography (GC) techniques at T = 298 ± 2 K and 760 Torr in dry conditions. The rate coefficients and branching ratios were also evaluated using the canonical variational transition (CVT) state theory coupled with small curvature tunneling (CVT/SCT) in the range 278–350 K. The experimental rate coefficient at 298 K was (1.46 ± 0.17) × 10−18 cm3 molecule−1 s−1, in good agreement with the theoretical rate. The two primary carbonyls formation yields, glyoxal and propanal, were 57 ± 10% and 42 ± 12%, respectively, with OH scavenger compared to 38 ± 8% for glyoxal and 26 ± 5% for propanal without OH scavenger. Acetaldehyde and 2-hydroxypropanal were also identified and quantified with yields of 9 ± 3% and 5 ± 2%, respectively, in the presence of OH scavenger. For the OH production, an upper limit of 24% was estimated using mesitylene as OH tracer. Combining experimental and theoretical findings enabled the establishment of a chemical mechanism. Finally, the SOA formation was observed with mass yields of about 1.5%. This work provides additional information on the effect of the aldehyde functional group on the fragmentation of the primary ozonide.
Spatiotemporal Rainfall Variability and Drought Assessment during Past Five Decades in South Korea Using SPI and SPEI
Authors: Moazzam Muhammad Farhan Ul , Rahman Ghani , Munawar Saira , Farid Nasir , Lee Byung Gul
Published: February 2022

About 41% of the earth is drought-affected, which has impacted nearly 2 billion people, and it is expected that more than 90% of terrestrial areas will be degraded by 2050. To evade and mitigate the harmful impacts of drought, it is necessary to study the rainfall variability and assess the drought trend at a global and regional level. This study utilized 70 meteorological stations in South Korea to evaluate the rainfall variability, drought, and its trend during the past five decades using the standardized precipitation evapotranspiration index (SPEI) and the standardized precipitation index (SPI). Rainfall data normality was assessed with mean, standard deviation, skewness, and kurtosis. The highest amount of rainfall was observed in the months of June, July, and August. The SPI and SPEI 12-month results revealed that 1982, 1988, 2008, 2015, and 2017 were dry years throughout the country, while from 2013 to 2017 mixed drought events were observed for the 6-month time series. The Mann-Kendall trend test was applied to the 1- and 12-month time series, and the results revealed that the months of January, March, April, May, June, and August had a significant negative trend, which means drought is increasing in these months, while the months of September, October, and December had a significant positive trend, which means wetter conditions prevailed in these months during the study period. It was observed in the 12-month time series that only two met stations had a significant negative trend, while only one had a significant positive trend. It was found that January and March were the driest months, and October was the wettest month. The detected drought events in this research are consistent with ENSO events. We have observed differences in drought characteristics (duration and frequency) for both indices. Climatic data revealed that South Korea has faced drought conditions (rainfall deficit) due to a shortened monsoon season. This study can provide guidance on water management strategies under the changing pattern of drought in South Korea.
Influence of Absorption Cross-Sections on Retrieving the Ozone Vertical Distribution at the Siberian Lidar Station
Authors: Dolgii Sergey , Nevzorov Alexey A. , Nevzorov Alexey V. , Gridnev Yurii , Kharchenko Olga , Romanovskii Oleg A.
Published: February 2022

The purpose of this paper is to study how the application of different sets of absorption cross-sections influence the ozone vertical distribution (OVD) in the upper layers of the troposphere—stratosphere in the altitude range ~(5–45) km, using a differential absorption lidar (DIAL), operating at the sensing wavelengths 299/341 nm and 308/353 nm. We analyzed the results of lidar measurements of OVD obtained in 2021 using meteorological data from the IASI/MetOp satellite at the Siberian Lidar Station (SLS). The retrieval was performed using the data of four groups concerning the absorption cross-sections: Gorshelev et al., Malicet et al., SCIAMACHY, and GOME. To estimate how the absorption cross-sections influence the OVD retrieval from lidar measurements, we calculated the average deviations between the profiles retrieved using different sets both in a particular case on 2 January 2021 and throughout 2021. Our study showed that, out of the four absorption cross-section sets, the data of Gorshelev et al. should be used for long-term lidar monitoring of the ozone. These data show a more discrete dependence of the absorption cross-sections on the temperature values, which is more urgent for tropospheric and stratospheric ozone measurements.
Hydroclimatology of the Chitral River in the Indus Basin under Changing Climate
Authors: Syed Zain , Ahmad Shakil , Dahri Zakir Hussain , Azmat Muhammad , Shoaib Muhammad , Inam Azhar , Qamar Muhammad Uzair , Hussain Syed Zia , Ahmad Sarfraz
Published: February 2022

Biased distribution of hydro-climate stations in high elevations are major obstacles for reliable appraisal of the hydro-climatic regime of the Chitral Basin located in the extreme north of Pakistan. We modeled this regime in the ARC-SWAT hydrological model forced with the latest gridded reanalysis ERA5 Land dataset, bias-corrected against a good quality reference dataset. The performance of the gridded dataset was cross-validated by comparing the model flow simulation against the observed flows. The ERA5 Land overall provided reasonably good estimates. The calibrated model on the daily time scale was able to provide excellent values of the employed statistical measures (NSE, KGE, PBIAS, RMSE and MAE). For a future climate change analysis, climate series was devised using two future projection scenarios (RCP4.5 and RCP8.5) using the best performing GCM (MIROC5_rlilp1) out of five investigated GCMs. The results of the climate change analysis reveal increment in the average temperature up to +3.73 °C and +5.62 °C for RCP4.5 and RCP8.5, respectively, while the analysis of precipitation suggests an annual decrease up to −16% and −35% against RCP4.5 and RCP8.5, respectively, by the end of century. A future simulated flow analysis showed an increment of +0.25 % and decrease of −6.82% for RCP4.5 and RCP8.5, respectively. Further analysis of climate suggests seasonal deflections especially in precipitation and flow regimes. A notable climb in flow quantities was observed during spring season (MAM) in spite of the major reduction in precipitation amounts for that season. This implicitly supports a high rate of glacial/snow melt especially in the spring season during that period. Frequent droughts and floods are also projected by examining flow durations at each interval of the 21st century.
Dry Sliding Behavior and Particulate Emissions of a SiC-graphite Composite Friction Material Paired with HVOF-Coated Counterface
Authors: Jayashree Priyadarshini , Sinha Ankur , Gialanella Stefano , Straffelini Giovanni
Published: February 2022

Dry sliding wear tests and corresponding particulate matter (PM) analysis were conducted on a newly developed SiC-graphite-based composite friction material, paired with two types of HVOF counterface/discs: WC-CoCr and WC-FeCrAlY coatings, with a conventional martensitic stainless steel counterface as a reference. The trials were conducted on a pin-on-disc testing equipment at room temperature and a constant sliding velocity and contact pressure of 7 m/s and 0.5 MPa, respectively. The coefficient of friction (CoF) curves with the uncoated disc exhibited considerable fluctuations. On the other hand, the coated discs featured an increase in the CoF at the beginning of the tests, followed by either a continuous reduction until the end of the testing duration or the attainment of a steady state regime. The pin wear and emissions with both coatings were appreciably lower when compared to the trials with the uncoated disc. The evaluation of the friction layer observed a significant contribution of the counterface for all the pairings. The PM analysis was conducted on the particles that were lying in the range of 10 μm and 2.5 μm on a scanning electron microscope (SEM), and particles from 2.5 μm and 1 μm on transmission electron microscope (TEM), with an emphasis on the particles that were detached from the pin surface and friction layer to explain the wear mechanisms for each pairing. Through this, the need for the proper selection of both friction material and counterface to avoid the emission of harmful compounds in the environment was highlighted.
A New PM Sampler with a Built-In Black Carbon Continuous Monitor
Authors: Caponi Lorenzo , Cazzuli Gianluca , Gargioni Giulio , Massabò Dario , Brotto Paolo , Prati Paolo
Published: February 2022

We introduce a new instrument for sampling the airborne particulate matter (PM) while monitoring the black carbon (BC) atmospheric concentration. The concentration of PM and BC are usually measured by separate instruments with possible systematics differences even in the collecting inlets. The new equipment is based on a low-volume sequential PM sampler, fully compliant with the EU-CEN and US-EPA regulatory standards, with a built-in optical BC monitor. The BC concentration is continuously measured during the sampling in the PM accumulated on the filter while the PM concentration can be obtained off-line by a standard gravimetric analysis. The optical set-up, upstream the collecting filter, is composed by a single wavelength light source (λ = 635 nm) and a photodiode, placed in way to receive the light backscattered by the filter surface at a fixed angle. The mechanical arrangement does not introduce any perturbation to the PM sampling. Thanks to an original calibration curve, the sample absorbance is deduced from the output signal of the photodiode. Finally, the BC concentration is obtained through the Mass Absorption Coefficient (MAC). After the sampling and the PM gravimetric determination, the same filter can be sent to other compositional analyses. Thermo-optical quantification of the Elemental and Organic Carbon (EC and OC) in the filter sample can thus be exploited to tune the MAC value to the PM composition of a particular site. The main features of the new instrument and the set of validation tests against other PM samplers and BC monitors of widespread use (i.e.,: Multi Angle Absorption Photometer and aethalometer) are detailed and discussed.
Statistical Convergence via q-Calculus and a Korovkin’s Type Approximation Theorem
Authors: Ayman Mursaleen Mohammad , Serra-Capizzano Stefano
Published: February 2022

In this paper, we define and study q-statistical limit point, q-statistical cluster point, q-statistically Cauchy, q-strongly Cesàro and statistically C1q-summable sequences. We establish relationships of q-statistical convergence with q-statistically Cauchy, q-strongly Cesàro and statistically C1q-summable sequences. Further, we apply q-statistical convergence to prove a Korovkin type approximation theorem.
Quantifying Circulating IgY Antibody Responses against Select Opportunistic Bacterial Pathogens and Correlations with Body Condition Factors in Wild American Alligators, Alligator mississippiensis
Authors: Alston Bailey M. , Rainwater Thomas R. , Parrott Benjamin B. , Wilkinson Philip M. , Bowden John A. , Rice Charles D.
Published: February 2022

Little is known about the disease ecology of American alligators (Alligator mississippiensis), and especially how they respond immunologically to emerging infectious diseases and zoonotic pathogens. In this study, we examined serum samples collected from wild alligators in Florida (2010–2011) and South Carolina (2011–2012, 2014–2017) for antibody responses to multiple bacteria. Immunoglobulin Y (IgY) was purified from serum to generate a mouse monoclonal antibody (mAb AMY-9) specific to the IgY heavy chain. An indirect ELISA was then developed for quantifying antibody responses against whole cell Escherichia coli,Vibrio parahaemolyticus, Vibrio vulnificus, Mycobacterium fortuitum, Erysipelothrix rhusiopthiae, and Streptococcus agalactiae. In Florida samples the primary differences in antibody levels were between January–March and late spring through summer and early fall (May-October), most likely reflecting seasonal influences in immune responses. Of note, differences over the months in antibody responses were confined to M. fortuitum, E. rhusiopthiae, V. vulnificus, and E. coli. Robust antibody responses in SC samples were observed in 2011, 2014, and 2015 against each bacterium except E. coli. All antibody responses were low in 2016 and 2017. Some of the highest antibody responses were against V. parahaemolyticus, M. fortuitum, and E. rhusiopthiae. One SC alligator estimated to be 70+ years old exhibited the highest measured antibody response against V. parahaemolyticus and M. fortuitum. By combining data from both sites, we show a clear correlation between body-mass-indices (BMI) and antibody titers in all six of the bacteria examined. Our study provides a critical antibody reagent and a proof-of-concept approach for studying the disease ecology of alligators in both the wild and in captivity.
Insect and Plant Diversity in Hot-Spring Ecosystems during the Jurassic-Cretaceous Boundary from Spain (Aguilar Fm., Palencia)
Authors: Santos Artai A. , Nel André , Rodríguez-Barreiro Iván , Sender Luis M. , Wappler Torsten , Diez José B.
Published: February 2022

Hydrothermal palaeoenvironments are very uncommon in Upper Jurassic and Lower Cretaceous deposits worldwide. We present new plant and insect remains from travertines formed during the Jurassic-Cretaceous boundary in northern Spain (Aguilar Fm., Palencia province). A total of 136 plant specimens and three insect wings were collected and studied. This entomofauna consists of dragonfly (Odonata) wings including Cymatophlebiidae and an undetermined new genus and species of Aktassiidae, representing the first report of these families for the Iberian Peninsula. The fossil flora shows different morphotypes of plants, which have been tentatively assigned to three different genera. The taphocoenosis of the flora was dominated by Bennettitales (98.5%) including cf. Pterophyllum sp., Ptilophyllum cf. acutifolium, Ptilophyllum cf. pecten, Ptilophyllum cf. pectiniformis and cf. Ptilophyllum sp., and the occasional presence of ferns (1.5%) represented by the taxon Cladophlebis cf. denticulata. The presence of the Anisoptera Cymatophlebia cf. longialata suggests a higher affinity for a Tithonian age of the studied site, and the anatomy and palaeogeographical distribution of this species suggest capacity to migrate for rather long distances. The floristic composition of the site differs remarkably from other Tithonian-Berriasian floras of the Iberian Peninsula. The presence of Odonata and the distinctive flora in (semi)arid conditions could be due to the hot-spring providing an environmental niche with constant conditions of warmth and humidity forming an ‘ecological oasis’.
Systemic Administration of the TLR7/8 Agonist Resiquimod (R848) to Mice Is Associated with Transient, In Vivo-Detectable Brain Swelling
Authors: Zahr Natalie May , Zhao Qingyu , Goodcase Ryan , Pfefferbaum Adolf
Published: February 2022

Peripheral administration of the E. coli endotoxin lipopolysaccharide (LPS) to rats promotes secretion of pro-inflammatory cytokines and in previous studies was associated with transient enlargement of cortical volumes. Here, resiquimod (R848) was administered to mice to stimulate peripheral immune activation, and the effects on brain volumes and neurometabolites determined. After baseline scans, 24 male, wild-type C57BL mice were triaged into three groups including R848 at low (50 μg) and high (100 μg) doses and saline controls. Animals were scanned again at 3 h and 24 h following treatment. Sickness indices of elevated temperature and body weight loss were observed in all R848 animals. Animals that received 50 μg R848 exhibited decreases in hippocampal N-acetylaspartate and phosphocreatine at the 3 h time point that returned to baseline levels at 24 h. Animals that received the 100 μg R848 dose demonstrated transient, localized, volume expansion (~5%) detectable at 3 h in motor, somatosensory, and olfactory cortices; and pons. A metabolic response evident at the lower dose and a volumetric change at the higher dose suggests a temporal evolution of the effect wherein the neurochemical change is demonstrable earlier than neurostructural change. Transient volume expansion in response to peripheral immune stimulation corresponds with previous results and is consistent with brain swelling that may reflect CNS edema.
Ibuprofen in Therapeutic Concentrations Affects the Secretion of Human Bone Marrow Mesenchymal Stromal Cells, but Not Their Proliferative and Migratory Capacity
Authors: Kulesza Agnieszka , Zielniok Katarzyna , Hawryluk Jakub , Paczek Leszek , Burdzinska Anna
Published: February 2022

Mesenchymal stromal cells (MSCs) are able to modulate the immune system activity and the regeneration processes mainly through the secretion of multiple soluble factors, including prostaglandin E2 (PGE2). PGE2 is produced as a result of cyclooxygenases (COX) activity. In the present study, we investigated how ibuprofen, a nonselective COX inhibitor, affects the proliferation, migration and secretion of human bone marrow MSCs (hBM-MSCs). For this purpose, six hBM-MSCs populations were treated with ibuprofen at doses which do not differ from maximum serum concentrations during standard pharmacotherapy. Ibuprofen treatment (25 or 50 µg/mL) substantially reduced the secretion of PGE2 in all tested populations. Following ibuprofen administration, MSCs were subjected to proliferation (BrdU), transwell migration, and scratch assays, while its effect on MSCs secretome was evaluated by Proteome Profiler and Luminex immunoassays. Ibuprofen did not cause statistically significant changes in the proliferation rate and migration ability of MSCs (p > 0.05). However, ibuprofen (25 µg/mL for 3 days) significantly decreased mean secretion of: CCL2 (by 44%), HGF (by 31%), IL-6 (by 22%), VEGF (by 20%) and IL-4 (by 8%) compared to secretion of control MSCs (p < 0.05). Our results indicate that ibuprofen at therapeutic concentrations may impair the pro-regenerative properties of hBM-MSCs.
Glomerular Biomechanical Stress and Lipid Mediators during Cellular Changes Leading to Chronic Kidney Disease
Authors: Sharma Mukut , Singh Vikas , Sharma Ram , Koul Arnav , McCarthy Ellen T. , Savin Virginia J. , Joshi Trupti , Srivastava Tarak
Published: February 2022

Hyperfiltration is an important underlying cause of glomerular dysfunction associated with several systemic and intrinsic glomerular conditions leading to chronic kidney disease (CKD). These include obesity, diabetes, hypertension, focal segmental glomerulosclerosis (FSGS), congenital abnormalities and reduced renal mass (low nephron number). Hyperfiltration-associated biomechanical forces directly impact the cell membrane, generating tensile and fluid flow shear stresses in multiple segments of the nephron. Ongoing research suggests these biomechanical forces as the initial mediators of hyperfiltration-induced deterioration of podocyte structure and function leading to their detachment and irreplaceable loss from the glomerular filtration barrier. Membrane lipid-derived polyunsaturated fatty acids (PUFA) and their metabolites are potent transducers of biomechanical stress from the cell surface to intracellular compartments. Omega-6 and ω-3 long-chain PUFA from membrane phospholipids generate many versatile and autacoid oxylipins that modulate pro-inflammatory as well as anti-inflammatory autocrine and paracrine signaling. We advance the idea that lipid signaling molecules, related enzymes, metabolites and receptors are not just mediators of cellular stress but also potential targets for developing novel interventions. With the growing emphasis on lifestyle changes for wellness, dietary fatty acids are potential adjunct-therapeutics to minimize/treat hyperfiltration-induced progressive glomerular damage and CKD.
Phosphoproteomic Analysis of Breast Cancer-Derived Small Extracellular Vesicles Reveals Disease-Specific Phosphorylated Enzymes
Authors: Minic Zoran , Hüttmann Nico , Poolsup Suttinee , Li Yingxi , Susevski Vanessa , Zaripov Emil , Berezovski Maxim V.
Published: February 2022

Small membrane-derived extracellular vesicles have been proposed as participating in several cancer diseases, including breast cancer (BC). We performed a phosphoproteomic analysis of breast cancer-derived small extracellular vesicles (sEVs) to provide insight into the molecular and cellular regulatory mechanisms important for breast cancer tumor progression and metastasis. We examined three cell line models for breast cancer: MCF10A (non-malignant), MCF7 (estrogen and progesterone receptor-positive, metastatic), and MDA-MB-231 (triple-negative, highly metastatic). To obtain a comprehensive overview of the sEV phosphoproteome derived from each cell line, effective phosphopeptide enrichment techniques IMAC and TiO2, followed by LC-MS/MS, were performed. The phosphoproteome was profiled to a depth of 2003 phosphopeptides, of which 207, 854, and 1335 were identified in MCF10A, MCF7, and MDA-MB-231 cell lines, respectively. Furthermore, 2450 phosphorylation sites were mapped to 855 distinct proteins, covering a wide range of functions. The identified proteins are associated with several diseases, mostly related to cancer. Among the phosphoproteins, we validated four enzymes associated with cancer and present only in sEVs isolated from MCF7 and MDA-MB-231 cell lines: ATP citrate lyase (ACLY), phosphofructokinase-M (PFKM), sirtuin-1 (SIRT1), and sirtuin-6 (SIRT6). With the exception of PFKM, the specific activity of these enzymes was significantly higher in MDA-MB-231 when compared with MCF10A-derived sEVs. This study demonstrates that sEVs contain functional metabolic enzymes that could be further explored for their potential use in early BC diagnostic and therapeutic applications.
Caregiver Burden in Partners of Parkinsonian Patients with Deep Brain Stimulation
Authors: Gülke Eileen , Pötter-Nerger Monika
Published: February 2022

In Parkinson’s disease (PD) patients, the progressive nature of the disease and the variability of disabling motor and non-motor symptoms contribute to the growing caregiver burden of PD partners and conflicts in their relationships. Deep brain stimulation (DBS) improves PD symptoms and patients’ quality of life but necessitates an intensified therapy optimization after DBS surgery. This review illuminates caregiver burden in the context of DBS, framing both pre- and postoperative aspects. We aim to provide an overview of perioperative factors influencing caregiver burden and wish to stimulate further recognition of caregiver burden of PD patients with DBS.
Global Patient Involvement in Sarcoma Care—A Collaborative Initiative of the Connective Tissue Oncology Society (CTOS) & Sarcoma Patients EuroNet (SPAEN)
Authors: Kasper Bernd , Schuster Kathrin , Wilson Roger , Bickley Sorrel , Blay Jean-Yves , Reinke Denise , Wartenberg Markus , Haas Rick
Published: February 2022

Sarcomas are a grouping of rare cancers with a wide variety of histological types that are difficult to diagnose and treat. This leads to many varying challenges not only for sarcoma patients, but also for doctors, researchers, and caregivers. Patient advocacy groups have an important role to play in rare cancers such as sarcomas, especially in collaboration with experts and their medical societies. To this end, patients and patient advocates from Sarcoma Patients EuroNet (SPAEN), a global network of national Sarcoma Patient Advocacy Groups, and medical experts from the scientifically driven Connective Tissue Oncology Society (CTOS) came together on 9 November 2021 at an official ancillary event to the CTOS 2021 Annual Meeting. At the event, representatives of CTOS and SPAEN jointly discussed gaps and challenges in global sarcoma care and management. This resulting position paper highlights the main findings and possible future steps.
Second-Harmonic Generation Imaging Reveals Changes in Breast Tumor Collagen Induced by Neoadjuvant Chemotherapy
Authors: Desa Danielle E. , Wu Wencheng , Brown Robert M. , Brown Edward B. , Hill Robert L. , Turner Bradley M. , Brown Edward B.
Published: February 2022

Breast cancer is the most common invasive cancer in women, with most deaths attributed to metastases. Neoadjuvant chemotherapy (NACT) may be prescribed prior to surgical removal of the tumor for subsets of breast cancer patients but can have diverse undesired and off-target effects, including the increased appearance of the ‘tumor microenvironment of metastasis’, image-based multicellular signatures that are prognostic of breast tumor metastasis. To assess whether NACT can induce changes in two other image-based prognostic/predictive signatures derived from tumor collagen, we quantified second-harmonic generation (SHG) directionality and fiber alignment in formalin-fixed, paraffin-embedded sections of core needle biopsies and primary tumor excisions from 22 human epidermal growth factor receptor 2-overexpressing (HER2+) and 22 triple-negative breast cancers. In both subtypes, we found that SHG directionality (i.e., the forward-to-backward scattering ratio, or F/B) is increased by NACT in the bulk of the tumor, but not the adjacent tumor-stroma interface. Overall collagen fiber alignment is increased by NACT in triple-negative but not HER2+ breast tumors. These results suggest that NACT impacts the collagenous extracellular matrix in a complex and subtype-specific manner, with some prognostic features being unchanged while others are altered in a manner suggestive of a more metastatic phenotype.
Recent Developments of Circulating Tumor Cell Analysis for Monitoring Cutaneous Melanoma Patients
Authors: Shoji Yoshiaki , Bustos Matias A. , Gross Rebecca , Hoon Dave S. B.
Published: February 2022

Circulating tumor cells (CTCs) have been studied using multiple technical approaches for interrogating various cancers, as they allow for the real-time assessment of tumor progression, disease recurrence, treatment response, and tumor molecular profiling without the need for a tumor tissue biopsy. Here, we will review studies from the last 15 years on the assessment of CTCs in cutaneous melanoma patients in relation to different clinical outcomes. The focus will be on CTC detection in blood samples obtained from cutaneous melanoma patients of different clinical stages and treatments utilizing multiple platforms. Assessment of multiple molecular melanoma-associated antigen (MAA) markers by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was the most common assay allowing for the improvement of assay sensitivity, tumor heterogeneity, and to predict patient outcomes. Multicenter studies demonstrate the utility of CTC assays reducing the bias observed in single- center trials. The recent development of CTC enrichment platforms has provided reproducible methods. CTC assessment enables both multiple mRNAs and DNAs genomic aberration profiling. CTC provides specific important translational information on tumor progression, prediction of treatment response, and survival outcomes for cutaneous melanoma patients. The molecular studies on melanoma CTCs have provided and may set standards for other solid tumor CTC analyses.
Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain
Authors: Stroet Marcus , de Blois Erik , de Jong Marion , Seimbille Yann , Mezzanotte Laura , Löwik Clemens , Panth Kranthi
Published: February 2022

Purpose: To assess our improved NACA for the detection of tumor necrosis. Methods: We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead or alive cultured cells and performed SPECT and fluorescence imaging of both spontaneous and treatment-induced necrosis in murine breast cancer models. We simultaneously recorded [18F]FDG-PET and bioluminescence images for complementary detection of tumor viability. Results: We generated two albumin-binding IRDye800CW derivatives which were labeled with indium-111 with high radiochemical purity. Surprisingly, both albumin-binding NACAs had >10x higher in vitro binding towards dead cells. We selected [111In]3 for in vivo experiments which showed higher dead cell binding in vitro and in vivo stability. The doxorubicin-treated tumors showed increased [111In]3-uptake (1.74 ± 0.08%ID/g after saline treatment, 2.25 ± 0.16%ID/g after doxorubicin treatment, p = 0.044) and decreased [18F]FDG-uptake (3.02 ± 0.51%ID/g after saline treatment, 1.79 ± 0.11%ID/g after doxorubicin treatment, p = 0.040), indicating therapy efficacy. Moreover, we detected increased [111In]3-uptake and tumor necrosis in more rapidly growing EMT6 tumors. Conclusions: Our albumin-binding NACA based on IRDye800CW facilitates tumor-necrosis imaging for assessment of therapy efficacy and aggressiveness in solid tumors using both fluorescence and SPECT imaging.
Circular RNAs Modulate Cancer Hallmark and Molecular Pathways to Support Cancer Progression and Metastasis
Authors: Yarmishyn Aliaksandr A. , Ishola Afeez Adekunle , Chen Chieh-Yu , Verusingam Nalini Devi , Rengganaten Vimalan , Mustapha Habeebat Aderonke , Chuang Hao-Kai , Teng Yuan-Chi , Phung Van Long , Hsu Po-Kuei , Lin Wen-Chang , Ma Hsin-I , Chiou Shih-Hwa , Wang Mong-Lien
Published: February 2022

Circular RNAs (circRNAs) are noncoding products of backsplicing of pre-mRNAs which have been established to possess potent biological functions. Dysregulated circRNA expression has been linked to diseases including different types of cancer. Cancer progression is known to result from the dysregulation of several molecular mechanisms responsible for the maintenance of cellular and tissue homeostasis. The dysregulation of these processes is defined as cancer hallmarks, and the molecular pathways implicated in them are regarded as the targets of therapeutic interference. In this review, we summarize the literature on the investigation of circRNAs implicated in cancer hallmark molecular signaling. First, we present general information on the properties of circRNAs, such as their biogenesis and degradation mechanisms, as well as their basic molecular functions. Subsequently, we summarize the roles of circRNAs in the framework of each cancer hallmark and finally discuss the potential as therapeutic targets.
hPG80 (Circulating Progastrin), a Novel Blood-Based Biomarker for Detection of Poorly Differentiated Neuroendocrine Carcinoma and Well Differentiated Neuroendocrine Tumors
Authors: Chauhan Aman , Prieur Alexandre , Kolesar Jill , Arnold Susanne , Payen Léa , Mahi Younes , Vire Berengere , Sands Madison , Evers B. Mark , Joubert Dominique , Anthony Lowell
Published: February 2022

Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG80) is a novel biomarker that can be easily measured in plasma by ELISA. This study is the first to examine hPG80 in NENs. Plasma hPG80 was quantified from 95 stage IV NEN patients, using DxPG80 technology (ECS Progastrin, Switzerland) and compared with hPG80 concentrations in two cohorts of healthy donor controls aged 50–80 (n = 252) and 18–25 (n = 137). Median hPG80 in NENs patients was 5.54 pM compared to 1.5 pM for the 50–80 controls and 0.29 pM the 18–25 cohort (p < 0.0001). Subgroup analysis revealed median hPG80 levels significantly higher than for either control cohort in neuroendocrine carcinoma (NEC; n = 25) and neuroendocrine tumors (NET; n = 70) including the small-cell lung cancer (SCLC) sub-cohort (n = 13). Diagnostic accuracy, estimated by AUCs, was high for NENs, as well as both sub-groups (NEC/NET) when compared to the younger and older control groups. Plasma hPG80 in NENs may be a diagnostic blood biomarker for both low- and high-grade NENs; further study is warranted. A prospective multi-center trial is ongoing in NET to evaluate hPG80 as a means of monitoring disease (NCT04750954).
Circular RNAs and Drug Resistance in Genitourinary Cancers: A Literature Review
Authors: Long Gongwei , Ma Siquan , Shi Runlin , Sun Yi , Hu Zhiquan , Chen Ke
Published: February 2022

In recent years, systematic treatment has made great progress in genitourinary tumors. However, some patients develop resistance to the treatments, resulting in an increase in mortality. Circular RNAs (circRNAs) form a class of non-coding RNAs with high stability and significant clinical relevance. Accumulating evidence indicates that circRNAs play a vital role in cancer development and tumor chemotherapy resistance. This review summarizes the molecular and cellular mechanisms of drug resistance mediated by circRNAs to common drugs used in the treatment of genitourinary tumors. Several circRNAs were identified to regulate the responsiveness to systemic treatments in genitourinary tumors, including chemotherapies such as cisplatin and targeted therapies such as enzalutamide. Canonically, cicrRNAs participate in the competing endogenous RNA (ceRNA) network, or in some cases directly interact with proteins, regulate downstream pathways, and even some circRNAs have the potential to produce proteins or polypeptides. Several cellular mechanisms were involved in circRNA-dependent drug resistance, including autophagy, cancer stem cells, epithelial-mesenchymal transition, and exosomes. The potential clinical prospect of circRNAs in regulating tumor drug resistance was also discussed.
Harnessing RKIP to Combat Heart Disease and Cancer
Authors: Lorenz Kristina , Rosner Marsha Rich
Published: February 2022

Cancer and heart disease are leading causes of morbidity and mortality worldwide. These diseases have common risk factors, common molecular signaling pathways that are central to their pathogenesis, and even some disease phenotypes that are interdependent. Thus, a detailed understanding of common regulators is critical for the development of new and synergistic therapeutic strategies. The Raf kinase inhibitory protein (RKIP) is a regulator of the cellular kinome that functions to maintain cellular robustness and prevent the progression of diseases including heart disease and cancer. Two of the key signaling pathways controlled by RKIP are the β-adrenergic receptor (βAR) signaling to protein kinase A (PKA), particularly in the heart, and the MAP kinase cascade Raf/MEK/ERK1/2 that regulates multiple diseases. The goal of this review is to discuss how we can leverage RKIP to suppress cancer without incurring deleterious effects on the heart. Specifically, we discuss: (1) How RKIP functions to either suppress or activate βAR (PKA) and ERK1/2 signaling; (2) How we can prevent cancer-promoting kinase signaling while at the same time avoiding cardiotoxicity.
Concepts and Outcomes of Perioperative Therapy in Stage IA-III Pancreatic Cancer—A Cross-Validation of the National Cancer Database (NCDB) and the German Cancer Registry Group of the Society of German Tumor Centers (GCRG/ADT)
Authors: Bolm Louisa , Zemskov Sergii , Zeller Maria , Baba Taisuke , Roldan Jorge , Harrison Jon M. , Petruch Natalie , Sato Hiroki , Petrova Ekaterina , Lapshyn Hryhoriy , Braun Ruediger , Honselmann Kim C. , Hummel Richard , Dronov Oleksii , Kirichenko Alexander V. , Klinkhammer-Schalke Monika , Kleihues-van Tol Kees , Zeissig Sylke R. , Rades Dirk , Keck Tobias , Fernandez-del Castillo Carlos , Wellner Ulrich F. , Wegner Rodney E.
Published: February 2022

(1) Background: The aim of this study is to assess perioperative therapy in stage IA-III pancreatic cancer cross-validating the German Cancer Registry Group of the Society of German Tumor Centers—Network for Care, Quality, and Research in Oncology, Berlin (GCRG/ADT) and the National Cancer Database (NCDB). (2) Methods: Patients with clinical stage IA-III PDAC undergoing surgery alone (OP), neoadjuvant therapy (TX) + surgery (neo + OP), surgery+adjuvantTX (OP + adj) and neoadjuvantTX + surgery + adjuvantTX (neo + OP + adj) were identified. Baseline characteristics, histopathological parameters, and overall survival (OS) were evaluated. (3) Results: 1392 patients from the GCRG/ADT and 29,081 patients from the NCDB were included. Patient selection and strategies of perioperative therapy remained consistent across the registries for stage IA-III pancreatic cancer. Combined neo + OP + adj was associated with prolonged OS as compared to neo + OP alone (17.8 m vs. 21.3 m, p = 0.012) across all stages in the GCRG/ADT registry. Similarly, OS with neo + OP + adj was improved as compared to neo + OP in the NCDB registry (26.4 m vs. 35.4 m, p < 0.001). (4) Conclusion: The cross-validation study demonstrated similar concepts and patient selection criteria of perioperative therapy across clinical stages of PDAC. Neoadjuvant therapy combined with adjuvant therapy is associated with improved overall survival as compared to either therapy alone.
Long-Term Results of Kyocera Modular Limb Salvage System after Resection of Tumors in the Distal Part of the Femur: Report from Japanese Musculoskeletal Oncology Group Study
Authors: Nakamura Tomoki , Matsumine Akihiko , Toda Yu , Takenaka Satoshi , Outani Hidetatsu , Fujiwara Tomohiro , Nishida Yoshihiro , Tsukushi Satoshi , Tome Yasunori , Kawamoto Teruya , Kito Munehisa , Shinohara Naohiro , Tomita Masato , Torigoe Tomoaki , Sudo Akihiro , Kawano Hirotaka
Published: February 2022

Background: The distal femur is a common site of bone tumors. After surgical resection, prosthetic replacement is a major reconstruction method. We aimed to elucidate the long-term outcomes of the Kyocera Modular Limb Salvage (KMLS) systems after resection of tumors in the distal part of the femur. Methods: Between 1998 and 2014, 125 patients were treated at 14 institutions. There were 59 males and 66 females, with a mean age of 35 years. The mean follow-up period was 132 months. Results: There had been 65 additional surgeries, including 56 revisions and 9 amputations: 15 for aseptic loosening, 14 for stem breakage, 13 for deep infection, 13 for rotator-hinge bushing failure, 5 for local recurrence, and 5 for others. Implant survival rates at 10 and 15 years were 58.5% and 39.4%. The cumulative incidence of 15-year revision for femoral stem breakage was 31.7% in patients with cementless fixation. The 15-year cumulative incidence of revision for aseptic loosening was 19.8% in patients with cement fixation. Conclusions: KMLS systems represent a reliable system with long-term results. Stem breakage should be considered in patients with cementless and/or smaller femoral stem sizes. Aseptic loosening should be considered in patients with cement systems after 10 years.
Humoral Immunity to Allogeneic Immunoproteasome-Expressing Mesenchymal Stromal Cells Requires Efferocytosis by Endogenous Phagocytes
Authors: Bikorimana Jean-Pierre , Abusarah Jamilah , Salame Natasha , El-Hachem Nehme , Shammaa Riam , Rafei Moutih
Published: February 2022

The extensive use of mesenchymal stromal cells (MSCs) over the last decade has revolutionized modern medicine. From the delivery of pharmacological proteins to regenerative medicine and immune modulation, these cells have proven to be highly pleiotropic and responsive to their surrounding environment. Nevertheless, their role in promoting inflammation has been fairly limited by the questionable use of interferon-gamma, as this approach has also been proven to enhance the cells’ immune-suppressive abilities. Alternatively, we have previously shown that de novo expression of the immunoproteasome (IPr) complex instills potent antigen cross-presentation capabilities in MSCs. Interestingly, these cells were found to express the major histocompatibility class (MHC) II protein, which prompted us to investigate their ability to stimulate humoral immunity. Using a series of in vivo studies, we found that administration of allogeneic ovalbumin (OVA)-pulsed MSC-IPr cells elicits a moderate antibody titer, which was further enhanced by the combined use of pro-inflammatory cytokines. The generated antibodies were functional as they blocked CD4 T-cell activation following their co-culture with OVA-pulsed MSC-IPr and mitigated E.G7 tumor growth in vivo. The therapeutic potency of MSC-IPr was, however, dependent on efferocytosis, as phagocyte depletion prior to vaccination abrogated MSC-IPr-induced humoral responses while promoting their survival in the host. In contrast, antibody-mediated neutralization of CD47, a potent “do not eat me signal”, enhanced antibody titer levels. These observations highlight the major role played by myeloid cells in supporting antibody production by MSC-IPr and suggest that the immune outcome is dictated by a net balance between efferocytosis-stimulating and -inhibiting signals.
Control of Synapse Structure and Function by Actin and Its Regulators
Authors: Gentile Juliana E. , Carrizales Melissa G. , Koleske Anthony J.
Published: February 2022

Neurons transmit and receive information at specialized junctions called synapses. Excitatory synapses form at the junction between a presynaptic axon terminal and a postsynaptic dendritic spine. Supporting the shape and function of these junctions is a complex network of actin filaments and its regulators. Advances in microscopic techniques have enabled studies of the organization of actin at synapses and its dynamic regulation. In addition to highlighting recent advances in the field, we will provide a brief historical perspective of the understanding of synaptic actin at the synapse. We will also highlight key neuronal functions regulated by actin, including organization of proteins in the pre- and post- synaptic compartments and endocytosis of ion channels. We review the evidence that synapses contain distinct actin pools that differ in their localization and dynamic behaviors and discuss key functions for these actin pools. Finally, whole exome sequencing of humans with neurodevelopmental and psychiatric disorders has identified synaptic actin regulators as key disease risk genes. We briefly summarize how genetic variants in these genes impact neurotransmission via their impact on synaptic actin.
Harnessing Natural Killer Cells in Non-Small Cell Lung Cancer
Authors: Russell Éilis , Conroy Melissa J. , Barr Martin P.
Published: February 2022

Lung cancer is the leading cause of cancer-related deaths worldwide. There are two main subtypes: small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). NSCLC accounts for 85% of lung cancer diagnoses. Early lung cancer very often has no specific symptoms, and many patients present with late stage disease. Despite the various treatments currently available, many patients experience tumor relapse or develop therapeutic resistance, highlighting the need for more effective therapies. The development of immunotherapies has revolutionized the cancer treatment landscape by enhancing the body’s own immune system to fight cancer. Natural killer (NK) cells are crucial anti-tumor immune cells, and their exclusion from the tumor microenvironment is associated with poorer survival. It is well established that NK cell frequencies and functions are impaired in NSCLC; thus, placing NK cell-based immunotherapies as a desirable therapeutic concept for this malignancy. Immunotherapies such as checkpoint inhibitors are transforming outcomes for NSCLC. This review explores the current treatment landscape for NSCLC, the role of NK cells and their dysfunction in the cancer setting, the advancement of NK cell therapies, and their future utility in NSCLC.