bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the bacterial community structure and fermentation characteristics of fresh and ensiled paper mulberry
Authors: Cheng Qiming , Chen Yulian , Bai Shiqie , Chen Liangyin , You Minhong , Zhang Kun , Li Ping , Chen Chao
Published: November 2021

Two experiments were conducted to investigate the bacterial community of fresh and ensiled paper mulberry prepared with or without lactic acid bacteria (LAB) inoculants in South China. In Experiment 1, the bacterial community, chemical composition, and fermentation products of paper mulberry were analyzed. The results showed that fresh paper mulberry had high crude protein content, buffering capacity value, and amounts of uncultured bacteria. Ensiled paper mulberry showed poor fermentation with high pH value, ammonia–N content, and butyric acid content. In addition, Enterobacter was the dominant genus in silage, followed by Lactobacillus and Enterococcus. Water‐soluble carbohydrates, ammonia–N, propionic acid, pH, and lactic acid (LA) were the main factors affecting bacterial community of silage. In Experiment 2, the BP17 (Lactobacillus plantarum) from natural fermented paper mulberry silage and two commercial inoculants (Silage‐help [SH] and Chikuso‐1 [CH]) were used as additives. Compared with other treatments, BP17 inoculant decreased (p < 0.05) pH and ammonia–N content and increased (p < 0.05) LA content of silage. Inoculation of BP17 also increased the dominance of desirable Lactobacillus and inhibited the growth of harmful bacteria in silage. These results confirmed that paper mulberry could be ensiled and epiphytic LAB inoculant can improve its fermentation quality.
Predicting completion of clinical trials in pregnant women: Cox proportional hazard and neural network models
Authors: Kim Bomee , Jang Yun Ji , Cho Hae Ram , Kim So Yeon , Jeong Ji Eun , Shim Mi Kyoung , Kim Myeong Gyu
Published: November 2021

This study aimed to develop a model for predicting the completion of clinical trials involving pregnant women using the Cox proportional hazard model and neural network model (DeepSurv) and to compare the predictive performance of both methods. We collected data on 819 clinical trials performed on pregnant women and intervention studies using at least one drug as intervention from 2009 to 2018 from ClinicalTrials.gov. The Cox proportional hazard model and DeepSurv were used to develop models that predict clinical trial completion. The concordance index (C‐index) was used to evaluate the predictive performance. The Cox proportional hazard model revealed that a sample size of n ≥ 329 (hazard ratio [HR] = 0.53), very high human development index (HDI) country (HR = 0.28), abortion (HR = 3.30), labor (HR = 2.16), and iron deficiency anemia (HR = 2.29) were significantly related to the probability of clinical trial completion (all p value < 0.01). The C‐index of the model development dataset and test dataset were 0.72 and 0.73, respectively. DeepSurv model consisted of one hidden layer with 16 nodes. DeepSurv showed the C‐index comparable to the Cox proportional hazard model. The C‐index of the training dataset and test dataset were 0.76 and 0.72, respectively. Further a nomogram that calculate a probability of clinical trial completion at 1 year, 3 years, and 5 years was developed. Both the Cox proportional hazard model and DeepSurv yielded sufficient predicting performance. We hope that this study will contribute to the execution of future clinical trials in pregnant women.
Crime and safety in urban public spaces: Experiences of Ghanaian women traders in the Makola market in Accra, Ghana
Authors: Wrigley‐Asante Charlotte , Owusu George , Amu Jane B. , Commodore Tracy S.
Published: November 2021

Although traditional markets and women traders in West African cities have long attracted the attention of scholars, limited studies exist on women’s experiences of crime and safety issues in this economic space that they dominate. This paper contributes to the growing geographical scholarship on gender and crime from the Ghanaian perspective as a result of the increasing urbanisation process that has raised concerns about crime and safety among urban dwellers. Using in‐depth interviews, the paper explores the experiences of three categories of Ghanaian women traders in a traditional urban market, Makola, in Accra, Ghana’s capital city. Theft cases appeared to be the most common criminal activity that women traders experience and this results in significant economic, social, psychological, and emotional effects on the lives of the women, with the most vulnerable being those who do not have enough resources to secure their livelihoods. We recommend that city authorities, the police, and other stakeholders support the efforts of these women traders through gender‐sensitive and equitable approaches to improve security in market spaces because market trade contributes significantly to city and national socio‐economic development.
Relationship between orchardgrass (Dactylis glomerata) dominance and the soil chemical characteristics of nonallophanic Andosol under cutting and cattle grazing
Authors: Kakihara Hidetoshi , Ogura Shin‐ichiro
Published: November 2021

Soil acidity affects botanical compositions and pasture production, but the relationship between orchardgrass persistence and the soil nutrients in acidic soils with different management methods is understudied in production fields. Here, using exchangeable acidity (y1) as an indicator of exchangeable aluminum (Al), we conducted a survey to investigate the relationship between orchardgrass dominance and the soil characteristics in sown pastures under different management practices. The botanical composition and soil chemical conditions were investigated in six orchardgrass–tall fescue mixed pastures (two cutting meadows and four cattle grazing pastures) from June 18 to July 17, 2018. Six‐ and three‐line transects were fixed in each meadow or pasture, respectively, and five measurement locations were set along each transect at 10‐m intervals. Each location had three square plots (20 × 20 cm) for the vegetation survey and three consecutive soil sampling plots (4‐cm diameter) adjacent to the middle square plot. The dominant plant species in each plot was recorded, and soil samples were collected at 0‐ to 5‐cm depth to measure y1 and major soil nutrients. The y1 ranged from 3.55 to 25.83 in the cutting meadows, which was wider than in the grazing pastures (1.85–16.29). In the cutting meadows, the dominance frequency of orchardgrass increased with the rise in y1, whereas that of tall fescue decreased in cutting meadows. No significant relationship was found between dominance frequencies and y1 in the grazing pastures. Although concentration of some soil nutrients varied with y1, these nutrients were not related to the dominance frequencies of orchardgrass for either management strategy. These results suggest that orchardgrass declines are prevented at high exchangeable Al sites by the non‐establishment of less Al‐tolerant plant species under cutting conditions.
Predictive role of endothelial cell activation in cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukaemia
Authors: Hong Fei , Shi Ming , Cao Jiang , Wang Ying , Gong Yanqing , Gao Hui , Li Zhenyu , Zheng Junnian , Zeng Lingyu , He Aili , Xu Kailin
Published: November 2021

CD19‐target chimeric antigen receptor (CAR)‐T cell therapy is highly effective for relapsed/refractory (R/R) acute lymphoblastic leukaemia (ALL), but is often complicated by cytokine release syndrome (CRS), which is potentially life‐threatening. Endothelial cells are the core regulator of CRS in many infectious diseases and may also play a key role after CAR‐T cell therapy. We provided a detailed clinical, laboratory description and endothelial cell activation biomarkers in patients with CRS. Endothelial cell activation was associated with occurrence, development and severity of CRS, manifested by decreased serum angiopoietin (Ang)‐1 levels and increased levels of von Willebrand Factor (VWF), Ang‐2, Ang‐2:Ang‐1, sE‐selectin, soluble intercellular adhesion molecule (sICAM‐1) and soluble vascular cell adhesion molecule (sVCAM)‐1. Besides, the endothelial activation was correlated with the hepatic, kidney and hematopoietic dysfunction in CRS patients. After infusion of CAR‐T cells, we detected changes of endothelial activation‐related biomarkers within 36 hours in patients who subsequently developed CRS, especially severe CRS. Using top tree models, we could predict which patients would develop CRS, especially severe CRS, or identify the severity of CRS by certain biomarkers of endothelial activation. These data provide a new idea and will help identify new targets for early intervention and prevention of CRS.
Meteorite terrestrial ages in Oman based on gamma spectrometry and sediment dating, focusing on the Ramlat Fasad dense collection area
Authors: Rosén Åke V. , Hofmann Beda A. , Preusser Frank , Gnos Edwin , Eggenberger Urs , Schumann Marc , Szidat Sönke
Published: November 2021

We combine the search for young meteorites in the Omani‐Swiss collection (˜1140 fall events collected 2001–2018) using 22Na and 44Ti with luminescence and 14C sediment ages from the Ramlat Fasad (RaF) dense collection area (DCA) of Oman to obtain combined terrestrial ages and maximum accumulation times, and test whether the proportion of young meteorites is consistent with the models of meteorite flux and weathering. Gamma‐ray spectrometry data for 22Na show that two (0.17%) of the meteorites in the collection fell during the 20 yr preceding this study, consistent with the rates of meteorite accumulation. In the RaF DCA, meteorites are found on Quaternary to Neogene sediments, providing constraints for their maximum terrestrial ages. 44Ti activities of the RaF 032 L6 strewn field found on deflated parts of active dunes indicate an age of 0.2–0.3 ka while dune sand optically stimulated luminescence ages constrain an upper age of 1.6 ka. Extensive sediment dating using luminescence methods in the RaF DCA area showed that all other meteorite finds were made on significantly older sediments (>10 ka). Dense accumulations of meteorites in RaF are found on blowouts of the Pliocene Marsawdad formation. Our combined results show that the proportion of meteorites with low terrestrial ages is low compared to other find areas, consistent with the previously determined high average terrestrial age Oman meteorites and significantly older than suggested by models of exponential decay. Oman meteorites may commonly have been buried within dunes and soils over extended periods, acting as a temporary protection against erosion.
Intimate partner violence and growth outcomes through infancy: A longitudinal investigation of multiple mediators in a South African birth cohort
Authors: Barnett Whitney , Nhapi Raymond , Zar Heather J. , Halligan Sarah L. , Pellowski Jennifer , Donald Kirsten A. , Stein Dan J.
Published: November 2021

Intimate partner violence (IPV) has been linked to poor fetal and infant growth. However, factors underlying this relationship are not well understood, particularly in the postnatal time period. In a South African cohort, we investigated (1) associations between IPV in pregnancy and growth at birth as well as postnatal IPV and child growth at 12 months and (2) whether maternal depression, tobacco or alcohol use or infant hospitalizations mediated IPV‐growth relationships. Mothers were enrolled in pregnancy. Maternal IPV was measured during pregnancy and 10 weeks postpartum; depression, alcohol and tobacco use were measured during pregnancy and at 6 months postpartum. Child weight and length were measured at birth and 12 months and converted to z‐scores for analysis. Linear regression and structural equation models investigated interrelationships between IPV and potential mediators of IPV‐growth relationships. At birth, among 1,111 mother–infant pairs, maternal emotional and physical IPV were associated with reduced weight‐for‐age z‐scores (WFAZ). Only physical IPV was associated with length‐for‐age z‐scores (LFAZ) at birth. Antenatal maternal alcohol and tobacco use mediated IPV‐growth relationships at birth. Postnatally, among 783 mother–infant pairs, emotional and physical IPV were associated with reduced WFAZ at 12 months. Only emotional IPV was associated with LFAZ at 12 months. Maternal tobacco use was a mediator postnatally. Findings highlight the role of physical and emotional IPV as risk factors for compromised fetal and infant growth. Findings underscore the importance of programmes to address interrelated risk factors for compromised infant growth, specifically IPV and substance use, which are prevalent in high‐risk settings.
Clinical analysis of the therapeutic effect of plasma exchange on hypertriglyceridemic acute pancreatitis: A retrospective study
Authors: Lin Yongxu , Yu Shufang , Wu Xiaofan , Huang Letong , Huang Simei , Huang Yongzhu , Ding Jian , Li Dan
Published: November 2021

Background

The therapeutic effect of plasma exchange (PE) on hypertriglyceridemic acute pancreatitis (HTGAP) is unclear. Therefore, we aimed to explore this therapeutic effect.

Study design and methods

This study included 204 patients with HTGAP who underwent treatment at two provincial tertiary grade A hospitals in Fujian Province from October 2012 to May 2021. Patients were divided into a conventional group and a PE group. The Student's t‐test and chi‐square test were used for data analysis.

Results

Among 204 patients, 56 and 148 were included in the PE and conventional groups, respectively. After propensity score matching (PSM), the PE and conventional groups each had 42 patients. There was no significant difference in age; sex; pregnancy; comorbidities; laboratory findings; incidences of complications, and multiple organ dysfunction syndrome (MODS); organ support treatment; surgical rate; mortality; and hospital stay between the groups (p > 0.05). The total expenses were significantly higher in the PE group than in the conventional group (p < 0.05). There was no statistically significant difference in the times of PE; total volume of PE; incidences of complications, and MODS; organ support treatment; surgical rate; mortality; and hospital stay between the early PE and delayed PE groups (p > 0.05). All patients in the PE group and conventional group with acute renal failure had significantly higher D‐dimer levels than those without acute renal failure (p < 0.05).

Discussion

Compared with conventional treatment, PE does not have a better therapeutic effect on HTGAP. The D‐dimer level can predict whether patients with HTGAP will have acute renal failure.
Steenrod operators, the Coulomb branch and the Frobenius twist
Authors: Lonergan Gus
Published: November 2021

We observe a fundamental relationship between Steenrod operations and the Artin–Schreier morphism. We use Steenrod's construction, together with some new geometry related to the affine Grassmannian, to prove that the quantum Coulomb branch is a Frobenius-constant quantization. We also demonstrate the corresponding result for the $K$-theoretic version of the quantum Coulomb branch. At the end of the paper, we investigate what our ideas produce on the categorical level. We find that they yield, after a little fiddling, a construction which corresponds, under the geometric Satake equivalence, to the Frobenius twist functor for representations of the Langlands dual group. We also describe the unfiddled answer, conditional on a conjectural ‘modular derived Satake’, and, though it is more complicated to state, it is in our opinion just as neat and even more compelling.
Boundaries Definition for Modeling Transients in Oil Terminals
Authors: Vargas Molina Wilfredo
Published: November 2021

Terminals are an integral part of transmission pipelines that can operate in different modes. The two most common modes are single injection and single delivery. Because pressure waves generated after accidental valve closures, pump trips, or others can travel many miles in a few seconds, it is a current practice to simulate the whole mainline to the next pump station, upstream or downstream, due to the lack of a standard method to identify boundaries.

This paper proposes a method to define the minimum modeling boundary. This boundary is especially useful when the available data is limited, when multiple suppliers / pipeline owners are connected to a terminal, when advanced simulation software or powerful computers are not available, or when the goal is to avoid unnecessary, complex labor-intensive simulations.

The technique consists of identifying a boundary located far enough in the mainline so that pressure waves do not interfere with the development of pressure surges after transient events in the facility piping or in a segment of a pipeline that has the weakest pipe.

This straightforward method is supported by concepts published by well-known authorities in the transient hydraulics field and tested with available pipeline simulation software.

After reading this paper, the reader will be able to answer these questions:

• How much data do I need?

• How many permutations?

• What info is critical for this method?

• Where is the boundary?

• What causes a wrong selection?

In summary, the hydraulic engineer will be able to shorten the current boundary to small fractions: up to 1/25 in the case of injection facilities and up to 2/25 in the case of delivery facilities. As well, readers will confirm that the hydraulic conditions in the mainlines beyond these boundaries don’t have any effect on the facilities’ piping due to transient events such as accidental valve closures or pumps trips, the most common initiators of large pressure surges.
Maximizing Efficiencies and De-Risking a Flare-to-Fuel Technology
Authors: Lagutchik Stephen , Ramos-Gomez Martha , Martin Paul , Kennon Terry
Published: November 2021

Technology qualification is a vital process for de-risking new technologies. This paper provides an overview of a recent technology qualification for a system which converts the normally burned and wasted energy in flare gas into a usable fuel for various applications (flare-to-fuel), thereby reducing the need for other high emissions fuels and providing decarbonization benefits to the end user and the environment. The scope of the qualification process followed a risk-based approach that included the review of technical documents, a technical workshop to identify novel technology aspects and potential threats, and a list of mitigation actions summarized in a Technology Qualification Plan. After successful completion of this first phase of the technology qualification process, according to DNV-RP-A203 [1], DNV issued a Statement of Endorsement of the Qualification Plan.
Midair transformations of aerosols
Authors: Ruiz-Lopez Manuel F.
Published: November 2021

Spontaneous reactions play an important role in shaping the chemistry of aerosols
Pig kidney transplant obscures value of engineered animals
Authors: Dolgin Elie
Published: November 2021

Skin and nerves from pigs lacking immune-provoking sugar could help patients today
Microbial Diversity Analysis Using 16S rRNA Gene Amplicon Sequencing of Rhizosphere Soils from Double-Cropping Rice and Rice-Shrimp Farming Systems in Soc Trang, Vietnam
Authors: Do Thi-Xuan , Huynh Van-Phuc , Le Lan-Anh , Nguyen Thuy-Vy , Nguyen-Pham Anh-Thi , Bui-Thi Minh-Dieu , Chau-Thi Anh-Thy , Tran Sy-Nam , Nguyen Van-Thanh , Ho-Huynh Thuy-Duong
Published: November 2021

Different rice farming systems affect the soil microbial communities. Here, we report the results of 16S rRNA gene amplicon sequencing of soils collected from intensive rice cultivation and rice-shrimp farming systems in Soc Trang, Vietnam. The dominant phyla in these systems were
Firmicutes
,
Actinobacteriota
,
Chloroflexi
,
Myxococcota
, and
Acidobacteriota
.
Assessing the Impact of Flavophospholipol and Virginiamycin Supplementation on the Broiler Microbiota: a Prospective Controlled Intervention Study
Authors: Mysara Mohamed , Berkell Matilda , Xavier Basil Britto , De Backer Sarah , Lammens Christine , Hautekiet Veerle , Petkov Spas , Goossens Herman , Kumar-Singh Samir , Malhotra-Kumar Surbhi
Published: November 2021

Antibiotic growth promoters (AGPs) are commonly used within poultry farming to increase muscle growth. Microbial composition in the gut is known to be influenced by AGP use although exact AGP-induced changes remain unclear.
Supplemental Material: Magmatic evolution and architecture of an arc-related, rhyolitic caldera complex: The late Pleistocene to Holocene Cerro Blanco volcanic complex, southern Puna, Argentina
Authors: de Silva S.L. , al. et
Published: November 2021

Methodology, calculations, and data analysis.
Evolution of mafic lavas in Central Anatolia: Mantle source domains
Authors: Furman Tanya , Hanan Barry B. , Sjoblom Megan Pickard , Kürkcüoğlu Biltan , Sayit Kaan , Şen Erdal , Şen Pinar Alıcı , Yürür Tekin
Published: November 2021

We present new Sr-Nd-Pb-Hf isotopic data on mafic lavas from the Sivas, Develidağ, Erciyes, and Erkilet volcanic complexes in central Turkey and Tendürek in eastern Turkey to evaluate the mantle sources for volcanism in the context of the geodynamic evolution of the Anatolian microplate. Early Miocene through Quaternary volcanism in Western Anatolia and latest Miocene through Quaternary activity in Central Anatolia were dominated by contributions from two distinct source regions: heterogeneous metasomatized or subduction-modified lithosphere, and roughly homogeneous sublithospheric ambient upper mantle; we model the source contributions through mixing between three end members. The sublithospheric mantle source plots close to the Northern Hemisphere reference line (NHRL) with radiogenic 206Pb/204Pb of ∼19.15, while the other contributions plot substantially above the NHRL in Pb isotope space. The lithospheric source is heterogeneous, resulting from variable pollution by subduction-related processes likely including direct incorporation of sediment and/or mélange; its range in radiogenic isotopes is defined by regional oceanic sediment and ultrapotassic melts of the subcontinental lithospheric mantle. The geochemical impact of this contribution is disproportionately large, given that subduction-modified lithosphere and/or ocean sediment dominates the Pb isotope signatures of mafic Anatolian lavas. Subduction of the Aegean or Tethyan seafloor, associated with marked crustal shortening, took place throughout the region until ca. 16–17 Ma, after which time broad delamination of the thickened lower crust and/or the Tethyan slab beneath Central Anatolia allowed for sediment and/or mélange and slab-derived fluids to be released into the overlying evolving modified mantle. Aggregation of melts derived from both mantle and lithospheric domains was made possible by upwelling of warm asthenospheric material moving around and through the complexly torn younger Aegean-Cyprean slab that dips steeply to the north beneath southern Anatolia.
Effects of covid-19 pandemic on life expectancy and premature mortality in 2020: time series analysis in 37 countries
Authors: Islam Nazrul , Jdanov Dmitri A , Shkolnikov Vladimir M , Khunti Kamlesh , Kawachi Ichiro , White Martin , Lewington Sarah , Lacey Ben
Published: November 2021

Objective

To estimate the changes in life expectancy and years of life lost in 2020 associated with the covid-19 pandemic.

Design

Time series analysis.

Setting

37 upper-middle and high income countries or regions with reliable and complete mortality data.

Participants

Annual all cause mortality data from the Human Mortality Database for 2005-20, harmonised and disaggregated by age and sex.

Main outcome measures

Reduction in life expectancy was estimated as the difference between observed and expected life expectancy in 2020 using the Lee-Carter model. Excess years of life lost were estimated as the difference between the observed and expected years of life lost in 2020 using the World Health Organization standard life table.

Results

Reduction in life expectancy in men and women was observed in all the countries studied except New Zealand, Taiwan, and Norway, where there was a gain in life expectancy in 2020. No evidence was found of a change in life expectancy in Denmark, Iceland, and South Korea. The highest reduction in life expectancy was observed in Russia (men: −2.33, 95% confidence interval −2.50 to −2.17; women: −2.14, −2.25 to −2.03), the United States (men: −2.27, −2.39 to −2.15; women: −1.61, −1.70 to −1.51), Bulgaria (men: −1.96, −2.11 to −1.81; women: −1.37, −1.74 to −1.01), Lithuania (men: −1.83, −2.07 to −1.59; women: −1.21, −1.36 to −1.05), Chile (men: −1.64, −1.97 to −1.32; women: −0.88, −1.28 to −0.50), and Spain (men: −1.35, −1.53 to −1.18; women: −1.13, −1.37 to −0.90). Years of life lost in 2020 were higher than expected in all countries except Taiwan, New Zealand, Norway, Iceland, Denmark, and South Korea. In the remaining 31 countries, more than 222 million years of life were lost in 2020, which is 28.1 million (95% confidence interval 26.8m to 29.5m) years of life lost more than expected (17.3 million (16.8m to 17.8m) in men and 10.8 million (10.4m to 11.3m) in women). The highest excess years of life lost per 100 000 population were observed in Bulgaria (men: 7260, 95% confidence interval 6820 to 7710; women: 3730, 2740 to 4730), Russia (men: 7020, 6550 to 7480; women: 4760, 4530 to 4990), Lithuania (men: 5430, 4750 to 6070; women: 2640, 2310 to 2980), the US (men: 4350, 4170 to 4530; women: 2430, 2320 to 2550), Poland (men: 3830, 3540 to 4120; women: 1830, 1630 to 2040), and Hungary (men: 2770, 2490 to 3040; women: 1920, 1590 to 2240). The excess years of life lost were relatively low in people younger than 65 years, except in Russia, Bulgaria, Lithuania, and the US where the excess years of life lost was >2000 per 100 000.

Conclusion

More than 28 million excess years of life were lost in 2020 in 31 countries, with a higher rate in men than women. Excess years of life lost associated with the covid-19 pandemic in 2020 were more than five times higher than those associated with the seasonal influenza epidemic in 2015.
DPP inhibition alters the CXCR3 axis and enhances NK and CD8+ T cell infiltration to improve anti-PD1 efficacy in murine models of pancreatic ductal adenocarcinoma
Authors: Fitzgerald Allison A , Wang Shangzi , Agarwal Veena , Marcisak Emily F , Zuo Annie , Jablonski Sandra A , Loth Melanie , Fertig Elana J , MacDougall John , Zhukovsky Eugene , Trivedi Shubhendu , Bhatia Dimple , O'Neill Vince , Weiner Louis M
Published: November 2021

Background

Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer death in the USA by 2030. Immune checkpoint inhibitors fail to control most PDAC tumors because of PDAC’s extensive immunosuppressive microenvironment and poor immune infiltration, a phenotype also seen in other non-inflamed (ie, ‘cold’) tumors. Identifying novel ways to enhance immunotherapy efficacy in PDAC is critical. Dipeptidyl peptidase (DPP) inhibition can enhance immunotherapy efficacy in other cancer types; however, the impact of DPP inhibition on PDAC tumors remains unexplored.

Methods

We examined the effects of an oral small molecule DPP inhibitor (BXCL701) on PDAC tumor growth using mT3-2D and Pan02 subcutaneous syngeneic murine models in C57BL/6 mice. We explored the effects of DPP inhibition on the tumor immune landscape using RNAseq, immunohistochemistry, cytokine evaluation and flow cytometry. We then tested if BXCL701 enhanced anti-programmed cell death protein 1 (anti-PD1) efficacy and performed immune cell depletion and rechallenged studies to explore the relevance of cytotoxic immune cells to combination treatment efficacy.

Results

In both murine models of PDAC, DPP inhibition enhanced NK and T cell immune infiltration and reduced tumor growth. DPP inhibition also enhanced the efficacy of anti-PD1. The efficacy of dual anti-PD1 and BXCL701 therapy was dependent on both CD8+ T cells and NK cells. Mice treated with this combination therapy developed antitumor immune memory that cleared some tumors after re-exposure. Lastly, we used The Cancer Genome Atlas (TCGA) to demonstrate that increased NK cell content, but not T cell content, in human PDAC tumors is correlated with longer overall survival. We propose that broad DPP inhibition enhances antitumor immune response via two mechanisms: (1) DPP4 inhibition increases tumor content of CXCL9/10, which recruits CXCR3+ NK and T cells, and (2) DPP8/9 inhibition activates the inflammasome, resulting in proinflammatory cytokine release and Th1 response, further enhancing the CXCL9/10-CXCR3 axis.

Conclusions

These findings show that DPP inhibition with BXCL701 represents a pharmacologic strategy to increase the tumor microenvironment immune cell content to improve anti-PD1 efficacy in PDAC, suggesting BXCL701 can enhance immunotherapy efficacy in ‘cold’ tumor types. These findings also highlight the potential importance of NK cells along with T cells in regulating PDAC tumor growth.
Surface enhanced infrared spectroelectrochemistry using a microband electrode
Authors: Morhart Tyler A. , Tu Kaiyang , Read Stuart T. , Rosendahl Scott M. , Wells Garth , Achenbach Sven , Burgess Ian J.
Published: November 2021

The successful use of a microband electrode printed on a silicon internal reflection element to perform time resolved infrared spectroscopy is described. Decreasing the critical dimension of the microband electrode to several hundred micrometers provides a sub-microsecond time constant in a Kretschmann configured spectroelectrochemical cell. The high brilliance of synchrotron sourced infrared radiation has been combined with a specially designed horizontal attenuated total reflectance (ATR) microscope to focus the infrared beam on the microband electrode. The first use of a sub-microsecond time constant working electrode for ATR surface enhanced infrared absorption spectroscopy (ATR-SEIRAS) is reported. Measurements show that the advantage afforded by the high brilliance of the synchrotron source is at least partially offset by increased noise from the experimental floor. The test system was the potential induced desorption of an adsorbed monolayer of 4-methoxypyridine (MOP) as measured using step-scan interferometry. Based on diffusion considerations alone, the expected time scale of the process was less than 10 microseconds but was experimentally measured to be three orders of magnitude slower. A defect-mediated dissolution of the condensed film is speculated to be the underlying cause of the unexpected slow kinetics.
Investigating the Material Removal Rate Parameters in ECM for Al 5086 Alloy‐Reinforced Silicon Carbide/Flyash Hybrid Composites by Using Minitab‐18
Authors: Gugulothu Bhiksha , Satheesh Kumar P. S. , Srinivas Bathula , Ramakrishna Alapati , Vijayakumar S.
Published: November 2021

This study explained about machining parameters of Al5086/Flyash/Sic hybrid metal matrix composites by the Taguchi technique. Al5086 reinforced in SiC (5–10 wt %) and 8% weight of flyash are retained as constants. The specimens are prepared with the help of the stir casting method. The material removal rate was examined by electrochemical machining under various parameters such as feed rate (0.15–0.30 mm/min), voltage (10–20 V), and electrolyte concentration (20–35 g/litre). Taguchi’s L16 orthogonal array was selected for design of experiments (DOEs), and 16 experimental tests were conducted to examine the effect of the selected machining parameters employed to identify the best optimal levels and also to investigate the effect of electrochemical machining parameters on MRR determined by Minitab‐18.
Severe Hypernatremia in a Significantly Underweight Female Child
Authors: Coriell Megan B. , Gandham Prasanthi , Wintergerst Kupper , Thrasher Bradly
Published: November 2021

In this study, we present the case of a 5-year-old female who presented for evaluation of dehydration with labs that revealed significant hypernatremia concerning for diabetes insipidus (DI). Further evaluation revealed that she had underlying chronic malnutrition. Her diagnostic work up for DI produced some evidence consistent with DI while other data indicated otherwise, bringing up the possibility of partial DI. She was ultimately diagnosed with sporadic vasopressin release secondary to her chronic malnutrition. This case illustrates another effect chronic malnutrition can have on pediatric patients along with the importance of a broad differential for patients with severe hypernatremia.
Upgrade Path and Strategy of Logistics Industry Cluster Based on the Internet of Things
Authors: Du Jie
Published: November 2021

As the economy grows rapidly and IoT technology advances rapidly, the logistics industry as a service industry is growing rapidly around the world. The logistics industry, meanwhile, is the one that can best play the role of IoT. The rapid development of the logistics industry has brought great competition challenges to the logistics industry. To solve the competitive problems of the logistics industry cluster, this article introduces the research on the upgrade path and strategy of the logistics industry cluster based on the Internet of Things and uses the analytic hierarchy process, investigation method, and expert evaluation method to build the IoT technology information model and logistics cost. According to the established optimization model, the following are proposed: analyzing the problems existing in the logistics industry cluster, giving an upgrade path from the four aspects of manufacturing, technology, structure, and service, and giving specific strategic suggestions from the aspects of talents and enterprises. The accuracy rate of current analysis is as high as 90%, and the implementation rate of upgrade paths and strategy recommendations is as high as 95%.
ROS Pleiotropy in Melanoma and Local Therapy with Physical Modalities
Authors: Sagwal Sanjeev Kumar , Bekeschus Sander
Published: November 2021

Metabolic energy production naturally generates unwanted products such as reactive oxygen species (ROS), causing oxidative damage. Oxidative damage has been linked to several pathologies, including diabetes, premature aging, neurodegenerative diseases, and cancer. ROS were therefore originally anticipated as an imperative evil, a product of an imperfect system. More recently, however, the role of ROS in signaling and tumor treatment is increasingly acknowledged. This review addresses the main types, sources, and pathways of ROS in melanoma by linking their pleiotropic roles in antioxidant and oxidant regulation, hypoxia, metabolism, and cell death. In addition, the implications of ROS in various physical therapy modalities targeting melanoma, such as radiotherapy, electrochemotherapy, hyperthermia, photodynamic therapy, and medical gas plasma, are also discussed. By including ROS in the main picture of melanoma skin cancer and as an integral part of cancer therapies, a greater understanding of melanoma cell biology is presented, which ultimately may elucidate additional clues on targeting therapy resistance of this most deadly form of skin cancer.
RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant
Authors: Damavandi Elia , Vand-Rajabpour Fatemeh , Javadi-Arjmand Maliheh , Mohajeri Tehrani Mohammad-Reza , Larijani Bagher , Kabuli Majid , Ghadami Mohsen
Published: November 2021

Background. The aim of this study was to identify germline mutation of the RET (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. Methods/Patients. We examined all six hot spot exons (exons 10, 11, 13, and 14–16) of the RET gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases. First-degree relatives of RET positive cases were also genotyped for index mutation. Moreover, presymptomatic carriers were referred to the endocrinologist for further clinical management and prophylactic thyroidectomy if needed. Results. Overall, the genetic status of all of the participants was determined by RET mutation screening, including 61 affected individuals, 22 presymptomatic carriers, and 29 genetically healthy subjects. In 37.5% (17 of 45) of the MTC referral index patients, 8 distinct RET germline mutations were found, including p.C634R (35.3%), p.M918T (17.6%), p.C634Y (11.8%), p.C634F (5.9%), p.C611Y (5.9%), p.C618R (5.9%), p.C630R (5.9%), p.L790F (5.9%), and one uncertain variant p.V648I (5.9%). Also, we found a novel variant p.H648R in one of our apparently sporadic patients. Conclusion. RET mutation detection is a promising/golden screening test and provides an accurate presymptomatic diagnostic test for at-risk carriers (the siblings and offspring of the patients) to consider prophylactic thyroidectomy. Thus, according to the ATA recommendations, the screening of the RET proto-oncogene is indicated for patients with MTC.
Loss of FBXW7 Correlates with Increased IDH1 Expression in Glioma and Enhances IDH1-Mutant Cancer Cell Sensitivity to Radiation
Authors: Yang Zhuo , Hu Nan , Wang Weiwei , Hu Weihua , Zhou Shaolong , Shi Jianxiang , Li Minghe , Jing Zhou , Chen Chao , Zhang Xuyang , Yang Ruyi , Fu Xudong , Wang Xinjun
Published: November 2021

F-box and WD repeat domain containing 7 (FBXW7) is a substrate receptor of the ubiquitin ligase SKP1-Cullin1-F-box complex and a potent tumor suppressor that prevents unregulated cell growth and tumorigenesis. However, little is known about FBXW7-mediated control of cell metabolism and related functions in cancer therapy. Here, we report that FBXW7 expression inversely correlates with the expression levels of the key metabolic enzyme isocitrate dehydrogenase 1 (IDH1) in patients with glioma and public glioma datasets. Deletion of FBXW7 significantly increased both wild-type (WT) and mutant IDH1 expression, which was mediated by blocking degradation of sterol regulatory element binding protein 1 (SREBP1). The upregulation of neomorphic mutant IDH1 by FBXW7 deletion stimulated production of the oncometabolite 2-hydroxyglutarate at the expense of increasing pentose phosphate pathway activity and NADPH consumption, limiting the buffering ability against radiation-induced oxidative stress. In addition, FBXW7 knockout and IDH1 mutations induced nonhomologous end joining and homologous recombination defects, respectively. In vitro and in vivo, loss of FBXW7 dramatically enhanced the efficacy of radiation treatment in IDH1-mutant cancer cells. Taken together, this work identifies FBXW7 deficiency as a potential biomarker representing both DNA repair and metabolic vulnerabilities that sensitizes IDH1-mutant cancers to radiotherapy.

Significance:

Deficiency of FBXW7 causes defects in DNA repair and disrupts NADPH homeostasis in IDH1-mutant glioma cells, conferring high sensitivity to radiotherapy.
Vertical Inhibition of the RAF–MEK–ERK Cascade Induces Myogenic Differentiation, Apoptosis, and Tumor Regression inH/NRASQ61XMutant Rhabdomyosarcoma
Authors: Garcia Natalia , Del Pozo Vanessa , Yohe Marielle E. , Goodwin Craig M. , Shackleford Terry J. , Wang Long , Baxi Kunal , Chen Yidong , Rogojina Anna T. , Zimmerman Sara M. , Peer Cody J. , Figg William D. , Ignatius Myron S. , Wood Kris C. , Houghton Peter J. , Vaseva Angelina V.
Published: November 2021

Oncogenic RAS signaling is an attractive target for fusion-negative rhabdomyosarcoma (FN-RMS). Our study validates the role of the ERK MAPK effector pathway in mediating RAS dependency in a panel of H/NRASQ61X mutant RMS cells and correlates in vivo efficacy of the MEK inhibitor trametinib with pharmacodynamics of ERK activity. A screen is used to identify trametinib-sensitizing targets, and combinations are evaluated in cells and tumor xenografts. We find that the ERK MAPK pathway is central to H/NRASQ61X dependency in RMS cells; however, there is poor in vivo response to clinically relevant exposures with trametinib, which correlates with inefficient suppression of ERK activity. CRISPR screening points to vertical inhibition of the RAF–MEK–ERK cascade by cosuppression of MEK and either CRAF or ERK. CRAF is central to rebound pathway activation following MEK or ERK inhibition. Concurrent CRAF suppression and MEK or ERK inhibition, or concurrent pan-RAF and MEK/ERK inhibition (pan-RAFi + MEKi/ERKi), or concurrent MEK and ERK inhibition (MEKi + ERKi) all synergistically block ERK activity and induce myogenic differentiation and apoptosis. In vivo assessment of pan-RAFi + ERKi or MEKi + ERKi potently suppress growth of H/NRASQ61X RMS tumor xenografts, with pan-RAFi + ERKi being more effective and better tolerated. We conclude that CRAF reactivation limits the activity of single-agent MEK/ERK inhibitors in FN-RMS. Vertical targeting of the RAF–MEK–ERK cascade and particularly cotargeting of CRAF and MEK or ERK, or the combination of pan-RAF inhibitors with MEK or ERK inhibitors, have synergistic activity and potently suppress H/NRASQ61X mutant RMS tumor growth.
A Novel Partial PPARγ Agonist Has Weaker Lipogenic Effect in Adipocytes and Stimulates GLUT4 Translocation in Skeletal Muscle Cells via AMPK-Dependent Signaling
Authors: Guru Bhavimani , Tamrakar Akhilesh K. , Mandal Subhankar P. , Kumar Prashantha B.R. , Sharma Aditya , Manjula Santhepete Nanjundaiah
Published: November 2021

Introduction: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are highly effective in treating insulin resistance. However, associated side effects such as weight gain due to increase in adipogenesis and lipogenesis hinder their clinical use. The aim of the study was to design and synthesize novel partial PPARγ agonists with weaker lipogenic effect in adipocytes and enhanced glucose transporter 4 (GLUT4) translocation stimulatory effect in skeletal muscle cells. Methods: Novel partial PPARγ agonists (GS1, GS2, and GS3) were designed and screened to predict their binding interactions with PPARγ by molecular docking. The stability of the docked ligand-PPARγ complex was studied by molecular dynamics (MD) simulation. The cytotoxicity of synthesized compounds was tested in 3T3-L1 adipocytes and L6 myoblasts by MTT assay. The lipogenic effect was investigated in 3T3-L1 adipocytes using oil red O staining and GLUT4 translocation stimulatory effect in L6-GLUT4myc myotubes by an antibody-coupled colorimetric assay. Results: The molecular docking showed the binding interactions between designed agonists and PPARγ. MD simulation demonstrated good stability between the GS2-PPARγ complex. GS2 and GS3 did not show any significant effect on cell viability up to 80 or 100 μM concentration. Pioglitazone treatment significantly increased intracellular lipid accumulation in adipocytes compared to control. However, this effect was significantly less in GS2- and GS3-treated conditions compared to pioglitazone at 10 μM concentration, indicating weaker lipogenic effect. Furthermore, GS2 significantly stimulated GLUT4 translocation to the plasma membrane in a dose-dependent manner via the AMPK-dependent signaling pathway in skeletal muscle cells. Conclusion: GS2 may be a promising therapeutic agent for the treatment of insulin resistance and type 2 diabetes mellitus without adiposity.
Objetivo de PO2 arterial de acuerdo con la patología subyacente: mini-revisión de los datos disponibles en pacientes ventilados mecánicamente
Authors: Demiselle Julien , Calzia Enrico , Hartmann Clair , Messerer David Alexander Christian , Asfar Pierre , Radermacher Peter , Datzmann Thomas
Published: November 2021

Actualmente se discute si la hiperoxia – es decir, la ventilación con altas concentraciones de O2 inspirado (FIO2) – y la hiperoxemia resultante – o sea, la existencia de tensiones arteriales de O2 (PaO2) suprafisiológicas – tienen utilidad durante el manejo agudo del choque circulatorio. Este concepto se basa en la evidencia experimental de que la hiperoxemia podría contribuir a compensar el desbalance entre la provisión y los requerimientos de O2. Sin embargo, a pesar de que aún es una práctica común, su uso se ve limitado debido a la posible toxicidad del oxígeno debido a una mayor formación de especies reactivas de oxígeno (ROS), especialmente bajo condiciones de isquemia/reperfusión. Varios estudios han reportado que existe una relación con forma de U entre la PaO2 y la mortalidad/morbilidad en pacientes en la UCI. Es interesante que estos estudios, retrospectivos en su mayor parte, encontraron que la mortalidad más baja coincide con una PaO2 ∼150 mmHg durante las primeras 24 h de estancia en la UCI; es decir, con niveles suprafisiológicos. La mayoría de los análisis retrospectivos de gran escala publicados recientemente estudiaron poblaciones generales en UCI, pero existen diferencias significativas de acuerdo con la patología subyacente estudiada, así como si se trata de pacientes bajo tratamiento médico o quirúrgico. Por tanto, hasta donde lo permiten los datos publicados, nos centramos en la necesidad de ventilación mecánica, y en la distinción entre la ausencia o la presencia de choque circulatorio. No parece haber un objetivo ideal de PaO2, excepto que debe evitarse la exposición prolongada (>24 h) a la hipoxemia (PaO2 < 55–60 mmHg) o a tensiones suprafisiológicas (PaO2 >100 mmHg). Por otra parte, la necesidad de ventilación mecánica, la ausencia o presencia de choque circulatorio y la etiología de la disoxia tisular – es decir, si se debe principalmente a un transporte macro- o microcirculatorio de O2 deficiente o a alteraciones en la utilización celular del O2 – pueden determinar si algún grado de hiperoxia tiene efectos colaterales nocivos.
Assistência técnica em habitação de interesse social para promoção do habitat saudável
Authors: Scotton Josiane Andréia , Miron Luciana Inês Gomes , Lersch Inês Martina
Published: November 2021

A precariedade das condições de moradia no Brasil tem sérias implicações sobre o habitat saudável. No ano de 2020, o advento da pandemia de Covid-19 acrescentou urgência às discussões acerca da habitação saudável, principalmente nas periferias das cidades; onde se encontram as maiores carências: de habitabilidade, de fornecimento de água, de infraestrutura e saneamento básico. Nesse contexto, a aplicação da Lei 11.888 de 2008, da Assistência Técnica em Habitação de Interesse Social (ATHIS), tem oportunizado o acesso ao trabalho dos profissionais de arquitetura para a população de baixa renda. Além disso, as iniciativas de ATHIS têm buscado a consolidação de projetos de habitação de interesse social que resultem na produção de unidades habitacionais mais saudáveis. O presente artigo apresenta um estudo de caso sobre o processo de desenvolvimento da ATHIS para uma comunidade de 68 famílias da cidade de São Leopoldo, Região Metropolitana de Porto Alegre, estado do Rio Grande do Sul. O objetivo deste estudo é compreender como o processo de ATHIS pôde contribuir para a promoção do habitat saudável naquela comunidade. As técnicas de coleta de dados utilizadas foram: análise de documentos, observação assistemática não-participante e entrevistas semiestruturadas. Os resultados permitiram constatar que:  i) a ATHIS envolvendo a população através de processo participativo, apresenta contribuições para a melhoria das condições de habitabilidade das populações envolvidas; ii) a ATHIS pode contribuir para a consolidação de um habitat saudável através da melhoria da qualidade do ambiente urbano e habitacional, destacando-se as condições básicas de saneamento.
A new species and a key to eleven species of the genus Conophyma Zubovsky, 1898 (Orthoptera, Acridoidea, Catantopidae, Conophyminae) from China
Authors: LIU YU-SHENG , SUN DAQING , ZHANG JINYU , YIN ZHAN
Published: November 2021

A new species and a key to eleven species of of the genus Conophyma Zobovsky, 1898 from China is described in this paper. The new species Conophyma lini sp. nov. is similar to C. xiai Zhang et al, 2015, but differs from latter by: vertex longer, apex narrower; minimum width of interspace 1.6 times length in mesosternum; posterior margin of epiproct waved, with angular projection in the middle, furculae small and width of Epiphallus 2.5 times high. Type specimens are deposited in the Northwest Plateau Institute of Biology, Chinese Academy of Sciences, Xining, Qinghai 810001, China.