bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial and socioeconomic disparity associates with differences in cardiac DNA methylation among men with end-stage heart failure
Authors: Pepin Mark E. , Ha Chae-Myeong , Potter Luke A. , Bakshi Sayan , Barchue Joseph P. , Haj Asaad Ayman , Pogwizd Steven M. , Pamboukian Salpy V. , Hidalgo Bertha A. , Vickers Selwyn M. , Wende Adam R.
Published: March 2021

A bimodal signature of cardiac DNA methylation in heart failure corresponds with racial differences in all-cause mortality following mechanical circulatory support. Racial differences in promoter methylation disproportionately affect metabolic signaling pathways. Socioeconomic factors are associated with racial differences in the cardiac methylome among men with end-stage heart failure.
Epidemiological and Diagnostic Aspects of Bladder Bilharziomas in the Urology Department of Idrissa Pouye General Hospital (HOGIP)
Authors: Gaye Oumar , Jalloh Mohamed , Thiam Ngor M , Ndoye Medina , Dansokho Khadidiatou , Bellamine Youssef , Kouka Saint C. N , Dial Cherif , Mbodji Mouhamadou M , Cassell Ayun , Labou Issa , Niang Lamine , Gueye Serigne
Published: March 2021

Objective. The aim of our study is to assess the diagnostic aspects of bladder bilharzioma in the Urology Department of Idrissa Pouye General Hospital (Senegal). Materials and Methods. It is a descriptive study from January 2013 to December 2018. The patients included in the study were those who had anatomopathological examination of bladder biopsy that showed a schistosomiasis pseudotumor of the bladder. The variables studied were sociodemographic, clinical symptoms, imaging findings, histology, and treatment. The data have been saved and analyzed by the 2013 Excel software. Results. Thirteen patients were included in our study. The average age was 27 ± 12.1 years. Sex ratio was 1.6. The majority of the patients were from the northern part of Senegal. Hematuria was the main symptom for all the patients. Cystoscopy was performed for all the patients and showed 5 granulomas and 8 fibrocalcic polyps. A transurethral resection of the bladder was performed, and treatment with praziquantel (40 mg/kg of bodyweight) has been carried out. One patient presented precancerous lesions such as metaplasia and dysplasia of the bladder mucosa. After a median follow-up of 40 months (6–57 months), ten patients had a favorable clinical and endoscopic outcome. Conclusion. Granulomas and fibrocalcic polyps of the bladder mucosa are, respectively, confused with squamous cell carcinoma and bladder lithiasis in endemic areas of schistosomiasis. Good cystoscopy interpretation can provide the diagnosis of bladder bilharzioma and start the treatment.
Development of New Chip Products from Brewer’s Spent Grain
Authors: Garrett Reann , Bellmer Danielle , McGlynn William , Rayas-Duarte Patricia
Published: March 2021

Brewer’s spent grain (BSG) is a processing waste generated in large quantities by the brewing industry. It is estimated that over 38 million tons of BSG is produced worldwide each year and is usually used as animal feed, composted, or thrown into landfills. BSG contains valuable nutritional components, including protein, fiber, and antioxidants. Due to its brittle texture, strong nutty flavors, and dark color profiles, BSG has seen limited use in food products for human consumption. The objective of this study was to develop a palatable chip product that maximized the level of inclusion of BSG. Chips were produced that contained BSG levels ranging from 8% to 40%, and the physical and sensory properties of the chips were evaluated. Spent grain samples were provided by Iron Monk in Stillwater and were dried at a low temperature and milled into flour for use in the chip formulation. BSG chips were evaluated for water activity, color, and texture (fracture force). An informal sensory evaluation was conducted to evaluate flavor, texture, and probability of purchase using a 5-point hedonic rating scale. Results showed that there were no significant differences in the texture of the chips containing different levels of BSG. The color measurements showed no significant differences between

L

∗

and a

∗

values for the chips containing different inclusion levels of BSG, but there were some differences in the b

∗

values. Results from the sensory evaluation showed that consumers preferred the texture of chips with 40% BSG over chips with 8% BSG, and they were also more likely to purchase the 40% BSG chips. There were no significant differences in flavor among the chips containing different inclusion levels of BSG. These results suggest that, for a chip-type product, BSG inclusion levels up to 40% are possible with positive consumer responses. Development of an alternative value-added product represents an opportunity for breweries nationwide to turn a processing waste into a future asset.
Yield Stability Analysis of Maize (Zea mays L.) Hybrids Using Parametric and AMMI Methods
Authors: Shojaei Seyed Habib , Mostafavi Khodadad , Omrani Ali , Omrani Saeed , Nasir Mousavi Seyed Mohammad , Illés Árpád , Bojtor Csaba , Nagy Janos
Published: March 2021

The present study investigated the stability and adaptability of maize (Zea mays L.) hybrids. In this study, 12 maize hybrids were planted and examined considering the grain yield. The experiment was arranged in a randomized complete block design (RCBD) with three replications in four research stations in Iran during two crop years. The combined analysis of variance showed that genotype-environment interactions were significant at one percent probability level. The grain yield can stabilize, and hybrids with specific adaptability are recommended to each environment. Hybrids with specific adaptability can be recommended to all types of the environment. Means comparison yield of the genotypes identified DC370 as a high-yield genotype. Regarding AMMI analysis, genotype × environment interactions (GEIs) and two first components were found significant. The SC647 genotype was identified as the most stable genotype. Regarding the stability parameters, SC647 and KSC705 genotypes were selected as the most stable genotypes. From AMMI1 and AMMI2 graphs, the SC647 genotype was identified as the most stable genotype compared with other hybrids.
Prognostic Value of Inflammatory and Tumour Markers in Small-Duct Subtype Intrahepatic Cholangiocarcinoma after Curative-Intent Resection
Authors: Ma Bingqi , Meng Huijuan , Shen An , Ma Yuwen , Zhao Dianpeng , Liu Guiling , Zheng Shujuan , Tian Ye , Zhang Wei , Li Qiang , Li Shiping
Published: March 2021

Intrahepatic cholangiocarcinoma (ICC) is characterised by heterogeneity, and it can be subdivided into small-duct and large-duct types. Inflammatory and tumour markers could effectively predict prognosis in many cancers, but no similar studies have been conducted in the histological subtypes of ICC. A total of 102 and 72 patients with ICC undergoing curative-intent resection were retrospectively subclassified into large-duct and small-duct types by chemical staining, respectively. The prognostic value of inflammatory and tumour markers was studied for the first time in histological subtypes of ICC by using a Cox regression model. A novel predictor named prognostic inflammatory index (PII) was proposed and defined as

neutrophil
×
monocyte
/
lymphocyte
 
count

(109/L). Survival analysis showed that PII, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA242, and ferritin were all predictors of DFS and OS in patients with ICC (

P
<
0.040

). Subgroup analysis showed that PII, CA19-9, and ferritin were risk predictors of disease-free survival (DFS) and overall survival (OS) in small-duct type ICC (

P
<
0.015

). In addition, in small-duct type ICC, NLR and LMR were correlated with OS (

P
<
0.025

), whilst CEA and CA242 were correlated with DFS (

P
≤
0.010

). In conclusion, PII is a convenient and efficient inflammatory predictor of DFS and OS in ICCs and their small-duct type. NLR and LMR, rather than platelet-to-lymphocyte ratio, were correlated with OS in small-duct type ICC. In addition, ferritin may be a supplement to CA19-9 in stratifying the survival outcome of patients with small-duct type ICC.
Gut Immunity and Microbiota Dysbiosis Are Associated with Altered Bile Acid Metabolism in LPS‐Challenged Piglets
Authors: Xiao Xiao , Cheng Yuanzhi , Fu Jie , Lu Zeqing , Wang Fengqin , Jin Mingliang , Zong Xin , Wang Yizhen
Published: March 2021

Bacterial infections are among the major factors that cause stress and intestinal diseases in piglets. Lipopolysaccharide (LPS), a major component of the Gram‐negative bacteria outer membrane, is commonly employed for inducing an immune response in normal organisms for convenience. The association between LPS stimulation and gut immunity has been reported. However, the effects of gut immunity on microbial homeostasis and metabolism of host, especially bile acid and lipid metabolism in piglets, remain unclear. Hence, in the current study, we elucidated the effect of gut immunity on microbial balance and host metabolism. Twenty‐one‐day‐old healthy piglets (male) were randomly assigned into the CON and LPS groups. After 4 hours of treatment, related tissues and cecal contents were obtained for further analysis. The obtained results showed that stimulated LPS considerably damaged the morphology of intestinal villi and enhanced the relative expression of proinflammatory cytokines. Besides, LPS partially changed the microbial structure as indicated by β‐diversity and increased operational taxonomic units (OTUs) related to Oxalobacter and Ileibacterium. Furthermore, bile acid, a large class of gut microbiota metabolites, was also assessed by many proteins related to the enterohepatic circulation of bile acids. It was also revealed that LPS markedly inhibited the mRNA and protein expression of TGR5 and FXR (bile acid receptors) in the ileum, which expressed negative feedback on bile acid de novo synthesis. Additionally, results indicated upregulated mRNA of genes associated with the production of bile acid in the liver tissues. Moreover, LPS reduced the expression of bile acid transporters in the ileum and liver tissues and further disturbed the normal enterohepatic circulation. Taken together, gut immunity and microbial dysbiosis are associated with altered bile acid metabolism in LPS‐challenged piglets, which provided theoretical basis for revealing the potential mechanism of intestinal inflammation in swine and seeking nutrients to resist intestinal damage.
Nonuniform Rational Basis Spline Interpolation for Off-Axis Aspheric Mirror Grinding Based on Wheel Path Planning
Authors: Xi Jianpu , Zhang Laibang , Yang Qing , Li Bin , Zhao Zexiang , Zhang Cong
Published: March 2021

Large-diameter aspheric mirrors made of hard and brittle materials suffer from low efficiency in the grinding stage, making them difficult to process. In this study, a nonuniform rational basis spline (NURBS) interpolation method is proposed and developed based on the grinding wheel path planning. The characteristic parameters of NURBS machining program are calculated to ensure the accuracy of curve interpolation path planning, and a series of control points are selected according to the normal vector points of the grinding wheel path. The control points were determined by the distance between the aspheric tangent and the next type value point at a fixed distance d. We then established a mathematical model for the knot point and simulated the relationship between the knot point and d. This indicated that d must be optimized according to the number of points to reduce the number of control points. According to this established model, a comparison experiment was conducted using an off-axis aspheric mirror, with a 280 mm diameter. Straight line and NURBS grinding were compared, and the NURBS interpolation method was shown to effectively improve grinding accuracy and efficiency by about 30%.
Day-to-Day Dynamic Multivehicle Assignment: Deterministic Process Models
Authors: Cantarella Giulio E. , Fiori Chiara
Published: March 2021

In the near future, transportation systems modelers and planners will likely be challenged by more complex scenarios. This is due to the different types of vehicles that include different (i) powertrains (conventional, hybrid, electric, etc.), (ii) ownerships (privately-owned vs. shared vehicles), and (iii) levels of automation (from human-driven to fully autonomous). All these different vehicle types compete for the same arcs and jointly participate to congestion. Thus, existing methods for travel demand assignment to a transportation network, the main tools for transportation systems analysis to support transportation project assessment and evaluation, need to be extended to cope with mixed traffic. In this paper, deterministic process models for day-to-day dynamic multivehicle assignment are presented, including fixed-point models for equilibrium assignment as a special case. Vehicle types may be distinguished with respect to several parameters, such as flow equivalence coefficient, occupancy factor, cost equivalence coefficient, and behavioral parameters. Results of an application to a toy network are also discussed showing that advanced vehicles (AVs) may or may not have a positive effect of equilibrium stability.
The Age-AST-D Dimer (AAD) Regression Model Predicts Severe COVID-19 Disease
Authors: Higuera-de-la-Tijera Fátima , Servín-Caamaño Alfredo , Reyes-Herrera Daniel , Flores-López Argelia , Robiou-Vivero Enrique J. A. , Martínez-Rivera Felipe , Galindo-Hernández Victor , Rosales-Salyano Victor H. , Casillas-Suárez Catalina , Chapa-Azuela Oscar , Chávez-Morales Alfonso , Jiménez-Bobadilla Billy , Hernández-Medel María L. , Orozco-Zúñiga Benjamín , Zacarías-Ezzat Jed R. , Camacho Santiago , Pérez-Hernández José L.
Published: March 2021

Aim. Coronavirus disease (COVID-19) ranges from mild clinical phenotypes to life-threatening conditions like severe acute respiratory syndrome (SARS). It has been suggested that early liver injury in these patients could be a risk factor for poor outcome. We aimed to identify early biochemical predictive factors related to severe disease development with intensive care requirements in patients with COVID-19. Methods. Data from COVID-19 patients were collected at admission time to our hospital. Differential biochemical factors were identified between seriously ill patients requiring intensive care unit (ICU) admission (ICU patients) versus stable patients without the need for ICU admission (non-ICU patients). Multiple linear regression was applied, then a predictive model of severity called Age-AST-D dimer (AAD) was constructed (

n
=
166

) and validated (

n
=
170

). Results. Derivation cohort: from 166 patients included, there were 27 (16.3%) ICU patients that showed higher levels of liver injury markers (

P
<
0.01

) compared with non-ICU patients: alanine aminotrasnferase (ALT)

225.4
±
341.2

vs.

41.3
±
41.1

, aspartate aminotransferase (AST)

325.3
±
382.4

vs.

52.8
±
47.1

, lactic dehydrogenase (LDH)

764.6
±
401.9

vs.

461.0
±
185.6

, D-dimer (DD)

7765
±
9109

vs.

1871
±
4146

, and age

58.6
±
12.7

vs.

49.1
±
12.8

. With these finding, a model called Age-AST-DD (AAD), with a cut-point of <2.75 (

sensitivity
=
0.797

and

specificity
=
0.391

,

c
−
statistic
=
0.74

; 95%IC: 0.62-0.86,

P
<
0.001

), to predict the risk of need admission to ICU (

OR
=
5.8

; 95% CI: 2.2-15.4,

P
=
0.001

), was constructed. Validation cohort: in 170 different patients, the

AAD
 
model
<
2.75

(

c
−
statistic
=
0.80

(95% CI: 0.70-0.91,

P
<
0.001

) adequately predicted the risk (

OR
=
8.8

, 95% CI: 3.4-22.6,

P
<
0.001

) to be admitted in the ICU (27 patients, 15.95%). Conclusions. The elevation of AST (a possible marker of early liver injury) along with DD and age efficiently predict early (at admission time) probability of ICU admission during the clinical course of COVID-19. The AAD model can improve the comprehensive management of COVID-19 patients, and it could be useful as a triage tool to early classify patients with a high risk of developing a severe clinical course of the disease.
Failure Analysis of Static Analysis Software Module Based on Big Data Tendency Prediction
Authors: Zhu Jian , Li Qian , Ying Shi
Published: March 2021

With the continuous development of software, it is inevitable that there will be various unpredictable problems in computer software or programs that will damage the normal operation of the software. In the paper, static analysis software is taken as the research object, the errors or failures caused by the potential defects of the software modules are analyzed, and a software analysis method based on big data tendency prediction is proposed to use the software defects of the stacked noise reduction sparse analyzer to predict. This method can learn features from original defect data, directly and efficiently extract required features of all levels from software defect data by setting different number of hidden layers, sparse regularization parameters, and noise ratio, and then classify and predict the extracted features by combining with big data. Through experimental tests, the performance of the presented method is better than that of the comparison method in correct rate, accuracy rate, recall rate, F1‐measurement, AUC value, and running time, which proves that the research results in this paper have more accurate failure prediction effect and can timely eliminate software failures.
Peripheral Nerve Resident Macrophages and Schwann Cells Mediate Cancer-Induced Pain
Authors: De Logu Francesco , Marini Matilde , Landini Lorenzo , Souza Monteiro de Araujo Daniel , Bartalucci Niccolò , Trevisan Gabriela , Bruno Gennaro , Marangoni Martina , Schmidt Brian L. , Bunnett Nigel W. , Geppetti Pierangelo , Nassini Romina
Published: March 2021

Although macrophages (MΦ) are known to play a central role in neuropathic pain, their contribution to cancer pain has not been established. Here we report that depletion of sciatic nerve resident MΦs (rMΦ) in mice attenuates mechanical/cold hypersensitivity and spontaneous pain evoked by intraplantar injection of melanoma or lung carcinoma cells. MΦ-colony stimulating factor (M-CSF) was upregulated in the sciatic nerve trunk and mediated cancer-evoked pain via rMΦ expansion, transient receptor potential ankyrin 1 (TRPA1) activation, and oxidative stress. Targeted deletion of Trpa1 revealed a key role for Schwann cell TRPA1 in sciatic nerve rMΦ expansion and pain-like behaviors. Depletion of rMΦs in a medial portion of the sciatic nerve prevented pain-like behaviors. Collectively, we identified a feed-forward pathway involving M-CSF, rMΦ, oxidative stress, and Schwann cell TRPA1 that operates throughout the nerve trunk to signal cancer-evoked pain.

Significance:

Schwann cell TRPA1 sustains cancer pain through release of M-CSF and oxidative stress, which promote the expansion and the proalgesic actions of intraneural macrophages.
The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age
Authors: Sehl Mary E. , Henry Jill E. , Storniolo Anna M. , Horvath Steve , Ganz Patricia A.
Published: March 2021

Background:

Estrogens are thought to contribute to breast cancer risk through cell cycling and accelerated breast aging. We hypothesize that lifetime estrogen exposure drives early epigenetic breast aging observed in healthy women. In this study, we examined associations between hormonal factors and epigenetic aging measures in healthy breast tissues.

Methods:

We extracted DNA from breast tissue specimens from 192 healthy female donors to the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center. Methylation experiments were performed using the Illumina EPIC 850K array platform. Age-adjusted regression models were used to examine for associations between factors related to estrogen exposure and five DNA methylation–based estimates: Grim age, pan-tissue age, Hannum age, phenotypic age, and skin and blood clock age.

Results:

Women were aged 19–90 years, with 95 premenopausal, and 97 nulliparous women. The age difference (Grim age − chronologic age) was higher at earlier ages close to menarche. We found significant associations between earlier age at menarche and age-adjusted accelerations according to the Grim clock, the skin and blood clock, and between higher body mass index (BMI) and age-adjusted accelerations in the Grim clock, Hannum clock, phenotypic clock, and skin and blood clock.

Conclusions:

Earlier age at menarche and higher BMI are associated with elevations in DNA methylation–based age estimates in healthy breast tissues, suggesting that cumulative estrogen exposure drives breast epigenetic aging.

Impact:

Epigenetic clock measures may help advance inquiry into the relationship between accelerated breast tissue aging and an elevated incidence of breast cancer in younger women.
Facts and Hopes in Multiple Myeloma Immunotherapy
Authors: Sperling Adam S. , Anderson Kenneth C.
Published: March 2021

Among the hallmarks of cancer is the ability of neoplastic cells to evade and suppress immune surveillance to allow their growth and evolution. Nowhere is this as apparent as in multiple myeloma, a cancer of antibody-producing plasma cells, where a complex interplay between neoplastic cells and the immune microenvironment is required for the development and progression of disease. Decades of research has led to the discovery of a number of therapeutic agents, from cytotoxic drugs to genetically engineered cells that mediate their antimyeloma effects at least partially through altering these immune interactions. In this review, we discuss the history of immunotherapy and current practices in multiple myeloma, as well as the advances that promise to one day offer a cure for this deadly disease.
Single-cell Spatial Proteomic Revelations on the Multiparametric MRI Heterogeneity of Clinically Significant Prostate Cancer
Authors: Pachynski Russell K. , Kim Eric H. , Miheecheva Natalia , Kotlov Nikita , Ramachandran Akshaya , Postovalova Ekaterina , Galkin Ilia , Svekolkin Viktor , Lyu Yang , Zou Qiong , Cao Dengfeng , Gaut Joseph , Ippolito Joseph E. , Bagaev Alexander , Bruttan Maria , Gancharova Olga , Nomie Krystle , Tsiper Maria , Andriole Gerald L. , Ataullakhanov Ravshan , Hsieh James J.
Published: March 2021

Purpose:

Multiparametric MRI (mpMRI) has become an indispensable radiographic tool in diagnosing prostate cancer. However, mpMRI fails to visualize approximately 15% of clinically significant prostate cancer (csPCa). The molecular, cellular, and spatial underpinnings of such radiographic heterogeneity in csPCa are unclear.

Experimental Design:

We examined tumor tissues from clinically matched patients with mpMRI-invisible and mpMRI-visible csPCa who underwent radical prostatectomy. Multiplex immunofluorescence single-cell spatial imaging and gene expression profiling were performed. Artificial intelligence–based analytic algorithms were developed to examine the tumor ecosystem and integrate with corresponding transcriptomics.

Results:

More complex and compact epithelial tumor architectures were found in mpMRI-visible than in mpMRI-invisible prostate cancer tumors. In contrast, similar stromal patterns were detected between mpMRI-invisible prostate cancer and normal prostate tissues. Furthermore, quantification of immune cell composition and tumor-immune interactions demonstrated a lack of immune cell infiltration in the malignant but not in the adjacent nonmalignant tissue compartments, irrespective of mpMRI visibility. No significant difference in immune profiles was detected between mpMRI-visible and mpMRI-invisible prostate cancer within our patient cohort, whereas expression profiling identified a 24-gene stromal signature enriched in mpMRI-invisible prostate cancer. Prostate cancer with strong stromal signature exhibited a favorable survival outcome within The Cancer Genome Atlas prostate cancer cohort. Notably, five recurrences in the 8 mpMRI-visible patients with csPCa and no recurrence in the 8 clinically matched patients with mpMRI-invisible csPCa occurred during the 5-year follow-up post-prostatectomy.

Conclusions:

Our study identified distinct molecular, cellular, and structural characteristics associated with mpMRI-visible csPCa, whereas mpMRI-invisible tumors were similar to normal prostate tissue, likely contributing to mpMRI invisibility.
Back from the Brink: EGFR Inhibition in Gastroesophageal Cancer
Authors: Openshaw Mark R. , Pinato David J. , Valeri Nicola
Published: March 2021

Gastroesophageal adenocarcinomas (GEA) remain difficult to treat with limited targeted therapeutics. Negative results from randomized trials of EGFR inhibitors (EGFRi) in patients with molecularly unselected GEA have hampered the development of EGFRi in the gastroesophageal cancer space. A recent study reopens the game.

See related article by Corso et al., p. 3126
Defects in Emerin–Nucleoskeleton Binding Disrupt Nuclear Structure and Promote Breast Cancer Cell Motility and Metastasis
Authors: Liddane Alexandra G. , McNamara Chelsea A. , Campbell Mallory C. , Mercier Isabelle , Holaska James M.
Published: March 2021

Nuclear envelope proteins play an important role in regulating nuclear size and structure in cancer. Altered expression of nuclear lamins are found in many cancers and its expression is correlated with better clinical outcomes. The nucleus is the largest organelle in the cell with a diameter between 10 and 20 μm. Nuclear size significantly impacts cell migration. Nuclear structural changes are predicted to impact cancer metastasis by regulating cancer cell migration. Here we show emerin regulates nuclear structure in invasive breast cancer cells to impact cancer metastasis. Invasive breast cancer cells had 40% to 50% less emerin than control cells, which resulted in decreased nuclear size. Overexpression of GFP-emerin in invasive breast cancer cells rescued nuclear size and inhibited migration through 3.0 and 8.0 μm pores. Mutational analysis showed emerin binding to nucleoskeletal proteins was important for its regulation of nuclear structure, migration, and invasion. Importantly, emerin expression inhibited lung metastasis by 91% in orthotopic mouse models of breast cancer. Emerin nucleoskeleton-binding mutants failed to inhibit metastasis. These results support a model whereby emerin binding to the nucleoskeleton regulates nuclear structure to impact metastasis. In this model, emerin plays a central role in metastatic transformation, because decreased emerin expression during transformation causes the nuclear structural defects required for increased cell migration, intravasation, and extravasation.

Implications:

Modulating emerin expression and function represents new targets for therapeutic interventions of metastasis, because increased emerin expression rescued cancer metastasis.
TAGLN Is Downregulated by TRAF6-Mediated Proteasomal Degradation in Prostate Cancer Cells
Authors: Wen Fuping , Sun Xiaochen , Sun Chenxia , Dong Zhenyang , Jia Gaozhen , Bao Wei , Yu Haolan , Yang Chenghua
Published: March 2021

Transgelin (TAGLN, also named SM22) is an actin-associated protein and affects dynamics of actin filaments. Deregulation of TAGLN contributes to the development of different cancers, and it is commonly considered to be a tumor suppressor. TAGLN is usually downregulated in prostate cancer; however, the detailed functions of TAGLN in prostate cancer and how TAGLN is regulated remains unclear. In this study, we confirmed that TAGLN is downregulated in prostate cancer tissues and demonstrated that the downregulation of TAGLN occurs through proteasomal degradation. Next, we found that the expression level of TAGLN is inversely correlated with TRAF6. We screened more than 20 E2–E3 pairs by in vitro ubiquitination assay and found that the E2A–TRAF6 pair catalyzed mono ubiquitination of TAGLN. We then identified the ubiquitination sites of TAGLN to be on K89 or K108 residues and demonstrated that ubiquitination of TAGLN on K89/K108 are important for TRAF6-mediated proteasomal degradation. Furthermore, we investigated the function of TAGLN in prostate cancer cells. We found that ablation of TAGLN promoted prostate cancer cell proliferation and suppressed their migration via activation of NF-κB and Myc signaling pathways. Overall, our study provided new insights into the mechanisms underlying TAGLN expression and activity in prostate cancer.

Implications:

E3 ligase TRAF6 mediate mono-ubiquitination and degradation of TAGLN, which leads to activation of NF-κB and Myc signaling pathways in prostate cancer cells.
An IFNγ/STAT1/JMJD3 Axis Induces ZEB1 Expression and Promotes Aggressiveness in Lung Adenocarcinoma
Authors: Yang Jianjian , Wang Xue , Huang Bing , Liu Rong , Xiong Hui , Ye Fan , Zeng Chenxi , Fu Xiangning , Li Lequn
Published: March 2021

Active IFNγ signaling is a common feature of tumors responding to PD-1 checkpoint blockade. IFNγ exhibits both anti- and protumor activities. Here, we show that the treatment of lung adenocarcinoma cells with IFNγ led to a rapid increase of ZEB1 expression and a significant change in epithelial-to-mesenchymal transition (EMT)-associated gene expression pattern. Moreover, functional analyses show that IFNγ promoted cell migration in vitro and metastasis in vivo. We demonstrate that ZEB1 is required for IFNγ-promoted EMT, cell migration, and metastasis, as RNAi-mediated knockdown of ZEB1 abrogated EMT, cell migration, and metastasis induced by IFNγ. We show that IFNγ induced upregulation of JMJD3 significantly reduced H3K27 trimethylation in the promoter of the ZEB1 gene, which led to activation of ZEB1 gene transcription. IFNγ-induced JMJD3 expression was JAK1/2-STAT1 dependent. Inhibition of JMJD3 abrogated IFNγ-induced ZEB1 expression. IFNγ-induced ZEB1 also reduced miR-200 expression. Downregulation of ZEB1 increased miR-200 expression, which led to a reduction of PD-L1 expression induced by IFNγ. It is worth noting that knockdown of ZEB1 did not affect IFNγ-mediated antiproliferation and induction of CXCL9 and CXCL10. Thus, downregulation of ZEB1 may prevent the protumor activity of IFNγ while retaining its antitumor function. This study expands our understanding of IFNγ-mediated signaling and helps to identify therapeutic targets to improve current immunotherapies.

Implications:

IFNγ increases ZEB1 expression in a STAT1-JMJD3 dependent manner, and consequently promotes cancer cell aggressiveness. This study provides a potential target to minimize the procancer effect of IFNγ while preserving its antitumor function.
A Rare Case Report of Unusual Path of Left Internal Jugular Central Line
Authors: Mudaraddi Rajashekar Rangappa , Greiss Hany Fawzi , Manickam Navin Kumar
Published: March 2021

Central venous cannulation is the most common procedure performed in perioperative setting and intensive care unit. Many case reports reported unusual positioning of central line catheters. Here, we would like to report a case of central line path in persistent left superior vena cava, a rare entity with a course similar to the right internal jugular central line. Preoperative computed tomography chest showed duplex superior vena cava which was not reported.
Fertility of Women Treated during Childhood with Triptorelin (Depot Formulation) for Central Precocious Puberty: The PREFER Study
Authors: Martinerie Laetitia , de Mouzon Jacques , Blumberg Joelle , di Nicola Luigi , Maisonobe Pascal , Carel Jean-Claude ,   on behalf of the PREFER study group
Published: March 2021

Background: Gonadotropin-releasing hormone analogues (GnRHa) administered as depot formulations are the standard of care for children with central precocious puberty (CPP). Puberty resumes after treatment discontinuation, but little is known concerning fertility in women who have been treated with GnRHa for CPP during childhood. Methods: The PREFER (PREcocious puberty, FERtility) study prospectively analysed fertility, via a series of questionnaires, in women treated during childhood with triptorelin (depot formulation) for CPP. Co-primary endpoints were the proportion of women wanting a pregnancy any time before study inclusion and during the follow-up period but not pregnant 6 and 12 months after stopping contraception and the waiting time to pregnancy (WTP). Results: A total of 574 women were identified, and 194 women were included in the analysis. Although there were not enough data for primary endpoint assessment, few women (1.7%) reported issues with fertility or were unable to become pregnant despite trying to conceive. Most pregnancies (84.4%, 95% CI [67.2–94.7%]) occurred within 1 year of trying to conceive, in line with the WTP for women without previous CPP. Conclusion: The results, based on a limited sample of patients, suggest that CPP treated with triptorelin does not negatively impact women’s fertility in adulthood. These results need to be consolidated with a subsequent study performed when these women will have reached their mid-thirties.
Developing Brain Glucose Transporters, Serotonin, Serotonin Transporter, and Oxytocin Receptor Expression in Response to Early-Life Hypocaloric and Hypercaloric Dietary, and Air Pollutant Exposures
Authors: Ye Xin , Shin Bo-Chul , Baldauf Claire , Ganguly Amit , Ghosh Shubhamoy , Devaskar Sherin U.
Published: March 2021

Perturbed maternal diet and prenatal exposure to air pollution (AP) affect the fetal brain, predisposing to postnatal neurobehavioral disorders. Glucose transporters (GLUTs) are key in fueling neurotransmission; deficiency of the neuronal isoform GLUT3 culminates in autism spectrum disorders. Along with the different neurotransmitters, serotonin (5-HT) and oxytocin (OXT) are critical for the development of neural connectivity. Serotonin transporter (SERT) modulates synaptic 5-HT levels, while the OXT receptor (OXTR) mediates OXT action. We hypothesized that perturbed brain GLUT1/GLUT3 regulated 5-HT-SERT imbalance, which serves as a contributing factor to postnatal neuropsychiatric phenotypes, with OXT/OXTR providing a counterbalance. Employing maternal diet restriction (intrauterine growth restriction [IUGR]), high-fat (HF) dietary modifications, and prenatal exposure to simulated AP, fetal (E19) murine brain 5-HT was assessed by ELISA with SERT and OXTR being localized by immunohistochemistry and measured by quantitative Western blot analysis. IUGR with lower head weights led to a 48% reduction in male and female fetal brain GLUT3 with no change in GLUT1, when compared to age- and sex-matched controls, with no significant change in OXTR. In addition, a ∼50% (p = 0.005) decrease in 5-HT and SERT concentrations was displayed in fetal IUGR brains. In contrast, despite emergence of microcephaly, exposure to a maternal HF diet or AP caused no significant changes. We conclude that in the IUGR during fetal brain development, reduced GLUT3 is associated with an imbalanced 5-HT-SERT axis. We speculate that these early changes may set the stage for altering the 5HT-SERT neural axis with postnatal emergence of associated neurodevelopmental disorders.
Revisiting the taxonomy of Strobilanthes lawsonii and S. pushpangadanii (Acanthaceae), two endemic taxa of Western Ghats, India
Authors: Cherian Blessy , Prabhukumar K.M. , Jagadeesan R. , Kumar V.V. Naveen , Balachandran Indira
Published: March 2021

Strobilanthes lawsonii was described by Gamble based on a collection made from Sispara Ghat of Nilgiri District, Tamil Nadu.  Later researchers reported its distribution in Kerala, and S. gamblei and S. pushpangadanii, two endemic species of the Western Ghats, were synonymised with S. lawsonii during the genus revision in southern India in 2006.  During a recent expedition to Muthikulam forest of Palakkad, Kerala the authors collected typical S. lawsonii.  After comparing the new collections with S. gamblei and S. pushpangadanii, it was found that both taxa are distinct from S. lawsonii, with the most notable morphological differences being partially fused corolla lobes and exserted stamens.  A detailed comparison of the three taxa is provided here, along with color photographs and a taxonomic key for easy species identification.
Potential phytophagous insects of Pteridium revolutum (Blume) Nakai, an invasive fern
Authors: Arjun M.S. , Gopakumar S.
Published: March 2021

The article reports an observation on the phytophagous behaviour by the insect larvae of two insect species on a fern, Pteridium revolutum, which is fast emerging as an invasive plant species threatening local biodiversity and wildlife in Kerala State, India.
Catalogue of selected insect groups of Lalwan Community Reserve and Ranjit Sagar Conservation Reserve, Punjab, India
Authors: Singh Amar Paul , Chandra Agni , Uniyal Virendra Prasad , Adhikari Bhupendra Singh
Published: March 2021

We present the first documentation of the insect fauna of Lalwan Community Reserve and Ranjit Sagar Conservation Reserve, Punjab.  The survey was conducted in the months of May and June 2019.  Selected insect groups were focused on for the rapid documentation of the entomofauna.  Overall, we recorded 91 species of insects belonging to the orders Lepidoptera, Coleoptera, and Odonata.  A total of 68 species including 46 species of order Lepidoptera, nine species of Odonata, and 13 species of Coleoptera were reported from Lalwan Community Reserve. Thirty-seven species consisting of 23 species of Odonata and 14 species of Lepidoptera were recorded from Ranjit Sagar Conservation Reserve, Punjab.
Actinor radians (Moore, 1878) (Hesperiidae: Hesperiinae: Aeromachini): addition to the butterfly fauna of Haryana, India
Authors: Boruah Bitupan , Chahal Rajesh , Das Abhijit
Published: March 2021

We report a rare skipper butterfly from Kalesar National Park, Haryana, which is the first record for the state and the lowermost elevation record for the species.
Relocation of a GPS collared conflict Sloth Bear Melursus ursinus (Mammalia: Carnivora) in Karnataka, India
Authors: Arun Attur Shanmugam , Shanmugavelu Swaminathan , Pannerselvam Yogaraj , Sharp Thomas Robert , Stephens Sydney , Satyanarayan Kartick , Seshamani Geeta
Published: March 2021

The relocation of conflict bears has been a tool used widely across the United States and Canada with mixed results.  It has also been used in India with Sloth Bears, though without follow-up it remains unknown how successful these relocation efforts have been.  We documented the capture and relocation of a conflict female Sloth Bear from a rural area near Bangalore, Karnataka, India to Bannerghatta National Park roughly 30km away.  This female bear, approximately six years old, was fitted with a VHF/GPS store-on-board collar, and her movements tracked.  She did not attempt to return to her capture location but during the first two-month period after being released she did roam over an area roughly six times that of typical female Sloth Bear home range.  Over the subsequent months the area over which she roamed continued to decline.  She was least active mid-day and more active in the evening, night, and early morning.  During her last few weeks in January, before she was killed by an explosive device just outside of the park, her movement pattern shrank considerably.  The post-mortem examination showed that she had been pregnant when killed and would have given birth within the next two weeks.  These reduced movements were consistent with those of periparturient female bears or potentially with a bear becoming more acclimated to her new surroundings.  The relocation effort appeared successful up until the Sloth Bear was killed by poacher activity.
Implementation of a Myocardial Perfusion Imaging Risk Algorithm to Inform Appropriate Downstream Invasive Testing and Treatment
Authors: Kumar Anirudh , Patel Divyang R. , Harb Serge C. , Greenberg Neil L. , Bhargava Ajay , Menon Venu , Ellis Stephen G. , Kapadia Samir R. , Hachamovitch Rory , Jaber Wael A. , Cremer Paul C.
Published: March 2021

Background:

To risk stratify patients undergoing single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in accordance with appropriate use criteria for referral to coronary angiography, we developed a risk classification algorithm incorporating appropriate use criteria–defined risk features. We evaluated the association between this algorithm with downstream angiography, revascularization, and all-cause mortality.

Methods:

We studied consecutive patients who underwent SPECT-MPI from January 1, 2015, to December 31, 2017, and assigned a scan risk of low, intermediate, high, or indeterminate. With this stratification, we assessed referral for angiography and revascularization within 3 months of SPECT-MPI and intermediate-term mortality.

Results:

Among 12 799 patients, the mean age was 66 years, and a majority were men (56.8%). Most patients were low risk (83.6%) followed by intermediate (9.9%) and high risk (5.2%). Compared with low-risk patients, intermediate- and high-risk patients were more frequently referred for angiography (14.8% and 13.6% versus 2.0%;
P
<0.001) and revascularization (7.7% and 6.8% versus 0.7%;
P
<0.001). In 1008 propensity-matched patients, scan risk was independently associated with angiography after adjustment for ischemia, scar, or stress ejection fraction. At a mean follow-up of 2.3 years, mortality was higher with increased scan risk (high, 10.4%; intermediate, 7.1%; low, 4.1%;
P
<0.001). Compared with low scan risk, intermediate (hazard ratio, 1.37 [95% CI, 1.09–1.72];
P
=0.008) and high scan risk (hazard ratio, 1.98 [95% CI, 1.53–2.56];
P
<0.001) were associated with mortality in multivariable analysis. Similar findings were observed for those undergoing pharmacological and exercise SPECT-MPI with comparatively worse prognosis among pharmacological patients.

Conclusions:

This appropriate use criteria–derived risk classification algorithm for SPECT-MPI guided referral for coronary angiography and revascularization and was significantly associated with mortality. This algorithm may serve as an important tool to reaffirm appropriate use criteria and direct management of patients with stable ischemic heart disease undergoing stress testing.
Humility and Influence
Authors: Oleas-Mogollón Isabel
Published: March 2021

In June 1773 Doña Luisa García de Medina filed a lawsuit against the Spanish colonial government demanding the return of her generous donation to the confraternity of Saint Rosalia in Cuenca (Audiencia of Quito). This dispute provides a clear testimony of the influence of religious devotion and the power of female self-fashioning and agency. Doña Luisa’s piety, her promotion of the cult of Saint Rosalia, and her substantial donation allowed her to establish associations with leading local institutions and shape Cuenca’s sacred landscape and its inhabitants’ religious experience. Doña Luisa’s control of the processional route also identified her oratory as a space for spiritual introspection, self-representation, and social exchange. This article illustrates the importance of humility in the advancement of female agency in the colonial period. This research also proves that the study of religious confraternities supports a more inclusive construction of Spanish American history and shows the impact of female patronage in the civic space.
“When You Stop Pretending That You Know”
Authors: DeCoste D. Marcel
Published: March 2021

Increasingly addressing the religious dimension of Cormac McCarthy’s work, critics have frequently rooted it in a Gnosticism which holds, first, that the world is a place of evil and suffering and, second, that salvation is attained through knowledge made available only to the elect. The Stonemason, however, seems intent on refuting just such a thesis. Focusing on Ben and his grandfather Papaw, a centenarian stonemason, the play presents Ben as seeking, through mastery of the mason’s secrets, to become custodian to knowledge that will unlock the mysteries not just of a trade but of the cosmos. Yet this Gnostic quest fosters in him a moral negligence that leads to the deaths of two family members. Indeed, Ben’s tragedy stems precisely from his Gnostic prizing of secret lore and indifference to the Christian lessons Papaw himself most values—lessons not in god-like knowledge but in the practice of faith, humility, and love.
Studying the Bible in the “Post-Truth” Era
Authors: Brisman Leslie
Published: March 2021

When Jesus tells Pilate “my kingdom is not of this world” (John 18:36), he may be reassuring Pilate that Jesus and his followers pose no political threat. In our time, however, the secular idea of “alternate facts” has become something of a new religion and affects both our politics and our academic study. The difficult questions of what constitutes facts or credible critical interpretation of literary facts is particularly vexed when there is a question of citation. This article does not deal with questionable abbreviations of citation (such as “The Lord is merciful and compassionate” Exod. 34:6 without the deflected punishment clauses) or expanded citation (such as “You have heard it said, ‘Love your neighbor and hate your enemies’ ” [Matt. 5:43]). It concerns rather some instances where a verse may or may not be a citation and where extra-biblical ideology can interfere with the interpretation of what is being quoted, if it is being quoted. “The poor you have always with you” (Mark 14:7, possibly citing Deut. 15:11) is one such example.
Environmental and Collective Rights: Differences between Indigenous and Non-Indigenous ngo s Involved with the United Nations Human Rights Council
Authors: Hallward Maia , Butcher Charity , Downs Jonathan Taylor , Cook Emily
Published: March 2021

Scholarship on human rights and environmental justice suggests that organizations vary in their messaging regarding outcomes related to environmental protection and sustainability, differences often found in the divide between the Global North and Global South. The literature also suggests that Indigenous organizations represent groups that traditionally focus on issues of sovereignty, while grappling with unique problems related to assimilation, cultural preservation, and oppression. This study utilizes empirical data gathered from 333 non-governmental organizations affiliated with the United Nations Human Rights Council to explore whether Indigenous and non-Indigenous organizations, which share many aspects of their mission with one another at the transnational level, differ on issues related to environment sustainability and collective identity rights. Our results indicate that Indigenous organizations take a more holistic approach in addressing the relationship between humans and the natural world, centring marginalized perspectives through restorative justice and the needs of current and future generations.