bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competition between type I activin and BMP receptors for binding to ACVR2A regulates signaling to distinct Smad pathways
Authors: Szilágyi Szabina Szófia , Amsalem-Zafran Ayelet R. , Shapira Keren E. , Ehrlich Marcelo , Henis Yoav I. 
Published: February 2022

Abstract
Background
Activins and bone morphogenetic proteins (BMPs) play critical, sometimes opposing roles, in multiple physiological and pathological processes and diseases. They signal to distinct Smad branches; activins signal mainly to Smad2/3, while BMPs activate mainly Smad1/5/8. This gives rise to the possibility that competition between the different type I receptors through which activin and BMP signal for common type II receptors can provide a mechanism for fine-tuning the cellular response to activin/BMP stimuli. Among the transforming growth factor-β superfamily type II receptors, ACVR2A/B are highly promiscuous, due to their ability to interact with different type I receptors (e.g., ALK4 vs. ALK2/3/6) and with their respective ligands [activin A (ActA) vs. BMP9/2]. However, studies on complex formation between these full-length receptors situated at the plasma membrane, and especially on the potential competition between the different activin and BMP type I receptors for a common activin type II receptor, were lacking.

Results
We employed a combination of IgG-mediated patching-immobilization of several type I receptors in the absence or presence of ligands with fluorescence recovery after photobleaching (FRAP) measurements on the lateral diffusion of an activin type II receptor, ACVR2A, to demonstrate the principle of competition between type I receptors for ACVR2. Our results show that ACVR2A can form stable heteromeric complexes with ALK4 (an activin type I receptor), as well as with several BMP type I receptors (ALK2/3/6). Of note, ALK4 and the BMP type I receptors competed for binding ACVR2A. To assess the implications of this competition for signaling output, we first validated that in our cell model system (U2OS cells), ACVR2/ALK4 transduce ActA signaling to Smad2/3, while BMP9 signaling to Smad1/5/8 employ ACVR2/ALK2 or ACVR2/ALK3. By combining ligand stimulation with overexpression of a competing type I receptor, we showed that differential complex formation of distinct type I receptors with a common type II receptor balances the signaling to the two Smad branches.

Conclusions
Different type I receptors that signal to distinct Smad pathways (Smad2/3 vs. Smad1/5/8) compete for binding to common activin type II receptors. This provides a novel mechanism to balance signaling between Smad2/3 and Smad1/5/8.
Immunological characterization of the chemically prepared ghosts of Salmonella Typhimurium as a vaccine candidate
Authors: Rabea Sameh , Yassin Aymen S. , Mohammed Aly Fahmy , Salem-Bekhit Mounir M. , Alanazi Fars K. , Esmail Eman Amin , Moneib Nayera A. , Hashem Abd Elgawad M. 
Published: February 2022

Abstract
Background
Bacterial ghosts are the evacuated bacterial cellular membranes from most of the genetic and protein contents which preserved their surface characters. Recently, bacterial ghosts exploited for different biomedical applications, for instance, vaccination. The purpose of this study is to measure the immunogenic protective response of bacterial ghosts of Salmonella Typhimurium in animals and to allow future testing this response in humans. The immunologic response was qualitatively, quantitatively, and functionally measured. We have measured the humoral and cellular immune responses, such as immunoglobulins elevation (IgG), increased granulocytes, serum antibacterial activity, clearance of virulence in feces and liver, and the survival rate.

Results
The bacterial ghosts’ vaccine was able to protect 100% of subcutaneously vaccinated rats and 75% of adjuvant subcutaneously vaccinated rats. The lowest survival rate was in the orally vaccinated group (25%). The maximum level of serum IgG titers, as well as serum and feces bactericidal activity (100% eradication), was exhibited in the subcutaneously vaccinated group with adjuvant vaccines followed by the subcutaneously vaccinated one. Additionally, the highest granulocytes’ number was observed in the adjuvant vaccine subcutaneously immunized group. The bacterial load in liver homogenate was eliminated in the subcutaneously vaccinated rats after the virulence challenge.

Conclusions
The bacterial ghosts of Salmonella enterica serovar Typhimurium that prepared by Tween 80 Protocol showed an effective vaccine candidate that protected animals, eliminated the virulence in feces and liver. These findings show that chemically induced bacterial ghosts of Salmonella Typhimurium can be a promising vaccine.
Comprehensive analysis of retracted journal articles in the field of veterinary medicine and animal health
Authors: Christopher Mary M. 
Published: February 2022

Abstract
Background
Retractions are a key proxy for recognizing errors in research and publication and for reconciling misconduct in the scientific literature. The underlying factors associated with retractions can provide insight and guide policy for journal editors and authors within a discipline. The goal of this study was to systematically review and analyze retracted articles in veterinary medicine and animal health. A database search for retractions of articles with a veterinary/animal health topic, in a veterinary journal, or by veterinary institution-affiliated authors was conducted from first available records through February 2019 in MEDLINE/PubMed, Web of Science, Scopus, Retraction Watch, and Google Scholar. Annual frequency of retractions, journal and article characteristics, author affiliation and country, reasons for retraction, and retraction outcomes were recorded.

Results
Two-hundred-forty-two articles retracted between 1993 and 2019 were included in the study. Over this period, the estimated rate of retraction increased from 0.03/1000 to 1.07/1000 veterinary articles. Median time from publication to retraction was 478 days (range 0-3653 days). Retracted articles were published in 30 (12.3%) veterinary journals and 132 (81.5%) nonveterinary journals. Veterinary journals had disproportionately more retractions than nonveterinary journals (P = .0155). Authors/groups with ≥2 retractions accounted for 37.2% of retractions. Authors from Iran and China published 19.4 and 18.2% of retracted articles respectively. Authors were affiliated with a faculty of veterinary medicine in 59.1% of retracted articles. Of 242 retractions, 204 (84.3%) were research articles, of which 6.4% were veterinary clinical research. Publication misconduct (plagiarism, duplicate publication, compromised peer review) accounted for 75.6% of retractions, compared with errors (20.6%) and research misconduct (18.2%). Journals published by societies/institutions were less likely than those from commercial publishers to indicate a reason for retraction. Thirty-one percent of HTML articles and 14% of PDFs were available online but not marked as retracted.

Conclusions
The rate of retraction in the field of veterinary and animal health has increased by ~ 10-fold per 1000 articles since 1993, resulting primarily from increased publication misconduct, often by repeat offenders. Veterinary journals and society/institutional journals could benefit from improvement in the quality of retraction notices.
Fine particulate matter and polycystic ovarian morphology
Authors: Fruh Victoria , Cheng Jay Jojo , Aschengrau Ann , Mahalingaiah Shruthi , Lane Kevin J. 
Published: February 2022

Abstract
Background
Polycystic ovary morphology (PCOM) is an ultrasonographic finding that can be present in women with ovulatory disorder and oligomenorrhea due to hypothalamic, pituitary, and ovarian dysfunction. While air pollution has emerged as a possible disrupter of hormone homeostasis, limited research has been conducted on the association between air pollution and PCOM.

Methods
We conducted a longitudinal cohort study using electronic medical records data of 5,492 women with normal ovaries at the first ultrasound that underwent a repeated pelvic ultrasound examination during the study period (2004–2016) at Boston Medical Center. Machine learning text algorithms classified PCOM by ultrasound. We used geocoded home address to determine the ambient annual average PM2.5 exposures and categorized into tertiles of exposure. We used Cox Proportional Hazards models on complete data (n = 3,994), adjusting for covariates, and additionally stratified by race/ethnicity and body mass index (BMI).

Results
Cumulative exposure to PM2.5 during the study ranged from 4.9 to 17.5 µg/m3 (mean = 10.0 μg/m3). On average, women were 31 years old and 58% were Black/African American. Hazard ratios and 95% confidence intervals (CI) comparing the second and third PM2.5 exposure tertile vs. the reference tertile were 1.12 (0.88, 1.43) and 0.89 (0.62, 1.28), respectively. No appreciable differences were observed across race/ethnicity. Among women with BMI ≥ 30 kg/m2, we observed weak inverse associations with PCOM for the second (HR: 0.93, 95% CI: 0.66, 1.33) and third tertiles (HR: 0.89, 95% CI: 0.50, 1.57).

Conclusions
In this study of reproductive-aged women, we observed little association between PM2.5 concentrations and PCOM incidence. No dose response relationships were observed nor were estimates appreciably different across race/ethnicity within this clinically sourced cohort.
Exosomes as a new frontier of cancer liquid biopsy
Authors: Yu Dan , Li Yixin , Wang Maoye , Gu Jianmei , Xu Wenrong , Cai Hui , Fang Xinjian , Zhang Xu 
Published: February 2022

AbstractLiquid biopsy, characterized by minimally invasive detection through biofluids such as blood, saliva, and urine, has emerged as a revolutionary strategy for cancer diagnosis and prognosis prediction. Exosomes are a subset of extracellular vesicles (EVs) that shuttle molecular cargoes from donor cells to recipient cells and play a crucial role in mediating intercellular communication. Increasing studies suggest that exosomes have a great promise to serve as novel biomarkers in liquid biopsy, since large quantities of exosomes are enriched in body fluids and are involved in numerous physiological and pathological processes. However, the further clinical application of exosomes has been greatly restrained by the lack of high-quality separation and component analysis methods. This review aims to provide a comprehensive overview on the conventional and novel technologies for exosome isolation, characterization and content detection. Additionally, the roles of exosomes serving as potential biomarkers in liquid biopsy for the diagnosis, treatment monitoring, and prognosis prediction of cancer are summarized. Finally, the prospects and challenges of applying exosome-based liquid biopsy to precision medicine are evaluated.
NCAPG promotes the oncogenesis and progression of non-small cell lung cancer cells through upregulating LGALS1 expression
Authors: Sun Huanhuan , Zhang Hong , Yan Yan , Li Yushi , Che Gang , Zhou Cuiling , Nicot Christophe , Ma Haiqing 
Published: February 2022

Abstract
Background
Numerous common oncogenic driver events have been confirmed in non-small cell lung cancer (NSCLC). Although targeted therapy has revolutionized NSCLC treatment, some patients still do not respond. NCAPG, also known as non-SMC condensin I complex subunit G, was positively associated with proliferation and migration in several tumor types.

Methods
We used transcriptional sequencing and TCGA database analysis to identify NCAPG as a new therapeutic target for NSCLC. The oncogenic roles of NCAPG in NSCLC tumor growth and metastasis were detected in vitro and in vivo. Ncapg+/+ or Ncapg+/− mice with urethane treatment were analyzed for oncogenesis of NSCLC.

Results
We investigated NCAPG as a new oncogenic driver which promoted NSCLC tumorigenesis and progression. We used transcriptome sequencing and the Cancer Genome Atlas (TCGA) database analysis to screen and found that NCAPG was negatively correlated with NSCLC survival. Using immunohistochemistry, we demonstrated that NCAPG overexpression was an independent risk factor for NSCLC survival. Functionally, NCAPG knockdown inhibited proliferation, migration, and invasion of NSCLC cells in vitro and in vivo. We exposed wildtype or Ncapg+/− mice to urethane and discovered that urethane-induced lung tumors were reduced in Ncapg+/− mice. Mechanistically, the function of NCAPG in promoting initiation and progression of NSCLC was closely related to LGALS1, which was also upregulated in NSCLC and might interact directly with NCAPG.

Conclusions
This study indicates that NCAPG is one of the essential factors for NSCLC oncogenesis and progression, providing a new target for prognosis prediction and treatment of NSCLC.
Elevated expression of the rhythm gene NFIL3 promotes the progression of TNBC by activating NF-κB signaling through suppression of NFKBIA transcription
Authors: Yang Weiwei , Li Jing , Zhang Minghui , Yu Haichuan , Zhuang Yuan , Zhao Lingyu , Ren Lili , Gong Jinan , Bi Hongjie , Zeng Lixuan , Xue Yang , Yang Jinjin , Zhao Yan , Wang Shuoshuo , Gao Shuangshu , Fu Zitong , Li Dongze , Zhang Jinxing , Wang Tianzhen , Shan Ming , Tang Bo , Li Xiaobo 
Published: February 2022

Abstract
Background
Epidemiological studies have confirmed that abnormal circadian rhythms are associated with tumorigenesis in breast cancer. However, few studies have investigated the pathological roles of rhythm genes in breast cancer progression. In this study, we aimed to evaluate the aberrant expression of 32 rhythm genes in breast cancer and detect the pathological roles and molecular mechanisms of the altered rhythm gene in regulating the progression of triple negative breast cancer (TNBC).

Methods
The aberrant expression of rhythm genes in breast cancer was screened by searching the GEPIA database and validated by using qRT-PCR and immunohistochemistry staining. Bioinformatics analysis combined with luciferase reporter experiment and chromatinimmunopercitation (ChIP) were used to investigate the molecular mechanism about aberrant expression of identified rhythm gene in breast cancer. The pathological roles of identified rhythm gene in TNBC progression was evaluated by colony formation assay, wound healing experiment, transwell assay, subcutaneous tumor formation and the mouse tail vein injection model through gain-of-function and loss-of-function strategies respectively. mRNA array, bioinformatics analysis, luciferase reporter experiment, ChIP and immunoflurescence assay were employed to investigate the key molecules and signaling pathways by which the identified rhythm gene regulating TNBC progression.

Results
We identified that nuclear factor interleukin 3 regulated (NFIL3) expression is significantly altered in TNBC compared with both normal breast tissues and other subtypes of breast cancer. We found that NFIL3 inhibits its own transcription, and thus, downregulated NFIL3 mRNA indicates high expression of NFIL3 protein in breast cancer. We demonstrated that NFIL3 promotes the proliferation and metastasis of TNBC cells in vitro and in vivo, and higher expression of NFIL3 is associated with poor prognosis of patients with TNBC. We further demonstrated that NFIL3 enhances the activity of NF-κB signaling. Mechanistically, we revealed that NFIL3 directly suppresses the transcription of NFKBIA, which blocks the activation of NF-κB and inhibits the progression of TNBC cells in vitro and in vivo. Moreover, we showed that enhancing NF-κB activity by repressing NFKBIA largely mimics the oncogenic effect of NFIL3 in TNBC, and anti-inflammatory strategies targeting NF-κB activity block the oncogenic roles of NFIL3 in TNBC.

Conclusion
NFIL3 promotes the progression of TNBC by suppressing NFKBIA transcription and then enhancing NF-κB signaling-mediated cancer-associated inflammation. This study may provide a new target for TNBC prevention and therapy.

Graphical Abstract
PLCG2 is associated with the inflammatory response and is induced by amyloid plaques in Alzheimer’s disease
Authors: Tsai Andy P. , Dong Chuanpeng , Lin Peter Bor-Chian , Messenger Evan J. , Casali Brad T. , Moutinho Miguel , Liu Yunlong , Oblak Adrian L. , Lamb Bruce T. , Landreth Gary E. , Bissel Stephanie J. , Nho Kwangsik 
Published: February 2022

AbstractBackgroundAlzheimer’s disease (AD) is characterized by robust microgliosis and phenotypic changes that accompany disease pathogenesis. Accumulating evidence from genetic studies suggests the importance of phospholipase C γ 2 (PLCG2) in late-onset AD (LOAD) pathophysiology. However, the role ofPLCG2in AD is still poorly understood.MethodsUsing bulk RNA-Seq (N=1249) data from the Accelerating Medicines Partnership-Alzheimer’s Disease Consortium (AMP-AD), we investigated whetherPLCG2expression increased in the brains of LOAD patients. We also evaluated the relationship betweenPLCG2expression levels, amyloid plaque density, and expression levels of microglia specific markers (AIF1 and TMEM119). Finally, we investigated the longitudinal changes ofPLCG2expression in the 5xFAD mouse model of AD. To further understand the role ofPLCG2in different signaling pathways, differential gene expression and co-expression network analyses were performed using bulk RNA-Seq and microglial single-cell RNA-Seq data. To substantiate the human analyses, we performed differential gene expression analysis on wild-type (WT) and inactivatedPlcg2mice and used immunostaining to determine if the differentially expressed genes/pathways were altered by microglial cell coverage or morphology.ResultsWe observed significant upregulation ofPLCG2expression in three brain regions of LOAD patients and significant positive correlation ofPLCG2expression with amyloid plaque density. These findings in the human brain were validated in the 5xFAD amyloid mouse model, which showed disease progression-dependent increases inPlcg2expression associated with amyloid pathology. Of note, increasedPlcg2expression levels in 5xFAD mice were abolished by reducing microglia. Furthermore, using bulk RNA-Seq data, we performed differential expression analysis by comparing cognitively normal older adults (CN) with 75th percentile (high) and 25th percentile (low)PLCG2gene expression levels to identify pathways related to inflammation and the inflammatory response. The findings in the human brain were validated by differential expression analyses between WT andplcg2inactivated mice.PLCG2co-expression network analysis of microglial single-cell RNA-Seq data identified pathways related to the inflammatory response including regulation of I-kappaB/NF-kappa B signaling and response to lipopolysaccharide.ConclusionsOur results provide further evidence thatPLCG2plays an important role in AD pathophysiology and may be a potential target for microglia-targeted AD therapies.
Aggressive (deep) angiomyxoma of the vulva: a case report
Authors: Goyal Lajya Devi , Garg Priyanka , Badyal Rama , Bhalla Shivali 
Published: February 2022

Abstract
Background
Aggressive angiomyxoma of the vulva is a benign, slow-growing tumor originating from myxoid cells of connective tissue. The tumor is known for multiple local recurrences with a low tendency to metastasize. Only around 350 cases have been documented in the scientific literature so far.

Case presentation
We report a case of a 40-year-old North Indian, unmarried woman with a swelling on the left labium majora for 7 years, along with surface ulceration over the mass. Local examination showed a well-circumscribed, 8 × 8 cm pedunculated mass arising from the left labium majora with an overlying ulcer measuring 6 cm × 4 cm. After taking informed written consent, wide local excision of the mass and surrounding margins was done under anesthesia. Histopathology was suggestive of aggressive angiomyxoma. Immunohistochemistry was done, which was positive for estrogen and progesterone receptors. Her postoperative recovery was uneventful. The patient was given three doses of gonadotropin-releasing hormone agonist (injection, leuprolide 3.75 mg) once a month. No recurrence has been reported so far on follow-up visits for 1 year.

Conclusion
Aggressive angiomyxoma is one of the differential diagnoses for vulvovaginal growth in a female. As the tumor is well known for local recurrences, correct diagnosis and appropriate management using a multidisciplinary approach are crucial to managing such patients.
Homogenization of periodic structures: One layer is “bulk”
Authors: Hossain A. N. M. Shahriyar , Tsukerman Igor , Markel Vadim A. 
Published: February 2022

Abstract
In homogenization theories of periodic electromagnetic structures, such as photonic crystals or metamaterials, it is commonly assumed that the accuracy of the effective medium representation is affected by the thickness of the sample in two different ways. The first factor is the optical length (OL) of wave propagation within the sample. For a large OL, minor deviations in the wave number may strongly affect transmission and reflection. The second factor is the putative convergence to bulk characteristics (CB), once the number of layers in the sample has approached or passed a certain threshold. The theoretical analysis and numerical examples of this letter show that, while the OL influence is real, CB is not actually relevant; in a sense, one layer is already “bulk”.
Incretin Hypersecretion in Gestational Diabetes Mellitus
Authors: Fritsche Louise , Heni Martin , Eckstein Sabine S , Hummel Julia , Schürmann Anette , Häring Hans-Ulrich , Preißl Hubert , Birkenfeld Andreas L , Peter Andreas , Fritsche Andreas , Wagner Robert 
Published: February 2022

Abstract

Context
Incretins are crucial stimulators of insulin secretion following food intake. Data on incretin secretion and action during pregnancy are sparse.

Objective
The aim of the study was to investigate the incretin response during an oral glucose tolerance test (OGTT) in pregnant women with and without gestational diabetes mellitus (GDM).

Design
We analyzed data from the ongoing observational PREG study (NCT 04270578).

Setting
The study was conducted at the University Hospital Tübingen.

Participants
We examined 167 women (33 with GDM) during gestational week 27 ± 2.2.

Intervention
Subjects underwent 5-point OGTT with a 75-g glucose load.

Main outcome measures
We assessed insulin secretion and levels of total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glicentin, and glucagon during OGTT. Linear regression was used to analyze the relation of GLP-1 and glucose with insulin secretion and the association of incretin levels on birth outcome.

Results
Insulin secretion was significantly lower in women with GDM (P &lt; 0.001). Postload GLP-1 and GIP were ~20% higher in women with GDM (all P &lt; 0.05) independent of age, body mass index, and gestational age. GLP-1 increase was associated with insulin secretion only in GDM, but not in normal glucose tolerance. Postprandial GLP-1 levels were negatively associated with birth weight.

Conclusions
The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. Higher GLP-1 levels might be protective against fetal overgrowth.