bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined extract of heated TC1, a heat-killed preparation of Lactobacillus casei and alpha-galactosyl ceramide in a mouse model of cervical cancer
Authors: Haghighi Dorsa , Yazdani Shaghayegh , Farzanehpour Mahdieh , Esmaeili Gouvarchinghaleh Hadi 
Published: September 2022

Abstract
Background
Nowadays, cancer is the leading cause of death among threats to humanity, necessitating prompt action and preparation. Cervical cancer is one of the most common cancers in women and is currently treated with surgery, radiation, chemotherapy, and immunotherapy, among other treatments. Current oncology approaches focused on the simultaneous development of safe and effective cancer multi-agent therapies. The present study aimed to evaluate the effects of a combined extracts of heated TC1, a heat-killed preparation of Lactobacilluscasei, and alpha-galactosyl ceramide (α-GalCer) in a mouse model of cervical cancer.

Material and methods
Cervical cancer in the mouse model was prepared by TC1 cells subcutaneous injection into the left flank of female C57BL/6 mouse aged 6–8 weeks (n = 80). After the appearance of the palpable tumor, the mice with cervical cancer were randomly devoted to 8 (ten-member) groups. The mice in some groups were treated with PBS, TC1 cell extract, L. casei extract, α-GalCer, and a combination of the mentioned treatments. Then, they were evaluated the splenocytes proliferation, lactate dehydrogenase production and nitric oxide. Moreover, IL-4, IFN-γ, and TGF-β cytokine levels of splenocytes supernatant the mice were measured. In all evaluations, a statistical difference of less than 0.05 (P ˂ 0.05) was considered as a significant level.

Result
The findings revealed that the combination therapy group (heated TC1 cell and L. casei extracts with α-GalCer) significantly increases the splenocytes proliferation (MTT) (0.358 ± 0.04 OD), LDH production (45.9 ± 2.3 U/L), NO rate (38.4 ± 2.8 µM), and IFN-γ cytokine level (46.6 ± 3.7 pg/ml) (P < 0.05). Also, observes a significantly reduces the production of IL-4 (11.6 ± 2.5 pg/ml) and TGF-β cytokines levels (7.8 ± 2.5 pg/ml) (P < 0.05) in comparison to the control group.

Conclusion
The study showed that combination therapy of L. casei and α-GalCer is an efficient treatment for cervical cancer in the mouse model.
DNA methylation underpins the epigenomic landscape regulating genome transcription in Arabidopsis
Authors: Zhao Lun , Zhou Qiangwei , He Li , Deng Li , Lozano-Duran Rosa , Li Guoliang , Zhu Jian-Kang 
Published: September 2022

AbstractBackgroundIt is challenging to determine the effect of DNA methylation on the epigenetic landscape and the function in higher organisms due to the lack of DNA methylation-free mutants.ResultsHere, the analysis of a recently generatedArabidopsismutant completely devoid of DNA methylation reveals that DNA methylation underpins the genome-wide landscape of histone modifications. Complete loss of DNA methylation causes an upheaval of the histone modification landscape, including complete loss of H3K9me2 and widespread redistribution of active and H3K27me3 histone marks, mostly owing to the role of DNA methylation in initiating H3K9me2 deposition and excluding active marks and repressive mark H3K27me3; CG and non-CG methylation can act independently at some genomic regions while they act cooperatively at many other regions. The transcriptional reprogramming upon loss of all DNA methylation correlates with the extensive redistribution or switches of the examined histone modifications. Histone modifications retained or gained in the DNA methylation-free mutant serve as DNA methylation-independent transcriptional regulatory signals: active marks promote genome transcription, whereas the repressive mark H3K27me3 compensates for the lack of DNA hypermethylation/H3K9me2 at multiple transposon families.ConclusionsOur results show that an intact DNA methylome constitutes the scaffolding of the epigenomic landscape inArabidopsisand is critical for controlled genome transcription and ultimately for proper growth and development.
Effects of salvianolic acid A on intestinal microbiota and lipid metabolism disorders in Zucker diabetic fatty rats
Authors: Wang Xufeng , Sun Xiangjun , Abulizi Abulikemu , Xu Jinyao , He Yun , Chen Qian , Yan Ruicheng 
Published: September 2022

AbstractSalvianolic acid A (SalA) is the main water-soluble component isolated from Salvia miltiorrhiza. This study explored the influences of SalA on intestinal microbiota composition and lipid metabolism in Zucker diabetic fatty (ZDF) rats. The 6-week-old male ZDF rats were treated with distilled water (N = 10) and low dose (SalA 0.5 mg/kg/d, N = 10), medium dose (SalA 1 mg/kg/d, N = 10), and high dose (SalA 2 mg/kg/d, N = 10) of SalA, with the male Zucker lean normoglycemic rats of the same week age as controls (given distilled water, N = 10). The blood glucose, body weight, and food intake of rats were examined. After 7 and 8 weeks of continuous administration, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed, respectively. Serum fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) were determined. Liver tissues were stained using hematoxylin–eosin (HE) and oil red O staining. Fecal samples were analyzed by 16S rRNA gene sequencing. Small intestinal tissues were stained using HE and immunohistochemistry. The tight junction proteins (ZO-1/Occludin/Claudin-1) and serum levels of LPS/TNF-α/IL-6 were evaluated. SalA reduced insulin resistance, liver injury, serum FFA, liver TC and TG levels in ZDF rats, and improved lipid metabolism. After SalA treatment, intestinal microbiota richness and diversity of ZDF rats were promoted. SalA retained the homeostasis of intestinal core microbiota. SalA reduced intestinal epithelial barrier damage, LPS, and inflammatory cytokines in ZDF rats. Overall, SalA can sustain intestinal microbiota balance and improve the lipid metabolism of ZDF rats.
Promoting trust in research and researchers: How open science and research integrity are intertwined
Authors: Haven Tamarinde , Gopalakrishna Gowri , Tijdink Joeri , van der Schot Dorien , Bouter Lex 
Published: September 2022

AbstractProponents of open science often refer to issues pertaining to research integrity and vice versa. In this commentary, we argue that concepts such as responsible research practices, transparency, and open science are connected to one another, but that they each have a different focus. We argue that responsible research practices focus more on the rigorous conduct of research, transparency focuses predominantly on the complete reporting of research, and open science’s core focus is mostly about dissemination of research. Doing justice to these concepts requires action from researchers and research institutions to make research with integrity possible, easy, normative, and rewarding. For each of these levels from the Center for Open Science pyramid of behaviour change, we provide suggestions on what researchers and research institutions can do to promote a culture of research integrity. We close with a brief reflection on initiatives by other research communities and stakeholders and make a call to those working in the fields of research integrity and open science to pay closer attention to one other’s work.
Multilevel analysis of undernutrition and associated factors among adolescent girls and young women in Ethiopia
Authors: Negash Wubshet Debebe , Fetene Samrawit Mihret , Shewarega Ever Siyoum , Fentie Elsa Awoke , Asmamaw Desale Bihonegn , Teklu Rediet Eristu , Aragaw Fantu Mamo , Belay Daniel Gashaneh , Alemu Tewodros Getaneh , Eshetu Habitu Birhan 
Published: September 2022

AbstractBackgroundThe consequences of undernutrition have serious implication for the health and future reproductive periods of adolescent girls and young women aged 15–24 years. Inspite of this, they are neglected age groups and there is limited information about the nutritional status of this age group in Ethiopia. Therefore, estimating the extent and associated factors of undernutrition among adolescent girls and young women in a national context using multilevel analysis is essential.MethodsSecondary data analysis was conducted from the Ethiopian Demographic and Health Survey 2016. A total sample weight of 5362 adolescent girls and young women was included in this study. A multilevel mixed-effect binary logistic regression model with cluster-level random effects was fitted to determine the associated factors of undernutrition among adolescent girls and young women in Ethiopia. Finally, the odds ratios along with the 95% confidence interval was generated to determine the individual and community level factors of undernutrition. Ap-value less than 0.05 was declared as the level of statistical significance.ResultsOverall, 25.6% (95%CI: 24.5–26.9) of adolescent girls and young women were undernourished. Statistically significant individual level factors includes adolescent girls and young women aged 15–19 years (AOR: 1.53, 95%CI: 1.32–1.77), individual media exposure (AOR: 0.82, 95%CI: 0.69–0.97), and unprotected drinking water source (AOR: 1.24, 95%CI: 1.04–1.48). Whereas, Southern Nations, Nationalities, and Peoples' Region (AOR: 0.33, 95%CI: 0.13–0.83) and rural residence (AOR: 1.69, 95%CI: 1.24–2.32), were community level factors for adolescent girls and young women undernutrition.ConclusionOne quarter of the Ethiopian adolescent girls and young women were undernourished. Therefore, the Ethiopian government should better engage this age group in different aspects of the food system. To improve nutritional status, public health interventions such as increased media exposure for rural residents and interventions that improve access to protected water sources will be critical.
Psychometric properties of a Saudi Arabian version of the Positive Mental Health (PMH) scale
Authors: Almubaddel Abdulmohsen 
Published: September 2022

AbstractThe Positive Mental Health (PMH) scale has been shown to be a reliable and valid tool for assessing positive mental health and well-being in different languages and cultures. However, the PMH scale has not yet been translated into Arabic and validated for the Saudi Arabian population. Therefore, the current study aimed to translate the English version of the PMH scale into Arabic for the Saudi Arabian context and validate the translated scale. A total of 1148 adult participants from Saudi public universities took part in the study. Based on exploratory and confirmatory factor analyses in different subsamples, the results of the current study revealed that the unifactorial model satisfactorily fits the data. Additionally, the Arabic version of the PMH scale demonstrated sufficient levels of reliability and had a high negative correlation with the Beck Depression Inventory-II, indicating convergent validity. Taken together, the findings of the current study suggest that the Arabic version of the PMH scale has appropriate levels of validity and reliability for the Saudi Arabian population.
High-grade transformation of adenoid cystic carcinoma of parotid gland with isolated intratemporal facial nerve involvement: a case report and literature review
Authors: Balakrishnan Manu Coimbatore , Bhatia Abhijeet , Lyngdoh Bifica Sofia , Harris Caleb , Lynser Donboklang , Kalita Pranjal 
Published: September 2022

Abstract
Background
High-grade transformation Adenoid cystic carcinoma (HGT-AdCC) of the parotid gland is a rare transformation noted in slow growing low grade AdCC. Perineural invasion and spread is an important feature of this tumor. Temporal bone involvement is rare. A total of only 10 cases of HGT-AdCC in parotid gland has been reported in literature so far predominantly in the elderly with peak incidence in 5th–6th decade.

Case presentation
We present a young lady of HGT-AdCC of right parotid gland with temporal bone involvement in the form of isolated perineural invasion (PNI) of facial nerve till the tympanic segment. She underwent right radical parotidectomy with modified radical neck dissection with modified lateral temporal bone resection and pectoralis major myocutaneous flap reconstruction. Histopathological examination revealed both low- and high-grade areas. Sections from facial nerve showed tumor invasion.

Conclusion
The radiological features of isolated perineural spread in intratympanic part of facial nerve can be easily missed if not specifically looked for. Every attempt should be made preoperatively and intraoperatively to determine the complete extent of the tumor for adequate disease clearance. A combined clinico-radiological approach aided by histopathology examination helps in early detection of this carcinoma and in better patient management.
Team Science Principles Enhance Cancer Care Delivery Quality Improvement: Interdisciplinary Implementation of Breast Cancer Screening Shared Decision Making
Authors: Burnside Elizabeth S. , Schrager Sarina , DuBenske Lori , Keevil Jon , Little Terry , Trentham-Dietz Amy , Rolland Betsy , Shah Dhavan , Alagoz Oguzhan 
Published: September 2022

PURPOSE:Implementing shared decision making (SDM), recommended in screening mammography by national guidelines for women age 40-49 years, faces challenges that innovations in quality improvement and team science (TS) are poised to address. We aimed to improve the effectiveness, patient-centeredness, and efficiency of SDM in primary care for breast cancer screening.METHODS:Our interdisciplinary team included primary and specialty care, psychology, epidemiology, communication science, engineering, and stakeholders (patients and clinicians). Over a 6-year period, we executed two iterative cycles of plan-do-study-act (PDSA) to develop, revise, and implement a SDM tool using TS principles. Patient and physician surveys and retrospective analysis of tool performance informed our first PDSA cycle. Patient and physician surveys, toolkit use, and clinical outcomes in the second PDSA cycle supported SDM implementation. We gathered team member assessments on the importance of individual TS activities.RESULTS:Our first PDSA cycle successfully generated a SDM tool called Breast Cancer Risk Estimator, deemed valuable by 87% of patients surveyed. Our second PDSA cycle increased Breast Cancer Risk Estimator utilization, from 2,000 sessions in 2017 to 4,097 sessions in 2019 while maintaining early-stage breast cancer diagnoses. Although TS activities such as culture, trust, and communication needed to be sustained throughout the project, shared goals, research/data infrastructure support, and leadership were more important earlier in the project and persisted in the later stages of the project.CONCLUSION:Combining rigorous quality improvement and TS principles can support the complex, interdependent, and interdisciplinary activities necessary to improve cancer care delivery exemplified by our implementation of a breast cancer screening SDM tool.
Oncologists' Perspectives on Individualizing Dose Selection for Patients With Metastatic Cancer
Authors: Jimenez Rachel B. , Schenkel Caroline , Levit Laura A. , Hu Bonnie , Lei Xiudong Jennifer , Harvey R. Donald , Morrison Vicki A. , Pollastro Teri , Waterhouse David , Weekes Colin , Williams Grant R. , Bruinooge Suanna , Garrett-Mayer Elizabeth , Peppercorn Jeffrey 
Published: September 2022

PURPOSE: Treatment goals for patients with metastatic cancer include prolongation and maintenance of quality of life. Patients and oncologists have questioned the current paradigm of initial dose selection for systemic therapy; however, data on oncologists' dose selection strategies and beliefs are lacking. METHODS: We conducted an electronic international survey of medical oncologists who treat patients with breast and/or gastrointestinal cancers. Survey questions addressed experiences with, and attitudes toward, dose reduction at initiation (DRI) of a new systemic therapy for patients with metastatic cancer. RESULTS: Among 3,099 eligible oncologists, 367 responded (response rate 12%). Most (52%) reported using DRI at least 10% of the time to minimize toxicities. Gastrointestinal specialists were more likely to report DRI ≥ 10% of the time (72% v 50% of generalists and 51% of breast specialists, P < .005). Of those who dose reduced ≥ 10% of the time, 89% reported discussing potential tradeoffs between efficacy and toxicity with patients. Overall, 65% agreed it is acceptable to lower starting doses to reduce side effects even if it compromises efficacy; younger clinicians were more likely to agree ( P < .005). There was strong support (89%) for future trials to determine optimal effective, rather than maximum tolerated, dose. CONCLUSION: Oncology practice varies with regard to discussion and individualized selection of starting doses in the metastatic setting. This study demonstrates a need for consideration of shared decision making regarding initial dose selection and strong support among oncologists for clinical studies to define optimal dosing and best practices for individualizing care.
C. elegans srGAP is an α-catenin M domain-binding protein that strengthens cadherin-dependent adhesion during morphogenesis
Authors: Serre Joel M. , Lucas Bethany , Martin Sterling C. T. , Heier Jonathon A. , Shao Xiangqiang , Hardin Jeff 
Published: September 2022

ABSTRACT
The cadherin-catenin complex (CCC) is central to embryonic development and tissue repair, yet how CCC binding partners function alongside core CCC components remains poorly understood. Here, we establish a previously unappreciated role for an evolutionarily conserved protein, the slit-robo GTPase-activating protein SRGP-1/srGAP, in cadherin-dependent morphogenetic processes in the Caenorhabditis elegans embryo. SRGP-1 binds to the M domain of the core CCC component, HMP-1/α-catenin, via its C terminus. The SRGP-1 C terminus is sufficient to target it to adherens junctions, but only during later embryonic morphogenesis, when junctional tension is known to increase. Surprisingly, mutations that disrupt stabilizing salt bridges in the M domain block this recruitment. Loss of SRGP-1 leads to an increase in mobility and decrease of junctional HMP-1. In sensitized genetic backgrounds with weakened adherens junctions, loss of SRGP-1 leads to late embryonic failure. Rescue of these phenotypes requires the C terminus of SRGP-1 but also other domains of the protein. Taken together, these data establish a role for an srGAP in stabilizing and organizing the CCC during epithelial morphogenesis by binding to a partially closed conformation of α-catenin at junctions.
LATS1/2 control TGFB-directed epithelial-to-mesenchymal transition in the murine dorsal cranial neuroepithelium through YAP regulation
Authors: Martínez Traverso Idaliz M. , Steimle Jeffrey D. , Zhao Xiaolei , Wang Jun , Martin James F. 
Published: September 2022

ABSTRACT
Hippo signaling, an evolutionarily conserved kinase cascade involved in organ size control, plays key roles in various tissue developmental processes, but its role in craniofacial development remains poorly understood. Using the transgenic Wnt1-Cre2 driver, we inactivated the Hippo signaling components Lats1 and Lats2 in the cranial neuroepithelium of mouse embryos and found that the double conditional knockout (DCKO) of Lats1/2 resulted in neural tube and craniofacial defects. Lats1/2 DCKO mutant embryos had microcephaly with delayed and defective neural tube closure. Furthermore, neuroepithelial cell shape and architecture were disrupted within the cranial neural tube in Lats1/2 DCKO mutants. RNA sequencing of embryonic neural tubes revealed increased TGFB signaling in Lats1/2 DCKO mutants. Moreover, markers of epithelial-to-mesenchymal transition (EMT) were upregulated in the cranial neural tube. Inactivation of Hippo signaling downstream effectors, Yap and Taz, suppressed neuroepithelial defects, aberrant EMT and TGFB upregulation in Lats1/2 DCKO embryos, indicating that LATS1/2 function via YAP and TAZ. Our findings reveal important roles for Hippo signaling in modulating TGFB signaling during neural crest EMT.
The oncogenic transcription factor FOXQ1 is a differential regulator of Wnt target genes
Authors: Pizzolato Giulia , Moparthi Lavanya , Söderholm Simon , Cantù Claudio , Koch Stefan 
Published: September 2022

ABSTRACT
The forkhead box transcription factor FOXQ1 contributes to the pathogenesis of carcinomas. In colorectal cancers, FOXQ1 promotes tumour metastasis by inducing epithelial-to-mesenchymal transition (EMT) of cancer cells. FOXQ1 may exacerbate cancer by activating the oncogenic Wnt/β-catenin signalling pathway. However, the role of FOXQ1 in the Wnt pathway remains to be resolved. Here, we report that FOXQ1 is an activator of Wnt-induced transcription and regulator of β-catenin target gene expression. Upon Wnt pathway activation, FOXQ1 synergises with the β-catenin nuclear complex to boost the expression of major Wnt targets. In parallel, we find that FOXQ1 controls the differential expression of various Wnt target genes in a β-catenin-independent manner. Using RNA sequencing of colorectal cancer cell lines, we show that Wnt signalling and FOXQ1 converge on a transcriptional programme linked to EMT and cell migration. Additionally, we demonstrate that FOXQ1 occupies Wnt-responsive elements in β-catenin target gene promoters and recruits a similar set of co-factors to the β-catenin-associated transcription factor Tcf7l1. Taken together, our results indicate a multifaceted role of FOXQ1 in Wnt/β-catenin signalling, which may drive the metastasis of colorectal cancers.
Characterization of two novel ammonia transporters, Hiat1a and Hiat1b, in the teleost model system Danio rerio
Authors: Zhouyao Haonan , Zimmer Alex M. , Fehsenfeld Sandra , Liebenstein Thomas , Richter David O. , Begemann Gerrit , Eck Peter , Perry Steve F. , Weihrauch Dirk 
Published: September 2022

ABSTRACT
Ammonia excretion in fish excretory epithelia is a complex interplay of multiple membrane transport proteins and mechanisms. Using the model system of zebrafish (Danio rerio) larvae, here we identified three paralogues of a novel ammonia transporter, hippocampus-abundant transcript 1 (DrHiat1), also found in most vertebrates. When functionally expressed in Xenopus laevis oocytes, DrHiat1a and DrHiat1b promoted methylamine uptake in a competitive manner with ammonia. In situ hybridization experiments showed that both transporters were expressed as early as the 4-cell stage in zebrafish embryos and could be identified in most tissues 4 days post-fertilization. Larvae experiencing morpholino-mediated knockdown of DrHiat1b exhibited significantly lower whole-body ammonia excretion rates compared with control larvae. Markedly decreased site-specific total ammonia excretion of up to 85% was observed in both the pharyngeal region (site of developing gills) and the yolk sac (region shown to have the highest NH4+ flux). This study is the first to identify DrHiat1b/DrHIAT1 in particular as an important contributor to ammonia excretion in larval zebrafish. Being evolutionarily conserved, these proteins are likely involved in multiple other general ammonia-handling mechanisms, making them worthy candidates for future studies on nitrogen regulation in fishes and across the animal kingdom.