bluuebunny/crossref_metadata_2025_split huggingface dataset:
A concealed inguinal presentation of a gastrointestinal stromal tumor (GIST): a case report and literature review
Authors: Yuan Yujie , Ding Li , Tan Min , Han An-jia , Zhang Xinhua 
Published: March 2021

Abstract
Background
Gastrointestinal stromal tumor (GIST) can arise anyplace along the gastrointestinal (GI) tract. The uncommon tumor location in groin area is rarely reported.

Case presentation
We herein reported a metastasized case presented as GI hemorrhage complicated with indirect hernia, and underwent tumor cytoreduction, herniorrhaphy and chemotherapy for jejunal GIST. The case was described consecutively based on the process of surgical management, with a good follow-up result. A literature review by searching similar case reports from two national medical databases was performed to summarize clinical features of such unusual presentation of GIST, which included hernia characteristics, short- and long-term outcomes of this disease. It showed GIST presenting as groin hernia was rarely reported and all available 11 cases suggested a primary tumor and required both tumor resection and hernia repair. The long-term results indicated 64.3% overall survival at 5 years after the incidental diagnosis.

Conclusions
Inguinal hernia is an extremely rare presentation of GIST, with limited case reports available in the literature. A radical involving tumor resection plus hernia repair is an optimal surgical approach for such uncommon condition. An adjuvant medication mounting on mutated KIT gene should be strictly followed for high risk cases.
Outcomes of endoscopic transsphenoidal surgery for Cushing's disease
Authors: Brady Zarina , Garrahy Aoife , Carthy Claire , O’Reilly Michael W. , Thompson Christopher J. , Sherlock Mark , Agha Amar , Javadpour Mohsen 
Published: March 2021

Abstract
Background
Transsphenoidal surgery (TSS) to resect an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment for Cushing’s disease (CD), with increasing usage of endoscopic transsphenoidal (ETSS) technique. The aim of this study was to assess remission rates and postoperative complications following ETSS for CD.

Methods
A retrospective analysis of a prospective single-surgeon database of consecutive patients with CD who underwent ETSS between January 2012–February 2020. Post-operative remission was defined, according to Endocrine Society Guidelines, as a morning serum cortisol < 138 nmol/L within 7 days of surgery, with improvement in clinical features of hypercortisolism. A strict cut-off of < 50 nmol/L at day 3 post-op was also applied, to allow early identification of remission.

Results
A single surgeon (MJ) performed 43 ETSS in 39 patients. Pre-operative MRI localised an adenoma in 22 (56%) patients; 18 microadenoma and 4 macroadenoma (2 with cavernous sinus invasion). IPSS was carried out in 33 (85%) patients. The remission rates for initial surgery were 87% using standard criteria, 58% using the strict criteria (day 3 cortisol < 50 nmol/L). Three patients had an early repeat ETSS for persistent disease (day 3 cortisol 306-555 nmol/L). When the outcome of repeat early ETSS was included, the remission rate was 92% (36/39) overall. Remission rate was 94% (33/35) when patients with macroadenomas were excluded. There were no cases of CSF leakage, meningitis, vascular injury or visual deterioration. Transient and permanent diabetes insipidus occurred in 33 and 23% following first ETSS, respectively. There was one case of recurrence of CD during the follow-up period of 24 (4–79) months.

Conclusion
Endoscopic transsphenoidal surgery produces satisfactory remission rates for the primary treatment of CD, with higher remission rates for microadenomas. A longer follow-up period is required to assess recurrence rates. Patients should be counselled regarding risk of postoperative diabetes insipidus.
Systematic review: bioethical implications for COVID-19 research in low prevalence countries, a distinctly different set of problems
Authors: Skapetis Tony , Law Constance , Rodricks Rohan 
Published: March 2021

Abstract
Background
The COVID-19 pandemic has presented extraordinary challenges to worldwide healthcare systems, however, prevalence remains low in some countries. While the challenges of conducting research in high-prevalence countries are well published, there is a paucity from low COVID-19 countries.

Methods
A PRISMA guided systematic review was conducted using the databases Ovid-Medline, Embase, Scopus and Web of Science to identify relevant articles discussing ethical issues relating to research in low prevalence COVID-19 countries.

Results
The search yielded 133 original articles of which only 2 fit the inclusion criteria and aim, with neither specific to low prevalence. Most of the available literature focused on clinical management and resource allocation related to high prevalence countries. These results will be discussed under the ethical dimensions of equity, individual liberty, privacy and confidentiality, proportionality, public protection, provision of care, reciprocity, stewardship and trust..

Conclusions
A systematic review failed to identify articles relating to COVID-19 research ethics, specific to low prevalence countries. It shows that there is a significant gap in the literature that warrants further investigation. Common ethical principles were used to present a distinct set of challenges experienced by a country with a low prevalence of COVID-19. This unique perspective of some of the common ethical problems surrounding research, may help guide further discussion and guide research in similar countries.
GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo
Authors: Arcones Alba C. , Vila-Bedmar Rocío , Mirasierra Mercedes , Cruces-Sande Marta , Vallejo Mario , Jones Ben , Tomas Alejandra , Mayor Federico , Murga Cristina 
Published: March 2021

Abstract
Background
Insulin secretion from the pancreatic β-cell is finely modulated by different signals to allow an adequate control of glucose homeostasis. Incretin hormones such as glucagon-like peptide-1 (GLP-1) act as key physiological potentiators of insulin release through binding to the G protein-coupled receptor GLP-1R. Another key regulator of insulin signaling is the Ser/Thr kinase G protein-coupled receptor kinase 2 (GRK2). However, whether GRK2 affects insulin secretion or if GRK2 can control incretin actions in vivo remains to be analyzed.

Results
Using GRK2 hemizygous mice, isolated pancreatic islets, and model β-cell lines, we have uncovered a relevant physiological role for GRK2 as a regulator of incretin-mediated insulin secretion in vivo. Feeding, oral glucose gavage, or administration of GLP-1R agonists in animals with reduced GRK2 levels (GRK2+/− mice) resulted in enhanced early phase insulin release without affecting late phase secretion. In contrast, intraperitoneal glucose-induced insulin release was not affected. This effect was recapitulated in isolated islets and correlated with the increased size or priming efficacy of the readily releasable pool (RRP) of insulin granules that was observed in GRK2+/− mice. Using nanoBRET in β-cell lines, we found that stimulation of GLP-1R promoted GRK2 association to this receptor and that GRK2 protein and kinase activity were required for subsequent β-arrestin recruitment.

Conclusions
Overall, our data suggest that GRK2 is an important negative modulator of GLP-1R-mediated insulin secretion and that GRK2-interfering strategies may favor β-cell insulin secretion specifically during the early phase, an effect that may carry interesting therapeutic applications.
Effectiveness and cost-effectiveness of eliminating cervical cancer through a tailored optimal pathway: a modeling study
Authors: Xia Changfa , Xu Xiaoqian , Zhao Xuelian , Hu Shangying , Qiao Youlin , Zhang Yong , Hutubessy Raymond , Basu Partha , Broutet Nathalie , Jit Mark , Zhao Fanghui 
Published: March 2021

Abstract
Background
The World Health Assembly has adopted a global strategy to eliminate cervical cancer. However, neither the optimal pathway nor the corresponding economic and health benefits have been evaluated. We take China as an example to assess the optimal pathway towards elimination and the cost-effectiveness of tailored actions.

Methods
A validated hybrid model was used to assess the costs and benefits of alternative strategies combining human papillomavirus vaccination, cervical screening, and treatment of pre-invasive lesions and invasive cancer for females with different immunization history. All Chinese females living or projected to be born during 2015–2100, under projected trends in aging, urbanization, and sexual activity, were considered. Optimal strategies were determined by cost-effectiveness efficiency frontiers. Primary outcomes were cervical cancer cases and deaths averted and incremental cost-effectiveness ratios (ICERs). We employed a lifetime horizon from a societal perspective. One-way and probabilistic sensitivity analyses evaluate model uncertainty.

Results
The optimal pathway represents an integration of multiple tailored strategies from females with different immunization history. If China adopts the optimal pathway, the age-standardized incidence of cervical cancer is predicted to decrease to fewer than four new cases per 100,000 women (i.e., elimination) by 2047 (95% confidence interval 2043 to 2050). Compared to the status quo, the optimal pathway would avert a total of 7,509,192 (6,922,744 to 8,359,074) cervical cancer cases and 2,529,873 (2,366,826 to 2,802,604) cervical cancer deaths in 2021–2100, with the discounted ICER being $− 339 (− 687 to − 79) per quality-adjusted life-year.

Conclusions
By adopting an optimal pathway from 2021 (namely, the year of the first Chinese Centennial Goals) onwards, cervical cancer could be eliminated by the late 2040s (namely, ahead of the second Chinese Centennial Goals) while saving net economic costs in China.
Rheumatoid cachexia: the underappreciated role of myoblast, macrophage and fibroblast interplay in the skeletal muscle niche
Authors: Ollewagen T. , Myburgh K. H. , van de Vyver M. , Smith C. 
Published: March 2021

AbstractAlthough rheumatoid arthritis affects 1% of the global population, the role of rheumatoid cachexia, which occurs in up to a third of patients, is relatively neglected as research focus, despite its significant contribution to decreased quality of life in patients. A better understanding of the cellular and molecular processes involved in rheumatoid cachexia, as well as its potential treatment, is dependent on elucidation of the intricate interactions of the cells involved, such as myoblasts, fibroblasts and macrophages. Persistent RA-associated inflammation results in a relative depletion of the capacity for regeneration and repair in the satellite cell niche. The repair that does proceed is suboptimal due to dysregulated communication from the other cellular role players in this multi-cellular environment. This includes the incomplete switch in macrophage phenotype resulting in a lingering pro-inflammatory state within the tissues, as well as fibroblast-associated dysregulation of the dynamic control of the extracellular matrix. Additional to this endogenous dysregulation, some treatment strategies for RA may exacerbate muscle wasting and no multi-cell investigation has been done in this context. This review summarizes the most recent literature characterising clinical RA cachexia and links these features to the roles of and complex communication between multiple cellular contributors in the muscle niche, highlighting the importance of a targeted approach to therapeutic intervention.
Pien Tze Huang (PZH) as a Multifunction Medicinal Agent in Traditional Chinese Medicine (TCM): a review on cellular, molecular and physiological mechanisms
Authors: Chen Zhiliang 
Published: March 2021

Abstract
Relevance
Pien Tze Huang (PZH) is a well-known Traditional Chinese Medicine (TCM), characterized by a multitude of pharmacological effects, such as hepatoprotection and inhibition of inflammation and cell proliferative conditions. Many of these effects have been validated at the cellular, molecular and physiological levels but, to date, most of these findings have not been comprehensively disclosed.

Objectives
This review aims to provide a critical summary of recent studies focusing on PZH and its multiple pharmacological effects. As a result, we further discuss some novel perspectives related to PZH’s mechanisms of action and a holistic view of its therapeutic activities.

Methods
A systematic review was performed focusing on PZH studies originated from original scientific resources. The scientific literature retrieved for this work was obtained from International repositories including NCBI/PubMed, Web of Science, Science Direct and China National Knowledge Infrastructure (CNKI) databases.

Results
The major active componentes and their potential functions, including hepatoprotective and neuroprotective effects, as well as anti-cancer and anti-inflammatory activities, were summarized and categorized accordingly. As indicated, most of the pharmacological effects were validated in vitro and in vivo. The identification of complex bioactive components in PZH may provide the basis for further therapeutic initiatives.

Conclusion
Here we have collectively discussed the recent evidences covering most, if not all, pharmacological effects driven by PZH. This review provides novel perspectives on understanding the modes of action and the holistic view of TCM. The rational development of future clinical trials will certainly provide evidence-based medical evidences that will also confirm the therapeutic advantages of PZH, based on the current information available.
LINC00958 promotes the proliferation of TSCC via miR-211-5p/CENPK axis and activating the JAK/STAT3 signaling pathway
Authors: Jia Bo , Dao Junfeng , Han Jiusong , Huang Zhijie , Sun Xiang , Zheng Xianghuai , Xiang Shijian , Zhou Huixi , Liu Shuguang 
Published: March 2021

Abstract
Background
Tongue squamous cell carcinoma (TSCC) is one of the most common oral tumors. Recently, long intergenic noncoding RNA 00958 (LINC00958) has been identified as an oncogene in human cancers. Nevertheless, the role of LINC00958 and its downstream mechanisms in TSCC is still unknown.

Methods
The effect of LINC00958 on TSCC cells proliferation and growth were assessed by CCK-8, colony formation, 5-Ethynyl-2′-deoxyuridline (EdU) assay and flow cytometry assays in vitro and tumor xenograft model in vivo. Bioinformatics analysis was used to predict the target of LINC00958 in TSCC, which was verified by RNA immunoprecipitation and luciferase reporter assays.

Results
LINC00958 was increased in TSCC tissues, and patients with high LINC00958 expression had a shorter overall survival. LINC00958 knockdown significantly decreased the growth rate of TSCC cells both in vitro and in vivo. In mechanism, LINC00958 acted as a ceRNA by competitively sponging miR-211-5p. In addition, we identified CENPK as a direct target gene of miR-211-5p, which was higher in TSCC tissues than that in adjacent normal tissues. Up-regulated miR-211-5p or down-regulated CENPK could abolish LINC00958-induced proliferation promotion in TSCC cells. Furthermore, The overexpression of CENPK promoted the expression of oncogenic cell cycle regulators and activated the JAK/STAT3 signaling.

Conclusions
Our findings suggested that LINC00958 is a potential prognostic biomarker in TSCC.
Breastfeeding rates are high in a prenatal community support program targeting vulnerable women and offering enhanced postnatal lactation support: a prospective cohort study
Authors: Francis Jane , Mildon Alison , Stewart Stacia , Underhill Bronwyn , Ismail Samantha , Di Ruggiero Erica , Tarasuk Valerie , Sellen Daniel W. , O’Connor Deborah L. 
Published: March 2021

Abstract
Background
In Canada, 91% of all mothers initiate breastfeeding, but 40–50% stop by 6 months and only 34% breastfeed exclusively for 6 months, with lower rates among socially and/or economically vulnerable women. The Canada Prenatal Nutrition Program (CPNP) aims to support breastfeeding among vulnerable women, but there is no formal framework or funding for sites to integrate proactive postnatal breastfeeding support. This research aimed to i) describe infant feeding practices among clients of one Toronto CPNP site using charitable funds to offer a lactation support program (in-home lactation consultant visits, breast pumps); ii) determine whether breastfeeding outcomes at 6 months differ based on maternal sociodemographics and food insecurity; and iii) assess utilization of the lactation support program.

Methods
Infant feeding practices were collected prospectively at 2 weeks, 2, 4 and 6 months postpartum via telephone questionnaires (n = 199). Maternal sociodemographics were collected at 2 weeks and food insecurity data at 6 months postpartum. Program monitoring records were used to determine utilization of the lactation support program.

Results
Ninety-one percent of participants were born outside of Canada; 55% had incomes below the Low-Income Cut-Off; and 55% reported food insecurity. All participants initiated breastfeeding, 84% continued for 6 months and 16% exclusively breastfed for 6 months. Among breastfed infants, ≥76% received vitamin D supplementation. Approximately 50% of infants were introduced to solids before 6 months. Only high school education or less and food insecurity were associated with lower breastfeeding rates. Overall, 75% of participants received at least one visit with a lactation consultant and 95% of these received a breast pump.

Conclusions
This study provides initial evidence that postnatal lactation support can be delivered within a CPNP site, with high uptake by clients. While all participants initiated breastfeeding and 84% continued for 6 months, adherence to the recommended 6 months of exclusive breastfeeding was low. Further research is needed to better understand the barriers to exclusive breastfeeding and how to support this practice among vulnerable women.
Study registered at clinicaltrials.gov as NCT03400605.
Epigenetic silencing of miR-144/451a cluster contributes to HCC progression via paracrine HGF/MIF-mediated TAM remodeling
Authors: Zhao Junlong , Li Huichen , Zhao Shoujie , Wang Enxin , Zhu Jun , Feng Dayun , Zhu Yejing , Dou Weijia , Fan Qingling , Hu Jie , Jia Lintao , Liu Lei 
Published: March 2021

Abstract
Background & Aims
Hepatocellular carcinoma (HCC) is among the malignancies with the highest mortality. The key regulators and their interactive network in HCC pathogenesis remain unclear. Along with genetic mutations, aberrant epigenetic paradigms, including deregulated microRNAs (miRNAs), exert profound impacts on hepatocyte transformation and tumor microenvironment remodeling; however, the underlying mechanisms are largely uncharacterized.

Methods
We performed RNA sequencing on HCC specimens and bioinformatic analyses to identify tumor-associated miRNAs. The miRNA functional targets and their effects on tumor-infiltrating immune cells were investigated. The upstream events, particularly the epigenetic mechanisms responsible for miRNA deregulation in HCC, were explored.

Results
The miR-144/miR-451a cluster was downregulated in HCC and predicted a better HCC patient prognosis. These miRNAs promoted macrophage M1 polarization and antitumor activity by targeting hepatocyte growth factor (HGF) and macrophage migration inhibitory factor (MIF). The miR-144/miR-451a cluster and EZH2, the catalytic subunit of polycomb repressive complex (PRC2), formed a feedback circuit in which miR-144 targeted EZH2 and PRC2 epigenetically repressed the miRNA genes via histone H3K27 methylation of the promoter. The miRNA cluster was coordinately silenced by distal enhancer hypermethylation, disrupting chromatin loop formation and enhancer-promoter interactions. Clinical examinations indicated that methylation of this chromatin region is a potential HCC biomarker.

Conclusions
Our study revealed novel mechanisms underlying miR-144/miR-451a cluster deregulation and the crosstalk between malignant cells and tumor-associated macrophages (TAMs) in HCC, providing new insights into HCC pathogenesis and diagnostic strategies.
Confirmatory and bi-factor analysis of the Short Form Health Survey 8 (SF-8) scale structure in a German general population sample
Authors: Wirtz M. A. , Schulz A. , Brähler E. 
Published: March 2021

Abstract
Background
The SF-8 is a short form of the SF-36 Health Survey, which is used for generic assessment of physical and mental aspects of health-related quality of life (HRQoL). Each of the 8 dimensions of the SF-36 is covered by a single item in the SF-8. The aim of the study was to examine the latent model structure of the SF-8.

Method
One-, two- and three dimensional as well as bi-factor structural models were defined and estimated adopting the ML- as well as the WLSMV-algorithm for ordinal data. The data were collected in a German general population sample (N = 2545 persons).

Results
A two- (physical and mental health) and a three-dimensional CFA structure (in addition overall health) represent the empirical data information adequately [CFI = .987/.995; SRMR = .024/.014]. If a general factor is added, the resulting bi-factor models provide a further improvement in data fit [CFI = .999/.998; SRMR = .001]. The individual items are much more highly associated with the general HRQoL factor (loadings: .698 to .908) than with the factors physical, mental, and overall health (loadings: −.206 to .566).

Conclusions
In the SF-8, each item reflects mainly general HRQoL (general factor) as well as one of the three components physical, mental, and overall health. The findings suggest in particular that the evaluation of the information of the SF-8 items can be validly supplemented by a general value HRQoL.
A Beckwith-Wiedemann syndrome case with de novo 24 Mb duplication of chromosome 11p15.5p14.3
Authors: Jiang Huling , Ping Zepeng , Wang Jianguo , Liu Xiaodan , Jin Yuxia , Li Suping , Zhou Chiyan , Huang Pinghua , Jin Yi , Ai Ling , Chen Jie 
Published: March 2021

AbstractBackgroundMolecular genetic testing for the 11p15-associated imprinting disorder Beckwith-Wiedemann syndrome (BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. An integrated molecular approach to analyze the epigenetic-genetic alterations is required for accurate diagnosis of BWS.Case presentation: We reported a Chinese case with BWS detected by SNP array analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The genetic analysis showed a de novo duplication of 24 Mb at 11p15.5p14.3 is much longer than ever reported. MS-MLPA showed copy number changes with a peak height ratio value of 1.5 (three copies) at 11p15. The duplication of paternal origin with increase of methylation index of 0.68 atH19and decreased methylation index of 0.37 atKCNQ1OT1.ConclusionCombined chromosome microarray analysis and methylation profiling provided reliable diagnosis for this paternally derived duplication of BWS. The phenotype associated with 11p15 duplications depends on the size, genetic content, parental inheritance and imprinting status. Identification of these rare duplications is crucial for genetic counselling.