bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: An Unusual Case of Pulmonary Metastatic Adenocarcinoma From Low-Grade Appendiceal Mucinous Neoplasms
Authors: Zhao Xin-Yu , Li Chun-Qiang , Zhang Shi-Yao , Liu Gang 
Published: July 2022

BackgroundLow-grade appendiceal mucinous neoplasms (LAMNs) are indolent tumors with low-grade cytology. Although peritoneal dissemination is common due to tumor rupture and mucinous deposits on the visceral peritoneal surface, distant involvement, such as lung, is rarely seen due to lack of invasiveness.Case PresentationA 70-year-old woman presented to the hospital due to continuously elevated carcinoembryonic antigen (CEA) levels for 10 months without any symptoms. PET/CT revealed two lesions located in the left lung and appendix. The postoperative pathology results revealed pulmonary mucinous adenocarcinoma and LAMN. Then we performed next-generation sequencing (NGS) to clarify the relationship between the two tumors. The sequencing result showed that both tumors harbored the common tumor mutations, KRAS (p.G12D), GNAS (p.R201H), and BRAF (p.R735Q), which indicated that the pulmonary tumor was a metastasis of LAMN.ConclusionThis case is unusual in that the primary LAMN and the pulmonary metastasis are present at the time of diagnosis. This study reported the first pulmonary metastasis from LAMN verified by NGS.
Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial
Authors: Nilsson Magnus , Olafsdottir Halla , Alexandersson von Döbeln Gabriella , Villegas Fernanda , Gagliardi Giovanna , Hellström Mats , Wang Qiao-Li , Johansson Hemming , Gebski Val , Hedberg Jakob , Klevebro Fredrik , Markar Sheraz , Smyth Elizabeth , Lagergren Pernilla , Al-Haidari Ghazwan , Rekstad Lars Cato , Aahlin Eirik Kjus , Wallner Bengt , Edholm David , Johansson Jan , Szabo Eva , Reynolds John V. , Pramesh CS , Mummudi Naveen , Joshi Amit , Ferri Lorenzo , Wong Rebecca KS , O’Callaghan Chris , Lukovic Jelena , Chan Kelvin KW , Leong Trevor , Barbour Andrew , Smithers Mark , Li Yin , Kang Xiaozheng , Kong Feng-Ming , Chao Yin-Kai , Crosby Tom , Bruns Christiane , van Laarhoven Hanneke , van Berge Henegouwen Mark , van Hillegersberg Richard , Rosati Riccardo , Piessen Guillaume , de Manzoni Giovanni , Lordick Florian 
Published: July 2022

BackgroundThe globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC.MethodsThis is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04460352.
ZFAND5 Is an Independent Prognostic Biomarker of Perihilar Cholangiocarcinoma
Authors: Liu Pei , Wang Yijia , Duan Lingling 
Published: July 2022

BackgroundCholangiocarcinoma (CCA) is a highly aggressive malignancy with extremely poor prognosis. Perihilar CCA (pCCA) is the most common subtype of CCA, but its biomarker study is much more lagged behind other subtypes. ZFAND5 protein can interact with ubiquitinated proteins and promote protein degradation. However, the function of ZFAND5 in cancer progression is rarely investigated, and the role of ZFAND5 in pCCA is never yielded.Materials and MethodsIn this study, we established a pCCA cohort consisting of 72 patients. The expression of ZFAND5 in pCCAs, and the paired liver tissues, intrahepatic bile duct tissues and common bile ducts (CBD) tissues were detected with IHC. ZFAND5 mRNA in pCCAs and CBDs was detected with qRT-PCR. The pCCA cohort was divided into ZFAND5low and ZFAND5high subsets according to the IHC score. The correlations between ZFAND5 expression and clinicopathological parameters were assessed bychi-square test. The prognostic significance of ZFAND5 expression and clinicopathological parameters was estimated by univariate analysis with Kaplan-Meier method, and by multivariate analysis with Cox-regression model.ResultsExpression of ZFAND5 in pCCAs was substantially higher than that in interlobular bile ducts and common bile ducts, but lower than that in liver tissues. The ZFAND5low and ZFAND5high subsets accounted for 44.4% and 55.6% of all pCCAs respectively. ZFAND5 high patients had much lower survival rates than the ZFAND5low patients, with the average survival time as 31.2 months and 19.5 months respectively. ZFAND5 was identified as an independent unfavorable prognostic biomarker of pCCA with multivariate analysis.ConclusionZFAND5 expression was up-regulated in pCCAs compared with the CBDs. We identified ZFAND5 as an independent biomarker of pCCA, which could provide more evidence for the molecular classification of pCCA, and help stratify the high-risk patients based on the molecular features.
Use of Non-pharmacological Therapies in Individuals With Migraine Eligible for Treatment With Monoclonal Antibodies Targeting Calcitonin Gene-Related Peptide (CGRP)-Signaling: A Single-Center Cross-Sectional Observational Study
Authors: Rundblad Lucas , Cullum Christopher Kjaer , Sacco Simona , Gil-Gouveia Raquel , Uludüz Derya , Do Thien Phu , Amin Faisal Mohammad 
Published: July 2022

IntroductionAccessibility of treatment with monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) signaling pathway is impeded by regulatory restrictions. Affected individuals may seek out other services including non-pharmacological therapies. Thus, we found it timely to ascertain the use of non-pharmacological therapies in individuals with treatment-resistant migraine eligible for and naïve to treatment with CGRP-signaling targeting monoclonal antibodies.MethodsWe conducted a single-center cross-sectional observational study of patients eligible for and naïve to treatment with monoclonal antibodies targeting CGRP or its receptor. We recorded demographical information (gender, age, educational level, employment status, and income), disease burden (frequency of headache days and migraine days), previous use of preventive pharmacological medications for migraine, and use of non-pharmacological therapies over the past 3 months including frequency of interventions, costs, and patient-reported assessment of efficacy on a 6-point scale (0: no efficacy, 5: best possible efficacy).ResultsWe included 122 patients between 17 June 2019 and 6 January 2020; 101 (83%) were women and the mean age was 45.2 ± 13.3 years. One-third (n = 41 [34%]) had used non-pharmacological therapy within the past 3 months. Among these participants, the median frequency of different interventions was 1 (IQR: 1–2), the median number of monthly visits was 2.3 (IQR: 1.3–4), mean and median monthly costs were 1,086 ± 1471, and 600 (IQR: 0–1200) DKK (1 EUR = ~7.5 DKK), respectively, and median patient-reported assessment of the efficacy of interventions was 2 (IQR: 0–3).ConclusionEven in a high-income country with freely accessible headache services and universal healthcare coverage, there was a non-negligible direct cost in parallel with low satisfaction for non-pharmacological therapies among patients at a tertiary headache center.
Up to the Challenge: Adapting Pediatric Intensive Care During a Global Pandemic
Authors: Pereira Myra , Akinkugbe Olugbenga , Buckley Laura , Gilfoyle Elaine , Ibrahim Sarah , McCradden Melissa , Somerton Sarah , Dryden-Palmer Karen 
Published: July 2022

BackgroundThe COVID-19 pandemic has strained health systems world wide. In our region, surging numbers of critically ill adult patients demanded urgent system-wide responses. During the peak of the pandemic, our Pediatric Intensive Care Unit (PICU) team redesigned the existing educational resources and processes of care to ensure for adult patients for the first time in the hospital’s history.AimDescribe the experiences and impacts of the rapidly initiated Adult COVID-19 Program on health care providers (HCP) and family members. Havelock’s Theory of Change framed the examination of Adult COVID-19 Program participant experiences and surfaced lessons learned.Materials and MethodsA quality improvement review was employed to collect feedback about the program experience from the health care team and patient’s family members. HCP completed a questionnaire 10 months following the implementation of the program and feedback from family members was provided during the program was obtained. Havelock’s Theory of Change was used to explore trends and frame participants’ experiences.ResultsPediatric Intensive Care Unit bedside team members and clinical leaders (n = 17), adult hospital partners (n = 3), and family members (n = 8) participated. HCP describe; motivation and readiness; concern for personal safety and uncertainty experienced in the early program phases; the importance of supports and resources; use of relationships and collaboration to facilitate change; the emotional impacts of this unique experience; and opportunities for individual and team growth. An overarching theme of ‘doing our part to help’ emerged. Family members described the positive impacts of family-centered interventions offered, individualized care, and shock at their family member’s illness.ConclusionThe PICU team rapidly adapted to provide care for adults at the peak of the pandemic. Family members expressed feeling grateful for the care their loved ones received in the pediatric setting. The experience of caring for adult patients with COVID-19 was a source of tension, personal growth, and meaning for the pediatric intensive care team.
Improving Post-discharge Practice of Kangaroo Mother Care: Perspectives From Communities in East-Central Uganda
Authors: Kwesiga Doris , Wanduru Phillip , Ssegujja Eric , Inhensiko Justine , Waiswa Peter , Franck Linda 
Published: July 2022

IntroductionKangaroo mother care (KMC) is among the most cost-effective and easily accessible solutions for improving the survival and wellbeing of small newborns. In this study, we examined the barriers and facilitators to continuity of KMC at home following hospital discharge in rural Uganda.MethodsWe conducted this study in five districts in east-central Uganda, within six hospitals and at the community level. We used a qualitative approach, with two phases of data collection. Phase 1 comprised in-depth interviews with mothers who practiced KMC with their babies and caretakers who supported them and key informant interviews with health workers, district health office staff, community health workers, and traditional birth attendants. We then conducted group discussions with mothers of small newborns and their caretakers. We held 65 interviews and five group discussions with 133 respondents in total and used a thematic approach to data analysis.ResultsIn hospital, mothers were sensitized and taught KMC. They were expected to continue practicing it at home with regular returns to the hospital post-discharge. However, mothers practiced KMC for a shorter time at home than in the hospital. Reasons included being overburdened with competing domestic chores that did not allow time for KMC and a lack of community follow-up support by health workers. There were increased psycho-social challenges for mothers, alongside some dangerous practices like placing plastic cans of hot water near the baby to provide warmth. Respondents suggested various ways to improve the KMC experience at home, including the development of a peer-to-peer intervention led by mothers who had successfully done KMC and community follow-up of mothers by qualified health workers and community health workers.ConclusionDespite wide acceptance of KMC by health workers, challenges to effective implementation persist. Amid the global and national push to scale up KMC, potential difficulties to its adherence post-discharge in a rural, resource-limited setting remain. This study provides insights on KMC implementation and sustainability from the perspectives of key stakeholders, highlighting the need for a holistic approach to KMC that incorporates its adaptability to community settings and contexts.
Prevalence of Heavy Menstrual Bleeding and Its Associated Cognitive Risks and Predictive Factors in Women With Severe Mental Disorders
Authors: Shan Jianmin , Tian Hongjun , Zhou Chunhua , Wang Haibo , Ma Xiaoyan , Li Ranli , Yu Haiping , Chen Guangdong , Zhu Jingjing , Cai Ziyao , Lin Chongguang , Cheng Langlang , Xu Yong , Liu Sha , Zhang Congpei , Luo Qinghua , Zhang Yunshu , Jin Shili , Liu Chuanxin , Zhang Qiuyu , Lv Luxian , Yang Lei , Chen Jiayue , Li Qianchen , Liu Wei , Yue Weihua , Song Xueqin , Zhuo Chuanjun ,   China; MODMD Group of China (CMODG)
Published: July 2022

There has been limited studies examining treatment-induced heavy menstrual bleeding (HMB) in women with severe mental illnesses. The aim of this study was to examine HMB prevalence and HMB-associated factors in young women (18–34 years old) diagnosed with bipolar disorder (BP), major depressive disorder (MDD), or schizophrenia (SCZ) who have full insight and normal intelligence. Eighteen-month menstruation histories were recorded with pictorial blood loss assessment chart assessments of HMB. Multivariate analyses were conducted to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Drug effects on cognition were assessed with the MATRICS Consensus Cognitive Battery (MCCB). HMB prevalence were: BP, 25.85%; MDD, 18.78%; and SCH, 13.7%. High glycosylated hemoglobin (HbA1c) level was a strong risk factor for HMB [BP OR, 19.39 (16.60–23.01); MDD OR, 2.69 (4.59–13.78); and SCZ OR, 9.59 (6.14–12.43)]. Additional risk factors included fasting blood sugar, 2-h postprandial blood glucose, and use of the medication valproate [BP: OR, 16.00 (95%CI 12.74–20.22); MDD: OR, 13.88 (95%CI 11.24–17.03); and SCZ OR, 11.35 (95%CI 8.84–19.20)]. Antipsychotic, antidepressant, and electroconvulsive therapy use were minor risk factors. Pharmacotherapy-induced visual learning impairment was associated with HMB [BP: OR, 9.01 (95%CI 3.15–13.44); MDD: OR, 5.99 (95%CI 3.11–9.00); and SCZ: OR, 7.09 (95%CI 2.99–9.20)]. Lithium emerged as a protective factor against HMB [BP: OR, 0.22 (95%CI 0.14–0.40); MDD: OR, 0.30 (95%CI 0.20–0.62); and SCZ: OR, 0.65 (95%CI 0.33–0.90)]. In SCZ patients, hyperlipidemia and high total cholesterol were HMB-associated factors (ORs, 1.87–2.22). Psychiatrist awareness of HMB risk is concerningly low (12/257, 2.28%). In conclusion, prescription of VPA should be cautioned for women with mental illness, especially BP, and lithium may be protective against HMB.
QiShenYiQi Pill Ameliorates Cardiac Fibrosis After Pressure Overload-Induced Cardiac Hypertrophy by Regulating FHL2 and the Macrophage RP S19/TGF-β1 Signaling Pathway
Authors: Anwaier Gulinigaer , Xie Ting-Ting , Pan Chun-Shui , Li An-Qing , Yan Li , Wang Di , Chen Fan-Kai , Weng Ding-Zhou , Sun Kai , Chang Xin , Fan Jing-Yu , Han Jing-Yan , Liu Jian 
Published: July 2022

Purpose: Heart failure (HF) is a leading cause of morbidity and mortality worldwide, and it is characterized by cardiac hypertrophy and fibrosis. However, effective treatments are not available to block cardiac fibrosis after cardiac hypertrophy. The QiShenYiQi pill (QSYQ) is an effective treatment for chronic HF. However, the underlying mechanism remains unclear.Methods: In the present study, a pressure overload-induced cardiac hypertrophy model was established in rats by inducing ascending aortic stenosis for 4 weeks. QSYQ was administered for 6 weeks, and its effects on cardiac fibrosis, myocardial apoptosis, RP S19 release, macrophage polarization, TGF-β1 production, and TGF-β1/Smad signaling were analyzed. In vitro studies using H9C2, Raw264.7, and RDF cell models were performed to confirm the in vivo study findings and evaluate the contribution to the observed effects of the main ingredients of QSYQ, namely, astragaloside IV, notoginsenoside R1, 3,4-dihydroxyl-phenyl lactic acid, and Dalbergia odorifera T. C. Chen oil. The role of four-and-a-half LIM domains protein 2 (FHL2) in cardiac fibrosis and QSYQ’s effects were assessed by small interfering RNAs (siRNAs).Results: QSYQ ameliorated cardiac fibrosis after pressure overload-induced cardiac hypertrophy and attenuated cardiomyocyte apoptosis, low FHL2 expression, and TGF-β1 release by the injured myocardium. QSYQ also inhibited the following: release of RP S19 from the injured myocardium, activation of C5a receptors in monocytes, polarization of macrophages, and release of TGF-β1. Moreover, QSYQ downregulated TGF-βR-II expression induced by TGF-β1 in fibroblasts and inhibited Smad protein activation and collagen release and deposition.Conclusion: The results showed that QSYQ inhibited myocardial fibrosis after pressure overload, which was mediated by RP S19-TGF-β1 signaling and decreased FHL2, thus providing support for QSYQ as a promising therapy for blocking myocardial fibrosis.
Preclinical Evaluation of Fingolimod in Rodent Models of Stroke With Age or Atherosclerosis as Comorbidities
Authors: Diaz Diaz Andrea C. , Malone Kyle , Shearer Jennifer A. , Moore Anne C. , Waeber Christian 
Published: July 2022

Preclinical data indicate that fingolimod improves outcome post-ischaemia. This study used a rigorous study design in normal male C57BL/6JOlaHsd mice and in mice with common stroke comorbidities to further evaluate the translational potential of fingolimod. Stroke was induced via middle cerebral artery electrocoagulation in 8–9-week old mice (young mice), 18 month old mice (aged mice), and in high-fat diet-fed 22-week old ApoE−/− mice (hyperlipidaemic mice). Recovery was evaluated using motor behavioural tests 3 and 7 days after stroke. Tissue damage was evaluated at 7 days. A lower dose of fingolimod, 0.5 mg/kg, but not 1 mg/kg, increased lesion size but decreased ipsilateral brain atrophy in younger mice, without an effect on behavioural outcomes. Fingolimod-treated aged mice showed a significant improvement over saline-treated mice in the foot fault test at 7 days. Fingolimod-treated hyperlipidaemic mice showed a decreased infarct size but no difference in behavioural performance. Increasing fingolimod treatment time to 10 days showed no benefit in young mice. Pooled data showed that fingolimod improved performance in the foot fault test. Flow cytometry studies showed that fingolimod had marked effects on T cell frequencies in various tissues. The results show that the effects of fingolimod in stroke are less robust than the existing literature might indicate and may depend on the inflammatory status of the animals.
Epimedium koreanum Nakai–Induced Liver Injury—A Mechanistic Study Using Untargeted Metabolomics
Authors: Li Pin , Zhang Lin , Guo Zhaojuan , Kang Qianjun , Chen Cong , Liu Xiaoyao , Ma Quantao , Zhang Jingxuan , Hu Yujie , Wang Ting 
Published: July 2022

Epimedii Folium is widely used worldwide as an herbal supplement, and the risk of its induced liver damage has emerged in recent years. Our preliminary study has found that, among several Epimedii Folium species specified in the Chinese Pharmacopoeia, Epimedium koreanum Nakai has a more severe propensity for hepatotoxicity. However, the mechanism of hepatotoxicity of Epimedium koreanum Nakai is still unclear. In this study, untargeted metabolomics was performed to analyze the serum and liver tissue to explore the mechanism of hepatotoxicity of Epimedium koreanum Nakai. The results of experiments in vivo showed that, after 28 days of exposure to Epimedium koreanum Nakai ethanol extract (EEE), the liver weight, levels of AST, ALP, TBIL, etc. in serum of rats in the EEE group were significantly increased, as well as severe cytoplasmic vacuolation appeared in the liver tissue, which suggested that EEE has significant hepatotoxicity. Subsequently, the results of metabolomics revealed significant changes in the metabolic profile in the liver and serum of rats after EEE exposure, in which metabolites in serum such as flavin mononucleotide, phenylacetylglycine, glutathione, l-tryptophan, and sphingomyelin were able to accurately identify liver injury caused by EEE and could be used as serum markers to reflect EEE-induced liver injury. The KEGG pathway enrichment analysis revealed that EEE caused extensive effects on rats' metabolic pathways. Some of the most affected pathways included glutathione metabolism, glutamate metabolism pathway, primary bile acid biosynthesis pathway, and sphingolipid metabolism pathway, which were all directed to the biological process of ferroptosis. Then, the main markers related to ferroptosis in the liver were examined, and the results demonstrated that the content of malondialdehyde was significantly increased, the activity of superoxide dismutase was significantly reduced, the ferroptosis inhibitory proteins GPX4 and System xc− were significantly downregulated, and the ferroptosis-promoting protein ACSL4 was significantly up-regulated. Judging from these results, we concluded that the mechanism of hepatotoxicity of Epimedium koreanum Nakai was probably related to the induction of ferroptosis in hepatocytes.
Are the 50 m Race Segments Changed From Heats to Finals at the 2021 European Swimming Championships?
Authors: Arellano Raúl , Ruiz-Navarro Jesús J. , Barbosa Tiago M. , López-Contreras Gracia , Morales-Ortíz Esther , Gay Ana , López-Belmonte Óscar , González-Ponce Ángela , Cuenca-Fernández Francisco 
Published: July 2022

This study explored in the 50 m races of the four swimming strokes the performance parameters and/or technical variables that determined the differences between swimmers who reach the finals and those who do not. A total of 322 performances retrieved from the 2021 Budapest European championships were the focus of this study. The results of the performances achieved during the finals compared to the heats showed that the best swimmers did not excel during the heats, as a significant progression of performance was observed in most of the strokes as the competition progressed. Specifically, combining men and women, the swimmers had in freestyle a mean coefficient of variation (CV) of ∼0.6%, with a mean range of performance improvement (∆%) of ∆ = ∼0.7%; in breaststroke a mean CV of ∼0.5% and ∆ = −0.2%; in backstroke a mean CV of ∼0.5% and ∆ = −0.6%, and; in butterfly a mean CV of ∼0.7% and ∆ = −0.9%. For all strokes, it was a reduction of the underwater phase with the aim of increasing its speed. However, this result was not always transferred to the final performance. In any case, most of the swimmers tried to make improvements from the start of the race up to 15 m. Furthermore, the swimmers generated an overall increase in stroke rate as the rounds progressed. However, a decrease in stroke length resulted and, this balance appeared to be of little benefit to performance.