bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing causal relationships between sarcopenia and nonalcoholic fatty liver disease: A bidirectional Mendelian randomization study
Authors: Zhao Ze-Hua , Zou Juanjuan , Huang Xin , Fan Yu-Chen , Wang Kai 
Published: November 2022

Background and aimsSarcopenia has been demonstrated to be closely associated with nonalcoholic fatty liver disease (NAFLD). However, whether there are causal relationships between sarcopenia and NAFLD remains undetermined. Here, we aim to address the question using a two-sample bidirectional Mendelian randomization (MR) analysis approach.MethodsWe performed a two-sample bidirectional MR study using summary-level data from genome-wide association studies (GWAS) of the whole body lean mass (n = 38,292), appendicular (arms and legs) lean mass (n = 28,330), and NAFLD (1,483 biopsy-proven NAFLD cases and 17,781 controls). We first conducted MR analysis with five single nucleotide polymorphisms (SNPs) as genetic instruments for whole body lean mass and three SNPs as instruments for appendicular lean mass to estimate the causal effect of genetically predicted sarcopenia on the risk of NAFLD using the inverse-variance weighted (IVW) method. Then we performed reverse MR analysis with four SNPs as instruments to examine the causality of genetically predicted NAFLD with whole body lean mass and appendicular lean mass. Further sensitivity analysis was conducted to testify the reliability of the MR results.ResultsGenetic predisposition to decreased whole body lean mass was not associated with NAFLD [IVW-random effects, odds ratio (OR) = 1.054, 95%CI: 0.750–1.482, P = 0.761]. Similar results were observed using genetic instruments of appendicular lean mass (IVW-random effects, OR = 0.888, 95%CI: 0.386–2.042, P = 0.780). Reverse MR analysis revealed that genetically predicted NAFLD using four genetic instruments was not associated with whole body lean mass (IVW, β = −0.068, 95%CI: −0.179 to 0.043, P = 0.229) and appendicular lean mass (IVW, β = −0.020, 95%CI: −0.092 to 0.051, P = 0.574). MR analyses using other methods and sensitivity analysis showed consistent results.ConclusionThese results suggested no causal relationships between sarcopenia and NAFLD, indicating that sarcopenia may not be directly involved in the pathogenesis of NAFLD and vice versa.
Identification and validation of a potential key gene SGOL1 for poor prognosis in hepatocellular carcinoma based on a bioinformatics approach
Authors: Fei Xiaobin , Liu Songbai , Liu Peng , Wang Xing , Zhu Changhao , Hou Junyi , Cai Junzhe , Pan Yaozhen 
Published: November 2022

ObjectiveHepatocellular carcinoma (HCC) is one of the most prevalent types of cancer worldwide. Shugoshin 1 (SGOL1) plays a crucial role in cell mitosis and its aberrant expression level in human tumors has shown to promote chromosomal instability (CIN) and accelerate tumor growth. SGOL1 expression level in HCC cells and tissues, whether it has an influence on HCC patients’ prognosis, and its mechanism of action have not yet been studied.MethodsWe carried out the bioinformatics analysis of SGOL1 expression level and survival analysis in 8 different malignancies, including HCC. In addition, we analyzed SGOL1 expression level in HCC tissues, as well as HCC patients’ clinical features, enrichment analysis of SGOL1 function and mechanism of action in HCC and tumor immune cells. The effects of SGOL1 expression level and cell viability on HCC were confirmed by in vitro cytological assays.ResultsIt was found that SGOL1 mRNA expression level was significantly higher in several tumor tissues, including HCC, than in corresponding normal tissues, and the elevated SGOL1 expression level was strongly associated with HCC patients’ poor prognosis. It was also revealed that SGOL1 expression level in HCC tissue was positively correlated with disease stage, tumor grade, and tumor size, and the results of multivariate logistic regression analysis showed that SGOL1 was one of the independent influential factors of the prognosis of HCC. Enrichment analysis revealed that SGOL1 expression level in HCC tissue was mainly associated with tumor proliferation, cell cycle, and other factors. The results of the immune infiltration analysis indicated that SGOL1 expression level was associated with immune cell infiltration and immune checkpoints in HCC. In vitro experiments demonstrated the high SGOL1 expression level in HCC tissues and cells, and silencing of SGOL1 resulted in altered cell cycle markers and decreased proliferation, invasion, and migration of HCC cells.ConclusionThe findings revealed that SGOL1 is highly expressed in HCC tissues, it is a biomarker of a poor prognosis, which may be related to immune cell infiltration in HCC, and may enhance the proliferation, invasion, and migration of HCC cells. The results may provide new insights into targeted treatment of HCC and improve HCC patients’ prognosis.
Phenolic diterpenes from Rosemary supercritical extract inhibit non-small cell lung cancer lipid metabolism and synergise with therapeutic drugs in the clinic
Authors: Bouzas Adrián , Gómez de Cedrón Marta , Colmenarejo Gonzalo , Laparra-Llopis José Moisés , Moreno-Rubio Juan , Montoya Juan José , Reglero Guillermo , Casado Enrique , Tabares Beatriz , Sereno María , Ramírez de Molina Ana 
Published: November 2022

Lung cancer is one of the most deadly and common cancers in the world. The molecular features of patient’s tumours dictate the different therapeutic decisions, which combines targeted therapy, chemotherapy, and immunotherapy. Altered cellular metabolism is one of the hallmarks of cancer. Tumour cells reprogram their metabolism to adapt to their novel requirements of growth, proliferation, and survival. Together with the Warburg effect, the role of lipid metabolism alterations in cancer development and prognosis has been highlighted. Several lipid related genes have been shown to promote transformation and progression of cancer cells and have been proposed as biomarkers for prognosis. Nevertheless, the exact mechanisms of the regulation of lipid metabolism and the biological consequences in non-small cell lung cancer (NSCLC) have not been elucidated yet. There is an urgent necessity to develop multidisciplinary and complementary strategies to improve NSCLC patients´ well-being and treatment response. Nutrients can directly affect fundamental cellular processes and some diet-derived ingredients, bioactive natural compounds and natural extracts have been shown to inhibit the tumour growth in preclinical and clinical trials. Previously, we described a supercritical extract of rosemary (SFRE) (12 - 16% composition of phenolic diterpenes carnosic acid and carnosol) as a potential antitumoral agent in colon and breast cancer due to its effects on the inhibition of lipid metabolism and DNA synthesis, and in the reduction of resistance to 5-FluoroUracil (5-FU). Herein, we demonstrate SFRE inhibits NSCLC cell bioenergetics identifying several lipid metabolism implicated targets. Moreover, SFRE synergises with standard therapeutic drugs used in the clinic, such as cisplatin, pemetrexed and pembrolizumab to inhibit of cell viability of NSCLC cells. Importantly, the clinical relevance of SFRE as a complement in the treatment of NSCLC patients is suggested based on the results of a pilot clinical trial where SFRE formulated with bioactive lipids (PCT/ES2017/070263) diminishes metabolic and inflammatory targets in peripheral-blood mononuclear cells (PBMC), such as MAPK (p=0.04), NLRP3 (p=0.044), and SREBF1 (p=0.047), which may augment the immune antitumour function. Based on these results, SFRE merits further investigation as a co-adjuvant in the treatment of NSCLC.Clinical trial registrationClinicalTrials.gov Identifier NCT05080920
Study protocol for HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer refractory to anti-EGFR antibodies
Authors: Nakatsumi Hiroshi , Komatsu Yoshito , Muranaka Tetsuhito , Yuki Satoshi , Kawamoto Yasuyuki , Harada Kazuaki , Dazai Masayoshi , Tateyama Miki , Sasaki Yusuke , Miyagishima Takuto , Tsuji Yasushi , Katagiri Masaki , Nakamura Michio , Sogabe Susumu , Hatanaka Kazuteru , Meguro Takashi , Kobayashi Tomoe , Ishiguro Atsushi , Muto Osamu , Shindo Yoshiaki , Kotaka Masahito , Ando Takayuki , Takagi Ryo , Sakamoto Naoya , Sakata Yu 
Published: November 2022

BackgroundThe first-line chemotherapy for patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies.MethodsFOLFIRI (irinotecan 180 mg/m2, l-leucovorin 200 mg/m2, bolus 5-FU 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi.DiscussionThere is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy.Clinical trial registrationJapan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs011190006.
Developing and validating a prognostic nomogram for ovarian clear cell carcinoma patients: A retrospective comparison of lymph node staging schemes with competing risk analysis
Authors: Li Yiling , Xiu Lin , Ma Mingyuan , Seery Samuel , Lou Xiaoying , Li Kexin , Wu Yue , Liang Shuang , Wu Yuxin , Cui Wei 
Published: November 2022

PurposeLymph node (LN) involvement is a key factor in ovarian clear cell carcinoma (OCCC) although, there several indicators can be used to define prognosis. This study examines the prognostic performances of each indicator for OCCC patients by comparing the number of lymph nodes examined (TNLE), the number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS).Methods1,300 OCCC patients who underwent lymphadenectomy between 2004 and 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Primary outcomes were Overall Survival (OS) and the cumulative incidence of Cancer-Specific Survival (CSS). Kaplan–Meier’s and Fine-Gray’s tests were implemented to assess OS and CSS rates. After conducting multivariate analysis, nomograms using OS and CSS were constructed based upon an improved LN system. Each nomograms’ performance was assessed using Receiver Operating Characteristics (ROC) curves, calibration curves, and the C-index which were compared to traditional cancer staging systems.ResultsMultivariate Cox’s regression analysis was used to assess prognostic factors for OS, including age, T stage, M stage, SEER stage, and LODDS. To account for the CSS endpoint, a proportional subdistribution hazard model was implemented which suggested that the T stage, M stage, SEER stage, and LNR are all significant. This enabled us to develop a LODDS-based nomogram for OS and a LNR-based nomogram for CSS. C-indexes for both the OS and CSS nomograms were higher than the traditional American Joint Committee on Cancer (AJCC), 8th edition, staging system. Area Under the Curve (AUC) values for predicting 3- and 5-year OS and CSS between nomograms also highlighted an improvement upon the AJCC staging system. Calibration curves also performed with consistency, which was verified using a validation cohort.ConclusionsLODDS and LNR may be better predictors than N stage, TNLE, and PLNs. For OCCC patients, both the LODDS-based and LNR-based nomograms performed better than the AJCC staging system at predicting OS and CSS. However, further large sample, real-world studies are necessary to validate the assertion.
NEO-SPEAK: A conceptual framework that underpins breaking bad news in neonatology
Authors: Seifart Carola , Falch Mirjam , Wege Mirjam , Maier Rolf F. , Pedrosa Carrasco Anna J. 
Published: November 2022

ObjectiveBreaking bad news in neonatology is a frequent and difficult challenge. Although there are guidelines for communicating with parents in pediatrics and neonatology, the specific framework for breaking bad news in neonatology has not been studied in more detail. Therefore, we aimed to identify determinants that are important for successful managing breaking bad news in neonatology from professionals' perspective and to develop a conceptual framework that underpins this challenging task.MethodsWe conducted seventeen semi-structured interviews with senior neonatologists of six perinatal centers of the highest level of care in Germany. The transcripts were analyzed according to Mayring's method of qualitative content analysis using inductive and deductive coding.ResultsEight determinants of breaking bad news in neonatology could be identified from the interviews. From these, we developed the conceptual framework NEO-SPEAK. The first three determinants, Neonatal prognostic uncertainty, Encounter in (triangular-)partnerships, Organization and teamwork (NEO) are directly related to the specific care situation in neonatology, whereas the others, Situational stress, Processuality, Emotional burden, Attention to individuality, Knowledge and experience, play a role for difficult conversations in general, but are subject to special modifications in neonatology (SPEAK). In addition, the results show that the context in neonatology as well as reciprocal effects on the team and the individual level of the physicians are important influencing factors in breaking bad news.ConclusionOn the one hand, the constitutional framework NEO-SPEAK shows which special aspects play a role in neonatology for the delivery of bad news, and on the other hand, it can help to identify and consider these aspects in clinical routine and training. Considering or reinforcing each NEO-SPEAK element when planning or delivering bad news may guide healthcare professionals through communication with parents of critically ill or premature newborns and support the resilience of the caring team.
The conservative treatment of congenital scoliosis with hemivertebra: Report of three cases
Authors: Caredda Matteo , Bandinelli Diletta , Falciglia Francesco , Giordano Marco , Aulisa Angelo Gabriele 
Published: November 2022

IntroductionScoliosis is the most common type of congenital vertebral disease. This spinal disorder may be due to a failure of formation, segmentation, or a combination thereof. Complete failure of formation causes hemivertebra which can lead to unbalanced growth and deformation. Statistically, 25% of congenital curves do not evolve, 25% progress slightly, while the remaining 50% develop quickly and require treatment. Hemivertebrae can be divided into three types: non-segmented, semi-segmented, and fully-segmented. The fully-segmented types are most likely to progress. Hemivertebra in the thoracolumbar region shows higher rates of progression compared with those in the lumbar area. The treatment may be either conservative or surgical. In general, bracing is not recommended in short and rigid curves, although it may help process secondary curves.ObjectiveTo assess the effectiveness of bracing in congenital scoliosis due to hemivertebra.Cases presentationSearching in our database, we found three cases of patients with congenital scoliosis due to fully-segmented hemivertebra. The first of them was 6 years old at the time of diagnosis with a fully-segmented hemivertebra in L5, determining an L1-L5 (S1) lumbar curve. The second one was 10 years old at the time of diagnosis with a fully-segmented hemivertebra in L2 and a T11-L4 (L5 sacralized) thoracolumbar curve. The last one was 3 years old at the time of diagnosis with a fully-segmented hemivertebra in L3 (in six lumbar bodies), determining a thoracolumbar curve T12-L4.ResultsWe utilized a Milwaukee brace for the first patient, a Boston brace for the second patient, and a Progressive Action Short Brace (PASB) for the third patient. At the beginning of the treatment, the Cobb angles measured 23°, 53°, and 25°, respectively. During treatment, the Cobb angles measured 22°, 35°, and 15°, respectively. At the end of treatment, the Cobb angles measured 18°, 45°, and 12°, respectively. At long-term follow-up, the curves measured 20°, 45°, and 12° Cobb angles, respectively.ConclusionsComparing our cases with those found in the literature we can confirm the ability of conservative treatment to change the natural history of congenital lumbar scoliosis due to failure of formation. From our experience, in all cases of CS with hemivertebra, before considering a surgical approach, conservative treatment should be implemented as early as possible without waiting for the progressive deformation of the adjacent normal vertebrae.
Institutionalizing health technology assessment in Egypt: Situational analysis and roadmap
Authors: Pinilla-Dominguez Pilar , Taha Shorouk , McGuire Hugh , Elagamy Ahmed , Sedrak Amal , Gamal Mary , Eldebeiky Mariam , Dawoud Dalia 
Published: November 2022

Objective: To conduct a situational analysis with the aim to inform future health technology assessment efforts (HTA) in Egypt.Introduction: The Egyptian government has set universal health coverage as a 2030 target. Several agencies have been created in the context of the ongoing healthcare reform. The Egyptian Authority for Unified Procurement, Medical Supply and the Management of Medical Technology (UPA) is one of them and was established to support strategic procurement using HTA.Methods: Description of the development of HTA in Egypt supported by a literature search as part of a scoping exercise, and a stakeholder analysis and identification of HTA capacity survey, based on previous surveys, with relevant stakeholders conducted in 2022. This was followed by a stakeholder event where results were shared and further contextualized.Results: The UPA is expected to evaluate the cost-effectiveness of health technologies and public health programs. The HTA process is being developed, focusing on the assessment of the value of new pharmaceuticals being introduced to the Egyptian market. A total of 16 participants responded on behalf of their organizations to the stakeholder analysis and identification of HTA capacity survey. More than 80% of the respondents were familiar with current efforts conducted by UPA and strongly support the implementation of HTA in Egypt. Transparency was highlighted as an important criterion. Over 90% of the respondents mentioned economic analyses as an HTA product being developed in Egypt, and medicines were the type of technology that stakeholders ranked as first in the rank of health technologies that need the output from HTA urgently. Capability building and training were highlighted as areas in which further support is required.Conclusion: This study represents the first attempt to describe the current path for HTA in Egypt. There seems to be momentum in Egypt to proceed and advance with HTA institutionalization. It would be important that next steps are built on the skills and capabilities already in place in Egypt, ensure methods and processes are in place and up to date and involve the wider system in Egypt so stakeholders can appropriately contribute and participate in the HTA process.
Artificial intelligence-based internet hospital pharmacy services in China: Perspective based on a case study
Authors: Bu Fengjiao , Sun Hong , Li Ling , Tang Fengmin , Zhang Xiuwen , Yan Jingchao , Ye Zhengqiang , Huang Taomin 
Published: November 2022

Background: Recently, internet hospitals have been emerging in China, saving patients time and money during the COVID-19 pandemic. In addition, pharmacy services that link doctors and patients are becoming essential in improving patient satisfaction. However, the existing internet hospital pharmacy service mode relies primarily on manual operations, making it cumbersome, inefficient, and high-risk.Objective: To establish an internet hospital pharmacy service mode based on artificial intelligence (AI) and provide new insights into pharmacy services in internet hospitals during the COVID-19 pandemic.Methods: An AI-based internet hospital pharmacy service mode was established. Initially, prescription rules were formulated and embedded into the internet hospital system to review the prescriptions using AI. Then, the “medicine pick-up code,” which is a Quick Response (QR) code that represents a specific offline self-pick-up order, was created. Patients or volunteers could pick up medications at an offline hospital or drugstore by scanning the QR code through the window and wait for the dispensing machine or pharmacist to dispense the drugs. Moreover, the medication consultation function was also operational.Results: The established internet pharmacy service mode had four major functional segments: online drug catalog search, prescription preview by AI, drug dispensing and distribution, and AI-based medication consultation response. The qualified rate of AI preview was 83.65%. Among the 16.35% inappropriate prescriptions, 49% were accepted and modified by physicians proactively and 51.00% were passed after pharmacists intervened. The “offline self-pick-up” mode was preferred by 86% of the patients for collecting their medication in the internet hospital, which made the QR code to be fully applied. A total of 426 medication consultants were served, and 48.83% of them consulted outside working hours. The most frequently asked questions during consultations were about the internet hospital dispensing process, followed by disease diagnosis, and patient education. Therefore, an AI-based medication consultation was proposed to respond immediately when pharmacists were unavailable.Conclusion: The established AI-based internet hospital pharmacy service mode could provide references for pharmacy departments during the COVID-19 pandemic. The significance of this study lies in ensuring safe/rational use of medicines and raising pharmacists’ working efficiency.