bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of immune-related target and prognostic biomarkers in PBMC of hepatocellular carcinoma
Authors: Hu Rui , Zhang Wei , Han Zhiyi , Ma Mengqing , Huang Qi , Lv Minling , Ma Wenfeng , Sun Xinfeng , Feng Wenxing , Li Jing , Zhong Xin , Sun Jialing , Yao Wei , Zhou Xiaozhou 
Published: July 2023

Abstract
Background
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and is characterized by insidious onset, rapid progression, and poor prognosis. Immunotherapy is a first-line treatment for advanced HCC. The identification of immune-related prognostic markers may be an effective strategy to predict and improve clinical response rate of immunotherapy.

Methods
The DESeq2, edgeR, and limma R packages were used to compare the transcriptomes of HCC with different prognoses. Cancer-related databases such as UALCAN, TNMplot, GEPIA, muttarget and Human Protein Atlas (HPA), and the Kaplan–Meier Plotter platform were used to analyze the relationship between CLDN18 and the clinical characteristics, as well as prognosis of HCC. The co-expressed genes of CLDN18 were obtained from LinkedOmics platform, and GO functional enrichment and KEGG pathway analysis were performed. The CIBERSORT, TIMER, Timer 2.0 and TISIDB algorithms were used to analyze immune infiltration.

Results
CLDN18 was differentially expressed in HCC patients with different prognoses, and its expression level in PBMC was positively correlated with the stage of BCLC. In addition, CLDN18 was significantly overexpressed in HCC tumor tissues compared to adjacent non-tumor tissues, which was consistent with PBMC sequencing results and immunohistochemical data from human protein profiles. CLDN18 was also positively correlated with HCC staging and grading, and high expression levels of CLDN18 predicted shorter overall survival. Functional annotation of CLDN18 in HCC revealed enrichment of the cellular senescence and protein activation cascade, along with biological processes such as cell cycle, inflammatory response, and cellular ketone metabolism. In addition, CLDN18 was also associated with tumor infiltrating immune cells, suppressive immune cell markers, T lymphocyte depletion and activation of HCC, and low expression of CLDN18 was associated with higher CD8 + T cell infiltration and better survival rates.

Conclusions
CLDN18 is a potential prognostic marker and immunotherapeutic target for HCC.
The modified lymphocyte C-reactive protein score is a promising indicator for predicting 3-year mortality in elderly patients with intertrochanteric fractures
Authors: He Zile , Zhang Chuangxin , Ran Mingzi , Deng Xin , Wang Zilin , Liu Yanhong , Li Hao , Lou Jingsheng , Mi Weidong , Cao Jiangbei 
Published: July 2023

Abstract
Background
Hip fractures are common in elderly patients, and almost all the patients undergo surgery. This study aimed to develop a novel modified lymphocyte C-reactive protein (CRP) score (mLCS) to simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery.

Methods
A retrospective study was conducted on elderly patients who underwent intertrochanteric fracture surgery between January 2014 and December 2017. The mLCS was developed according to the value of CRP and lymphocyte counts. Univariate and multivariate Cox regression analyses were used to identify independent risk factors for 3-year mortality after surgery. The performances of the lymphocyte CRP score (LCS) and mLCS to predict 3-year mortality were then compared using C-statistics, decision curve analysis (DCA), net reclassification index (NRI) and integrated discrimination improvement (IDI).

Results
A total of 291 patients were enrolled, of whom 52 (17.9%) died within 3 years after surgery. In the multivariate Cox regression analysis, mLCS (hazard ratio (HR), 5.415; 95% confidence interval (CI), 1.743–16.822; P = 0.003) was significantly associated with postoperative 3-year mortality. The C-statistics of LCS and mLCS for predicting 3-year mortality were 0.644 and 0.686, respectively. The NRI (mLCS vs. LCS, 0.018) and IDI (mLCS vs. LCS, 0.017) indicated that the mLCS performed better than the LCS. DCA also showed that mLCS had a higher clinical net benefit.

Conclusions
mLCS is a promising predictor that can simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery.
Possible-sarcopenic screening with disturbed plasma amino acid profile in the elderly
Authors: Duan Yushuang , Tao Kuan , Fang Zilong , Lu Yifan 
Published: July 2023

Abstract
Background
The mass and strength of skeletal muscle decline with age, leading to its progressive dysfunction. High-throughput metabolite profiling provides the opportunity to reveal metabolic mechanisms and the identification of biomarkers. However, the role of amino acid metabolism in possible sarcopenia remains unclear.

Objectives
The aim of this study included exploring variations in plasma amino acid concentrations in elderly individuals who have possible sarcopenia and further attempting to characterize a distinctive plasma amino acid profile through targeted metabolomics.

Methods
A cross-sectional, correlational research design was used for this study. Thirty possible-sarcopenic elderly participants were recruited (n = 30), as determined by the Asian Working Group for Sarcopenia (AWGS). Meanwhile, a reference group of non-sarcopenic (sex-, age-, and Appendicular Skeletal muscle Mass Index (ASMI)-matched non-sarcopenic controls, n = 36) individuals was included to compare the potential differences in metabolic fingerprint of the plasma amino acids associated with sarcopenia. Both groups were conducted the body composition analysis, physical function examination, and plasma amino acid-targeted metabolomics. The amino acids in plasma were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS–MS). Also, orthogonal partial least-squares-discriminant analysis (OPLS-DA) was applied to characterize the plasma amino acid profile.

Results
With respect to Handgrip Strength (HGS), the Five-Repetition Chair Stand Test (CS-5), the Six-Minute Walking Test (6MWT), the arm curl, the 30 s-Chair Stand Test (CST), the 2-Minute Step Test (2MST), the Timed Up-and-Go Test (TUGT), there was a decline in skeletal muscle function in the possible-sarcopenic group compared to the non-sarcopenic group. The mean plasma concentrations of arginine, asparagine, phenylalanine, serine, lysine, glutamine, and threonine were significantly lower in the possible sarcopenia group, whereas cirulline, proline, serine, and glutamic acid concentrations were higher. According to the multi-analysis, glutamine, serine, lysine, threonine, and proline were determined as the potential markers that indicated possible sarcopenia.

Conclusions
The findings characterize significantly altered plasma amino acid metabolisms in the elderly with possible sarcopenia, which aids to screening people who are at a high risk of developing condition, and motivating to design new preventive and therapeutic approaches.
Outcomes in deprescribing implementation trials and compliance with expert recommendations: a systematic review
Authors: Nizet Pierre , Evin Adrien , Brociero Emma , Vigneau Caroline Victorri , Huon Jean-François 
Published: July 2023

Abstract
Background
Deprescribing, defined as discontinuing or reducing the dose of medications that are no longer needed or for which the risks outweigh the benefits is a way to reduce polypharmacy. In 2022, the US Deprescribing Research Network (USDeN) published recommendations concerning the measurement of outcomes for deprescribing intervention studies. The objectives of this systematic review were to identify the outcome categories used in deprescribing intervention trials and to relate them to the previously published recommendations.

Methods
We searched MEDLINE, Embase, PsychInfo, and the Cochrane library from January 2012 through January 2022. Studies were included if they were randomized controlled trials evaluating a deprescribing intervention. After data extraction, outcomes were categorized by type: medication outcomes, clinical outcomes, system outcomes, implementation outcomes, and other outcomes based on the previously published recommendations.

Results
Thirty-six studies were included. The majority of studies focused on older adults in nursing homes and targeted inappropriate medications or polypharmacy. In 20 studies, the intervention was a medication review; in seven studies, the intervention was educational or informative; and three studies based their intervention on motivational interviewing or patient empowerment. Thirty-one studies presented a medication outcome (primary outcome in 26 studies), 25 a clinical outcome, 18 a system outcome, and seven an implementation outcome. Only three studies presented all four types of outcomes, and 10 studies presented three types of outcomes.

Conclusions
This review provides an update on the implementation of gold standard deprescribing studies in clinical practice. Implementation outcomes need to be developed and specified to facilitate the implementation of these practices on a larger scale and clinical outcome need to be prioritized. Finally, this review provides new elements for future real-life deprescribing studies.
Immune regulation and prognosis indicating ability of a newly constructed multi-genes containing signature in clear cell renal cell carcinoma
Authors: Gui Ziwei , Du Juan , Wu Nan , Shen Ningning , Yang Zhiqing , Yang Huijun , Wang Xuzhi , Zhao Na , Zeng Zixin , Wei Rong , Ma Wenxia , Wang Chen 
Published: July 2023

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy, although newly developing targeted therapy and immunotherapy have been showing promising effects in clinical treatment, the effective biomarkers for immune response prediction are still lacking. The study is to construct a gene signature according to ccRCC immune cells infiltration landscape, thus aiding clinical prediction of patients response to immunotherapy.

Methods
Firstly, ccRCC transcriptome expression profiles from Gene Expression Omnibus (GEO) database as well as immune related genes information from IMMPORT database were combine applied to identify the differently expressed meanwhile immune related candidate genes in ccRCC comparing to normal control samples. Then, based on protein–protein interaction network (PPI) and following module analysis of the candidate genes, a hub gene cluster was further identified for survival analysis. Further, LASSO analysis was applied to construct a signature which was in succession assessed with Kaplan–Meier survival, Cox regression and ROC curve analysis. Moreover, ccRCC patients were divided as high and low-risk groups based on the gene signature followed by the difference estimation of immune treatment response and exploration of related immune cells infiltration by TIDE and Cibersort analysis respectively among the two groups of patients.

Results
Based on GEO and IMMPORT databases, a total of 269 differently expressed meanwhile immune related genes in ccRCC were identified, further PPI network and module analysis of the 269 genes highlighted a 46 genes cluster. Next step, Kaplan–Meier and Cox regression analysis of the 46 genes identified 4 genes that were supported to be independent prognosis indicators, and a gene signature was constructed based on the 4 genes. Furthermore, after assessing its prognosis indicating ability by both Kaplan–Meier and Cox regression analysis, immune relation of the signature was evaluated including its association with environment immune score, Immune checkpoint inhibitors expression as well as immune cells infiltration. Together, immune predicting ability of the signature was preliminary explored.

Conclusions
Based on ccRCC genes expression profiles and multiple bioinformatic analysis, a 4 genes containing signature was constructed and the immune regulation of the signature was preliminary explored. Although more detailed experiments and clinical trials are needed before potential clinical use of the signature, the results shall provide meaningful insight into further ccRCC immune researches.
RUNX3 regulates the susceptibility against EGFR-targeted non-small cell lung cancer therapy using 47Sc-conjugated cetuximab
Authors: Kim Da-Mi , Lee So-Young , Lim Jae-Cheong , Cho Eun-Ha , Park Ul-Jae 
Published: July 2023

Abstract
Background
Radioimmunotherapy with cetuximab and conjugates with various radioisotopes is a feasible treatment option for different tumor models. Scandium-47 (47Sc), one of several β−-particle-emitting radioisotopes, displays favorable physical and chemical properties for conjugation to monoclonal antibodies. However, the therapeutic efficacy of 47Sc in preclinical and clinical studies is largely unknown. Given that intrinsic alterations in tumors greatly contribute to resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy, research on overcoming resistance to radioimmunotherapy using cetuximab is required.

Methods
47Sc was produced by irradiation of a CaCO3 target at the HANARO research reactor in KAERI (Korea Atomic Energy Research Institute) and prepared by chromatographic separation of the irradiated target. Cetuximab was conjugated with 47Sc using the bifunctional chelating agent DTPA. Radiochemical purity was determined using instant thin-layer chromatography. The immunoreactivity of 47Sc-DTPA-cetuximab was evaluated using the Lindmo method and an in vitro cell-binding assay. The inhibitory effects of cetuximab and 47Sc-DTPA-cetuximab were confirmed using cell growth inhibition and BrdU cell proliferation assays. Differences in protein expression levels between cetuximab- and 47Sc-DTPA-cetuximab-treated cells were confirmed using western blotting. Complex formation between RUNX3 and DNA repair components was confirmed using immunoprecipitation and western blotting.

Results
Cetuximab induces cell cycle arrest and cell death in EGFR-overexpressing NSCLC cells. Radiolabeling of cetuximab with 47Sc led to increased therapeutic efficacy relative to cetuximab alone. Application of 47Sc-DTPA-cetuximab induced DNA damage responses, and activation of RUNX3 significantly enhanced the therapeutic efficacy of 47Sc-DTPA-cetuximab. RUNX3 mediated susceptibility to EGFR-targeted NSCLC therapy using 47Sc-DTPA-cetuximab via interaction with components of the DNA damage and repair machinery.

Conclusions
47Sc-DTPA-cetuximab promoted cell death in EGFR-overexpressing NSCLC cells by targeting EGFR and inducing DNA damage as a result of β irradiation emitted from the conjugated 47Sc. Activation of RUNX3 played a key role in DNA damage and repair processes in response to the ionizing radiation and inhibited cell growth, thus leading to more effective tumor suppression. RUNX3 can potentially moderate susceptibility to 47Sc-conjugated cetuximab by modulating DNA damage and repair process mechanisms.
Optical coherence tomography angiography biomarkers in a bi-monthly maintenance dosing aflibercept in patients with neovascular age-related macular degeneration
Authors: Park Jong Beom , Kim Kiyoung , Kang Min Seok , Kim Eung Suk , Yu Seung-Young 
Published: July 2023

Abstract
Purpose
To evaluate the correlations between swept-source optical coherence tomography angiography (SS-OCTA) parameters and clinical outcomes in eyes with neovascular age-related macular degeneration (nAMD) administered a bimonthly intravitreal aflibercept regimen.

Methods
This prospective, single-arm, interventional study enrolled 33 patients with treatment-naïve nAMD. The eyes received three monthly aflibercept injections followed by five bi-monthly regimens (total 50 weeks). The structural parameters including central subfield thickness (CST) and 5 mm pigment epithelial detachment (PED) volume and microvascular parameters including macular neovascularization (MNV) area, vessel density (VD), and vessel length density (VLD) were recorded every before and 1 week after treatment.

Results
Patients who gained > 5 letters of best-corrected visual acuity (BCVA) from the baseline showed greater decreases in VD and VLD during the loading phase. Patients without recurrent or persistent fluid during the maintenance phase showed greater decreases in CST and 5 mm PED volume after the first injection. The decrease in mean VD during the loading phase was significantly correlated with the final BCVA (r = -0.820, p = 0.004). Moreover, the decrease in mean VLD during the loading phase was significantly correlated with the improvement in the final BCVA (r = -0.726, p = 0.017).

Conclusions
The decrease in mean VD during the loading phase was significantly negatively correlated with the final BCVA at the last visit. The decrease in mean VLD during the loading phase, mean CST during the loading phase, and the improvement in final BCVA showed significant correlations. Therefore, early changes in OCTA microvascular and OCT structural parameters could help predict clinical outcomes in nAMD.

Trial Registration
The trial was registered with the Clinical Research Information Service (CRIS), which joined the WHO International Clinical Trials Registry Platform (ICTRP) (Registration number: KCT0007375, Date of first trial registration: 10/06/2022).
Congenital heart diseases with airway stenosis: a predictive nomogram to risk-stratify patients without airway intervention
Authors: He Qiyu , Liu Yuze , Dou Zheng , Ma Kai , Li Shoujun 
Published: July 2023

AbstractBackgroundThis study focused on congenital heart disease (CHD) patients complicated with airway stenosis (AS) without airway intervention and aimed to identify the patients with potential risks.MethodsPatients diagnosed with CHD and AS were enrolled in this retrospective study. The primary outcome was defined as a postoperative mechanical ventilation duration of more than two weeks. We constructed a prediction model to predict the risk of prolonged mechanical ventilation (PMV).ResultsA total of 185 patients diagnosed with CHD and AS in Fuwai Hospital from July 2009 to December 2022 were included in the study. Weight at CHD surgery, cardiopulmonary bypass (CPB) duration, complex CHD and comorbid tracheobronchomalacia were identified as risk factors and included in the model. The ROC curve showed a good distinguishing ability, with an AUC of 0.847 (95% CI: 0.786–0.908). According to the optimal cut-off value of the ROC curve, patients were divided into high- and low-risk groups, and the subsequent analysis showed significant differences in peri-operative characteristics and in-hospital deaths.ConclusionsWith the predictive model, several factors could be used to assess the risky patients with PMV. More attention should be paid to these patients by early identification and routine surveillance.
Alcohol use disorder among healthcare professional students: a structural equation model describing its effect on depression, anxiety, and risky sexual behavior
Authors: Kintu Timothy Mwanje , Kaggwa Mark Mohan , Namagembe Robinah , Muganzi David Jolly , Kihumuro Bernard Raymond , Luyinda Garvin Ssali , Nabwana Brenda Wafana , Moses Muwanguzi , Nnyombi Marvin , Kirega Alex , Kabakyenga Jerome Kahuma , Maling Samuel 
Published: July 2023

Abstract
Background
Mental health problems such as depression, anxiety and alcohol use disorders are among the leading causes of disability worldwide. Among university students, alcohol use and poor mental health are associated with risky sexual behavior. Given the syndemic occurrence of these disorders most especially in young adults, we describe the relationship between them so as to guide and intensify current interventions on reducing their burden in this population.

Methods
This was a cross-sectional study based on an online survey among healthcare professional university students that captured sociodemographic characteristics, risky sexual behavior, alcohol use disorder, generalized anxiety disorder, and depression. Structural equation modelling was used to describe the relationship between these variables using RStudio.

Results
We enrolled a total of 351 participants of which 11% (37/351) had Alcohol Use Disorder, 33% (117/351) had depressive symptoms and 32% (111/351) had symptoms of anxiety. A model describing the relationship between these variables was found to fit well both descriptively and statistically [χ2 = 44.437, df = 21, p-value = 0.01, CFI = 0.989, TFI = 0.980, RMSEA = 0.056]. All observed variables were found to fit significantly and positively onto their respective latent factors (AUD, anxiety, depression and risky sexual behavior). AUD was found to be significantly associated with risky sexual behavior (β = 0.381, P < 0.001), depression (β = 0.152, P = 0.004), and anxiety (β = 0.137, P = 0.001).

Conclusion
AUD, depression and anxiety are a significant burden in this health professional student population and there’s need to consider screening for anxiety and depression in students reporting with AUD so as to ensure appropriate interventions. A lot of attention and efforts should be focused on the effect of AUD on risky sexual behavior and continued health education is still required even among health professional students.
“It is worth hanging in there” – Psychotherapeutic experiences shaping future motivation for outpatient psychotherapy with refugee clients in Germany
Authors: Potter Flurina , Zehb Marlene , Dohrmann Katalin , Müller-Bamouh Veronika , Rockstroh Brigitte , Crombach Anselm 
Published: July 2023

Abstract
Background
A high prevalence of mental disorders in refugees contrasts with a low rate of treatment and limited access to health care services. In addition to pre-, peri- and post-migration stress, language, cultural barriers together with lack of information about cost reimbursement, and access to German (mental) health care institutions are discussed as barriers to use of available services. Such barriers together with insufficient experience of treating traumatized refugee clients may lower therapists’ motivation and facilities to accept refugee clients. A model project called “Fearless” trained, and supervised therapists, translators, and peer counsellors to reduce these barriers and increase therapists’ motivation and engagement in future treatment of refugees.

Methods
From a total 14 therapists participating in the project N = 13 were available for semi-structured interviews. The interviews were scheduled during or after their outpatient psychotherapy of refugee clients and lasted one hour on average. Based on qualitative assessment strategies, open questions addressed the therapists’ experience of challenges, enrichments, and motivation throughout the therapy. Therapists’ responses were analyzed using content structuring qualitative content analysis.

Results
Three major challenges modulated therapists’ future motivation for treating refugee clients: specific bureaucratic efforts (e.g., therapy application), organizational difficulties (e.g., scheduling appointments), and clients’ motivation (e.g., adherence, reliability). Still, most interviewed therapists (n = 12) evaluated the therapy as enriching and expressed their motivation to accept refugee clients in the future (n = 10).

Conclusion
Results recommend the reduction of bureaucratic effort (e.g., regular health insurance cover for all refugees) and implementation of organizational support (e.g., peer counsellors) in support of therapists’ motivation for future treatment of refugee clients. Further structural support e.g., with organizing and financing professional translators and referring refugee clients to psychotherapists should be deployed nationwide. We recommend the training in, and supervision of, the treatment of refugee clients as helpful additional modules in psychotherapy training curricula to raise therapists’ motivation to work with refugee clients.