bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic features, genomic profiles and outcomes of younger vs. older Chinese hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer patients
Authors: Wang Jinhao , Liu Yaxin , Liang Yuehua , Zhang Yue , Dong Hang , Zheng Tiantian , Yu Jianjun , Du Pan , Jia Shidong , King Bonnie L. , Wang Jing , Liu Xiaoran , Li Huiping 
Published: June 2023

BackgroundPoor outcomes have been widely reported for younger vs. older breast cancer patients, but whether this is due to age itself or the enrichment of aggressive clinical features remains controversial. We have evaluated the clinicopathologic characteristics and genomic profiles of real-world hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) patients to examine the determinants of outcome for younger vs. older patients in a single clinical subtype undergoing treatment in the same clinic.Patients and methodsThis study included patients presenting at the Peking University Cancer Hospital with primary stage IV or first-line metastatic HR+/HER2- breast cancer who consented to an additional blood draw for genomic profiling prior to treatment. Plasma samples were analyzed with a targeted 152-gene NGS panel to assess somatic circulating tumor DNA (ctDNA) alterations. Genomic DNA (gDNA) extracted from peripheral blood mononuclear cells was analyzed for germline variants using a targeted 600-gene NGS panel. Kaplan-Meier survival analysis was performed to analyze disease free survival (DFS), progression free survival (PFS) and overall survival (OS) in association with clinicopathologic and genomic variables.ResultsSixty-three patients presenting with HR+/HER2- MBC were enrolled in this study. Fourteen patients were &lt; 40 years, 19 were 40-50 years, and 30 were &gt; 50 years at the time of primary cancer diagnosis. No significant associations were observed between age and DFS, PFS or OS. Shorter OS was associated with de novo Stage IV disease (p = 0.002), Luminal B subtype (p = 0.006), high Ki67 index (p = 0.036), resistance to adjuvant endocrine therapy (p = 0.0001) and clinical stage (p = 0.015). Reduced OS was also observed in association with somatic alterations in FGFR1 (p = 0.008), CCND2 (p = 0.012), RB1 (p = 0.029) or TP53 (p = 0.029) genes, but not in association with germline variants.ConclusionIn this group of real-world HR+/HER2- MBC breast cancer patients younger age was not associated with poor outcomes. While current guidelines recommend treatment decisions based on tumor biology rather than age, young HR+ breast cancer patients are more likely to receive chemotherapy. Our findings support the development of biomarker-driven treatment strategies for these patients.
Development, comparison, and validation of four intelligent, practical machine learning models for patients with prostate-specific antigen in the gray zone
Authors: Liu Taobin , Zhang Xiaoming , Chen Ru , Deng Xinxi , Fu Bin 
Published: June 2023

PurposeMachine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier for patients in the prostate-specific antigen gray zone are to be developed and compared, identifying valuable predictors. Predictive models are to be integrated into actual clinical decisions.MethodsPatient information was collected from December 01, 2014 to December 01, 2022 from the Department of Urology, The First Affiliated Hospital of Nanchang University. Patients with a pathological diagnosis of prostate hyperplasia or prostate cancer (any PCa) and having a prostate-specific antigen (PSA) level of 4–10 ng/mL before prostate puncture were included in the initial information collection. Eventually, 756 patients were selected. Age, total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), fPSA/tPSA, prostate volume (PV), prostate-specific antigen density (PSAD), (fPSA/tPSA)/PSAD, and the prostate MRI results of these patients were recorded. After univariate and multivariate logistic analyses, statistically significant predictors were screened to build and compare machine learning models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier to determine more valuable predictors.ResultsMachine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier exhibit higher predictive power than individual metrics. The area under the curve (AUC) (95% CI), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score of the LogisticRegression machine learning prediction model were 0.932 (0.881–0.983), 0.792, 0.824, 0.919, 0.652, 0.920, and 0.728, respectively; of the XGBoost machine learning prediction model were 0.813 (0.723–0.904), 0.771, 0.800, 0.768, 0.737, 0.793 and 0.767, respectively; of the GaussianNB machine learning prediction model were 0.902 (0.843–0.962), 0.813, 0.875, 0.819, 0.600, 0.909, and 0.712, respectively; and of the LGBMClassifier machine learning prediction model were 0.886 (0.809–0.963), 0.833, 0.882, 0.806, 0.725, 0.911, and 0.796, respectively. The LogisticRegression machine learning prediction model has the highest AUC among all prediction models, and the difference between the AUC of the LogisticRegression prediction model and those of XGBoost, GaussianNB, and LGBMClassifier is statistically significant (p &lt; 0.001).ConclusionMachine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier algorithms exhibit superior predictability for patients in the PSA gray area, with the LogisticRegression model yielding the best prediction. The aforementioned predictive models can be used for actual clinical decision-making.​
Tumor cuproptosis and immune infiltration improve survival of patients with hepatocellular carcinoma with a high expression of ferredoxin 1
Authors: Quan Yingyao , Li Wei , Yan Rongrong , Cheng Jing , Xu Heng , Chen Lin 
Published: June 2023

BackgroundCuproptosis is a novel cell death pathway dependent on cellular copper ions and ferredoxin 1 (FDX1). Hepatocellular carcinoma (HCC) is derived from healthy liver as a central organ for copper metabolism. It remains no conclusive evidence whether cuproptosis is involved in survival improvement of patients with HCC.MethodA 365–liver hepatocellular carcinoma (LIHC) cohort with RNA sequencing data and paired clinical and survival information was obtained from the The Cancer Genome Atlas (TCGA) dataset. A retrospective cohort of 57 patients with HCC with stages I/II/III was collected by Zhuhai People’s Hospital from August 2016 to January 2022. Low- or high-FDX1 groups were divided according to the median value of FDX1 expression. Cibersort, single-sample gene set enrichment analysis, and multiplex immunohistochemistry analyzed immune infiltration in LIHC and HCC cohorts. Cell proliferation and migration of HCC tissues and hepatic cancer cell lines were evaluated using the Cell Counting Kit-8. Quantitative real-time PCR and RNA interference measured and downregulated FDX1 expression. Statistical analysis was conducted by R and GraphPad Prism software.ResultsHigh FDX1 expression significantly enhanced survival of patients with LIHC from the TCGA dataset, which was also demonstrated through a retrospective cohort with 57 HCC cases. Immune infiltration was different between the low– and high–FDX1 expression groups. Natural killer cells, macrophages, and B cells were significantly enhanced, and PD-1 expression was low in the high-FDX1 tumor tissues. Meanwhile, we found that a high expression of FDX1 decreased cell viability in HCC samples. HepG2 cells with FDX1 expression are sensitive to Cu2+, and interference of FDX1 promoted proliferation and migration of tumor cells. The consistent results were also demonstrated in Hep3B cells.ConclusionThis study reveals that cuproptosis and tumor immune microenvironment were together involved in improvement of survival in patients with HCC with a high expression of FDX1.
Governor vessel moxibustion for cancer-related fatigue in colorectal patients: a randomized trial
Authors: Li Huakang , Huang Wei , Du Kangming , Liu Wei , Wu Ziliang , Xu Bo , Li Qiang , Wang Yue , Lin Bing 
Published: June 2023

ObjectiveThis study aimed to investigate the efficacy and mechanism of action of Governor Vessel Moxibustion (GVM) in the treatment of Cancer-Related Fatigue (CRF) in patients who have completed treatment for colorectal cancer.MethodsWe randomly assigned 80 CRF patients in a 1:1 ratio to either the experimental group or the control group. During the three-week treatment period, both groups of patients received usual care for CRF provided by professional nurses. The experimental group received additional GVM treatment (three times a week, nine times total). The primary outcome was the mean change in total fatigue score from baseline to the end of treatment, assessed using the Chinese version of the Piper Fatigue Scale.ResultsAt baseline, the total fatigue scores were 6.20 ± 0.12 in the experimental group and 6.16 ± 0.14 in the control group. At the end of treatment, the total fatigue scores decreased by 2.03 points (32.7% decrease from baseline) in the experimental group and by 0.99 points (15.6% decrease from baseline) in the control group. The absolute reduction in total fatigue scores in the experimental group was 1.04 points higher than in the control group (95% CI, 0.93 to 1.15; P&lt;0.001), corresponding to a relative difference of 17.1% (95% CI, 15.2% to 18.9%; P&lt;0.001). At the end of treatment, the experimental group showed greater reductions in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels compared to the control group. No serious adverse events related to GVM treatment were observed.ConclusionGVM appears to be safe and effective for alleviating CRF in patients who have completed colorectal cancer treatment, which may be related to the modulation of IL-6 and TNF-α levels.Trial registrationChinese Clinical Trials Registry: ChiCTR2300069208.
A meta-analysis: single or double dartos flap layer in tubularized incised plate urethroplasty to prevent urethrocutaneous fistula?
Authors: Yuan Yi , Wang Yu-wen , Liang Yan-nei , Wang Yu-ying , Ho Jun-jie , Peng Tong-yu , Zhao Zhang , Deng Nan 
Published: June 2023

BackgroundsUrethrocutaneous fistula is one of the most common complications after urethroplasty. This meta-analysis aims to evaluate the superiority of double dartos flap to single dartos flap in preventing fistula during tubularized incised plate urethroplasty (TIPU), which is one of the most frequently used operations for hypospadias.MethodsWe extracted clinical trials under the following included criteria: (1) children with TIPU; (2) a comparison of single and double flap layer; and (3) record of complications with the following excluded criteria: (1) non-comparison and (2) lack of data. Finally, 13 studies from PubMed, Cochrane Library, Scopus, and Embase have been investigated, with a total of 1,185 patients from 2005 to 2022. The quality assessment was conducted according to the Cochrane handbook and the Newcastle–Ottawa scale. A mixed-effect model was utilized to weigh the risk of fistula, phallic rotation, meatal stenosis, and wound dehiscence by the Review Manager V.5.4 software.ResultsThe double dartos flap layer group excels in descending the risk of postoperative fistula [odds ratio (OR) = 9.56; 95% confidence interval (CI) (4.76, 19.22); P &lt; 0.00001] and phallic rotation [OR = 31.26; 95% CI (9.60, 101.84); P &lt; 0.00001], while there are no differences in the rate of meatal stenosis [OR = 1.49; 95% CI (0.73, 2.70); P = 0.31] and wound dehiscence [OR = 2.30; 95% CI (0.80, 6.63); P = 0.12].ConclusionsThe routine utility of a double dartos flap layer is recommended as a potential treatment during the tubularized incised plate urethroplasty.Systematic Review Registrationidentifier PROSPERO CRD42022366294.
Efficacy and safety of consolidation durvalumab after chemoradiation therapy for stage III non-small-cell lung cancer: a systematic review, meta-analysis, and meta-regression of real-world studies
Authors: Zhang Yatong , Tian Yumei , Zheng Li , Sun Xuelin , Zhao Zinan , Zheng Yujing , Tian Jinhui 
Published: June 2023

Background: The current review aimed to pool real-world evidence on the efficacy and toxicity of consolidation durvalumab for stage III unresectable non-small cell lung cancer (NSCLC) after curative chemoradiotherapy.Methods: PubMed, CENTRAL, ScienceDirect, Embase, and Google Scholar were searched for observational studies reporting the use of durvalumab for NSCLC till 12th April 2022. Twenty-three studies with 4,400 patients were included.Results: The pooled 1-year overall survival (OS) and progression-free survival rates (PFS) were 85% (95% CI: 81%–89%) and 60% (95% CI: 56%–64%) respectively. Pooled incidence of all-grade pneumonitis, grade ≥3 pneumonitis and discontinuation of durvalumab due to pneumonitis were 27% (95% CI: 19%–36%), 8% (95% CI: 6%–10%) and 17% (95% CI: 12%–23%) respectively. The pooled proportion of patients experiencing endocrine, cutaneous, musculoskeletal, and gastrointestinal adverse events was 11% (95% CI: 7%–18%), 8% (95% CI: 3%–17%), 5% (95% CI: 3%–6%), and 6% (95% CI: 3%–12%), respectively.Conclusion: Meta-regression indicated that performance status significantly influenced PFS, while age, time to durvalumab, and programmed death-ligand 1 status significantly affected pneumonitis rates. Real-world evidence suggests that the short-term efficacy and safety of durvalumab are consistent with that of the PACIFIC trial. The congruence of results lends support to durvalumab use in improving outcomes of unresectable stage III NSCLC.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324663, identifier CRD42022324663.
N-linoleyltyrosine resisted the growth of non-small cell lung cancer cells via the regulation of CB1 and CB2 involvement of PI3K and ERK pathways
Authors: Hu Yan , Zhao Zhe , Liu Yuan-Ting , Xu Ze-Cheng , Li Jing-Yi , Yang Zheng-Yu , Rui-Wang  , Yang Yun-Qi , Zhang Jia-Hui , Qiu Si-Yuan , He Tao , Wu Yi-Ying , Liu Sha 
Published: June 2023

Background: N-linoleyltyrosine (NITyr), one of the anandamide analogs, exerts activity via the endocannabinoid receptors (CB1 and CB2), which showed anti-tumor effects in various tumors. Therefore, we speculated that NITyr might show anti-non-small cell lung cancer (NSCLC) effects via the CB1 or CB2 receptor. The purpose of the investigation was to reveal the anti-tumor ability of NITyr on A549 cells and its mechanisms.Methods: The viability of A549 cells was measured by MTT assay, and the cell cycle and apoptosis were both examined by flow cytometry; in addition, cell migration was tested by wound healing assay. Apoptosis-related markers were measured by immunofluorescence. The downstream signaling pathways (PI3K, ERK, and JNK) of CB1 or CB2 were examined through Western blotting. The expressions of CB1 and CB2 were detected by immunofluorescence. Finally, the AutoDock software was used to validate the binding affinity between the targets, such as CB1 and CB2, with NITyr.Results: We found that NITyr inhibited cell viability, hindered the cell cycle, resulted in apoptosis, and inhibited migration. The CB1 inhibitor, AM251, and the CB2 inhibitor, AM630, weakened the aforementioned phenomenon. The immunofluorescence assay suggested that NITyr upregulated the expression of CB1 and CB2. Western blot analysis indicated that NITyr upregulated the expression of p-ERK, downregulated the expression of p-PI3K, and did not affect p-JNK expression. In conclusion, NITyr showed a role in inhibiting NSCLC through the activation of CB1 and CB2 receptors involved in PI3K and ERK pathways.
Paraben exposure through drugs in the neonatal intensive care unit: a regional cohort study
Authors: Iacobelli Silvia , Commins Marie , Lorrain Simon , Gouyon Beatrice , Ramful Duksha , Richard Magali , Grondin Anthony , Gouyon Jean-Bernard , Bonsante Francesco 
Published: June 2023

Background and objectives: Environmental factors influence the development of very preterm infants (VPIs, born at less than 32 weeks of gestation). It is important to identify all potential sources of paraben exposure in these vulnerable infants. We aimed to quantify paraben exposure via drug administration in a cohort of VPI cared for in neonatal intensive care units (NICUs).Methods: A prospective, observational study was carried out over a five-year period in a regional setting (two NICUs using the same computerized order-entry system). The main outcome was exposure to paraben-containing drugs. The secondary outcomes were: time of the first exposure, daily intake, number of infants exceeding paraben acceptable daily intake (ADI: 0–10 mg/kg/d), duration of exposure, and cumulative dose.Results: The cohort consisted of 1,315 VPIs [BW 1129.9 (±360.4) g]. Among them, 85.5% were exposed to paraben-containing drugs. In 40.4% of infants, the first exposure occurred during the second week of life. Mean paraben intake and duration of exposure were, respectively, 2.2 (±1.4) mg/kg/d and 33.1 (±22.3) days. The cumulative paraben intake was 80.3 (±84.6) mg/kg. The ADI was exceeded in 3.5% of exposed infants. Lower GA was associated with higher intake and longer exposure (p &lt; 0.0001). The main molecules involved in paraben exposure were: sodium iron feredetate, paracetamol, furosemide, and sodium bicarbonate + sodium alginate.Conclusion: Commonly used drugs are potential source of parabens, and ADI can be easily exceeded in VPIs cared for in NICUs. Efforts are needed to identify paraben-free alternative formulations for these vulnerable infants.
Cold water immersion of the hand and forearm during half-time improves intermittent exercise performance in the heat
Authors: Iwahashi Manami , Chaen Yudai , Yanaoka Takuma , Kurokawa Yasutsugu , Hasegawa Hiroshi 
Published: June 2023

The present study aimed to investigate the effect of cold water immersion of the hand and forearm during half-time (HT) on intermittent exercise performance and thermoregulation by imitating intermittent athletic games in the heat. In a randomized crossover design, 11 physically active men performed the first half (first and second block) and second half (third and fourth block) intermittent cycling exercise protocol, which consisted of a 5-s maximal power pedalling (body weight × 0.075 kp) every minute separated by 25-s of unloaded pedalling and rest (30 s) in the heat (33°C, 50% relative humidity). The two-halves were separated by a 15-min HT. During HT, the participants were assigned to the CON (sedentary resting) or COOL (immersion of hands and forearms in cold water at 15–17°C) condition. The mean power output in the second half was significantly greater (third and fourth block:p&lt; 0.05) in the COOL than in the CON condition. Moreover, there was a significant decrease in the rectal (0.54 ± 0.17°C,p&lt; 0.001) and mean skin (1.86 ± 0.34°C,p&lt; 0.05) temperatures of the COOL condition during HT. Furthermore, the heart rate (16 ± 7 bpm,p&lt; 0.05) and skin blood flow (40.2 ± 10.5%,p&lt; 0.001) decreased at the end of HT in the COOL condition. In the second half, thermal sensation was more comfortable in the COOL condition (p&lt; 0.001). Cold water immersion of the hand and forearm during HT improved physiological and reduced perceived heat stress. Moreover, it prevented a reduction in intermittent exercise performance in the second half.
Chromosome-level genome and multi-omics analyses provide insights into the geo-herbalism properties of Alpinia oxyphylla
Authors: Pan Kun , Dai Shuiping , Tian Jianping , Zhang Junqing , Liu Jiaqi , Li Ming , Li Shanshan , Zhang Shengkui , Gao Bingmiao 
Published: June 2023

IntroductionAlpinia oxyphylla Miquel (A. oxyphylla), one of the “Four Famous South Medicines” in China, is an essential understory cash crop that is planted widely in the Hainan, Guangdong, Guangxi, and Fujian provinces. Particularly, A. oxyphylla from Hainan province is highly valued as the best national product for geo-herbalism and is an important indicator of traditional Chinese medicine efficacy. However, the molecular mechanism underlying the formation of its quality remains unspecified.MethodsTo this end, we employed a multi-omics approach to investigate the authentic quality formation of A. oxyphylla.ResultsIn this study, we present a high-quality chromosome-level genome assembly of A. oxyphylla, with contig N50 of 76.96 Mb and a size of approximately 2.08Gb. A total of 38,178 genes were annotated, and the long terminal repeats were found to have a high frequency of 61.70%. Phylogenetic analysis demonstrated a recent whole-genome duplication event (WGD), which occurred before A. oxyphylla’s divergence from W. villosa (~14 Mya) and is shared by other species from the Zingiberaceae family (Ks, ~0.3; 4DTv, ~0.125). Further, 17 regions from four provinces were comprehensively assessed for their metabolite content, and the quality of these four regions varied significantly. Finally, genomic, metabolic, and transcriptomic analyses undertaken on these regions revealed that the content of nootkatone in Hainan was significantly different from that in other provinces.DiscussionOverall, our findings provide novel insights into germplasm conservation, geo-herbalism evaluation, and functional genomic research for the medicinal plant A. oxyphylla.
Obstacles and facilitators of cancer-related dyadic efficacy experienced by couples coping with non-metastatic cancers
Authors: Brosseau Danielle C. , Peláez Sandra , Ananng Bethsheba , Körner Annett 
Published: June 2023

IntroductionCancer-related dyadic efficacy is an individual’s confidence to work together with a partner to conjointly manage the effects of cancer and its treatment. In other health contexts, higher levels of dyadic efficacy have been associated with fewer symptoms of psychological distress and higher ratings of relationship satisfaction. The aim of the current study was to explore patient and partner perspectives on what obstructs and facilitates cancer-related dyadic efficacy.MethodsThese aims were accomplished through a secondary analysis of data collected as a part of a collective qualitative case study. Participants (N = 17 participants) were patients undergoing treatment or recently completed treatment (within 6 months) for a non-metastatic cancer and their partners. To enable in-depth discussions among participants, data was collected through five focus groups. Participants described obstacles and facilitators of dyadic efficacy as dimensions of a common influence. Consistent with these descriptions, reflexive thematic analysis was used to identify influences on cancer-related dyadic efficacy and their subsequent obstructive and facilitative dimensions.ResultsFour main categories of influence with the potential to obstruct or facilitate cancer-related dyadic efficacy were identified along with their subthemes: appraisals of the couple relationship (quality and togetherness), communication (pattern and interest in information), coping (strategy and evaluation), and responses to change (in tasks and roles and sex life). Eight obstructive and seven facilitative dimensions of these subthemes were described.Discussion: This first analysis of obstacles and facilitators of couples’ cancer-related dyadic efficacy capitalized on the experiential expertise of individuals with cancer and their partners. These thematic results are instructive for the design of dyadic efficacy-enhancing interventions for couples coping with cancer.