bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of coffee intake with bone mineral density: a Mendelian randomization study
Authors: Ye Yang , Zhong Rui , Xiong Xiao-ming , Wang Chuan-en 
Published: March 2024

BackgroundIn observational studies, the relationship between coffee intake and bone mineral density (BMD) is contradictory. However, residual confounding tends to bias the results of these studies. Therefore, we used a two-sample Mendelian randomization (MR) approach to further investigate the potential causal relationship between the two.MethodsGenetic instrumental variables (IVs) associated with coffee intake were derived from genome-wide association studies (GWAS) of the Food Frequency Questionnaire (FFQ) in 428,860 British individuals and matched using phenotypes in PhenoScanner. Summarized data on BMD were obtained from 537,750 participants, including total body BMD (TB-BMD), TB-BMD in five age brackets ≥60, 45-60, 30-45, 15-30, and 0-15 years, and BMD in four body sites: the lumbar spine, the femoral neck, the heel, and the ultradistal forearm. We used inverse variance weighting (IVW) methods as the primary analytical method for causal inference. In addition, several sensitivity analyses (MR-Egger, Weighted median, MR-PRESSO, Cochran’s Q test, and Leave-one-out test) were used to test the robustness of the results.ResultsAfter Bonferroni correction, Coffee intake has a potential positive correlation with total body BMD (effect estimate [Beta]: 0.198, 95% confidence interval [Cl]: 0.05-0.35, P=0.008). In subgroup analyses, coffee intake was potentially positively associated with TB-BMD (45-60, 30-45 years) (Beta: 0.408, 95% Cl: 0.12-0.69, P=0.005; Beta: 0.486, 95% Cl: 0.12-0.85, P=0.010). In addition, a significant positive correlation with heel BMD was also observed (Beta: 0.173, 95% Cl: 0.08-0.27, P=0.002). The results of the sensitivity analysis were generally consistent.ConclusionThe results of the present study provide genetic evidence for the idea that coffee intake is beneficial for bone density. Further studies are needed to reveal the biological mechanisms and offer solid support for clinical guidelines on osteoporosis prevention.
Comparison of ultrasound risk stratification systems for pediatric thyroid nodules
Authors: Yu Jing , Cui Yiyang , Fu Chao , Ma Xiao , Si Caifeng , Huang Yuanjing , Cui Kefei , Zhang Yan 
Published: March 2024

BackgroundThere is currently insufficient data to validate adult-based US risk stratification systems (RSSs) for the identification of malignant thyroid nodules in a pediatric population.MethodsFrom October 2016 and May 2023, 173 thyroid nodules of pediatric patients (age ≤ 18 years) with definitive pathology results and ultrasound (US) examination within 1 month before surgery or fine-needle aspiration (FNA) biopsy in our institution were enrolled in this study. The clinical and US characteristics of these nodules were retrospectively reviewed and categorized according to the ACR-TIRADS, C-TIRADS, and ATA guidelines. The diagnostic performance of US-based FNA criteria (original and simulating) of the three guidelines in thyroid cancer detection was estimated.ResultsThe three RSSs had similar AUC according to the categories(0.849-0.852, all P &gt; 0.05). When combined with the original FNA criteria of the three RSSs to manage the nodules, the FNA rate of ACR-TIRADS and C-TIRADS were significantly less than ATA guidelines (53.18% vs. 64.63%, P &lt; 0.05, and 52.60% vs. 64.63%, P &lt; 0.05). The missed malignancy rate (MMR) and unnecessary FNA rate (UFR) of ATA guidelines (50.00%, 35.85%) was highest among the three RSSs, followed by the C-TIRADS (37.80%, 19.57%) and the ACR-TIRADS (37.04%, 19.57%). When nodules &lt; 1 cm with the highest category in each RSS biopsied, that is when using the simulating FNA thresholds, the MMR was reduced overall (all P &lt; 0.001), without a change in the UFR (all P &gt; 0.05). All the three RSSs showed a substantial improvement in accuracy and malignant detection rate (all P &lt; 0.05).ConclusionThe ACR-TIRADS, C-TIRADS, and ATA guidelines showed high missed malignancy rates when using their original recommended FNA criteria. When nodules &lt; 1 cm with the highest category in each RSS biopsied, the missed malignancy rate of each RSS was decreased. Decreasing the FNA thresholds for highly suspicious malignant nodules may therefore be an effective means of managing malignant thyroid nodules in pediatric patients.
The impact of thyroid autoimmunity on pregnancy outcomes in women with unexplained infertility undergoing intrauterine insemination: a retrospective single-center cohort study and meta-analysis
Authors: Li Jiaxu , Yu Jiaxin , Huang Yingqin , Xie Baoli , Hu Qianwen , Ma Nana , Qin Rongyan , Luo Jianxin , Wu Hao , Liao Ming , Qin Aiping 
Published: March 2024

IntroductionInfertility affects 8-12% of couples worldwide, with 15-30% classified as unexplained infertility (UI). Thyroid autoimmunity (TAI), the most common autoimmune disorder in women of reproductive age, may impact fertility and pregnancy outcomes. However, the underlying mechanism is unclear. This study focuses on intrauterine insemination (IUI) and its potential association with TAI in UI patients. It is the first meta-analysis following a comprehensive literature review to improve result accuracy and reliability.MethodsRetrospective cohort study analyzing 225 women with unexplained infertility, encompassing 542 cycles of IUI treatment. Participants were categorized into TAI+ group (N=47, N= 120 cycles) and TAI- group (N=178, N= 422 cycles). Additionally, a systematic review and meta-analyses following PRISMA guidelines were conducted, incorporating this study and two others up to June 2023, totaling 3428 IUI cycles. ResultsAnalysis revealed no significant difference in independent variables affecting reproductive outcomes. However, comparison based on TAI status showed significantly lower clinical pregnancy rates (OR: 0.43, P= 0.028, 95%CI: 0.20-0.93) and live birth rate (OR: 0.20, P= 0.014, 95%CI: 0.05 ~ 0.71) were significantly lower than TAI- group. There was no significant difference in pregnancy rate between the two groups (OR: 0.61, P= 0.135, 95%CI: 0.32-1.17). However, the meta-analysis combining these findings across studies did not show statistically significant differences in clinical pregnancy rates (OR:0.77, P=0.18, 95%CI: 0.53-1.13) or live birth rates (OR: 0.68, P=0.64, 95%CI: 0.13-3.47) between the TAI+ and TAI- groups. DiscussionOur retrospective cohort study found an association between TAI and reduced reproductive outcomes in women undergoing IUI for unexplained infertility. However, the meta-analysis incorporating other studies did not yield statistically significant associations. Caution is required in interpreting the relationship between thyroid autoimmunity and reproductive outcomes. Future studies should consider a broader population and a more rigorous study design to validate these findings. Clinicians dealing with women with unexplained infertility and TAI should be aware of the complexity of this field and the limitations of available evidence.
A study on the correlations of PRL levels with anxiety, depression, sleep, and self-efficacy in patients with prolactinoma
Authors: Miao Xiaoju , Fu Zhongmin , Luo Xian , Wang Jun , Yuan Lili , Zhao Shunjun , Feng Yi , Huang Shiming , Xiao Shunwu 
Published: March 2024

PurposeThe purpose of this study was to explore the factors influencing PRL levels in patients with prolactinoma and to investigate the correlations between anxiety, depression, sleep, self-efficacy, and PRL levels.MethodsThis retrospective study included 176 patients with prolactinoma who received outpatient treatment at the Affiliated Hospital of Zunyi Medical University from May 2017 to August 2022. The general information questionnaire, Hospital Anxiety and Depression Scale (HADS), Athens Insomnia Scale (AIS), and General Self-Efficacy Scale (GSES) were used for data collection. A generalized estimating equation (GEE) model was used to analyze the factors influencing PRL levels in patients with prolactinoma. GEE single-effect analysis was used to compare PRL levels at different time points between anxiety group and nonanxiety group, between insomnia group and normal group, and between low, medium, and high self-efficacy groups.ResultsThe median baseline PRL level and the PRL levels at 1, 3, 6, and 12 months of follow-up were 268.50 ng/ml, 122.25 ng/ml, 21.20 ng/ml, 19.65 ng/ml, and 16.10 ng/ml, respectively. Among patients with prolactinoma, 59.10% had anxiety (HADS-A score = 7.35 ± 3.34) and 28.98% had depression (HADS-D score = 5.23 ± 3.87), 9.10% had sleep disorders (AIS score = 6.10 ± 4.31) and 54.55% had low self-efficacy (GSES score = 2.13 ± 0.83). Educational level, tumor size, number of visits, sleep quality, anxiety level, and self-efficacy level were found to be factors influencing PRL levels in patients with prolactinoma (P&lt;0.05). Higher PRL levels were observed in the anxiety group compared to the non-anxiety group (P&lt;0.001), in the insomnia group compared to the normal group (P&lt;0.05), and in the low self-efficacy group compared to the medium and high self-efficacy groups (P&lt;0.05).ConclusionPRL levels in patients with prolactinoma are related to education level, tumor size, number of visits, anxiety, self-efficacy, and sleep but not depression. PRL levels were higher in patients with anxiety, low self-efficacy, and sleep disorders.
The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing
Authors: Singh Jarnail , Randle Michelle R. , Walters Bradley J. , Cox Brandon C. 
Published: March 2024

IntroductionHair cells (HCs) of the cochlea are responsible for sound transduction and hearing perception in mammals. Genetic mutations in the transcription factor Pou4f3 cause non-syndromic autosomal dominant hearing loss in humans (DFNA15) which varies in the age of onset depending on the individual mutation. Mouse models with germline deletion or mutations in Pou4f3 have previously demonstrated its critical role in the maturation and survival of cochlear HCs during embryonic development. However, the role of Pou4f3 in auditory function and in the survival or maintenance of cochlear HCs after birth and during adulthood has not been studied.MethodsTherefore, using the inducible CreER-loxP system, we deleted Pou4f3 from mouse cochlear HCs at different postnatal ages, relevant to specific stages of HC maturation and hearing function.Results and discussionElevated auditory brainstem response thresholds and significant HC loss were detected in mice with Pou4f3 deletion compared to their control littermates, regardless of the age when Pou4f3 was deleted. However, HC loss occurred more rapidly when Pou4f3 was deleted from immature HCs. Additionally, HC loss caused by Pou4f3 deletion did not affect the number of cochlear supporting cells, but caused a delayed loss of spiral ganglion neurons at 4 months after the deletion. In conclusion, Pou4f3 is necessary for the survival of cochlear HCs and normal hearing at all postnatal ages regardless of their maturation state. Our data also suggest that Pou4f3 indirectly regulates the survival of spiral ganglion neurons.
Comparison of outcomes between preoperative and postoperative systemic treatment in patients with hepatocellular carcinoma: a SEER database-based study
Authors: Liu Yadi , Sun Shuangshuang , Chu Zhaoyin , Liu Caixia , Chen Lina , Ruan Zhengshang 
Published: March 2024

BackgroundSignificant advancements in systemic treatment for hepatocellular carcinoma have been made in recent years. However, the optimal timing of systemic treatment before or after surgery remains unknown. This study aims to evaluate the impact of sequencing systemic treatment and surgical intervention on the long-term prognosis of hepatocellular carcinoma patients.MethodsIn our study, we analyzed data from patients diagnosed with primary liver cancer (2004-2015) extracted from the SEER database. Patients who underwent both systemic treatment and surgical intervention were selected, divided into preoperative and postoperative systemic therapy groups. The primary endpoint of the study is overall survival(OS), and the secondary endpoint is cancer-specific survival (CSS). Propensity score matching (PSM) reduced the influence of confounding factors, while Kaplan-Meier curves and a multivariable Cox proportional hazards model accounted for variables during survival analysis.ResultsA total of 1918 eligible HCC patients were included, with 1406 cases in the preoperative systemic treatment group and 512 cases in the postoperative systemic treatment group. Survival analysis showed that both the preoperative group demonstrated longer median overall survival (OS) and median cancer-specific survival (CSS) before and after PSM. After conducting multivariate COX regression analysis with stepwise adjustment of input variables, the postoperative systemic treatment group continued to exhibit a higher risk of all-cause mortality (HR: 1.84, 95% CI: 1.55-2.1) and cancer-specific mortality (HR: 2.10, 95% CI: 1.73-2.54). Subgroup analysis indicated consistent results for overall survival (OS) across different subgroups.ConclusionsHepatocellular carcinoma patients from the SEER database who received preoperative systemic therapy had superior OS and CSS compared to those who received postoperative systemic therapy.
Breast cancer risk prediction using machine learning: a systematic review
Authors: Hussain Sadam , Ali Mansoor , Naseem Usman , Nezhadmoghadam Fahimeh , Jatoi Munsif Ali , Gulliver T. Aaron , Tamez-Peña Jose Gerardo 
Published: March 2024

BackgroundBreast cancer is the leading cause of cancer-related fatalities among women worldwide. Conventional screening and risk prediction models primarily rely on demographic and patient clinical history to devise policies and estimate likelihood. However, recent advancements in artificial intelligence (AI) techniques, particularly deep learning (DL), have shown promise in the development of personalized risk models. These models leverage individual patient information obtained from medical imaging and associated reports. In this systematic review, we thoroughly investigated the existing literature on the application of DL to digital mammography, radiomics, genomics, and clinical information for breast cancer risk assessment. We critically analyzed these studies and discussed their findings, highlighting the promising prospects of DL techniques for breast cancer risk prediction. Additionally, we explored ongoing research initiatives and potential future applications of AI-driven approaches to further improve breast cancer risk prediction, thereby facilitating more effective screening and personalized risk management strategies.Objective and methodsThis study presents a comprehensive overview of imaging and non-imaging features used in breast cancer risk prediction using traditional and AI models. The features reviewed in this study included imaging, radiomics, genomics, and clinical features. Furthermore, this survey systematically presented DL methods developed for breast cancer risk prediction, aiming to be useful for both beginners and advanced-level researchers.ResultsA total of 600 articles were identified, 20 of which met the set criteria and were selected. Parallel benchmarking of DL models, along with natural language processing (NLP) applied to imaging and non-imaging features, could allow clinicians and researchers to gain greater awareness as they consider the clinical deployment or development of new models. This review provides a comprehensive guide for understanding the current status of breast cancer risk assessment using AI.ConclusionThis study offers investigators a different perspective on the use of AI for breast cancer risk prediction, incorporating numerous imaging and non-imaging features.
Clinical study on the prediction of ALN metastasis based on intratumoral and peritumoral DCE-MRI radiomics and clinico-radiological characteristics in breast cancer
Authors: Wang Yunxia , Shang Yiyan , Guo Yaxin , Hai Menglu , Gao Yang , Wu Qingxia , Li Shunian , Liao Jun , Sun Xiaojuan , Wu Yaping , Wang Meiyun , Tan Hongna 
Published: March 2024

ObjectiveTo investigate the value of predicting axillary lymph node (ALN) metastasis based on intratumoral and peritumoral dynamic contrast-enhanced MRI (DCE-MRI) radiomics and clinico-radiological characteristics in breast cancer.MethodsA total of 473 breast cancer patients who underwent preoperative DCE-MRI from Jan 2017 to Dec 2020 were enrolled. These patients were randomly divided into training (n=378) and testing sets (n=95) at 8:2 ratio. Intratumoral regions (ITRs) of interest were manually delineated, and peritumoral regions of 3 mm (3 mmPTRs) were automatically obtained by morphologically dilating the ITR. Radiomics features were extracted, and ALN metastasis-related radiomics features were selected by the Mann-Whitney U test, Z score normalization, variance thresholding, K-best algorithm and least absolute shrinkage and selection operator (LASSO) algorithm. Clinico-radiological risk factors were selected by logistic regression and were also used to construct predictive models combined with radiomics features. Then, 5 models were constructed, including ITR, 3 mmPTR, ITR+3 mmPTR, clinico-radiological and combined (ITR+3 mmPTR+ clinico-radiological) models. The performance of models was assessed by sensitivity, specificity, accuracy, F1 score and area under the curve (AUC) of receiver operating characteristic (ROC), calibration curves and decision curve analysis (DCA).ResultsA total of 2264 radiomics features were extracted from each region of interest (ROI), 3 and 10 radiomics features were selected for the ITR and 3 mmPTR, respectively. 5 clinico-radiological risk factors were selected, including lesion size, human epidermal growth factor receptor 2 (HER2) expression, vascular cancer thrombus status, MR-reported ALN status, and time-signal intensity curve (TIC) type. In the testing set, the combined model showed the highest AUC (0.839), specificity (74.2%), accuracy (75.8%) and F1 Score (69.3%) among the 5 models. DCA showed that it had the greatest net clinical benefit compared to the other models.ConclusionThe intra- and peritumoral radiomics models based on DCE-MRI could be used to predict ALN metastasis in breast cancer, especially for the combined model with clinico-radiological characteristics showing promising clinical application value.
Design, synthesis, and evaluation of the novel ozagrel–paeonol codrug with antiplatelet aggregation activities as a potent anti-stroke therapeutic agent
Authors: Zuo Chijing , Yan Fulong , Wang Jie , Zhu Yulong , Luo Wenhui , Liu Yan , Liang Wanhui , Yu Weidong , Zhang Jingwei , Peng Daiyin , Ma Xiaodong , Peng Can 
Published: March 2024

Introduction: Ischemic stroke is the second most common chronic disease worldwide and is associated with high morbidity and mortality. Thromboembolism and platelet aggregation are the most characteristic features of stroke. Other than aspirin, no standard, accepted, or effective treatment for acute ischemic stroke has been established. Consequently, it is essential to identify novel therapeutic compounds for this condition.Methods: In this study, novel ozagrel/paeonol-containing codrugs were synthesized and characterized using 1H-NMR, 13C-NMR, and mass spectroscopy. Their antiplatelet aggregation activity was evaluated, with compound PNC3 found to exhibit the best effect. Subsequently, studies were conducted to assess its neuroprotective effect, pharmacokinetic properties and model its binding mode to P2Y12 and TXA2, two proteins critical for platelet aggregation.Results: The results indicated that PNC3 has good bioavailability and exerts protective effects against oxygen-glucose deprivation injury in PC12 cells. Molecular docking analysis further demonstrated that the compound interacts with residues located in the active binding sites of the target proteins.Conclusion: The codrugs synthesized in this study display promising pharmacological activities and have the potential for development as an oral formulation.
Safety assessment of Acori Tatarinowii Rhizoma: acute and subacute oral toxicity
Authors: Liu Jia , Ping Xin , Sun Shu-jie , Yang Jiali , Lu Ye , Pei Lin 
Published: March 2024

Introduction: Acori Tatarinowii Rhizoma (ATR) is a well-known traditional Chinese medicine that is used for treating neuropathic diseases. However, there is little information about the safety of ATR.Methods: The present study evaluated the acute and subacute oral toxicity of a water extract of ATR in Institute of Cancer Research (ICR) mice. In acute trials, a single administration of extract at a dose 5,000 mg/kg body weight led to no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) exceeded 5,000 mg/kg. A subacute toxicity test was done using daily doses of 1,250, 2,500, and 5,000 mg/kg of the ATR extract for 28 days, which did not show any adverse clinical symptoms or mortality. However, the male renal organ index and urea level in mice given 5,000 mg/kg was obviously abnormal, which was consistent with pathological results and suggested that this dose might cause kidney injury.Results: Doses of ATR lower than 2,500 mg/kg could be regarded as safe, although the potential cumulative effects of long-term use of high doses of ATR need to be considered.Discussion: The study highlights the function of ATR in reducing blood lipids and provides a new idea for its widespread clinical use in the future.
Hair dehydroepiandrosterone sulfate as biomarker of employees’ well-being? A longitudinal investigation of support, resilience, and work engagement during COVID-19 pandemic
Authors: Girardi Damiano , Dal Corso Laura , Arcucci Elvira , Yıldırım Murat , Pividori Isabella , Prandi Alberto , Falco Alessandra 
Published: March 2024

IntroductionBuilding on the motivational process of the job demands-resources (JD-R) theory, in the current research we investigated the longitudinal association between supervisor support/resilience as job/personal resources, work engagement (WE) and hair dehydroepiandrosterone sulfate, or DHEA(S), as a possible biomarker of employees’ well-being.MethodsIn the context of the COVID-19 pandemic, 122 workers completed two self-report questionnaires (i.e., psychological data): the former at Time 1 (T1) and the latter three months afterwards, at Time 2 (T2). Participants also collected a strand of hair (i.e., biological data) at T2.ResultsResults from path analysis showed that both SS and resilience at T1 were positively related to WE at T2, which, in its turn, was positively related to hair DHEA(S) at T2. Both SS and resilience at T1 had a positive indirect effect on hair DHEA(S) at T2 through WE at T2, which fully mediated the association between job/personal resources and hair DHEA(S).DiscussionOverall, results are consistent with the motivational process of the JD-R. Furthermore, this study provides preliminary evidence for the role of hair DHEA(S) as a biomarker of WE, a type of work-related subjective well-being that plays a central role in the motivational process of the JD-R, leading to favorable personal and organizational outcomes. Finally, the article outlines practical implications for organizations and professionals to foster WE within the workplace.