bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroid Hormone Secretion Over the Course of the Perimenopause: Findings From the Swiss Perimenopause Study
Authors: Grub Jessica , Süss Hannah , Willi Jasmine , Ehlert Ulrike 
Published: December 2021

Background: Perimenopause is characterized by a decline in the steroid hormones, estradiol, and progesterone. By contrast, the steroid hormone cortisol, a marker of the hypothalamic–pituitary–adrenal (HPA) axis, increases. Recent longitudinal studies reported fluctuations in steroid hormone levels during perimenopause, and even increases in estradiol levels. To understand these confounding results, it is necessary to conduct a longitudinal, highly standardized assessment of steroid hormone secretion patterns in perimenopausal women.Methods: This longitudinal study investigated 127 perimenopausal women aged 40–56 years for 13 months. Estradiol, progesterone, and cortisol were assessed using saliva samples, which were collected for two (during months 2 and 12 for estradiol and progesterone) or three (during months 2, 7, and 12 for cortisol) non-consecutive months over the course of the study. A total of 14 saliva samples per participant were analyzed to investigate the courses of estradiol and progesterone. Cortisol awakening response and fluctuations of cortisol throughout the day were measured using a total of 11 saliva samples per participant (on awakening, +30 min, +60 min, at 12:00 p.m., and before going to bed) for months 2, 7, and 12.Results: Multilevel analyses revealed variance in intercept and slope across participants for estradiol [intercept: SD = 5.16 (95% CI: 4.28, 6.21), slope: SD = 0.50 (95% CI: 0.39, 0.64)], progesterone [intercept: SD = 34.77 (95% CI: 25.55, 47.31), slope: SD = 4.17 (95% CI: 2.91, 5.99)], and cortisol (intercept: SD = 0.18 (95% CI: 0.14, 0.23), slope: SD = 0.02 (95% CI: 0.01, 0.02)]. Time predicted cortisol levels [b = −0.02, t(979) = −6.63, p &lt; 0.0001]. Perimenopausal status (early vs. late) did not predict estradiol [b = −0.36, t(1608) = −0.84, p = 0.400], progesterone [b = −4.55, t(1723) = −0.87, p = 0.385], or cortisol [b = 0.01, t(1124) = 0.61, p = 0.542] scores over time.Discussion: Our results are consistent with previous findings emphasizing highly individual fluctuations of estradiol and progesterone levels during perimenopause. However, our findings do not suggest a continuous decline during the observed transition phase, implying relatively stable periods of fluctuating hormone levels. Furthermore, given the lack of significant group differences, it may not be necessary to differentiate between early and late perimenopause from the standpoint of hormonal progression.
Disseminated Human Parvovirus B19 Infection Induced Multiple Organ Dysfunction Syndrome in an Adult Patient With Alcoholic Hepatitis Complicated by Hemolytic Anemia: A Case Report and Literature Review
Authors: Luo Jinmei , Zhang Jingcong , Lai Wenxing , Wang Shaofang , Zhou Laizhi , Shi Yunfeng , Ba Junhui , Hu Jiajia , Wang Yanhong , Li Laisheng , Wu Ben-Quan 
Published: December 2021

BackgroundHuman parvovirus B19 (B19) can cause acute hepatitis and is attributed to the high mortality of alcoholic hepatitis (AH). B19 infection is generally self-healing in previously healthy people, but it can cause fatal effects in some high-risk groups and increase its virulence and infectivity. Disseminated B19 infection-induced multiple organ dysfunction syndrome (MODS) in patients with AH has not been reported yet. Here, we described B19 viremia in an adult patient with AH accompanied by hemolytic anemia (HA), leading to disseminated infection and secondary MODS, as well as self-limiting B19 infections in seven nurses caring for him. Meanwhile, we reviewed the literature on AH and B19 infection.Case PresentationA 43-year-old male patient with AH accompanied by HA was transferred to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, on March 31, 2021. After supportive treatment, his transaminase and bilirubin levels were reduced, but his anemia worsened. He received a red blood cell (RBC) infusion on April 9 for hemoglobin (Hb) lower than 6 g/dl. On April 13, he suddenly had a high fever. Under empirical anti-infection, his high fever dropped and maintained at a low fever level; however, his anemia worsened. On April 25, he was transferred to the medical intensive care unit (MICU) due to severe pneumonia, acute respiratory distress syndrome (ARDS), acute aplastic crisis (AAC), and hemophagocytic syndrome (HPS), which were subsequently confirmed to be related to B19 infection. After methylprednisolone, intravenous immunoglobulin (IVIG), empirical anti-infection, and supportive treatment, the lung infection improved, but hematopoietic and liver abnormalities aggravated, and systemic B19 infection occurred. Finally, the patient developed a refractory arrhythmia, heart failure, and shock and was referred to a local hospital by his family on May 8, 2021. Unfortunately, he died the next day. Fourteen days after he was transferred to MICU, seven nurses caring for him in his first two days in the MICU developed self-limiting erythema infectiosum (EI).ConclusionsB19 infection is self-limiting in healthy people, with low virulence and infectivity; however, in AH patients with HA, it can lead to fatal consequences and high contagion.
Serum Uric Acid and Risk of Chronic Heart Failure: A Systematic Review and Meta-Analysis
Authors: Miao Lina , Guo Ming , Pan Deng , Chen Pengfei , Chen Zhuhong , Gao Jie , Yu Yanqiao , Shi Dazhuo , Du Jianpeng 
Published: December 2021

Objectives: A systematic review and meta-analysis was performed to evaluate the potential prognostic role of serum uric acid (SUA) in patients with chronic heart failure (CHF).Methods: The Embase, PubMed, Web of Science and Cochrane Library databases were searched up to 5 April 2021 for relevant publications. Random effects model was used to pool data. STATA15.0 software was used to perform meta-analysis. Heterogeneity was assessed using the Cochran Q statistic (significance level of P &lt; 0.10) and I2 statistics (significance level of 50%).Results: Ultimately, 18 publications reporting adverse events in CHF patients were included. The results indicate reveal associations between a high level of SUA and the risk of all-cause mortality (HR 2.24, 95% CI 1.49–3.37), cardiovascular mortality (HR 1.14, 95% CI 1.06–1.23), and the composite of death or cardiac events (HR 1.26, 95% CI 1.01–1.56) in CHF patients. A 1 mg/dL increase in serum uric acid led to 4% (HR 1.04, 95% CI 1.02–1.05) and 9% (HR 1.09, 95% CI 1.03–1.17) increases in the risk of all-cause mortality and the composite endpoint of death or cardiac events in CHF patients, respectively.Conclusion: Serum uric acid is positively associated with the risk of adverse events in CHF patients. This study protocol has been registered at PROSPERO as CRD42021247084 (https://www.crd.york.ac.uk/PROSPERO).Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO.
WAY-100635 Alleviates Corneal Lesions Through 5-HT1A Receptor-ROS-Autophagy Axis in Dry Eye
Authors: Zhou Xujiao , Dai Yiqin , Zhai Zimeng , Hong Jiaxu 
Published: December 2021

Purpose: To explore whether 5-HT1A receptors are involved in the dry eye disease (DED) mouse model and reveal its underlying mechanism.Methods: A C57BL/6J mouse DED model was established via the administration of 0.2% benzalkonium chloride twice a day for 14 days. Corneal fluorescein sodium staining score and Schirmer I test were checked before, and on days 7, 14, and 21 after treatment. The experiment was randomly divided into control, DED, 5-HT1A receptor agonist with or without N-acetylcysteine (NAC) and 5-HT1A receptor antagonist with or without NAC groups. The mRNA expression of inflammatory cytokines was measured by reverse transcription-quantitative polymerase chain reaction. Cellular reactive oxygen species (ROS) were detected by 2', 7'-dichlorodihydrofluorescein diacetate assays. Western blot analysis was used to measure the expression levels of autophagic proteins microtubule-associated protein 1 light chain 3 (LC3B-I/II) and autophagy-related gene 5 (ATG5).Results: 5-HT1A receptor agonist (8-OH-DPAT) increased corneal fluorescein sodium staining spots and 5-HT1A receptor antagonist (WAY-100635) decreased them. Treatment with 8-OH-DPAT was associated with the gene expression of more inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) compared with treatment with WAY-100635. An increased expression of LC3B-I/II and ATG5 was observed in corneal epithelial cells in the mouse model of DED. 8-OH-DPAT significantly enhanced the expression of LC3B-I/II and ATG5 by disrupting ROS levels. WAY-100635 alleviates autophagy by inhibiting ROS production.Conclusion: Excessive ROS release through 8-OH-DPAT induction can lead to impaired autophagy and increased inflammatory response in DED. WAY-100635 reduces corneal epithelial defects and inflammation in DED, as well as alleviates autophagy by inhibiting ROS production. The activation of the 5-HT1A receptor-ROS-autophagy axis is critically involved in DED development.
An Integrated Fibrosis Signature for Predicting Survival and Immunotherapy Efficacy of Patients With Hepatocellular Carcinoma
Authors: Liu Long , Liu Zaoqu , Meng Lingfang , Li Lifeng , Gao Jie , Yu Shizhe , Hu Bowen , Yang Han , Guo Wenzhi , Zhang Shuijun 
Published: December 2021

Introduction: Fibrosis, a primary cause of hepatocellular carcinoma (HCC), is intimately associated with inflammation, the tumor microenvironment (TME), and multiple carcinogenic pathways. Currently, due to widespread inter- and intra-tumoral heterogeneity of HCC, the efficacy of immunotherapy is limited. Seeking a stable and novel tool to predict prognosis and immunotherapy response is imperative.Methods: Using stepwise Cox regression, least absolute shrinkage and selection operator (LASSO), and random survival forest algorithms, the fibrosis-associated signature (FAIS) was developed and further validated. Subsequently, comprehensive exploration was conducted to identify distinct genomic alterations, clinical features, biological functions, and immune landscapes of HCC patients.Results: The FAIS was an independent prognostic predictor of overall survival and recurrence-free survival in HCC. In parallel, the FAIS exhibited stable and accurate performance at predicting prognosis based on the evaluation of Kaplan–Meier survival curves, receiver operator characteristic curves, decision curve analysis, and Harrell’s C-index. Further investigation elucidated that the high-risk group presented an inferior prognosis with advanced clinical traits and a high mutation frequency of TP53, whereas the low-risk group was characterized by superior CD8+ T cell infiltration, a higher TIS score, and a lower TIDE score. Additionally, patients in the low-risk group might yield more benefits from immunotherapy.Conclusion: The FAIS was an excellent scoring system that could stratify HCC patients and might serve as a promising tool to guide surveillance, improve prognosis, and facilitate clinical management.
Effect of Diabetes on Post-stroke Recovery: A Systematic Narrative Review
Authors: Yang Seoyon , Boudier-Revéret Mathieu , Kwon SuYeon , Lee Min Yong , Chang Min Cheol 
Published: December 2021

Background: Patients with stroke often have comorbid diabetes. Considering its detrimental effects on brain function, diabetes may increase the risk of poor recovery.Methods: The aim of this review was to investigate the effect of diabetes on post-stroke recovery by a systematic review. Several specific aspects of post-stroke recovery, including activities of daily living (ADL), motor, cognitive, and quality of life (QOL) recovery, were examined. We searched the PubMed, SCOPUS, Embase, and Cochrane Library databases for relevant studies on the effect of diabetes on post-stroke recovery, published until May 26, 2021. A total of 52,051 potentially relevant articles were identified. After reading the titles and abstracts and assessing their eligibility based on full-text articles, 34 publications were included in this review.Results: Of 29 studies that assessed ADL recovery after stroke, 22 studies suggested that diabetes had a negative effect on recovery of ADL after stroke. Regarding motor recovery, only one out of four studies showed that diabetes had some effect on motor recovery after stroke. Of the two studies on cognitive recovery, one reported that diabetes was an independent predictor of poor cognitive recovery after stroke. Three studies on QOL reported that a poor QOL after stroke was associated with the presence of diabetes.Conclusions: The current review suggests that the post-stroke recovery of ADL seems to be poorer in patients with diabetes than patients without diabetes. Further, there are insufficient data to conclude the effect of diabetes on motor and cognitive recovery, but it may have some influence on the quality of life after stroke.Systematic Review Registration: doi: 10.37766/inplasy2021.11.0032, identifier: INPLASY2021110032.
Genetic Alteration Profiling of Chinese Lung Adenocarcinoma and Its Effect on Targeted Therapy Efficacy
Authors: Liu Jie , Xu Wang-yang , Ye Maosong , Liu Zilong , Li Chun 
Published: December 2021

BackgroundNon-small cell lung cancer (NSCLC) is the most common type of lung cancer and a highly heterogeneous disease with a diversity of phenotypes and genotypes in different populations. The purpose of this study is to investigate oncogenic alterations of lung adenocarcinoma (LUAD) in eastern China and their significance in targeted therapies.MethodsThis study enrolled 101 LUAD patients and used a customized DNA panel to detect molecular alterations. Comprehensive analysis of mutations and clinical application of genomic profiling was carried out.ResultsThe most commonly mutated genes were epidermal growth factor receptor (EGFR) (53%) and tumor protein p53 (TP53) (32%). The less frequently mutated genes were erb-b2 receptor tyrosine kinase 2 (ERBB2) (25%), ATR serine/threonine kinase (ATR) (20%), CCAAT enhancer binding protein alpha (CEBPA) (16%), RB transcriptional corepressor 1 (RB1) (16%), transcription factor 7 like 2 (TCF7L2) (14%), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) (12%) and spectrin alpha, erythrocytic 1 (SPTA1) (12%). Among them, the frequency of ERBB2, ATR, CEBPA, RB1 and TCF7L2 mutations was much higher than that in the databases. Seventy percent of the patients harbored at least one actionable alteration according to the OncoKB evidence. CEBPA mutations affected the efficacy of EGFR-tyrosine kinase inhibitors. ERBB2, CEBPA and TCF7L2 mutated tumors tend to have higher tumor mutation burden (TMB).ConclusionsLUAD patients from eastern China have a unique profile of mutations. The targeted DNA panel is helpful for personalized treatment decision of LUAD patients, and specific mutations may affect the efficacy of targeted therapies.
MRI Radiomic Features: A Potential Biomarker for Progression-Free Survival Prediction of Patients With Locally Advanced Cervical Cancer Undergoing Surgery
Authors: Cai Mengting , Yao Fei , Ding Jie , Zheng Ruru , Huang Xiaowan , Yang Yunjun , Lin Feng , Hu Zhangyong 
Published: December 2021

ObjectivesTo investigate the prognostic role of radiomic features based on pretreatment MRI in predicting progression-free survival (PFS) of locally advanced cervical cancer (LACC).MethodsAll 181 women with histologically confirmed LACC were randomly divided into the training cohort (n = 126) and the validation cohort (n = 55). For each patient, we extracted radiomic features from whole tumors on sagittal T2WI and axial DWI. The least absolute shrinkage and selection operator (LASSO) algorithm combined with the Cox survival analysis was applied to select features and construct a radiomic score (Rad-score) model. The cutoff value of the Rad-score was used to divide the patients into high- and low-risk groups by the X-tile. Kaplan–Meier analysis and log-rank test were used to assess the prognostic value of the Rad-score. In addition, we totally developed three models, the clinical model, the Rad-score, and the combined nomogram.ResultsThe Rad-score demonstrated good performance in stratifying patients into high- and low-risk groups of progression in the training (HR = 3.279, 95% CI: 2.865–3.693, p &lt; 0.0001) and validation cohorts (HR = 2.247, 95% CI: 1.735–2.759, p &lt; 0.0001). Otherwise, the combined nomogram, integrating the Rad-score and patient’s age, hemoglobin, white blood cell, and lymph vascular space invasion, demonstrated prominent discrimination, yielding an AUC of 0.879 (95% CI, 0.811–0.947) in the training cohort and 0.820 (95% CI, 0.668–0.971) in the validation cohort. The Delong test verified that the combined nomogram showed better performance in estimating PFS than the clinical model and Rad-score in the training cohort (p = 0.038, p = 0.043).ConclusionThe radiomics nomogram performed well in individualized PFS estimation for the patients with LACC, which might guide individual treatment decisions.
FOLFOXIRI/Bevacizumab Plus Nivolumab as First-Line Treatment in Metastatic Colorectal Cancer RAS/BRAF Mutated: Safety Run-In of Phase II NIVACOR Trial
Authors: Damato Angela , Bergamo Francesca , Antonuzzo Lorenzo , Nasti Guglielmo , Iachetta Francesco , Romagnani Alessandra , Gervasi Erika , Larocca Mario , Pinto Carmine 
Published: December 2021

The NIVACOR trial is a phase II study assessing the efficacy and safety of nivolumab in combination with FOLFOXIRI/bevacizumab in first-line setting in patients affected by metastatic colorectal cancer (mCRC) RAS/BRAF mutated. We report safety run-in results in the first 10 patients enrolled. Patients received triplet chemotherapy with FOLFOXIRI scheme plus bevacizumab, in association with nivolumab every 2 weeks for 8 cycles (induction phase) followed by bevacizumab plus nivolumab every 2 weeks (maintenance phase), until progression of disease or unacceptable toxicities. The first ten patients were evaluated: 7 experienced at least one adverse event (AE) related to FOLFOXIRI/bevacizumab and 2 related to nivolumab. The most frequent grade 1–2 AEs related to FOLFOXIRI/bevacizumab were diarrhea and fatigue (71%), nausea and vomiting (57%); 3 (43%) had grade 3–4 neutropenia, and 2 (20%) patients developed grade 1–2 AEs nivolumab related: skin rash and salivary gland infection. Two patients delayed the dose because of serious AEs, proteinuria and salivary gland infection; one patient discontinued experimental treatment due to the ileo-urethral fistula and concurrent Clostridium infection diarrhea. No treatment- related death occurred. The safety run-in analysis of NIVACOR trial reassured using co-administration of FOLFOXIRI/bevacizumab and nivolumab was well tolerated with an acceptable toxicity profile.Clinical Trial Registrationhttps://clinicaltrials.gov/, (NCT04072198).
Treatment Dynamics in People Who Initiate Metformin or Sulfonylureas for Type 2 Diabetes: A National Cohort Study
Authors: Wood Stephen , Magliano Dianna J. , Bell J Simon , Shaw Jonathan E. , Ilomäki Jenni 
Published: December 2021

Aim: To investigate the incidence of, and factors associated with addition and switching of glucose-lowering medications within 12-months of initiating metformin or a sulfonylurea for type 2 diabetes (T2D).Methods: We identified 109,573 individuals aged 18–99 years who initiated metformin or a sulfonylurea between July 2013 and April 2015 using Australian National Diabetes Service Scheme (NDSS) data linked with national dispensing data. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CI) for factors associated with time to addition to or switch from metformin or sulfonylurea over a 12-months follow-up.Results: Treatment addition or switching occurred in 18% and 4% of individuals who initiated metformin and in 28% and 13% of individuals who initiated sulfonylureas. Median time to addition was 104 days for metformin and 82 days for sulfonylureas. Median time to switching was 63 days for metformin and 52 days for sulfonylureas. Congestive heart failure, nicotine dependence, end stage renal disease and dispensing of systemic corticosteroids were associated with higher likelihood of treatment additions and switching in individuals initiating metformin. Antipsychotic dispensing was associated with a higher likelihood of treatment addition in individuals initiating sulfonylureas. Women initiating metformin were less likely to receive treatment additions but more likely to switch treatment than men.Conclusion: Nearly one quarter of Australians who initiate treatment for T2D with metformin or sulfonylureas switch or receive additional treatment within 12-months, with those who initiate sulfonylureas more likely to switch or receive additional treatment than those who initiate metformin.
High-Intensity Interval Training and Sprint-Interval Training in National-Level Rowers
Authors: Turner Kirstie Jodie , Pyne David Bruce , Périard Julien D. , Rice Anthony John 
Published: December 2021

Purpose: The effects of two different high-intensity training methods on 2,000 m rowing ergometer performance were examined in a feasibility study of 24 national-level rowers aged 18–27 years (17 males, 2,000 m ergometer time trial 6:21.7 ± 0:14.6 (min:s) and seven females, 2,000 m ergometer 7:20.3 ± 0:12.1. Habitual training for all participants was ~12–16 h per week).Methods: 16 high-intensity ergometer sessions were completed across two 3-week periods. Participants were allocated into two groups according to baseline 2,000 m time. High-intensity interval session-sprint-interval session (HIIT-SIT) completed eight HIIT (8 × 2.5 min intervals; 95% of 2,000 m wattage) followed by eight SIT (three sets of 7 × 30 s intervals; maximum effort). SIT-HIIT completed eight SIT sessions followed by eight HIIT sessions. Both a 2,000-m time trial and a progressive incremental test finishing with 4 min “all-out” performance were completed before and after each 3-week phase.Results: Both groups showed similar improvements in 2,000 m time and 4 min “all-out” distance after the first 3 weeks (2,000 m time: HIIT-SIT: −2.0 ± 0.6%, mean ± 90% CL, p = 0.01; SIT-HIIT: −1.5 ± 0.3%, p = 0.01) with no significant difference between groups. HIIT-SIT demonstrated the greatest improvements in submaximal heart rate (HR) during the progressive incremental test with eight sessions of HIIT showing a greater reduction in submaximal HR than eight sessions of SIT. The net improvement of 16 high-intensity sessions on 2,000 m time was −2.5% for HIIT-SIT (−10.6 ± 3.9 s, p = 0.01) and − 2.2% for SIT-HIIT (−9.0 ± 5.7 s, p = 0.01) and for 4 min “all-out” performance was 3.1% for HIIT-SIT (36 ± 25 m, p = 0.01) and 2.8% for SIT-HIIT (33 ± 27 m, p = 0.01).Conclusion: Eight sessions of high-intensity training can improve 2,000 m ergometer rowing performance in national-level rowers, with a further eight sessions producing minimal additional improvement. The method of high-intensity training appears less important than the dose.