bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal exposure to genistein during pregnancy and oxidative DNA damage in testes of male mouse offspring
Authors: Godschalk Roger W. L. , Janssen Margit C. M. , Vanhees Kimberly , Doorn-Khosrovani Sahar Barjesteh van Waalwijk van , Schooten Frederik-Jan van 
Published: July 2022

BackgroundGenistein is a dietary supplement with phyto-estrogenic properties. Therefore, high intake of genistein during pregnancy may have adverse effects on the genetic integrity of testes and germ cells of male offspring. In this study, we examined whether maternal exposure to genistein during pregnancy induced oxidative DNA damage in the male germline at adolescence.MethodsAtm-ΔSRI mice have lower glucose-6-phosphate dehydrogenase (G6PDH) activity, which is important for maintaining levels of reduced glutathione and therefore these mice have an increased susceptibility to oxidative stress. Parental heterozygous Atm-ΔSRI mice received a genistein-rich or control diet, after which they were mated to obtain offspring. During pregnancy, mothers remained on the respective diets and after delivery all animals received control diets. Redox status and oxidative DNA damage were assessed in testes and sperm of 12 weeks old male offspring. Gene expression of Cyp1b1, Comt, and Nqo1 was assessed in testes, and DNA methylation as possible mechanism for transmission of effects to later life.ResultsIntake of genistein during pregnancy increased oxidative DNA damage in testes of offspring, especially in heterozygous Atm-ΔSRI mice. These increased DNA damage levels coincided with decreased expression of Comt and Nqo1. Heterozygous Atm-ΔSRI mice had higher levels of DNA strand breaks in sperm compared to wild type littermates, and DNA damage was further enhanced by a genistein-rich maternal diet. G6PDH activity was higher in mice with high maternal intake of genistein compared to control diets, suggesting compensation against oxidative stress. A positive correlation was observed between the levels of DNA methylation and oxidative DNA damage in testes.ConclusionThese data indicate that prenatal exposure to genistein altered gene expression and increased DNA damage in testes and sperm of adolescent male offspring. These effects of genistein on DNA damage in later life coincided with alterations in DNA methylation.
The effect of urinary essential and non-essential elements on serum albumin: Evidence from a community-based study of the elderly in Beijing
Authors: Li Ang , Zhou Quan , Mei Yayuan , Zhao Jiaxin , Liu Liu , Zhao Meiduo , Xu Jing , Ge Xiaoyu , Xu Qun 
Published: July 2022

Background &amp; aimsFew epidemiological studies have investigated the relationships of urinary essential and non-essential elements with serum albumin, an indicator of nutritional status, especially for the elderly in China.MethodsA community-based study among elderly participants (n = 275) was conducted in Beijing from November to December 2016. We measured 15 urinary elements concentrations and serum albumin levels. Three statistical methods including the generalized linear model (GLM), quantile g-computation model (qgcomp) and bayesian kernel machine regression (BKMR) were adapted.ResultsIn GLM analysis, we observed decreased serum albumin levels associated with elevated urinary concentrations of aluminum, arsenic, barium, cobalt, chromium, copper, iron, manganese, selenium, strontium, and zinc. Compared with the lowest tertile, the highest tertile of cadmium and cesium was also negatively associated with serum albumin. Urinary selenium concentration had the most significant negative contribution (30.05%) in the qgcomp analysis. The negative correlations of element mixtures with serum albumin were also observed in BKMR analysis.ConclusionsOur findings suggested the negative associations of essential and non-essential elements with serum albumin among the elderly. Large-scare cohort studies among the general population are required to validate our findings and elucidate the relevant underlying mechanisms.
The Predictive Value of Pretreatment Lactate Dehydrogenase and Derived Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Patients Treated With PD-1/PD-L1 Inhibitors: A Meta-Analysis
Authors: Zhang Qianning , Gong Xiaoling , Sun Lei , Miao Liyun , Zhou Yujie 
Published: July 2022

BackgroundThe Lung Immune Prognostic Index (LIPI) combines the lactate dehydrogenase (LDH) level and the derived neutrophil-to-lymphocyte ratio (dNLR). A lot of studies have shown that LDH and dNLR are associated with the prognosis of advanced non-small cell lung cancer (NSCLC) in patients treated with programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. However, previous results were inconsistent, and the conclusions remain unclear. This meta-analysis aimed to investigate the predictive value of pretreatment LDH and dNLR for NSCLC progression in patients treated with PD-1/PD-L1 inhibitors.MethodsPubMed, Embase, and the Cochrane Library were searched by two researchers independently for related literature before March 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) were extracted to assess the predictive value of LDH and dNLR. STATA 15. 0 was used to perform the meta-analysis.ResultsA total of 3,429 patients from 26 studies were included in this meta-analysis. The results revealed that high pretreatment LDH was related to poor OS (HR = 1.19, 95%CI = 1.11–1.24, p &lt; 0.001), but not closely related to poor PFS (HR = 1.02, 95%CI = 1.00–1.04, p = 0.023 &lt; 0.05). The pooled results for dNLR suggested that high pretreatment dNLR was related to poor OS (HR = 1.55, 95%CI = 1.33–1.80, p &lt; 0.001) and PFS (HR = 1.33, 95%CI = 1.16–1.54, p &lt; 0.001).ConclusionBoth pretreatment LDH and dNLR have the potential to serve as peripheral blood biomarkers for patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors. However, more studies on LDH are needed to evaluate its predictive value for PFS in patients with NSCLC.
Efficacy and Safety of Minimally Invasive Surgery Versus Open Laparotomy for Interval Debulking Surgery of Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: A Systematic Review and A Meta-Analysis
Authors: Zeng Siyuan , Yu Yongai , Cui Yuemei , Liu Bing , Jin Xianyu , Li Zhengyan , Liu Lifeng 
Published: July 2022

ObjectiveThe selection of minimally invasive surgery (MIS) or open laparotomy for ovarian cancer (OC) after neoadjuvant chemotherapy still remains controversial. This study aimed to assess the efficacy and safety of MIS versus open laparotomy following neoadjuvant chemotherapy for advanced OC, so as to provide another option to select optimal surgical procedures for patients with OC.MethodsRelevant literature studies about the risks of progression or mortality between women receiving MIS and open laparotomy for interval debulking surgery (IDS) were searched in the online databases, including PubMed, Embase, and the Cochrane Library with the following keywords: “ovarian neoplasms”, “minimally invasive surgical procedures”, “laparotomy”, and “neoadjuvant therapy”. Eligible studies were screened out for further meta-analysis.ResultsSix eligible literature studies, with 643 patients in the MIS group and 2,885 patients in the open laparotomy group, were included in this meta-analysis. No significant differences were detected in the overall survival (OS) of patients with OC who were treated with MIS or open laparotomy [hazard ratio (HR) = 0.85; 95% confidence interval (CI) = 0.59–1.23; heterogeneity: P = 0.051, I2 = 57.6%]. However, the progression-free survival (PFS) was significantly higher in patients with OC treated with MIS than those treated with laparotomy (HR = 0.73; 95% CI = 0.57 to 0.92; heterogeneity: P = 0.276, I2 = 22.4%). The completeness of debulking removal (R0 rate) in the open laparotomy group was not statistically higher compared with the control group (RR = 1.07; 95% CI = 0.93 to 1.23; heterogeneity: P = 0.098, I2 = 52.3%), and no significant differences in residual disease of ≤1 cm (R1) (RR = 1.08; 95% CI = 0.91 to 1.28; heterogeneity: P = 0.330, I2 = 12.6%) and postoperative complications were found between the two groups (RR = 0.72; 95% CI = 0.34 to 1.54; heterogeneity: P = 0.055, I2 = 60.6%). Furthermore, the length of stays in hospital was significantly shorter in patients with OC treated with MIS than those treated with open laparotomy (Standard Mean Difference (SMD) = −1.21; 95% CI = −1.78 to −0.64; heterogeneity: P &lt; 0.001, I2 = 92.7%].ConclusionsFor IDS after NACT in patients with advanced OC, complete cytoreductive surgery with MIS is another feasible and effective choiceSystematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022298519, identifier CRD42022298519
Predictors predisposing to orocutaneous fistula occurrence following free flap reconstruction
Authors: Li Wenlu , Wu Shuang , Yuan Junhui , Meng Fan , Xu Chunmiao , Li Hailiang 
Published: July 2022

ObjectivesTo explore the possible risk factors of orocutaneous fistula (OCF) development in free flap reconstruction of the tongue/floor of the mouth (TFOM).MethodsData of patients who underwent free flap reconstruction of the TFOM were retrospectively analyzed. The association between clinicopathologic variables and OCF occurrence was analyzed using univariate and multivariate analyses.ResultsAltogether, 469 patients were enrolled. OCF occurred in 43 patients with a rate of 9.2%. The univariate analysis revealed the negative effects of smoking, preoperative albumin level, cachexia, T4 stage, neck dissection, entire resection of the floor of the mouth (FOM), segmental mandibulectomy, and surgical site infection on OCF occurrence. The multivariate analysis confirmed the independence of cachexia (p&lt;0.001, 4.386[1.883–9.472]), tumor stage (p&lt;0.001, 2.738[1.482–6.629]), entire FOM resection (p&lt;0.001, 6.332[2.110–14.432]), and surgical site infection (p&lt;0.001, 5.376[1.998–11.218]) in affecting the OCF development.ConclusionsOCF development following free flap reconstruction of the TFOM was relatively uncommon, but significantly associated with presence of cachexia, T4 stage, entire FOM resection, and surgical site infection.
Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology
Authors: Chiu Peter K. F. , Lee Eric K. C. , Chan Marco T. Y. , Chan Wilson H. C. , Cheung M. H. , Lam Martin H. C. , Ma Edmond S. K. , Poon Darren M. C. 
Published: July 2022

BackgroundIn recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations.MethodsA joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose “Accept Completely” (Option A) or “Accept with Some Reservation” (Option B).ResultsThe consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients.ConclusionThis consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications.
Prevalence of osteopathologies in a single center cohort of survivors of childhood primary brain tumor
Authors: Schündeln Michael M. , Fritzemeier Sebastian , Goretzki Sarah C. , Hauffa Pia K. , Munteanu Martin , Kiewert Cordula , Hauffa Berthold P. , Fleischhack Gudrun , Tippelt Stephan , Grasemann Corinna 
Published: July 2022

BackgroundChildhood primary brain tumors (CPBT) are the second largest group of childhood malignancies and associated with a high risk for endocrine late effects.ObjectiveTo assess endocrine late effects and their relevance for the development of osteopathologies in survivors.MethodsThis single center cross sectional study investigated data from 102 CPBT survivors with a mean age of 13.0 years and a mean age at diagnosis of 8.7 years. Clinical, biochemical, radiographic, and anamnestic data regarding endocrine and bone health were obtained at study visits. In addition, data regarding tumor stage and therapy was obtained by chart review. An expert opinion was applied to define presence of osteopathologies.ResultsImpaired bone health, defined by at least one pathological screening parameter, was present in 65% of patients. 27.5% were found to have overt osteopathologies per expert opinion. 37.8% displayed a severe vitamin D deficiency (25-OH vitamin D &lt; 10 ng/ml) and 11% a secondary hyperparathyroidism. Patients with osteopathologies had lower 25-OH vitamin D levels compared to patients without osteopathologies. Multiple endocrine late effects were present: diabetes insipidus in 10.8%, aberrant pubertal development in 13.7%, central hypocortisolism in 14.9%, thyroid dysfunction in 23.8% and growth hormone deficiency in 21.8%. A total of 31.3% of survivors displayed any endocrinopathy. Tumors located near hypothalamic structures and patients who received irradiation had a higher likelihood of endocrine morbidity.ConclusionThis study indicates that endocrine deficiencies are common in pediatric survivors of CPBTs. Osteopathologies are present in this cohort. A prominent effect of hormonal deficiencies on bone health was not detected, possibly because patients were sufficiently treate for their endocrine conditions or indicating resilience of the childhood bone remodeling process. Vitamin D deficiency is frequent and should be treated as recommended.
Frequencies, Modalities, Doses and Duration of Computerized Prescriptions for Sedative, Analgesic, Anesthetic and Paralytic Drugs in Neonates Requiring Intensive Care: A Prospective Pharmacoepidemiologic Cohort Study in 30 French NICUs From 2014 to 2020
Authors: Tauzin Manon , Gouyon Béatrice , Hirt Déborah , Carbajal Ricardo , Gouyon Jean-Bernard , Brunet Anne-Claire , Ortala Matthieu , Goro Seydou , Jung Camille , Durrmeyer Xavier 
Published: July 2022

Objectives: No consensus exists about the doses of analgesics, sedatives, anesthetics, and paralytics used in critically ill neonates. Large-scale, detailed pharmacoepidemiologic studies of prescription practices are a prerequisite to future research. This study aimed to describe the detailed prescriptions of these drug classes in neonates hospitalized in neonatal intensive care units (NICU) from computerized prescription records and to compare prescriptions by gestational age.Materials and Methods: We included all neonates requiring intensive care in 30 French level III units from 2014 through 2020 with a computerized prescription for an analgesic, sedative, anesthetic, or paralytic agent. We described frequencies of prescription, methods of administration, concomitant drug prescriptions, and dosing regimen, and compared them across gestational ages.Results: Among 65,555 neonates, 29,340 (44.8%) were prescribed at least one analgesic (acetaminophen in 37.2% and opioids in 17.8%), sedative (9.8%), anesthetic (8.5%), and/or paralytic agent (1%). Among preterm infants born before 28 weeks, 3,771/4,283 (88.0%) were prescribed at least one of these agents: 69.7% opioids, 41.2% sedatives, 32.5% anesthetics, and 5.8% paralytics. The most frequently prescribed agents were sufentanil (in 10.3% of neonates) and morphine (in 8.0% of neonates) for opioids, midazolam (9.3%) for sedatives, ketamine (5.7%) and propofol (3.3%) for anesthetics. In most neonates, opioids and sedatives were prescribed as continuous infusion, whereas anesthetics were prescribed as single doses. Opioids, sedatives and paralytics were mostly prescribed in association with another agent. Doses varied significantly by gestational age but within a limited range. Gestational age was inversely related to the frequency, cumulative dose and duration of prescriptions. For example, morphine prescriptions showed median (IQR) cumulative doses of 2601 (848–6750) vs. 934 (434–2679) µg/kg and median (IQR) durations of 7 (3–15) vs. 3 (2–5) days in infants born &lt;28 vs. ≥ 37 weeks of gestation, respectively (p-value&lt;0.001).Conclusion: The prescriptions of analgesic, sedative, anesthetic, or paralytic agent were frequent and often combined in the NICU. Lower gestational age was associated with higher frequencies, longer durations and higher cumulative doses of these prescriptions. Dose-finding studies to determine individualized dosing regimens and studies on long-term neurodevelopmental outcome according to received cumulative doses are required.
(±)-5-bromo-2-(5-fluoro-1-hydroxyamyl) Benzoate Protects Against Oxidative Stress Injury in PC12 Cells Exposed to H2O2 Through Activation of Nrf2 Pathway
Authors: Qi Saidan , Zhang Xiaojiao , Fu Zhenzhen , Pi Anran , Shi Feiyan , Fan Yanan , Zhang Jiahua , Xiao Tingting , Shang Dong , Lin Meng , Gao Na , Chang Junbiao , Gao Yuan 
Published: July 2022

Background: Oxidative stress is associated with the pathogenesis of ischemic stroke (±)-5-bromo-2-(5-fluoro-1-hydroxyamyl) benzoate (BFB) is a novel compound modified by dl-3-n-butylphthalide (NBP). Here, we hypothesized that BFB may protect the PC12 cells against H2O2-induced oxidative stress injury through activation of the Nrf2 pathway.Methods: We measured the cell viability and levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) to determine the construction of the H2O2-induced models of oxidative stress in PC12 cells. Additionally, apoptotic cell death, mitochondrial membrane potential, and cellular morphology were examined to determine the effect of BFB on oxidative stress injury in H2O2-treated PC12 cells. The expression levels of Nrf2-related and autophagy-related genes and proteins were detected using real time quantative PCR (RT-qPCR), Western Blot, and immunofluorescence analyses.Results: Our study showed that BFB treatment reduced the elevated levels of MDA, LDH, and ROS, and decreased cell viability and GSH in H2O2-treated PC12 cells. We also observed the elevated expression of Nrf2 pathway-related factors and intranuclear transitions and found that Nrf2 inhibitors (ML385) could block the protective effect of BFB. The inhibitory effect of BFB on oxidative stress may be partially regulated by Nrf2 activation, and the initiation and induction of autophagy.Conclusion: BFB inhibited H2O2-induced oxidative stress injury in PC12 cells by activating the Nrf2 pathway, initiating and inducing autophagy, suggesting that BFB may be a promising therapeutic agent in treating neurological disorders like cerebral ischemia.
Challenges and Opportunities for Companies to Build HTA/Payer Perspectives Into Drug Development Through the Use of a Dynamic Target Product Profile
Authors: Wang Ting , McAuslane Neil , Goettsch Wim G. , Leufkens Hubert G. M. , De Bruin Marie L. 
Published: July 2022

Background: The target product profile (TPP) outlines the desired profile of a target product aimed at a particular disease and is used by companies to plan clinical development. Considering the increasing importance of health technology assessment (HTA) in informing reimbursement decisions, a robust TPP needs to be built to address HTA needs, to guide an integrated evidence generation plan that will support HTA submissions. This study assessed current practices and experiences of companies in building HTA considerations into TPP development.Methods: An opinion survey was designed and conducted in 2019, as a cross-sectional questionnaire consisting of multiple-choice questions. The questionnaire provided a qualitative assessment of companies’ strategies and experiences in building HTA considerations into the TPP. Eligible survey participants were the senior management of Global HTA/Market Access Departments at 18 top international pharmaceutical companies.Results: 11 companies responded to the survey. All companies included HTA requirements in TPP development, but the timing and process varied. The key focus of HTA input related to health problems and treatment pathways, clinical efficacy/effectiveness, and safety. Variance of HTA methods and different value frameworks were identified as a challenge for development plans. Stakeholder engagement, such as HTA scientific advice, was used to pressure test the TPP.Conclusion: This research provides insight into current practice and potential opportunities for value-based drug development. It demonstrates the evolution of the TPP to encompass HTA requirements and suggests that the TPP could have a role as an iterative communication tool for use with HTA agencies to enhance an integrated evidence generation plan.
The Impact of COVID-19 and Muscle Fatigue on Cardiorespiratory Fitness and Running Kinetics in Female Recreational Runners
Authors: Jafarnezhadgero Amir Ali , Noroozi Raha , Fakhri Ehsan , Granacher Urs , Oliveira Anderson Souza 
Published: July 2022

Background: There is evidence that fully recovered COVID-19 patients usually resume physical exercise, but do not perform at the same intensity level performed prior to infection. The aim of this study was to evaluate the impact of COVID-19 infection and recovery as well as muscle fatigue on cardiorespiratory fitness and running biomechanics in female recreational runners.Methods: Twenty-eight females were divided into a group of hospitalized and recovered COVID-19 patients (COV, n = 14, at least 14 days following recovery) and a group of healthy age-matched controls (CTR, n = 14). Ground reaction forces from stepping on a force plate while barefoot overground running at 3.3 m/s was measured before and after a fatiguing protocol. The fatigue protocol consisted of incrementally increasing running speed until reaching a score of 13 on the 6–20 Borg scale, followed by steady-state running until exhaustion. The effects of group and fatigue were assessed for steady-state running duration, steady-state running speed, ground contact time, vertical instantaneous loading rate and peak propulsion force.Results: COV runners completed only 56% of the running time achieved by the CTR (p &lt; 0.0001), and at a 26% slower steady-state running speed (p &lt; 0.0001). There were fatigue-related reductions in loading rate (p = 0.004) without group differences. Increased ground contact time (p = 0.002) and reduced peak propulsion force (p = 0.005) were found for COV when compared to CTR.Conclusion: Our results suggest that female runners who recovered from COVID-19 showed compromised running endurance and altered running kinetics in the form of longer stance periods and weaker propulsion forces. More research is needed in this area using larger sample sizes to confirm our study findings.