bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organophosphate‐pesticides induced survival mechanisms and APE1‐mediated Nrf2 regulation in non‐small‐cell lung cancer cells
Authors: Thakur Shweta , Sarkar Bibekananda , Dhiman Monisha , Mantha Anil K. 
Published: October 2020

AbstractEpidemiological and molecular studies have indicated that environmental exposure to organophosphate pesticides (OPPs) is associated with increased cancer risk; however, the underlying molecular mechanisms still need to be explained. Increasing cancer incidence is linked to OPPs‐induced oxidative stress (OS). Our study evaluates monocrotophos (MCP) and chlorpyrifos (CP)‐induced OS responses and apurinic/apyrimidinic endonuclease 1 (APE1) role in human non‐small‐cell lung cancer (NSCLC) cells. Our prior study has implicated OPPs‐induced base excision repair (BER)‐pathway dysregulation and APE1‐mediated regulation of transcription factor (TF) c‐jun in A549 cells. We further investigated the effects of MCP and CP on apoptosis, proliferation, and APE1's redox‐regulation of nuclear factor‐like 2 (Nrf2). Data demonstrates that MCP and CP at subtoxic concentrations induced reactive oxygen species generation and oxidative DNA base damage 8‐oxo‐dG lesions in NCI‐H1299 cells. CP moderately upregulated the apoptosis‐inducing factor (AIF) in A549 cells, however, it did not trigger other pro‐apoptotic factors viz. caspase‐9 and caspase‐3, suggesting early caspase‐independent apoptosis. However, dose‐dependent AIF‐downregulation was observed for MCP treatment. Furthermore, CP and MCP treatments upregulated proliferating cell nuclear antigen levels. Immunofluorescent confocal imaging showed the colocalization of APE1 with Nrf2 in 10 µM CP‐ and MCP‐treated NCI‐H1299 cells. Immunoprecipitation confirmed that APE1 and Nrf2 physically interacted, indicating the role of APE1‐mediated Nrf2 activation following OPPs treatment. This study suggests that low concentration MCP and CP exposure generates OS along with DNA damage, and modulates apoptosis, and APE1‐mediated Nrf2 activation, which might be considered as the possible mechanism promoting lung cancer cell survival, suggesting that APE1 may have the potential to become a therapeutic target for the treatment of NSCLC.
Negative affect interference and fear of happiness are independently associated with depressive symptoms
Authors: Jordan D. Gage , Collins Amanda C. , Dunaway Matthew G. , Kilgore Jenna , Winer E. Samuel 
Published: October 2020

AbstractObjectivesReward devaluation theory (RDT) posits that some depressed individuals avoid positivity due to its previous association with negative outcomes. Behavioral indicators of avoidance of reward support RDT, but self‐report indicators have yet to be examined discriminantly. Two candidate self‐report measures were examined in relation to depression: negative affect interference (NAI), or the experience of negative affect in response to positivity, and fear of happiness, a fear of prospective happiness.MethodParticipants completed measures assessing NAI, fear of happiness scale, and depression online via Amazon's Mechanical Turk at three time points (N = 375). Multilevel modeling examined the relationship between NAI, fear of happiness, and depressive symptoms longitudinally.ResultsNAI and fear of happiness were both positively associated with depressive symptoms. They both uniquely predicted depressive symptoms when included within the same model.ConclusionsThese findings suggest that different conceptualizations of positivity avoidance are uniquely associated with depressive symptoms.
Epigenetic regulation of angiogenesis in lung cancer
Authors: Tan Heng Wee , Xu Yan‐Ming , Qin San‐Hai , Chen Guo‐Feng , Lau Andy T. Y. 
Published: October 2020

AbstractLung cancer is the leading cause of cancer‐related deaths worldwide, in which angiogenesis is highly required for lung cancer cell growth and metastasis. Genetic regulation of this multistep process is being studied extensively, however, relatively less is known about the epigenetic regulation of angiogenesis in lung cancer. Several epigenetic alterations contribute to regulating angiogenesis, such as epimodifications of DNA, posttranslational modification of histones, and expression of noncoding RNAs. Here, we review the current knowledge of the epigenetic regulation of angiogenesis and discuss the potential clinical applications of epigenetic‐based anticancer therapy in lung cancer. Overall, epigenetic‐based therapy will likely emerge as a prominent approach to treat lung cancer in the future.
Cancer‐associated mutations in the condensin II subunit CAPH2 cause genomic instability through telomere dysfunction and anaphase chromosome bridges
Authors: Weyburne Emily , Bosco Giovanni 
Published: October 2020

AbstractGenome instability in cancer drives tumor heterogeneity, undermines the success of therapies, and leads to metastasis and recurrence. Condensins are conserved chromatin‐binding proteins that promote genomic stability, mainly by ensuring proper condensation of chromatin and mitotic chromosome segregation. Condensin mutations are found in human tumors, but it is not known how or even if such mutations promote cancer progression. In this study, we focus on condensin II subunit CAPH2 and specific CAPH2 mutations reported to be enriched in human cancer patients, and we test how CAPH2 cancer‐specific mutations may lead to condensin II complex dysfunction and contribute to genome instability. We find that R551P, R551S, and S556F mutations in CAPH2 cause genomic instability by causing DNA damage, anaphase defects, micronuclei, and chromosomal instability. DNA damage and anaphase defects are caused primarily by ataxia telangiectasia and Rad3‐related‐dependent telomere dysfunction, as anaphase bridges are enriched for telomeric repeat sequences. We also show that these mutations decrease the binding of CAPH2 to the ATPase subunit SMC4 as well as the rest of the condensin II complex, and decrease the amount of CAPH2 protein bound to chromatin. Thus, in vivo the R551P, R551S, and S556F cancer‐specific CAPH2 mutant proteins are likely to impair condensin II complex formation, impede condensin II activity during mitosis and interphase, and promote genetic heterogeneity in cell populations that can lead to clonal outgrowth of cancer cells with highly diverse genotypes.
Target‐Mediated Drug Disposition—A Class Effect of Soluble Epoxide Hydrolase Inhibitors
Authors: An Guohua , Lee Kin Sing Stephen , Yang Jun , Hammock Bruce D. 
Published: October 2020

AbstractPharmacological target‐mediated drug disposition (TMDD) represents a special source of nonlinear pharmacokinetics, and its occurrence in large‐molecule compounds has been well recognized because numerous protein drugs have been reported to have TMDD due to specific binding to their pharmacological targets. Although TMDD can also happen in small‐molecule compounds, it has been largely overlooked. In this mini‐review, we summarize the occurrence of TMDD that we discovered recently in a series of small‐molecule soluble epoxide hydrolase (sEH) inhibitors. Our journey started with an accidental discovery of target‐mediated kinetics of 1‐(1‐propanoylpiperidin‐4‐yl)‐3‐[4‐(trifluoromethoxy)phenyl]urea (TPPU), a potent sEH inhibitor, in a pilot clinical study. To confirm what we observed in humans, we conducted a series of mechanism experiments in animals, including pharmacokinetic experiments using sEH knockout mice as well as in vivo displacement experiments with co‐administration of another potent sEH inhibitor. Our mechanism studies confirmed that the TMDD of TPPU is due to its pharmacological target sEH. We further expanded our evaluation to various other sEH inhibitors and found that TMDD is a class effect of this group of small‐molecule sEH inhibitors. In addition to summarizing the occurrence of TMDD in sEH inhibitors, in this mini‐review we also highlighted the importance of recognizing TMDD of small‐molecule compounds and its impact in clinical development as well as using pharmacometric modeling in facilitating quantitative understanding of TMDD.
Characteristics of medical malpractice claims involving emergency medicine physicians
Authors: Myers Laura C. , Einbinder Jonathan , Camargo Carlos A. , Aaronson Emily L. 
Published: October 2020

BackgroundIdentifying characteristics of malpractice claims involving emergency medicine (EM) physicians allows leaders to develop patient safety initiatives to prevent future harm events.MethodsA retrospective study was performed of paid/unpaid claims closed 2007 to 2016 from Comparative Benchmarking System. Claims were identified by physician specialty involved (EM, internal medicine, general surgery). Various characteristics were compared by physician specialty. Multivariable regression was performed to identify factors associated with claim payment, in which (1) physician specialty was included as a predictor and (2) only the subset involving EM physicians was analyzed.ResultsOf 54,772 claims, 2760 involved EM physicians, 5886 involved internists, and 3207 involved surgeons. Death was the most common severity among EM claims (34%). Diagnosis‐related allegations accounted for 58%, higher than 42% and 11% of claims involving internists and surgeons, respectively (P < 0.0001). Thirty‐one percent was paid. The median indemnity paid on behalf of any defendant was $206,261 (interquartile range $55,065‐527,651). The most common final diagnoses were myocardial infarction (2%), pulmonary embolus (2%), and cardiac arrest (2%). Procedure‐related claims were associated with increased payment likelihood (odds ratio 1.21, 95% confidence interval 1.10‐1.34).ConclusionMalpractice claims in EM are often diagnosis‐ or procedure related. Our findings suggest that diagnostic accuracy and procedural competency should shape future quality improvement work.
Impact of social distancing on incidence of vaccine‐preventable diseases, South Korea
Authors: Yun Hyo Eun , Ryu Bo Young , Choe Young June 
Published: October 2020

AbstractWhile vaccination remains the cornerstone of controlling vaccine‐preventive diseases (VPD), little is known about the effect of social distancing on incidence of VPDs. We investigated the impact of social distancing practiced during the coronavirus disease 2019 (COVID‐19) pandemic on the incidence of selected VPDs in South Korea. National surveillance data on monthly incidence of hepatitis A, hepatitis B, varicella, mumps, invasive pneumococcal disease (IPD), and pertussis were retrieved and compared the VPD incidences in 2020 to the average of the last 4 years (2015–2019) of the corresponding months. In 2020, there were 44% decline for mumps, 44% decline for varicella, 28% decline for pertussis, 22% decline for IPD, 14% decline in incidence of hepatitis A, and no change for hepatitis B incidences, compared to baseline years (2015–2019). The largest decline of total VPDs was in April (65%) and in May (67%), during the intensified social distancing measures. In the setting of sustained vaccination coverage, social distancing may provide additional public health benefit in controlling the VPDs.
Time‐restricted feeding prevents depressive‐like and anxiety‐like behaviors in male rats exposed to an experimental model of shift‐work
Authors: Guerrero‐Vargas Natalí N. , Zárate‐Mozo Carmen , Guzmán‐Ruiz Mara A. , Cárdenas‐Rivera Alfredo , Escobar Carolina 
Published: October 2020

AbstractIndividuals who regularly shift their sleep timing, like night and/or shift‐workers suffer from circadian desynchrony and are at risk of developing cardiometabolic diseases and cancer. Also, shift‐work is are suggested to be a risk factor for the development of mood disorders such as the burn out syndrome, anxiety, and depression. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental health effects associated with circadian disruption. Here, we explored whether adult male Wistar rats exposed to an experimental model of shift‐work (W‐AL) developed depressive and/or anxiety‐like behaviors and whether this was associated with neuroinflammation in brain areas involved with mood regulation. We also tested whether time‐restricted feeding (TRF) to the active phase could ameliorate circadian disruption and therefore would prevent depressive and anxiety‐like behaviors as well as neuroinflammation. In male Wistar rats, W‐AL induced depressive‐like behavior characterized by hypoactivity and anhedonia and induced increased anxiety‐like behavior in the open field test. This was associated with increased number of glial fibrillary acidic protein and IBA‐1‐positive cells in the prefrontal cortex and basolateral amygdala. Moreover W‐AL caused morphological changes in the microglia in the CA3 area of the hippocampus indicating microglial activation. Importantly, TRF prevented behavioral changes and decreased neuroinflammation markers in the brain. Present results add up evidence about the importance that TRF in synchrony with the light–dark cycle can prevent neuroinflammation leading to healthy mood states in spite of circadian disruptive conditions.
Migraine and risk of sudden sensorineural hearing loss: A systematic review and meta‐analysis
Authors: Mohammadi Masoud , Taziki Balajelini Mohammad Hosein , Rajabi Abdolhalim 
Published: October 2020

AbstractObjectiveThe pathophysiology of idiopathic sudden sensorineural hearing loss (SSNHL) is poorly understood. This study aimed to explore the association of migraine and risk of SSNHL in a meta‐analysis of population‐based cohort studies.MethodsA systematic literature search of studies published until December 2019 was carried out in Medline, Embase, Scopus, Web of Science, and Google Scholar using appropriate keywords. References of the retrieved articles were also examined for inclusion. Random‐effects meta‐analysis was performed by calculating pooled hazard ratio (HR) and associated 95% confidence interval (CI) using the DerSimonian and Laird method while considering conceptual heterogeneity.ResultsThree eligible cohort studies, with 282 250 participants, were included. In total, 56 450 had migraine, and 225 800 had no migraine. Of those with migraine, 0.88% had SSNHL, and among those without migraine, 0.59% had SSNHL. Pooled HR for the risk of SSNHL was 1.84 (95% CI: 1.11‐2.57; P < .001). In cohort studies on females, migraine was not significantly the risk of SSHL than no migraine. However, in male cohort studies, the migraine had a higher risk of SSHL than no migraine (HR = 1.50; 95% CI: 1.17‐1.83; P < .001). The pooled HR of migraine with the risk of SSNHL was 1.37 (95% CI: 1.16‐1.58, P < .001) in people with <40 years old and 1.39 (95% CI: 1.17‐1.60; P < .001) in people >40 years old.ConclusionsIndividuals with migraine patients are at a higher risk of developing SSHL. Different age and sex migraine subgroups showed a higher proportion of SSNHL cases compared to nonmigraineurs.
Electrospinning for the manufacture of biosensor components: A mini‐review
Authors: Ahmed Jubair 
Published: October 2020

AbstractOne of the key modern advancements of the biomaterial's world has been the recent progress with fibre manufacturing techniques which have allowed for novel approaches to biosensor fabrication. Electrospinning is capable of producing ultrafine and highly tailored fibres that can be made from a wide variety of natural and synthetic materials to be exploited for use as medical sensors. In recent years, electrospinning has been more widely researched and great strides have been made in its ability to produce fibres with more desirable properties. In this mini‐review, the process of electrospinning is overviewed with an emphasis on its properties in producing biosensor components. It is seen how the advancements of nanotechnology allows for easier incorporation of bioreceptors to a larger range of membranes that are capable of higher sensitivity and broader applications. Furthermore, newer manufacturing techniques that are also capable of producing ultra‐thin fibres are elaborated and the future of biosensor production in taking advantage of micro‐ and nano‐scaled components are discussed.
Free‐breathing simultaneous myocardial T1 and T2 mapping with whole left ventricle coverage
Authors: Guo Rui , Cai Xiaoying , Kucukseymen Selcuk , Rodriguez Jennifer , Paskavitz Amanda , Pierce Patrick , Goddu Beth , Thompson Richard B. , Nezafat Reza 
Published: October 2020

PurposeTo develop a free‐breathing sequence, that is, Multislice Joint T1‐T2, for simultaneous measurement of myocardial T1 and T2 for multiple slices to achieve whole left‐ventricular coverage.MethodsMultislice Joint T1‐T2 adopts slice‐interleaved acquisition to collect 10 single‐shot electrocardiogram‐triggered images for each slice prepared by saturation and T2 preparation to simultaneously estimate myocardial T1 and T2 and achieve whole left‐ventricular coverage. Prospective slice‐tracking using a respiratory navigator and retrospective image registration are used to reduce through‐plane and in‐plane motion, respectively. Multislice Joint T1‐T2 was validated through numerical simulations and phantom and in vivo experiments, and compared with saturation‐recovery single‐shot acquisition and T2‐prepared balanced Steady‐State Free Precession (T2‐prep SSFP) sequences.ResultsPhantom T1 and T2 from Multislice Joint T1‐T2 had good accuracy and precision, and were insensitive to heart rate. Multislice Joint T1‐T2 yielded T1 and T2 maps of nine left‐ventricular slices in 1.4 minutes. The mean left‐ventricular T1 difference between saturation‐recovery single‐shot acquisition and Multislice Joint T1‐T2 across healthy subjects and patients was 191 ms (1564 ± 60 ms versus 1373 ± 50 ms; P < .05) and 111 ms (1535 ± 49 ms vs 1423 ± 49 ms; P < .05), respectively. The mean difference in left‐ventricular T2 between T2‐prep SSFP and Multislice Joint T1‐T2 across healthy subjects and patients was −6.3 ms (42.4 ± 1.4 ms vs 48.7 ± 2.5; P < .05) and −5.7 ms (41.6 ± 2.5 ms vs 47.3 ± 2.7; P < .05), respectively.ConclusionMultislice Joint T1‐T2 enables quantification of whole left‐ventricular T1 and T2 during free breathing within a clinically feasible scan time of less than 2 minutes.
Attitudes and beliefs of nurses and physicians about managing sexual health in primary care: A multi‐site cross‐sectional comparative study
Authors: Leyva‐Moral Juan M. , Aguayo‐Gonzalez Mariela , Palmieri Patrick A. , Guevara‐Vasquez Genesis , Granel‐Grimenez Nina , Dalfó‐Pibernat Artur 
Published: October 2020

AbstractAimTo understand the attitudes and beliefs of nurses and physicians about managing the sexual health of patients during office visits in primary care centres.DesignA questionnaire‐based, cross‐sectional multi‐centre study.MethodsThe study was performed in 15 primary care centres in Barcelona (Spain), from December 2017–February 2018. Obtained data were analysed with descriptive and bivariate statistics.ResultsNearly half the participants believed they should manage sexual health in primary care, but a third of them disagreed this is a priority. Participants also believed patients are not comfortable speaking with them about sex. Statistically significant differences were observed between the professions as nurses more often reported receiving sexual health questions from patients and believed they had enough knowledge to appropriately respond. Most participants wanted additional education to speak with patients more comfortably and confidently about sex.
Analysis of the US FDA adverse event reporting system to identify adverse cardiac events associated with hydroxychloroquine in older adults
Authors: Nishtala Prasad S. , Gill Sakirat , Chyou Te‐yuan 
Published: October 2020

AbstractPurposeThe purpose of this study is to analyze the US FDA Adverse Event Reporting System (FAERS) to identify adverse cardiac events of hydroxychloroquine in older adults.MethodA case/non‐case method was used to determine adverse events associated with hydroxychloroquine as the primary suspect drug between January 1, 2004, and December 31, 2019, for older adults (≥65 years). Adverse events are preferred terms (PTs) defined in MedDRA. We used frequentist approaches, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) to measure disproportionality. We used Bayesian approaches to derive information component (IC) value and Empirical Bayesian Geometric Mean (EBGM) score. Signals were defined as the number of reports > 3 and the lower limit of 95% confidence intervals (CI) of ROR ≥ 2, PRR ≥ 2, IC > 0, EBGM > 1.ResultsWe identified 334 adverse cardiac events comprising 71 different MedDRA PTs from 2004 to 2019 for hydroxychloroquine in older adults. Strong disproportionality signals were noted for “Restrictive cardiomyopathy” (ROR = 272.43 (138.09–537.47); EBGM = 149.78 (77.34–264.67), “Right ventricular hypertrophy” (219.49 (85.32–564.70); 102.74 (39.67–222.81), “Cardiac septal hypertrophy” (226.77 (78.65–653.80); 93.82 (32.19–219.81), “Myocardial fibrosis” (57.29 (21.06–155.85); 42.99 (14.74–100.75), and “Cardiotoxicity” (43.90 (26.66–72.27); 40.28 (24.02–63.72).ConclusionsThe risk of cardiomyopathy and myocardial disorders is high following exposure to hydroxychloroquine in older adults. Due to the current lack of safety data from randomized controlled trials as well as large observational studies to confirm the risk of adverse cardiac events associated with hydroxychloroquine, findings from analyses of post‐marketing data may serve as interim guidance.
Comparison of Various Phase I Combination Therapy Designs in Oncology for Evaluation of Early Tumor Shrinkage Using Simulations
Authors: Seurat Jérémy , Girard Pascal , Goteti Kosalaram , Mentré France 
Published: October 2020

There is still a lack of efficient designs for identifying the dose response in oncology combination therapies in early clinical trials. The concentration response relationship can be identified using the early tumor shrinkage time course, which has been shown to be a good early response marker of clinical efficacy. The performance of various designs using an exposure–tumor growth inhibition model was explored using simulations. Different combination effects of new drug M and cetuximab (reference therapy) were explored first assuming no effect of M on cetuximab (to investigate the type I error (α)), and subsequently assuming additivity or synergy between cetuximab and M. One‐arm, two‐arm, and four‐arm designs were evaluated. In the one‐arm design, 60 patients received cetuximab + M. In the two‐arm design, 30 patients received cetuximab and 30 received cetuximab + M. In the four‐arm design, in addition to cetuximab and cetuximab + M as standard doses, combination arms with lower doses of cetuximab were evaluated (15 patients/arm). Model‐based predictions or “simulated observations” of early tumor shrinkage at week 8 (ETS8) were compared between the different arms. With the same number of individuals, the one‐arm design showed better statistical power than other designs but led to strong inflation of α in case of misestimated reference for ETS8 value. The two‐arm design protected against this misestimation and, with the same total number of subjects, would provide higher statistical power than a four‐arm design. However, a four‐arm design would be helpful for exploring more doses of cetuximab in combination with M to better understand the interaction.