bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of testosterone microdosing in healthy females
Authors: Savkovic Sasha , Ly Lam P. , Desai Reena , Howa John , Nair Vinod , Eichner Daniel , Handelsman David J. 
Published: November 2021

AbstractThe ready detectability of synthetic androgens by mass spectrometry (MS)‐based antidoping tests has reoriented androgen doping to using testosterone (T), which must be distinguished from its endogenous counterpart making detection of exogenous T harder. We investigated urine and serum steroid and hematological profiling individually and combined to determine the optimal detection model for T administration in women. Twelve healthy females provided six paired blood and urine samples over 2 weeks prior to treatment consisting of 12.5‐mg T in a topical transdermal gel applied daily for 7 days. Paired blood and urine samples were then obtained at the end of treatment and Days 1, 2, 4, 7, and 14 days later. Compliance with treatment and sampling was high, and no adverse effects were reported. T treatment significantly increased serum and urine T, serum dihydrotestosterone (DHT), urine 5α‐androstane‐3α,17β‐diol (5α‐diol) epitestosterone (E), and urine T/E ratio with a brief window of detection (2–4 days) as well as total and immature (medium and high fluorescence) reticulocytes that remained elevated over the full 14 posttreatment days. Carbon isotope ratio MS and the OFF score and Abnormal Blood Profile score (ABPS) were not discriminatory. The optimal multivariate model to identify T exposure combined serum T, urine T/E ratio with three hematological variables (% high fluorescence reticulocytes, mean corpuscular hemoglobin, and volume) with the five variables providing 93% correct classification (4% false positive, 10% false negatives). Hence, combining select serum and urine steroid MS variables with reticulocyte measures can achieve a high but imperfect detection of T administration to healthy females.
Eligibility of patients with heart failure with preserved ejection fraction for sacubitril/valsartan according to the PARAGON‐HF trial
Authors: Lund Lars H. , Savarese Gianluigi , Venkateshvaran Ashwin , Benson Lina , Lundberg Anna , Donal Erwan , Daubert Jean‐Claude , Oger Emmanuel , Linde Cecilia , Hage Camilla 
Published: November 2021

AbstractAimsIn the heart failure (HF) with preserved ejection fraction (HFpEF) PARAGON‐HF trial, sacubitril/valsartan vs. valsartan improved mortality/morbidity in patients with left ventricular ejection fraction (LVEF) below median (57%). We assessed eligibility for sacubitril/valsartan based on four scenarios.Methods and resultsEligibility was assessed in the Karolinska‐Rennes study (acute HFpEF, LVEF ≥ 45%, and N‐terminal pro‐B‐type natriuretic peptide ≥300 pg/mL subsequently assessed as outpatients including echocardiography) in (i) a trial scenario (all trial criteria); (ii) a pragmatic scenario (selected trial criteria); (iii) LVEF below lower limit of normal range (<54% in women and <52% in men); and (iv) LVEF below mean of normal range (<64% in women and <62% in men). Among 425 patients [age 78 (72–83) years, 57% women, 28% LVEF ≤ 57% (median in PARAGON‐HF), the trial scenario, identified 34% as eligible. Left atrial enlargement and/or left ventricular hypertrophy were present in 99%. Inclusion criteria not met were diuretic treatment and New York Heart Association class. Important exclusion criteria were estimated glomerular filtration rate <30 mL/min/1.73 m2, haemoglobin <10 g/day, and cancer. In the pragmatic scenario, 63% were eligible. In LVEF below lower limit of normal range, 5.4% were eligible, and in LVEF below mean of normal range, 41% were eligible. In patients with LVEF ≤ 57%, eligibility was 42%, 69%, 21%, and 91% according to the trial scenario, pragmatic scenario, LVEF below lower limit of normal range, and LVEF below mean of normal range, respectively.ConclusionsIn real‐world HFpEF (LVEF ≥ 45%) with N‐terminal pro‐B‐type natriuretic peptide and cardiac structure/function assessed, eligibility for sacubitril/valsartan was according to PARAGON‐HF complete criteria 34%, pragmatic criteria 63%, LVEF below lower limit of normal range 5.4%, and LVEF below mean of normal range 41%. Cardiac structural impairment was almost ubiquitous. Ineligibility was more due to exclusion criteria than failing to meet inclusion criteria.
Long‐term impact of β‐blocker in elderly patients without myocardial infarction after percutaneous coronary intervention
Authors: Fukase Tatsuya , Dohi Tomotaka , Koike Takuma , Yasuda Hidetoshi , Takeuchi Mitsuhiro , Takahashi Norihito , Chikata Yuichi , Endo Hirohisa , Doi Shinichiro , Nishiyama Hiroki , Okai Iwao , Iwata Hiroshi , Okazaki Shinya , Miyauchi Katsumi , Daida Hiroyuki , Minamino Tohru 
Published: November 2021

AbstractAimsLittle is known about the long‐term outcomes of β‐blockers use in patients with coronary artery disease (CAD) without myocardial infarction (MI) and reduced ejection fraction (rEF). However, more attention should be paid to the oral administration of β‐blockers in elderly patients who are susceptible to heart failure (HF), sinus node dysfunction, or rate response insufficiency. We aimed to evaluate the long‐term impact of β‐blockers in elderly patients with CAD without MI or systolic HF who have undergone percutaneous coronary intervention.Methods and resultsA total of 1018 consecutive elderly patients with CAD (mean age, 72 ± 7 years; 77% men) who underwent their first intervention between 2010 and 2018 were included in this study. According to the presence or absence of the use of β‐blockers, 514 patients (50.5%) were allocated to the β‐blocker group, and 504 (49.5%) to the non‐β‐blocker group. We evaluated the incidence of 4‐point major adverse cardiovascular events (4P‐MACE), including cardiovascular death, non‐fatal MI, non‐fatal stroke, admission for HF, target vessel revascularization (TVR), and all‐cause death. We focused on the association between chronotropic incompetence of β‐blockers and incidence of a new HF and analysed the results using an exercise electrocardiogram regularly performed in the outpatient department after percutaneous coronary intervention. During a median follow‐up duration of 5.1 years, 83 patients (8.3%) developed 4P‐MACE, including cardiovascular death in 17, non‐fatal MI in 13, non‐fatal stroke in 25, and admission for HF in 39 patients. Additionally, 124 patients (12.2%) had a TVR and 104 (10.2%) died of other causes. Kaplan–Meier analysis showed that the cumulative incidence rate of 4P‐MACE in the β‐blocker group was significantly higher than that in the non‐β‐blocker group (15.4% vs. 10.0%, log‐rank test, P = 0.015). Above all, the cumulative incidence rate of admission for HF in the β‐blocker group was significantly higher (8.8% vs. 3.2%, log‐rank test, P < 0.001). The β‐blocker group had significantly lower resting heart rate, stress heart rate, and stress‐rest Δ heart rate on exercise electrocardiogram. Multivariate Cox hazard analysis revealed that EF, β‐blocker use, stress‐rest Δ heart rate, and CKD were strong independent predictors of admission for HF.ConclusionsLong‐term β‐blocker use was significantly associated with an increased risk of adverse cardiovascular events in elderly patients with CAD without MI or systolic HF. In particular, the chronotropic incompetence action of β‐blockers could increase the risk of admission for HF in elderly patients with CAD without MI and systolic HF, and the present findings warrant further investigation.
Copper‐Catalyzed Cascade N‐Dealkylation/N‐Methyl Oxidation of Aromatic Amines by Using TEMPO and Oxygen as Oxidants
Authors: Wang Shihaozhi , Yang Jiale , Li Dianjun , Yang Jinhui 
Published: November 2021

AbstractA novel tandem N‐dealkylation and N‐methyl aerobic oxidation of tertiary aromatic amines to N‐arylformamides using copper and TEMPO has been developed. This methodology suggested an alternative synthetic route from N‐methylarylamines to N‐arylformamides.
Shared functional connections within and between cortical networks predict cognitive abilities in adult males and females
Authors: Dhamala Elvisha , Jamison Keith W. , Jaywant Abhishek , Kuceyeski Amy 
Published: November 2021

AbstractA thorough understanding of sex‐independent and sex‐specific neurobiological features that underlie cognitive abilities in healthy individuals is essential for the study of neurological illnesses in which males and females differentially experience and exhibit cognitive impairment. Here, we evaluate sex‐independent and sex‐specific relationships between functional connectivity and individual cognitive abilities in 392 healthy young adults (196 males) from the Human Connectome Project. First, we establish that sex‐independent models comparably predict crystallised abilities in males and females, but only successfully predict fluid abilities in males. Second, we demonstrate sex‐specific models comparably predict crystallised abilities within and between sexes, and generally fail to predict fluid abilities in either sex. Third, we reveal that largely overlapping connections between visual, dorsal attention, ventral attention, and temporal parietal networks are associated with better performance on crystallised and fluid cognitive tests in males and females, while connections within visual, somatomotor, and temporal parietal networks are associated with poorer performance. Together, our findings suggest that shared neurobiological features of the functional connectome underlie crystallised and fluid abilities across the sexes.
The expression pattern of β‐carotene ketolase gene restricts the accumulation of astaxanthin in Dunaliella under salt stress
Authors: Chen Hao‐Hong , He Yu‐Jing , Liang Ming‐Hua , Yan Bing , Jiang Jian‐Guo 
Published: November 2021

AbstractDunaliella salina can accumulate a large amount of β‐carotene which is generally considered to be its terminal product of carotenoid metabolism. In this study, it was proved that D. salina has the ketolase (DsBKT) of catalyzing the synthesis of astaxanthin, the downstream products of β‐carotene. Therefore, the reason why D. salina does not synthesize astaxanthin is the purpose of this study. The enzymatic activity of DsBKT was detected by functional complementation assays in Escherichia coli, results showed that DsBKT had efficient ketolase activity toward β‐carotene and zeaxanthin to produce astaxanthin, indicating that there were complete astaxanthin‐producing genes in Dunaliella. Unlike the induced expression of Lycopene cyclase (catalyzing β‐carotene synthesis) under salt stress, the expression of DsBKT was very low under both normal and stress conditions, which may be the main reason why D. salina cannot accumulate astaxanthin. On the contrary, with the astaxanthin‐rich Haematococcus pluvialis as a control, its BKT gene was significantly upregulated under salt stress. Further study showed that DsBKT promoter had strong promoter ability and could stably drive the expression of ble‐egfp in D. salina. Obviously, DsBKT promoter is not the reason of DsBKT not being expressed which may be caused by Noncoding RNA.
MyD88 deficiency ameliorates weight loss caused by intestinal oxidative injury in an autophagy‐dependent mechanism
Authors: Qi Ming , Liao Simeng , Wang Jing , Deng Yuankun , Zha Andong , Shao Yirui , Cui Zhijuan , Song Tongxing , Tang Yulong , Tan Bie , Yin Yulong 
Published: November 2021

AbstractBackgroundGut health plays a vital role in the overall health and disease control of human and animals. Intestinal oxidative stress is a critical player in the induction and progression of cachexia which is conventionally diagnosed and classified by weight loss. Therefore, reduction of intestinal oxidative injury is a common and highly effective strategy for the maintenance of human and animal health. Here we identify intestinal myeloid differentiation primary response gene 88 (MyD88) as a novel target for intestinal oxidative stress using canonical oxidative stress model induced by paraquat (PQ) in vitro and in vivo.MethodsIntestinal oxidative stress was induced by administration of PQ in intestinal epithelial cells (IECs) and mouse model. Cell proliferation, apoptosis, DNA damage, mitochondrial function, oxidative status, and autophagy process were measured in wild‐type and MyD88‐deficient IECs during PQ exposure. Autophagy inhibitor (3‐methyladenine) and activator (rapamycin) were employed to assess the role of autophagy in MyD88‐deficient IECs during PQ exposure. MyD88 specific inhibitor, ST2825, was used to verify function of MyD88 during PQ exposure in mouse model.ResultsMyD88 protein levels and apoptotic rate of IECs are increased in response to PQ exposure (P < 0.001). Intestinal deletion of MyD88 blocks PQ‐induced apoptosis (~42% reduction) and DNA damage (~86% reduction), and improves mitochondrial fission (~37% reduction) and function including mitochondrial membrane potential (~23% increment) and respiratory metabolism capacity (~26% increment) (P < 0.01). Notably, there is a marked decrease in reactive oxygen species in MyD88‐deficient IECs during PQ exposure (~70% reduction), which are consistent with high activity of antioxidative enzymes (~83% increment) (P < 0.001). Intestinal ablation of MyD88 inhibits mTOR signalling, and further phosphorylates p53 proteins during PQ exposure, which eventually promotes intestinal autophagy (~74% increment) (P < 0.01). Activation of autophagy (rapamycin) promotes IECs growth as compared with 3‐methyladenine‐treatment during PQ exposure (~173% increment), while inhibition of autophagy (3‐methyladenine) exacerbates oxidative stress in MyD88‐deficient IECs (P < 0.001). In mouse model, inhibition of MyD88 using specific inhibitor ST2825 followed by PQ treatment effectively ameliorates weight loss (~4% increment), decreased food intake (~92% increment), gastrocnemius and soleus loss (~24% and ~20% increment, respectively), and intestinal oxidative stress in an autophagy dependent manner (P < 0.01).ConclusionsMyD88 modulates intestinal oxidative stress in an autophagy‐dependent mechanism, which suggests that reducing MyD88 level may constitute a putative therapeutic target for intestinal oxidative injury‐induced weight loss.
circRNAome profiling reveals circFgfr2 regulates myogenesis and muscle regeneration via a feedback loop
Authors: Yan Junyu , Yang Yalan , Fan Xinhao , Liang Guoming , Wang Zishuai , Li Jiju , Wang Liyuan , Chen Yun , Adetula Adeyinka Abiola , Tang Yijie , Li Kui , Wang Dazhi , Tang Zhonglin 
Published: November 2021

AbstractBackgroundCircular RNAs (circRNAs) represent a novel class of non‐coding RNAs formed by a covalently closed loop and play crucial roles in many biological processes. Several circRNAs associated with myogenesis have been reported. However, the dynamic expression, function, and mechanism of circRNAs during myogenesis and skeletal muscle development are largely unknown.MethodsStrand‐specific RNA‐sequencing (RNA‐seq) and microarray datasets were used to profile the dynamic circRNAome landscape during skeletal muscle development and myogenic differentiation. Bioinformatics analyses were used to characterize the circRNAome and identify candidate circRNAs associated with myogenesis. Bulk and single‐cell RNA‐seq were performed to identify the downstream genes and pathways of circFgfr2. The primary myoblast cells, C2C12 cells, and animal model were used to assess the function and mechanism of circFgfr2 in myogenesis and muscle regeneration in vitro or in vivo by RT‐qPCR, western blotting, dual‐luciferase activity assay, RNA immunoprecipitation, RNA fluorescence in situ hybridization, and chromatin immunoprecipitation.ResultsWe profiled the dynamic circRNAome in pig skeletal muscle across 27 developmental stages and detected 52 918 high‐confidence circRNAs. A total of 2916 of these circRNAs are conserved across human, mouse, and pig, including four circRNAs (circFgfr2, circQrich1, circMettl9, and circCamta1) that were differentially expressed (|log2 fold change| > 1 and adjusted P value < 0.05) in various myogenesis systems. We further focused on a conserved circRNA produced from the fibroblast growth factor receptor 2 (Fgfr2) gene, termed circFgfr2, which was found to inhibit myoblast proliferation and promote differentiation and skeletal muscle regeneration. Mechanistically, circFgfr2 acted as a sponge for miR‐133 to regulate the mitogen‐activated protein kinase kinase kinase 20 (Map3k20) gene and JNK/MAPK pathway. Importantly, transcription factor Kruppel like factor 4 (Klf4), the downstream target of the JNK/MAPK pathway, directly bound to the promoter of circFgfr2 and affected its expression via an miR‐133/Map3k20/JNK/Klf4 auto‐regulatory feedback loop. RNA binding protein G3BP stress granule assembly factor 1 (G3bp1) inhibited the biogenesis of circFgfr2.ConclusionsThe present study provides a comprehensive circRNA resource for skeletal muscle study. The functional and mechanistic analysis of circFgfr2 uncovered a circRNA‐mediated auto‐regulatory feedback loop regulating myogenesis and muscle regeneration, which provides new insight to further understand the regulatory mechanism of circRNAs.
Do universal adhesives provide the benefits from double‐application or an extra bonding layer in composite repair?
Authors: Karadas Muhammet 
Published: November 2021

AbstractThis study aimed to determine whether the application of extra hydrophobic resin (EHR) or double layer (DL) improves microtensile bond strength (μTBS) of two universal adhesives to composite resin. Composite blocks were fabricated and exposed to thermal cycles. The specimens were horizontally sectioned into two halves. Scotch Bond Universal (SBU) and Clearfil S3 Bond Universal (CSBU) were applied to the ground composite surface according to the manufacturers' instructions, or with DL application or EHR application. The repair composite was incrementally placed to bonded planes. Composite sticks were achieved and tensed with a universal testing machine, followed by examining the fracture surfaces by a scanning electron microscope. Data were evaluated by Weibull analysis (shape and scale [σθ and σ0.10] parameters) using the maximum likelihood method. The σθ and σ0.10, respectively, estimate strength at 63.2 and 10% probability of failure. Shape parameter values showed significant differences among treatments. DL application of CSBU did not affect μTBS values at σθ of failure but caused to decrease μTBS values at σ0.10 of failure. DL application of SBU reduced μTBS values at σθ of failure. DL or EHR coating did not improve μTBS of SBU. EHR application increased μTBS of CSBU, whereas DL application did not benefit.
Mental health and initiation of antiretroviral treatment at enrolment into HIV care in Cameroon under a national “treat all” policy: a cross‐sectional analysis
Authors: Parcesepe Angela M. , Filiatreau Lindsey M. , Ebasone Peter Vanes , Dzudie Anastase , Pence Brian W. , Wainberg Milton , Yotebieng Marcel , Anastos Kathryn , Pefura‐Yone Eric , Ajeh Rogers , Nash Denis 
Published: November 2021

AbstractIntroductionRapid antiretroviral treatment (ART) initiation reduces time from HIV infection to viral suppression, decreasing HIV transmission risk. Mental health symptoms may influence timing of ART initiation. This study estimated the prevalence of ART initiation at enrolment into HIV care and the relationship between mental health and ART initiation at enrolment into HIV care.MethodsWe conducted interviews with 426 individuals initiating HIV care in Cameroon between June 2019 and March 2020 to estimate the association between mental health and timing of ART initiation. Depression (Patient Health Questionnaire‐9; cut‐point 10), anxiety (Generalized Anxiety Disorder‐7; cut‐point 10), post‐traumatic stress disorder (PTSD) (PTSD Checklist for DSM‐5; cut‐point 31) and harmful alcohol use (Alcohol Use Disorders Identification Test; cut‐point 16) were dichotomized to represent those with and without each exposure at first HIV care appointment. Date of ART initiation (date ART prescribed) was ascertained from medical records. Separate multivariable log‐binomial regression models were used to estimate the association between mental health exposures and ART initiation at enrolment into care.Results and discussionOverall, 87% initiated ART at enrolment into HIV care. Approximately 20% reported depressive symptoms, 15% reported PTSD symptoms, 12% reported anxiety symptoms and 13% reported harmful alcohol use. In multivariable analyses, individuals with moderate to severe depressive symptoms had 1.7 (95% confidence interval [CI] 1.1, 2.7) times the prevalence of not initiating ART at enrolment into HIV care compared to those with no or mild depressive symptoms. Those with symptoms of PTSD, compared to those without, had 1.9 (95% CI 1.2, 2.9) times the prevalence of not initiating ART at enrolment into HIV care. Symptoms of anxiety or harmful drinking were not associated with ART initiation at enrolment into HIV care in multivariable models.ConclusionsSymptoms of depression and PTSD were associated with lower prevalence of ART initiation at enrolment into HIV care among this sample of individuals initiating HIV care in Cameroon under a “treat all” policy. Research should examine barriers to timely ART initiation, whether incorporating mental health services into HIV care improves timely ART initiation, and whether untreated symptoms of depression and PTSD drive suboptimal HIV care outcomes.
Seroprevalence of coxsackievirus A21 neutralizing antibodies in Yamagata, Japan, between 1976 and 2019; coxsackievirus A21 has rarely affected young children
Authors: Tanaka Waka , Komabayashi Kenichi , Ikeda Yoko , Aoki Yoko , Itagaki Tsutomu , Mizuta Katsumi 
Published: November 2021

AbstractAlthough coxsackievirus A21 (CV‐A21) has been associated with an acute respiratory infection (ARI) as well as poliomyelitis‐like paralysis, reports of CV‐A21 detection have been quite limited both globally and in Japan. CV‐A21 strains were isolated from five sporadic pediatric cases with ARI in 2019 in Yamagata, Japan. Neutralizing antibodies (NT Abs) were then measured against CV‐A21 using sera collected in 1976, 1985, 1999, 2009, and 2019 in Yamagata, to clarify the longitudinal epidemiology of CV‐A21. The total Ab‐positive rate in each year was 15.2% (35/233), 10.7% (30/281), 14.3% (28/196), 3.1% (7/236), and 1.3% (3/226), respectively. Ab‐positive rates generally increased with age, especially between 1976 and 1999. Among the total Ab‐positive cases, the Ab titers were relatively low; 50 cases belonged to the 1:8–1:16, 40 to 1:32–1:64, 12 to 1:128–1:256, and 1 to 1:1024< groups, respectively. No Ab‐positive cases under the age of 10 were observed in any of the years analyzed. In conclusion, this study and previous works suggested that CV‐A21 is a unique enterovirus, which is not transmitted readily among young children but causes sporadic ARI cases mainly among those ≥15 years of age in the community.