bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between Sensitivity to Thyroid Hormones and Risk of Arrhythmia in Patients with Coronary Heart Disease: A RCSCD-TCM study in China
Authors: Liu Fanfan , Liu Yijia , Li Zhu , Yu Lu , Li Lin , Ma Mei , Lai Ziqin , Li JiaYing , Wang Xianliang , Yang Rongrong , Yu ChunQuan 
Published: June 2022

Abstract
BackgroundThyroid dysfunction is closely related to arrhythmia. However, the relationship between sensitivity to thyroid hormone and risk of arrhythmia remains unknown. This study aimed to investigate the association between the thyroid system complex index and risk of arrhythmia in patients with coronary heart disease (CHD).MethodsThis large, multi-center study included 28,413 patients with CHD. Central sensitivity to thyroid hormone was assessed by calculating the thyroid feedback quantile-based index (TFQI). Logistic regression was used to analyze the relationship between sensitivity to thyroid hormone and risk of arrhythmia. This study also assessed the relationship between sensitivity to thyroid hormone and risk of arrhythmia in different sexes, ages, and glucose regulation and blood lipid states.ResultsOf the 28,413 participants, 8,935 (31.4%) patients with CHD had arrhythmia. There was a remarkable association between TFQI and risk of arrhythmia (odds ratio [OR]: 0.783; 95% confidence interval [CI], 0.735–0.836). Furthermore, the association between the TFQI and risk of arrhythmia in women (OR: 0.731; 95% CI: 0.667–0.802) was stronger than that in men (OR: 0.894; 95% CI: 0.816–0.910), as well as higher in elder (OR: 0.779; 95% CI: 0.721–0.843) than middle-aged (OR: 0.789; 95% CI: 0.703–0.886) patients. Furthermore, the association was stronge in the state of diabetes (OR: 0.635; 95% 0.569–0.709) and dyslipidemia (OR: 0.706; 95% CI: 0.644–0.774).ConclusionThere is a remarkable association between sensitivity to thyroid hormone and risk of arrhythmia in patients with CHD, which is more pronounced among women and the elderly. The association is also stronger in patients with dyslipidemia or diabetes.
Rebaudioside B attenuates lung ischemia-reperfusion injury associated apoptosis and inflammation
Authors: Huang Jian , Yang Jianbao , Zhang Rongzhi , Wang Shixiong , Cheng Xingdong , Li Jian , Li Yongnan , Gao Bingren 
Published: June 2022

Abstract
Currently no proven effective treatment exists for lung ischemia-reperfusion injury (LIRI). Natural compounds represent a source of new drugs for the treatment of different diseases. The present study aims to investigate Rebaudioside B (Reb B) as a potential compound to the treatment of LIRI in vivo and in vitro. The present study includes the human pulmonary alveolar cells line with epithelial type II A549 under oxygen-glucose deprivation/recovery (OGD/R) to high-throughput in vitro cell viability screening to identify the most promising compound tested candidates. Moreover, an in vivo rat model of lung ischemia-reperfusion was used to assess the potential protective effect of Reb B. Reb B was identified as the most promising compound among the natural compounds tested, being identified by high-throughput screening. Reb B enhances cell viability by reducing apoptosis in A549 OGD/R models. In the in vivo model of LIRI, preconditioning with Reb B significantly reduced apoptotic cells, perivascular edema, and neutrophil infiltration in lung tissues. In addition, Reb B inhibits LIRI lung inflammation mainly by increasing IL-10 levels, while decreasing IL-1β and IL-8 levels. The overall results suggest that Reb B has a promising protective effect in LIRI caused by the inhibition of the mitochondrial apoptotic pathway and by decreasing the inflammatory response.
Virtual classroom proficiency-based progression for robotic surgery training (VROBOT): a randomised, prospective, cross-over, effectiveness study
Authors: Nathan Arjun , Patel Sonam , Georgi Maria , Fricker Monty , Asif Aqua , Ng Alexander , Mullins William , Hang Man Kien , Light Alexander , Nathan Senthil , Francis Nader , Kelly John , Collins Justin , Srid Ashwin 
Published: June 2022

Abstract
IntroductionRobotic surgery training has lacked evidence-based standardisation. We aimed to determine the effectiveness of adjunctive interactive virtual classroom training (VCT) in concordance with the self-directed Fundamentals of Robotic Surgery (FRS) curriculum.MethodsThe virtual classroom is comprised of a studio with multiple audio-visual inputs to which participants can connect remotely via the BARCO weConnect platform. 11 novice surgical trainees were randomly allocated to two training groups (A and B). In week one, both groups completed a robotic skills induction. In week two, Group A received training with the FRS curriculum and adjunctive VCT; Group B only received access to the FRS curriculum. In week three, the groups received the alternate intervention.The primary outcome was measured using the validated robotic-objective structured assessment of technical skills (R-OSAT) at the end of week two (timepoint 1) and three (timepoint 2).ResultsAll participants completed the training curriculum and were included in the final analyses. At timepoint 1, Group A achieved a statistically significant greater mean proficiency score compared to Group B (44.80vs35.33 points, p=0.006). At timepoint 2, there was no significant difference in mean proficiency score in Group A from timepoint 1. In contrast, Group B, who received further adjunctive VCT showed significant improvement in mean proficiency by 9.67 points from timepoint 1 (95% CI 5.18-14.15, p=0.003).ConclusionVCT is an effective, accessible training adjunct to self-directed robotic skills training. With the steep learning curve in robotic surgery training, VCT offers interactive, expert-led learning and can increase training effectiveness and accessibility.
Deeper Insights into the Biochemical, Hematological and Histological Changes Induced by Bisphenol A Exposure in Adult Male African Catfish (Clarias gariepinus)
Authors: Asenuga Ebunoluwa R. , Olajuyigbe Folasade M , Akinmoladun Afolabi C. , Fasakin Emmanuel A. 
Published: June 2022

Abstract
Exposure to Bisphenol A (BPA) has been associated with several health challenges in humans and animals. This study investigated the effect of BPA toxicity on African catfish (Clarias gariepinus) with emphasis on biochemical, hematological and histological changes. Seventy healthy adult male fish were used for the study. Fish were divided into seven groups in duplicates. Group A was the water control group, and Group B served as the solvent control group. In contrast, Groups C, D, E, F and G were exposed to BPA at varying concentrations (10 mg/L, 15 mg/L, 20 mg/L, 25 mg/L, and 50 mg/L of water, respectively) for 96 h. Results showed that the lethal concentration (LC50) of BPA was 26.9 mg/L. Physicochemical parameters assessment of water showed a significant increase in the conductivity level and total dissolved solids. Markers of hepatorenal dysfunction (alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, blood urea nitrogen, creatinine, total protein, albumin and globulin) increased with BPA concentration. A significant decrease in hematocrit (HCT), hemoglobin (Hb), red blood cell (RBC) was observed. A significant increase in mean corpuscular volume (MCV), white blood cell (WBC), and lymphocyte counts were also observed in C. gariepinus exposed to BPA. Histological examination showed centrilobular hepatocellular atrophy in the liver, lamellae atrophy and fusion of the gills, atrophy and vacuolation of goblet and club cells of the skin tissue. Findings from this study provide deeper insights into the effects of BPA exposure on hepatorenal functions, hematological profile and histology of selected tissues of adult male C. gariepinus.
Evaluation of the Eeffectiveness of Two Surgical Methods of Tension-free Vaginal Tape (Transversal and Longitudinal Incision of the Vagina) in Women with Stress Urinary Incontinence
Authors: Bartani Zohreh , Mousavi Seyedeh Roqayeh 
Published: June 2022

Abstract
The aim of this study was to determine the effectiveness of two surgical methods of Tension-free Vaginal Tape (TVT) (transversal and longitudinal incision of the vagina) on stress urinary incontinence in women referred to Imam Reza Hospital during 2012–2019. The present study was a clinical trial study which was conducted on 138 women with stress urinary incontinence. TVT surgery. Patients were randomly divided into two groups with transversal (n = 69) and longitudinal incision (n = 69) based on purposive sampling. All patients before surgery underwent cystoscopy, Marshall test and cough stress test, urinary tract mobility test and, if necessary, urodynamic test, pelvic examination and post-void residual (PVR) urine test and completed the incontinence impact questionnaire-7 (IIQ-7). Then, mesh survival at 60 months after surgery was assessed by trans-libial ultrasonography. Statistical analysis was conducted by SPSS 24 (Chi-square test, Fisher's exact test).There was no statistically significant difference between the two groups with longitudinal and transverse incisions in terms of mean age, duration of surgery and the amount of urine remaining in the bladder before and after surgery (P-Value > 0.05). The recovery rate was higher in the transverse incision group compared to the longitudinal incision group and this difference was statistically significant (P-Value = 0.023). Also, the mesh retention rate was higher in the middle position of the duct in the transverse incision group .TVT surgery with transversal incision of the vagina can be effective and safe in treating stress urinary incontinence of women.
Extracranial arteriovenous malformations demonstrate dysregulated TGF-β/BMP signaling and increased circulating TGF-β1
Authors: Wei Ting , Richter Gresham T. , Zhang Haihong , BE Ravi Sun , Smith Conor , Strub Graham 
Published: June 2022

Abstract
Background: Extracranial arteriovenous malformations (AVMs) are characterized by anomalous arterial-to-venous connections, aberrant angiogenesis, local inflammation and hypoxia, and disorganized histological architecture; however, the precise molecular perturbations leading to this phenotype remain elusive. We hypothesized that extracranial AVM tissue would demonstrate deregulation of the TGF-β/BMP signaling pathway, which may serve as a potential target in the development of molecular-based therapies for AVMs. Methods: AVM tissue was harvested during resection from 10 patients with AVMs and compared to control tissue. Blood was collected from 14 AVM patients and 10 patients without AVMs as controls. Expression of TGF-β/BMP pathway components was analyzed using RT-PCR, western blotting, and immunohistochemistry. Circulating levels of TGF-β1 were analyzed by ELISA. Paired t tests were utilized to perform statistical analysis. Results: The mRNA levels of TGF-β1, ALK1, Endoglin (ENG), Smad6, Smad7, and Smad8 were significantly elevated in AVM tissue when compared to controls. Protein levels of TGF-β1 and Smad3 were elevated in AVM tissue while protein levels of BMP-9, ALK1, Smad1, Smad6, and Smad8 were significantly decreased in AVMs. Immunohistochemistry demonstrated significantly increased TGF-β1 in the perivascular cells of AVMs compared to normal controls, and circulating levels of TGF-β1 were significantly higher in AVM patients.Conclusions: Patients with AVMs demonstrate aberrant TGF-β/BMP expression in AVM tissue and blood compared to controls. Targeting aberrantly expressed components of the TGF-β/BMP pathway in extracranial AVMs may be a viable approach in the development of novel molecular therapies, and monitoring circulating TGF-β1 levels may be a useful indicator of treatment success.
Peripheral Blood Biomarkers in ART-Suppressed, SIV-Infected Rhesus Macaques Predict Viral Rebound Following ART Discontinuation
Authors: Barouch Dan , Aid Malika , Colarusso Alessandro , Walker-Sperling Victoria 
Published: June 2022

Abstract
The development of biomarkers that can predict viral rebound following discontinuation of antiretroviral therapy (ART) in HIV-1-infected humans would be an important advance in HIV-1 cure research. In a prior study, we initiated ART in 20 rhesus macaques on days 0, 1, 2, and 3 following SIVmac251 infection prior to plasma viremia. Following 6 months of suppressive ART, we discontinued ART and observed viral rebound in 9 of 20 animals. Here we show that transcriptomic and proteomic signatures of inflammation and immune activation in peripheral blood during ART suppression predicted viral rebound following ART discontinuation. Higher levels of proinflammatory and cellular immune activation pathways, including TNF, IL-1, IL-6, monocyte, and T cell activation signaling pathways, correlated with viral rebound following ART discontinuation. Immune modulatory IL-10 and TGF-beta signaling also correlated with viral rebound. These data suggest that persistent upregulation of inflammatory and immune activation pathways despite suppressive ART represents a peripheral blood biomarker signature of the rebound-competent viral reservoir. The development of interventions that target the viral reservoir and modulate this signature may open new avenues in HIV-1 cure research.
Non-Vitamin K Antagonist Anticoagulants versus Warfarin in newly diagnosed Atrial Fibrillation and CKD: the Korean National Health Insurance Data
Authors: Kee Youn Kyung , Jeon Hee Jung , Oh Jieun , Yoo Tae-Hyn , Kang Dongwoo , lee Jungkuk , Shin Dong Ho 
Published: June 2022

Abstract
Background: Despite the benefits of non-vitamin K antagonist oral anticoagulants (NOACs), whether NOAC therapy has a better risk-benefit profile than warfarin therapy in patients with non-valvular atrial fibrillation (AF) and chronic kidney disease (CKD), including end-stage renal disease (ESRD), remains uncertain. We investigated the efficacy and safety of NOACs compared to warfarin in these patients using a nationwide database.Methods: We evaluated patients with incident non-valvular AF and CKD in the Korea National Health Insurance Database from 2013 to 2018. The primary and secondary efficacy outcomes were ischemic stroke and all-cause mortality, respectively. The primary safety outcomes included intracranial hemorrhage, gastrointestinal bleeding, and extracranial or unclassified major bleeding.Results: Among the 1,885 patients, 970 (51.5%) initiated warfarin therapy, whereas 915 (48.5%) initiated NOAC therapy. Although NOAC users had a lower proportion of patients with ESRD than warfarin users (6.6% vs. 32.5%, p <0.001), NOAC users had a higher Charlson comorbidity index, CHA2DS2-VASC score, and modified HAS-BLED score compared with warfarin users. During a mean follow-up period of 23.8 months, there were 293 and 214 cases of ischemic stroke and all-cause death, respectively. There was no difference in ischemic stroke between the two groups. However, Kaplan-Meier survival analysis showed that all-cause mortality was significantly lower in NOAC users than in warfarin users. In multivariate Cox regression analyses, the hazard ratio for all-cause mortality compared to warfarin therapy was 0.41 (95% CI, 0.30-0.56; p < 0.001) in NOAC therapy. Additionally, NOAC therapy significantly reduced intracranial hemorrhage and gastrointestinal bleeding in multivariate Cox regression analyses.Conclusions: This study showed that NOAC therapy had a better risk-benefit profile than warfarin therapy in patients with AF and CKD. To clarify the benefits of NOACs in patients with AF and CKD, further well-designed clinical trials are needed.
Kairomonal effect of aphid alarm pheromones and analogues on the parasitoid Diaeretiella rapae
Authors: Qin Yaoguo , Zhang Shangyang , Li Zhengxi 
Published: June 2022

Abstract
Aphid alarm pheromones as important semiochemicals not only mediate behavioral response of aphids, but can act as kairomones to attract their natural enemies. The sesquiterpene (E)-β-farnesene (EβF), the major alarm pheromone component of most aphid species, has been shown to have a kairomonal effect on the predators of aphids, but other alarm pheromone components, especially the monoterpenes and analogues, are rarely investigated. Here, two EβF analogues were successfully synthesized via nucleophilic substitution reaction, and then we examined the kairomonal effects of four alarm pheromone components and two EβF analogues on the aphid parasitoid Diaeretiella rapae. In olfactory bioassays, D. rapae females generally showed no significant behavioral response to these alarm pheromone components and analogues under low concentration (0.1 µg/µL). Nevertheless, their olfactory response to these compounds gradually enhanced with increasing concentrations. Among the four pheromone components, EβF showed the highest attractive activity, but the parasitoid preferred the mixtures over single compounds. Moreover, the olfactory response time was shortened with increasing concentrations. We confirmed the kairomonal effect of monoterpene alarm pheromone components and their mixtures in addition to EβF on the natural enemy of aphid. This is the first report that the mixture of alarm pheromone components and their analogues has a stronger kairomonal effect than single components on the natural enemy of aphid. This study contributes to our understanding of the mechanisms involved in regulation of parasitoid behaviors by kairomones, and provides a promising opportunity for designing kairomones for the aphid parasitoid to mediate aphid populations in the field.
Development of doubled haploid population and QTL mapping for Fusarium stalk rot (FSR) resistance in tropical maize
Authors: CHANDAPPA LOHITHASWA HIRENALLUR , Babu B. M. Showkath , Mallikarjuna M G , Mallikarjuna N. 
Published: June 2022

Abstract
Fusarium stalk rot disease (FSR) caused by Fusarium verticilloides is emerging as the major production constraint in maize across the world. As a prelude to develop maize hybrids resistant to FSR, an attempt was made to identify QTL as the genetics of resistance was found to be quantitative in nature. Two doubled haploid (DH) mapping populations induced from F2 of crosses VL1043 × CM212 and VL121096 × CM202 were challenged with FSR during two seasons. The FSR response was influenced by significant DHs × season interaction. The DH populations were genotyped employing 164 and 132 polymorphic SNP markers in the DHs induced from the crosses VL1043 × CM212 and VL121096 × CM202, respectively. Inclusive composite interval mapping was performed to detect significant QTL, QTL × QTL, QTL × season interaction effects. Two and one QTL were identified in rabi 2019 and summer 2020, respectively. The QTL identified on the linkage group 10 (qFSR_10_1) was common across two seasons in DHs derived from the cross VL1043 × CM212. Similarly, two QTL each in rabi 2019, summer 2020 and one common QTL (qFSR_6_2) were identified for FSR resistance in DHs derived from F2 of the cross VL121096 × CM202. The QTL qFSR_10_1 was common in both the crosses. The position and effect of the QTL were varied with the seasons. Seven di-QTL interactions were detected for FSR resistance in both DH populations.
General Practice Pharmacists’ experience of Advanced Clinical Assessment courses: a theoretically underpinned qualitative exploration
Authors: Rushworth Gordon F , Jebara Tesnime , Tonna Antonella Pia , Rudd Ian , Stewart Fiona , MacVicar Ronald , Cunningham Scott 
Published: June 2022

Abstract
BACKGROUND: The role of General Practice Clinical Pharmacists is becoming more clinically complex. Some are undertaking Advanced Clinical Examination & Assessment courses to further develop their skillsets.AIM To explore General Practice Clinical Pharmacists’ experience of Advanced Clinical Examination and Assessment courses, skills development and implementation. METHOD: This research used qualitative methods with theoretical underpinning at each stage. General Practice Clinical Pharmacists working in the Scottish National Health Service who had completed the relevant course were invited for qualitative online mini-focus groups. Informed written consent was obtained. A topic guide was developed using the Theoretical Domains Framework and piloted. Mini-focus groups were recorded, transcribed verbatim and analysed using a framework analysis informed by Theoretical Domains Framework and the “Capability, Opportunity, Motivation Behaviour System”. Ethics approval was granted. RESULTS: Fourteen pharmacists participated from eight Health Boards across Scotland. Themes were identified and mapped to frameworks underpinning this research. Participants reported that the course allowed them to gain skills needed to become clinically autonomous and supported them in taking a more holistic approach when reviewing patients. However, the pharmacist-product from the course in terms of skillset acquisition, and its potential application in general practice, was perceived by participants as poorly understood at the micro, meso and macro level. There was frustration among participants at the perceived lack of advanced practice opportunities within the current contractual healthcare system in general practice. CONCLUSION: Policy drivers should be urgently devised to reform general practice pharmacy services to best utilise pharmacists with these skills.
MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer
Authors: Chung Jae Heun , Choi Ho Jung , Kang Yong Jung , Kim Yun Seong , Lee Sang-Yull , Kwon Ryuk Jun , Jeong Han-Sol , Park Su-Jung , Jeong Yeongmu , Kang Dongwan , Ko Jeongin , Noh SangGyun , Chung Hae Young , Moon Hyung Ryong , Yoon Seong Hoon 
Published: June 2022

Abstract
Background: The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC.Methods: We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma.Results: MHY4571 inhibited PKA activity (>70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions: Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.