bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual‐target inhibitors of bromodomain and extra‐terminal proteins in cancer: A review from medicinal chemistry perspectives
Authors: Feng Lu , Wang Guan , Chen Yi , He Gu , Liu Bo , Liu Jie , Chiang Cheng‐Ming , Ouyang Liang 
Published: October 2021

AbstractBromodomain‐containing protein 4 (BRD4), as the most studied member of the bromodomain and extra‐terminal (BET) family, is a chromatin reader protein interpreting epigenetic codes through binding to acetylated histones and non‐histone proteins, thereby regulating diverse cellular processes including cell cycle, cell differentiation, and cell proliferation. As a promising drug target, BRD4 function is closely related to cancer, inflammation, cardiovascular disease, and liver fibrosis. Currently, clinical resistance to BET inhibitors has limited their applications but synergistic antitumor effects have been observed when used in combination with other tumor inhibitors targeting additional cellular components such as PLK1, HDAC, CDK, and PARP1. Therefore, designing dual‐target inhibitors of BET bromodomains is a rational strategy in cancer treatment to increase potency and reduce drug resistance. This review summarizes the protein structures and biological functions of BRD4 and discusses recent advances of dual BET inhibitors from a medicinal chemistry perspective. We also discuss the current design and discovery strategies for dual BET inhibitors, providing insight into potential discovery of additional dual‐target BET inhibitors.
A Systematic Review of Metabolic Alterations Underlying IgE‐Mediated Food Allergy in Children
Authors: De Paepe Ellen , Van Gijseghem Lynn , De Spiegeleer Margot , Cox Eric , Vanhaecke Lynn 
Published: October 2021

ScopeImmunoglobulin E‐mediated food allergies (IgE‐FA) are characterized by an ever‐increasing prevalence, currently reaching up to 10.4% of children in the European Union. Metabolomics has the potential to provide a deeper understanding of the pathogenic mechanisms behind IgE‐FA.Methods and ResultsIn this work, literature is systematically searched using Web of Science, PubMed, Scopus, and Embase, from January 2010 until May 2021, including human and animal metabolomic studies on multiple biofluids (urine, blood, feces). In total, 15 studies on IgE‐FA are retained and a dataset of 277 potential biomarkers is compiled for in‐depth pathway mapping. Decreased indoleamine 2,3‐dioxygenase‐1 (IDO‐ 1) activity is hypothesized due to altered plasma levels of tryptophan and its metabolites in IgE‐FA children. In feces of children prior to IgE‐FA, aberrant metabolization of sphingolipids and histidine is noted. Decreased fecal levels of (branched) short chain fatty acids ((B)SCFAs) compel a shift towards aerobic glycolysis and suggest dysbiosis, associated with an immune system shift towards T‐helper 2 (Th2) responses. During animal anaphylaxis, a similar switch towards glycolysis is observed, combined with increased ketogenic pathways. Additionally, altered histidine, purine, pyrimidine, and lipid pathways are observed.ConclusionTo conclude, this work confirms the unprecedented opportunities of metabolomics and supports the in‐depth pathophysiological qualification in the quest towards improved diagnostic and prognostic biomarkers for IgE‐FA.
Technical overview of magnetic resonance fingerprinting and its applications in radiation therapy
Authors: Chen Yong , Lu Lan , Zhu Tong , Ma Dan 
Published: October 2021

AbstractMagnetic resonance fingerprinting (MRF) is an emerging imaging technique for rapid and simultaneous quantification of multiple tissue properties. The technique has been developed for quantitative imaging of different organs. The obtained quantitative measures have the potential to improve multiple steps of a typical radiotherapy workflow and potentially further improve integration of magnetic resonance imaging guided clinical decision making. In this review paper, we first provide a technical overview of the MRF method from data acquisition to postprocessing, along with recent development in advanced reconstruction methods. We further discuss critical aspects that could influence its usage in radiation therapy, such as accuracy and precision, repeatability and reproducibility, geometric distortion, and motion robustness. Finally, future directions for MRF application in radiation therapy are discussed.
The patient pathway for overactive bladder management: A quantitative analysis
Authors: Seinen Auke. J. , Elburg Rogier , Hollegien Lianne M. , Blanker Marco H. , Witte Lambertus P. W. 
Published: October 2021

AbstractPurposeWe aimed to explore the pathways followed by patients with overactive bladder (OAB) from referral to the urologist to final treatment.MethodsThis was a single‐center, retrospective cohort study of female patients diagnosed with OAB in a large Dutch nonacademic teaching hospital. The number, sequence, and duration of treatment steps offered were analyzed, and the effectiveness, reasons for discontinuation, and possible case‐mix variables influencing OAB treatment were studied.ResultsIn total, 120 patients were enrolled and required a median of 2 steps (range, 1–6) of treatment over a median total duration of 28 weeks (range, 5–256). Treatment typically started with drug therapy, including antimuscarinics (38%; 95% CI, 30%–47%), antimuscarinics plus pelvic floor muscle therapy (21%; 95% CI, 15%–29%), or mirabegron (11%; 95% CI, 6%–18%). However, 52% of patients required further treatment, with botulinum toxin A (BoNT‐A) injections being most effective (67%; 95% CI, 42%–85%), followed by antimuscarinics plus percutaneous tibial nerve stimulation (50%; 95% CI, 25%–75%), and antimuscarinics plus pelvic floor muscle therapy (36%; 95% CI, 21%–54%). Other therapies showed lower effectiveness. Common reasons for discontinuation were insufficient response and side effects. Overall, 22 patients were lost to follow‐up.ConclusionMost patients try at least two treatments before they experience satisfactory symptom relief, with treatment evaluations requiring time because therapeutic onsets differ by patient and treatment. Our data can help to manage expectations among urologists and patients when seeking treatment for OAB.
Adjustable continence therapy (ACT®) balloons to treat neurogenic and non‐neurogenic female urinary incontinence
Authors: Demeestere Amélie , de Guerry Marie‐Liesse , Bergot Christophe , de Hauteclocque Astrid , Hascoet Juliette , Gamé Xavier , Bajeot Anne‐Sophie , Peyronnet Benoit , Capon Grégoire , Perrouin‐Verbe Marie‐Aimée , Biardeau Xavier 
Published: October 2021

AbstractAimsTo compare efficacy and safety between neurogenic and non‐neurogenic women after adjustable continence therapy (ACT®) balloons implantation to treat stress urinary incontinence (SUI) due to intrinsic sphincter deficiency.MethodsIn the present retrospective multicentric study, all neurogenic and non‐neurogenic women implanted with ACT® balloons between 2000 and 2018 were considered for inclusion. Efficacy was compared 1 year after implantation, and women were allocated in three different groups as follows. Success: maximum 1 pad per day and patient's impression of improvement assessed using a numeral rating scale (NRS) ≥8/10. Improvement: decrease of daily pad use and/or NRS ≥5/10. Failure: increase or stability of daily pad use or NRS <5/10. Overall surgical complications and explantations were compared 1 year after implantation.ResultsAmong the 277 included women, 51 presented with a neurologic underlying disease. Mean age at implantation was 68.5 years. There was no significant difference in efficacy between neurogenic and non‐neurogenic women with a success rate of 39.2% and 36.3%, respectively (p = 0.69). Similarly, improvement rate was reported to be 31.4% and 33.6%, in neurogenic and non‐neurogenic women, respectively (p = 0.92). The overall surgical complications rate (24% vs. 34.5%, p = 0.15) and the explantation rate (19.6% vs. 28.8%, p = 0.18) were not significantly different.ConclusionACT balloons may be proposed to treat mixed or SUI in females with ISD. Efficacy and safety profiles appear to be similar in both neurogenic and non‐neurogenic patients.
Fish vertebrae as archeological biomarkers of past marine ecological conditions: Comparison of mercury levels in Chilean swordfish between the Middle Holocene and the modern period
Authors: Biton‐Porsmoguer Sebastian , Bouchoucha Marc , Marco‐Miralles Françoise , Salazar Diego , Béarez Philippe 
Published: October 2021

AbstractThe ocean has always been a source of inspiration for past and present civilizations, especially for those involved in fishing activities. The regular fishing of large pelagic fish by past societies using harpoons has been demonstrated, with several studies reporting the discovery of an important fishery of large pelagic fish (including swordfish) dating from as early as the sixth millennium BCE on the North Chilean Pacific Coast. The swordfish (Xiphias gladius) is a cosmopolitan, highly migratory species found in all warm and temperate oceans and seas, and mercury is known to bioamplify along food webs, increasing with the trophic level of organisms up to these top predators. This study, therefore, analyzes and compares the mercury levels of archeological and modern vertebrae in swordfish. The archeological fish remains were recovered during excavation of the Zapatero archeological site on the northern coast of Chile, and the modern vertebrae were collected from specimens caught in the Pacific Ocean. The archeological vertebrae showed lower levels of mercury in comparison with those of current individuals, despite their larger size. However, the elevated Hg levels in archeological vertebrae proved the presence of naturally occurring mercury in the mid‐Holocene. Analyses on modern vertebrae confirmed the anthropic origin of mercury in the marine food web. Mercury biomagnifies through the marine food chain to swordfish (and humans) and did so even during the Holocene (bioaccumulation phenomenon). This study evidences that vertebrae and bones are potentially good biomarkers of mercury, including for archeological fish remains, and that the possible harmful effects on the health of past human communities can be analyzed and explained by the high consumption of fish.
Inhibition of human prostate smooth muscle contraction by the inhibitors of protein kinase C, GF109203X, and Go6983
Authors: Huang Ru , Liu Yuhan , Li Bingsheng , Wang Ruixiao , Tamalunas Alexander , Waidelich Raphaela , Strittmatter Frank , Stief Christian G. , Hennenberg Martin 
Published: October 2021

AbstractIntroductionProstate smooth muscle contraction is promoted by receptor‐induced activation of intracellular signaling pathways. The presumed involvement in etiology and medical treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) imparts a high clinical relevance to prostate smooth muscle contraction, which is contrasted by incomplete understanding at the molecular level. Involvement of protein kinase C (PKC) has been commonly assumed, but available studies were limited to nonhuman prostate smooth muscle or cell cultures. Here, we examined the effects of the PKC inhibitors Go6983 and GF109203x on contractions of human prostate tissues.MethodsProstate tissues were obtained from radical prostatectomy. Contractions were induced by electric field stimulation (EFS), α1‐adrenergic agonists (noradrenaline, phenylephrine, methoxamine), thromboxane A2 analog U46619, endothelin‐1, or calcium chloride in an organ bath.ResultsGF109203X (500 nM) and Go6983 (300  nM) reduced EFS‐, noradrenaline‐, phenylephrine‐, methoxamine‐, and U46619‐induced contractions of human prostate tissues, with maximum inhibitions approaching up to 55%. Using concentrations of 3 µM, GF109203X and Go6983 inhibited EFS‐ and noradrenaline‐induced contractions, with similar effect sizes as 500 and 300 nM, respectively. Endothelin‐1‐induced contractions were not inhibited by GF109203X, and to neglectable extent by Go6983. After depolarization in calcium‐free solution, calcium chloride‐induced concentration‐dependent contractions, which were inhibited by GF109203X and Go6983.ConclusionsGF109203X and Go6983 inhibit neurogenic, α1‐adrenergic, and thromboxane A2‐induced smooth muscle contractions in the human prostate, suggesting a role of PKC for human prostate smooth muscle contraction. The inhibition may by be imparted by inhibition of calcium sensitivity.
Pretherapeutic estimated glomerular filtration rate predicts development of chronic kidney disease in patients receiving PSMA‐targeted radioligand therapy
Authors: Widjaja Liam , Derlin Thorsten , Ross Tobias L. , Bengel Frank M. , Werner Rudolf A. 
Published: October 2021

AbstractBackgroundProstate‐specific membrane antigen (PSMA)‐targeted radioligand therapy (RLT) may be associated with renal toxicity. We aimed to identify predictive parameters for the development of chronic kidney disease (CKD) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing RLT.MethodsIn 46 mCRPC patients scheduled for Lu‐177‐PSMA‐RLT, pretherapeutic estimated glomerular filtration rate (eGFR [ml/min/1.73 m2]), Tc‐99m‐mercaptoacetyltriglycine (Tc‐99m‐MAG3) clearance and baseline Ga‐68‐PSMA‐ligand positron emission tomography (PET)‐derived renal cortical uptake and PSMA‐tumor volume (TV) were determined. We tested the predictive capability of these parameters and clinical risk factors for the occurrence of CKD (defined as CTCAE vers. 5.0 grade 2 or higher) during follow‐up.ResultsAfter 4 ± 3 cycles of RLT average eGFR declined from 76 ± 17 to 72 ± 20 ml/min/1.73 m2(p = 0.003). Increased estimated renal radiation dose (eRRD) was significantly associated with renal functional decline (p = 0.008). During follow‐up, 16/46 (30.4%) developed CKD grade 2 (no grade 3 or higher). In receiver operating characteristic (ROC) analysis, pretherapeutic eGFR was highly accurate in identifying the occurrence of CKD vs no CKD with an area under the curve (AUC) of 0.945 (p < 0.001; best threshold, 77 ml/min/1.73 m2), followed by Tc‐99m‐MAG3‐derived tubular extraction rate (TER; AUC, 0.831,p < 0.001; best threshold, 200 ml/min/1.73 m2). Renal PET signal (p = 0.751) and PSMA‐TV (p = 0.942), however, were not predictive. Kaplan–Meier analyses revealed adverse renal outcome for patients with lower eGFR (p = 0.001) and lower scintigraphy‐derived TER (p = 0.009), with pretherapeutic eGFR emerging as the sole predictive parameter in multivariate analysis (p = 0.007).ConclusionSerious adverse renal events are not a frequent phenomenon after PSMA‐targeted RLT. However, in patients developing moderate CKD after RLT, pretherapeutic eGFR is an independent predictor for renal impairment during follow‐up.
Dissipation kinetics of imidacloprid in cotton flower, nectariferous tissue, pollen and Apis mellifera products using QuEChERS method
Authors: Brar Pushpinder Kaur , Kang Balpreet Kaur , Rozy‐Rasool  , Chhuneja Pardeep Kumar , Sahoo Sanjay Kumar 
Published: October 2021

AbstractBACKGROUNDExposure of Apis mellifera to neonicotinoid insecticides is one of the factors attributed to the recent decline in A. mellifera populations resulting in economic and ecological losses due to loss of pollination services. Honey bees can get exposed to neonicotinoids like imidacloprid directly in the field at the time of application as well as during consumption of pollen and nectar from treated plants. So, the fate of imidacloprid in commodities to which honey bees get exposed needs to be overhauled.RESULTSResidue of imidacloprid was investigated following imidacloprid application as seed treatment (2.4 and 4.8 g a.i. kg‐1 seed) at the time of sowing and as foliar spray (17.8 and 35.6 g a.i. ha‐1) at 70 days after sowing when the crop was at full bloom stage.  The imidacloprid residue was below limit of quantification (LOQ) in flowers, necatariferous tissue, pollen from seed‐treated cotton plants and honey collected from hives kept in plots with seed‐treated cotton plants. However, average initial imidacloprid residue (2 h after spray) was 1.84 and 1.95 mg kg−1 in flowers; 0.22 and 0.24 mg kg−1 in nectariferous tissue; 0.88 and 0.96 mg kg−1 in pollen collected from plants sprayed with imidacloprid @ 17.8 g a.i. ha−1 at locations Faridkot and Bathinda, respectively. The average initial imidacloprid residue (21 days after spray) in honey collected from hives was 0.01 mg kg−1.CONCLUSIONThe residue in different substrates sampled from seed treated cotton plants was below LOQ. However, its foliar spray at bloom time resulted in imidacloprid residue in flower, nectariferous tissue, pollen and honey sampled from hives placed in plots. © 2021 Society of Chemical Industry.
Understanding the post‐monsoon tropical cyclone variability and trend over the Bay of Bengal during the satellite era
Authors: Tiwari Gaurav , Rameshan Arathi , Kumar Pankaj , Javed Aaquib , Mishra Alok K. 
Published: October 2021

AbstractAn effort is made to investigate the tropical cyclone (TC) variability over the Bay of Bengal in the warming climate scenario during the satellite era (1979–2018). In this study, the authors investigate interannual variations in the overall capacity of the Bay of Bengal (BoB) basin in the post‐monsoon season to produce either intense or moderate TCs. Globally accepted and widely used metrics accumulated cyclone energy (ACE) and power dissipation index (PDI) are used to examine the energy and damage generated by TCs. A statistical change‐point analysis is conducted to detect the shift in the tropical cyclone frequency and ACE during the study period, indicating the year 1999 as a change point. The results show the increasing trend in ACE in the BoB during the post‐monsoon season with a statistical significance of 95%. On the contrary, the overall frequency is almost unchanged but has shown an increasing trend in the last decade of the study period. Additionally, atmospheric and ocean factors influencing the TC intensity are investigated by applying principal component analysis for three categories of TCs, viz. the very severe cyclonic storm, severe cyclonic storm, and cyclonic storm. Implementation of principal component analysis and correlations of maximum sustained wind speed (MSW2; intensity) with relative vorticity, minimum sea‐level pressure (MSLP), sea‐surface temperature (SST), specific rainwater content, and vertical wind shear revealed relative vorticity as the most dominating parameter amongst all governing factors which determine the final intensity of the BoB TCs. On the contrary, SST shows the different nature of the relationship with different TC categories.
Fixed‐time stability analysis and stabilization control of a class of nonlinear systems with output constraints
Authors: Chen Xiandong , Zhang Xianfu , Qian Chunjiang 
Published: October 2021

AbstractThis article investigates the fixed‐time stabilization problem for a class of high‐order nonlinear systems with monotone degrees and output constraints. Firstly, a new fixed‐time stability criterion is established, which is less conservative in the explicit and delicate selection of Lyapunov functions. Then, by choosing a novel ‐type barrier Lyapunov function (BLF) and using the generalized adding a power integrator (AAPI) technique, a fixed‐time stabilization controller is explicitly constructed while achieving the requirement of state constraints. The novelty of the proposed control strategy can tackle simultaneously the fixed‐time stabilization of the involved systems with and without output constraints, without changing the controller structure. A simulation example is given to show the effectiveness of the proposed control strategy.
Weld line recognition and path planning with spherical tank inspection robots
Authors: Li Jie , Jin Shanshan , Wang Cunjin , Xue Jiameng , Wang Xingsong 
Published: October 2021

AbstractPeriodic inspections are required for the safe operation of large pressure vessels such as spherical tanks. Inspection robots have been applied in large pressure vessels due to their low cost and high efficiency. This paper presents a robotic system for the inspection of spherical tanks, which can identify and track weld lines on the shortest running route. Two‐dimensional (2D) weld maps were prepared for robot path planning on the basis of the actual distribution of weld lines. In 2D weld maps, indispensable repetitive lines were added to form an Eulerian circuit that traversed all weld lines. In addition, an improved Fleury algorithm was proposed to solve Eulerian circuit and plan an optimal running route for robot inspection. To accurately identify weld lines, deep learning networks were constructed and trained with weld line data sets, which were captured by the camera mounted in the front of the robot. The laboratory experiments indicated that the inspection robot could identify weld lines within 0.2–0.25 s and track weld lines with a maximum offset of ±20 mm. The experiment results demonstrated that the robot could plan the shortest path to traverse all weld lines on the experimental platform. In the field tests, the virtual simulation of weld path planning on spherical tanks was explored in detail. The field tests of a spherical tank (3000 m3) verified that the robotic system could improve the efficiency and stability of inspection operations and replace manual inspection with automated weld line recognition and weld path planning.
Trained to lead: Evidence from industrial research
Authors: Gagliardi Luisa , Mariani Myriam 
Published: October 2021

AbstractResearch SummaryThis study investigates the importance of early life training for people's leadership roles later in the workplace. We focus on team leaders in industrial research and analyze changes in team leadership after the abandonment of the military draft by the United States in 1973. This policy produced a twofold effect on leadership training opportunities: it eliminated the training provided during the draft and reduced the incentives to pursue long‐term education to defer conscription. Our results show a decrease in the probability of team leadership for men subject to the policy change. This effect, which is likely explained by the education channel, reduces over time. We discuss the implications of our findings for the formation of human capital to fulfill strategic leadership roles.Managerial SummaryThe progressive shift toward team‐based innovation practices puts organizations in need of new leaders. Whether leaders can be trained as such is, however, a controversial topic. We argue that one can learn to become a leader through life‐changing experiences. Our results show that people who undergo pervasive leadership‐enhancing opportunities early in life have higher chances of fulfilling leadership positions later in the workplace. Therefore, our study calls for the provision of early life, inclusive leadership enhancing opportunities to shape leadership attitudes and capabilities. These include formal education, corporate internships, and on‐the‐job training but could also span to other domains, such as political activism, associationism, and sporting activities.