bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new underlying mechanism for the neuroprotective effect of bosutinib: Reverting toxicity‐induced PARylation in SIN1‐mediated neurotoxicity
Authors: Yilmaz Sinem , Alkan Tolgaç , Ballar Kirmizibayrak Petek 
Published: September 2021

AbstractIncreased levels of reactive oxygen and nitrogen species play an important role in the development and progression of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. The overproduction of these highly reactive chemical species leads to DNA damage and subsequent activation of the poly(ADP‐ribose)polymerase (PARP) enzyme. Several studies have demonstrated the potential use of PARP inhibitors for neuroprotection. We previously reported that the dual Src/Abl kinase inhibitor bosutinib (BOS) decreases PARP activity and acts as a chemosensitizer in cancer cells. In this study, we evaluated the neuroprotective potential of BOS with respect to its inhibitory effect on cellular poly(ADP‐ribos)ylation (PARylation) using a 3‐morpholinosydnonimine (SIN1)‐mediated cellular toxicity model. Our data suggest that pretreatment with BOS, especially at lower doses, significantly decreased the level of SIN1‐induced cellular PARylation. This regulation pattern of PARylation was found to be associated with the protective effect of BOS against SIN1 on the viability of retinoic acid‐differentiated SH‐SY5Y cells. Furthermore, while PARP‐1 expression was decreased, phosphorylation of SAPK/JNK was not reverted at the observed neuroprotective doses of BOS. In conclusion, we suggest a novel mechanism for the neuroprotective effect of BOS involving the inhibition of cellular PARylation.
Evaluation of a new point‐of‐care quantitative reverse transcription polymerase chain test for detecting severe acute respiratory syndrome coronavirus 2
Authors: Watanabe Yoshiyuki , Oikawa Ritsuko , Suzuki Toshio , Funabashi Hidemitsu , Asai Daisuke , Hatori Yutaka , Takemura Hiromu , Yamamoto Hiroyuki , Itoh Fumio 
Published: September 2021

AbstractBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is rapidly spreading worldwide, and the resultant disease, coronavirus disease (COVID‐19), has become a global pandemic. Although there are multiple methods for detecting SARS‐CoV‐2, there are some issues with such tests, including long processing time, expense, low sensitivity, complexity, risk of contamination, and user friendly. This study evaluated the reproducibility and usability of a new point‐of‐care test (POCT) using real‐time quantitative reverse transcription polymerase chain reaction (qRT‐PCR) for detecting SARS‐CoV‐2.MethodsSamples from 96 patients with suspected SARS‐CoV‐2 infection were assessed using the real‐time qRT‐PCR‐based POCT and the conventional real‐time qRT‐PCR method based on the Japanese National Institute of Infectious Diseases guidelines (registration number: jRCT1032200025).ResultsThe real‐time qRT‐PCR‐based POCT had a positive agreement rate of 90.0% (18/20), a negative agreement rate of 100% (76/76), and a total agreement rate of 97.9% (94/96), and the significantly high score of questionnaire survey (total score p < 0.0001). In the two cases in which real‐time qRT‐PCR‐based POCT results did not match conventional real‐time qRT‐PCR test results, the SARS‐CoV‐2 RNA copy numbers were 8.0 copies per test in one case and below the detection limit in the other case when quantified using conventional real‐time qRT‐PCR. All patients could be triaged within 1 day using the real‐time qRT‐PCR‐based POCT without invalid reports.ConclusionsThe real‐time qRT‐PCR‐based POCT not only had high reproducibility and useability but also allowed rapid patient triage. Therefore, it may be helpful in clinical settings.
Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases
Authors: Alghamdi Malak A. , Tohary Mohammed , Alzaidan Hamad , Imtiaz Faiqa , Al‐Hassnan Zuhair N. 
Published: September 2021

AbstractSuccinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiency is an inherited metabolic disease caused by mutated OXCT1 gene resulting in recurrent ketoacidosis. Analysis of longitudinal data in such an ultra‐rare disease is warranted to delineate genotype–phenotype correlations and management outcome. A retrospective analysis of 17 patients, from nine unrelated families, with SCOT deficiency who were followed up in the Medical Genetics Clinic at King Faisal Specialist Hospital and Research Centre was conducted. All the patients were homozygous for p.R468C in OXCT1 gene. Most of the patients (n = 15, 88.2%) were symptomatic presenting with recurrent ketoacidosis, the onset of which ranged from 6 months to 4 years (median 2 years). A striking inter‐ and intrafamilial variability that ranged from being entirely asymptomatic to death during the first episode. All patients were instructed to avoid fasting, restrict protein in diet, and receive carnitine supplementation. However, there was no correlation between following instructions of chronic management and outcome. Most of the patients had their crises resolved and all of them had normal neurodevelopmental outcome. Our data suggest that SCOT deficiency caused by homozygous p.R468C has variable clinical presentation and incomplete penetrance. The apparent lack of correlation between protein restriction +/− carnitine supplementation and outcome suggests that chronic dietary restriction may not be warranted. However, a longer follow‐up on larger and heterogenous cohort of cases is needed before a clear conclusion on the long‐term management can be reached.
Multiscale modeling and numerical analyses of the electric conductivity of CNT/polymer nanocomposites taking into account the tunneling effect
Authors: Lu Xiaoxin , Pichon Lionel , Bai Jinbo 
Published: September 2021

AbstractTunneling effect plays a significant part in the extremely low electric percolation threshold and large conductivity of carbon nanotube (CNT)/polymer nanocomposites, which allows electric conduction between two CNTs separated at nanometric distances. In this work, a numerical model taking into account the nonlinear tunneling effect is proposed to evaluate the effective electric conductivity of CNT nanocomposites. The nonlinear finite element formulation is introduced, as well as the definitions of effective quantities for homogenization. Moreover, the CNTs are modeled by highly conducting line segments in order to avoid meshing the thin cylindrical tubes. With this technique, the percolation behavior of the composites has been simulated, and the effects of barrier height, CNT length distribution, CNT aspect ratio as well as alignment have been estimated. It turns out that the barrier height dominates the maximum electric conductivity, while the CNT aspect ratio determines the percolation threshold value, respectively. In addition, the anisotropic behavior is obtained by aligning the CNTs, which also results in higher percolation threshold compared with randomly distributed CNTs. Finally, the results are validated by available experimental data.
Loss of CX3CR1 augments neutrophil infiltration into cochlear tissues after acoustic overstimulation
Authors: Zhang Celia , Frye Mitchell D. , Riordan Juliana , Sharma Ashu , Manohar Senthilvelan , Salvi Richard , Sun Wei , Hu Bo Hua 
Published: September 2021

AbstractThe cochlea, the sensory organ for hearing, has a protected immune environment, segregated from the systemic immune system by the blood‐labyrinth barrier. Previous studies have revealed that acute acoustic injury causes the infiltration of circulating leukocytes into the cochlea. However, the molecular mechanisms controlling immune cell trafficking are poorly understood. Here, we report the role of CX3CR1 in regulating the entry of neutrophils into the cochlea after acoustic trauma. We employed B6.129P‐Cx3cr1tm1Litt/J mice, a transgenic strain that lacks the gene, Cx3cr1, for coding the fractalkine receptor. Our results demonstrate that lack of Cx3cr1 results in the augmentation of neutrophil infiltration into cochlear tissues after exposure to an intense noise of 120 dB SPL for 1 hr. Neutrophil distribution in the cochlea is site specific, and the infiltration level is positively associated with noise intensity. Moreover, neutrophils are short lived and macrophage phagocytosis plays a role in neutrophil clearance, consistent with typical neutrophil dynamics in inflamed non‐cochlear tissues. Importantly, our study reveals the potentiation of noise‐induced hearing loss and sensory cell loss in Cx3cr1−/− mice. In wild‐type control mice (Cx3cr1+/+) exposed to the same noise, we also found neutrophils. However, neutrophils were present primarily inside the microvessels of the cochlea, with only a few in the cochlear tissues. Collectively, our data implicate CX3CR1‐mediated signaling in controlling neutrophil migration from the circulation into cochlear tissues and provide a better understanding of the impacts of neutrophils on cochlear responses to acoustic injury.
Evaluating the aptitude of global climate models fromCMIP5andCMIP6in capturing the historical observations of monsoon rainfall over Sudan from 1946 to 2005
Authors: Hamadalnel Monzer , Zhu Zhiwei , Lu Rui , Almazroui Mansour , Shahid Shamsuddin 
Published: September 2021

AbstractSudan is one of the most vulnerable countries to climate change in the African Sahel region. Given the urgent need to understand the potential behaviour of the future climate, this study assessed the skill of 32 global climate models (GCMs) from the fifth (CMIP5) and the sixth (CMIP6) phases of the Coupled Model Intercomparison Project (CMIP) in simulating summer monsoon precipitation over Sudan for the period 1946–2005. The models were ranked based on the Skills Score, estimated using three statistical metrics, correlation coefficient, index of agreement, and normalized root mean square error. The best performing models and their ensembles were used for long‐term trend quantification, empirical orthogonal function (EOF) analysis, and assessment of precipitation associations with atmospheric circulation. GISS‐E2‐H, IPSL‐CM5A‐MR, and MPI‐ESM‐LR of CMIP5 and BCC‐CSM2‐MR, INM‐CM4‐8, and MPI‐ESM1‐2‐LR of CMIP6 showed the best performance in Sudan. Instead of August's unimodal peak rainfall, the GCMs, especially the CMIP5 GCMs, showed an unrealistic rainfall peak in May and a shift of the August rainfall peak to September. Only the CMIP6 multi‐model ensemble reliably reproduced the unimodal rainfall property. All models of both phases failed to reconstruct the dominant mode of monsoon precipitation as determined using EOF analysis, particularly in the country's southern parts. The models also failed to reproduce the long‐term rainfall trends in different climate zones. Only MPI‐ESM‐LR (CMIP5) and MPI‐ESM1‐2‐LR (CMIP6) were successful in simulating monsoon rainfall associations with sea surface temperature, El Niño‐Southern Oscillation teleconnection, and winds components at 850 hPa.
Effects of essential oil mixtures on nitrogen metabolism and odor emission via in vitro simulated digestion and in vivo growing pig experiments
Authors: Hsu Jui‐En , Lo Shih‐Hua , Lin Yuan‐Yu , Wang Hang‐Tsung , Chen Ching‐Yi 
Published: September 2021

AbstractBACKGROUNDEssential oils (EOs) are extensively used in swine production because of their bioactive action in gut health. In addition, some EOs have the potential to reduce waste emission. The present study aimed to find an optimal combination of carvacrol, thymol and cinnamaldehyde to promote nitrogen utilization and reduce waste emission by a model in vitro and an animal study.RESULTSIn the study in vitro, various dosages of essential oils (EOs) were used to evaluate the effect on nitrogen metabolism through a three‐step model. Compared with other EO combinations, 2EO (10 ppm cinnamaldehyde and 20 ppm thymol), and 3EO (10 ppm cinnamaldehyde, 20 ppm thymol and 200 ppm carvacrol) displayed greater nitrogen digestibility, lesser ammonia production and lower activity of microbial enzymes. In the animal study, growing male Landrace × Yorkshire pigs (initial body weight: 31.8 ± 3.3 kg, n = 18) were randomly divided into three groups and fed the control, 2EO or 3EO diet for 4 weeks. Pigs fed 3EO exhibited the greatest nitrogen digestibility (85.4%, P < 0.05). EO supplementation decreased the emission of ammonia (130–140 vs. 223 mg g−1) and total fecal nitrogen (8.0–9.9 vs. 12.4 g d−1) (P < 0.05). Microbial protease and urease activities were inhibited by EO treatments (P < 0.01). Both 2EO and 3EO reduced the content of indole and 3‐methylindole (P < 0.01), whereas only 2EO caused a decrease in p‐cresol (P < 0.1).CONCLUSION2EO was suitable for reducing waste emission and odorous compounds in growing pigs, whereas 3EO was optimal for increasing nitrogen utilization and partially reducing waste odorous compounds. © 2021 Society of Chemical Industry.
Effects of curcumin‐mediated photodynamic treatment on lipid degradation of oysters during refrigerated storage
Authors: Zhang Xu , Lu Na , Li Zhaojie , Meng Xianghong , Cao Wanxiu , Xue Yong , Xue Changhu , Tang Qingjuan 
Published: September 2021

AbstractBACKGROUNDOyster's lipid degradation leads to a decrease in edible and nutritional value. Curcumin‐mediated photodynamic treatment (PDT) is an innovative non‐thermal technology, although evaluation of the oyster's lipid degradation has been scarce. In the present study, we investigated peroxide value, thiobarbituric acid reactive substance, triacylglycerol and free fatty acids to evaluate the effect of curcumin‐mediated PDT on lipid degradation of oysters during refrigerated storage.RESULTSThe results showed that curcumin‐mediated PDT could delay oyster's lipid degradation. Next, the activities of enzymes were detected to determine the mechanisms behind the effects of curcumin‐mediated PDT. It was revealed that the activities of lipase, phospholipase A2 (PLA2), phospholipase C (PLC), phospholipase D (PLD) and lipoxygenase (LOX) were significantly inhibited after curcumin‐mediated PDT (P < 0.05). Furthermore, 16 s rRNA analysis established that the relative abundances of Pseudoalteromonas and Psychrilyobacter were reduced by 51.58% and 43.82%, respectively, after curcumin‐mediated PDT.CONCLUSIONCurcumin‐mediated PDT could delay oyster's lipid degradation by inhibiting the activities of lipase, PLA2, PLC, PLD and LOX, as well as by changing the oyster's microbial composition, reducing the relative abundance of Pseudoalteromonas and Psychrilyobacter. © 2021 Society of Chemical Industry.
Heritage hotel experiences in Nizwa, Oman
Authors: Al Riyami Hafidh , Almuhrzi Hamed , Scott Noel 
Published: September 2021

AbstractOman is a developing tourism destination providing a range of cultural heritage experiences. The Omani Government has focused on preservation of tangible heritage such as forts, souqs and archaeology sites, where there is a separation between heritage experiences and resident's everyday life. Recently, small entrepreneurs in Nizwa, Oman have begun to reuse traditional houses as heritage accommodation and thus embedding the tourist in the social fabric. This research examines the development of these private sector heritage hotels and their implications for the development of tourism in Nizwa. Data were collected through face‐to‐face interviews with government, entrepreneurs, tourists, and residents. This study contextualises the practices framework of Richards (2018), illustrating the mutually dependent and evolving interrelationships between meanings, resources and competences in a developing destination. The reuse of heritage hotels as a way to provide tourists with intangible cultural heritage and contemporary life experiences has changed the meanings of these resources from valueless to valuable. This supports the further development of intangible cultural heritage tourism experiences, but implies stakeholders need new competencies in experience design and destination management. The study indicates that cultural practices are dynamic and that various stakeholder groups (government, residents, businesses, and tourists) may have different meanings and competences. Further research is required to determine if these dynamic relationships form patterns across destinations.
Enhancement of the corrosion properties of cold sprayed Ti–6Al–4V coatings on mild steel via silica sealer
Authors: Morks Magdi F. , Zahiri Saden , Chen Xiao‐Bo , Gulizia Stefan , Cole Ivan S. 
Published: September 2021

AbstractThe pore formation associated with the cold spray process requires the development of an economical sealer to enhance the corrosion resistance of Ti–6Al–4V coatings on a mild steel substrate. Herein, a sound method is developed to seal pores in the cold sprayed Ti–6Al–4V coatings with silica sealer. Potentiodynamic polarization tests in 3.5 wt% sodium chloride electrolyte were employed to investigate the corrosion resistance of cold sprayed Ti–6Al–4V coatings fabricated at two standoff distances (30 and 70 mm) before and after the sealing process. The polarization resistance of cold sprayed Ti–6Al–4V coatings significantly increased by >80% after the sealing process. The electrochemical responses of cold sprayed Ti–6Al–4V were dependant on sealing the pores with agglomerated silica nanoparticles as observed by scanning electron microscopy and energy‐dispersive X‐ray analysis. The increase in polarization resistance makes the sealer an effective treatment for cold sprayed Ti–6Al–4V coatings used in marine environments and other engineering applications. This sophisticated sealing process can reduce the deposition cost by reducing the thickness of Ti–6Al–4V coatings and increasing their lifetime on metal components.
Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms
Authors: Yabumoto Megan , Kianmahd Jessica , Singh Meghna , Palafox Maria F. , Wei Angela , Elliott Kathryn , Goodloe Dana H. , Dean S. Joy , Gooch Catherine , Murray Brianna K. , Swartz Erin , Schrier Vergano Samantha A. , Towne Meghan C. , Nugent Kimberly , Roeder Elizabeth R. , Kresge Christina , Pletcher Beth A. , Grand Katheryn , Graham John M. , Gates Ryan , Gomez‐Ospina Natalia , Ramanathan Subhadra , Clark Robin Dawn , Glaser Kimberly , Benke Paul J. , Cohen Julie S. , Fatemi Ali , Mu Weiyi , Baranano Kristin W. , Madden Jill A. , Gubbels Cynthia S. , Yu Timothy W. , Agrawal Pankaj B. , Chambers Mary‐Kathryn , Phornphutkul Chanika , Pugh John A. , Tauber Kate A. , Azova Svetlana , Smith Jessica R. , O’Donnell‐Luria Anne , Medsker Hannah , Srivastava Siddharth , Krakow Deborah , Schweitzer Daniela N. , Arboleda Valerie A. 
Published: September 2021

AbstractThe phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say‐Barber‐Biesecker‐Young‐Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B‐related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10/18) of individuals receive diagnoses before the age of 2 years (median age = 1.96 years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the KAT6B gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with KAT6B‐related disorders.
Fully automated noncoplanar radiation therapy treatment planning
Authors: Huang Charles , Yang Yong , Xing Lei 
Published: September 2021

AbstractPurposeTo perform fully automated noncoplanar (NC) treatment planning, we propose a method called NC‐POPS to produce NC plans using the Pareto optimal projection search (POPS) algorithm.MethodsNC radiation therapy treatment planning has the potential to improve dosimetric quality as compared to traditional coplanar techniques. Likewise, automated treatment planning algorithms can reduce a planner's active treatment planning time and remove inter‐planner variability. Our NC‐POPS algorithm extends the original POPS algorithm to the NC setting with potential applications to both intensity‐modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). The proposed algorithm consists of two main parts: (1) NC beam angle optimization (BAO) and (2) fully automated inverse planning using the POPS algorithm.ResultsWe evaluate the performance of NC‐POPS by comparing between various NC and coplanar configurations. To evaluate plan quality, we compute the homogeneity index (HI), conformity index (CI), and dose–volume histogram statistics for various organs‐at‐risk (OARs). As compared to the evaluated coplanar baseline methods, the proposed NC‐POPS method achieves significantly better OAR sparing, comparable or better dose conformity, and similar dose homogeneity.ConclusionsOur proposed NC‐POPS algorithm provides a modular approach for fully automated treatment planning of NC IMRT cases with the potential to substantially improve treatment planning workflow and plan quality.
Technical Note: Effects of rotating gantry on magnetic field and eddy currents in 0.35 T MRI‐guided radiotherapy (MR‐IGRT) system
Authors: Michael Gach H. , Curcuru Austen N. , Kim Taeho , Yang Deshan 
Published: September 2021

AbstractPurposeThe purpose of this study was to identify the cause of severe image artifacts that occurred during gantry rotation in a 0.35 T MRI‐Linac by comparing measurements of eddy currents, center frequency, and field inhomogeneities made with the gantry in motion and stationary.MethodsGradient and B0 eddy currents were calculated from the free induction decays (FIDs) resulting from selective excitation at a temporal resolution of 200 ms/measurement. B0 eddy currents were also calculated from FIDs acquired with nonselective excitation at a temporal resolution of 100 ms/measurement. Center frequencies and B0 inhomogeneities were measured by acquiring FIDs with a repetition time (TR) of 290 ms. Cartesian and radial 2D true fast imaging with steady‐state precession (TrueFISP) pulse sequences used in real‐time MRI‐guided radiation therapy (MR‐IGRT) were acquired. To assess artifact severity, the normalized root mean square error (nRMSE) was calculated between a reference MRI (static gantry) and MRIs acquired during gantry rotation for each serial acquisition. Image artifacts were qualitatively graded as nominal, minor, or severe. Measurements were conducted while the gantry was rotated through its entire range for both clockwise and counterclockwise. Measurements during gantry rotation were compared to measurements with a stationary gantry (every 30°).ResultsSevere image artifacts were observed 22–35% of the time while the gantry was rotating. Short time constant eddy currents were not affected by gantry rotation. The peak to peak center frequency and FWHM rose by factors of 13.2–14.5 and 1.1–1.6, respectively, for the rotating versus stationary gantry. The magnitude of the center frequency offset and field inhomogeneities depended on the direction of the gantry rotation.ConclusionsImage artifacts during gantry rotation were primarily caused by center frequency variations and field inhomogeneities. Therefore, dynamic B0 compensation techniques should be able to reduce artifacts during gantry rotation.