bluuebunny/crossref_metadata_2025_split huggingface dataset:
The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma
Authors: Zhu Jie , Fang Peiqi , Wang Chong , Gu Meixiu , Pan Baishen , Guo Wei , Yang Xinrong , Wang Beili 
Published: October 2021

AbstractBackgroundLenvatinib is a novel multiple receptor tyrosine kinase inhibitor used for hepatocellular carcinoma (HCC) treatment. Although its main function is to suppress VEGFR and FGFR pathway, its immunomodulatory activity in HCC is not elucidated. Thus, this study aimed to investigate the immunomodulatory capability of lenvatinib in HCC.Material and methodsTotally 47 patients with HCC were enrolled in this study, and the immune cells and serum cytokine profiles before initiation of treatment and after 1 and 3 months were measured. The immune checkpoint receptors on the immune cells were also evaluated. Kaplan–Meier survival estimate and log rank tests were used to assess the prognostic value.ResultThe frequency of T helper (Th) cells and T regulatory (Treg) cells reduced after lenvatinib treatment, while cytotoxic T lymphocyte (CTL) cells increased significantly. The cytokine profiles showed IL‐2, IL‐5, IFN‐γ increased; other cytokines including IL‐6, IL‐10, TNF‐ α and TNF‐ β decreased with lenvatinib therapy. Furthermore, the PD‐1 and TIM‐3 expressed on CTL had greatly decreased; the expression of TIM‐3 and CTLA‐4 was reduced on Treg cells as well. Besides, the new index CTL/Treg ratio was created, and low ratio was associated with the unfavorable outcome of HCC patients.ConclusionOur results confirmed that lenvatinib is capable of improving patients’ immune status, saving the effector cells from exhaustion status and inhibiting the number and function of immunosuppressive cells. The novel index CTL/Treg ratio qualifies as a predictor for the outcome of patients with lenvatinib therapy.
First report of invasive Aspergillus rhinosinusitis in a critically ill COVID‐19 patient affected by acute myeloid leukemia, northeastern Iran
Authors: Hosseinikargar Neginsadat , Basiri Reza , Asadzadeh Mohammad , Najafzadeh Mohammad Javad , Zarrinfar Hossein 
Published: October 2021

AbstractThis is a report of established invasive Aspergillus rhinosinusitis in a patient diagnosed with COVID‐19 and afflicted by AML, which was initially considered to be rhinocerebral mucormycosis.
COVID‐19 outbreak as a probable cause of increased risk of intracranial rebleeding in partially treated cerebral arteriovenous malformations
Authors: Ghorbani Mohammad , Lafta Ghazwan , Rahbarian Farhad 
Published: October 2021

AbstractPatients who are infected with COVID‐19 and have cerebral arteriovenous malformations which are partially treated or untreated may be more liable to rupture or bleed than not infected patients.
Hereditary hemochromatosis and JAK2‐positive polycythemia vera
Authors: Radwan Ahmed , Othman Ibraheem 
Published: October 2021

AbstractA 59‐year‐old man was diagnosed with JAK2‐positive polycythemia vera. Subsequently, further laboratory testing revealed elevated ferritin and iron saturation. Genetic testing for HFE gene mutation screen revealed that the patient was positive for heterozygous C282Y mutation. The patient was ultimately diagnosed with both polycythemia vera and hereditary hemochromatosis.
Scanning Electrochemical Cell Microscopy in a Glovebox: Structure‐Activity Correlations in the Early Stages of Solid‐Electrolyte Interphase Formation on Graphite
Authors: Martín‐Yerga Daniel , Kang Minkyung , Unwin Patrick R. 
Published: October 2021

AbstractUnderstanding the formation and properties of the solid‐electrolyte interphase (SEI) will enable the development of enhanced Li‐ion batteries (LiBs) and other battery types. Herein, we report scanning electrochemical cell microscopy (SECCM) in a glovebox to characterize the SEI formation on the basal surface of highly oriented pyrolytic graphite (HOPG) as a model system of negative LiB electrodes with nonaqueous electrolytes. Different grades of HOPG have been studied, which provide a range of step edge densities on the basal surface. The high‐throughput and spatially‐resolved character of SECCM allows thousands of measurements across a surface, revealing how surface heterogeneity in graphite affects the early stages of the SEI formation and its properties. Step edges promote electrolyte reduction resulting in a more passivating SEI than that formed on smoother surfaces. A strongly insulating but relatively unstable SEI is detected under fast formation conditions, while slow formation rates induce the steady growth of an increasingly passivating SEI. This work provides new insights on the SEI dynamic formation and demonstrates SECCM as a powerful technique to probe the effect of local structure in heterogeneous battery materials under inert atmosphere. The demonstration that SECCM can readily be deployed in a glovebox serves as a foundation for future experiments to explore high resolution electrochemical imaging of battery electrode materials.
Push‐Pull Stiff‐Stilbene: Proton‐Gated Visible‐Light Photoswitching and Acid‐Catalyzed Isomerization
Authors: Villarón David , Duindam Nol , Wezenberg Sander J. 
Published: October 2021

AbstractDonor‐acceptor substituted stiff‐stilbene is shown to undergo isomerization induced by visible light avoiding the need for harmful UV light. This visible‐light photoswitching is inhibited by protonation of the dimethylamino‐donor unit, disrupting the push‐pull character and thus, gating of the photochromic properties is allowed by acid/base addition. Remarkably, the addition of a mild acid also triggers fast thermal back‐isomerization, which is unprecedented for stiff‐stilbene photoswitches usually having a very high energy barrier for this process. These combined features offer unique orthogonal control over switching behavior by light and protonation, which is investigated in detail by 1H NMR and UV/Vis spectroscopy. In addition, TD‐DFT calculations are used to gain further insight into the absorption properties. Our results will help elevating the level of control over dynamic behavior in stiff‐stilbene applications.
A diffuse interface method for simulation‐based screening of heat transfer processes with complex geometries
Authors: Monte Elizabeth J. , Lowman James , Abukhdeir Nasser Mohieddin 
Published: October 2021

AbstractFrequently, the simulation‐based design of physicochemical processes requires screening of large numbers of alternative designs with complex geometries. These geometries may result in conformal meshes which introduce stability issues, significant computational complexity, and require user‐interaction for their creation. In this work, a method for simulation of heat transfer using the diffuse interface method to capture a complex geometry is presented as an alternative to conformal meshing, with analysis and comparisons given. The methods presented include automated non‐iterative generation of phase fields from CAD geometries and an extension of the diffuse interface method for mixed boundary conditions. Simple measures of diffuse interface quality are presented and used to predict performance. The method is applied to a realistic three‐dimensional heat transfer problem (LED heat sink) and compared to the traditional conformal mesh approach. It is found to enable reasonable accuracy at an order‐of‐magnitude reduction in simulation time or comparable accuracy for equivalent simulation times.
Scope, Limitations and Mechanistic Analysis of the HyperBTM‐Catalyzed Acylative Kinetic Resolution of Tertiary Heterocyclic Alcohols**
Authors: Smith Samuel M. , Greenhalgh Mark D. , Feoktistova Taisiia , Walden Daniel M. , Taylor James E. , Cordes David B. , Slawin Alexandra M. Z. , Cheong Paul Ha‐Yeon , Smith Andrew D. 
Published: October 2021

AbstractThe full scope and limitations of the catalytic acylative kinetic resolution of a range of tertiary heterocyclic alcohols (78 examples,sup to >200) is reported under operationally‐simple conditions, using low loadings of a commercially available Lewis basic isothiourea catalyst, HyperBTM (generally 1 mol %). The protocol is highly effective for the kinetic resolution of 3‐substituted 3‐hydroxyoxindole and α‐substituted α‐hydroxylactam derivatives bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. The full power of this methodology has been showcased through the synthesis of highly enantioenriched biologically‐active target compounds in both enantiomeric forms. To provide further insight into the reaction mechanism, a detailed kinetic analysis of this Lewis base‐catalyzed acylation of tertiary alcohols is reported using the variable time normalization analysis (VTNA) method.
Use composite coating of chitosan‐chia seed gum enriched with microliposomes of Bay laurel essential oil to increase the shelf life of quail fillets
Authors: Eslamian Amiri Motahareh , Ahmady Mohammad , Ariaii Peiman , Golestan Leila , Ghorbani‐HasanSaraei Azade 
Published: October 2021

AbstractIn this study, the effect of composite chitosan‐chia seed coating (CH‐CG) with Bay laurel (Laurus nobilis) essential oil (BE) in two forms including free and nanocapsulated on the shelf life of quail fillets during the 16‐day refrigeration (4 ± 1℃) period was investigated. For this purpose, first, BE was extracted by Clevenger apparatus. Then, nanoliposomes BE were produced, and the properties of BE and nanoliposomes BE were investigated. In order to investigate the shelf life of quail, 6 treatments were produced including 1: control (C), 2: CH‐CG, CH‐CG+BE at 800 ppm, 3: CH‐CG+BE at 1600 ppm, 4: CH‐CG+nano BE at 800 ppm, 5: CH‐CG+nano BE at 1600 ppm, and periodically chemical parameters (peroxide value, free fatty acid, total volatile basic nitrogen, texture firmness, and chewing ability) and microbial (total viable bacteria (TVC) and psychrotrophic bacteria), and the effect of different treatments on control in Escherichia coli and Staphylococcus aureus inoculated populations in quail was also investigated. The BE had high antioxidant and antimicrobial properties. The particle size and microencapsulation efficiency of BE nanoliposome were 98.3 nm and 75.95%, respectively. The results of chemical and microbial analysis showed that in general, the coating with essential oil slowed down the increasing trend of oxidation and microbial indices compared to the control treatment and nanocapsulation of essential oil has increased its antimicrobial and antioxidant properties (p < .05). At the end of storage period, in all tests, treatments of 3, 4, and 5 had the allowed microbial and chemical range and they also inhibited the growth of these bacteria (p < .05). Overall, considering the higher sensory score of treatment 4 and economic efficiency, it seems that this treatment can be used as a natural preservative in the meat industry.
Development and Molecular Understanding of a Pd‐Catalyzed Cyanation of Aryl Boronic Acids Enabled by High‐Throughput Experimentation and Data Analysis
Authors: De Jesus Silva Jordan , Bartalucci Niccolò , Jelier Benson , Grosslight Samantha , Gensch Tobias , Schünemann Claas , Müller Bernd , Kamer Paul C. J. , Copéret Christophe , Sigman Matthew S. , Togni Antonio 
Published: October 2021

AbstractA synthetic method for the palladium‐catalyzed cyanation of aryl boronic acids using bench stable and non‐toxic N‐cyanosuccinimide has been developed. High‐throughput experimentation facilitated the screen of 90 different ligands and the resultant statistical data analysis identified that ligand σ‐donation, π‐acidity and sterics are key drivers that govern yield. Categorization into three ligand groups – monophosphines, bisphosphines and miscellaneous – was performed before the analysis. For the monophosphines, the yield of the reaction increases for strong σ‐donating, weak π‐accepting ligands, with flexible pendant substituents. For the bisphosphines, the yield predominantly correlates with ligand lability. The applicability of the designed reaction to a wider substrate scope was investigated, showing good functional group tolerance in particular with boronic acids bearing electron‐withdrawing substituents. This work outlines the development of a novel reaction, coupled with a fast and efficient workflow to gain understanding of the optimal ligand properties for the design of improved palladium cross‐coupling catalysts.
Long‐term risk of colorectal cancer after removal of adenomas during screening colonoscopies in a large community‐based population in China
Authors: Zhu Yingshuang , Huang Yanqin , Hu Yeting , Fang Yimin , Kong Xiangxing , Xiao Qian , He Jinjie , Zhu Yunfeng , Li Qilong , Yang Jinhuan , Dong Qi , Jin Mingjuan , Wang Meilin , Chen Kun , Zheng Shu , Ding Kefeng 
Published: October 2021

AbstractPatients with conventional adenoma removal are recommended to undergo colonoscopy surveillance to prevent colorectal cancer (CRC). However, evidence supporting the guidelines of colonoscopy surveillance is limited, especially among the Chinese population. We investigated the association between colonoscopy adenoma findings and CRC risk among individuals aged 40 to 74 years who underwent baseline colonoscopy from 2007 to 2016 in Jiashan and Haining, Zhejiang, China; 34 382 participants were categorized into advanced adenoma, nonadvanced adenoma and no adenoma based on adenoma findings. A multivariable Cox regression model was used to estimate the hazard ratio (HR) of CRC incidence with adjustment for potential confounding factors. After a median follow‐up time of 7.7 years, 113 incident cases of CRC were identified (18 occurred in 1632 participants with advanced adenoma, 16 in 3973 participants with nonadvanced adenoma and 79 in 28 777 participants with no adenoma). Compared to no adenoma group, the adjusted HR for CRC in advanced adenoma group was 4.01 (95% CI, 2.37‐6.77). For nonadvanced adenomas, individuals with ≥3 adenomas showed an increased risk of CRC (HR, 3.65; 95% CI, 1.43‐9.31), but no significantly increased risk of CRC was found for 1 to 2 nonadvanced adenomas, compared to those with no adenoma. Our study suggested that the risk of subsequent CRC increased in individuals with high‐risk adenoma (at least one advanced adenoma or ≥3 nonadvanced adenomas), but not in those with 1 to 2 nonadvanced adenomas. These results provide the first evidence from the Chinese population for the current surveillance guidelines.
Chronic endometritis: A prevalent yet poorly understood entity
Authors: Margulies Samantha L. , Flores Valerie , Parkash Vinita , Pal Lubna 
Published: October 2021

AbstractObjectiveTo examine the prevalent understanding of and management approaches to chronic endometritis among obstetricians/gynecologists.MethodsIn a cross‐sectional observational study, 262 members of national and international professional obstetrician/gynecologist societies were surveyed via anonymous electronic survey that investigated knowledge of the pathophysiology, diagnostic criteria, clinical implications, and treatment strategies for chronic endometritis. Statistical analyses of results were performed using Fisher's exact tests, chi square tests and odds ratios with 95% confidence intervals. A two‐sided P < 0.05 was deemed statistically significant.ResultsResponses identified a concerning spectrum of deficiencies in the understanding of the pathophysiology of chronic endometritis, in awareness of clinical presentation of chronic endometritis, and in the understanding of methodology/ies that allow diagnosis of chronic endometritis. Heterogeneities in management approaches to chronic endometritis were apparent.ConclusionOur findings underscore a need for targeted efforts to gain clarity on chronic endometritis and to establish evidence‐based consensus for good clinical practice. In the absence of a clear understanding of chronic endometritis diagnosis, we posit that the prevalent inconsistencies are likely inflicting unquantified and underappreciated burdens on patients and healthcare systems. We propose consideration for a task force to examine existing literature and create standards for good practice for a prevalent condition.
Maternal outcomes before and after new oxytocin protocol at cesarean delivery
Authors: Kotze Adri , Adam Yasmin , Naidoo Poovangela 
Published: October 2021

AbstractObjectiveThe primary objective was to describe the incidence of post‐partum hemorrhage at cesarean delivery before and after implementation of a new high dose oxytocin protocol at Chris Hani Baragwanath Academic Hospital.MethodsThis was a cross sectional retrospective record review 3 months before and 3 months after the implementation of a high dose oxytocin protocol. The study included all women that underwent cesarean delivery between 1 November 2016 and 30 April 2017 with a gestation of >24 weeks.ResultsA total of 4604 Cesarean deliveries were performed during the study period, 2162 before the implementation of the new protocol and 2442 after. The incidence of post‐partum hemorrhage was 4.8% (n = 91) in the Before group and 3.9% (n = 89) in the After group (P = 0.17). There was a 17.9% change in incidence of postpartum hemorrhage between the groups (P = 0.17). There was no significant difference in uterine atony between the Before and After groups (21.8% and 30.1%, P = 0.30).ConclusionThere was no difference in the incidence of postpartum hemorrhage at cesarean delivery after the implementation of a high dose oxytocin protocol.
Thymoquinone upregulates miR‐125a‐5p, attenuates STAT3 activation, and potentiates doxorubicin antitumor activity in murine solid Ehrlich carcinoma
Authors: Atteia Hebatallah H. , Arafa Manar H. , Mohammad Nanies S. , Amin Dalia M. , Sakr Amr T. 
Published: October 2021

AbstractIn breast cancer, there has been evidence of atypical activation of signal transduction and activators of transcription 3 (STAT3). Thymoquinone (TQ) exerts its anti‐neoplastic effect through diverse mechanisms, including STAT3 inhibition. The tumor suppressor, microRNA‐125a‐5p was reported to be downregulated in various breast cancer cells. Therefore, we investigated the influence of TQ and/or doxorubicin on microRNA‐125a‐5p and its correlation with STAT3 activation as well as tumor growth in mice bearing solid Ehrlich tumors. We found that TQ markedly suppressed inducible and constitutive phosphorylation of STAT3 in tumor tissue without affecting STAT5. Moreover, it attenuated tumor growth, downregulated STAT3 downstream target proteins, and increased the apoptotic activities of caspase‐3 and ‐9. Interestingly, TQ‐elicited synergism of doxorubicin anti‐neoplastic activity was coupled with upregulation of tumoral microRNA‐125a‐5p. Taken together, the current findings raise the potential of TQ as a promising chemomodulatory adjuvant to augment mammary carcinoma sensitivity to doxorubicin.
Mitochondrial dysfunction in skeletal muscle contributes to the development of acute insulin resistance in mice
Authors: Lee Hyunjung , Ha Tae Youl , Jung Chang Hwa , Nirmala Farida Sukma , Park So‐Young , Huh Yang Hoon , Ahn Jiyun 
Published: October 2021

AbstractBackgroundAlthough mounting evidence indicates that insulin resistance (IR) co‐occurs with mitochondrial dysfunction in skeletal muscle, there is no clear causal link between mitochondrial dysfunction and IR pathogenesis. In this study, the exact role of mitochondria in IR development was determined.MethodsSix‐week‐old C57BL/6 mice were fed a high‐fat diet for 2 weeks to induce acute IR or for 24 weeks to induce chronic IR (n = 8 per group). To characterize mitochondrial function, we measured citrate synthase activity, ATP content, mitochondrial DNA (mtDNA) content, and oxygen consumption rate in gastrocnemius and liver tissues. We intraperitoneally administered mitochondrial division inhibitor 1 (mdivi‐1) to mice with acute IR and measured mitochondrial adaptive responses such as mitophagy, mitochondrial unfolded protein response (UPRmt), and oxidative stress (n = 6 per group).ResultsAcute IR occurred coincidently with impaired mitochondrial function, including reduced citrate synthase activity (−37.8%, P < 0.01), ATP production (−88.0%, P < 0.01), mtDNA (−53.1%, P < 0.01), and mitochondrial respiration (−52.2% for maximal respiration, P < 0.05) in skeletal muscle but not in liver. Administration of mdivi‐1 attenuated IR development by increasing mitochondrial function (+58.5% for mtDNA content, P < 0.01; 4.06 ± 0.69 to 5.84 ± 0.95 pmol/min/mg for citrate synthase activity, P < 0.05; 13.06 ± 0.70 to 34.87 ± 0.70 pmol/min/g for maximal respiration, P < 0.001). Western blot analysis showed acute IR resulted in increased autophagy (mitophagy) and UPRmt induction in muscle tissue. This adaptive response was inhibited by mdivi‐1, which reduced the mitochondrial oxidative stress of skeletal muscle during acute IR.ConclusionsAcute IR induced mitochondrial oxidative stress that impaired mitochondrial function in skeletal muscle. Improving mitochondrial function has important potential for treating acute IR.
Anthropogenic influence on extreme temperatures in China based on CMIP6 models
Authors: Hu Ting , Sun Ying 
Published: October 2021

AbstractWith rapid warming since the mid‐20th century, China has experienced remarkable changes in the extreme temperatures. We use the updated observational data and the newest generation of climate models from Coupled Model Intercomparison Project Phase 6 (CMIP6) to investigate the relative contribution from different external forcing to the temperature extremes. We find that both intensity and frequency indices of extreme temperature experience continuous warming during 1951–2018. More intense and more frequent warm extremes and less intense and less frequent cold extremes are observed in most regions. An exception is a warming slowdown in the intensity of the coldest extremes since the late 1990s in northeast China. These observed changes are generally well reproduced by CMIP6 climate models, especially for the warm days and nights. Detection analyses based on an optimal fingerprinting method show that anthropogenic forcing (ANT) is the main driver for these changes, with cold extremes less detectability than warm extremes. Three‐signal detections show that both greenhouse gas (GHG) and anthropogenic aerosols (AA) influences can be detected and separated in most warm extreme indices but not in the cold extremes, while the natural forcing influence is negligible for most indices. GHG forcing plays a dominant role, accounting for about 1.6 (1.1–2) times of observed warming in changes of most indices, while the AA offset about 35% (10–60%) of GHG induced warming for warm extremes. Anthropogenic factors including land use and ozone may have a very small positive contribution to the extreme temperatures.