bluuebunny/crossref_metadata_2025 huggingface dataset:
PF‐06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity
Authors: Su Limin , Yuan Haoxing , Zhang Haoran , Wang Ruoqi , Fu Kequan , Yin Long , Ren Ying , Liu Hongli , Fang Qian , Wang Junqi , Guo Dong
Published: June 2022

Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves over‐proliferation of cyst‐lining epithelial cells and excessive cystic fluid secretion. While metformin effectively inhibits renal cyst growth in mouse models of ADPKD it exhibits low potency, and thus an adenosine monophosphate‐activated protein kinase (AMPK) activator with higher potency is required. Herein, we adopted a drug repurposing strategy to explore the potential of PF‐06409577, an AMPK activator for diabetic nephropathy, in cellular, ex vivo and in vivo models of ADPKD. Our results demonstrated that PF‐06409577 effectively down‐regulated mammalian target of rapamycin pathway‐mediated proliferation of cyst‐lining epithelial cells and reduced cystic fibrosis transmembrane conductance regulator‐regulated cystic fluid secretion. Overall, our data suggest that PF‐06409577 holds therapeutic potential for ADPKD treatment.
Grammar and Electronic Communication
Authors: Herring Susan C.
Published: June 2022

How digital communication technologies are affecting language, literacy, and language change has excited considerable speculation and inspired a growing body of scholarship. At the heart of this question is the notion of grammar, or the set of structural rules that govern the composition of words, phrases, and sentences in a language. Grammatical usage in computer‐mediated communication (CMC), referred to here as e‐grammar, often deviates from prescriptive norms of written language. This entry describes nonstandard structural characteristics of e‐grammar at the levels of typography, orthography, morphology, and syntax in text‐based English CMC. Separate sections address emoji grammar, e‐grammar and language change, and e‐grammar and literacy.
Language Teaching and Learning: Quantitative Methods
Authors: Collentine Joseph , Collentine Karina
Published: June 2022

Quantitative methods help researchers to determine objectively the comparative effectiveness of different approaches to language instruction. This entry delineates essential statistical techniques for comparing the effectiveness of two approaches to task‐based language teaching (TBLT) in a typical pretest–posttest study. Step‐by‐step procedures are outlined for conducting a repeated measures analysis in SPSS, including the presentation and interpretation of descriptive and inferential statistics.
Clinical validation of novel lightning dose optimizer for gamma knife radiosurgery of irregular‐shaped arteriovenous malformations and pituitary adenomas
Authors: Pokhrel Damodar , Bernard Mark E. , Knight James , St. Clair William , Fraser Justin F.
Published: June 2022

Purpose

To demonstrate the clinical feasibility of a novel treatment planning algorithm via lightning dose optimizer (LDO) on Leksell Gamma Knife (LGK) GammaPlan with significantly faster planning times for stereotactic radiosurgery (SRS) of the complex and difficult arteriovenous malformations (AVMs) and pituitary adenomas.

Methods and materials

After completing the in‐house end‐to‐end phantom testing and independent dose verification of the recently upgraded LDO algorithm on GammaPlan using the MD Anderson's IROC anthropomorphic SRS head phantom irradiation credentialing, 20 previously treated GK‐SRS patients (10 AVM, average volume 3.61 cm3 and 10 pituitary adenomas, average volume 0.86 cm3) who underwent manual forward planning on GammaPlan were retrospectively replanned via LDO. These pathologies were included because of the need for adequate dose delivery with organs at risk in very close proximity. LDO finds the target curvature boundary by well‐formulated linear programing objectives and inversely optimizes the GK‐SRS plan by isocenter placement, optimization, and sequencing. For identical target coverage, the LDO and original manual plans were compared for target conformity, gradient index, dose to critical organs, and surrounding normal brain. Additionally, various treatment delivery parameters, including beam‐on time were recorded.

Results

For both patient cohorts, LDO provided similar target coverage with better dose conformity, tighter radiosurgical dose distribution with a lower value of gradient indices (all p < 0.001), and lower dose to critical organs. For AVMs, there was a significant reduction of normal brain V10Gy, V12Gy, and V14Gy by 4.74, 3.67, and 2.67 cm3 (all p < 0.001). LDO had twice the number of shots (p < 0.001), and longer beam‐on time (p = 0.012) by a factor of 1.44. For pituitary adenomas, LDO provided systematically lower values of V10Gy, V12Gy, and V14Gy by 1.08, 0.86, and 0.68 cm3 (all p < 0.001), and lower maximum dose to optic pathway by 0.7 Gy (p = 0.005), but had almost twice the numbers of shots (p < 0.001) and increased beam‐on time (p = 0.005) by a factor of 1.2. However, for both patient groups, the average planning time for the LDO was <5 min, compared to the estimated 30–90 min of manual planning times.

Conclusion

GK‐SRS treatment on Leksell Perfexion GammaPlan using the LDO provided highly conformal target coverage with a steep dose gradient, spared critical organs, and significantly reduced normal brain dose for complex targets at the cost of slightly higher treatment times. LDO generated high‐quality treatment plans and could significantly reduce planning time. If available, the LDO algorithm is suggested for validation and clinical use for complex and difficult GK cases.
EMBRACE: One Small Story in Lupus—One Giant Challenge in Clinical Trials
Authors: Sheikh Saira Z. , Englund Tessa R. , Burriss Susan W. , Bull Jonca , Harry Anya , Groark James G. , Hall Ashley M. , Miller Michelle , Roth David A.
Published: June 2022

Clinical trials of novel therapeutics in the United States have not been adequately representative of diverse populations, particularly racial and ethnic minorities. The challenges and consequences of underrepresentation in clinical trial recruitment are exemplified by the case of belimumab, a biologic treatment for systemic lupus erythematosus (SLE), a disease that is more prevalent in patients of Black African ancestry and of Hispanic/Latino ethnicity than in other patient populations. Although belimumab was found to be effective in phase 2 and 3 clinical trials in the general population, post hoc analyses of efficacy data in patients of Black African ancestry showed inconsistent results. Consequently, a cautionary statement regarding belimumab use in this population was added to the product label. To alleviate concerns that belimumab may not be safe and effective for patients of Black African ancestry, the Efficacy and Safety of Belimumab in Black Race Patients with SLE (EMBRACE) study was conducted in a post‐marketing commitment to the Food and Drug Administration. The study recruited only patients who self‐identified as being of Black race; its findings led to the removal of the cautionary labeling of belimumab use in patients of Black African ancestry. Our manuscript highlights the critical lessons learned from the successes and failures of the EMBRACE study. It also provides suggestions for overcoming health disparities, highlighting strategies for conducting well‐designed clinical trials to overcome systematic barriers to diversity in recruitment, with a focus on enacting long‐term support to ensure equity in the process, products, and benefits from drug development and clinical trials.
Fast finite‐time adaptive neural fault‐tolerant tracking control for multi‐input multi‐output systems with full‐state constraints
Authors: Wang Huanqing , Shen Liya , Wang Ding , Niu Ben , Zhao Xudong
Published: June 2022

This article investigates the problem of fast finite‐time adaptive neural fault‐tolerant tracking control for multi‐input multi‐output (MIMO) nonlinear systems with full‐state constraints and actuator faults. The radial basis function neural networks are introduced to deal with unknown nonlinear functions. In addition, an additive transformation and one‐to‐one mapping method are employed to deal with the control problem of MIMO nonlinear systems with full‐state constraints. Based on the fast finite‐time stability theory and adaptive backstepping technique, which guarantees all the closed‐loop system signals are bounded, the tracking error eventually converges to a small neighborhood of the origin in a fast finite‐time and full‐state constraints are not violated. Finally, simulation results demonstrate the feasibility of the proposed control scheme.
Finite‐time synchronization of multi‐weighted fractional‐order coupled neural networks with fixed and adaptive couplings
Authors: Ma Ben , Tong Dongbing , Chen Qiaoyu , Zhou Wuneng , Wei Yunbing
Published: June 2022

This article concentrates on the finite‐time synchronization (FTS) for multi‐weighted fractional‐order coupled neural networks (MFCNNs) with fixed and adaptive couplings. A new dynamic model, which involves coupled neural networks with fractional order and multi‐weighted couplings, is proposed. Furthermore, an adaptive law to adjust the coupling weights is devised to ensure the FTS of such a complex model. First, by using fractional‐order calculus properties and inequality techniques, a finite‐time fractional differential inequality is presented, which considerably extends the prior result. Second, by the Lyapunov stability theory and the fractional‐order inequality, several sufficient conditions are acquired to make sure the FTS for MFCNNs. Moreover, the influence of the system's order on the FTS is also uncovered. Finally, a numerical simulation example and a practical simulation example are provided to demonstrate the validity of the obtained criteria.
NIAAA provides information in multiple languages
Authors: Knopf Alison
Published: June 2022

To extend its reach, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) is now providing resources in many different languages. This reflects the fact that people from other countries, not just the U.S., search the NIAAA website for information, according to the agency. It also reflects the Obama‐era executive order, from 2000, that requires all federal agencies to provide access to their services to individuals with limited English proficiency. The U.S. Census Bureau and the National Institutes of Health have identified certain languages as being of greatest need.
House passes H.R. 7666, setting stage for revamping SAMHSA
Authors: Knopf Alison
Published: June 2022

On June 22, the House of Representatives overwhelmingly passed H.R. 7666, the Restoring Hope for Mental Health and Well‐Being Act of 2022. The bill, if passed by the Senate and signed, will revamp many programs in the Substance Abuse and Mental Health Services Administration (SAMHSA). The 462‐page bill includes many provisions fought for by the American Society of Addiction Medicine (ASAM) and others.
Spontaneous Construction of Nucleophilic Carbonyl‐Containing Interphase toward Ultrastable Zinc‐Metal Anodes
Authors: Wang Pinji , Liang Shuquan , Chen Chen , Xie Xuesong , Chen Jiawen , Liu Zhenhan , Tang Yan , Lu Bingan , Zhou Jiang
Published: June 2022

Multifunctional interfacial engineering on the Zn anode to conquer dendrite growth, hydrogen evolution, and the sluggish kinetics associated with Zn deposition is highly desirable for boosting the commercialization of aqueous zinc‐ion batteries. Herein, a spontaneous construction of carbonyl‐containing layer on a Zn anode (Zn@ZCO) is rationally designed as an ion redistributor and functional protective interphase. It has strong zincphilicity and dendrite suppression ability due to the significant interaction of the highly electronegative and highly nucleophilic carbonyl oxygen, favoring ion transport and homogenizing Zn deposition effectively. On the other side, the hydrogen bond formed by the proton acceptor of oxygen atom in ZCO regulates the Zn‐ion desolvation process at the interfaces, thus bounding water activity and then mitigating water‐induced parasitic reactions. Consequently, the Zn@ZCO anode exhibits an extended cycling lifespan of 5000 h (>208 days) with a dendrite‐free surface and negligible by‐products. More encouragingly, the effectiveness is also convincing in NH4V4O10‐based full‐cells with excellent rate performance and cyclic stability. The stabilized Zn anode enabled by the strategy of spontaneous construction of functional solid electrolyte interphase brings forward a facile and instructive approach toward high‐performance zinc‐storage systems.
Promoting Dinuclear‐Type Catalysis in Cu1–C3N4 Single‐Atom Catalysts
Authors: Song Jingting , Chen Zhongxin , Cai Xiangbin , Zhou Xin , Zhan Gaolei , Li Runlai , Wei Pingping , Yan Ning , Xi Shibo , Loh Kian Ping
Published: June 2022

Reducing particle size in supported metal catalysts to single‐atom level isolates the active metal sites and maximizes the atomic utilization efficiency. However, the large inter‐atom distance, particularly in low‐loading single‐atom catalyst (SAC), is not favorable for a complex reaction where two (or more) reactants have to be activated. A key question is how to control the inter‐atom distances to promote dinuclear‐type coactivation at the adjacent metal sites. Here, it is reported that reducing the average inter‐atom distance of copper SACs supported on carbon nitride (C3N4) to 0.74 ± 0.13 nm allows these catalysts to exhibit a dinuclear‐type catalytic mechanism in the nitrile–azide cycloaddition. Operando X‐ray absorption fine structure study reveals a dynamic ligand exchange process between nitrile and azide, followed by their coactivation on dinuclear Cu SAC sites to form the tetrazole product. This work highlights that reducing the nearest‐neighbor distance of SAC allows the mechanistic pathway to diversify from single‐site to multisite catalysis.
Highly Retentive, Anti‐Interference, and Covert Individual Marking Taggant with Exceptional Skin Penetration
Authors: Zhong Lianggen , Li Jiguang , Zu Baiyi , Zhu Xiaodan , Lei Da , Wang Guangfa , Hu Xiaoyun , Zhang Tianshi , Dou Xincun
Published: June 2022

The development of high‐performance individual marking taggants is of great significance. However, the interaction between taggant and skin is not fully understood, and a standard for marking taggants has yet to be realized. To achieve a highly retentive, anti‐interference, and covert individual marking fluorescent taggant, Mn2+‐doped NaYF4:Yb/Er upconversion nanoparticles (UCNPs), are surface‐functionalized with polyethyleneimine (PEI) to remarkably enhance the interaction between the amino groups and skin, and thus to facilitate the surface adhesion and chemical penetration of the taggant. Electrostatic interaction between PEI600‐UCNPs and skin as well as remarkable penetration inside the epidermis is responsible for excellent taggant retention capability, even while faced with robust washing, vigorous wiping, and rubbing for more than 100 cycles. Good anti‐interference capability and reliable marking performance in real cases are ensured by an intrinsic upconversion characteristic with a distinct red luminescent emission under 980 nm excitation. The present methodology is expected to shed light on the design of high‐performance individual marking taggants from the perspective of the underlying interaction between taggant and skin, and to help advance the use of fluorescent taggants for practical application, such as special character tracking.
Giant Orbital Anisotropy with Strong Spin–Orbit Coupling Established at the Pseudomorphic Interface of the Co/Pd Superlattice
Authors: Kim Sanghoon , Pathak Sachin , Rhim Sonny H. , Cha Jongin , Jekal Soyoung , Hong Soon Cheol , Lee Hyun Hwi , Park Sung‐Hun , Lee Han‐Koo , Park Jae‐Hoon , Lee Soogil , Steinrück Hans‐Georg , Mehta Apurva , Wang Shan X. , Hong Jongill
Published: June 2022

Orbital anisotropy at interfaces in magnetic heterostructures has been key to pioneering spin–orbit‐related phenomena. However, modulating the interface's electronic structure to make it abnormally asymmetric has been challenging because of lack of appropriate methods. Here, the authors report that low‐energy proton irradiation achieves a strong level of inversion asymmetry and unusual strain at interfaces in [Co/Pd] superlattices through nondestructive, selective removal of oxygen from Co3O4/Pd superlattices during irradiation. Structural investigations corroborate that progressive reduction of Co3O4 into Co establishes pseudomorphic growth with sharp interfaces and atypically large tensile stress. The normal component of orbital to spin magnetic moment at the interface is the largest among those observed in layered Co systems, which is associated with giant orbital anisotropy theoretically confirmed, and resulting very large interfacial magnetic anisotropy is observed. All results attribute not only to giant orbital anisotropy but to enhanced interfacial spin–orbit coupling owing to the pseudomorphic nature at the interface. They are strongly supported by the observation of reversal of polarity of temperature‐dependent Anomalous Hall signal, a signature of Berry phase. This work suggests that establishing both giant orbital anisotropy and strong spin–orbit coupling at the interface is key to exploring spintronic devices with new functionalities.
Plenary Sessions in a Paradigm of Presumptive and Virtual Mediation
Authors: Feit Norman
Published: June 2022

The traditional mediation model contemplates a preliminary discussion with counsel to address logistics including setting a mediation date, ensuing submission of mediation statements and key documents to orient the mediator, and ultimately a formal session attended by client representatives kicked off with a plenary joint session potentially followed by private alternating caucuses.
Opto‐regulation for the 2D to 3D transformation of a liquid crystal network membrane
Authors: Liu Xiao , Liu Ying
Published: June 2022

Light loading mode plays essential roles in the deformation morphology of the photosensitive liquid crystal network (LCN) membrane. However, owing to the strong non‐linearity of membrane deformation and the constraint effect of membrane boundary, the precise surface pattern control of a LCN membrane through pre‐designing the light loading pattern have not been fully carried out. In this article, a second light‐engraving strategy is proposed to decouple the local and integral deformation of the LCN membrane, and the accurate opto‐regulation of the 2D to 3D pattern transformation could be realized. Firstly, the opto‐deformation governing equations for the LCN membrane under nonuniform illumination are established, and solved by the finite difference method. The deformation characteristics of the LCN membrane under nonuniform illumination has been discussed, and the relation between the light loading mode and the spontaneous deformation in the LCN membrane is clarified. Then a second‐engraving technology based on the deformed membrane is proposed, and the precise opto‐tuning of the 2D to 3D deformation for a LCN membrane is realized. “Robert face” and three‐dimensional word printing is presented as example. This work provides theoretical and numerical guidance on the LCN membrane based three dimensional modeling technology.
Grape‐clustered polyaniline grafted with carbon nanotube woven film as a flexible electrode material for supercapacitors
Authors: Li Bingjian , Liu Shi , Xu Xixi , Yang Haicun , Zhou Yinjie , Yang Dan , Zhang Yun , Li Jinchun
Published: June 2022

The continuously reinforced carbon nanotube woven film (CNWF) prepared via the floating catalytic chemical vapor deposition (FCCVD) was modified by mixed acid and vinyltrimethoxysilane (VTMS) respectively to obtain carbon nanotube woven film (CNWF@VTMS) grafted with CH2CH group. A series of novel self‐supporting composite electrode materials (CNWF@VTMS/PANI) for supercapacitors were then prepared by in‐situ chemical oxidative polymerization of aniline in the presence of the CNWF@VTMS film substrate as a conductive network framework. The results showed that CNWF@VTMS/PANI14 flexible electrode with grape‐clustered structure exhibited the highest specific capacitance of 531.3 F/g and the highest energy density of 26.5 Wh/kg at the current density of 1 A/g. It could maintain 75.1% of the initial value at a high current density of 10 A/g. The excellent electrochemical cycle and the structural stability have been confirmed on the condition of the higher capacitance retention of 96.6% after 2000 times of galvanostatic charge/discharge, and the almost unchanged electrochemical performances after 300 times of bending and twisting. Meanwhile, the stronger interfacial bonding between CNWF and PANI endowed a higher tensile strength of 129.2 MPa. In this article, CNWF@VTMS/PANI14 composite electrode could be a potential application in the field of deformable supercapacitors.
Fast Charge and High Stability of Solid‐State Graphite Organic Ionic Plastic Crystal Composite Anodes
Authors: Ueda Hiroyuki , Mizuno Fuminori , Kerr Robert , Forsyth Maria , Howlett Patrick C.
Published: June 2022

Invited for this month's cover picture is the group of Dr. Hiroyuki Ueda and Prof. Patrick C. Howlett at Deakin University (Australia) jointly working with Toyota Motor Corporation (Japan). The cover picture shows the fast lithium‐ion conduction pathways in the graphite anode of all‐solid‐state batteries (ASSBs) enabled by the incorporation of an organic ionic plastic crystal (OIPC) electrolyte. Read the full text of the Research Article at 10.1002/batt.202200057.
Selective parenchymal clamping in open partial nephrectomy: Early experience with a low cost, reusable novel parenchymal clamp
Authors: Macneil James , Liu Shuo , Iqbal Ramiz , Macneil Finlay
Published: June 2022

Objectives

The objective of this study is to present our initial experience with a novel parenchymal clamp (NPC) developed to allow partial nephrectomies (PN) to be performed without whole kidney ischaemia. We compare patients who underwent PN with the NPC with those undergoing standard PNs.

Methods

The NPC applies pressure only to the portion of the parenchyma containing the small renal mass (≤3.5 cm) and interrupts regional blood flow.

A retrospective analysis was conducted on patients that underwent open PN within our unit. Minimum follow‐up was 12 months. Patient and disease characteristics, perioperative outcomes and renal function estimated Glomerular Filtration Rate (eGFR) were compared.

Results

Data were collected on 63 patients, of whom 33 had their procedure performed with the NPC. Demographic characteristics and comorbidity profiles were not significantly different between groups (p between 1.0 and 0.08). RENAL nephrometry scores were 5.6 in the NPC group versus 6.2 in the standard PN group (p = 0.146).

Perioperative, operative and postoperative data did not show significant differences. There was no difference in the rates of Clavien‐Dindo III or above complications between the two groups (NPC 3/33 vs. standard PN 5/30, p = 0.416). There was also no statistically significant difference to changes in renal functional at 12 months (change −5.2 and −6.4, p = 0.712).

Conclusions

Despite the limited sample size and follow‐up, this study establishes the safety of the NPC. In the future, we intend to perform a prospective study on the laparoscopic version.
Spontaneous bilateral intraorbital hematoma: A particular form of sickle cell disease complications in children
Authors: Andriamiarintsoa Haritanjona , Ramanandafy Herveat , Andriamiadanalisoa Orlando Andoniaina , Randriantianarisoa Koloina , Randrianarivelo Prosper Harinarivo , Andrianah Emmylou Prisca Gabrielle , Rajaonarison Lova Hasina Ny Ony Narindra , Raobela Léa , Rakotoson Joëlson Lovaniaina , Vololontiana Hanta Marie Danielle , Ahmad Ahmad
Published: June 2022

Spontaneous bilateral intraorbital hematoma is a rare complication of sickle cell disease in children. Imaging examinations are of paramount importance in the diagnosis and conditioning of the management processes in order to avoid complications that can compromise the visual function prognosis.
CO2 Stripping from Monoethanolamine through a Polypropylene/CH3SiO2 Composite Hollow‐Fiber Membrane Contactor
Authors: Amirabedi Parya , Akbari Ali , Yegani Reza , Raveshiyan Saba
Published: June 2022

To remove CO2 through a membrane contactor system, composite polypropylene (PP) hollow‐fiber membranes were fabricated by dispersing methyl‐grafted silica nanoparticles in a PP membrane matrix. A set of characterization tests including FTIR spectroscopy, FESEM, AFM, TEM, porosity, contact angle, mechanical strength, and CO2 stripping experiments was carried out. The results showed that the porosity, hydrophobicity, roughness, and CO2 stripping flux of the composite membranes increased with increasing content of inorganic NPs. At an absorbent flow rate of 2.5 m s−1, the CO2 stripping flux of composite membranes containing 1.5 wt % NPs was higher than those of most other hydrophobic membrane contactors.
Herbage accumulation, nutritive value, and persistence of new warm‐season perennial grasses
Authors: de Paula Herico V. G. , Vendramini Joao M. B. , Sollenberger Lynn E. , Moriel Philipe , Siqueira da Silva Hiran Marcelo , Garzon Jaime Eduardo , de Oliveira Hugo M. R. , Machado Igor M. , dos Santos Antonio C.
Published: June 2022

‘Camello’ brachiariagrass (Urochloa spp.) and Spain guineagrass [Megathyrsus maximus (Jacq.) B.K. Simon & S.W.L. Jacobs] are new warm‐season perennial forages with potential for use in subtropical livestock production systems. There are no data in the United States describing their agronomic performance. This study aimed to evaluate the herbage accumulation (HA) and nutritive value of Camello and Spain in north‐central (Citra) and south (Ona) Florida. Experiments were conducted from April to October in 2019 and 2020. Treatments were four warm‐season grasses: Spain guineagrass, Camello brachiariagrass, ‘Mombaça’ guineagrass (not included at Ona), and Jiggs bermudagrass [Cynodon dactylon (L.) Pers.] distributed in a randomized complete block design with four replicates. In Ona, Camello and Spain had similar HA but outyielded Jiggs. Jiggs had greater crude protein (CP) than Camello and Spain during summer but less in vitro digestible organic matter (IVDOM). After 2 yr, there was no difference in groundcover among genotypes at Ona. In Citra, Spain had the greatest HA, followed by Camello and Mombaça, with Jiggs having the least. Jiggs had the greatest CP concentration among the grasses but less IVDOM. Camello, Spain, and Mombaça had generally similar IVDOM, with few differences among months. After 2 yr at Citra, Jiggs had the greatest groundcover, followed by Camello. Mombaça and Spain had the least and did not persist after the 2020–2021 winter. Camello and Spain are promising warm‐season perennial grasses for lower subtropical latitudes, but in the cooler subtropics, the longevity of Spain stands is compromised by frequent winter freezing.
Release of bitumen from mature fine tailings in the presence of a polymeric dispersant
Authors: Alizadeh Hamid , MacIver Michael R. , Pawlik Marek
Published: June 2022

The effect of the addition of a polymeric dispersant, sodium lignosulphonate (LS), on the dispersion of mature fine tailings (MFT) was studied using zeta potential and total organic carbon measurements. Three different types of LSs were investigated to determine the importance of molecular weight and level of anionicity of LSs on the treatment of MFT. The presence of two fractions of bitumen was identified in the tested MFT sample. A small portion of bitumen was found to occur in the form of weakly held aggregates between bitumen and fine solids. This fraction was easily dispersed by small dosages of LS, resulting in bitumen liberation to the tailings surface. A much larger amount of bitumen was found to be strongly attached to the solids, and only very high dosages of LS were capable of partly liberating this fraction. The zeta potential promoted an understanding of the mechanism of adsorption of LS on the particles and liberation of bitumen from MFT. Carbon measurements facilitated determination of the adsorption density of the selected types of LS on solid particles.
DPP‐4 inhibitor linagliptin ameliorates imiquimod‐induced psoriasis‐like skin alterations in type 2 diabetic mice by inhibiting the MAPK/NF‐κB inflammatory pathway
Authors: Shao Zhulin , Li Xiaohong , Xu Xiangjin , Chen Pin
Published: June 2022

Studies have shown that the DPP‐4 inhibitor was effective in improving skin damage in patients with psoriasis, but the exact mechanism was not known. To investigate the therapeutic effects of linagliptin in mice with type 2 diabetes mellitus (T2DM) with psoriasis and its possible therapeutic mechanisms. A total of 32 db/db mice and 16 db/m mice were randomly divided into six groups: normal group, psoriasis group, diabetes group, diabetes combined with psoriasis group, linagliptin‐treated diabetes group, and linagliptin‐treated diabetes combined with psoriasis group. The levels of serum fasting blood glucose, total cholesterol (TC), triglyceride (TG), high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol were measured; the levels of serum FINS were determined by enzyme‐linked immunoassay and the insulin resistance index was calculated. Basic parameters of diabetes, Psoriasis Area and Severity Index, histopathology of skin, the expression of interleukin (IL)‐17A, IL‐23, IL‐22, and tumor necrosis factor (TNF)‐α, and expression levels of measuring p‐ERK, p‐MAPK and p‐nuclear factor kappa B (NF‐κB) in skin tissues were measured. After treatment with linagliptin, insulin resistance, and TC and TG levels were reduced in mice with T2DM and psoriasis (p < .05). Moreover, the degree of epidermal tissue thickening, number of keratinized layers, and inflammatory cell infiltration were also reduced (p < .05), as well as the expression levels of inflammatory factors: TNF‐α, IL‐1β, IL‐17A, IL‐23, and p‐P38/P38, p‐ERK/ERK, p‐P65/P65 proteins (p < .05). Linagliptin significantly reduced the extent of skin lesions and skin inflammation. The underlying mechanism of this compound may be related to the inhibition of MAPK/NF‐κB inflammatory pathways and the consequential improvement of insulin resistance.Significance Statement: In this study, we evaluated the therapeutic effect of the DPP‐4 inhibitor linagliptin using a murine model of type 2 diabetes combined with psoriasis, and its potential mechanisms of action were further explored. The results of this study will help to uncover the pathogenesis of type 2 diabetes and psoriasis and, more importantly, provide a theoretical basis for the search for safe and effective drugs in the treatment of this specific patient population.
Design, synthesis, and biological evaluation of thienopyrimidine and thienotriazine derivatives as multitarget anti‐Alzheimer agents
Authors: Eissa Kholoud I. , Kamel Mona M. , Mohamed Lamia W. , Galal Mai A. , Kassab Asmaa E.
Published: June 2022

A series of tetrahydrobenzothienopyrimidines and tetrahydrobenzothienotriazines incorporating a pharmacophore from donepezil molecule were designed and synthesized. The 12 newly synthesized compounds were screened for their inhibition activity against acetylcholinesterase enzyme (AChE). Compounds that exerted the most potent AChE inhibitory action were further evaluated for their BChE inhibitory activity. In addition, the inhibitory effects of all newly synthesized compounds on Aβ and reactive oxygen species were assessed. Compounds 4d, 10b, and 10c showed potent inhibitory activity on AChE comparable to donepezil. Compound 10b (IC50 = 0.124 ± 0.006 nM) showed the greatest AChE inhibitory action and the most potent BChE inhibitory action (IC50 = 0.379 ± 0.02 nM). These three compounds showed more inhibitory action on Aβ accumulation than donepezil. Moreover, they showed potent antioxidant activity. The binding pattern of compounds 4d and 10b into AChE active site rationalized their remarkable AChE inhibitory activity. Taken together, these results indicated that these derivatives could be promising multifunctional agents for Alzheimer's disease management.
Downregulation of CPT1A exerts a protective effect in dextran sulfate sodium‐induced ulcerative colitis partially by inhibiting PPARα signaling pathway
Authors: Chen Wenxiao , Zou Jinyan , Shi Xinyuan , Huang Huifeng
Published: June 2022

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that may progress to colorectal cancer in severe cases. Carnitine palmitoyltransferase‐1A (CPT1A) has been reported to be upregulated in colorectal cancer. This paper aims to explore the role of CPT1A in UC and its pathogenesis. An in vivo mice model of UC was constructed by administrating 3% dextran sulfate sodium (DSS). The expression level of CPT1A was examined by quantitative real‐time polymerase chain reaction and Western blot. The intestinal damage, inflammatory response and oxidative stress were assessed by hematoxylin and eosin staining, colon length, and commercial kits. Thereafter, an in vitro cell model of UC was established by stimulating HT‐29 cells with 2% DSS. The peroxisome proliferator‐activated receptor α (PPARα) signaling agonist GW7647 was used for treatment. Cell viability and apoptosis was assayed by cell counting kit‐8 assay and terminal dUTP nick‐end labeling assay, respectively. The inflammatory cytokines and oxidative stress‐related factors was evaluated using corresponding commercial detection kits. In DSS‐induced mice model of UC, CPT1A expression was upregulated. Interference of CPT1A attenuated histological damage, the disease activity index and colon length in colitis. We also found downregulation of CPT1A inhibited inflammatory response and oxidative stress, and inhibited PPARα signaling pathway in UC mice. Additionally, in DSS‐induced HT‐29 cells, downregulation of CPT1A promoted cell viability, reduced cell apoptosis, inflammatory response, and oxidative stress, which was partly abolished by additional treatment with GW7647. In summary, downregulation of CPT1A exerts a protective effect in DSS‐induced UC partially through suppressing PPARα signaling, suggesting that CPT1A might be a potential target for the treatment of UC.
Trazodone and patient outcomes in dementia—Limitations of naturalistic cohort data
Authors: Sidhom Emad , Padilla Mc Stephen , Lewis Jonathan , White Simon , O’Brien John T. , Mallucci Giovanna R. , Underwood Benjamin R.
Published: June 2022

The unfolded protein response has been increasingly implicated as an important pathological pathway and target for therapeutic intervention in neurodegeneration. The licensed antidepressant trazodone is one drug which has been proposed to act on this pathway and may therefore be a potential therapy. Previous examination of existing data for patients with dementia prescribed trazodone did not find a signal suggesting a disease modifying effect. Here we add to that literature by examining the electronic patient record of patients with dementia in Cambridgeshire UK. We found that trazodone is rarely prescribed and where it is used it is at a dose less than half that predicted to be disease modifying. We also found that patients prescribed trazodone had higher levels of neuropsychiatric symptoms and were relatively late in the disease course, likely beyond the optimal point for therapeutic intervention. We suggest it is therefore premature to discard potential therapies based on observational data alone, particularly when experimental medicine approaches to examine the effects of trazodone are feasible.
Robot‐assisted laparoscopy repair of uterine isthmocele: A two‐center observational study
Authors: Cardaillac Claire , Salmon Caroline , Vaucel Edouard , Gueudry Pauline , Lavoue Vincent , Nyangoh Timoh Krystel , Thubert Thibault
Published: June 2022

Objective

To analyze outcomes and postoperative complications in patients undergoing robot‐assisted isthmocele repair.

Method

This retrospective cohort study included 33 patients who had robot‐assisted laparoscopic surgical management of an isthmocele between September 2013 and August 2020 in two French university hospitals. All charts were reviewed to identify patient characteristics, preoperative and postoperative anatomical findings, complications, and postoperative fertility and symptoms. Patients who had undergone this procedure were asked to complete a telephone questionnaire about their treatment satisfaction and symptoms.

Results

The isthmocele was discovered most often as a result of subfertility (57.6%), but also ectopic pregnancy (18.2%), pelvic pain (15.2%), and postmenstrual bleeding (9.1%). Robot‐assisted repair of the isthmocele significantly improved myometrial thickness (from 1.55 mm before surgery to 4.26 mm after surgery [mean difference 2.71; 95% confidence interval, 1.91–3.51], P = 0.0005). Among 20 patients who still desired a child after surgery, 15 became pregnant and 14 had full‐term live births. Among the nine patients who had surgery for disabling symptoms, five had no persistent symptoms, three reported global improvement, and one had the same gynecologic discomfort. Seventeen patients agreed to complete the questionnaires (51.5%), and all stated that they would choose to have this surgery again.

Conclusion

Robot‐assisted repair of an isthmocele is a viable minimally invasive procedure.
Survey of critical care practices for alcohol withdrawal syndrome in the intensive care unit
Authors: Cucci Michaelia D. , Palm Nicole , Vazquez Daniel , Mullen Chanda , Heavner Mojdeh S.
Published: June 2022

Introduction

Alcohol use disorder affects up to 60% of intensive care unit (ICU) patients. Alcohol withdrawal syndrome (AWS) is associated with increased length of stay, mechanical ventilation, and mortality. The lack of clinical practice guidelines specific to ICU patients leads to ambiguity about the standard management of AWS in this population.

Objectives

The aim of this study was to describe current practice patterns employed for AWS management in ICU settings across the United States.

Methods

This was a cross‐sectional survey of practicing critical care pharmacists identified via a pharmacy professional organization critical care listserv. Emails were sent four times to the recipient list from May 14, 2021 to June 25, 2021. Retired pharmacists and trainees on the listserv were excluded. The survey was conducted by REDCap and descriptive statistics were performed.

Results

There were a total of 144/1534 (9.4%) responses. Predominant characteristics included university hospital settings (n = 71/143, 49.7%) with greater than 75 ICU beds (n = 54/144, 37.5%), and medical (n = 53/144, 36.8%) or mixed (n = 52/144, 36.1%) ICU populations. The majority reported having an institutional AWS guideline (n = 96/140, 68.6%). A total of 139/143 (97.2%) preferred benzodiazepines, with lorazepam (n = 136/143, 97.8%) as the primary benzodiazepine agent. Most preferred lorazepam as needed, rather than preemptively (n = 137/138, 99.3%). Phenobarbital use was reported by 82.6% (n = 119/144) of respondents, primarily for treatment of benzodiazepine‐refractory withdrawal (n = 96/117, 82.1%). Similarly, dexmedetomidine use was reported by 86.1% (n = 124/144) of respondents, primarily for refractory withdrawal (n = 48/121, 39.7%). Propofol was primarily preferred for patients on mechanical ventilation (n = 56/98, 57.1%) or refractory withdrawal (n = 51/98, 52.0%). Clonidine was preferred by 45.8% (n = 66/144) and atypical antipsychotics by 33.6% (n = 48/143) of respondents.

Conclusions

Most ICU pharmacists prefer symptom‐triggered benzodiazepines first line, followed by propofol in intubated patients and dexmedetomidine and/or phenobarbital for refractory cases. Clinical practice guidelines may help provide guidance for the management of these patients.
Ultrasound and magnetic resonance imaging features of fetal intracranial cystic lesions: A pictorial essay
Authors: Moradi Behnaz , Golezar Mohammad Hossein , Saleh Gargari Soraya , Kazemi Mohammad Ali , Golezar Samira , Taheri Morteza Sanei , Tahmasebpour Ahmad‐Reza
Published: June 2022

This pictorial essay focuses on ultrasound (US) and magnetic resonance imaging (MRI) features of fetal intracranial cysts. Intracranial cysts are common findings in prenatal imaging, and if great attention is paid to their size, location, and imaging features, they can be diagnosed accurately. They are usually detected by fetal ultrasound exams. However, when ultrasound data on cystic lesion characteristics is insufficient, MRI and fetal neurosonogram are the best options for detecting other associated anomalies. The prognosis is highly dependent on their location and whether they are associated with other fetal anomalies.
Inactivating BTK mutations in large B‐cell lymphoma in a real‐world cohort: Strong correlation with BCL2 translocation
Authors: Schejbel Lone , Breinholt Marie Fredslund , Gang Anne Ortved , Nielsen Torsten Holm , Pedersen Lars Møller , Høgdall Estrid , Nørgaard Peter
Published: June 2022

Inactivating mutations in Bruton's tyrosine kinase (BTK) in patients with follicular lymphoma (FL) have recently been reported. These mutations were found in BTK inhibitor‐treatment naïve patients. Here, we report the BTK mutation status in a real‐world cohort of patients with non‐Hodgkin lymphoma. We found primary BTK mutations in 7.7% of patients with large B‐cell lymphoma (LBCL) and in 14.1% of patients with FL. All patients with BTK‐mutated LBCL were BCL2 translocation positive, and the correlation between BCL2 translocation and BTK mutation persisted even when patients with known transformation from FL were excluded.
Determination of isotope abundance for deuterium‐labeled compounds by quantitative 1H NMR + 2H NMR
Authors: Xie Long , Zhao Yameng , Sheng Liyan , Feng Shancheng , Shen An , Chen Yanqiu , Zhao Cheng , Song Mingming , Hu Yucai , Lei Wen
Published: June 2022

Deuterated reagents have been used in many research fields. Isotope abundance, as the feature parameter of deuterated reagents, the precise quantification, is of great importance. Based on quantitative nuclear magnetic resonance technology, a novel method that combines 1H NMR + 2H NMR was systematically established to determine the isotopic abundance of deuterated reagents. The results showed that the isotopic abundance of partially labeled and fully labeled compounds calculated by this new method was even more accurate than that calculated by classical 1H NMR and mass spectrometry (MS) methods. In brief, this new method is a robust strategy for the determination of isotope abundance in large‐scale deuterated reagents.
A meta‐analysis of the association between shame and dissociation
Authors: Rudy Justine A. , McKernan Scott , Kouri Nicole , D'Andrea Wendy
Published: June 2022

Shame and dissociation have been implicated theoretically and empirically in trauma exposure and its sequelae, with shame understood as an intense negative emotion and dissociation as a reaction to intense negative emotions. Understanding the connection between shame and dissociation is important for theory and practice; however, the strength of this association remains unclear. For example, in therapy, both shame and dissociation serve as a barrier to engaging with emotion. Theoretically, these two states should be distinct, as one (dissociation) confers low affective intensity and the other (shame) high intensity. The present meta‐analysis focused on the magnitude of the association between these two phenomena and investigated the extent to which gender, trauma exposure, psychiatric comorbidities, and demographic characteristics influence this association given their independent links to shame and dissociation. An initial search of six databases identified 151,844 articles. Duplicates were removed, and additional articles were excluded based on abstract and title screening. After contacting authors for missing data, a full‐text screen yielded 25 articles for the present analysis. The results indicate that shame and dissociation were moderately correlated (k = 33, n = 4,705), r = .42, 95% CI [.35, .48], p < .001, but no clear clinical moderators emerged. Despite this association, very few studies utilized experimental designs to examine the association between these constructs. Future research should focus on experimental study designs to investigate the extent to which shame induces dissociation or vice versa.
Revealing the scale‐ and location‐specific variation and control factors of soil salinity using bi‐dimensional empirical modal decomposition
Authors: Zhu Chuanmei , Ding Jianli , Zhang Zipeng
Published: June 2022

The key to saline land management and soil salinity control is to clarify the dynamics of soil salinity and the characteristics of environmental factors. However, due to the high heterogeneity of soil salinity, the influence of environmental factors on soil salinity variation at specific scales and locations is still unclear. The purpose of this study is to reveal the variability characteristics and controlling factors of soil salinity in the Wei‐Ku Oasis during different seasons. One hundred and eighty‐two topsoil samples (0–20 cm) were acquired during the irrigation and non‐irrigation seasons (IRRS and NIRRS) in the study area. This study predicted soil surface salinity at 90 m spatial resolution from randomForest (RF) models and measured data. Based on the mapping, a bi‐dimensional empirical modal decomposition (BEMD) algorithm was applied to extract the variation of the soil salinity at different scales and locations in the IRRS and NIRRS. Subsequently, correlation analysis, semi‐variance functions, and redundancy analysis were applied to dissect the correlation and main control factors between soil salinity and the environment at three different scales. The results indicated that soil salinity was greater in the NIRRS at the Weiku Oasis. Soil salinity was decomposed into five intrinsic modal functions with spatial variability scales of 6.20–50.61 km and 7.93–50.18 km during the IRRS and NIRRS, respectively. The relationships between environmental factors and soil salinity were scale‐ and location‐specific, suggesting a complex interrelationship between topography, temperature, vegetation cover, and soil salinity. The normalized difference vegetation index was found to be the main factor affecting small‐scale seasonal variation in soil salinity, whereas the large‐scale spatial distribution of soil salinity was most affected by evapotranspiration and temperature. These findings highlight the effectiveness of BEMD in revealing the scale and location control of soil salinity.