bluuebunny/crossref_metadata_2025 huggingface dataset:
Satellite‐derived NDVI underestimates the advancement of alpine vegetation growth over the past three decades
Authors: Wang Hao , Liu Huiying , Huang Ni , Bi Jian , Ma Xuanlong , Ma Zhiyuan , Shangguan Zijian , Zhao Hongfang , Feng Qisheng , Liang Tiangang , Cao Guangmin , Schmid Bernhard , He Jin‐Sheng
Published: August 2021

Satellite‐derived normalized difference vegetation index (NDVI) data are increasingly relied on to reveal the growth responses of vegetation to climate change, yet the vegetation growth tracking accuracy of these data remains unclear due to a lack of long‐term field data. Here, we adopted a unique field‐measured seasonal aboveground biomass dataset from 1982–2014 to assess the potential of using satellite‐derived NDVI data to match field data in regard to the interannual variability in seasonal vegetation growth in a Tibetan alpine grassland. We revealed that Global Inventory Monitoring and Modeling System (GIMMS) NDVI data captured the advancement of field‐measured vegetation growth throughout the entire study period but not from 2000–2014, while MODIS NDVI data still observed this advancing trend after 2000 to a limited extent. However, satellite‐derived NDVI data consistently underestimated the advancement degree of field‐measured vegetation growth, regardless of whether GIMMS or MODIS NDVI data were considered. We tentatively attribute this underestimation to an increased ratio of grass biomass to forb biomass, which could delay the advancement of NDVI development but not affect that of field‐measured biomass development. Our results suggest that satellite‐derived NDVI data may miss critical responses of vegetation growth to global climate change, potentially due to long‐term shifts in plant community composition.
Petrology and geochemistry of ultramafic rocks in the Mogok belt, Myanmar: Cumulates from high‐pressure crystallization of hydrous arc melts
Authors: Liu Tong , Liu Chuan‐Zhou , Chen Yi , Guo Shun , Sein Kyaing , Dong Xiao‐Tao
Published: August 2021

The Mogok metamorphic belt (MMB) in central Myanmar is well known for its complex tectonics, magmatism, and metamorphism in the framework of Tethyan subduction and India–Asia collision. It is also world renowned due to the gemstone‐class rubies and sapphires. Identification and discrimination of those petrological units in this region therefore are important for understanding the gemstone mineralization. Ultramafic massifs also crop out together with the gemstone‐bearing metamorphic rocks in the MMB. It is still poorly constrained about their origin (i.e., mantle peridotites of Jurassic–Cretaceous ophiolites or cumulate rocks) and their relationship with the gemstone generation. Here, we report petrological and geochemical data for the Mogok ultramafic rocks. Petrographic observations show that they have typical cumulate textures, with a crystallization order of olivine/spinel‐orthopyroxene‐clinopyroxene. They have low whole‐rock Al2O3 and CaO, and extremely high spinel Cr# (=Cr/[Cr + Al]; up to 0.86). Clinopyroxenes of these rocks show light rare earth element enriched patterns when normalized to CI chondrite. The results suggest that the Mogok ultramafic rocks have different compositions, both whole‐rock and mineral, from mantle peridotites of Myanmar ophiolites, such as the Kalaymyo and Myitkyina ophiolites, but resemble typical Alaskan‐type ultramafic cumulates. Therefore, the Mogok ultramafic rocks are cumulates generated by high‐pressure crystallization of hydrous arc melts, probably during the subduction of the Tethyan oceanic slab. We argue that the emplacement of these arc melts may have provided additional heat for the earlier magmatic rocks and regional high‐temperature metamorphism, although there is a need to further constrain the ages of these rocks. This, along with magmatism and metamorphism during post‐collisional extension, probably collectively contributed to the generation of world‐class coloured gemstone mineralization.
New observations on Devonian in the Baoshan Block of western Yunnan, China
Authors: Qiao Li , Qie Wen‐Kun , Mao Ying‐Yan , Song Jun‐Jun , Lu Jian‐Feng , Mu Lin , Liang Kun , Li Yue
Published: August 2021

The Devonian Heyuanzhai Formation was re‐investigated in its type area in Shidian, Baoshan Block, western Yunnan, China. The sequences crop out at the Douyashan section adjacent to the Heyuanzhai village where they were measured. They are represented by thick fossiliferous successions of carbonate deposits interbedded with calcareous shale and mudstone. A great number of fossils were collected from the formation, with detailed documentation of brachiopods, crinoids, and ostracods in this paper. In the lower and middle parts of the Heyuanzhai Formation, the brachiopod Gypidula‐Schizophoria‐Spinatrypa assemblage is recognized and generally correlated to the Eifelian–Givetian. Whereas, in the upper part, the brachiopod Pugnax‐Hypothyridina‐Tenticospirifer assemblage is recognized for the first time, indicating an Early‐Middle Frasnian by occurrences of new species of rhynchonellid and cyrtospiriferid brachiopods, as well as the middle Late Devonian crinoids (Megaradialocrinus, Halocrinites, and Melocrinites) and ostracods (Palaeocopida, Platycopida, Metacopina, Podocopida). The sedimentary facies association and fossil assemblages herein indicate that the Heyuanzhai faunas from the Douyashan section inhabited a turbulent mid‐ramp with depth between the fair‐weather wave‐base and storm wave‐base, and were possibly accumulated in an environment that was derived from immediately adjacent habitats after short‐distance transportation.
Shared and distinct brain fMRI response during performance of working memory tasks in adult patients with schizophrenia and major depressive disorder
Authors: Wang Xiuli , Cheng Bochao , Roberts Neil , Wang Song , Luo Ya , Tian Fangfang , Yue Suping
Published: August 2021

Working memory (WM) impairments are common features of psychiatric disorders. A systematic meta‐analysis was performed to determine common and disorder‐specific brain fMRI response during performance of WM tasks in patients with SZ and patients with MDD relative to healthy controls (HC). Thirty‐four published fMRI studies of WM in patients with SZ and 18 published fMRI studies of WM in patients with MDD, including relevant HC, were included in the meta‐analysis. In both SZ and MDD there was common stronger fMRI response in right medial prefrontal cortex (MPFC) and bilateral anterior cingulate cortex (ACC), which are part of the default mode network (DMN). The effects were of greater magnitude in SZ than MDD, especially in prefrontal‐temporal‐cingulate‐striatal‐cerebellar regions. In addition, a disorder‐specific weaker fMRI response was observed in right middle frontal gyrus (MFG) in MDD, relative to HC. For both SZ and MDD a significant correlation was observed between the severity of clinical symptoms and lateralized fMRI response relative to HC. These findings indicate that there may be common and distinct anomalies in brain function underlying deficits in WM in SZ and MDD, which may serve as a potential functional neuroimaging‐based diagnostic biomarker with value in supporting clinical diagnosis, measuring illness severity and assessing the efficacy of treatments for SZ and MDD at the brain level.
Probabilistic mapping of thalamic nuclei and thalamocortical functional connectivity in idiopathic generalised epilepsy
Authors: Chen Yachin , Fallon Nicholas , Kreilkamp Barbara A. K. , Denby Christine , Bracewell Martyn , Das Kumar , Pegg Emily , Mohanraj Rajiv , Marson Anthony G. , Keller Simon S.
Published: August 2021

It is well established that abnormal thalamocortical systems play an important role in the generation and maintenance of primary generalised seizures. However, it is currently unknown which thalamic nuclei and how nuclear‐specific thalamocortical functional connectivity are differentially impacted in patients with medically refractory and non‐refractory idiopathic generalised epilepsy (IGE). In the present study, we performed structural and resting‐state functional magnetic resonance imaging (MRI) in patients with refractory and non‐refractory IGE, segmented the thalamus into constituent nuclear regions using a probabilistic MRI segmentation method and determined thalamocortical functional connectivity using seed‐to‐voxel connectivity analyses. We report significant volume reduction of the left and right anterior thalamic nuclei only in patients with refractory IGE. Compared to healthy controls, patients with refractory and non‐refractory IGE had significant alterations of functional connectivity between the centromedian nucleus and cortex, but only patients with refractory IGE had altered cortical connectivity with the ventral lateral nuclear group. Patients with refractory IGE had significantly increased functional connectivity between the left and right ventral lateral posterior nuclei and cortical regions compared to patients with non‐refractory IGE. Cortical effects were predominantly located in the frontal lobe. Atrophy of the anterior thalamic nuclei and resting‐state functional hyperconnectivity between ventral lateral nuclei and cerebral cortex may be imaging markers of pharmacoresistance in patients with IGE. These structural and functional abnormalities fit well with the known importance of thalamocortical systems in the generation and maintenance of primary generalised seizures, and the increasing recognition of the importance of limbic pathways in IGE.
Up‐regulation of thioesterase superfamily member 2 in skeletal muscle promotes hepatic steatosis and insulin resistance in mice
Authors: Imai Norihiro , Nicholls Hayley T. , Alves‐Bezerra Michele , Li Yingxia , Ivanova Anna A. , Ortlund Eric A. , Cohen David E.
Published: August 2021

Background and Aims

Thioesterase superfamily member 2 (Them2) is highly expressed in liver and oxidative tissues, where it hydrolyzes long‐chain fatty acyl‐CoA esters to free fatty acids and CoA. Although mice globally lacking Them2 (Them2
−/−) are protected against diet‐induced obesity, hepatic steatosis (HS), and insulin resistance (IR), liver‐specific Them2
−/− mice remain susceptible. The aim of this study was to test whether Them2 activity in extrahepatic oxidative tissues is a primary determinant of HS and IR.

Approach and Results

Upon observing IR and up‐regulation of Them2 in skeletal, but not cardiac, muscle of high‐fat‐diet (HFD)‐fed wild‐type compared to Them2
−/− mice, we created mice with Them2 specifically deleted in skeletal (S‐Them2
−/−) and cardiac muscle (C‐Them2
−/−), as well as in adipose tissue (A‐Them2
−/−). When fed an HFD, S‐Them2
−/−, but not C‐Them2
−/− or A‐Them2
−/−, mice exhibited reduced weight gain and improved glucose homeostasis and insulin sensitivity. Reconstitution of Them2 expression in skeletal muscle of global Them2
−/− mice, using adeno‐associated virus, was sufficient to restore excess weight gain. Increased rates of fatty acid oxidation in skeletal muscle of S‐Them2
−/− mice contributed to protection from HFD‐induced HS by increasing VLDL triglyceride secretion rates in response to greater demand. Increases in insulin sensitivity were further attributable to alterations in production of skeletal muscle metabolites, including short‐chain fatty acids, branched‐chain amino acids, and pentose phosphate pathway intermediates, as well as in expression of myokines that modulate insulin responsiveness.

Conclusions

These results reveal a key role for skeletal muscle Them2 in the pathogenesis of HS and IR and implicate it as a target in the management of NAFLD.
Capsid Allosteric Modulators Enhance the Innate Immune Response in Hepatitis B Virus–Infected Hepatocytes During Interferon Administration
Authors: Fukutomi Keisuke , Hikita Hayato , Murai Kazuhiro , Nakabori Tasuku , Shimoda Akiyoshi , Fukuoka Makoto , Yamai Takuo , Higuchi Yuichiro , Miyakawa Kei , Suemizu Hiroshi , Ryo Akihide , Yamada Ryoko , Kodama Takahiro , Sakamori Ryotaro , Tatsumi Tomohide , Takehara Tetsuo
Published: August 2021

Capsid allosteric modulators (CAMs) inhibit the encapsidation of hepatitis B virus (HBV) pregenomic RNA (pgRNA), which contains a pathogen‐associated molecular pattern motif. However, the effect of CAMs on the innate immune response of HBV‐infected hepatocytes remains unclear, and we examined this effect in this study. Administration of a CAM compound, BAY41‐4109 (BAY41), to HBV‐infected primary human hepatocytes (PHHs) did not change the total cytoplasmic pgRNA levels but significantly reduced intracapsid pgRNA levels, suggesting that BAY41 increased extracapsid pgRNA levels in the cytoplasm. BAY41 alone did not change the intracellular interferon (IFN)–stimulated gene (ISG) expression levels. However, BAY41 enhanced antiviral ISG induction by IFN‐α in HBV‐infected PHHs but did not change ISG induction by IFN‐α in uninfected PHHs. Compared with BAY41 or IFN‐α alone, coadministration of BAY41 and IFN‐α significantly suppressed extracellular HBV‐DNA levels. HBV‐infected human liver–chimeric mice were treated with vehicle, BAY41, pegylated IFN‐α (pegIFN‐α), or BAY41 and pegIFN‐α together. Compared with the vehicle control, pegIFN‐α highly up‐regulated intrahepatic ISG expression levels, but BAY41 alone did not change these levels. The combination of BAY41 and pegIFN‐α further enhanced intrahepatic antiviral ISG expression, which was up‐regulated by pegIFNα. The serum HBV‐DNA levels in mice treated with the combination of BAY41 and pegIFN‐α were the lowest observed in all the groups. Conclusion: CAMs enhance the host IFN response when combined with exogenous IFN‐α, likely due to increased cytoplasmic extracapsid pgRNA.
The Detrimental Role of Regulatory T Cells in Nonalcoholic Steatohepatitis
Authors: Dywicki Janine , Buitrago‐Molina Laura Elisa , Noyan Fatih , Davalos‐Misslitz Ana C. , Hupa‐Breier Katharina L. , Lieber Maren , Hapke Martin , Schlue Jerome , Falk Christine S. , Raha Solaiman , Prinz Immo , Koenecke Christian , Manns Michael P. , Wedemeyer Heiner , Hardtke‐Wolenski Matthias , Jaeckel Elmar
Published: August 2021

Nonalcoholic steatohepatitis (NASH) is induced by steatosis and metabolic inflammation. While involvement of the innate immune response has been shown, the role of the adaptive immune response in NASH remains controversial. Likewise, the role of regulatory T cells (Treg) in NASH remains unclear although initial clinical trials aim to target these regulatory responses. High‐fat high‐carbohydrate (HF‐HC) diet feeding of NASH‐resistant BALB/c mice as well as the corresponding recombination activating 1 (Rag)‐deficient strain was used to induce NASH and to study the role of the adaptive immune response. HF‐HC diet feeding induced strong activation of intrahepatic T cells in BALB/c mice, suggesting an antigen‐driven effect. In contrast, the effects of the absence of the adaptive immune response was notable. NASH in BALB/c Rag1−/−
mice was substantially worsened and accompanied by a sharp increase of M1‐like macrophage numbers. Furthermore, we found an increase in intrahepatic Treg numbers in NASH, but either adoptive Treg transfer or anti‐cluster of differentiation (CD)3 therapy unexpectedly increased steatosis and the alanine aminotransferase level without otherwise affecting NASH. Conclusion: Although intrahepatic T cells were activated and marginally clonally expanded in NASH, these effects were counterbalanced by increased Treg numbers. The ablation of adaptive immunity in murine NASH led to marked aggravation of NASH, suggesting that Tregs are not regulators of metabolic inflammation but rather enhance it.
Radical Silyl‐ and Germylzincation of Propargylic Alcohols
Authors: de la Vega‐Hernández Karen , Isaac Kevin , Chemla Fabrice , Ferreira Franck , Jackowski Olivier , Perez‐Luna Alejandro
Published: August 2021

The silyl‐ and germylzincation of terminal or internal propargylic alcohols by reaction with (Me3Si)3SiH/Et2Zn, [(Me3Si)3Si]2Zn/Et2Zn or Ph3GeH/Et2Zn is examined. These reactions proceed through the addition of silicon‐ or germanium‐centered radicals across the carbon≡carbon triple bond followed by the trapping by diethylzinc of the produced vinyl radical through homolytic substitution at the zinc atom. The influence of the hydroxy unit on the regio‐ and stereoselectivity of these reactions is discussed and compared to its role played in radical hydrosilylation and hydrogermylation reactions. Protocols developed to achieve the β‐regioselective silylzincation of propargyl alcohol and the α‐regioselective germylzincation of internal propargylic alcohols are particularly important, as they occur with trans stereoselectivity. For both procedures the C(sp2)−Zn bond remains available for subsequent in‐situ electrophilic substitution leading overall to net alkyne trans difunctionalization.
Outcomes of hematopoietic cell transplantation for transformed follicular lymphoma
Authors: Ida Hanae , Inamoto Yoshihiro , Fukuhara Suguru , Maeshima Akiko Miyagi , Takeda Wataru , Hirakawa Tsuneaki , Kuno Masatomo , Aoki Jun , Tanaka Takashi , Ito Ayumu , Kim Sung‐Won , Izutsu Koji , Fukuda Takahiro
Published: August 2021

This study characterized the outcomes of patients who underwent hematopoietic cell transplantation (HCT) for transformed follicular lymphoma (tFL), and clarified the association of low‐dose anti‐thymocyte globulin use with outcomes after allogeneic HCT. The retrospective study cohort included 74 consecutive patients who underwent autologous (n = 23) or allogeneic (n = 51) HCT at our center from 2000 to 2017. Compared with the allogeneic HCT group, the autologous HCT group underwent fewer systemic regimens before HCT (median 2 vs. 5, p < 0.001) and were more likely to have chemosensitive disease at HCT (100% vs. 82%, p = 0.05), while age, sex and HCT‐specific comorbidity index were similar between the two groups. With a median follow‐up of 5.8 years among survivors, the 5‐year probability of progression‐free survival was 64% after autologous HCT and 55% after allogeneic HCT (p = 0.21). The 5‐year cumulative incidence of non‐relapse mortality was 0% after autologous HCT and 9.5% after allogeneic HCT (p = 0.062). The 5‐year cumulative incidence of disease progression was similar between autologous and allogeneic HCT (36% vs. 36%, respectively, p = 0.88). In the allogeneic HCT group, the use of low‐dose anti‐thymocyte globulin was associated with a lower incidence of severe acute GVHD but not with an increased risk of mortality or disease progression. More than half of patients with early phase chemosensitive tFL and approximately half of those with advanced‐phase tFL achieved long‐term progression‐free survival with autologous and allogeneic HCT, respectively. Disease progression was the major cause of treatment failure after both types of HCT. Further strategies are needed to reduce the risk of disease progression.
Computation of unsteady generalized Couette flow and heat transfer in immiscible dusty and non‐dusty fluids with viscous heating and wall suction effects using a modified cubic B‐spine differential quadrature method
Authors: Chandrawat Rajesh Kumar , Joshi Varun , Anwar Bég O. , Tripathi Dharmendra
Published: August 2021

In this paper, the unsteady flow of two immiscible fluids with heat transfer is studied numerically with a modified cubic B‐spine Differential Quadrature Method. Generalized Couette flow of two immiscible dusty (fluid–particle suspension) and pure (Newtonian) fluids are considered through rigid horizontal channelsfor three separate scenarios: first fornonporous plates with heat transfer, second forporous plates with uniform suction and injection and heat transfer, and third fornonporous plates with interface evolution. The stable liquid–liquid interface is considered for the two immiscible fluids in the first two cases. In the third case, it is assumed that the interface travels from one position to another and may undergo serious deformation; hence the single momentum equation based on the volume of fluid method is combined with the continuum surface approach model, and an interface tracking is proposed. The flow cases are considered to be subjected to three different pressure gradients, of relevance to energy systems—namely,applied constant, decaying, and periodic pressure gradients. For each case, the coupled partial differential equations are formulated and solved numerically using MCB‐DQM to compute the fluids velocities, fluid temperatures, interface evolution. The effects of emerging thermo‐fluid parameters, that is, Eckert (dissipation), Reynolds, Prandtl, and Froude numbers, particle concentration parameter, volume fraction parameter, pressure gradient, time, and the ratio of viscosities, densities, thermal conductivities, and specific heats on velocity and temperature characteristics are illustrated through graphs.
Red bermudagrass mite severely reduces growth in hybrid bermudagrass
Authors: Loch Donald S.
Published: August 2021

Mite infestations are widely recognized as reducing the growth of affected warm‐season turfgrasses. This observation is, however, a qualitative assessment, albeit based on extensive field observations over the past >60 yr, and the level of reduced growth has never previously been quantified. In three replicated pot experiments, the dry matter production of hybrid bermudagrass [Cynodon dactylon (L.) Pers. × Cynodon transvaalensis Burtt Davy] infested by the red bermudagrass mite [Dolichotetranychus australianus (Womersley)] was reduced by 84, 67, and 50% compared with that of a mite‐free control treatment in Experiments 1, 2, and 3, respectively. These results are discussed in relation to the inherent variability of red bermudagrass mite infestations in both time and in space.
A reaction route network for methanol decomposition on a Pt(111) surface
Authors: Sugiyama Kanami , Saita Kenichiro , Maeda Satoshi
Published: August 2021

A reaction route network for the decomposition reaction of methanol on a Pt(111) surface was constructed by using the artificial force‐induced reaction (AFIR) method, which can search for reaction paths automatically and systematically. Then, the network was kinetically analyzed by applying the rate constant matrix contraction (RCMC) method. Specifically, the time hierarchy of the network, the time evolution of the population initially given to CH3OH to the other species on the network, and the most favorable route from CH3OH to major and minor products were investigated by the RCMC method. Consistently to previous studies, the major product on the network was CO+4H, and the most favorable route proceeded through the following steps: CH3OH → CH2OH+H → HCOH+2H → HCO+3H → CO+4H. Furthermore, paths to byproducts found on the network and their kinetic importance were discussed. The present procedure combining AFIR and RCMC was thus successful in explaining the title reaction without using any information on its product or the reaction mechanism.
Discoidin domain receptors (DDRs): Potential implications in periodontitis
Authors: Ma Rui , Xie Xudong , Zhao Lei , Wu Yafei , Wang Jun
Published: August 2021

Periodontitis is a chronic inflammatory disease leading to the destruction of periodontal tissues associated with high prevalence and significant economic burden. As special collagen‐binding tyrosine kinase receptors, the discoidin domain receptors (DDRs) can control cell migration, adhesion, proliferation, and extracellular matrix remodeling. DDRs are constitutively expressed and widely distributed in periodontal tissues which are rich in collagen. Ddr1/2 knockout mice showed significant periodontal defects including connective tissue destruction, alveolar bone loss, and even tooth loss. It has been demonstrated that bone homeostasis, inflammation, matrix metalloproteinases, and autophagy are crucial characteristics involved in the pathogenesis of periodontitis. Of note, DDRs have been reported to participate in the above pathophysiological processes, implicating the potential roles of DDRs in periodontitis. In this review article, we aim to illustrate the possible roles of DDRs in periodontitis in an attempt to explore their potential value as therapeutic targets for periodontitis.
A Phase 1 Trial to Evaluate the Relationship Between Fluoride Intake and Urinary Fluoride Excretion in Healthy Participants
Authors: Gillespie Gillian , Jackson Rudd Deanne , Zhang Saijuan , Schaeffer Andrea , Tomek Charles , Larson Patrick , Stoch S. Aubrey , Iwamoto Marian
Published: August 2021

Chronic overexposure to fluoride can have deleterious effects in the musculoskeletal system. Some fluorine‐containing therapeutics, such as voriconazole, release fluoride through metabolism. Therefore, drug‐related fluoride exposure should be assessed for novel therapeutics suspected of releasing fluoride through metabolism. Two trials were conducted to identify the optimal method of assessing drug‐related fluoride exposure. In trial 1, designed to assess reproducibility of fluoride pharmacokinetics in urine and plasma, 14 participants were administered a fluoride‐restricted diet and once‐daily doses of sodium fluoride (2.2 mg [1 mg of fluoride] on days 1 and 2; and 13.2 mg of sodium fluoride [6 mg of fluoride] on days 3 and 4). In trial 2, designed to confirm the selected method for fluoride detection, 12 participants were administered a fluoride‐restricted diet and randomized to receive voriconazole (400 mg twice, 12 hours apart, on day 1 [131 mg/d of fluoride maximum], then 3 doses of 200 mg every 12 hours [65.3 mg/d of fluoride maximum]) or placebo. Plasma fluoride concentrations and urinary fluoride excretion were assessed in each trial. Assessment of plasma fluoride concentrations in trial 1 was limited by 301 of 854 samples (35.2%) below the lower limit of quantitation. Urine fluoride excretion was readily measured and demonstrated a decrease from baseline during the fluoride‐restricted diet phase, as well as dose‐proportional increases with fluoride administration. In trial 2, increases in urine fluoride were successfully observed in participants administered voriconazole. In conclusion, fluoride exposure was optimally assessed by urinary fluoride excretion in conjunction with strict dietary fluoride restrictions, as measurements were consistent and reproducible.
p21‐activated kinase 4 phosphorylates peroxisome proliferator‐activated receptor Υ and suppresses skeletal muscle regeneration
Authors: Mao Yuancheng , Han Chang Yeob , Hao Lihua , Bang In Hyuk , Bae Eun Ju , Park Byung‐Hyun
Published: August 2021

Background

Skeletal muscle regeneration is an adaptive response to injury that is crucial to the maintenance of muscle mass and function. A p21‐activated kinase 4 (PAK4) serine/threonine kinase is critical to the regulation of cytoskeletal changes, cell proliferation, and growth. However, PAK4's role in myoblast differentiation and regenerative myogenesis remains to be determined.

Methods

We used a mouse model of myotoxin (notexin)‐induced muscle regeneration. In vitro myogenesis was performed in the C2C12 myoblast cell line, primary myoblasts, and primary satellite cells. In vivo overexpression of PAK4 or kinase‐inactive mutant PAK4S474A was conducted in skeletal muscle to examine PAK4's kinase‐dependent effect on muscle regeneration. The regeneration process was evaluated by determining the number and size of multinucleated myofibres and expression patterns of myogenin and eMyHC. To explore whether PAK4 inhibition improves muscle regeneration, mice were injected intramuscularly with siRNA that targeted PAK4 or orally administered with a chemical inhibitor of PAK4.

Results

p21‐activated kinase 4 was highly expressed during the myoblast stage, but expression gradually and substantially decreased as myoblasts differentiated into myotubes. PAK4 overexpression, but not kinase‐inactive mutant PAK4S474A overexpression, significantly impeded myoblast fusion and MyHC‐positive myotube formation in C2C12 cells, primary myoblasts, and satellite cells (P < 0.01). Conversely, PAK4 silencing led to an 8.7% and a 20.3% increase in the number of multinucleated larger myotubes in C2C12 cells and primary myoblasts. Further, in vivo overexpression of PAK4 by adenovirus injection to mice prior to and after myotoxin‐induced injury led to a 52.6% decrease in the number of eMyHC‐positive myofibres on Day 5 in tibialis anterior muscles as compared with those injected with control adenoviruses (P < 0.01), while Ad‐PAK4S474A showed comparable muscle regeneration parameters. PAK4‐induced repression of muscle regeneration coincided with an increase in phosphatase and tensin homologue (PTEN) expression and a decrease in phosphoinositide 3‐kinase‐Akt signalling. In contrast, PAK4 silencing reduced PTEN expression in mice. Consistent with these findings, prodrug of PAK4 inhibitor CZh‐226 (30 mg/kg) orally administered to mice repressed PTEN expression and accelerated myotube formation. Subsequent mechanistic studies revealed that PAK4 directly phosphorylates PPARγ at S273 to increase its transcription activity, thereby up‐regulating PTEN expression. Importantly, an analysis of the Genotype‐Tissue Expression database showed a positive correlation between PAK4 and PTEN in human skeletal muscle tissues (P < 0.01).

Conclusions

p1‐activated kinase 4 is a new member of PPARγ kinase, and PAK4 inhibition may have a therapeutic role as an accelerant of muscle regeneration.
Dynamic analysis of a micro‐cantilever beam in non‐contact mode: Classic and Strain Gradient theories
Authors: Ali Mohammadi Mohammad , Farajollahi Meisam , Yousefi‐Koma Aghil
Published: August 2021

This article investigates the dynamic behavior of the micro‐cantilever beam in a non‐contact atomic force microscope based on classic and Strain Gradient continuum theories. Governing equation of the system is derived using Euler–Bernoulli and Strain Gradient theories as a nonlinear partial differential equation. Then, the equation is converted to a nonlinear ordinary differential equation using the Galerkin method, and the lumped model is derived. The effect of van der Waals repulsive term is investigated, and it is demonstrated that its repulsive term has no considerable effect on the dynamic of the system compared with its attractive term. The stability region of the system and the frequency response are computed and validated analytically and numerically. The obtained analytical equation is used for comparing the frequency response of the classic and Strain Gradient systems. It was observed that the classic theory predicts the nonlinear behavior of the system including softening for a specific dimension, while the dynamic behavior of the system is linear for the same dimensions from the Strain Gradient theory point of view. This difference probably roots in ignoring the size effect in submicron scales by the classic theory.

Highlights

The influence of the repulsive term of van der Waals force on the dynamic behavior of micro‐beam and this term is investigated.

A general closed‐form equation is derived for the stability region of AFM by an analytical approach.

Effect of size on the stability region is investigated.

The frequency response of the system is derived using the multiscale method (MSM) approach.
Pregnant women's experiences of non‐invasive prenatal testing (NIPT) in Japan: A qualitative study
Authors: Yamamoto Kayono , Chang Hyangri , Fukushima Akimune
Published: August 2021

In Japan, prenatal testing does not include a publicly insured routine health check‐up for pregnant women. Hence, taking advantage of such prenatal testing procedures is still not an option for a majority of Japanese women. However, social support systems for children and adults with disabilities have been developed with the assumption that people with disabilities will continue receiving support from their family members, especially their mothers. In this study, we described pregnant women's experiences regarding noninvasive prenatal testing (NIPT) within the context of their physical experiences during the NIPT process, Japanese society, and their medical circumstances. Women with no family history of genetic diseases or fetal disabilities and who had also received negative results after the NIPT explanation were recruited. Altogether, 15 women participated in the biographical narrative interview. The data were subjected to reflexive thematic analysis and signified advanced age for pregnancy as a trigger for both the women's consideration regarding receiving NIPT and interventions from their families and social group members. Participants considered themselves as the main caretaker for the older adults and individuals with disabilities and thus were afraid of the multiple responsibilities inherent in this reality. They were also concerned about the impact on any other siblings if the baby had disabilities. In addition, participants encounter physical and mental changes during the timeframe of the NIPT processes. Hence, as their fetuses mature, the psychological bonds the women develop with them are constantly evolving, and participants with histories of miscarriages or possible miscarriages expressed concerned not only about the results of NIPT but also about the specific possibility of losing their child in any way. In conclusion, the continuous support of these women throughout the NIPT process and social efforts for the improvement of the welfare system for people with disabilities are required to utilize NIPT effectively.
Bone formation effect of highly concentrated tricalcium phosphate biocomposite screws in a rabbit osteoporosis model
Authors: Jeong Je Hoon , Jin Eun‐Sun , Kim Ji Yeon , Min JoongKee , Jeon Sang Ryong , Lee Minsu , Choi Kyoung Hyo
Published: August 2021

The purpose of this study was to determine the efficacy of highly concentrated tricalcium phosphate (TCP) biocomposite screws on local bone formation in a rabbit model of osteoporosis induced by bilateral ovariohysterectomy (OHE). Fourteen 24‐week‐old female New Zealand rabbits (weight, 3–3.5 kg) were divided into two groups: (1) OHE and biodegradable poly(lactic‐co‐glycolic acid) (PLGA) without ß–TCP plate or screw insertion (OHE/Bio ScRew [BSR]) group and (2) OHE and biocomposite PLGA with highly concentrated ß–TCP plate and screw insertion (OHE/highly concentrated ß–triCalcium phosphate [HCCP]). Both groups underwent bilateral OHE and had two different types of screws and plates inserted at the proximal tibia. Bilateral tibiae were extracted at 25 weeks post‐OHE. The extracted tibiae were scanned with ex vivo microcomputed tomography (micro‐CT). Parameters including bone mineral density (BMD), trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb. Th), and trabecular separation (Tb. Sp) were evaluated after staining the tibial samples with hematoxylin and eosin (H&E) and Masson's trichrome. We then performed pathological assessments. Micro‐CT images revealed improved new bone formation near the implant in the OHE/HCCP group with higher values of BMD, BV/TV, and Tb.N but lower values of Tb. Th and Tb. Sp than the OHE/BSR group. Analyses of H&E and Masson's trichrome staining showed better new bone formation around the implant in the OHE/HCCP group than in the OHE/BSR group. The use of highly concentrated TCP biocomposite screw and plate might improve local bone formation and facilitate osteoconductivity in an osteoporotic rabbit model.
Location of brachial plexus birth injury affects functional outcomes in a rat model
Authors: Doshi Raveena M. , Reid Monique Y. , Dixit Nikhil N. , Fawcett Emily B. , Cole Jacqueline H. , Saul Katherine R.
Published: August 2021

Brachial plexus birth injury (BPBI) results in shoulder and elbow paralysis with shoulder internal rotation and elbow flexion contracture as frequent sequelae. The purpose of this study was to develop a technique for measuring functional movement and examine the effect of brachial plexus injury location (preganglionic and postganglionic) on functional movement outcomes in a rat model of BPBI, which we achieved through integration of gait analysis with musculoskeletal modeling and simulation. Eight weeks following unilateral brachial plexus injury, sagittal plane shoulder and elbow angles were extracted from gait recordings of young rats (n = 18), after which rats were sacrificed for bilateral muscle architecture measurements. Musculoskeletal models reflecting animal‐specific muscle architecture parameters were used to simulate gait and extract muscle fiber lengths. The preganglionic neurectomy group spent significantly less (p = 0.00116) time in stance and walked with significantly less (p < 0.05) elbow flexion and shoulder protraction in the affected limb than postganglionic neurectomy or control groups. Linear regression revealed no significant linear relationship between passive shoulder external rotation and functional shoulder protraction range of motion. Despite significant restriction in longitudinal muscle growth, normalized functional fiber excursions did not differ significantly between groups. In fact, when superimposed on a normalized force–length curve, neurectomy‐impaired muscle fibers (except subscapularis) accessed regions of the curve that overlapped with the control group. Our results suggest the presence of compensatory motor control strategies during locomotion following BPBI. The clinical implications of our findings support emphasis on functional movement analysis in treatment of BPBI, as functional and passive outcomes may differ substantially.
Impact of neoadjuvant therapy followed by laparoscopic radical gastrectomy with D2 lymph node dissection in Western population: A multi‐institutional propensity score‐matched study
Authors: Bracale Umberto , Corcione Francesco , Pignata Giusto , Andreuccetti Jacopo , Dolce Pasquale , Boni Luigi , Cassinotti Elisa , Olmi Stefano , Uccelli Matteo , Gualtierotti Monica , Ferrari Giovanni , De Martini Paolo , Bjelović Miloš , Gunjić Dragan , Cuccurullo Diego , Sciuto Antonio , Pirozzi Felice , Peltrini Roberto
Published: August 2021

Background and Objectives

In the setting of a minimally invasive approach, we aimed to compare short and long‐term postoperative outcomes of patients treated with neoadjuvant therapy (NAT) + surgery or upfront surgery in Western population.

Methods

All consecutive patients from six Italian and one Serbian center with locally advanced gastric cancer who had undergone laparoscopic gastrectomy with D2 lymph node dissection were selected between 2005 and 2019. After propensity score‐matching, postoperative morbidity and oncologic outcomes were investigated.

Results

After matching, 97 patients were allocated in each cohort with a mean age of 69.4 and 70.5 years. The two groups showed no difference in operative details except for a higher conversion rate in the NAT group (p = 0.038). The overall postoperative complications rate significantly differed between NAT + surgery (38.1%) and US (21.6%) group (p = 0.019). NAT was found to be related to a higher risk of postoperative morbidity in patients older than 60 years old (p = 0.013) but not in patients younger (p = 0.620). Conversely, no difference in overall survival (p = 0.41) and disease‐free‐survival (p = 0.34) was found between groups.

Conclusions

NAT appears to be related to a higher postoperative complication rate and equivalent oncological outcomes when compared with surgery alone. However, poor short‐term outcomes are more evident in patients over 60 years old receiving NAT.
Joint‐sparing versus nonjoint‐sparing reconstruction of the radius following oncologic resection: A systematic review
Authors: Lunn Kiera , Hoftiezer Yannick , Lans Jonathan , van der Heijden Brigitte , Chen Neal , Lozano‐Calderón Santiago A.
Published: August 2021

Background and Objectives

Reconstructions of the distal radius are uncommon procedures. This systematic review compares joints‐sparing (JS) versus nonjoint‐sparing (NJS) reconstructions following oncologic resection of the distal radius.

Methods

A search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Collected outcomes included patient‐reported outcome measures (PROMs), range of motion and grip strength, and complication and reoperation rates.

Results

A total of 52 nonrandomized cohort studies (n = 715) were included. PROMs were comparable between the cohorts, while the range of flexion‐extension was greater in JS reconstructions (78.1° vs. 25.6°) and the range of pronation‐supination was greater in NJS reconstructions (133.6° vs. 109.8°). Relative grip strength was greater following JS reconstruction (65.0% vs. 56.4%). About one in sixteen of the JS reconstructions were eventually revised to an NJS construct.

Conclusions

This systematic review demonstrates that JS reconstructive techniques can offer satisfying results in patients treated for oncologic distal radius defects. However, about 6% of JS reconstructions are eventually revised to a NJS construct. Further investigation is warranted to identify factors that affect or predict these findings, to aid in future in treatment selection and reduce the common need for reoperations following these procedures.
Perfluoro octanoic acid–modified magnetic hyperbranched polyamideamine as a sorbent for the extraction of fluorine‐containing pesticides from water samples
Authors: Meng Zilin , Liu Zikai , Fan Jiaxuan , Li Jing , Zhou Wenfeng , Gao Haixiang , Lu Runhua
Published: August 2021

Perfluoro octanoic acid was modified on the surface of magnetic hyperbranched polyamideamine by acid amine condensation. The morphology and chemical composition of perfluoro octanoic acid–modified magnetic hyperbranched polyamideamine was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, zeta potential, particle size analysis, Brunauer–Emmett–Teller measurement, and X‐ray photoelectron spectroscopy. Perfluoro octanoic acid–modified magnetic hyperbranched polyamideamine was applied in magnetic solid phase extraction for the separation and enrichment of four fluorine‐containing pesticides (indoxacarb, metaflumizone, cyflumetofen, and cyhalothrin). The magnetic solid phase extraction method based on perfluoro octanoic acid–modified magnetic hyperbranched polyamideamine has low method detection limits (0.30‒0.49 μg/L), a satisfactory coefficient of determination (0.9995‒0.9999), wide linear ranges (2.5‒250 μg/L), and good repeatability (intraday: 2.6‒4.7%; interday: 1.1‒7.9%). The enrichment factors and extraction efficiences varied from 55 to 76 and 69 to 96%, respectively. The sorbent‐to‐sorbent reproducibility was in the range of 3.2–7.6%, indicating that the synthesis of the sorbent was reliable. For the detection of actual water samples, the relative recoveries were in the range from 80.1 to 114.4% with relative standard deviations less than 9.6%. The calculation results of quantum chemistry calculations showed that after the modification of perfluoro octanoic acid, the interaction between the sorbent and four fluorine‐containing pesticides was stronger.
The Added Value of a Computer‐Aided Diagnosis System in Differential Diagnosis of Breast Lesions by Radiologists With Different Experience
Authors: Wei Qi , Zeng Shu‐E , Wang Li‐Ping , Yan Yu‐Jing , Wang Ting , Xu Jian‐Wei , Zhang Meng‐Yi , Lv Wen‐Zhi , Dietrich Christoph F. , Cui Xin‐Wu
Published: August 2021

Objectives

To evaluate the value of the computer‐aided diagnosis system, S‐Detect (based on deep learning algorithm), in distinguishing benign and malignant breast masses and reducing unnecessary biopsy based on the experience of radiologists.

Methods

From February 2018 to March 2019, 266 breast masses in 192 women were included in our study. Ultrasound (US) examination, including S‐Detect technique, was performed by the radiologist with about 10 years of clinical experience in breast US imaging. US images were analyzed by four other radiologists with different experience in breast imaging (radiologists 1, 2, 3, and 4 with 1, 4, 9, and 20 years, respectively) according to their clinical experience (with and without the results of S‐Detect). Diagnostic capabilities and unnecessary biopsy of radiologists and radiologists combined with S‐Detect were compared and analyzed.

Results

After referring to the results of S‐Detect, the changes made by less experienced radiologists were greater than experienced radiologists (benign or malignant, 44 vs 22 vs 14 vs 2; unnecessary biopsy, 34 vs 25 vs 10 vs 5). When combined with S‐Detect, less experienced radiologists showed significant improvement in accuracy, specificity, positive predictive value, negative predictive value, and area under curve (P < .05), but not for experienced radiologists (P > .05). Similarly, the unnecessary biopsy rate of less experienced radiologists decreased significantly (44.4% vs 32.7%, P = .006; 36.8% vs 28.2%, P = .033), but not for experienced radiologists (P > .05).

Conclusions

Less experienced radiologists rely more on S‐Detect software. And S‐Detect can be an effective decision‐making tool for breast US, especially for less experienced radiologists.
Estimating Population Growth and Recruitment Rates Across the Range of American Common Eiders
Authors: Giroux Jean‐François , Patenaude‐Monette Martin , Gilliland Scott G. , Milton G. Randy , Parsons Glen J. , Gloutney Mark L. , Mehl Katherine R. , Allen R. Bradford , McAuley Daniel G. , Reed Eric T. , McLellan Nic R.
Published: August 2021

Sound management of bird populations rests upon an adequate understanding of their population dynamics. Our study evaluated recruitment and population growth rates of 14 American common eider (Somateria mollissima dresseri) colonies from Labrador, Nova Scotia, Quebec, Canada, and Maine, USA, during various periods between 1970 and 2019. We used Pradel mark‐recapture models to estimate colony‐specific growth rates and the relative contributions of survival and recruitment on growth. We also validated this approach using annual nest counts (~8,000 pairs) conducted between 2003 and 2019 during down harvest operations in 3 colonies located in the Saint Lawrence estuary in Quebec. There was generally a good agreement between estimates derived using the 2 approaches. We considered that capture‐recapture data were suitable to estimate population trends of common eiders in other colonies, especially for colonies where accurate nest monitoring is impaired by dense vegetation. The breeding abundance declined at major colonies in Maine and Nova Scotia and increased or was stable in Quebec and Labrador. Female survival contributed the most to population growth, but variation in recruitment among colonies was more important than variation in survival to explain population growth. Management measures should thus strive to maximize local recruitment in colonies with declining populations. The assumption that apparent survival probabilities were homogeneous throughout an individual capture history was violated at several colonies in Quebec and Labrador. Using recaptures and band recoveries, we showed that the lower apparent survival for newly marked individuals compared to females that had been recaptured at least once was caused by a difference in site fidelity rather than true survival. But <1% of recaptured females dispersed to another colony for breeding, indicating that the lower site fidelity could be related to heterogeneity in capture probability among individuals. © 2021 The Wildlife Society.