bluuebunny/crossref_metadata_2025 huggingface dataset:
Les prépositions orphelines : un réexamen à la lumière du SP étendu
Authors: Troberg Michelle
Published: October 2021

Le présent article vise à apporter une nouvelle analyse à la distribution des prépositions et locutions prépositives par rapport à la construction orpheline (Zribi-Hertz 1984). La décomposition du syntagme prépositionnel en une hiérarchie de têtes sémantico-syntaxiques (suivant Svenonius 2010) nous permet d’entamer une formalisation des intuitions voulant que les prépositions orphelines aient un contenu lexical plus important que les prépositions qui n’admettent pas d’argument implicite, rappelant le continuum fonctionnel des prépositions dont celles dites « incolores » se trouvent sur une extrémité et celles dites « colorées » se situent sur l’autre. L’analyse propose une distinction syntaxique tripartite, Sp ; SP ; SD, pour laquelle p (à,de,en,par,sur...) n’admet pas d’argument implicite de façon catégorique. En revanche, le SD, composé d’un élément nominal faiblement référentiel et dénotant un composant axial (côté, face, pied, devant…) en admet facilement un. Pour ce qui est de la catégorie P (avec, après, contre…), elle légitime un argument implicite mais de façon moins prévisible. En s’appuyant sur la discussion de la légitimation des arguments nuls dans Roberge (2012) et des corrélations entre l’argument nul du verbe et celui de la préposition, une analyse unifiée de divers usages des prépositions émerge.
Cosmetic outcome after electrocautery versus non-electrocautery dissection of the temporalis muscle for pterional craniotomy
Authors: Lee Sang-Woo , Lee Yoon-Soo , Lee Min-Seok , Suh Sang-Jun , Lee Jeong-Ho , Kim Jin-Wook
Published: October 2021

Objective: Despite the usefulness of pterional craniotomy (PC), its cosmetic outcome is questionable. Electrocautery (EC) causes injuries to adjacent structures, and it could be a factor that affects the cosmetic outcome. Evaluation of cosmetic outcome is difficult because it is often determined by patient’s subjective criteria. The objective of this study is to compare the cosmetic outcome after EC versus non-electrocautery (NEC) dissection of the temporalis muscle for PC by analyzing long-term follow-up data determined from both physician and patient’s aspects.Methods: Patients at follow-ups between January 2014 and April 2021 after PCs were enrolled. The keyhole (KH) site, the inferior margin of the temporal line of the frontal bone (ITL), the mid-temporal (mid-T) area, and the posterior incision line (PIL) were inspected by a physician to check the presence of depressions. Patient’s cosmetic satisfaction was categorized into satisfactory, intermediate, or unsatisfactory by a survey. The presence of osteolysis was checked from the radiological images. Patients were classified into two groups; one with EC dissection and another with NEC retrograde dissection using a double-ended dissector.Results: The incidences of depression at the mid-T area and osteolysis were higher in the EC group (p=0.001, p＜0.001). The percentage of satisfactory cosmetic outcome was lower in the EC group (p=0.002). The presences of depression at the mid-T area and osteolysis were related with lower rate of satisfactory outcomes (p＜0.001, p＜0.001).Conclusions: NEC dissection causes less destruction to adjacent structures and brings better cosmetic outcome after PC.
Molecular dynamics simulation of effect of terahertz waves on the secondary structure of potassium channel proteins
Authors: Sun Yuan-Kun , Guo Liang-Hao , Wang Kai-Cheng , Wang Shao-Meng , Gong Yu-Bin ,   National Key Laboratory of Science and Technology on Vacuum Electronics, School of Electronic Science and Engineering (National Exemplary School of Microelectronics), University of Electronic Science and Technology of China, Chengdu 610054, China
Published: October 2021

Potassium channels play an important role in repolarizing the nerve cell action potentials. There are many types of potassium channel proteins, and potassium channels allow potassium ions to specifically pass through the cell membrane, thereby maintaining the resting potential of nerve cells. In this paper, molecular dynamics simulation method is used to simulate the effects of 53.7 THz terahertz wave with different amplitudes on the secondary structure of KcsA potassium channel protein and the potassium ions rate. It is found in this study that under the action of the 53.7 THz terahertz wave, the number of alpha helices in KcsA potassium channel protein decreases, and the number of beta sheets and the number of coils increase. In addition, the 53.7 THz terahertz wave can accelerate potassium ions through the KcsA potassium channel. In this article, the effects of terahertz waves on potassium channel proteins are analyzed through the secondary structure of proteins, and a new perspective for the interaction between terahertz waves and biological functional molecules is presented as well.
Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis
Authors: Gustafsson Jenny K , Davis Jazmyne E , Rappai Tracy , McDonald Keely G , Kulkarni Devesha H , Knoop Kathryn A , Hogan Simon P , Fitzpatrick James AJ , Lencer Wayne I , Newberry Rodney D
Published: October 2021

Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and yet sample lumenal substances for immune processing through formation of goblet cell associated antigen passages (GAPs). The cellular biology of GAPs and how these divergent processes are balanced and regulated by goblet cells remains unknown. Using high-resolution light and electron microscopy, we found that in mice, GAPs were formed by an acetylcholine (ACh)-dependent endocytic event remarkable for delivery of fluid-phase cargo retrograde into the trans-golgi network and across the cell by transcytosis – in addition to the expected transport of fluid-phase cargo by endosomes to multi-vesicular bodies and lysosomes. While ACh also induced goblet cells to secrete mucins, ACh-induced GAP formation and mucin secretion were functionally independent and mediated by different receptors and signaling pathways, enabling goblet cells to differentially regulate these processes to accommodate the dynamically changing demands of the mucosal environment for barrier maintenance and sampling of lumenal substances.
Short-chain fatty acids activate acetyltransferase p300
Authors: Thomas Sydney P , Denu John M
Published: October 2021

Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are produced in large quantities by the gut microbiome and contribute to a wide array of physiological processes. While the underlying mechanisms are largely unknown, many effects of SCFAs have been traced to changes in the cell’s epigenetic state. Here, we systematically investigate how SCFAs alter the epigenome. Using quantitative proteomics of histone modification states, we identified rapid and sustained increases in histone acetylation after the addition of butyrate or propionate, but not acetate. While decades of prior observations would suggest that hyperacetylation induced by SCFAs are due to inhibition of histone deacetylases (HDACs), we found that propionate and butyrate instead activate the acetyltransferase p300. Propionate and butyrate are rapidly converted to the corresponding acyl-CoAs which are then used by p300 to catalyze auto-acylation of the autoinhibitory loop, activating the enzyme for histone/protein acetylation. This data challenges the long-held belief that SCFAs mainly regulate chromatin by inhibiting HDACs, and instead reveals a previously unknown mechanism of HAT activation that can explain how an influx of low levels of SCFAs alters global chromatin states.
Endophytic Fungi as Potential Bio-Control Agents against Root Knot Nematode, Meloidogyne incognita in Banana
Authors: Ganeshan K. , Vetrivelkalai P. , Bhagawati B. , Gupta Nibha , Devrajan K. , Raveendran M. , Balachandar D.
Published: October 2021

A Survey was conducted in 12 districts of Assam to collect 92 healthy banana root samples. A total of 55 fungal isolates were successfully isolated from commercial banana cultivars. The culture filtrates were extracted from 55 endophytic fungal isolates and screened against root knot nematode, Meloidogyne incognita in vitro and pot culture studies. Among them, five fungal isolates viz., EF4, BF7, BF27, BF28 and BF35 showed 100% inhibition of egg hatching and 96.33 to 81.33% juvenile mortality of M. incognita with an exposure period of 72h when compared to other isolates and control. On paddy seed treatment with endophytic fungi of five promising isolates, two isolates viz., BF7 and BF28 significantly enhanced germination percentage (82.67%, 73.33%) and vigour index (62.91, 47.24%), respectively. The selected five endophytic fungal isolates were evaluated for their efficacy against M. incognita in banana under pot culture conditions. The study revealed that culture filtrates of BF7 and BF28 significantly reduced the soil and root nematode population, number of adult females, egg masses and root gall index of M.incognita compared to untreated control. The isolates BF7 and BF28 also significantly increased the growth parameters viz., pseudostem height, root length and pseudostem girth. These promising endophytic fungal isolates viz., BF7 and BF28 were identified as non-pathogenic Fusarium oxysporum strains (Accession no. MN567668) and (Accession no. MN567710), respectively by PCR -18S rRNA of ITS region of gene sequence and phylogenetic tree construction.
Binder‐Free Growth of Aluminum‐Based Metal–Organic Frameworks on Aluminum Substrate for Enhanced Water Adsorption Capacity
Authors: Yang Tianyu , Ge Lurong , Ge Tianshu , Zhan Guowu , Wang Ruzhu
Published: October 2021

Coating metal–organic frameworks (MOFs) on metal substrates is an important research orientation in the applications of MOFs. However, the existing binder‐based coating method needs repetitive operations and unavoidably plugs the pores of MOFs, resulting in a reduction of the adsorption capacity. Herein, a binder‐free method is proposed to construct the MOF‐on‐metal structure. The well‐intergrown polycrystalline Al‐MOF layer on aluminum substrate is prepared by in situ synthesizing Al‐based MOFs (MIL‐96 and MIL‐100) with aluminum ions from the dissolution of aluminum substrates. The morphology and chemical compositions of the MOF coating layer are systematically characterized, and a pH‐controlled strategy is proposed to regulate the relative proportion of the hybrid MOFs. Importantly, the MOF‐on‐metal structure displays ultrahigh water adsorption capacity of 192.5 g m−2, which is the highest of all reported desiccant‐coated metal structures, and superior cycling stability. Further, the performance of a desiccant heat pump system utilizing MOF‐on‐metal structure is predicted, demonstrating that the operation period is 80% longer than a system with a binder‐based silica gel coating, and the average dehumidification capacity can reach 8.36 g kg−1 dry air. In conclusion, the new method enables the formation of binder‐free, low‐cost, and high‐performance MOF coating and has a broad prospect in energy‐efficient adsorption‐based applications.
Charge‐Carrier Transport in Quasi‐2D Ruddlesden–Popper Perovskite Solar Cells
Authors: Yan Linfang , Ma Junjie , Li Pengwei , Zang Shuangquan , Han Liyuan , Zhang Yiqiang , Song Yanlin
Published: October 2021

In recent years, 2D Ruddlesden–Popper (2DRP) perovskite materials have been explored as emerging semiconductor materials in solar cells owing to their excellent stability and structural diversity. Although 2DRP perovskites have achieved photovoltaic efficiencies exceeding 19%, their widespread use is hindered by their inferior charge‐carrier transport properties in the presence of diverse organic spacer cations, compared to that of traditional 3D perovskites. Hence, a systematic understanding of the carrier transport mechanism in 2D perovskites is critical for the development of high‐performance 2D perovskite solar cells (PSCs). Here, the recent advances in the carrier behavior of 2DRP PSCs are summarized, and guidelines for successfully enhancing carrier transport are provided. First, the composition and crystal structure of 2DRP perovskite materials that affect carrier transport are discussed. Then, the features of 2DRP perovskite films (phase separation, grain orientation, crystallinity kinetics, etc.), which are closely related to carrier transport, are evaluated. Next, the principal direction of carrier transport guiding the selection of the transport layer is revealed. Finally, an outlook is proposed and strategies for enhancing carrier transport in high‐performance PSCs are rationalized.
Combining Experimental and DFT Investigation of the Mechanism Involved in Thermal Etching of Titanium Nitride Using Alternate Exposures of NbF5 and CCl4, or CCl4 Only
Authors: Sharma Varun , Kondati Natarajan Suresh , Elliott Simon D. , Blomberg Tom , Haukka Suvi , Givens Michael E. , Tuominen Marko , Ritala Mikko
Published: October 2021

Thermally activated chemical vapor‐phase etching of titanium nitride (TiN) is studied by utilizing either alternate exposures of niobium pentafluoride (NbF5) and carbon tetrachloride (CCl4) or by using CCl4 alone. Nitrogen (N2) gas purge steps are carried out in between every reactant exposure. Titanium nitride is etched in a non‐self‐limiting way by NbF5–CCl4 based binary chemistry or by CCl4 at temperatures between 370 and 460 °C. Spectroscopic ellipsometry and a weight balance are used to calculate the etch per cycle. For the binary chemistry, an etch per cycle of ≈0.8 Å is obtained for 0.5 and 3 s long exposures of NbF5 and CCl4, respectively at 460 °C. On the contrary, under the same conditions, the etch process with CCl4 alone gives an etch per cycle of about 0.5 Å. In the CCl4‐only etch process, the thickness of TiN films removed at 460 °C varies linearly with the number of etch cycles. Furthermore, CCl4 alone is able to etch TiN selectively over other materials such as Al2O3, SiO2, and Si3N4. X‐ray photoelectron spectroscopy and bright field transmission electron microscopy are used for studying the post‐etch surfaces. To understand possible reaction products and energetics, first‐principles calculations are carried out with density functional theory. From thermochemical analysis of possible reaction models, it is found that NbF5 alone cannot etch TiN while CCl4 alone can etch it at high temperatures. The predicted byproducts of the reaction between the CCl4 gas molecules and TiN surface are TiCl3 and ClCN. Similarly, TiF4, NbFCl3, and ClCN are predicted to be the likely products when TiN is exposed to both NbF5 and CCl4. A more favorable etch reaction is predicted when TiN is exposed to both NbF5 and CCl4 (ΔG = −2.7 eV at 640 K) as compared to exposure to CCl4 only (ΔG = −2 eV at 640 K) process. This indicates that an enhanced etch rate is possible when TiN is exposed alternately to both NbF5 and CCl4, which is in close agreement with the experimental results.
Broadband Nonlinear Photoresponse and Ultrafast Carrier Dynamics of 2D PdSe2
Authors: Chen Xin , Huang Jiawei , Chen Chenduan , Chen Meiling , Hu Guohang , Wang Hongqiang , Dong Ningning , Wang Jun
Published: October 2021

Palladium diselenide (PdSe2) exhibits considerable potential for application in broadband optoelectronic devices. In this work, the broadband nonlinear optical performance and ultrafast carrier dynamics from ultraviolet to near‐infrared of a trilayer PdSe2 are systematically studied. PdSe2 is found to achieve a giant saturable absorption performance. The modulation depth is 22.47% at 520 nm, whereas the nonsaturable loss and saturation intensity are only 3.83% and 15.47 GW cm−2, respectively, which are better than those of many 2D semiconductors. Based on these findings, a PdSe2‐based visible light thresholder is proposed, its function is to extract an undetectable pulse signal drowned in strong stochastic noise and thereby improve the signal‐to‐noise ratio. Pump–probe technique, along with first‐principles calculation and transient absorption spectra, reveals the intrinsic recombination mechanism, including Auger scattering and trap saturation. This work is expected to establish the foundation for the development of next‐generation PdSe2‐based devices in optoelectronics and visible light communication.
Twinning Enhances Efficiencies of Metallic Catalysts toward Electrolytic Water Splitting
Authors: Huang Chun‐Lung , Sasaki Kotaro , Senthil Raja Duraisamy , Hsieh Cheng‐Ting , Wu Yen‐Ju , Su Jing‐Ting , Cheng Chih‐Chieh , Cheng Po‐Yin , Lin Shin‐Hong , Choi YongMan , Lu Shih‐Yuan
Published: October 2021

Twinning is demonstrated to be an effective way of enhancing efficiencies of metallic catalysts toward electrolytic water splitting. Dendritic Cu possessing dense coherent nanotwin (NT) boundaries (NTCu‐5nm) is successfully prepared with an organic‐assisted electrodeposition at high pulse current densities. NT boundaries significantly improve electrocatalytic efficiencies and stability of NTCu‐5nm over nanocrystalline Cu (NCCu), reducing overpotentials at 10 mA cm−2 for the oxygen evolution reaction (OER) from 378 to 281 mV and from 235 to 88 mV for the hydrogen evolution reaction (HER), with a small chronoamperometric decay of 5% after 100 h continuous overall water splitting at an ultrahigh initial current density of 500 mA cm−2, largely outperforming the large chronoamperometric decay of 27% for only 1 h operation of the NCCu//NCCu couple. The defective twin boundaries enable formation of active CuIIIO2− at low overpotentials, thus enhancing OER performance. The synergistic geometric and electronic effects induced by the twin boundaries result in shifts in Gibbs free energies of hydrogen adsorption (ΔGH) toward the apex of a volcano plot of exchange current density versus ΔGH, leading to the remarkable improvement in HER activity.
Celastrol attenuates high‐fructose diet‐induced inflammation and insulin resistance via inhibition of 11β‐hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues
Authors: Abu Bakar Mohamad Hafizi , Mohamad Khalid Mohamad Shamil Faris , Nor Shahril Nor Shafiqah , Shariff Khairul Anuar , Karunakaran Thiruventhan
Published: October 2021

High fructose consumption has been linked to low‐grade inflammation and insulin resistance that results in increased intracellular 11ß‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) activity. Celastrol, a pentacyclic triterpene, has been demonstrated to exhibit multifaceted targets to attenuate various metabolic diseases associated with inflammation. However, the underlying mechanisms by which celastrol exerts its attributive properties on high fructose diet (HFrD)‐induced metabolic syndrome remain elusive. Herein, the present study was aimed to elucidate the mechanistic targets of celastrol co‐administrations upon HFrD in rats and evaluate its potential to modulate 11β‐HSD1 activity. Celastrol remarkably improved glucose tolerance, lipid profiles, and insulin sensitivity along with suppression of hepatic glucose production. In rat adipose tissues, celastrol attenuated nuclear factor‐kappa B (NF‐κB)‐driven inflammation, reduced c‐Jun N‐terminal kinases (JNK) phosphorylation, and mitigated oxidative stress via upregulated genes expression involved in mitochondrial biogenesis. Furthermore, insulin signaling pathways were significantly improved through the restoration of Akt phosphorylation levels at Ser473 and Thr308 residues. Celastrol exhibited a potent, selective and specific inhibitor of intracellular 11β‐HSD1 towards oxidoreductase activity (IC50 value = 4.3 nM) in comparison to other HSD‐related enzymes. Inhibition of 11β‐HSD1 expression in rat adipose microsomes reduced the availability of its cofactor NADPH and substrate H6PDH in couple to upregulated mRNA and protein expressions of glucocorticoid receptor. In conclusion, our results underscore the most likely conceivable mechanisms exhibited by celastrol against HFrD‐induced metabolic dysregulations mainly through attenuating inflammation and insulin resistance, at least via specific inhibitions on 11β‐HSD1 activity in adipose tissues.
Trends in patient‐reported outcome use in early phase dose‐finding oncology trials – an analysis of ClinicalTrials.gov
Authors: Lai‐Kwon Julia , Yin Zhulin , Minchom Anna , Yap Christina
Published: October 2021

Background

Patient‐reported adverse events (AEs) may be a useful adjunct to clinician‐assessed AEs for assessing tolerability in early phase, dose‐finding oncology trials (DFOTs). We reviewed DFOTs on ClinicalTrials.gov to describe trends in patient‐reported outcome (PRO) use.

Methods

DFOTs commencing 01 January 2007 – 20 January 2020 with ‘PROs’ or ‘quality of life’ as an outcome were extracted and inclusion criteria confirmed. Study and PRO characteristics were extracted. Completed trials that reported PRO outcomes and published manuscripts on ClinicalTrials.gov were identified, and PRO reporting details were extracted.

Results

5.3% (548/10 372) DFOTs included PROs as an outcome. 231 (42.2%) were eligible: adult (224, 97%), solid tumour (175, 75.8%), and seamless phase 1/2 (108, 46.8%). PRO endpoints were identified in more trials (2.3 increase/year, 95% CI: 1.6–2.9) from an increasing variety of countries (0.7/year) (95% CI: 0.4–0.9) over time. PROs were typically secondary endpoints (207, 89.6%). 15/77 (19.5%) completed trials reported results on the ClinicalTrials.gov results database, and of those eight included their PRO results. Eighteen trials had published manuscripts available on ClinicalTrials.gov. Three (16.7%) used PROs to confirm the maximum tolerated dose. No trials identified who completed the PROs or how PROs were collected.

Conclusions

PRO use in DFOT has increased but remains limited. Future work should explore the role of PROs in DFOT and determine what guidelines are needed to standardise PRO use.
Protocols for Characterization of Cdk5 Kinase Activity
Authors: Terse Anita , Amin Niranjana , Hall Bradford , Bhaskar Manju , B.K. Binukumar , Utreras Elias , Pareek Tej K. , Pant Harish , Kulkarni Ashok B.
Published: October 2021

Cyclin‐dependent kinases (Cdks) are generally known to be involved in controlling the cell cycle, but Cdk5 is a unique member of this protein family for being most active in post‐mitotic neurons. Cdk5 is developmentally important in regulating neuronal migration, neurite outgrowth, and axon guidance. Cdk5 is enriched in synaptic membranes and is known to modulate synaptic activity. Postnatally, Cdk5 can also affect neuronal processes such as dopaminergic signaling and pain sensitivity. Dysregulated Cdk5, in contrast, has been linked to neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Despite primarily being implicated in neuronal development and activity, Cdk5 has lately been linked to non‐neuronal functions including cancer cell growth, immune responses, and diabetes. Since Cdk5 activity is tightly regulated, a method for measuring its kinase activity is needed to fully understand the precise role of Cdk5 in developmental and disease processes. This article includes methods for detecting Cdk5 kinase activity in cultured cells or tissues, identifying new substrates, and screening for new kinase inhibitors. Furthermore, since Cdk5 shares homology and substrate specificity with Cdk1 and Cdk2, the Cdk5 kinase assay can be used, with modification, to measure the activity of other Cdks as well. © 2021 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Basic Protocol 1: Measuring Cdk5 activity from protein lysates

Support Protocol 1: Immunoprecipitation of Cdk5 using Dynabeads

Alternate Protocol: Non‐radioactive protocols to measure Cdk5 kinase activity

Support Protocol 2: Western blot analysis for the detection of Cdk5, p35, and p39

Support Protocol 3: Immunodetection analysis for Cdk5, p35, and p39

Support Protocol 4: Genetically engineered mice (+ and – controls)

Basic Protocol 2: Identifying new Cdk5 substrates and kinase inhibitors
Continuous Crystallization of Phosphoric Acid Using Suspension Crystallizer: Effect of Operating Conditions on Purity of Crystals
Authors: Tsushima Ippei , Maeda Kouji , Yamamoto Takuji , Arafune Koji , Miki Hideo
Published: October 2021

In this study, batch crystallization via indirect cooling and continuous crystallization via direct and indirect cooling of phosphoric acid hemihydrate (H3PO4.1/2H2O) from the mixed acid solution of phosphoric acid and acetic acid are performed. In batch crystallization, needle‐shaped crystals are obtained, and the impurity concentration of acetic acid in the crystals is 4.2 wt%. Primary nucleation occurred under a high degree of supersaturation, and the metastable zone width for secondary nuclei is narrow. In contrast, in continuous crystallization via indirect cooling, scaly crystals are obtained, and the acetic acid impurity concentration therein is 2.0 wt%. Additionally, continuous crystallization via direct contact cooling is performed, the crystal shape and impurity concentration under direct cooling are similar to those under indirect cooling, suggesting the possibility to downsize the apparatus. Through utilization of the equipment and approach elaborated herein, the correlation between the operating conditions and crystal quality can be assessed.
Electrochemical Detection of Phenol Removal by Using a Biosorbent Originated Factory Solid Waste
Authors: Congur Gulsah , Gül Ülküye Dudu
Published: October 2021

Biosorption is a preferable method for phenol (PNL) removal from water sources using a cheap and eco‐friendly biomass. The combination of the biosorption technique with practical, affordable, sensitive, and selective monitoring tools gives a new perspective to environmental monitoring applications. Herein, as the first time, the monitoring of PNL biosorption performed using a factory waste was done by pencil graphite electrodes (PGEs) and cyclic voltammetry (CV) technique. The monitoring of the biosorption process was completed with reproducible and reliable results in just 40s. The biosorption was achieved in different water samples and the presence of different phenolic compounds.
Hepatocellular Carcinoma Risk Assessment for Patients With Advanced Fibrosis After Eradication of Hepatitis C Virus
Authors: Tamaki Nobuharu , Kurosaki Masayuki , Yasui Yutaka , Mori Nami , Tsuji Keiji , Hasebe Chitomi , Joko Kouji , Akahane Takehiro , Furuta Koichiro , Kobashi Haruhiko , Kimura Hiroyuki , Yagisawa Hitoshi , Marusawa Hiroyuki , Kondo Masahiko , Kojima Yuji , Yoshida Hideo , Uchida Yasushi , Tada Toshifumi , Nakamura Shinichiro , Yasuda Satoshi , Toyoda Hidenori , Loomba Rohit , Izumi Namiki
Published: October 2021

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum‐based risk model that could identify patients with low‐risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma‐glutamyl transferase < 28 IU/L, alpha‐fetoprotein < 4.0 ng/mL, and Fibrosis‐4 Index < 4.28) were classified as low‐risk and others were classified as high‐risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low‐risk patients (0.5‐1.1 per 100 person‐years in the derivation cohort and 0.9‐1.1 per 100 person‐years in the validation cohort) than in high‐risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high‐risk to low‐risk (HCC incidence: 0.6 per 100 person‐years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person‐years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance.
Traf2 and NCK Interacting Kinase Is a Critical Regulator of Procollagen I Trafficking and Hepatic Fibrogenesis in Mice
Authors: Buchl Samuel C. , Hanquier Zachary , Haak Andrew J. , Thomason Yvonne M. , Huebert Robert C. , Shah Vijay H. , Maiers Jessica L.
Published: October 2021

Hepatic fibrosis is driven by deposition of matrix proteins following liver injury. Hepatic stellate cells (HSCs) drive fibrogenesis, producing matrix proteins, including procollagen I, which matures into collagen I following secretion. Disrupting intracellular procollagen processing and trafficking causes endoplasmic reticulum stress and stress‐induced HSC apoptosis and thus is an attractive antifibrotic strategy. We designed an immunofluorescence‐based small interfering RNA (siRNA) screen to identify procollagen I trafficking regulators, hypothesizing that these proteins could serve as antifibrotic targets. A targeted siRNA screen was performed using immunofluorescence to detect changes in intracellular procollagen I. Tumor necrosis factor receptor associated factor 2 and noncatalytic region of tyrosine kinase‐interacting kinase (TNIK) was identified and interrogated in vitro and in vivo using the TNIK kinase inhibitor NCB‐0846 or RNA interference‐mediated knockdown. Our siRNA screen identified nine genes whose knockdown promoted procollagen I retention, including the serine/threonine kinase TNIK. Genetic deletion or pharmacologic inhibition of TNIK through the small molecule inhibitor NCB‐0846 disrupted procollagen I trafficking and secretion without impacting procollagen I expression. To investigate the role of TNIK in liver fibrogenesis, we analyzed human and murine livers, finding elevated TNIK expression in human cirrhotic livers and increased TNIK expression and kinase activity in both fibrotic mouse livers and activated primary human HSCs. Finally, we tested whether inhibition of TNIK kinase activity could limit fibrogenesis in vivo. Mice receiving NCB‐0846 displayed reduced CCl4‐induced fibrogenesis compared to CCl4 alone, although α‐smooth muscle actin levels were unaltered. Conclusions: Our siRNA screen effectively identified TNIK as a key kinase involved in procollagen I trafficking in vitro and hepatic fibrogenesis in vivo.
Local anaesthesia for dental and oral surgery in cats and dogs
Authors: Oxford Matthew , Gurney Matt
Published: October 2021

Background: Local and regional anaesthetic techniques are growing in popularity within many areas of veterinary surgery, and rightly so owing to their important modulation of intra‐ and postoperative pain, and with the subsequent improvements in general anaesthesia. Oral local anaesthesia is no exception, with several articles and book chapters devoted to it. However, many of these articles reference a series of historical techniques and injection sites, which on closer evaluation, may not actually achieve what was intended.

Aim of the article: The aim of this article is to evaluate the tissues that are traumatised during oral and dental surgery, assess the afferent neural anatomy for these tissues and then discuss injection sites and techniques that are most likely to result in full anaesthesia of these tissues during surgery.
Controlled breeding in dairy cows. Part 1: bovine oestrus cycle and synchronisation
Authors: Lindley George , Willshire Jim , Martin Adam
Published: October 2021

Background: Timed artificial insemination (TAI) as part of a controlled breeding programme is a reproductive strategy that eliminates the requirement for oestrus detection, guarantees the submission of enrolled cows and attempts to optimise the timing of insemination relative to ovulation. However, the success of TAI requires careful cow selection, diligent herd management and the selection of an appropriate synchronisation protocol.

Aim of the article: This article, the first in a two‐part series, outlines the key ovarian follicular wave dynamics in the bovine oestrous cycle and the key goals of any synchronisation protocol. It describes the most commonly used drugs, their actions and how they can be combined into effective synchronisation protocols. The second part of the series, to be published in a subsequent issue of In Practice, discusses how to implement controlled breeding strategies on farms and considers factors aside from the TAI protocol that are essential for the success of any programme.
Inorganic phosphate‐induced cytotoxicity
Authors: Alexander Rachel , Debiec Nicholas , Razzaque Mohammad S. , He Ping
Published: October 2021

Phosphate, an essential nutrient, is available in organic and inorganic forms. The balance of phosphate is central for cellular homeostasis through the genomic roles of DNA and RNA synthesis and cell signaling processes. Therefore, an imbalance of this nutrient, manifested, either as a deficiency or excess in phosphate levels, can result in pathology, ranging from cytotoxicity to musculoskeletal defects. Inorganic phosphate (Pi) overdosing can result in a wide spectrum of cytotoxicity processes, as noted in both animal models and human studies. These include rewired cell signaling pathways, impaired bone mineralization, infertility, premature aging, vascular calcification, and renal dysfunction. This article briefly reviews the regulation of phosphate homeostasis and elaborates on cytotoxic effects of excessive Pi, as documented in cell‐based models.
Overview of approval procedures for bioadhesives in the United States of America and Canada
Authors: Dhandapani Vignesh , Saseedharan Prashanth , Groleau Denis , Vermette Patrick
Published: October 2021

Bioadhesives are useful medical devices to help reduce postoperative complications and as adjuncts to sutures and staples in sealing wounds. Biomedical companies have been promoting research and development into new bioadhesives. As for other medical devices, translating promising candidates to market involves the need to pass through several regulatory steps, wherein their safety and effectiveness are evaluated and the proper reimbursements from payors are assessed. The regulatory procedures involve classification based on the risk factors, support studies, submission of applications to relevant authorities, procurement of certification, and finally commercialization, while keeping a track record of the post‐market data. The importance of real‐world data has been recently realized. The aim of this review is to focus on the translational goals, expectations, and necessities of medical devices focusing on the bioadhesives to be commercialized. It should aid researchers inspired to discover and market new bioadhesives in understanding the need for basic regulatory procedures behind their commercialization for medical usage, most importantly for internal medicine specifically in the United States of America, Canada, and Europe, in part. The key differences in the regulatory aspects among those are highlighted. Regulations keep changing with the introduction of new products and governmental laws. They are updated in this manuscript till March 2021.
circCORO1C promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing the expression of PD‐L1 through NF‐κB pathway
Authors: Wu Fan , Sun Guoqiang , Zheng Wubin , Tang Weiwei , Cheng Ye , Wu LiangLiang , Li Xiao , Tao Jing , Ma Shijie , Cao Hongyong
Published: October 2021

Background

Circular RNA (circRNA) affects the occurrence and development of human cancers, but the specific mechanism of hepatocellular carcinoma (HCC) has not yet been fully understood.

Methods

CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Cell viability, migration, invasion, and other indicators were used for cell function analysis. Knockdown and overexpression techniques were used to explore the mechanism of circCORO1C in the occurrence and development of HCC by RNA sequencing, qRT‐PCR, western blot, and other methods.

Results

Among the thousands of circRNAs, 1238 circRNAs were significantly changed. As for the top 10 upregulated circRNAs, the expression of circRNAs, hsa_circ_0036412, hsa_circ_0036411, hsa_circ_0028071, hsa_circ_0036409, hsa_circ_0000437, hsa_circ_0021427, hsa_circ_0097182, hsa_circ_0028067, hsa_circ_0006852, and hsa_circ_0003620 were significantly increased. In regard to the top 10 downregulated circRNAs, the expression of hsa_circ_0123629, hsa_circ_0096121, hsa_circ_0038932, hsa‐circRNA3310‐44, hsa_circ_0045746, hsa_circ_0016836, hsa‐circRNA10899‐9, hsa_circ_0050116, hsa_circ_0035543, and hsa_circ_0092118 decreased significantly. About these circRNAs, the downregulation of hsa_circ_0006852 (circCORO1C) can inhibit the tumorigenesis of HCC cells in vivo and in vitro, and the overexpression of circCORO1C can enhance the proliferation and metastasis ability of HCC cells. Mechanistically, circCORO1C activated the NF‐κB signaling pathway, increased P65 phosphorylation and upregulation of c‐Myc and COX‐2, leading to increased PD‐L1 expression.

Conclusion

CircCORO1C upregulates c‐Myc and COX‐2 through NF‐κB signaling pathway, leading to the upregulation of PD‐L1, which jointly promotes the development of HCC, suggesting that circCORO1C is a promising biomarker and therapeutic target for HCC.
Effects of hormonal changes on sarcopenia in chronic kidney disease: where are we now and what can we do?
Authors: Gungor Ozkan , Ulu Sena , Hasbal Nuri Baris , Anker Stefan D. , Kalantar‐Zadeh Kamyar
Published: October 2021

Sarcopenia or muscle wasting is a progressive and generalized skeletal muscle disorder involving the accelerated loss of muscle mass and function, often associated with muscle weakness (dynapenia) and frailty. Whereas primary sarcopenia is related to ageing, secondary sarcopenia happens independent of age in the context of chronic disease states such as chronic kidney disease (CKD). Sarcopenia has become a major focus of research and public policy debate due to its impact on patient's health‐related quality of life, health‐care expenditure, morbidity, and mortality. The development of sarcopenia in patients with CKD is multifactorial and it may occur independently of weight loss or cachexia including under obese sarcopenia. Hormonal imbalances can facilitate the development of sarcopenia in the general population and is a common finding in CKD. Hormones that may influence the development of sarcopenia are testosterone, growth hormone, insulin, thyroid hormones, and vitamin D. Although the relationship between free testosterone level that is low in uraemic patients and sarcopenia in CKD is not well‐defined, functional improvement may be seen. Unlike testosterone, it is known that vitamin D is associated with muscle strength, muscle size, and physical performance in patients with CKD. Outcomes after vitamin D replacement therapy are still controversial. The half‐life of growth hormone (GH) is prolonged in patients with CKD. Besides, IGF‐1 levels are normal in patients with Stage 4 CKD—a minimal reduction is seen in the end‐stage renal disease. Unresponsiveness or resistance of IGF‐1 and changes in the GH/IGF‐1 axis are the main causes of sarcopenia in CKD. Low serum T3 level is frequent in CKD, but the net effect on sarcopenia is not well‐studied. CKD patients develop insulin resistance (IR) from the earliest period even before GFR decline begins. IR reduces glucose utilization as an energy source by hepatic gluconeogenesis, decreasing muscle glucose uptake, impairing intracellular glucose metabolism. This cascade results in muscle protein breakdown. IR and sarcopenia might also be a new pathway for targeting. Ghrelin, oestrogen, cortisol, and dehydroepiandrosterone may be other players in the setting of sarcopenia. In this review, we mainly examine the effects of hormonal changes on the occurrence of sarcopenia in patients with CKD via the available data.
Should we call it a (middle) class? A socio‐economic exploration of the Vietnamese middle‐income group
Authors: Rougier Eric , Berrou Jean‐Philippe , Clément Matthieu , Combarnous François , Darbon Dominique
Published: October 2021

By combining household survey data on the economic and social characteristics of middle‐income earners and primary survey data on their subjective perceptions, we show that the so‐called Vietnamese ‘middle class’ is strongly heterogeneous in terms of income, occupation and status and includes a large percentage of highly vulnerable households facing high individual risk not covered by social protection. Although marginally driven by public sector employment and formal private sector expansion, it shares common traits that might help consolidate class identification and could lead to more formally organised political influence if the political sphere becomes more open in the future.
Solvent‐Cast 3D Printing of Biodegradable Polymer Scaffolds
Authors: Tolbert John W. , Hammerstone Diana E. , Yuchimiuk Nathaniel , Seppala Jonathan E. , Chow Lesley W.
Published: October 2021

3D printing is a popular fabrication technique because of its ability to produce complex architectures. Melt‐based 3D printing is widely used for thermoplastic polymers like poly(caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic‐co‐glycolic acid) (PLGA) because of their low processing temperatures. However, traditional melt‐based techniques require processing temperatures and pressures high enough to achieve continuous flow, limiting the type of polymer that can be printed. Solvent‐cast printing (SCP) offers an alternative approach to print a wider range of polymers. Polymers are dissolved in a volatile solvent that evaporates during deposition to produce a solid polymer filament. SCP, therefore, requires optimizing polymer concentration in the ink, print pressure, and print speed to achieve desired print fidelity. Here, capillary flow analysis shows how print pressure affects the process‐apparent viscosity of PCL, PLA, and PLGA inks. Ink viscosity is also measured using rheology, which is used to link a specific ink viscosity to a predicted set of print pressure and print speed for all three polymers. These results demonstrate how this approach can be used to accelerate optimization by significantly reducing the number of parameter combinations. This strategy can be applied to other polymers to expand the library of polymers printable with SCP.
MHA State of Mental Health in America report finds suicidal ideation concerning
Authors: Canady Valerie A.
Published: October 2021

With the release of its eighth consecutive report on the state of mental health in this country, Mental Health America (MHA) reveals concerning trends, such as increased suicidal ideation among adults and findings revealing that more than half of adults (27 million) with a mental illness do not receive treatment — and these trends are pre‐pandemic; the data, the most current reported by states and available to the public, is from 2019.
A semi‐analytical approach for fractional order Boussinesq equation in a gradient unconfined aquifers
Authors: Rashid Saima , Kubra Khadija T. , Jafari Hossein , Lehre Sana Ullah
Published: October 2021

In this investigation, we propose a semi‐analytical technique to solve the fractional order Boussinesq equation (BsEq) that pertains the groundwater level in a gradient unconfined aquifer having an impervious extremity. With the aid of Antagana‐Baleanu fractional derivative operator and Laplace transform, several novel approximate‐analytical solutions of the fourth‐order time‐fractional BsEq in
and the 2nd‐order in
are derived. We analyze the most dominant ideology of differentiation, including the nonsingular kernel relying on the extended Mittag‐Leffler type function to modify BsEq. Furthermore, we demonstrate the existence and uniqueness of the solution for the non‐linear fractional BsEq. The present method is appealing and the simplistic methodology indicates that it could be straightforwardly protracted to solve various nonlinear fractional‐order partial differential equations.
Cascaded deep learning‐based auto‐segmentation for head and neck cancer patients: Organs at risk on T2‐weighted magnetic resonance imaging
Authors: Korte James C. , Hardcastle Nicholas , Ng Sweet Ping , Clark Brett , Kron Tomas , Jackson Price
Published: October 2021

Purpose

To investigate multiple deep learning methods for automated segmentation (auto‐segmentation) of the parotid glands, submandibular glands, and level II and level III lymph nodes on magnetic resonance imaging (MRI). Outlining radiosensitive organs on images used to assist radiation therapy (radiotherapy) of patients with head and neck cancer (HNC) is a time‐consuming task, in which variability between observers may directly impact on patient treatment outcomes. Auto‐segmentation on computed tomography imaging has been shown to result in significant time reductions and more consistent outlines of the organs at risk.

Methods

Three convolutional neural network (CNN)‐based auto‐segmentation architectures were developed using manual segmentations and T2‐weighted MRI images provided from the American Association of Physicists in Medicine (AAPM) radiotherapy MRI auto‐contouring (RT‐MAC) challenge dataset (n = 31). Auto‐segmentation performance was evaluated with segmentation similarity and surface distance metrics on the RT‐MAC dataset with institutional manual segmentations (n = 10). The generalizability of the auto‐segmentation methods was assessed on an institutional MRI dataset (n = 10).

Results

Auto‐segmentation performance on the RT‐MAC images with institutional segmentations was higher than previously reported MRI methods for the parotid glands (Dice: 0.860 ± 0.067, mean surface distance [MSD]: 1.33 ± 0.40 mm) and the first report of MRI performance for submandibular glands (Dice: 0.830 ± 0.032, MSD: 1.16 ± 0.47 mm). We demonstrate that high‐resolution auto‐segmentations with improved geometric accuracy can be generated for the parotid and submandibular glands by cascading a localizer CNN and a cropped high‐resolution CNN. Improved MSDs were observed between automatic and manual segmentations of the submandibular glands when a low‐resolution auto‐segmentation was used as prior knowledge in the second‐stage CNN. Reduced auto‐segmentation performance was observed on our institutional MRI dataset when trained on external RT‐MAC images; only the parotid gland auto‐segmentations were considered clinically feasible for manual correction (Dice: 0.775 ± 0.105, MSD: 1.20 ± 0.60 mm).

Conclusions

This work demonstrates that CNNs are a suitable method to auto‐segment the parotid and submandibular glands on MRI images of patients with HNC, and that cascaded CNNs can generate high‐resolution segmentations with improved geometric accuracy. Deep learning methods may be suitable for auto‐segmentation of the parotid glands on T2‐weighted MRI images from different scanners, but further work is required to improve the performance and generalizability of these methods for auto‐segmentation of the submandibular glands and lymph nodes.