bluuebunny/crossref_metadata_2025 huggingface dataset:
MSN‐CDF: New community detection framework to improve routing in mobile social networks
Authors: Moradi Saeed , Mohasefi Jamshid Bagherzadeh , Mahdipour Ebrahim
Published: September 2021

In mobile social networks (MSN), portable devices of mobile users communicate with each other. The contact and intercontact times are the two most important parameters that specify the behavior of MSN. Many social features such as similarity, centrality, closeness, and distance are derived from contact and intercontact time patterns. Those parameters and features can be used in the community detection process in community‐based routing as a vector weight of network graph edges. But there is no solution for proper exploitation of them as a multicriteria optimization of community detection algorithms so that the communities become more adaptive with the MSN quiddity and the computational complexity of the algorithms to be stay constant. In this paper, we propose the MSN‐adaptive community detection framework, MSN‐CDF, which meets these demands. We improve the quality function of community detection methods, for example, the Intensity in clique percolation methods and the Modularity in modularity‐based methods, through our new model‐based joint optimization of their quality functions. To this end, to express the MSN contact and social features, we develop a criterion called MCSF. It holds the contact time and intercontact time distributions parameters and implies their social features for MSN purposes. This criterion has as little traffic as possible and enjoys from the probabilistic joint distribution model. The simulations show that MSN‐CDF reduces the network overhead significantly compared with the DiBUBB, Epidemic, and Dynamic Routing. Moreover, it outperforms DiBUBB and Dynamic Routing in terms of delivery rate and delivery latency.
Location detection of the mobile sensor with fingerprinting‐based cascade artificial neural network model using received signal strength indicator in 3D indoor environment
Authors: Tuncer Taner , Erdem Ebubekir
Published: September 2021

The problem of localization of mobile sensor nodes has been extensively studied in the literature in recent years. In any localization technique, the aim is to determine the location of the sensor node of unknown location with low error. In this article, a cascading artificial neural network (ANN)‐based location detection algorithm is proposed, which detects the location of a mobile sensor node in 3D indoor environment. In a 3D indoor environment of 6 × 20 × 3 m3, received signal strength indicator (RSSI) signals were collected using a mobile node with XBee sensor, and a fingerprint database was created. Cascade ANN system was trained using this database. Then, while a mobile node is in any location, RSSIs measured by anchor nodes are given as an input to the cascade ANN system, and the location of the mobile node is determined. Fingerprint steps 1 and 0.5 m were taken, and two applications were carried out in the article. According to the RSSI values taken from 100 different coordinates for the test, the total error was 3216 and 2838 cm, respectively. The average error is 32.16 and 28.38 cm.
Kindergarten screening tools filled out by parents and teachers targeting dyslexia. Predictions and developmental trajectories from age 5 to age 15 years
Authors: Helland Turid , Morken Frøydis , Helland Wenche A.
Published: September 2021

The concept of early ‘efforts’ has led to discussions for and against introducing language assessment for all kindergarten children. Evidence‐based kindergarten screening tools completed by close caregivers could solve this controversy as the children themselves would only be indirectly involved. The aim of this study was to see whether the scores of such early screening tools aiming at developmental dyslexia could predict school marks of literacy competence 10 years later, and to see whether these screening tools would reveal different dyslexia trajectories. The study is part of the Bergen Longitudinal Dyslexia Study, and the results from individual testing are reported elsewhere. Here, the caregivers' views isolated from the rest of the study are focused. Three tools were used: the RI‐5, a questionnaire assessing the risk of dyslexia; the TRAS, a non‐standardized observation tool of children's communication skills; and the CCC‐2, a questionnaire assessing Developmental Language Disorders. Screening was performed at age 5 (TP1), age 11, (TP2) and age 15 (TP3). At TP2, when dyslexia was identified, 13 children formed the dyslexia group, and the rest formed the control group. At TP3, the RI‐5 and CCC‐2 turned out to be predictive of literacy competence as measured by school marks. Developmental trajectories were seen through the regroupings and scorings into a persistent group, a late onset group and a resolving group. Evidence‐based preschool screening tools filled out by close caregivers offer valid information on later literacy developmental trajectories.
Flyway‐scale analysis reveals that the timing of migration in wading birds is becoming later
Authors: Mondain‐Monval Thomas O. , Amos Matt , Chapman Jamie‐Leigh , MacColl Andrew , Sharp Stuart P.
Published: September 2021

Understanding the implications of climate change for migratory animals is paramount for establishing how best to conserve them. A large body of evidence suggests that birds are migrating earlier in response to rising temperatures, but many studies focus on single populations of model species.

Migratory patterns at large spatial scales may differ from those occurring in single populations, for example because of individuals dispersing outside of study areas. Furthermore, understanding phenological trends across species is vital because we need a holistic understanding of how climate change affects wildlife, especially as rates of temperature change vary globally.

The life cycles of migratory wading birds cover vast latitudinal gradients, making them particularly susceptible to climate change and, therefore, ideal model organisms for understanding its effects. Here, we implement a novel application of changepoint detection analysis to investigate changes in the timing of migration in waders at a flyway scale using a thirteen‐year citizen science dataset (eBird) and determine the influence of changes in weather conditions on large‐scale migratory patterns.

In contrast to most previous research, our results suggest that migration is getting later in both spring and autumn. We show that rates of change were faster in spring than autumn in both the Afro‐Palearctic and Nearctic flyways, but that weather conditions in autumn, not in spring, predicted temporal changes in the corresponding season. Birds migrated earlier in autumn when temperatures increased rapidly, and later with increasing headwinds.

One possible explanation for our results is that migration is becoming later due to northward range shifts, which means that a higher proportion of birds travel greater distances and therefore take longer to reach their destinations. Our findings underline the importance of considering spatial scale when investigating changes in the phenology of migratory bird species.
Electrocatalytic Hydrogen Evolution Reaction of Rhenium Metal and Rhenium‐Based Intermetallic in Acid and Alkaline Media
Authors: Dan Li , Suen Nian‐Tzu
Published: September 2021

Rhenium (Re) metal has been well known for the high corrosion resistance in strong acid and alkaline electrolyte, which makes it a potential electrocatalyst toward hydrogen evolution reaction (HER). However, the low HER activity (>100 mV @ 10 mA/cm2) is a fatal flaw and the reason Re metal does not receive much attention comparing to other noble metal such as Platinum (Pt), Iridium (Ir) and Ruthenium (Ru). To improve the HER activity of Re metal, in this work, we have incorporated a small amount of Zr atoms into Re lattice to form Re based intermetallic Zr5Re24. The large Zr atoms can expand the subunits of the structure and increase the Re−Re bond lengths while the low electronegativity of Zr atoms will donate electrons to Re atoms and fill more antibonding state of Re−Re bond. Both crystal‐structural and electronic‐structural factors will reduce the bond strength of Re−Re bond and thus weaken the corresponding hydrogen adsorption energy (ΔGHad). This can adjust the ΔGHad of Zr5Re24 to an optimal position and enhance the HER activity from Re metal (η10∼125 mV) to Zr5Re24 (η10∼90 mV). Moreover, it was realized that OH molecule on the surface of Zr5Re24 and Re metal will not occupy the most active site (i. e. poison effect) nor significantly influence the ΔGHad to the optimized position (i. e. 0 eV), which well elucidate the similar HER activity in acid or alkaline electrolyte.
Fluorosulfonylferrocene, (Trifluoromethylsulfonyl)ferrocene and New Ferrocenyl Sulfonates: Directed ortho Lithiation and New Anionic Thia‐Fries Rearrangements at Ferrocene
Authors: Boston Geanne M. R. , Philipp Hendrik M. , Butenschön Holger
Published: September 2021

Ferrocenyl triflates are known to undergo anionic thia‐Fries rearrangements at low temperature in high yields. In order to expand the scope of this reaction, ferrocenyl sulfonates and sulfonylferrocenes were prepared and their reactivity investigated. Treatment of ferrocenyl fluorosulfonate with lithium 2,2,6,6‐tetramethylpiperidide gave rise to a new anionic thia‐Fries rearrangement at ferrocene. The formation of a rare oxathiine was observed with ferrocenyl (pentafluorophenyl)sulfonate as a result of an ortho lithiation and a subsequent intramolecular nucleophilic aromatic substitution. In contrast to fluorinated ferrocenyl sulfonates, fluorosulfonylferrocene as well as (trifluoromethylsulfonyl)ferrocene underwent ortho lithiation under comparable reaction conditions.
Central sensitization of dorsal root potentials and dorsal root reflexes: An in vitro study in the mouse spinal cord.
Authors: Vicente‐Baz Jorge , Lopez‐Garcia Jose Antonio , Rivera‐Arconada Ivan
Published: September 2021

Background

Axo‐axonic contacts onto central terminals of primary afferents modulate sensory inputs to the spinal cord. These contacts produce primary afferent depolarization (PAD), which serves as a mechanism for presynaptic inhibition, and also produce dorsal root reflexes (DRRs), which may regulate the excitability of peripheral terminals and second order neurons. We aimed to identify changes in these responses as a consequence of peripheral inflammation.

Methods

In vitro spinal cord recordings of spontaneous activities in dorsal and ventral roots were performed in control mice and following paw inflammation. We also used pharmacological assays to define the neurotransmitter systems implicated in such responses.

Results

Paw inflammation increased the frequency and amplitude of spontaneous dorsal root depolarizations, the occurrence of DRRs and the amplitude of ventral roots depolarizations. PAD was classified in two different patterns based on their relation to ventral activity: time‐locked and independent events. Both patterns increased in amplitude after paw inflammation, and independent events also increased in frequency. The circuits that were responsible for this activity implicated both glutamatergic and GABAergic transmission. Adrenergic modulation differentially affected both types of PAD, and this modulation changed after paw inflammation.

Conclusions

Our findings suggest the existence of independent spinal circuits at the origin of PAD and DRRs. Inflammation modulates these circuits differentially, unveiling varied mechanisms of spinal sensitization. This in vitro approach provides an isolated model for the study of the mechanisms of central sensitization and for the performance of pharmacological assays with the purpose of identifying and testing novel antinociceptive targets.

Significance

Spinal circuits modulate activity of primary afferents acting on central terminals. Under in vitro conditions, dorsal roots show spontaneous activity in the form of depolarizations and action potentials. Our findings are consistent with the existence of several independent generator circuits. Experimental paw inflammation reduced mechanical withdrawal threshold and significantly increased the spontaneous activity of dorsal roots, which may be secondary to an enhanced output of spinal generators. This can be considered as a novel sign of central sensitization.
Nanocrystals as Model Systems for Studying the Interplay Between Crystallization and Chirality
Authors: Hananel Uri , Moshe Assaf Ben , Markovich Gil , Alivisatos A. Paul
Published: September 2021

The interplay between crystallization and chirality has fascinated chemists for over 170 years now. Many questions deal with the transfer of chirality from molecular level building blocks and crystal capping ligands to the macroscopic morphologies of crystals. Also the interest in nanoscale chiral crystallization and the relationship between chiral ligands and inorganic nanocrystals has recently arose. In this review we highlight several different topics related to studies of the interplay between chirality and crystallization that involve inorganic nanocrystals. Specifically, we differentiate between the effects of chiral molecules on inorganic nanocrystals with chiral or achiral crystal structures. In the first case, chirality may appear both at the atomic‐scale and the particle shape, and in the second case chirality may be induced only at the particle shape level. We also discuss recent progress on the relationship between the atomic scale chirality and crystal morphology.
Coinciding significance of the crystallographic orientation and nanostructuring on the biocompatibility of TZNT‐Ag1.5 alloy deformed by the cold rolling process
Authors: Zareidoost Amir , Yousefpour Mardali
Published: September 2021

In this study, the simultaneous significance of the crystallographic texture and nanostructuring on the cytocompatibility of as‐cast (Ti55Zr25Nb10Ta10)98.5‐Ag1.5 alloy (at. %, TZNT‐Ag1.5), subjected to cold rolling up to 90% reduction, along with the changes of Young's modulus and hardness under cold rolling were investigated. For this purpose, the as‐cast and cold‐rolled TZNT‐Ag1.5 alloy test specimens were analyzed by XRD, TEM, HRTEM, SEM, contact angle, nanoindentation, and OM techniques. Moreover, to evaluate the effect of severe cold deformation on the biocompatibility, MG‐63 osteoblastic cell was cultured on the surface of 90% cold‐rolled and as‐cast test specimens of TZNT‐Ag1.5 alloy. The results showed that severe cold deformation was led to fast grain refinement of grains of the as‐cast TZNT‐Ag1.5 alloy in the range of 50–100 nm. In addition to the nanostructuring, upon severe cold deformation, the ‐fiber (<111>// normal direction) texture was formed and after 90% reduction, the (111)<1 > γ‐fiber component was strengthened. The micro‐hardness and reduced Young's modulus are 235 ± 5.29, 246 ± 1.73, 271 ± 4.0, and 283 ± 6.25 (HV); and 73.725 ± 1.70, 83.98 ± 5.10, 81.26 ± 6.55, and 88.66 ± 7.16 (GPa) for TZNT‐Ag1.5 (as‐cast), TZNT‐Ag1.5 (20%CR), TZNT‐Ag1.5 (50%CR), and TZNT‐Ag1.5 (90%CR) test specimens, respectively. Further, with increasing the cold deformation degree, the dislocation density of TZNT‐Ag1.5 alloy increased as this parameter is 2.79 × 1015 (m−2) for the 90%CR test specimen. On the other hand, the values of the contact angle for the 90%CR test specimen (46.2 ± 3.5°) exhibit a higher hydrophilic and wettable surface as compared to the other studied test specimens. After 5 days of incubation, osteoblastic cells on the surface of the 90% cold‐rolled TZNT‐Ag1.5 test specimens revealed significant differences in cell proliferation and differentiation as compared to the as‐cast alloy test specimens and/or CP‐Ti. Finally, because the maximum orientation intensities were generally <3, it was deduced that grain refinement rather than the crystallographic texture plays a significant role in improving the surface biocompatibility of the new TZNT‐Ag1.5 alloy.
Best Performance Parameters of HR-pQCT to Predict Fragility Fracture: Systematic Review and Meta-Analysis
Authors: Cheung Wing-Hoi , Hung Vivian Wing-Yin , Cheuk Ka-Yee , Chau Wai-Wang , Tsoi Kelvin Kam-Fai , Wong Ronald Man-Yeung , Chow Simon Kwoon-Ho , Lam Tsz-Ping , Yung Patrick Shu-Hang , Law Sheung-Wai , Qin Ling
Published: September 2021

Osteoporosis is a systemic skeletal disease characterized by low bone mass and bone structural deterioration that may result in fragility fractures. Use of bone imaging modalities to accurately predict fragility fractures is always an important issue, yet the current gold standard of dual-energy X-ray absorptiometry (DXA) for diagnosis of osteoporosis cannot fully satisfy this purpose. The latest high-resolution peripheral quantitative computed tomography (HR-pQCT) is a three-dimensional (3D) imaging device to measure not only volumetric bone density, but also the bone microarchitecture in a noninvasive manner that may provide a better fracture prediction power. This systematic review and meta-analysis was designed to investigate which HR-pQCT parameters at the distal radius and/or distal tibia could best predict fragility fractures. A systematic literature search was conducted in Embase, PubMed, and Web of Science with relevant keywords by two independent reviewers. Original clinical studies using HR-pQCT to predict fragility fractures with available full text in English were included. Information was extracted from the included studies for further review. In total, 25 articles were included for the systematic review, and 16 articles for meta-analysis. HR-pQCT was shown to significantly predict incident fractures and/or major osteoporotic fractures (MOFs). Of all the HR-pQCT parameters, our meta-analysis revealed that cortical volumetric bone mineral density (Ct.vBMD), trabecular thickness (Tb.Th), and stiffness were better predictors. Meanwhile, HR-pQCT parameters indicated better performance in predicting MOFs than incident fractures. Between the two standard measurement sites of HR-pQCT, the non-weight-bearing distal radius was a more preferable site than distal tibia for fracture prediction. Furthermore, most of the included studies were white-based, whereas very few studies were from Asia or South America. These regions should build up their densitometric databases and conduct related prediction studies. It is expected that HR-pQCT can be used widely for the diagnosis of osteoporosis and prediction of future fragility fractures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Serum 25-Hydroxy-Vitamin D Status and Incident Hip Fractures in Elderly Adults: Looking Beyond Bone Mineral Density
Authors: Skuladottir Sigrun S. , Ramel Alfons , Eymundsdottir Hrafnhildur , Hjaltadottir Ingibjorg , Launer Lenore J. , Cotch Mary-Frances , Siggeirsdottir Kristin , Gudnason Vilmundur , Sigurdsson Gunnar , Steingrimsdottir Laufey , Halldorsson Thorhallur I.
Published: September 2021

Observational studies have consistently reported a higher risk of fractures among those with low levels of serum 25-hydroxyvitamin D (25(OH)D). Emerging evidence suggests that low serum 25(OH)D levels may increase the rate of falls through impaired physical function. Examine to what extent baseline measures of volumetric bone mineral density (vBMD), absolute bone mineral content (BMC), and markers of physical function may explain incident hip fractures in older adults with different serum levels of 25(OH)D. A prospective study of 4309 subjects (≥66 years) recruited between 2002 and 2006 into the Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) study. Hip fractures occurring until the end of 2012 were extracted from hospital records. Prevalence of serum 25(OH)D deficiency (<30 nmol/L), inadequacy (30–<50 nmol/L), and sufficiency (≥50 nmol/L) was 6%, 23%, and 71% for males; and 11%, 28%, and 53% for females, respectively. Female participants had ~30% lower absolute BMC compared to males. Serum 25(OH)D concentrations were positively associated with vBMD and BMC of the femoral neck and markers of physical function, including leg strength and balance. Those who had deficient compared to sufficient status at baseline had a higher age-adjusted risk of incidence hipfractures with hazard ratios (HRs) of 3.1 (95% confidence interval [CI], 1.9–5.2) and 1.8 (95% CI, 1.3–2.5) among males and females, respectively. When adjusting for vBMD and measures of physical function, the association was attenuated and became nonsignificant for males (1.3; 95% CI, 0.6–2.5) but remained significant for females (1.7; 95% CI, 1.1–2.4). Deficient compared to sufficient serum 25(OH)D status was associated with a higher risk of incident hip fractures. This association was explained by poorer vBMD and physical function for males but to a lesser extent for females. Lower absolute BMC among females due to smaller bone volume may account for these sex-specific differences. © 2021 American Society for Bone and Mineral Research (ASBMR).
Bone Mineral Density and Bone Turnover 10 Years After a Single 5 mg Dose or Two 5-Yearly Lower Doses of Zoledronate in Osteopenic Older Women: An Open-Label Extension of a Randomized Controlled Trial
Authors: Grey Andrew , Bolland Mark J , Horne Anne , Mihov Borislav , Gamble Greg , Reid Ian R
Published: September 2021

Intravenous zoledronate reduces fracture risk (5 mg at 18-month intervals) and prevents bone loss (doses of 1 to 5 mg for 3 to >5 years), but the duration of action of a single 5 mg dose and the effects of lower doses beyond 5 years are unknown. We report the second open-label extension (years 5 to 10) of a 2-year randomized, multidose, placebo-controlled, double-blinded trial. A total of 116 older women who completed 5 years of participation either continued observation without further treatment (zoledronate 5 mg and placebo at baseline) or received repeat doses of 1 or 2.5 mg zoledronate (zoledronate 1 mg and zoledronate 2.5 mg at baseline, respectively). Outcomes were spine, hip, and total body bone mineral density (BMD) and serum markers of bone turnover. After a single 5 mg dose of zoledronate, mean BMD at the lumbar spine and total hip was maintained at or above baseline levels for 9 and 10 years, respectively. The mean level of the bone resorption marker β-C-terminal telopeptide of type I collagen (β-CTX) was at least 25% lower than that in the placebo group for 9 years. In women administered 5-yearly doses of 2.5 mg zoledronate, mean BMD at the total hip and lumbar spine was maintained at or above baseline levels for 9 and 10 years, respectively. Redosing with 1 or 2.5 mg zoledronate at 5 years reduced bone turnover markers for 3 to 4 years. BMD increased for 3 to 4 years after redosing with 1 mg zoledronate. In the group given 5-yearly 2.5 mg zoledronate, β-CTX was at least 20% lower than that in the placebo group for 10 years. Both a single baseline 5 mg dose of zoledronate and 5-yearly doses of 1 and 2.5 mg zoledronate prevented bone loss at hip and spine for 8 to 10 years in older postmenopausal women. Clinical trials to evaluate the effects on fracture risk of these very infrequent and lower doses of zoledronate are justified. © 2021 American Society for Bone and Mineral Research (ASBMR).
miR‐138‐5p inhibits proliferation and invasion in kidney renal clear cell carcinoma by targeting SINA3 and regulation of the Notch signaling pathway
Authors: Liu Yang , Qu Hong‐chen
Published: September 2021

Background

The function of miR‐138‐5p as an oncogenic factor has been reported in certain cancers. This study was performed to analyze the potential involvement of miR‐138‐5p in kidney renal clear cell carcinoma (KIRC).

Methods

The Cancer Genome Atlas (TCGA) database was used to explain the expression of miR‐138‐5p in cancer and paired non‐cancer tissues of KIRC patients. Subsequently, miR‐138‐5p expression in KIRC tissues and cell lines, as well as that in normal tissues and normal renal tubular epithelial cell line, was detected. Artificial overexpressing of miR‐138‐5p was applied to observe its effect on the biological behaviors of KIRC cells. The target mRNA of miR‐138‐5p, SIN3A, was predicted and validated. Altered expression of miR‐138‐5p and SIN3A was introduced to confirm their functions in KIRC proliferation and invasion.

Results

We showed that miR‐138‐5p was down‐regulated in tumor tissues of KIRC patients comparing to adjacent healthy tissues and linked to dismal prognosis in patients. miR‐138‐5p could hinder KIRC proliferation and invasion, while artificial overexpression of SIN3A led to reversed trends. SIN3A was a target mRNA of miR‐138‐5p. miR‐138‐5p and SIN3A together affect the activation of the Notch signaling pathway.

Conclusion

This study evidenced that up‐regulated miR‐138‐5p inhibits proliferation and invasion of KIRC cells involving the transcription of SIN3A and the following regulation of the Notch signaling pathway.
Bile acid metabolism dysregulation associates with cancer cachexia: roles of liver and gut microbiome
Authors: Feng Lixing , Zhang Wanli , Shen Qiang , Miao Chunxiao , Chen Lijuan , Li Yiwei , Gu Xiaofan , Fan Meng , Ma Yushui , Wang Hui , Liu Xuan , Zhang Xiongwen
Published: September 2021

Background

Cancer cachexia is a multifactorial metabolic syndrome in which bile acid (BA) metabolism might be involved. The aim of the present study was to clarify the contribution of liver and gut microbiota to BA metabolism disturbance in cancer cachexia and to check the possibility of targeting BA metabolism using agents such as tauroursodeoxycholic acid (TUDCA) for cancer cachexia therapy.

Methods

The BA profiles in liver, intestine, and serum of mice with cancer cachexia induced by inoculation of colon C26 tumour cells were analysed using metabolomics methods and compared with that of control mice. Proteomic analysis of liver protein expression profile and 16S rRNA gene sequencing analysis of gut microbiota composition in cancer cachexia mice were conducted. Expression levels of genes related to farnesoid X receptor (FXR) signalling pathway in the intestine and liver tissues were analysed using RT–PCR analysis. The BA profiles in serum of clinical colon cancer patients with or without cachexia were also analysed and compared with that of healthy volunteers. The effects of TUDCA in treating cancer cachexia mice were observed.

Results

In the liver of cancer cachexia mice, expression of BA synthesis enzymes was inhibited while the amount of total BAs increased (P < 0.05). The ratios of conjugated BAs/un‐conjugated BAs significantly increased in cancer cachexia mice liver (P < 0.01). Gut microbiota dysbiosis such as decrease in Lachnospiraceae and increase in Enterobacteriaceae was observed in the intestine of cancer cachexia mice, and microbial metabolism of BAs was reduced. Increase in expression of FGF15 in intestine (P < 0.01) suggested the activation of FXR signalling pathway which might contribute to the regulation of BA synthesis enzymes, transporters, and metabolic enzymes. Increase in the BA conjugation was observed in the serum of cancer cachexia mice. Results of clinical patients showed changes in BA metabolism, especially the increase in BA conjugation, and also suggested compensatory mechanism in BA metabolism regulation. Oral administration of 50 mg/kg TUDCA could significantly ameliorate the decrease in body weight (P < 0.001), muscle loss (P < 0.001), and atrophy of heart and liver (P < 0.05) in cancer cachexia mice without influence on tumour growth.

Conclusions

Bile acid metabolism dysregulation such as decrease in BA synthesis, increase in BA conjugation, and decrease in BA microbial metabolism was involved in development of cancer cachexia in mice. Targeting BA metabolism using agents such as TUDCA might be helpful for cancer cachexia therapy.
Myasthenia gravis and paroxysmal nocturnal hemoglobinuria after thymectomy: A rare association
Authors: Galtier Jean , Duval Fanny , Machelart Irène , Greib Carine , Lazaro Estibaliz , Pellegrin Jean‐Luc , Viallard Jean‐François , de la Tour Regis Peffault , Rivière Etienne
Published: September 2021

Paroxysmal nocturnal hemoglobinuria (PNH) is a very rare clonal autoimmune disease manifesting with hemolysis, thrombosis, or bone marrow failure. We present an atypical association of myasthenia gravis, aplastic anemia, and PNH occurring years after thymectomy. While this association might be extremely rare, it may not be coincidental as there is a common pathophysiology between PNH and aplastic anemia, with the latter reported in several thymoma/thymectomy cases. Eculizumab was introduced with good efficacy and without safety concern in our patient, leading to long‐term control of PNH without worsening of myasthenia gravis.
Mechanism of chlorogenic acid in alveolar macrophage polarization in Klebsiella pneumoniae-induced pneumonia
Authors: Li Qing Rong , Tan Shi Rui , Yang Lu , He Wei , Chen Li , Shen Fen Xiu , Wang Zhuo , Wang Hai Feng
Published: September 2021

Chlorogenic acid (CA) has been discovered to regulate macrophage polarization in pneumonia. This study aims to analyze the functional mechanism of CA in alveolar macrophage (AM) polarization and provide a theoretical basis for treatment of Klebsiella pneumoniae (Kp)-induced pneumonia. Mice were infected with Kp, and treated with CA and silent information regulator 1 (SIRT1) inhibitor (Selisistat). Mouse survival rate was recorded and bacterial burden was detected. AM polarization and pathologic change of lung tissues were evaluated. Expressions of SIRT1 and HMGB1 and cytokine levels were detected. MH-S cells were infected with Kp to establish the pneumonia cell model, followed by transfection of si-SIRT1 and HMGB1 overexpression vector. The HMGB1 expression in the nucleus and cytoplasm was detected. HMGB1 subcellular localization and HMGB1 acetylation level were detected. Kp led to high death rates, SIRT down-regulation and increases in inflammatory factor level and bacterial burden, and promoted M1 polarization. CA treatment improved mouse survival rate and promoted M2 polarization and SIRT1 expression. SIRT1 decreased HMGB1 acetylation level to inhibit nuclear to the cytoplasm translocation. Silencing SIRT1 or HMGB1 overexpression reversed the effect of CA on Kp-induced pneumonia. Overall, CA activated SIRT1 to inhibit HMGB1 acetylation level and nuclear translocation, thereby promoting M2 polarization in AMs and alleviating Kp-induced pneumonia.
Infantile onset carnitine palmitoyltransferase 2 deficiency: Cortical polymicrogyria, schizencephaly, and gray matter heterotopias in an adolescent with normal development
Authors: Shelihan Ivan , Rossignol Elsa , Décarie Jean‐Claude , Bonnefont Jean‐Paul , Brivet Michèle , Brunel‐Guitton Catherine , Mitchell Grant A.
Published: September 2021

Objective

To report an adolescent with infantile‐onset carnitine palmitoyltransferase 2 (CPT2) deficiency and cerebral malformations and to review the occurrence of brain malformations in CPT2 deficiency. The patient presented clinically at age 5 months with dehydration and hepatomegaly. He also has an unrelated condition, X‐linked nephrogenic diabetes insipidus. He had recurrent rhabdomyolysis but normal psychomotor development. At age 17 years, he developed spontaneous focal seizures. Cerebral magnetic resonance imaging revealed extensive left temporo‐parieto‐occipital polymicrogyria, white matter heterotopias, and schizencephaly. Neuronal migration defects were previously reported in lethal neonatal CPT2 deficiency but not in later‐onset forms.

Design and Methods

We searched PubMed, Google Scholar, and the bibliographies of the articles found by these searches, for cerebral malformations in CPT2 deficiency. All antenatal, neonatal, infantile, and adult‐onset cases were included. Exclusion criteria included insufficient information about age of clinical onset and lack of confirmation of CPT2 deficiency by enzymatic assay or genetic testing. For each report, we noted the presence of cerebral malformations on brain imaging or pathological examination.

Results

Of 26 neonatal‐onset CPT2‐deficient patients who met the inclusion criteria, brain malformations were reported in 16 (61.5%). In 19 infantile‐onset cases, brain malformations were not reported, but only 3 of the 19 reports (15.8%) include brain imaging or neuropathology data. In 276 adult‐onset cases, no brain malformations were reported.

Conclusion

To the best of our knowledge, this is the first report of cerebral malformations in an infantile onset CPT2‐deficient patient. Brain imaging should be considered in patients with CPTII deficiency and neurological manifestations, even in those with later clinical onset.
The evaluation of both the expression and serum protein levels of Caspase‐3 gene in patients with different degrees of SARS‐CoV2 infection
Authors: Yildiz Gulhan Pinar , Eroz Recep , Ataoglu Ozlem , İnce Nevin , Davran Fatih , Öztürk Cihadiye Elif , Gamsızkan Zerrin , Balbay Oner Abidin
Published: September 2021

To evaluate the effects of Caspase‐3 (CASP3) gene expression and serum levels on preventing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. A total of 41 individuals (male: 21; female: 20) with SARS‐CoV‐2 infection were included in the current study. Hemograms were examined from patient blood samples, and CASP3 gene expression levels were detected. Also, human CASP3 levels were determined from the serum samples of patients. The mean age of patients was 56.220 ± 18.937 years. Significant differences were detected among all groups for CASP3  (p = 0.014) and CASP3 concentration (p = 0.024). The relationship between CASP3 levels and hemoglobin (p = 0.023), between CASP3 levels and C‐reactive protein (CRP) (p = 0.001), between CASP3 levels and ferritin (p = 0.003), between CASP3 levels and lactate dehydrogenase (p =  0.001), and between CASP3 levels and SpO2 (p = 0.006) were statistically significant. Also, the relationship between CASP3 concentration levels and SpO2 was statistically significant (p < 0.046). The CASP3 gene and/or its products have an important function to prevent injury caused by SARS‐CoV‐2 infection. They play crucial roles in maintaining cellular homeostasis and viability. Perhaps CASP3 levels may provide information about the severity of the disease.
Therapeutic strategies for systemic therapies of human papillomavirus‐related oropharyngeal cancer
Authors: Hung Tony K. W. , Ho Alan L. , Pfister David G.
Published: September 2021

Our understanding of human papillomavirus (HPV)‐related oropharyngeal cancer (OPC) and its molecular basis continues to evolve and produce important insights into customized therapeutic strategies. Novel therapeutics exploiting HPV‐related targets are being evaluated in the incurable setting, while the favorable prognosis of locoregionally advanced disease has stimulated investigation into de‐escalation strategies. There is much opportunity for better personalization of standard therapy according to HPV status. This review discusses both current and investigational therapeutic strategies for HPV‐related OPC.
Evaluation of triage tool for low‐grade cartilage tumors: Four‐quadrant approach
Authors: Schumacher Katherine M. , Damron Timothy A.
Published: September 2021

Background and Objectives

The “four‐quadrant approach” (FQA) for triage of benign enchondromas (E) and low‐grade malignant chondrosarcomas (LGC) divides patients into treatment categories based on the presence or absence of pain and observation of aggressive or benign radiographic features. This article evaluates the usefulness of the FQA in predicting E versus LGC and operative versus nonoperative outcome.

Methods

Patients had working diagnosis of E or LGC, 1‐year minimum follow‐up, imaging, clinical data, outcomes, and no radiographic evidence of high‐grade chondrosarcoma. Statistical analysis determined whether quadrant distribution correlated to E versus LGC and operative versus nonoperative intervention.

Results

Of 56 lesions (49 patients), 9 were LGC and 47 E. Twenty‐five lesions (all 9 LGC, 16 E) were treated operatively and 31 (all E) nonoperatively. There were statistically significant correlations between quadrant distribution and both tumor type (p = 1.9 × 10−6) and operative intervention (p = 6.28 × 10−6).

Conclusions

The FQA is a promising diagnostic tool to distinguish between E and LGC hyaline cartilage tumors, along with determining operative versus nonoperative intervention. Prospective evaluation is warranted.
Pancreas cancer trials for early stage disease: Surgeons leading therapeutic cooperative group trials
Authors: Snyder Rebecca A. , Ahmad Syed , Katz Matthew H. G.
Published: September 2021

Surgeon‐led clinical trials have defined the standard of care for locoregional pancreatic cancer to date. The infrastructure and collaborative nature of cooperative oncology groups offer many advantages, such as providing an ideal mechanism through which multidisciplinary pancreatic cancer trials are performed. As key members of the treatment team, surgeons bring experience and expertise to the design of surgical and multidisciplinary trials and are uniquely poised to be leaders of future pancreatic cancer trials.
Substrate integrated waveguide leaky wave antenna with circular polarization and improvement of the scan angle
Authors: Masoumi Mohsen , Dalili Oskouei Hamid Reza , Mohammadi Shirkolaei Mortez , Mirtaheri Ali Reza
Published: September 2021

In this paper, a leaky wave antenna is presented based on the substrate integrated waveguide structure. The proposed antenna has a periodic structure with a combination of rectangular and H‐shaped slots on the top of the antenna. By providing this new design for slots, a better angular scanning achieved rather than the previous designs from broadside to end‐fire, so that with this design, the leaky wave antenna can scan from 2.5 to 87° by changing the feeding frequency, which is the highest scanning angle relative to the design of uniform rectangular slots, the butterfly shaped slots and the H‐shaped slots. The proposed antenna was designed to have circular polarization in the entire operating frequency range.
Implementation and experimental validation of a robust hybrid direct aperture optimization approach for mixed‐beam radiotherapy
Authors: Heath Emily , Mueller Silvan , Guyer Gian , Duetschler Alisha , Elicin Olgun , Aebersold Daniel , Fix Michael K. , Manser Peter
Published: September 2021

Purpose

The objectives of the work presented in this paper were to (1) implement a robust‐optimization method for deliverable mixed‐beam radiotherapy (MBRT) plans within a previously developed MBRT planning framework; (2) perform an experimental validation of the delivery of robust‐optimized MBRT plans; and (3) compare PTV‐based and robust‐optimized MBRT plans in terms of target dose robustness and organs at risk (OAR) sparing for clinical head and neck and brain patient cases.

Methods

A robust‐optimization method, which accounts for translational setup errors, was implemented within a previously developed treatment planning framework for MBRT. The framework uses a hybrid direct aperture optimization method combining column generation and simulated annealing. A robust plan was developed and then delivered to an anthropomorphic head phantom using the Developer Mode of a TrueBeam linac. Planar dose distributions were measured and compared to the planned dose. Robust‐optimized and PTV‐based plans were developed for three clinical patient cases consisting of two head and neck cases and one brain case. The plans were compared in terms of the robustness to 5 mm shifts of the target volume dose as well as in terms of OAR sparing.

Results

Using a gamma criterion of 3%/2 mm and a dose threshold of 10%, the agreement between film measurements and dose calculations was better than 97.7% for the total plan and better than 95.5% for the electron component of the plan. For the two head and neck patient cases, the average clinical target volume (CTV) dose homogeneity index (V95%–V107%) over all the considered setup error scenarios was on average 19% lower for the PTV‐based plans and it had a larger standard deviation. The robust‐optimized plans achieved, on average, a 20% reduction in the OAR doses compared to the PTV‐based plans. For the brain patient case, the CTV dose homogeneity index was similar for the two plans, while the OAR doses were 22% lower, on average, for the robust‐optimized plan. No clear trend in terms of electron contributions was found across the three patient cases, although robust‐optimized plans tended toward higher electron beam energies.

Conclusions

A framework for robust optimization of deliverable MBRT plans has been developed and validated. PTV‐based MBRT were found to not be robust to setup errors, while the dose delivered by the robust‐optimized plans were clinically acceptable for all considered error scenarios and had better OAR sparing. This study shows that the robust optimization is a promising alternative to conventional PTV margins for MBRT.
New setup for multi‐parametric MRI in young and old rat gastrocnemius at 4.7 and 7 T during muscle stimulation
Authors: Loubrie Stéphane , Trotier Aurelien , Ribot Emeline , Massot Philippe , Lefrançois William , Thiaudière Eric , Dallaudière Benjamin , Miraux Sylvain , Bourdel‐Marchasson Isabelle
Published: September 2021

T1 and T2 relaxation times combined with 31P spectroscopy have been proven efficient for muscular disease characterization as well as for pre‐ and post‐muscle stimulation measurements. Even though 31P spectroscopy can already be performed during muscle exercise, no method for T1 and T2 measurement enables this possibility. In this project, a complete setup and protocol for multi‐parametrical MRI of the rat gastrocnemius before, during and after muscle stimulation at 4.7 and 7 T is presented. The setup is fully MRI compatible and is composed of a cradle, an electro‐stimulator and an electronic card in order to synchronize MRI sequences with muscle stimulation. A 2D triggered radial‐encoded Look‐Locker sequence was developed, and enabled T1 measurements in less than 2 min on stimulated muscle. Also, a multi‐slice multi‐echo sequence was adapted and synchronized for T2 measurements as well as 31P spectroscopy acquisitions in less than 4 min in both cases on stimulated muscle. Methods were validated on young rats using different stimulation paradigms. Then they were applied on older rats to compare quantification results, using the different stimulation paradigms, and allowed observation of metabolic changes related to aging with good reproducibility. The robustness of the whole setup shows wide application opportunities.
Instant determination of the artemisinin from various Artemisia annua L. extracts by LC‐ESI‐MS/MS and their in‐silico modelling and in vitro antiviral activity studies against SARS‐CoV‐2
Authors: Dogan Kubra , Erol Ebru , Didem Orhan Muge , Degirmenci Zehra , Kan Tugce , Gungor Aysen , Yasa Belkis , Avsar Timucin , Cetin Yuksel , Durdagi Serdar , Guzel Mustafa
Published: September 2021

Introduction

Numerous efforts in natural product drug development are reported for the treatment of Coronavirus. Based on the literature, among these natural plants Artemisia annua L. shows some promise for the treatment of SARS‐CoV‐2.

Objective

The main objective of our study was to determine artemisinin content by liquid chromatography electrospray ionisation tandem mass spectrometry (LC‐ESI‐MS/MS), to investigate the in vitro biological activity of artemisinin from the A. annua plants grown in Turkey with various extracted methods, to elaborate in silico activity against SARS‐CoV‐2 using molecular modelling.

Methodology

Twenty‐one different extractions were applied. Direct and sequential extractions studies were compared with ultrasonic assisted maceration, Soxhlet, and ultra‐rapid determined artemisinin active molecules by LC‐ESI‐MS/MS methods. The inhibition of spike protein and main protease (3CL) enzyme activity of SARS‐CoV‐2 virus was assessed by time resolved fluorescence energy transfer (TR‐FRET) assay.

Results

Artemisinin content in the range 0.062–0.066%. Artemisinin showed significant inhibition of 3CL protease activity but not Spike/ACE‐2 binding. The 50% effective concentration (EC50) of artemisinin against SARS‐CoV‐2 Spike pseudovirus was found greater than 50 μM (EC45) in HEK293T cell line whereas the cell viability was 94% of the control (P < 0.01). The immunosuppressive effects of artemisinin on TNF‐α production on both pseudovirus and lipopolysaccharide (LPS)‐induced THP‐1 cells were found significant in a dose dependent manner.

Conclusion

Further studies of these extracts for COVID‐19 treatment will shed light to seek alternative treatment options. Moreover, these natural extracts can be used as an additional treatment option with medicines, as well as prophylactic use can be very beneficial for patients.
Comparing newborn outcomes after prenatal exposure to individual antidepressants: A retrospective cohort study
Authors: Marks Claire , Silvola Rebecca , Teal Evgennia , Quinney Sara K. , Haas David M.
Published: September 2021

Objective

To compare associations between individual antidepressants and newborn outcomes.

Design

Retrospective cohort study.

Setting

Deliveries in a large, US medical system.

Population

Women who received at least one antidepressant prescription 3 months prior to conception through delivery.

Methods

Eligible women had maternal characteristics and newborn outcomes extracted from medical record data. Exposure was defined by the timing of the prescription during pregnancy.

Main outcome measures

Newborn outcomes (any adaptation syndrome, neonatal intensive care unit (NICU) admission) were analyzed for each antidepressant and compared using standard statistics and multivariable regression compared to exposure to bupropion. Odds of outcomes based on timing of exposure were also explored.

Results

A total of 3,694 women were analyzed. Rates of any adaptation syndrome (p < 0.001), NICU admission (p < 0.001), and transient tachypnea of newborn (TTN) (p = 0.006) were significantly different between drugs. Infants exposed to duloxetine had the highest rates of NICU admissions (39.6%) and adaptation syndromes (15.1%). Venlafaxine‐exposed infants had the highest rates of TTN (18.2%). Controlling for maternal age, race, insurance, and gestational age at delivery, early pregnancy antidepressant exposure was associated with adaptation syndrome and NICU admission for both duloxetine (adjusted odds ratio (aOR) 2.31 [95% Confidence Interval (CI) 1.11–4.80] and aOR 2.47 [95% CI 1.40–4.34], respectively) and escitalopram (aOR 1.72 [95% CI 1.09–2.70] and aOR 1.64 [95% CI 1.21–2.22], respectively). Exposure in the third trimester was associated with any adaptation syndrome for citalopram, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine and NICU admission for bupropion, citalopram, duloxetine, escitalopram, and fluoxetine.

Conclusion

Duloxetine and escitalopram appear to have the strongest associations with any adaptation syndrome and NICU admission whereas bupropion and sertraline tended to have among the lowest risks of these outcomes. These results can help providers and patients discuss choice of individual antidepressant drugs during pregnancy.