bluuebunny/crossref_metadata_2025 huggingface dataset:
SIRT1 Gene SNP rs932658 Is Associated With Medication-Related Osteonecrosis of the Jaw
Authors: Yang Guang , Collins Joseph M , Rafiee Roya , Singh Sonal , Langaee Taimour , McDonough Caitrin W , Holliday L Shannon , Wang Danxin , Lamba Jatinder K , Kim Young Sick , Pelliccioni Gian Andrea , Vaszilko Mihaly , Kosa Janos P , Balla Bernadett , Lakatos Peter A , Katz Joseph , Moreb Jan , Gong Yan
Published: September 2020

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug reaction. Our previous whole-exome sequencing study found SIRT1 intronic region single-nucleotide polymorphism (SNP) rs7896005 to be associated with MRONJ in cancer patients treated with intravenous (iv) bisphosphonates (BPs). This study aimed to identify causal variants for this association. In silico analyses identified three SNPs (rs3758391, rs932658, and rs2394443) in the SIRT1 promoter region that are in high linkage disequilibrium (r2 > 0.8) with rs7896005. To validate the association between these SNPs and MRONJ, we genotyped these three SNPs on the germline DNA from 104 cancer patients of European ancestry treated with iv BPs (46 cases and 58 controls). Multivariable logistic regression analysis showed the minor alleles of these three SNPs were associated with lower odds for MRONJ. The odds ratios (95% confidence interval) and p values were 0.351 (0.164–0.751; p = 0.007) for rs3758391, 0.351 (0.164–0.751; p = 0.007) for rs932658, and 0.331 (0.157–0.697; p = 0.0036) for rs2394443, respectively. In the reporter gene assays, constructs containing rs932658 with variant allele A had higher luciferase activity than the reference allele, whereas constructs containing SNP rs3758391 and/or rs2394443 did not significantly affect activity. These results indicate that the promoter SNP rs932658 regulates the expression of SIRT1 and presumably lowers the risk of MRONJ by increasing SIRT1 expression. © 2020 American Society for Bone and Mineral Research (ASBMR).
Bioinformatics analysis of differentially expressed miRNAs in non‐small cell lung cancer
Authors: Yu Hui , Pang Zhonghao , Li Gang , Gu Tianyi
Published: September 2020

Objective

Non‐small cell lung cancer (NSCLC) contains 85% of lung cancer. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the largest NSCLC subgroups. The aim of the study was to investigate the underlying mechanism in developing more effective subtype‐specific molecular therapeutic procedures.

Methods

A total of 876 specimens were used in this study: 494 LUAD tissues (ie, 449 LUAD tissues and 45 matched normal tissues) and 382 LUSC tissues (ie, 337 LUSC tissues and 45 matched normal tissues). The miRNA sequencing data were processed using R. The differential expressed miRNAs between lung cancer and normal tissues were analyzed using the limma package in R. Gene expression, Western blotting, hematoxylin and eosin staining, and luciferase assay were used to test LUAD and LUSC.

Results

LUAD and LUSC appear sharply distinct at molecular and pathological level. Let‐7a‐5p, miR‐338, miR‐375, miR‐217, miR‐627, miR‐140, miR‐147b, miR‐138‐2, miR‐584, and miR‐197 are top 10 relevant miRNAs and CLDN3, DSG3, KRT17, TMEM125, KRT5, NKX2‐1, KRT7, ABCC5, KRAS, and PLCG2 are top 10 relevant genes in NSCLC. At the same time, the miRNAs expression levels were also quite different between the two groups. Among the differential expressed miRNAs, let‐7a‐5p was significantly down‐regulated in LUAD while miR‐338 was markedly down‐regulated in LUSC. Bioinformatics analyses appeared that let‐7a‐5p directly targets high–molecular weight keratin 5 (KRT5) which were shown to be a strong risk factor for LUAD. And NK2 homeobox 1(NKX2‐1) which was associated with tumor progression in LUSC was identified as a target gene of miR‐338.

Conclusions

Distinct profile of miRNAs can take a part in the development of LUAD and LUSC and thus could serve as a subtype‐specific molecular therapeutic target to protect against LUAD and LUSC.
A missense mutation sheds light on a novel structure–function relationship of RANKL
Authors: Qiu Heng , Qin An , Cheng Taksum , Chim Shek M. , Smithers Luke , Chen Kai , Song Dezhi , Liu Qian , Zhao Jinmin , Wang Chao , Teguh Dian , Zhang Ge , Tickner Jennifer , Vrielink Alice , Pavlos Nathan J. , Xu Jiake
Published: September 2020

The tumor necrosis factor (TNF)‐like core domain of receptor activator of nuclear factor‐κB ligand (RANKL) is a functional domain critical for osteoclast differentiation. One of the missense mutations identified in patients with osteoclast‐poor autosomal recessive osteopetrosis (ARO) is located in residue methionine 199 that is replaced with lysine (M199K) amid the TNF‐like core domain. However, the structure–function relationship of this mutation is not clear. Sequence‐based alignment revealed that the fragment containing human M199 is highly conserved and equivalent to M200 in rat. Using site‐directed mutagenesis, we generated three recombinant RANKL mutants M200K/A/E (M200s) by replacing the methionine 200 with lysine (M200K), alanine (M200A), and glutamic acid (M200E), representative of distinct physical properties. TRAcP staining and bone pit assay showed that M200s failed to support osteoclast formation and bone resorption, accompanied by impaired osteoclast‐related signal transduction. However, no antagonistic effect was found in M200s against wild‐type rat RANKL. Analysis of the crystal structure of RANKL predicted that this methionine residue is located within the hydrophobic core of the protein, thus, likely to be crucial for protein folding and stability. Consistently, differential scanning fluorimetry analysis suggested that M200s were less stable. Western blot analysis analyses further revealed impaired RANKL trimerization by M200s. Furthermore, receptor–ligand binding assay displayed interrupted interaction of M200s to its intrinsic receptors. Collectively, our studies revealed the molecular basis of human M199‐induced ARO and elucidated the indispensable role of rodent residue M200 (equivalent to human M199) for the RANKL function.
Pilot Study of Peak Plasma Concentration After High‐Dose Oral Montelukast in Children With Acute Asthma Exacerbations
Authors: Arnold Donald H. , Van Driest Sara L. , Reiss Theodore F. , King Jennifer C. , Akers Wendell S.
Published: September 2020

Acute asthma exacerbations are primarily due to airway inflammation and remain one of the most frequent reasons for childhood hospitalizations. Although systemic corticosteroids remain the mainstay of therapy because of their anti‐inflammatory properties, not all inflammatory pathways are responsive to systemic corticosteroids, necessitating hospital admission for further management. Cysteinyl leukotrienes (LTs) are proinflammatory mediators that play an important role in systemic corticosteroids non‐responsiveness. Montelukast is a potent LT‐receptor antagonist, and an intravenous preparation caused rapid, sustained improvement of acute asthma exacerbations in adults. We hypothesized that a 30‐mg dose of oral montelukast achieves peak plasma concentrations (Cmax), comparable to the intravenous preparation (1700 ng/mL) and would be well tolerated in 15 children aged 5 to 12 years with acute asthma exacerbations. After administration of montelukast chewable tablets, blood samples were collected at 0, 15, 30, 45, 60, 120, 180, and 240 minutes. Plasma was separated and frozen at −80°C until analysis for montelukast concentration using liquid chromatography‐ tandem mass spectrometry. Median time to Cmax (tmax) was 3.0 hours. Six participants (40%) achieved Cmax of 1700 ng/mL or higher. However, there was high interindividual variability in peak plasma concentration (median Cmax of 1378 ng/mL; range, 16‐4895 ng/mL). No participant had side effects or adverse events. Plasma concentrations from this pilot study support the design of a weight‐based dose‐finding study aimed at selecting an optimal dose for future clinical trials to assess the efficacy of high‐dose oral montelukast in children with moderate to severe asthma exacerbations.
Seasonal ultrastructural changes in apocrine gland cells in back skin of male brown bears (Ursus arctos)
Authors: Tomiyasu Jumpei , Bochimoto Hiroki , Kondoh Daisuke , Sato Yoshikazu , Matsumoto Naoya , Sasaki Kazuyoshi , Haneda Shingo , Matsui Motozumi
Published: September 2020

Oily secretions from the back skin are involved in the marking behavior of male brown bears (Ursus arctos), and apocrine glands in back skin are activated during the breeding season. Here, we investigated seasonal changes in the intracellular organelles of apocrine gland cells in the back skin of male brown bears using transmission electron microscopy (TEM) and osmium‐maceration scanning electron microscopy (OM‐SEM). The morphological features of mitochondria and intracellular granules, and secretory mechanisms obviously differed between breeding and non‐breeding seasons. The TEM findings showed that contents of low‐density granules were released into the glandular lumen by frequent exocytosis, and sausage‐shaped mitochondria were located in the perinuclear region during the non‐breeding season. In contrast, high‐density granules appeared in the apical region and in projections during the breeding season, and swollen mitochondria and lysosome‐like organelles separating into high‐density granules were located in the perinuclear region. The OM‐SEM findings revealed swollen mitochondria with only a few partially developed cristae, and small mitochondria with cristae shaped like those in swollen mitochondria in the apical regions during the breeding season. These findings indicated that the small mitochondria corresponded to the high‐density granules identified by TEM. These findings suggested that mitochondria in apocrine gland cells swell, degenerate, fracture into small pieces, and are finally released by apocrine secretions during the breeding season. Small mitochondria released in this secretory manner might function as the source of chemical signals in the oily secretions of brown bears during the breeding season.
Pathological and immunohistochemical studies following the experimental infection of ayu (Plecoglossus altivelis) by Edwardsiella ictaluri
Authors: Gaafar Alkhateib Y. , Hassan Abdullah Ebtsam Sayed , Mahmoud Mahmoud Mostafa , Younes Abdelgayed M. , Nakai Toshihiro
Published: September 2020

In recent decades, several mass mortalities were recorded in riverine ayu (Plecoglossus altivelis) in Tokyo Metropolis, Hiroshima Prefecture, and Yamaguchi Prefecture, Japan; in these outbreaks, microbiological and pathological examinations revealed Edwardsiella ictaluri as the causative agent. In this study, histopathological findings and immunohistochemical localization of the bacteria following experimental infection of ayu were discussed. Infection experiments were performed using 44 healthy cultured ayu fingerlings using E. ictaluri isolate (H90). The fish were injected with the isolate intraperitoneally with a dose of 5.1 × 105 cfu/fish, while the control fish were injected with sterile phosphate buffered saline. The fish were observed for clinical signs, with daily collection of dead fish, and isolation of bacteria from the posterior kidney was performed and confirmed to be E. ictaluri by slide agglutination using anti‐PH0744 serum. Daily collection of five moribund fish for necropsy and tissue specimens collection from hepatopancreas, spleen, posterior kidney, gills, brain, heart, and intestine for histopathological and immunohistochemical examination. Post‐mortem lesions were recorded as exophthalmia, bloody ascitis, hemorrhagic kidney and distended gallbladder, meningio‐encephalitis, hemorrhagic vent, and petechial hemorrhages on viscera. Histopathological examination revealed diffuse severe congestion in blood vessels and several degenerative and necrotic changes inconcurrent with positive antigenic staining by immunohistochemistry.
Minimal residual disease negativity by next‐generation flow in non‐CR myeloma patients
Authors: Kim Sung‐Min , Yang Naery Euphrasia , Jeong Dajeong , Yun Jiwon , Ryu Sohee , Yoon Sung‐Soo , Ahn Yong‐Oon , Lee Dong Soon
Published: September 2020

Next‐generation flow (NGF) has detected minimal residual disease (MRD) in numerous myeloma patients who achieve a complete response (CR). However, when MRD is not detected via NGF in non‐CR patients, its clinical meaning is uncertain. Here, we investigated the correlation between MRD findings on NGF and the response criteria, paying special attention to patients with discrepant results. We performed NGS analysis of IgH rearrangements on bone marrow samples from the non‐CR patients with negative MRD on NGF. NGS detected residual abnormal clones in those patients, suggesting that NGF and NGS should be used in a complementary manner for MRD investigation.
Neutrophil dysfunction triggers inflammatory bowel disease in G6PC3 deficiency
Authors: Goenka Anu , Doherty John A , Al-Farsi Tariq , Jagger Christopher , Banka Siddharth , Cheesman Edmund , Fagbemi Andrew , Hughes Stephen M , Wynn Robert F , Hussell Tracy , Arkwright Peter D
Published: September 2020

The glucose-6-phosphatase catalytic subunit 3 (G6PC3) encodes a ubiquitously expressed enzyme that regulates cytoplasmic glucose availability. Loss-of-function biallelic G6PC3 mutations cause severe congenital neutropenia and a diverse spectrum of extra-hematological manifestations, among which inflammatory bowel disease (IBD) has been anecdotally reported. Neutrophil function and clinical response to granulocyte colony-stimulating factor (G-CSF) and hematopoietic stem cell transplantation (HSCT) were investigated in 4 children with G6PC3 deficiency-associated IBD. G6PC3 deficiency was associated with early-onset IBD refractory to treatment with steroids and infliximab. The symptoms of IBD progressed despite G-CSF treatment. In vitro studies on the patients’ blood showed that neutrophils displayed higher levels of activation markers (CD11b, CD66b, and CD14), excessive IL-8 and reactive oxygen species, and increased apoptosis and secondary necrosis. Secondary necrosis was exaggerated after stimulation with Escherichia coli and could be partially rescued with supplemental exogenous glucose. HSCT led to normalization of neutrophil function and remission of gastrointestinal symptoms. We conclude that neutrophils in G6PC3 deficiency release pro-inflammatory mediators when exposed to gut bacteria, associated with intestinal inflammation, despite treatment with G-CSF. HSCT is an effective therapeutic option in patients with G6PC3 deficiency-associated IBD refractory to immune suppressants.
Dietary docosahexaenoic acid inhibits neurodegeneration and prevents stroke
Authors: Yamagata Kazuo
Published: September 2020

Stroke severely impairs quality of life and has a high mortality rate. On the other hand, dietary docosahexaenoic acid (DHA) prevents neuronal damage. In this review, we describe the effects of dietary DHA on ischemic stroke‐associated neuronal damage and its role in stroke prevention. Recent epidemiological studies have been conducted to analyze stroke prevention through DHA intake. The effects of dietary intake and supply of DHA to neuronal cells, DHA‐mediated inhibition of neuronal damage, and its mechanism, including the effects of the DHA metabolite, neuroprotectin D1 (NPD1), were investigated. These studies revealed that DHA intake was associated with a reduced risk of stroke. Moreover, studies have shown that DHA intake may reduce stroke mortality rates. DHA, which is abundant in fish oil, passes through the blood–brain barrier to accumulate as a constituent of phospholipids in the cell membranes of neuronal cells and astrocytes. Astrocytes supply DHA to neuronal cells, and neuronal DHA, in turn, activates Akt and Raf‐1 to prevent neuronal death or damage. Therefore, DHA indirectly prevents neuronal damage. Furthermore, NDP1 blocks neuronal apoptosis. DHA, together with NPD1, may block neuronal damage and prevent stroke. The inhibitory effect on neuronal damage is achieved through the antioxidant (via inducing the Nrf2/HO‐1 system) and anti‐inflammatory effects (via promoting JNK/AP‐1 signaling) of DHA.
Rainy season drought severity trend analysis of the Indonesian maritime continent
Authors: Ferijal Teuku , Batelaan Okke , Shanafield Margaret
Published: September 2020

Drought is generally associated with a long‐term reduction in total precipitation. However, changes at shorter time‐scales can also induce drought conditions. This study analyses trends of meteorological drought severity during the rainy season in the Indonesian maritime continent. We propose a new dry spell index to characterize this drought severity. The anomalous accumulation definition was used to define a single most intense rainy season for region with one or two rainy seasons per year. The Mann–Kendall test was applied for trend analysis of the index. Temporal and spatial drought characterisations were compared between the dry spell index and standardized precipitation index. The results show that in semi‐annual and anti‐monsoonal regimes the rainy season precipitation increases, the number of dry days decreases, and long dry spell contribution decreases, overall causing a decrease in drought severity. Over the same period, the number of dry days, duration of the extreme dry spell, and long dry spell contribution increased in the monsoon regime, indicating a tendency towards a drier condition. In contrast, standardized precipitation index showed a strong tendency towards a wetter condition during the rainy season over this region.
Systemic bone loss following myocardial infarction in mice
Authors: Tjandra Priscilla M. , Paralkar Manali P. , Osipov Benjamin , Chen Yi‐Je , Zhao Fengdong , Ripplinger Crystal M. , Christiansen Blaine A.
Published: September 2020

Myocardial infarction (MI) and osteoporotic fracture are leading causes of morbidity and mortality, and epidemiological evidence linking their incidence suggests possible crosstalk. MI can exacerbate atherosclerosis through the sympathetic nervous system (SNS) activation and β3 adrenoreceptor‐mediated release of hematopoietic stem cells, leading to monocytosis. We hypothesized that this same pathway initiates systemic bone loss following MI, since osteoclasts differentiate from monocytes. In this study, MI was created with left anterior descending artery ligation in 12‐week‐old male mice (n = 24) randomized to β3‐adrenergic receptor (AR) antagonist (SR 59230A) treatment or no treatment for 10 days postoperatively. Additional mice (n = 21, treated and untreated) served as unoperated controls. Bone mineral density (BMD), bone mineral content (BMC), and body composition were quantified at baseline and 10 days post‐MI using dual‐energy x‐ray absorptiometry; circulating monocyte levels were quantified and the L5 vertebral body and femur were analyzed with microcomputed tomography 10 days post‐MI. We found that MI led to circulating monocyte levels increases, BMD and BMC decreases at the femur and lumbar spine in MI mice (−6.9% femur BMD, −3.5% lumbar BMD), and trabecular bone volume decreases in MI mice compared with control mice. β3‐AR antagonist treatment appeared to diminish the bone loss response (−5.3% femur BMD, −1.2% lumbar BMD), though these results were somewhat inconsistent. Clinical significance: These results suggest that MI leads to systemic bone loss, but that the SNS may not be a primary modulator of this response; bone loss and increased fracture risk may be important clinical comorbidities following MI or other ischemic injuries.
Altered mechanical behavior of demineralized bone following therapeutic radiation
Authors: Bartlow Christopher M. , Mann Kenneth A. , Damron Timothy A. , Oest Megan E.
Published: September 2020

Post‐radiotherapy (RTx) bone fragility fractures are a late‐onset complication occurring in bone within or underlying the radiation field. These fractures are difficult to predict, as patients do not present with local osteopenia. Using a murine hindlimb RTx model, we previously documented decreased mineralized bone strength and fracture toughness, but alterations in material properties of the organic bone matrix are largely unknown. In this study, 4 days of fractionated hindlimb irradiation (4 × 5 Gy) or Sham irradiation was administered in a mouse model (BALB/cJ, end points: 0, 4, 8, and 12 weeks, n = 15/group/end point). Following demineralization, the viscoelastic stress relaxation, and monotonic tensile mechanical properties of tibiae were determined. Irradiated tibiae demonstrated an immediate (day after last radiation fraction) and sustained (4, 8, 12 weeks) increase in stress relaxation compared to the Sham group, with a 4.4% decrease in equilibrium stress (p < .017). While tensile strength was not different between groups, irradiated tibiae had a lower elastic modulus (−5%, p = .027) and energy to failure (−12.2%, p = .012) with monotonic loading. Gel electrophoresis showed that therapeutic irradiation (4 × 5 Gy) does not result in collagen fragmentation, while irradiation at a common sterilization dose (25 kGy) extensively fragmented collagen. These results suggest that altered collagen mechanical behavior has a role in postirradiation bone fragility, but this can occur without detectable collagen fragmentation. Statement of Clinical Significance: Therapeutic irradiation alters bone organic matrix mechanics and which contribute to diminished fatigue strength, but this does not occur via collagen fragmentation.
Development of an aqueous ultrasound‐assisted extraction process of bioactive compounds from beet leaves: a proposal for reducing losses and increasing biomass utilization
Authors: Nutter Julia , Fernandez María V , Jagus Rosa J , Agüero María V
Published: September 2020

BACKGROUND

Red beet plants are cultivated worldwide for the consumption of their roots, generating large amounts of unexploited by‐products. In particular, beet leaves (BLs) represent about 50% of the whole plant and are usually discarded as waste. This constitutes not only an economic issue, since multiple resources invested in the production will be wasted, but also an environmental problem because of the pollution associated with their disposal. However, BLs comprise an important source of functional compounds (polyphenols and betalains) that could be recovered from the raw material, representing a sustainable solution for the underutilization of this by‐product. This study proposes the recovery of polyphenols and betalains using an aqueous ultrasound‐assisted extraction (UAE) process at different powers (35, 50, and 100 W) that was characterized and optimized.

RESULTS

UAE significantly enhanced the recovery of bioactive compounds and shortened the time required for extraction in comparison with traditional macerations (35 < 50 < 100 W). During UAE, the temperature of the systems increased as a function of the power applied, favouring the recovery of these phytochemicals. Additionally, a Box–Behnken design and response surface methodology were employed to optimize UAE conditions (90 W ultrasound power, 1:20 solid:liquid ratio, 16 min extraction time), under which the yields were 14.9 mg g−1 (polyphenols), 949.1 μg g−1 (betaxanthins), and 562.2 μg g−1 (betacyanins), consistent with the values predicted by the models.

CONCLUSION

This study enabled the development of a green‐solvent UAE process that constitutes an effective post‐harvest by‐products strategy to minimize losses and increase biomass utilization through the recovery of bioactive compounds from BLs, promoting sustainability in the agri‐food chain. © 2020 Society of Chemical Industry
Anatomical characterization of the inguinal lymph nodes using microcomputed tomography to inform radical inguinal lymph node dissections in penile cancer
Authors: Marshall Kaitlin , Nair Shiva M. , Willmore Katherine E. , Beveridge Tyler S. , Power Nicholas E.
Published: September 2020

Background & Objectives

Radical inguinal lymph node dissections (rILND) for penile cancer risk significant postoperative lymphocele and lymphedema. However, reducing the risk of lymphatic complications is limited by our understanding of lymphatic anatomy. Therefore, this study aims to elucidate the lymphatic anatomy within the current surgical borders of a rILND.

Methods

To visualize the position of the lymph nodes, tissue packets excised from the inguinal region of five fresh, male cadavers were imaged using microcomputed tomography (µCT). To standardize the position, rotation and size between specimens, each lymph node packet was aligned using a Generalized Procrustes analysis.

Results

There was a median of 13.5 lymph nodes (range = 8‐18) per packet, with the majority (99%) clustered within a 6 cm radius of the saphenofemoral junction; a region 39%‐41% smaller than current surgical borders. No difference existed between the number of nodes between sides, or distribution around the saphenofemoral junction.

Conclusions

This study provides the first 3D, in situ, standardized characterization of lymph node anatomy in the inguinal region using µCT. By using knowledge of the normal lymphatic anatomy, this study can help inform the reduction in borders of rILND to limit disruption and ensure a complete lymphadenectomy.
Video Demonstration of a Tunneled Temporoparietal Fascia Flap: How I Do It
Authors: London Nyall R. , Mohyeldin Ahmed , Silveira‐Bertazzo Giuliano , Prevedello Daniel M. , Carrau Ricardo L.
Published: September 2020

https://bcove.video/33MDx0u
Calvarium Thinning in Patients with Spontaneous Cerebrospinal Fluid Leaks of the Anterior Skull Base
Authors: Sharma Dhruv , Tucker Brady J. , Millay David S. , Rubel Kolin E. , Saltagi Mohamad , Nelson Rick F. , Illing Elisa A. , Ting Jonathan Y.
Published: September 2020

Objectives/Hypothesis

Patients with spontaneous cerebrospinal fluid leaks (sCSF‐L) of the temporal bone have isolated calvarial and skull base thinning that is independent of obesity. This study determines if anterior skull base (ASB) sCSF‐L patients also have calvarial thinning.

Study Design

Retrospective Cohort Study.

Methods

This was a retrospective cohort study of ASB sCSF‐L patients compared to nonobese (body mass index [BMI] < 30 kg/m2) and obese (BMI ≥ 30) control groups. Twenty‐one patients in the ASB sCSF‐L group and 25 patients in each control group were included. Calvarium and extracranial zygoma thicknesses were measured bilaterally with blinded, standardized, volumetric analysis.

Results

ASB sCSF‐L patients had a mean (SD) age of 50.43 (10.19) years, an average (SD) BMI of 38.81 (8.92) kg/m2, and most were female (85.71%). The calvarium in patients with ASB sCSF‐L was significantly thinner than the nonobese (2.55 mm [0.77] vs. 2.97 [0.67] mm; P = .006; 95% confidence intervals [CI], 0.12–0.30; Cohen d, 0.58) and obese control groups (2.55 [0.77] vs. 2.92 [0.76] mm; P = .02; 95% CI, 0.05–0.34; Cohen d, 0.66). The calvarium thickness of the nonobese patients was not significantly different from the obese patient controls (2.97 [0.67] vs. 2.92 [0.76] mm, P = .9). The extracranial zygoma was not significantly different among the groups (analysis of variance, P = .33).

Conclusions

ASB sCSF‐L patients have isolated calvarial thinning that is independent of obesity. Like lateral skull base sCSF‐L patients, these data suggest that the additional obesity‐associated intracranial process contributes to skull thinning.

Level of Evidence

4 Laryngoscope, 131:1271–1276, 2021
Phosphorus dynamics in the Barents Sea
Authors: Downes Patrick P. , Goult Stephen J. , Woodward E. Malcolm S. , Widdicombe Claire E. , Tait Karen , Dixon Joanna L.
Published: September 2020

The Barents Sea is considered a warming hotspot in the Arctic; elevated sea surface temperatures have been accompanied with increased inflow of Atlantic water onto the shelf sea. Such hydrodynamic changes and a concomitant reduction of sea ice coverage enables a prolonged phytoplankton growing season, which will inevitably affect nutrient stoichiometry and the controls on primary production. During the summer of 2018, we investigated the role of phosphorus in mediating primary production in the Barents Sea. Dissolved inorganic phosphorus (DIP), its most bioavailable form, had an average net turnover time of 9.4 ± 4.8 d. The most southern Atlantic influenced station accounted for both the highest rates of primary production (655 mg C m2 d−1) and shortest net DIP turnover (2.8 ± 0.5 d). The fraction of assimilated DIP released as dissolved organic phosphorus (DOP) at this station was < 4% compared to an average of 21% at all other stations. We observed significant differences between phytoplankton communities in Arctic and Atlantic waters within the Barents Sea. Slower DIP turnover and greater release of DOP was associated with Phaeocystis pouchetii dominated communities in Arctic waters. Faster turnover rates and greater phosphorus retention occurred among the Atlantic phytoplankton communities dominated by Emiliania huxleyi. These findings provide baseline measurements of P utilization in the Barents Sea, and suggest increased Atlantic intrusion of this region could be accompanied by more rapid DIP turnover, possibly leading to future P limitation (rather than N limitation) on primary production.
An All‐Optically Controlled Liquid‐Crystal Plasmonic Metasurface Platform
Authors: Sharma Mukesh , Ellenbogen Tal
Published: September 2020

The need for thin active metasurface based elements, opens an exciting research direction toward exploration of various active materials and their control mechanisms. Here, an all‐optical control mechanism of composite metasurfaces is studied, based on rapid laser‐induced thermo‐optical nonlinearities in nematic liquid crystals (NLCs). Specifically, the absorption of photons leads to local heating, which in turn facilitates a nematic‐to‐isotropic (N–I) phase transition of a twisted‐NLC (TNLC) layer that is sandwiched between an indium tin oxide (ITO) coated glass plate and the metasurface. This mechanism is used to experimentally demonstrate all‐optically switchable plasmonic metasurface color tag. The dependence of the switching on the laser power and the dynamic response of the device are characterized. Experimental results show that the pump beam power significantly affects the switching time, which can be further reduced by thermal management of the design. Such switching mechanisms have great potential in all‐optically controlled systems and can be applied to realize additional active and multifunctional optical devices at nanoscale.
Analyzing user sentiment in social media: Implications for online marketing strategy
Authors: Micu Adrian , Micu Angela Eliza , Geru Marius , Lixandroiu Radu Constantin
Published: September 2020

This article examines restaurant customers’ online activity following visits to restaurants. Differences in customers’ opinions based on gender and location are discussed. Sentiment analysis was used to analyze customers’ social media behavior in terms of liking, rating, and reviewing restaurants. User‐generated reviews and comments about experiences influence potential customers’ decisions. The results of this study show that gender and location of customers influence restaurant ratings. This article shows that sentiment analysis (using Natural Language Toolkit and TextBlob) can help marketers by providing a useful tool for big data analysis. Sentiment analysis can be used to interpret customer behavior and highlight how presales, sales, and after‐sales strategies can be improved.
ORGANOMETALLIC GAS‐PHASE ION CHEMISTRY AND CATALYSIS: INSIGHTS INTO THE USE OF METAL CATALYSTS TO PROMOTE SELECTIVITY IN THE REACTIONS OF CARBOXYLIC ACIDS AND THEIR DERIVATIVES
Authors: O'Hair Richard A. J.
Published: September 2020

Carboxylic acids are valuable organic substrates as they are widely available, easy to handle, and exhibit structural and functional variety. While they are used in many standard synthetic protocols, over the past two decades numerous studies have explored new modes of metal‐mediated reactivity of carboxylic acids and their derivatives. Mass spectrometry‐based studies can provide fundamental mechanistic insights into these new modes of reactivity. Here gas‐phase models for the following catalytic transformations of carboxylic acids and their derivatives are reviewed: protodecarboxylation; dehydration; decarbonylation; reaction as coordinated bases in C–H bond activation; remote functionalization and decarboxylative C–C bond coupling. In each case the catalytic problem is defined, insights from gas‐phase studies are highlighted, comparisons with condensed‐phase systems are made and perspectives are reached. Finally, the potential role for mechanistic studies that integrate both gas‐ and condensed‐phase studies is highlighted by recent studies on the discovery of new catalysts for the selective decomposition of formic acid and the invention of the new extrusion‐insertion class of reactions for the synthesis of amides, thioamides, and amidines. © 2020 John Wiley & Sons Ltd. Mass Spec Rev
Partial tibial nerve transfer for foot drop from deep peroneal palsy: Lessons from three pediatric cases
Authors: Crowe Christopher S. , Mosca Vincent S. , Osorio Marisa B. , Lewis Sarah P. , Tse Raymond W.
Published: September 2020

Peroneal nerve palsy with resultant foot drop has significant impacts on gait and quality of life. Traditional management includes ankle‐foot‐orthosis, tendon transfer, and arthrodesis—each with certain disadvantages. While nerve transfers for peroneal nerve injury have been reported in adults, with variable results, they have not been described in the pediatric population. We report the use of partial tibial nerve transfer for foot drop from deep peroneal nerve palsy in three pediatric patients. The first sustained a partial common peroneal nerve laceration and underwent transfer of a single tibial nerve branch to deep peroneal nerve 7 months after injury. Robust extensor hallucis longus and extensor digitorum longus reinnervation was obtained without satisfactory tibialis anterior function. The next patient sustained a thigh laceration with partial sciatic nerve injury and underwent transfer of two tibial nerve branches directly to the tibialis anterior component of deep peroneal nerve 9 months after injury. The final patient sustained a blast injury to the posterior knee and similarly underwent a double fascicular transfer directly to tibialis anterior 4 months after injury. The latter two patients obtained sufficient strength (MRC 4–5) at 1 year to discontinue orthosis. In all patients, we used flexor hallucis longus and/or flexor digitorum longus branches as donors without postoperative loss of toe flexion. Overall, our experience suggests that early double fascicular transfer to an isolated tibialis anterior target, combined with decompression, could produce robust innervation. Further study and collaboration are needed to devise new ways to treat lower extremity nerve palsies.
Nonparametric estimation of quadratic variation using high‐frequency data
Authors: Yu Xisheng
Published: September 2020

Estimating the quadratic variation (QV) using high‐frequency financial data is studied in this article, and this work makes two major contributions: first, the fundamental Itô isometry
is generalized to some extent, and as an application example, the widely known convergence property of realized volatility (RV) estimator of QV is analyzed by alternatively utilizing this generalized Itô isometry; second, we intuitively establish two types of new estimators of QV which permit volatility varying with time. To construct such estimators, the RV combined with realized bipower variation and RV with realized quarticity are employed, respectively. By applying the generalized Itô isometry, we further show that each of the proposed estimators can converge to QV, at a rate of O(n−1/2), almost surely and in mean square sense, both of which are stronger than the existing convergence in probability. Moreover, the error of approximation is also provided for each estimation. In addition, the obtained convergence property for both types of estimators is demonstrated by empirical investigations based on high‐frequency data of IBM stock.
Automatic contouring system for cervical cancer using convolutional neural networks
Authors: Rhee Dong Joo , Jhingran Anuja , Rigaud Bastien , Netherton Tucker , Cardenas Carlos E. , Zhang Lifei , Vedam Sastry , Kry Stephen , Brock Kristy K. , Shaw William , O’Reilly Frederika , Parkes Jeannette , Burger Hester , Fakie Nazia , Trauernicht Chris , Simonds Hannah , Court Laurence E.
Published: September 2020

Purpose

To develop a tool for the automatic contouring of clinical treatment volumes (CTVs) and normal tissues for radiotherapy treatment planning in cervical cancer patients.

Methods

An auto‐contouring tool based on convolutional neural networks (CNN) was developed to delineate three cervical CTVs and 11 normal structures (seven OARs, four bony structures) in cervical cancer treatment for use with the Radiation Planning Assistant, a web‐based automatic plan generation system. A total of 2254 retrospective clinical computed tomography (CT) scans from a single cancer center and 210 CT scans from a segmentation challenge were used to train and validate the CNN‐based auto‐contouring tool. The accuracy of the tool was evaluated by calculating the Sørensen‐dice similarity coefficient (DSC) and mean surface and Hausdorff distances between the automatically generated contours and physician‐drawn contours on 140 internal CT scans. A radiation oncologist scored the automatically generated contours on 30 external CT scans from three South African hospitals.

Results

The average DSC, mean surface distance, and Hausdorff distance of our CNN‐based tool were 0.86/0.19 cm/2.02 cm for the primary CTV, 0.81/0.21 cm/2.09 cm for the nodal CTV, 0.76/0.27 cm/2.00 cm for the PAN CTV, 0.89/0.11 cm/1.07 cm for the bladder, 0.81/0.18 cm/1.66 cm for the rectum, 0.90/0.06 cm/0.65 cm for the spinal cord, 0.94/0.06 cm/0.60 cm for the left femur, 0.93/0.07 cm/0.66 cm for the right femur, 0.94/0.08 cm/0.76 cm for the left kidney, 0.95/0.07 cm/0.84 cm for the right kidney, 0.93/0.05 cm/1.06 cm for the pelvic bone, 0.91/0.07 cm/1.25 cm for the sacrum, 0.91/0.07 cm/0.53 cm for the L4 vertebral body, and 0.90/0.08 cm/0.68 cm for the L5 vertebral bodies. On average, 80% of the CTVs, 97% of the organ at risk, and 98% of the bony structure contours in the external test dataset were clinically acceptable based on physician review.

Conclusions

Our CNN‐based auto‐contouring tool performed well on both internal and external datasets and had a high rate of clinical acceptability.
Determination of the absorbed dose to water for medium‐energy x‐ray beams using Fricke dosimetry
Authors: Rosado Paulo Henrique , Salata Camila , David Mariano Gazineu , Mantuano Andrea , Pickler Arissa , Mota Carla Lemos , de Almeida Carlos E.
Published: September 2020

Purpose

For x‐ray beams in the low and medium energy range, reference dosimetry is established in terms of air kerma. Fricke dosimetry has shown great potential in the absolute measurements of the absorbed dose to water for high‐energy ranges. Therefore, the main purpose of this work was to compare the absorbed dose to water for medium‐energy x‐ray beams obtained through Fricke dosimetry with that obtained from the air kerma rate.

Methods

To determine the absorbed dose to water using Fricke dosimetry, the polyethylene bags methodology was chosen. Fricke solution was irradiated at four different beam qualities. The absorbed dose to water values obtained using Fricke dosimetry were compared to those obtained using the standard protocol, using the Z‐score.

Results

Values of the Z‐score were <2 for all measurements of absorbed dose to water, which means that the values obtained using Fricke dosimetry are equivalent to those obtained using the reference protocol. The combined standard uncertainty for the absorbed dose to water obtained by Fricke dosimetry was lower than that obtained with the ionization chamber.

Conclusions

Chemical dosimetry using a standard FeSO4 solution has been demonstrated to be a potential option as a standard for the quantity absorbed dose to water for medium kV x‐ray qualities.
Technical Note: Scintillation markers for real‐time visual source tracking during skin high dose rate brachytherapy
Authors: Huynh Elizabeth , Bhagwat Mandar S.
Published: September 2020

Background

Treatment misadministration during high dose rate (HDR) brachytherapy is mainly caused due to gross errors in incorrect manual entry of catheter length and manual connection of hardware. The probability of these errors increases with increasing complexity of a surface applicator. A simple, real‐time visual verification method was developed using a scintillator to enhance quality assurance (QA) measures for HDR surface brachytherapy and thus reduce manual errors and improve patient safety.

Materials and methods

Scintillation markers were fabricated from cerium‐doped lutetium yttrium orthosilicate (LYSO) embedded in a polymer compound to form 5‐mm diameter markers. To verify catheter‐transfer tube connections, markers were attached to each channel of a Freiburg flap and irradiated with an 192Ir source. To determine if the source reached the edge of a target, markers were placed along the periphery. The HDR source was visually tracked by following the illumination from the markers. The response of the markers was also verified in the presence of thermoplastic material overlaid on the Freiburg applicator.

Results

Scintillation markers emitted intense blue visible light upon irradiation when the HDR source was beneath the marker, verifying the source’s presence in the correct catheter. The signal was clearly visible even when the marker was placed on top of the thermoplastic material covering the Freiburg Flap. Crosstalk from adjacent catheters was <50% of the maximum light intensity.

Conclusion

Scintillation markers and paint were developed to successfully meet the challenge of visually tracking of HDR source during brachytherapy by surface applicators. This direct visualization of source allows real‐time catheter verification during treatment, and correct superficial target coverage, thus preventing a medical event. It can easily be integrated into pre‐existing QA program.
Calibrationless parallel imaging reconstruction for multislice MR data using low‐rank tensor completion
Authors: Liu Yilong , Yi Zheyuan , Zhao Yujiao , Chen Fei , Feng Yanqiu , Guo Hua , Leong Alex T. L. , Wu Ed X.
Published: September 2020

Purpose

To provide joint calibrationless parallel imaging reconstruction of highly accelerated multislice 2D MR k‐space data.

Methods

Adjacent image slices in multislice MR data have similar coil sensitivity maps, spatial support, and image content. Such similarities can be utilized to improve image quality by reconstructing multiple slices jointly with low‐rank tensor completion. Specifically, the multichannel k‐space data from multiple slices are constructed into a block‐wise Hankel tensor and iteratively updated by promoting tensor low‐rankness through higher‐order SVD. This multislice block‐wise Hankel tensor completion was implemented for 2D spiral and Cartesian k‐space undersampling where sampling patterns vary between adjacent slices. The approach was evaluated with human brain MR data and compared to the traditional single‐slice simultaneous autocalibrating and k‐space estimation reconstruction.

Results

The proposed multislice block‐wise Hankel tensor completion approach robustly reconstructed highly undersampled multislice 2D spiral and Cartesian data. It produced substantially lower level of artifacts compared to the traditional single‐slice simultaneous autocalibrating and k‐space estimation reconstruction. Quantitative evaluation using error maps and root mean square error demonstrated its significantly improved performance in terms of residual artifacts and root mean square error.

Conclusion

Our proposed multislice block‐wise Hankel tensor completion method exploits the similar coil sensitivity and image content within multislice MR data through a tensor completion framework. It offers a new and effective approach to acquire and reconstruct highly undersampled multislice MR data in a calibrationless manner.
Chronic inflammatory demyelinating polyradiculoneuropathy—Diagnostic pitfalls and treatment approach
Authors: Stino Amro M. , Naddaf Elie , Dyck Peter J. , Dyck P. James B.
Published: September 2020

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by progressive weakness and sensory loss, often affecting patientsʼ ability to walk and perform activities of daily living independently. With the lack of a diagnostic biomarker, the diagnosis relies on clinical suspicion, clinical findings, and the demonstration of demyelinating changes on electrodiagnostic (EDx) testing and nerve pathology. As a result, patients can often be misdiagnosed with CIDP and unnecessarily treated with immunotherapy. Interpreting the EDx testing and cerebrospinal fluid findings in light of the clinical phenotype, recognizing atypical forms of CIDP, and screening for CIDP mimickers are the mainstays of the approach to patients suspected of having CIDP, and are detailed in this review. We also review the currently available treatment options, including intravenous immunoglobulin (IVIg), corticosteroids (CCS), and plasma exchange (PE), and discuss how to approach treatment‐refractory cases. Finally, we emphasize the need to adopt objective outcome measures to monitor treatment response.
Overexpression of ArabidopsismicroRNA167 induces salicylic acid‐dependent defense against Pseudomonas syringae through the regulation of its targets ARF6 and ARF8
Authors: Caruana Julie C. , Dhar Nikhilesh , Raina Ramesh
Published: September 2020

microRNAs are powerful regulators of growth, development, and stress responses in plants. The Arabidopsis thaliana microRNA miR167 was previously found to regulate diverse processes including flower development, root development, and response to osmotic stress by controlling the patterns of expression of its target genes AUXIN RESPONSE FACTOR 6 (ARF6), ARF8, and IAA‐Ala RESISTANT 3. Here, we report that miR167 also modulates defense against pathogens through ARF6 and ARF8. miR167 is differentially expressed in response to the bacterial pathogen Pseudomonas syringae, and overexpression of miR167 confers very high levels of resistance. This resistance appears to be due to suppression of auxin responses and is partially dependent upon salicylic acid signaling, and also depends upon altered stomatal behavior in these plants. Closure of stomata upon the detection of P. syringae is an important aspect of the basal defense response, as it prevents bacterial cells from entering the leaf interior and causing infection. Plants overexpressing miR167 constitutively maintain small stomatal apertures, resulting in very high resistance when the pathogen is inoculated onto the leaf surface. Additionally, the systemic acquired resistance (SAR) response is severely compromised in plants overexpressing miR167, in agreement with previous work showing that the activation of SAR requires intact auxin signaling responses. This work highlights a new role for miR167, and also emphasizes the importance of hormonal balance in short‐ and long‐term defense and of stomata as an initial barrier to pathogen entry.